Insecticide, novel compound having insecticidal activity, and use thereof

Abstract

To provide a novel insecticide having specific growth inhibitory activity.SOLUTION: In one aspect of the present invention, an insecticide contains, as an active ingredient, a compound represented by formula (I) or (II) or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof. In formulas (I) and (II), R1 and R2 are hydrogen, halogen or hydroxy, and A is a monovalent group represented by formula (A-1), (A-2), or (A-3).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to insecticides, novel compounds having insecticidal activity, and uses thereof. [Background technology]

[0002] The use of pesticides and insecticides is essential for stable crop yields and pest control. However, in Europe, insecticides that have been reported to be dangerous are being banned one after another (Non-Patent Documents 1 to 3). Furthermore, the emergence of insecticide-resistant insects has been reported worldwide (Non-Patent Documents 4 and 5). Therefore, there is a need to develop new insecticides that have a specific mechanism of action against pests and a chemical structure different from that of conventional insecticides.

[0003] Unlike mammals and plants, insects have unique developmental processes such as molting and / or metamorphosis. These processes are controlled by ecdysteroids such as ecdysone. Without ecdysteroids, insects cannot develop into adults. Ecdysteroids are known to be biosynthesized from cholesterol by several enzymes (Non-Patent Documents 6 and 7). Biosynthesized ecdysone is converted into active ecdysone, which binds to the ecdysone receptor (EcR) and regulates downstream gene expression, thereby promoting development.

[0004] Tebufenozide, an ecdysone receptor agonist, is commercially available as an insecticide that induces abnormal molting in lepidopteran insects (Non-Patent Documents 8-11). However, insect resistance to tebufenozide has been reported (Non-Patent Document 12). Insecticides that target insect-specific molecular mechanisms, such as tebufenozide, are called insect growth regulators (IGRs) (Non-Patent Document 13). IGRs generally target chitin, which is essential for cuticle formation, and juvenile hormone and ecdysone, which are insect hormones required for molting and / or metamorphosis (Non-Patent Document 14). Currently, insecticides that target the EcR, such as tebufenozide, are known, but no insecticides targeting ecdysone biosynthesis exist (Non-Patent Document 15).

[0005] Ecdysteroid biosynthetic enzymes that have been identified to date include the Halloween P450 group (Non-Patent Documents 16-21), the Rieske oxidase Neverland (Non-Patent Documents 22 and 23), the short-chain dehydrogenase / reductase Non-molting glossy / Shroud (Non-Patent Document 24), and the glutathione S-transferase (hereinafter also referred to as "GST") Noppera-bo (hereinafter also referred to as "Nobo") (Non-Patent Documents 25-27). [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Cressey, D. 2017, Nature, 551(7679), 156-158 [Non-patent document 2] Butler, D. 2018, Nature, 555(7695), 150-151 [Non-patent document 3] Sonne, C., & Alstrup, AKO 2019, Science, 363(6430), 938-939 [Non-patent document 4] Marcombe, S. et al., 2011, PLOS Neglected Tropical Diseases, 5(6), 1-9 [Non-patent document 5] Moyes, CL et al., 2021, PLOS Neglected Tropical Diseases, 15(1), e0009084 [Non-patent document 6] Spindler, KD et al., 2009, Cellular and Molecular Life Sciences, 66(24), 3837-3850 [Non-Patent Document 7] Niwa, R., & Niwa, YS 2014, Bioscience, Biotechnology and Biochemistry (Vol. 78, Issue 8, pp. 1283-1292). Japan Society for Bioscience Biotechnology and Agrochemistry [Non-licensed document 8] Dhadialla, TS, Carlson, GR, & Le, DP 1998, Annual Review of Entomology, 43(134), 545-569

Non-licensed literature 9

Non-licensed literature 10

Non-licensed Document 11

Non-licensed Document 12

Non-licensed Document 13

Non-licensed Document 14

Non-licensed Document 15

[0007] As mentioned above, there are currently no insecticides that target ecdysone biosynthesis, and therefore ecdysone biosynthetic enzymes are expected to be targets for new insecticides with mechanisms of action different from those of conventional insecticides. Among the known ecdysteroid biosynthetic enzymes, when targeting the Halloween P450 group, the Rieske oxidase Neverland, or the short-chain dehydrogenase / reductase Non-molting glossy / Shroud for new insecticides, problems have arisen, such as the difficulty of preparing recombinant proteins and the time required to detect enzyme activity.

[0008] In contrast, when targeting the GST Nobo for novel insecticides, not only can well-known affinity-tagged protein purification methods be used, but also established methods for measuring Nobo activity can be used. Nobo is also known to be specifically expressed in the ecdysteroid biosynthetic organelles (Non-Patent Documents 6 and 7). It has been reported that Nobo loss-of-function mutants in Drosophila and Bombyx mori are developmentally lethal due to defects in ecdysteroid biosynthesis (Non-Patent Document 28). Furthermore, Nobo is conserved only in Diptera and Lepidoptera (Non-Patent Document 26). Based on these facts, it is expected that targeting Nobo for novel insecticides will enable the development of novel insecticides with specific growth-inhibitory activity.

[0009] Therefore, an object of the present invention is to provide a novel insecticide having specific growth inhibitory activity. [Means for solving the problem]

[0010] The present inventors have investigated various means for solving the above-mentioned problems. Using a Nobo activity measurement method, the present inventors performed high-throughput screening of compounds with Nobo inhibitory activity and discovered compounds with high inhibitory activity against Nobo from a library of small molecule compounds. Based on these findings, the present inventors have completed the present invention.

[0011] That is, the gist of the present invention is as follows. (Embodiment 1) Formula (I) or (II): [ka] [In the formula, n is 0 or 1, R 1 and R 2 are, independently of one another, hydrogen, halogen (fluorine, chlorine, bromine or iodine), or hydroxy, A is a group represented by formula (A-1), (A-2) or (A-3): [ka] is a monovalent group represented by * indicates the bonding position to the nitrogen atom, X is a carbon atom or a nitrogen atom, R A1 , R A2 and R A4 are, independently of each other, hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryl aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted acylamino; R A3is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, oxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted acylamino; R A5is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, oxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted acylamino. or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof, as an active ingredient. (Embodiment 2) R A1 , R A2 and R A4are each independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 2. The insecticide of embodiment 1, which is an acylamino. (Embodiment 3) R A3 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 is acylamino, R A5 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 acylamino, The insecticide of embodiment 1 or 2. (Embodiment 4) Conditions (i) and (ii): Condition (i) n is 0, A is a monovalent group represented by formula (A-1), X is a carbon atom, R A1 , R A2 and R A4 are both hydrogen, and R A3 is nitro, or Condition (ii) n is 1, R A1 , R A2 and R A4 are each independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), or substituted or unsubstituted C1-C9 alkyl; R A3 is hydrogen, nitro, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C1-C 20 is acylamino, R A5 is hydrogen, nitro, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C1-C 20 acylamino, 4. The insecticide according to any one of embodiments 1 to 3, which satisfies any one of the conditions above. (Embodiment 5) A compound represented by formula (I) or (II) or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof, 2-[5-(trifluoromethyl)-2-pyridinyl]-1,2,3,4-tetrahydroisoquinoline (compound R-010); 6-(3,4-dihydro-2(1H)-isoquinolinyl)-N,N-diethyl-3-pyrimidinesulfonamide (compound R-018); 6-(3,4-dihydro-2(1H)-isoquinolinyl)-N,N-diisopropyl-3-pyrimidinesulfonamide (compound R-021); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinoline (compound R-022); 2-(3,4-dihydro-1H-isoquinolin-2-yl)-4-methyl-pyrimidine-5-carboxylate ethyl (compound R-025); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-6-ol (compound R-093); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-094); 2-(5-nitro-2-pyridinyl)-2,3-dihydro-1H-isoindol-5-ol (compound R-096); N-[6-(6,7-dihydrothieno[3,2-c]-5(4H)-pyridinyl)-3-pyridinyl]-2-(methylsulfonyl)acetamide (compound R-097); 2-(3-chloro-5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol Compound R-098); 2-(2-chloro-5-nitro-4-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-099); 6-(1,2,3,4-tetrahydro-2-isoquinolyl)-1H,3H-furo[3,4-c]pyridin-3-one (compound R-102); 6-fluoro-2-(5-nitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline (compound R-104); [6-(1,2,3,4-tetrahydroisoquinolin-2-yl)pyridin-3-yl]methanamide (compound K-068); 2-[4-methyl-6-(trifluoromethyl)pyridin-2-yl]-1,2,3,4-tetrahydroisoquinoline (compound K-076); or 1-[4-methyl-2-(1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidin-5-yl]ethan-1-one (compound K-080); or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof. (Embodiment 6) 6. The insecticide according to any one of embodiments 1 to 5, for controlling mosquitoes. (Embodiment 7) 10. An agrochemical composition comprising a compound of formula (I) or (II) or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof, as defined in any of embodiments 1 to 5, and one or more agriculturally acceptable carriers. (Embodiment 8) 8. The agrochemical composition of embodiment 7 for controlling mosquitoes. (Embodiment 9) Formula (Ia): [ka] [In the formula, n is 0 or 1, When n is 0, R 1 is hydroxy and R 2 is hydrogen, When n is 1, R 1 is hydrogen and R 2 is hydrogen or hydroxy, A is a group represented by formula (Aa-1), (Aa-2) or (Aa-3): [ka] is a monovalent group represented by * indicates the bonding position to the nitrogen atom, R A1 is hydrogen or a halogen (fluorine, chlorine, bromine or iodine), R A2 is a halogen (fluorine, chlorine, bromine or iodine), However, when A is a monovalent group represented by formula (Aa-1) or (Aa-2), R 1 , R 2 , R A1 and R A2 Neither of the is hydrogen. or a salt thereof, or a solvate thereof. (Embodiment 10) The compound of embodiment 9, or a salt thereof, or a solvate thereof, wherein n is 1. (Embodiment 11) 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-6-ol (compound R-093); 2-(5-nitro-2-pyridinyl)-2,3-dihydro-1H-isoindol-5-ol (compound R-096); 2-(3-chloro-5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-098); 2-(2-chloro-5-nitro-4-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-099); 6-(1,2,3,4-tetrahydro-2-isoquinolyl)-1H,3H-furo[3,4-c]pyridin-3-one (compound R-102); or 6-fluoro-2-(5-nitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline (compound R-104); 11. The compound of embodiment 9 or 10, or a salt thereof, or a solvate thereof, wherein: [Effects of the Invention]

[0012] According to the present invention, it is possible to provide a novel insecticide having specific growth inhibitory activity. [Brief explanation of the drawings]

[0013] [Figure 1] To determine the binding mode between Drosophila melanogaster Nobo (DmNobo) and compound R-022, we obtained a co-crystal structure of DmNobo with GSH and compound R-022 (DmNobo-GSH-R22) and performed X-ray crystallography. Figure 1 shows the results. In the figure, A is the electron density map omitting the overall structure of DmNobo and the ligands (GSH and compound R-022) bound to it, and B shows the structure of DmNobo in complex with compound R-022 relative to the A chain. [Figure 2] To determine the binding mode between Aedes aegypti Nobo (AeNobo) and compound R-022, we obtained a co-crystal structure of AeNobo with GSH and compound R-022 (AeNobo-GSH-R22) and performed X-ray crystallography. Figure 1 shows the results. In the figure, A represents the overall structure of AeNobo, B represents the biological unit of AeNobo, C represents the electron density map omitting GSH and compound R-022 in the AeNobo crystal, and D represents the structure of AeNobo complexed with compound R-022 relative to the A chain. [Figure 3] The results of FMO analysis of the DmNobo-GSH-R22 cocrystal complex are shown. In the figure, A is the result of FMO analysis of the DmNobo-GSH-R22 complex, and B is the result of FMO analysis of the AeNobo-GSH-R22 complex. The horizontal axis represents the amino acid residues of the enzyme protein or GSH, and the vertical axis represents the interaction energy (kcal / mol) of the energy component partitioning (PIEDA). [Figure 4]The results of examining the developmental stages of Culex mosquito larvae 24 hours after treatment with the test compound are shown. In the figure, A is a photograph of individuals from the untreated control group and individuals from the group treated with 1 ppm of compound R-022. The scale bar represents 1 mm. B is a graph showing the head diameters of individuals from the untreated control group and individuals from the group treated with 1 ppm of compound R-022. The vertical axis represents the head diameter (mm) of individuals from each group. ** indicates a significant difference from the control group in Student's t-test (**: p<0.01). n=79 (control group), n=56 (compound R-022-treated group). Error bars indicate standard deviation. [Figure 5] The results of RT-qPCR analysis of the expression levels of downstream genes involved in ecdysteroid biosynthesis in Culex mosquito larvae treated with compound R-022 are shown. The vertical axis represents the relative expression level of the E74B gene, normalized to the expression level of rp49 mRNA. * and ** indicate significant differences compared to the control group in Student's t-test (*: p<0.05, **: p<0.01). Error bars indicate standard deviation. DETAILED DESCRIPTION OF THE INVENTION

[0014] Preferred embodiments of the present invention will now be described in detail.

[0015] 1. Insecticides As used herein, "alkyl" refers to a straight-chain or branched-chain saturated aliphatic hydrocarbon group containing the specified number of carbon atoms. For example, "C1-C9 alkyl" refers to a straight-chain or branched-chain saturated aliphatic hydrocarbon group containing at least 1 and at most 9 carbon atoms. Suitable alkyls include, but are not limited to, straight-chain or branched-chain C1-C9 alkyls, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, and n-pentyl, and particularly straight-chain or branched-chain C1-C5 alkyls.

[0016] As used herein, "alkenyl" refers to a group in which one or more C-C single bonds of the alkyl are replaced with double bonds. Suitable alkenyl includes, but is not limited to, straight-chain or branched C2-C9 alkenyl such as vinyl, 1-propenyl, allyl, 1-methylethenyl (isopropenyl), 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, and 1-pentenyl, in particular straight-chain or branched C2-C5 alkenyl.

[0017] As used herein, "alkynyl" refers to a group in which one or more C-C single bonds of the alkyl are replaced with a triple bond. Suitable alkynyl includes, but is not limited to, straight-chain or branched-chain C2 to C9 alkynyl such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, and 1-pentynyl, in particular straight-chain or branched-chain C2 to C5 alkynyl.

[0018] As used herein, "cycloalkyl" refers to an alicyclic alkyl containing a specified number of carbon atoms. For example, "C3-C6 cycloalkyl" refers to a cyclic hydrocarbon group containing at least 3 and at most 6 carbon atoms. Suitable cycloalkyls include, but are not limited to, C3-C6 cycloalkyls such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0019] As used herein, "cycloalkenyl" refers to a group in which one or more C-C single bonds of the cycloalkyl are replaced with double bonds. Suitable cycloalkenyls include, but are not limited to, C4-C6 cycloalkenyls such as cyclobutenyl, cyclopentenyl, and cyclohexenyl.

[0020] As used herein, "cycloalkynyl" refers to a group in which one or more C-C single bonds of the cycloalkyl are replaced with a triple bond. Suitable cycloalkynyl groups include, but are not limited to, C4-C6 cycloalkynyl groups such as cyclobutynyl, cyclopentynyl, and cyclohexynyl.

[0021] As used herein, "heterocycloalkyl" refers to a group in which one or more carbon atoms of the cycloalkyl, cycloalkenyl, or cycloalkynyl group are each independently substituted with one or more heteroatoms selected from nitrogen (N), sulfur (S), and oxygen (O). In this case, substitution by N or S includes substitution by N-oxide, or oxide or dioxide of S, respectively. Suitable heterocycloalkyl groups include, but are not limited to, 3- to 6-membered heterocycloalkyl groups such as pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, and piperazinyl.

[0022] As used herein, "cycloalkylalkyl" refers to a group in which one hydrogen atom of the alkyl, alkenyl, or alkynyl is substituted with the cycloalkyl, cycloalkenyl, or cycloalkynyl. Suitable cycloalkylalkyls include, but are not limited to, C3-C6 cycloalkyl-C1-C5 alkyl such as cyclohexylmethyl and cyclohexenylmethyl.

[0023] As used herein, "heterocycloalkylalkyl" refers to a group in which one hydrogen atom of the alkyl, alkenyl, or alkynyl is substituted with the heterocycloalkyl. Suitable heterocycloalkylalkyls include, but are not limited to, 3- to 6-membered heterocycloalkyl-C1-C5 alkyls.

[0024] As used herein, "alkoxy" refers to a group in which the hydrogen atom of a hydroxyl group is substituted with the alkyl, alkenyl, or alkynyl group described above. Suitable alkoxy includes, but is not limited to, C1 to C9 alkoxy such as methoxy, ethoxy, propoxy, butoxy, and pentoxy, and particularly C1 to C5 alkoxy.

[0025] As used herein, "cycloalkoxy" refers to a group in which the hydrogen atom of a hydroxyl group is substituted with the above-mentioned cycloalkyl, cycloalkenyl, or cycloalkynyl. Suitable cycloalkoxy groups include, but are not limited to, C3 to C6 cycloalkoxy groups such as cyclopropoxy, cyclobutoxy, and cyclopentoxy.

[0026] As used herein, "heterocycloalkoxy" refers to a group in which the hydrogen atom of a hydroxyl group is substituted with the heterocycloalkyl group described above. Suitable cycloalkoxy groups include, but are not limited to, 3- to 6-membered heterocycloalkoxy groups.

[0027] As used herein, "aryl" refers to an aromatic ring group. Suitable aryls include, but are not limited to, C6-C8 alkyl groups such as phenyl, biphenyl, terphenyl, naphthyl, and anthracenyl. 18 Mention may be made of aryl.

[0028] As used herein, "arylalkyl" refers to a group in which one hydrogen atom of the alkyl, alkenyl, or alkynyl is substituted with the aryl. Suitable arylalkyls include, but are not limited to, C6-C aryls such as benzyl, 1-phenethyl, 2-phenethyl, biphenylmethyl, terphenylmethyl, and styryl. 15 Examples include aryl-C1-C5 alkyl.

[0029] As used herein, "heteroaryl" refers to an aryl group in which one or more carbon atoms are substituted with one or more heteroatoms each independently selected from N, S, and O. In this case, substitution with N or S includes substitution with N-oxide or S oxide or dioxide, respectively. Suitable heteroaryl groups include, but are not limited to, 5- to 15-membered heteroaryl groups such as furanyl, thienyl (thiopheneyl), pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, quinolinyl, isoquinolinyl, and indolyl.

[0030] As used herein, "heteroarylalkyl" refers to a group in which one hydrogen atom of the alkyl, alkenyl, or alkynyl is substituted with the heteroaryl. Suitable heteroarylalkyl includes, but is not limited to, 5-15 membered heteroaryl-C1-C5 alkyl such as pyridylmethyl.

[0031] In the present specification, "aryloxy" refers to a group in which the hydrogen atom of hydroxy is substituted with the aryl. Suitable aryloxy includes, but is not limited to, C6-C aryloxy such as phenoxy, biphenyloxy, naphthyloxy, and anthryloxy (anthracenyloxy). 15 Mention may be made of aryloxy.

[0032] As used herein, "arylalkyloxy" refers to a group in which the hydrogen atom of hydroxy is substituted with the arylalkyl. Suitable arylalkyloxy includes, but is not limited to, C6-C arylalkyloxy such as benzyloxy, 1-phenethyloxy, 2-phenethyloxy, and styryloxy. 15 Examples include aryl-C1-C5 alkyloxy.

[0033] As used herein, "heteroaryloxy" refers to a group in which the hydrogen atom of a hydroxyl group is substituted with the heteroaryl group. Suitable heteroaryloxy groups include, but are not limited to, 5- to 15-membered heteroaryloxy groups such as furanyloxy, thienyloxy (thiophenyloxy), pyrrolyloxy, imidazolyloxy, pyrazolyloxy, triazolyloxy, tetrazolyloxy, thiazolyloxy, oxazolyloxy, isoxazolyloxy, oxadiazolyloxy, thiadiazolyloxy, isothiazolyloxy, pyridyloxy, pyridazinyloxy, pyrazinyloxy, pyrimidinyloxy, quinolinyloxy, isoquinolinyloxy, and indolyloxy.

[0034] As used herein, "heteroarylalkyloxy" refers to a group in which the hydrogen atom of a hydroxyl group is substituted with the heteroarylalkyl group defined above. Suitable heteroarylalkyloxy groups include, but are not limited to, 5- to 15-membered heteroaryl-C1-C5 alkyloxy groups.

[0035] In this specification, "acyl" refers to a group in which a monovalent group selected from the groups described above is linked to a carbonyl. Suitable acyl groups include, but are not limited to, C1 to C5 aliphatic acyl groups such as formyl, acetyl, and propionyl, and C7 to C6 aliphatic acyl groups such as benzoyl. 20 C1-C including aromatic acyls 20 Acyl can be mentioned.

[0036] Each of the above-described groups can be independently unsubstituted or further substituted with one or more of the above-described monovalent groups.

[0037] As used herein, "halogen" or "halo" means fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0038] One aspect of the present invention is a compound represented by formula (I) or (II): [ka] or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof, as an active ingredient.

[0039] The present inventors conducted high-throughput screening of compounds that have inhibitory activity against Nobo, a GST conserved only in Diptera and Lepidoptera, among enzymes involved in the biosynthesis of ecdysone, a steroid hormone that controls insect molting and / or metamorphosis, and found a compound with high inhibitory activity against Nobo from a library of small molecule compounds. Therefore, an insecticide of this embodiment containing the compound as an active ingredient can exhibit high insecticidal activity against insects, for example, insects belonging to the orders Diptera or Lepidoptera.

[0040] In formula (I) or (II), n is 0 or 1. When n is 0, the compound represented by formula (I) has a dihydroindole ring, and the compound represented by formula (II) has a thieno[2,3-c]pyrrole ring. When n is 1, the compound represented by formula (I) has a tetrahydroisoquinoline ring, and the compound represented by formula (II) has a dihydrothieno[3,2-c]pyridine ring. n is preferably 1. When n is a number exemplified above, the insecticide of this embodiment containing the compound as an active ingredient can exhibit high insecticidal activity.

[0041] In formula (I) or (II), R 1 and R 2 are, independently of one another, hydrogen, halogen (fluorine, chlorine, bromine or iodine), or hydroxy. R 1 and R 2 are preferably, independently of each other, hydrogen or hydroxy; More preferably, one is hydrogen and the other is hydrogen or hydroxy; When n is 0, R 1 is hydroxy and R 2 is hydrogen and n is 1, R 1is hydrogen and R 2 More preferably, R is hydrogen or hydroxy. 1 and R 2 When is a group exemplified above, the insecticide of this embodiment containing the compound as an active ingredient can exhibit high insecticidal activity.

[0042] In formula (I) or (II), A is a group represented by formula (A-1), (A-2) or (A-3): [ka] It is a monovalent group represented by the formula: A is preferably a monovalent group represented by formula (A-1): When A is one of the groups exemplified above, the insecticide of this embodiment containing the compound as an active ingredient can exhibit high insecticidal activity.

[0043] In formula (A-1), (A-2) or (A-3), * indicates the bonding position to the nitrogen atom.

[0044] In the formula (A-1), (A-2) or (A-3), X is a carbon atom or a nitrogen atom. X is preferably a carbon atom. When X is one of the atoms exemplified above, the insecticide of this embodiment containing the compound as an active ingredient can exhibit high insecticidal activity.

[0045] In formula (A-1), (A-2) or (A-3), R A1 , R A2 and R A4are, independently of each other, hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryl The alkyl group is selected from the group consisting of aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, and substituted or unsubstituted acylamino. R A1 , R A2 and R A4are each independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C2-C9 alkenyl, substituted or unsubstituted C2-C9 alkynyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C4-C6 cycloalkenyl, substituted or unsubstituted C4-C6 cycloalkynyl, substituted or unsubstituted 3- to 6-membered heterocycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl-C1-C5 alkyl, substituted or unsubstituted 3- to 6-membered heterocycloalkyl-C1-C5 alkyl, substituted or unsubstituted C6-C 18 Aryl, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C9 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted C6-C 15 Aryl-C2-C5 alkenyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted C6-C 15 Arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted C6-C 15 Arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted C6-C 15Arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 Preferably it is acylamino; Independently from each other, hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 More preferably, it is acylamino; More preferably, they are independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), or substituted or unsubstituted C1-C9 alkyl; Even more preferably, R are independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), or methyl. A1 , R A2 and R A4 When is a group exemplified above, the insecticide of this embodiment containing the compound as an active ingredient can exhibit high insecticidal activity.

[0046] In formula (A-1), (A-2) or (A-3), R A3is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, oxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted acylamino. R A3is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C3 to C6 cycloalkyl, substituted or unsubstituted C4 to C6 cycloalkenyl, substituted or unsubstituted C4 to C6 cycloalkynyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted C3 to C6 cycloalkyl-C1 to C5 alkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl-C1 to C5 alkyl, substituted or unsubstituted C6 to C 18 Aryl, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C9 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted C6-C 15 Aryl-C2-C5 alkenyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted C6-C 15 Arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted C6-C 15 Arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted C6-C 15Arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 Preferably it is acylamino; Hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 More preferably, it is acylamino; Hydrogen, nitro, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C1-C 20 More preferably, it is acylamino; Even more preferably hydrogen, nitro, trifluoromethyl, aminomethyl, ethoxycarbonyl, acetyl, N,N-diethylaminosulfonyl, N,N-diisopropylaminosulfonyl, or methylsulfanylacetylamino; Nitro is particularly preferred. A3 When is a group exemplified above, the insecticide of this embodiment containing the compound as an active ingredient can exhibit high insecticidal activity.

[0047] In formula (A-1), (A-2) or (A-3), R A5is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, oxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted acylamino. R A5is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C3 to C6 cycloalkyl, substituted or unsubstituted C4 to C6 cycloalkenyl, substituted or unsubstituted C4 to C6 cycloalkynyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted C3 to C6 cycloalkyl-C1 to C5 alkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl-C1 to C5 alkyl, substituted or unsubstituted C6 to C 18 Aryl, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C9 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted C6-C 15 Aryl-C2-C5 alkenyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted C6-C 15 Arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted C6-C 15 Arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted C6-C 15Arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 Preferably it is acylamino; Hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 More preferably, it is acylamino; Hydrogen, nitro, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C1-C 20 More preferably, it is acylamino; Even more preferably hydrogen or nitro; Nitro is particularly preferred. A5 When is a group exemplified above, the insecticide of this embodiment containing the compound as an active ingredient can exhibit high insecticidal activity.

[0048] In formulae (I), (II), (A-1), (A-2) and (A-3), when the above groups are substituted, the substituents are each independently halogen (fluorine, chlorine, bromine or iodine), cyano, nitro, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted heteroaryl, and at least one monovalent group selected from the group consisting of substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted acyloxy, substituted or unsubstituted alkylsulfanyl, and substituted or unsubstituted amino; and at least one monovalent group selected from the group consisting of halogen (fluorine, chlorine, bromine, or iodine), cyano, nitro, hydroxy, substituted or unsubstituted C1 to C5 alkylsulfanyl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted acyloxy, substituted or unsubstituted alkylsulfanyl, and substituted or unsubstituted amino. Alkyl, substituted or unsubstituted C2-C5 alkenyl, substituted or unsubstituted C2-C5 alkynyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C4-C6 cycloalkenyl, substituted or unsubstituted C4-C6 cycloalkynyl, substituted or unsubstituted 3- to 6-membered heterocycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl-C1-C5 alkyl, substituted or unsubstituted 3- to 6-membered heterocycloalkyl-C1-C5 alkyl, substituted or unsubstituted C6-C 15 Aryl, substituted or unsubstituted C6-C 15Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C6 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C 20 It is more preferably at least one monovalent group selected from the group consisting of acyloxy, substituted or unsubstituted C1-C9 alkylsulfanyl, and substituted or unsubstituted amino; and even more preferably at least one monovalent group selected from the group consisting of halogen (fluorine, chlorine, bromine, or iodine), unsubstituted C1-C5 alkyl, unsubstituted C1-C9 alkylsulfanyl, and unsubstituted amino. When the monovalent group is substituted, the substituent may be further selected from the monovalent groups described above.

[0049] Preferably, the compound of formula (I) or (II) is n is 0 or 1, R 1 and R 2 are, independently of one another, hydrogen, halogen (fluorine, chlorine, bromine or iodine), or hydroxy, A is a monovalent group represented by formula (A-1), (A-2), or (A-3), * is the bonding position with the nitrogen atom, X is a carbon atom or a nitrogen atom, R A1 , R A2 and R A4are each independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C3 to C6 cycloalkyl, substituted or unsubstituted C4 to C6 cycloalkenyl, substituted or unsubstituted C4 to C6 cycloalkynyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted C3 to C6 cycloalkyl-C1 to C5 alkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl-C1 to C5 alkyl, substituted or unsubstituted C6 to C 18 Aryl, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C9 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted C6-C 15 Aryl-C2-C5 alkenyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted C6-C 15 Arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted C6-C 15 Arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted C6-C 15Arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 is acylamino, R A3 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C3 to C6 cycloalkyl, substituted or unsubstituted C4 to C6 cycloalkenyl, substituted or unsubstituted C4 to C6 cycloalkynyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted C3 to C6 cycloalkyl-C1 to C5 alkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl-C1 to C5 alkyl, substituted or unsubstituted C6 to C 18 Aryl, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C9 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted C6-C 15 Aryl-C2-C5 alkenyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted C6-C 15 Arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted C6-C 15Arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted C6-C 15 Arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 is acylamino, R A5 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C3 to C6 cycloalkyl, substituted or unsubstituted C4 to C6 cycloalkenyl, substituted or unsubstituted C4 to C6 cycloalkynyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted C3 to C6 cycloalkyl-C1 to C5 alkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl-C1 to C5 alkyl, substituted or unsubstituted C6 to C 18 Aryl, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C9 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted C6-C 15 Aryl-C2-C5 alkenyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted C6-C 15Arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted C6-C 15 Arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted C6-C 15 Arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 is acylamino, When the above groups are substituted, the substituents are each independently selected from halogen (fluorine, chlorine, bromine, or iodine), cyano, nitro, hydroxy, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C2-C5 alkenyl, substituted or unsubstituted C2-C5 alkynyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C4-C6 cycloalkenyl, substituted or unsubstituted C4-C6 cycloalkynyl, substituted or unsubstituted 3- to 6-membered heterocycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl-C1-C5 alkyl, substituted or unsubstituted 3- to 6-membered heterocycloalkyl-C1-C5 alkyl, substituted or unsubstituted C6-C 15 Aryl, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C6 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C 20At least one monovalent group selected from the group consisting of acyloxy, substituted or unsubstituted C1 to C9 alkylsulfanyl, and substituted or unsubstituted amino.

[0050] More preferably, the compound represented by formula (I) or (II) is n is 0 or 1, R 1 and R 2 are, independently of each other, hydrogen or hydroxy; A is a monovalent group represented by formula (A-1), (A-2), or (A-3), * is the bonding position with the nitrogen atom, X is a carbon atom or a nitrogen atom, R A1 , R A2 and R A4 are each independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 is acylamino, R A3 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 is acylamino, R A5 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C1 to C9 alkyl, substituted or unsubstituted C2 to C9 alkenyl, substituted or unsubstituted C2 to C9 alkynyl, substituted or unsubstituted C1 to C9 alkoxy, substituted or unsubstituted C1 to C9 alkoxycarbonyl, substituted or unsubstituted C1 to C 20 Acyl, substituted or unsubstituted C1-C9 alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C1-C9 alkylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted C1-C9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C1-C 20 is acylamino, When the group is substituted, the substituent is selected from the group consisting of halogen (fluorine, chlorine, bromine, or iodine), cyano, nitro, hydroxy, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C2-C5 alkenyl, substituted or unsubstituted C2-C5 alkynyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C4-C6 cycloalkenyl, substituted or unsubstituted C4-C6 cycloalkynyl, substituted or unsubstituted 3- to 6-membered heterocycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl-C1-C5 alkyl, substituted or unsubstituted 3- to 6-membered heterocycloalkyl-C1-C5 alkyl, substituted or unsubstituted C6-C 15 Aryl, substituted or unsubstituted C6-C 15Aryl-C1-C5 alkyl, substituted or unsubstituted 5-15 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C6 cycloalkoxy, substituted or unsubstituted 3-6 membered heterocycloalkoxy, substituted or unsubstituted C6-C 15 Aryloxy, substituted or unsubstituted C6-C 15 Aryl-C1-C5 alkyloxy, substituted or unsubstituted 5-15 membered heteroaryloxy, substituted or unsubstituted 5-15 membered heteroaryl-C1-C5 alkyloxy, substituted or unsubstituted C1-C6 alkoxycarbonyl, substituted or unsubstituted C3-C6 cycloalkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted C1-C 20 At least one monovalent group selected from the group consisting of acyloxy, substituted or unsubstituted C1 to C9 alkylsulfanyl, and substituted or unsubstituted amino.

[0051] More preferably, the compound represented by formula (I) or (II) is n is 0 or 1, R 1 and R 2 are, independently of each other, hydrogen or hydroxy; A is a monovalent group represented by formula (A-1), (A-2), or (A-3), * is the bonding position with the nitrogen atom, X is a carbon atom or a nitrogen atom, R A1 , R A2 and R A4 are each independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), or substituted or unsubstituted C1-C9 alkyl; R A3 is hydrogen, nitro, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C1-C 20Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C1-C 20 is acylamino, R A5 is hydrogen, nitro, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C1-C 20 is acylamino, When the group is substituted, the substituent is at least one monovalent group selected from the group consisting of halogen (fluorine, chlorine, bromine, or iodine), unsubstituted C1-C5 alkyl, unsubstituted C1-C9 alkylsulfanyl, and unsubstituted amino.

[0052] Even more preferably, the compound of formula (I) or (II) is n is 0 or 1, R 1 and R 2 one is hydrogen and the other is hydrogen or hydroxy; A is a monovalent group represented by formula (A-1), (A-2), or (A-3), * is the bonding position with the nitrogen atom, X is a carbon atom or a nitrogen atom, R A1 , R A2 and R A4 are, independently of one another, hydrogen, halogen (fluorine, chlorine, bromine or iodine), or methyl, R A3 is hydrogen, nitro, trifluoromethyl, aminomethyl, ethoxycarbonyl, acetyl, N,N-diethylaminosulfonyl, N,N-diisopropylaminosulfonyl, or methylsulfanylacetylamino; R A5 is hydrogen or nitro.

[0053] In one embodiment, the compound of formula (I) or (II) is Conditions (i) and (ii): Condition (i) n is 0, A is a monovalent group represented by formula (A-1), X is a carbon atom, R A1 , R A2 and R A4 are both hydrogen, and R A3 is nitro, or Condition (ii) n is 1, R A1 , R A2 and R A4 are each independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), or substituted or unsubstituted C1-C9 alkyl; R A3 is hydrogen, nitro, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C1-C 20 is acylamino, R A5 is hydrogen, nitro, substituted or unsubstituted C1-C9 alkyl, substituted or unsubstituted C1-C9 alkoxycarbonyl, substituted or unsubstituted C1-C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C1-C 20 is acylamino, When the group is substituted, the substituent is at least one monovalent group selected from the group consisting of halogen (fluorine, chlorine, bromine, or iodine), unsubstituted C1-C5 alkyl, unsubstituted C1-C9 alkylsulfanyl, and unsubstituted amino. It is preferable that any one of the above conditions is satisfied.

[0054] Particularly preferred compounds of formula (I) or (II) are: 2-[5-(trifluoromethyl)-2-pyridinyl]-1,2,3,4-tetrahydroisoquinoline (compound R-010); 6-(3,4-dihydro-2(1H)-isoquinolinyl)-N,N-diethyl-3-pyrimidinesulfonamide (compound R-018); 6-(3,4-dihydro-2(1H)-isoquinolinyl)-N,N-diisopropyl-3-pyrimidinesulfonamide (compound R-021); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinoline (compound R-022); 2-(3,4-dihydro-1H-isoquinolin-2-yl)-4-methyl-pyrimidine-5-carboxylate ethyl (compound R-025); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-6-ol (compound R-093); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-094); 2-(5-nitro-2-pyridinyl)-2,3-dihydro-1H-isoindol-5-ol (compound R-096); N-[6-(6,7-dihydrothieno[3,2-c]-5(4H)-pyridinyl)-3-pyridinyl]-2-(methylsulfonyl)acetamide (compound R-097); 2-(3-chloro-5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-098); 2-(2-chloro-5-nitro-4-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-099); 6-(1,2,3,4-tetrahydro-2-isoquinolyl)-1H,3H-furo[3,4-c]pyridin-3-one (compound R-102); 6-fluoro-2-(5-nitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline (compound R-104); [6-(1,2,3,4-tetrahydroisoquinolin-2-yl)pyridin-3-yl]methanamide (compound K-068); 2-[4-methyl-6-(trifluoromethyl)pyridin-2-yl]-1,2,3,4-tetrahydroisoquinoline (compound K-076); and 1-[4-methyl-2-(1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidin-5-yl]ethan-1-one (compound K-080); When the compound represented by formula (I) or (II) of this embodiment is any of the above compounds, the insecticide of this embodiment containing the compound as an active ingredient can exhibit particularly high insecticidal activity.

[0055] The compounds represented by formulas (I) and (II) according to one embodiment of the present invention, and the compounds represented by formula (Ia) described below, include not only the compounds themselves described above or below, but also salts thereof. Preferred salts of the above-mentioned or below-mentioned compounds include, but are not limited to, salts with cations such as sodium ion, potassium ion, calcium ion, magnesium ion, or substituted or unsubstituted ammonium ion, or salts with anions of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, carbonic acid, or phosphoric acid, or organic acids such as formic acid, acetic acid, maleic acid, fumaric acid, benzoic acid, ascorbic acid, succinic acid, bismethylenesalicylic acid, methanesulfonic acid, ethanedisulfonic acid, propionic acid, tartaric acid, salicylic acid, citric acid, gluconic acid, aspartic acid, stearic acid, palmitic acid, itaconic acid, glycolic acid, p-aminobenzoic acid, glutamic acid, benzenesulfonic acid, cyclohexylsulfamic acid, methanesulfonic acid, ethanesulfonic acid, isethionic acid, p-toluenesulfonic acid, or naphthalenesulfonic acid. Even when the compounds represented by formulas (I) and (II), and formula (Ia) are in the form of the salts, the insecticides of this embodiment containing the compounds as active ingredients can exhibit high insecticidal activity.

[0056] The compounds represented by formulas (I) and (II) of one embodiment of the present invention, as well as the compound represented by formula (Ia) described below, encompass not only the compounds themselves but also solvates of the compounds or salts thereof. Solvents that can form solvates with the compounds or salts thereof include, but are not limited to, lower alcohols (e.g., alcohols having 1 to 6 carbon atoms such as methanol, ethanol, or 2-propanol (isopropyl alcohol)), higher alcohols (e.g., alcohols having 7 or more carbon atoms such as 1-heptanol or 1-octanol), organic solvents such as dimethyl sulfoxide (DMSO), acetic acid, ethanolamine, or ethyl acetate, or water. Even when the compounds represented by formulas (I) and (II), and formula (Ia) or salts thereof are in the form of solvates with the solvents, insecticides of this embodiment containing the compounds as active ingredients can exhibit high insecticidal activity.

[0057] The compounds represented by formulas (I) and (II) according to one embodiment of the present invention, as well as the compound represented by formula (Ia) described below, encompass not only the compounds themselves but also their protected or deprotected forms. As used herein, the term "protected form" refers to a form in which a protecting group has been introduced into one or more functional groups (e.g., a hydroxy group, a carboxylic acid group, or an amino group), and the term "deprotected form" refers to a form in which a protecting group previously introduced into one or more functional groups (e.g., a hydroxy group, a carboxylic acid group, or an amino group) has been removed. In this specification, the protected form of a compound represented by each formula may be referred to as a protected derivative of the compound represented by each formula, and the deprotected form of a compound represented by each formula may be referred to as a deprotected derivative of the compound represented by each formula. Furthermore, as used herein, the term "protecting group" refers to a group introduced into a specific functional group to prevent an undesired reaction from proceeding, which is quantitatively removed under specific reaction conditions and is substantially stable, i.e., inert, under other reaction conditions. Protecting groups that can form the protected form of the compound include, but are not limited to, silyl (e.g., t-butyldimethylsilyl (TBS), triisopropylsilyl (TIPS), or tert-butyldiphenylsilyl (TBDPS)) or alkoxy (e.g., tert-butyloxy (tBu), methoxymethoxy (MOM), or methoxy (Me)) for protecting a hydroxy group; alkyl esters (e.g., methyl, ethyl, or isopropyl esters), arylalkyl esters (e.g., benzyl esters), or amides (e.g., amides with oxazolidinones) for protecting a carboxylic acid group; and t-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), 2-bromobenzyloxycarbonyl (BrZ), or 9-fluorenylmethoxycarbonyl (Fmoc) for protecting an amino group. Protection and deprotection using the above protecting groups can be carried out appropriately by those skilled in the art based on known reaction conditions. Even when the compounds represented by formulae (I) and (II) and formula (Ia) are protected by the above-mentioned protecting groups, they may still exhibit insecticidal activity.

[0058] When the compounds represented by formulas (I) and (II) according to one embodiment of the present invention and the compounds represented by formula (Ia) described below have one or more tautomers, the above-mentioned or below-mentioned compounds also encompass the individual tautomeric forms of the compounds.

[0059] Furthermore, when the compounds represented by formulas (I) and (II) according to one embodiment of the present invention and the compounds represented by formula (Ia) described below have one or more stereocenters (chiral centers), the compounds described above or below also encompass the individual enantiomers and diastereomers of the compounds, as well as mixtures thereof such as racemates.

[0060] By having the above characteristics, the insecticide of this embodiment containing the compound represented by formula (I) or (II) of one embodiment of the present invention as an active ingredient can exhibit high insecticidal activity.

[0061] <2. New compounds> The compound represented by formula (I) or (II), which is an active ingredient of the insecticide of one embodiment of the present invention, includes a novel compound. Therefore, another embodiment of the present invention is a novel compound represented by formula (Ia): [ka] or a salt thereof, or a solvate thereof.

[0062] In formula (Ia), n is 0 or 1. When n is 0, the compound represented by formula (Ia) has a dihydroindole ring. When n is 1, the compound represented by formula (Ia) has a tetrahydroisoquinoline ring. n is preferably 1. When n is a number exemplified above, the compound represented by formula (Ia) of this embodiment can exhibit high insecticidal activity.

[0063] In formula (Ia), when n is 0, R 1 is hydroxy and R 2 is hydrogen, and when n is 1, R 1 is hydrogen and R 2is hydrogen or hydroxy. 1 and R 2 When is a group exemplified above, the compound represented by formula (Ia) of this embodiment can exhibit high insecticidal activity.

[0064] In formula (Ia), A is a group represented by formula (Aa-1), (Aa-2) or (Aa-3): [ka] It is a monovalent group represented by the formula: A is preferably a monovalent group represented by formula (Aa-1). When A is a group exemplified above, the compound represented by formula (Ia) of this embodiment can exhibit high insecticidal activity.

[0065] In formula (Aa-1), (Aa-2) or (Aa-3), * indicates the bonding position to the nitrogen atom.

[0066] In formula (Aa-1), (Aa-2) or (Aa-3), R A1 is hydrogen or a halogen (fluorine, chlorine, bromine or iodine). A1 is preferably hydrogen, fluorine or chlorine. A1 When is a group exemplified above, the compound represented by formula (Ia) of this embodiment can exhibit high insecticidal activity.

[0067] In formula (Aa-1), (Aa-2) or (Aa-3), R A2 R is a halogen (fluorine, chlorine, bromine or iodine). A2 is preferably chlorine. A2 When is a group exemplified above, the compound represented by formula (Ia) of this embodiment can exhibit high insecticidal activity.

[0068] In formula (Ia), when A is a monovalent group represented by formula (Aa-1) or (Aa-2), R 1 , R 2 , R A1 and R A2Neither of these can be hydrogen.

[0069] Preferably, the compound of formula (Ia) is n is 0 or 1, When n is 0, R 1 is hydroxy and R 2 is hydrogen, When n is 1, R 1 is hydrogen and R 2 is hydrogen or hydroxy, A is a monovalent group represented by formula (Aa-1), (Aa-2), or (Aa-3), * indicates the bonding position to the nitrogen atom, R A1 is hydrogen, fluorine, or chlorine, R A2 is chlorine, However, when A is a monovalent group represented by formula (Aa-1) or (Aa-2), R 1 , R 2 , R A1 and R A2 Neither of these can be hydrogen.

[0070] Particularly preferred compounds of formula (Ia) are: 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-6-ol (compound R-093); 2-(5-nitro-2-pyridinyl)-2,3-dihydro-1H-isoindol-5-ol (compound R-096); 2-(3-chloro-5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-098); 2-(2-chloro-5-nitro-4-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-099); 6-(1,2,3,4-tetrahydro-2-isoquinolyl)-1H,3H-furo[3,4-c]pyridin-3-one (compound R-102); and 6-fluoro-2-(5-nitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline (compound R-104); When the compound represented by formula (Ia) of this embodiment is one of the above compounds, the compound can exhibit particularly high insecticidal activity.

[0071] 3. Method for producing compounds Another aspect of the present invention relates to a method for producing a compound represented by formula (I) or (II), which is an active ingredient of an insecticide according to an aspect of the present invention, or a compound represented by formula (Ia) according to an aspect of the present invention. The method of this aspect includes a ring bonding step. Each step will be described in detail below.

[0072] [3-1. Ring bonding process] This step is carried out by reacting a compound represented by formula (XI) or (X-II): [ka] or a protected derivative thereof, or a salt or solvate thereof, with a compound represented by formula (XA-1), (XA-2) or (XA-3): [ka] or a protected derivative thereof, or a salt or solvate thereof, to obtain a compound represented by formula (I) or (II) or a salt thereof, or a solvate thereof; or Formula (X-Ia): [ka] or a protected derivative thereof, or a salt or solvate thereof, and a compound represented by formula (X-Aa-1), (X-Aa-2) or (X-Aa-3): [ka] or a protected derivative thereof, or a salt or solvate thereof, to obtain a compound represented by formula (Ia) or a salt thereof, or a solvate thereof.

[0073] In formulae (XI), (X-II), (XA-1), (XA-2), (XA-3), (X-Ia), (X-Aa-1), (X-Aa-2) and (X-Aa-3), n, R 1 , R 2 , X, R A1 , R A2 , R A3 , R A4 and R A5 has the same meaning as above.

[0074] In the formulae (XA-1), (XA-2), (XA-3), (X-Aa-1), (X-Aa-2) and (X-Aa-3), Hal is a halogen (fluorine, chlorine, bromine or iodine). Hal is preferably chlorine.

[0075] In this step, the conditions for the reaction between a compound represented by formula (XI) or (X-II) or a protected derivative thereof, or a salt or solvate thereof, and a compound represented by formula (XA-1), (XA-2), or (XA-3) or a protected derivative thereof, or a salt or solvate thereof, or between a compound represented by formula (X-Ia) or a protected derivative thereof, or a salt or solvate thereof, and a compound represented by formula (X-Aa-1), (X-Aa-2), or (X-Aa-3) or a protected derivative thereof, or a salt or solvate thereof, can be appropriately determined by one skilled in the art based on the conditions for known cross-coupling reactions between aromatic halides and amines. The reaction in this step can be carried out, for example, in the presence of an organic amine (e.g., triethylamine) in a solvent such as a lower alcohol (e.g., an alcohol having 1 to 6 carbon atoms, such as methanol, ethanol, or 2-propanol (isopropyl alcohol)).

[0076] By carrying out the method of this embodiment under the above conditions, it is possible to provide a compound represented by formula (I) or (II), or a compound represented by formula (Ia), which can be an active ingredient of an insecticide, in large quantities with high purity and at low cost.

[0077] <4. Pesticides and other uses> The compounds represented by formulas (I) and (II), which are active ingredients of insecticides according to one embodiment of the present invention, have high inhibitory activity against Nobo, a GST conserved only in Diptera and Lepidoptera, among enzymes involved in the biosynthesis of ecdysone, a steroid hormone that regulates insect molting and / or metamorphosis. Therefore, another embodiment of the present invention relates to a Nobo inhibitor comprising, as an active ingredient, a compound represented by formula (I) or (II), a salt thereof, or a solvate thereof. The Nobo inhibitor of this embodiment can exhibit high inhibitory activity against Nobo in vivo or in vitro.

[0078] In each aspect of the present invention, the Nobo inhibitory activity of a compound represented by formula (I) or (II), or a compound represented by formula (Ia), can be determined, for example, by adding the compound to a Nobo protein derived from a target insect and measuring the rate of inhibition of the enzyme activity. The Nobo inhibitory activity of a compound represented by formula (I) or (II), or a compound represented by formula (Ia), can be determined, for example, by measuring the 50% inhibitory concentration (IC) of the compound against Drosophila melanogaster Nobo or Aedes aegypti Nobo. 50 ) is usually 1 μM or less, preferably 0.5 μM or less, and more preferably 0.1 μM or less.

[0079] In each aspect of the present invention, the insecticidal activity of a compound represented by formula (I) or (II), or a compound represented by formula (Ia), can be determined, for example, by adding the compound to a target insect (e.g., larvae of the insect), raising the insect for a predetermined period, and measuring the growth index (e.g., survival rate or head length of the larvae). Alternatively, the insecticidal activity can be determined by adding the compound to an ecdysone biosynthetic enzyme protein (e.g., Nobo) derived from a target insect, and measuring the rate of inhibition of the enzyme activity. The insecticidal activity of a compound represented by formula (I) or (II), or a compound represented by formula (Ia), can be determined, for example, by measuring the 50% killing concentration (LD ) against Culex mosquitoes. 50 ) is usually 5 ppm or less, preferably 2 ppm or less, and more preferably 1 ppm or less.

[0080] Ecdysone biosynthesis is a biosynthetic pathway specific to insects, and therefore the compounds represented by formulas (I) and (II) and the compound represented by formula (Ia), which specifically inhibit the ecdysone biosynthetic pathway, can exhibit high inhibitory activity specifically against insects.

[0081] In each aspect of the present invention, whether the compound represented by formula (I) or (II) or the compound represented by formula (Ia) has specific inhibitory activity against insects can be determined, for example, by adding the compound to a mammalian subject or its cultured cells, growing the subject for a predetermined period of time, and confirming that there is no substantial effect on the growth index.

[0082] In one embodiment of the present invention, the insecticide may contain, in addition to the compounds represented by formula (I) and (II) as active ingredients, one or more additional active ingredients and / or one or more agriculturally acceptable carriers. Therefore, another embodiment of the present invention relates to an agricultural chemical composition comprising a compound represented by formula (I) or (II) or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof, and one or more agriculturally acceptable carriers. The agricultural chemical composition of this embodiment may further contain one or more agriculturally acceptable adjuvants.

[0083] Examples of the one or more additional active ingredients include pyrethroid compounds, organophosphorus compounds, organosilicon compounds, amidinohydrazone compounds, phenylpyrazole compounds, neonicotinoid compounds, and oxadiazole compounds. Alternatively, the one or more additional active ingredients may be insect growth regulators (IGRs) having a mechanism of action different from that of the compounds represented by formulas (I) and (II) and the compound represented by formula (Ia). By including one or more of the additional active ingredients exemplified above, the insecticidal activity of the agrochemical composition of this embodiment can be further improved.

[0084] The one or more agriculturally acceptable carriers may include agriculturally acceptable liquid carriers such as water, mineral oil fractions such as kerosene or diesel oil, oils of vegetable or animal origin, cyclic or aromatic hydrocarbons (e.g., paraffin, tetrahydronaphthalene, alkylated naphthalenes or derivatives thereof, or alkylated benzenes or derivatives thereof), alcohols (e.g., methanol, ethanol, propanol, butanol, or cyclohexanol), ketones (e.g., cyclohexanone), amines (e.g., N-methylpyrrolidone), or mixtures thereof.

[0085] The one or more agriculturally acceptable adjuvants may include, for example, solid carriers, inert adjuvants, surfactants (e.g., dispersants, protective colloids, emulsifiers, and wetting agents), organic or inorganic thickeners, bactericides, antifreeze agents, antifoaming agents, and colorants.

[0086] The insecticide and agricultural chemical composition of one embodiment of the present invention can be used in the formulations and application methods commonly used in the art for agricultural chemicals. Suitable formulations include, for example, emulsifiable concentrates, wettable powders, liquids, water-soluble concentrates, dusts, powders, pastes, and granules. Suitable application methods include, for example, dusting, sprinkling, spraying, dipping, and coating.

[0087] The compounds represented by formulas (I) and (II), which are active ingredients in the insecticide and agrochemical composition of one aspect of the present invention, have high insecticidal activity. Therefore, the insecticide and agrochemical composition of one aspect of the present invention can effectively control targets. Furthermore, in a specific embodiment, the compounds represented by formulas (I) and (II), which are active ingredients in the insecticide and agrochemical composition of one aspect of the present invention, have selectively high insecticidal activity against insects belonging to the Culicidae family, particularly mosquitoes. Targets are usually insects, preferably insects belonging to the Diptera order, more preferably flies, horseflies, black flies, or crane flies, and particularly preferably mosquitoes. By applying the insecticide and agrochemical composition of one aspect of the present invention to the targets exemplified above, the targets can be effectively controlled.

[0088] In each aspect of the present invention, "control" means substantially inhibiting the growth of or killing the target.

[0089] The compounds represented by formula (I) and (II), which are active ingredients of the insecticide and agricultural chemical composition of one embodiment of the present invention, have high insecticidal activity. Therefore, yet another embodiment of the present invention relates to a method for controlling a target, which comprises applying a compound represented by formula (I) or (II), or the insecticide or agricultural chemical composition of one embodiment of the present invention, to the target or an environment in which the target lives.

[0090] In the method of this embodiment, the formulation, application method, and target of the compound represented by formula (I) or (II), or the insecticide or agrochemical composition of one embodiment of the present invention, are preferably the same as the formulation, application method, and target exemplified above. By applying the method of this embodiment to the target exemplified above using the formulation and application method exemplified above, the target can be effectively controlled.

[0091] As described in detail above, the compounds represented by formulas (I) and (II), and the compound represented by formula (Ia) have high insecticidal activity. In particular, the compounds represented by formulas (I) and (II), and the compound represented by formula (Ia) have high inhibitory activity against Nobo, an enzyme related to the biosynthetic system of ecdysone, which is a steroid hormone that controls insect molting and / or metamorphosis. Further, in a specific embodiment, the compounds represented by formulas (I) and (II), and the compound represented by formula (Ia) have selectively high insecticidal activity against insects belonging to the family Muscidae, particularly Musca. Therefore, by implementing each aspect of the present invention, insects, preferably insects belonging to the order Diptera, and particularly preferably Musca can be effectively controlled.

Example

[0092] Hereinafter, the present invention will be described more specifically using examples. However, the technical scope of the present invention is not limited to these examples.

[0093] <I. Production of Compounds> [I-1. Synthesis of Compound R-093] 2-(5-Nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-6-ol (R-093)

Chemical formula

[0094] 2-Chloro-5-nitropyridine (100 mg, 0.631 mmol) and 6-hydroxy-1,2,3,4-tetrahydroisoquinoline (113 mg, 0.757 mmol) were dissolved in ethanol (6.3 mL), and further triethylamine (105 μL, 0.757 mmol) was added. After stirring at room temperature for 48 hours, the precipitated solid was collected by filtration and washed with cold ethanol to obtain R-093 as a yellow solid (142 mg, 83%).

[0095] 1H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 8.99 (d, J = 3.2 Hz, 1H), 8.26 (dd, J = 9.6, 3.2 Hz, 1H), 7.05 (d, J = 9.1 Hz, 1H), 6.91 (d, J = 9.6 Hz, 1H), 6.50-6.70 (m, 2H), 4.75 (s, 2H), 3.87 (m, 2H), 2.85 (t, J = 6.0 Hz, 2H); 13 C NMR (100 MHz, DMSO-d6) δ 159.8 (C), 156.1 (C), 146.1 (CH), 136.1 (C), 134.1 (C), 132.7 (CH), 127.4 (CH), 123.5 (C), 114.4 (CH), 113.5 (CH), 105.6 (CH), 46.0 (CH2), 42.7 (CH2), 28.1 (CH2); HRMS (EI) m / z C 14 H 13 Calculated value of N3O3: 271.0957 [M] + ; Actual value: 271.0952.

[0096] [I-2. Synthesis of Compound R-096] 2-(5-nitro-2-pyridinyl)-2,3-dihydro-1H-isoindol-5-ol (R-096) [ka]

[0097] 2-Chloro-5-nitropyridine (100 mg, 0.631 mmol) and 5-hydroxyisoindoline (102 mg, 0.755 mmol) were dissolved in ethanol (6.3 mL), and triethylamine (105 μL, 0.757 mmol) was added. After stirring at room temperature for 48 hours, the precipitated solid was collected by filtration and washed with cold ethanol to give R-096 as a yellow solid (145 mg, 89%).

[0098] 1H NMR (400 MHz, DMSO-d6) δ 9.48 (s, 1H), 9.03 (d, J = 2.8 Hz, 1H), 8.30 (dd, J = 9.2, 2.8 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 6.78 (m, 1H), 6.73 (dd, J = 8.2, 2.3 Hz, 1H), 6.68 (d, J = 9.2 Hz, 1H), 4.65-4.95 (m, 4H); 13 C NMR (100 MHz, DMSO-d6) δ 158.4 (C), 157.1 (C), 146.5 (CH), 137.6 (C), 137.4 (C), 134.5 (C), 132.5 (CH), 126.3 (C), 126.1 (C), 123.6 HRMS (EI) m / z C 13 H 11 Calculated value of N3O3: 257.0800 [M] + ; Actual value: 257.0805.

[0099] [I-3. Synthesis of Compound R-098] 2-(3-chloro-5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (R-098) [ka]

[0100] 2,3-Dichloro-5-nitropyridine (127 mg, 0.658 mmol) and 1,2,3,4-tetrahydroisoquinoline (100 μL, 0.788 mmol) were dissolved in ethanol (6.5 mL), and triethylamine (110 μL, 0.794 mmol) was added. After stirring at room temperature for 40 hours, the precipitated solid was collected by filtration and washed with cold ethanol to give R-098 as a yellow solid (164 mg, 86%).

[0101] 1 H NMR (400 MHz, DMSO-d6) δ 8.99 (d, J = 2.3 Hz, 1H), 8.48 (d, J = 2.3 Hz, 1H), 7.12-7.28 (m, 4H), 4.82 (s, 2H), 3.93 (t, J = 6.0 Hz, 2H), 3.02 (t, J = 6.0 Hz, 2H); 13 C NMR (100 MHz, DMSO-d6) δ 159.1 (C), 142.5 (CH), 136.7 (C), 134.4 (CH), 134.2 (C), 133.4 (C), 128.5 (CH), 126.5 (CH), 126.5 (CH), 126.1 (CH), 116.3 (C), 50.0 (CH2), 46.6 (CH2), 28.3 (CH2); HRMS (ESI) m / z C 14 H 12 Calculated value for ClN3O2+Na: 312.0510 [M+Na] + ; Actual value: 312.0516.

[0102] [I-4. Synthesis of Compound R-099] 2-(2-chloro-5-nitro-4-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (R-099) [ka]

[0103] 2,4-Dichloro-5-nitropyridine (127 mg, 0.658 mmol) and 1,2,3,4-tetrahydroisoquinoline (100 μL, 0.788 mmol) were dissolved in ethanol (6.5 mL), and triethylamine (110 μL, 0.794 mmol) was added. After stirring at room temperature for 40 hours, the precipitated solid was collected by filtration and washed with cold ethanol to give R-099 as a yellow solid (166 mg, 87%).

[0104] 1 H NMR (400 MHz, DMSO-d6) δ 8.66 (s, 1H), 7.35 (s, 1H), 7.10-7.30 (m, 4H), 4.43 (s, 2H), 3.40 (t, J = 5.7 Hz, 2H), 2.94 (t, J = 5.7 Hz, 2H); 13 C NMR (100 MHz, DMSO-d6) δ 153.4 (C), 149.8 (C), 148.0 (CH), 134.8 (C), 134.7 (C), 132.6 (C), 127.9 (CH), 127.0 (CH), 126.4 (CH), 126.3 (CH), 110.9 (CH), 50.1 (CH2), 47.8 (CH2), 27.7 (CH2); HRMS (ESI) m / z C 14 H 12 Calculated value for ClN3O2+Na: 312.0510 [M+Na] + ; Actual value: 312.0512.

[0105] [I-5. Synthesis of Compound R-102] 6-(1,2,3,4-tetrahydro-2-isoquinolyl)-1H,3H-furo[3,4-c]pyridin-3-one (R-102) [ka]

[0106] 6-Chlorofuro[3,4-c]pyridin-3(1H)-one (16.6 mg, 0.098 mmol) and 1,2,3,4-tetrahydroisoquinoline (15 μL, 0.12 mmol) were synthesized as described in the literature (Zak, M.; Yuen, P.-w.; Liu, X.; Patel, S.; Sampath, D.; Oeh, J.; Liederer, B. M.; Wang, W.; O'Brien, T.; Xiao, Y.; Skelton, N.; Hua, R.; Sodhi, J.; Wang, Y.; Zhang, L.; Zhao, G.; Zheng, X.; Ho, Y.-C.; Bair, K.W.; Dragovich, P.S.J. Med. Chem. 2016, Vol. 59, pp. 8345-8368). The reaction mixture (16.5 μL, 0.119 mmol) was dissolved in N,N-dimethylformamide (DMF, 1 mL). Triethylamine (16.5 μL, 0.119 mmol) was added at room temperature, and the mixture was stirred at 85°C for 16 hours. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted three times with ethyl acetate. The combined organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The sodium sulfate was removed by filtration, and the mixture was concentrated under reduced pressure. Separation was performed by preparative TLC (silica gel as the stationary phase, dichloromethane as the mobile phase) to obtain R-102 as a white solid (22 mg, 84%).

[0107] 1 H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 7.15-7.35 (m, 4H), 6.55 (s, 1H), 5.20 (s, 2H), 4.82 (s, 2H), 3.94 (t, J = 5.7 Hz, 2H), 3.01 (t, J = 5.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 169.9 (C), 160.4 (C), 156.5 (C), 147.9 (CH), 135.2 (C), 133.4 (C), 128.2 (CH), 127.0 (CH), 126.6 (CH), 126.5 (CH), 110.5 (C), 96.8 (CH), 68.6 (CH2), 47.2 (CH2), 43.0 (CH2), 28.9 (CH2); HRMS (ESI) m / z C 16 H 14 Calculated value of N2O2+Na: 289.0947 [M+Na] + ; Actual value: 289.0955.

[0108] [I-6. Synthesis of Compound R-104] 6-Fluoro-2-(5-nitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline (R-104) [ka]

[0109] 2-Chloro-3-fluoro-5-nitropyridine (100 mg, 0.566 mmol) and 1,2,3,4-tetrahydroisoquinoline (90 μL, 0.71 mmol) were dissolved in ethanol (6 mL), and triethylamine (100 μL, 0.721 mmol) was added. After stirring at room temperature for 40 hours, the precipitated solid was collected by filtration and washed with cold ethanol to give R-104 as a yellow solid (120 mg, 78%).

[0110] 1 H NMR (400 MHz, CDCl3) δ 8.90 (dd, J = 2.3, 1.4 Hz, 1H), 7.98 (dd, J = 13.3, 2.3 Hz, 1H), 7.10-7.30 (m, 4H), 4.98 (s, 2H), 4.08 (t, J = 6.0 Hz, 2H), 4.08 (t, J = 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 151.5 (d, J = 4.8 Hz, C), 145.6 (d, J = 259.3 Hz, CF), 140.9 (d, J = 3.8 Hz, CH), 135.0 (C), 134.5 (C), 133.2 (C), HRMS (ESI) m / z C 14 H 12 Calculated value of FN3O2+Na: 296.0806 [M+Na] + ; Actual value: 296.0816.

[0111] [I-7. Preparation of Other Compounds] A chemical library containing 9,600 compounds was provided by the University of Tokyo Drug Discovery Initiative (Drug Discovery Institute, The University of Tokyo).

[0112] The following compounds were purchased from commercial suppliers: 2-[5-(trifluoromethyl)-2-pyridinyl]-1,2,3,4-tetrahydroisoquinoline (compound R-010); 6-(3,4-dihydro-2(1H)-isoquinolinyl)-N,N-diethyl-3-pyrimidinesulfonamide (compound R-018); 6-(3,4-dihydro-2(1H)-isoquinolinyl)-N,N-diisopropyl-3-pyrimidinesulfonamide (compound R-021); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinoline (compound R-022); 2-(3,4-dihydro-1H-isoquinolin-2-yl)-4-methyl-pyrimidine-5-carboxylate ethyl (compound R-025); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-094); N-[6-(6,7-Dihydrothieno[3,2-c]-5(4H)-pyridinyl)-3-pyridinyl]-2-(methylsulfonyl)acetamide (Compound R-097); [6-(1,2,3,4-Tetrahydroisoquinolin-2-yl)pyridin-3-yl]methanamide (Compound K-068); 2-[4-Methyl-6-(trifluoromethyl)pyridin-2-yl]-1,2,3,4-tetrahydroisoquinoline (Compound K-076); and 1-[4-Methyl-2-(1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidin-5-yl]ethan-1-one (Compound K-080).

[0113] <II. Enzyme Activity Inhibition Test of Compounds> [II-1. Introduction] Noppera-bo (Nobo) is a key enzyme in the biosynthesis of ecdysteroids, known as hormones that regulate insect molting and metamorphosis (Chanut-Delalande, H. et al., 2014, Nature Cell Biology, 16(11), 1035-1044; Enya, S. et al., 2014, Scientific Reports, 4(1), 6586; Enya, S. et al., 2015, Insect Biochemistry and Molecular Biology, 61, 1-7). Nobo is a member of the glutathione S-transferase (GST; EC 2.5.18) family of ecdysteroid biosynthetic enzymes. An E. coli expression system exists that facilitates large-scale cultivation of soluble recombinant protein and GST affinity chromatography. In addition, a high-throughput screening (HTS) system for Nobo enzyme activity in vitro has been established, which is ideal for screening inhibitors (Fujikawa, Y. et al., 2015, Chemical Communications, 51(57), 11459-11462). The evolutionary conservation of Nobo is limited to Diptera and Lepidoptera, including mosquitoes (Enya, S. et al., 2014, Scientific Reports, 4(1), 6586), making it a promising target for selective insecticides. In this study, we investigated the inhibitory activity of each compound against Drosophila melanogaster Nobo (DmNobo-GSTe14, hereafter referred to as "DmNobo") and Aedes aegypti Nobo (AeNobo-GSTe8, hereafter referred to as "AeNobo").

[0114] II-2. Materials and Methods (GST activity inhibition assay) 50% inhibitory concentration (IC) for enzyme activity 50) was measured using an in vitro assay system as described in the literature (Fujikawa, Y. et al., 2015, Chemical Communications, 51(57), 11459-11462). Test compounds were diluted in dimethyl sulfoxide (DMSO) to give 3-fold serial dilutions ranging from 2.5 μM to 1.27 nM. Five microliters of each diluted compound solution was mixed with 245 μL of solution A (100 mM sodium phosphate buffer (pH 6.5), 0.01% Tween 20, 2 mM GSH, and 25 ng / mL DmNobo or AeNobo). The mixture was added to a 96-well plate. Subsequently, 100 μL of solution B (0.2 μM 3,4-dinitrobenzamidodichlorofluorescein (3,4-DNADCF) and 100 mM sodium phosphate buffer (pH 6.5) was added to each well. The fluorescence intensity generated by the reaction product, 4-GS-3-NADCF, was then measured for 3 minutes. IC 50 Values ​​were estimated as described in the literature (Fujikawa, Y. et al., 2015, Chemical Communications, 51(57), 11459-11462). Absorbance at 538 nm was measured using a Fluoroskan Ascent™ FL microplate reader (Thermo Fisher Scientific).

[0115] [II-3. Results] Based on the literature (Koiwai, K. et al., 2020, Journal of Biological Chemistry, 295(20), 7154 - 7167; Koiwai, K. et al., 2021, Journal of Pesticide Science, 46(1), 75 - 87), a high - throughput screening (HTS) of compounds having DmNobo and AeNobo inhibitory activities was performed using the fluorescent substrate 3,4 - DNADCF from a library of 9,600 small - molecule compounds (Drug Discovery Initiative (DDI), The University of Tokyo, Japan). The results of the compounds showing high inhibitory activity against DmNobo and / or AeNobo in the HTS are shown in Table 1. In the table, the IC 50 values against DmNobo or AeNobo are shown as the average value and standard deviation (SD) from three or more replicates.

[0116] [Table 1]

[0117] As shown in Table 1, these compounds showed IC 50 values of 1 μM or less against DmNobo and / or AeNobo. In particular, compound R - 022 showed IC 50 values of 0.082 μM against DmNobo and 0.789 μM against AeNobo. In contrast, estrogen (EST), TDP011, TDP012, TDP013, and TDP015, which are known to have inhibitory activity against DmNobo, all showed IC 50 values exceeding 1 μM. From these results, it became clear that these compounds have higher inhibitory activity against DmNobo and / or AeNobo than known compounds.

[0118] [III. Co - crystal Structure Analysis of Enzyme Activity Inhibitor and Enzyme Protein] [III - 1. Materials and Methods] (Crystallization) DmNobo and AeNobo were crystallized based on literature (Koiwai, K. et al., 2020, Journal of Biological Chemistry, 295(20), 7154-7167; Inaba, K. et al., 2022, BMC Biology, 20, 43). DmNobo crystals were obtained by the hanging drop vapor diffusion method. The reservoir mixture contained 42.5% (v / v) polypropylene glycol 400, 0.1 M Bis-Tris (pH 6.5), 2 mM GSH, and 2 mM dithiothreitol (DTT). To prepare a drop, 1 μL of 15 mg / mL DmNobo in 150 mM NaCl, 25 mM Tris-HCl (pH 8.0), and 1 mM DTT was mixed with 1 μL of reservoir solution. The mixture was equilibrated against the reservoir at 20 °C. Crystalline complexes of DmNobo complexed with test compounds R-010, R-022, R-025, or R-093 were soaked in DMSO suspensions containing 10 mM GSH and 30 mM test compound at 20°C for 3 days. To prepare the GSH stock solution, a 100 mM solution was prepared in a buffer containing 150 mM NaCl, 25 mM Tris-HCl (pH 8.0), and 1 mM DTT. Crystals of AeNobo complexed with GSH and the test compound R-022 were obtained by the hanging drop vapor diffusion method. The AeNobo protein solution was centrifuged at 13,500 × g for 30 minutes to remove protein aggregates. The reservoir mixture contained 32.5% PEG 4000, 0.1 M Tris-HCl (pH 7.5), and 0.5 M calcium chloride. To prepare the droplets, 1 μL of 45 mg / mL AeNobo in 150 mM NaCl, 25 mM Tris-HCl (pH 8.0), and 5 mM DTT was mixed with 1 μL of reservoir solution. The mixture was equilibrated against the reservoir at 20°C. A crystalline complex of AeNobo complexed with GSH and the test compound R-022 was immersed in a DMSO suspension of 10 mM GSH and 30 mM test compound at 20°C for 1 day.

[0119] (X-ray crystal structure analysis)X-ray crystal structure analysis of DmNobo and AeNobo was performed based on literature (Koiwai, K. et al., 2020, Journal of Biological Chemistry, 295(20), 7154-7167; Inaba, K. et al., 2022, BMC Biology, 20, 43). DmNobo crystals were frozen in liquid nitrogen and collected using a MiTeGen cryoloop. The collected crystals were packed into Molecular Dimensions Unipacks. AeNobo crystals were cryoprotected by immersion in a solution containing 30% PVK15 and reservoir solution before collection. The crystals were then flash-frozen in liquid nitrogen and packed into Unipacks. Diffraction data were collected using beamlines AR-NE3A and BL-17A at the Photon Factory Laboratory (Tsukuba, Ibaraki Prefecture, Japan). The crystallization solution provided sufficient cryoprotection for data collection at 95 K. The exposure time, beam size, frame size, and number of frames were 0.25 seconds, 0.2 × 0.2 mm, 0.5°, and 360, respectively. The collected data sets were processed and scaled using XDS (Kabsch, W. 2010, XDS. Acta Crystallographica. Section D, Biological Crystallography, 66(Pt 2), 125-132), MOLREP (Vagin, A., & Teplyakov, A. 1997, Journal of Applied Crystallography, 30(6), 1022-1025), and AIMLESS (Evans, PR, & Murshudov, GN 2013, Acta Crystallographica Section D: Biological Crystallography, 69(7), 1204-1214). The phases of the DmNobo structure were calculated using molecular replacement with the DmNobo structure (PDB ID: 6KEL) as a template. For AeNobo-GSH-R22, the phases were calculated using the AeNobo-GSH-desmethylglycitein structure (PDB ID: 7EBW).The model was refined using COOT and PHENIX.REFINE (Emsley, P. et al., 2010, Acta Crystallographica Section D: Biological Crystallography, 66(4), 486-501; Afonine, PV et al., 2012, Acta Crystallographica Section D Biological Crystallography, 68(4), 352-367).

[0120] (FMO analysis) Based on the literature (Koiwai, K. et al., 2020, Journal of Biological Chemistry, 295(20), 7154-7167), ab initio fragment molecular orbital (ab initio FMO) calculations were performed on the cocrystal structures of the DmNobo-GSH-R22 complex and the AeNobo-GSH-R22 complex. Although DmNobo is a homodimer and AeNobo is a homotetramer, only the monomer structures were used for the FMO calculations. Therefore, the interactions between subunits were ignored in this analysis. The crystal structures were modified before the FMO calculations. Energy minimization of hydrogen atoms was performed using the Amber10: EHT force field, except for the main chain (tether = 0.5). Next, FMO calculations were performed on the monomeric DmNobo structure using the ABINIT-MP software (Mochizuki, Nakano, et al. 2004; Nakano et al. 2006; Gonze et al. 2009). Second-order Moller-Plesset perturbation (MP2) (Mochizuki, Y., Koikegami, S. et al., 2004, Chemical Physics Letters, 396(4-6), 473-479; Mochizuki, Y., Nakano, T. et al., 2004, Theoretical Chemistry Accounts, 112(5-6), 442-452) was used, with the theoretical calculation level set to 6-31G. * Basis set, i.e., FMO-MP2 / 6-31G *The FMO calculations were performed at the 3D level. For the FMO calculations, DmNobo protein and GSH were fragmented into amino acid units at the bonds between the C and Ca atoms of the main chain. Each ligand and water molecule was treated as a single fragment. The fragmentation process facilitated the calculation of the electronic structure and interfragment interaction energies (IFIEs) of the entire complex. The obtained IFIEs were further decomposed into four energy components, ES, EX, CT, and DI, using the energy component decomposition (PIEDA) method (Fedorov, DG, & Kitaura, K. 2007, Journal of Physical Chemistry A, 111(30), 6904-6914; Tsukamoto, T. et al., 2015, Journal of Computer Chemistry, Japan, 14(1), 1-9).

[0121] [III-2. Results] (Binding mode of compound R-022 to DmNobo or AeNobo) To determine the binding mode between DmNobo and compound R-022, we obtained a co-crystal structure of DmNobo with GSH and compound R-022 (DmNobo-GSH-R22) and performed X-ray crystal structure analysis. The results are shown in Figure 1. In the figure, A is an electron density map omitting the overall structure of DmNobo and the ligands (GSH and compound R-022) bound thereto, and B shows the structure of DmNobo complexed with compound R-022 relative to the A chain.

[0122] As shown in Figure 1, the binding mode of the co-crystal structure of DmNobo with GSH and compound R-022 (DmNobo-GSH-R22) was determined at 1.69 Å resolution (PDB code: 8X11). The space group of the obtained crystal was P212121, with lattice parameters a = 58.90, b = 75.44, c = 108.12 Å, and α = β = γ = 90°. The electron density of compound R-022 (R22) was observed in the hydrophobic site (H site) of DmNobo (Figure 1B). No complex structure was obtained in the absence of GSH. The cysteine ​​of GSH and carbon atom C6 of compound R-022 appear to form a covalent bond at a distance of 1.77 Å.

[0123] Similarly, to determine the binding mode between AeNobo and compound R-022, we obtained a co-crystal structure of AeNobo with GSH and compound R-022 (AeNobo-GSH-R22) and performed X-ray crystal structure analysis. The results are shown in Figure 2. In the figure, A is the overall structure of AeNobo, B is the biological unit of AeNobo, C is an electron density map omitting GSH and compound R-022 in the AeNobo crystal, and D shows the structure of AeNobo complexed with compound R-022 relative to the A chain.

[0124] As shown in Figure 2, we determined the binding mode of the co-crystal structure of AeNobo with GSH and compound R-022 (AeNobo-GSH-R22) at 1.75 Å resolution (PDB code: 8X12). The space group of the obtained crystal is P412 2, with lattice parameters a = 151.18, b = 151.18, c = 146.72 Å, α = β = γ = 90°, and four GST dimers (eight subunits) in the asymmetric unit. The H site of AeNobo is occupied by the electron density of compound R-022 (R22) (Figure 2D). The cysteine ​​of GSH forms a covalent bond with the carbon atom C6 of compound R-022 (R22) in all chains (chain A: 2.20 Å, chain B: 2.09 Å, chain C: 2.31 Å, chain D: 2.18 Å).

[0125] (Interaction between amino acid residues of DmNobo and compound R-022) The results of FMO analysis of the DmNobo-GSH-R22 cocrystal complex are shown in Figure 3. In the figure, A shows the results of FMO analysis of the DmNobo-GSH-R22 complex, and B shows the results of FMO analysis of the AeNobo-GSH-R22 complex. The horizontal axis represents the amino acid residues of the enzyme protein or GSH, and the vertical axis represents the interaction energy (kcal / mol) of PIEDA.

[0126] As shown in Figure 3A, in the DmNobo complex, GSH had the highest IFIE. Compound R-022 covalently binds to GSH through hydrophobic interactions. Aspartic acid 113 (D113) exhibited the highest electrostatic energy (ES), suggesting the formation of a hydrogen bond. Phenylanine 39 (F39) exhibited the highest dispersion energy (DI), suggesting the formation of a hydrophobic interaction. As shown in Figure 3B, in the AeNobo complex, GSH and histidine 43 had the highest IFIE. Compound R-022 formed a covalent bond with GSH, and histidine 43 and glutamic acid 113 each formed hydrogen bonds.

[0127] To evaluate the importance of amino acid residues of the enzyme protein, point mutant proteins of DmNobo and AeNobo were prepared, and the inhibitory activity of test compounds against the point mutant proteins was evaluated. As a result, in DmNobo, the inhibitory activity of compound R-022 against the mutant proteins of F39 or D113 decreased by about 10-fold compared with the inhibitory activity against the native protein. The inhibitory activities of compound R-022 against the double mutant (F39 and D113) and the mutant protein of F110 both decreased by about 40-fold compared with the inhibitory activity against the native protein. In addition, in AeNobo, the inhibitory activity of compound R-022 against the mutant proteins of F39, H43 or E113 decreased by about 2-fold compared with the inhibitory activity against the native protein. From these results, it can be concluded that compound R-022 forms multiple interactions with adjacent amino acid residues including D113, F39 and F110 of the DmNobo protein, and F39, H43 and E113 of the AeNobo protein. Also, the strength of the inhibitory activity is greatly affected by the covalent bond with GSH. Furthermore, it was revealed that compound R-022 has a binding mode different from that of conventional Nobo inhibitors.

[0128] <IV. Insecticidal Activity Test of Compounds> [IV-1. Materials and Methods] (Rearing of Mosquitoes) The Liverpool strain of Aedes aegypti was reared by the method described in the literature (Inaba, K. et al., 2022, BMC Biology, 20, 43). Larvae hatched from dry eggs attached to filter paper were used in this test. All mosquitoes were reared at a temperature of 27 ± 2°C.

[0129] (Larval Killing Assay of Mosquitoes) The dried eggs on the filter paper were submerged in distilled water containing mosquito food. After 3 hours, the first-instar larvae were transferred to 30 mL of fresh distilled water in a 50 mL plastic cup. The lid of the cup was breathable. 1.2 g of Hikari medium grains (Kyorin) were placed in the cup to serve as food for the mosquito larvae. The test compound was prepared as a 1,000 ppm stock solution dissolved in 100% ethanol. 30 mL of rearing water containing the test compound at concentrations ranging from 10 ppm to 0.0001 ppm and ethanol at a final concentration of 0.1% was added to each cup. 20 larvae were then placed in each cup. After 24 hours, the number of surviving and dead larvae was recorded. Based on the dose-response curve, the 50% lethal concentration (LD 50 ) was calculated.

[0130] (Reverse transcription quantitative PCR (RT-qPCR)) To obtain total RNA, larvae from the untreated control group and the compound R-022-treated group were prepared as described in the "Mosquito Larvae Killing Assay" section. 24 hours after compound treatment, 10 larvae from each group were homogenized with RNAiso Plus (TaKaRa) using a BioMasher II (KANTO CHEMICAL). cDNA was synthesized from the RNA by reverse transcription using ReverTra Ace qPCR RT Master Mix with gDNA Remover (Toyobo). qPCR was performed using the cDNA sample as a template and THUNDERBIRD SYBR qPCR Mix (Toyobo) on a CFX Duet Real-Time PCR System (Bio-Rad Laboratories). Plasmids containing the open reading frames of each gene were serially diluted and used as standards for each gene. The mRNA abundance of E74B, a downstream gene in ecdysteroid biosynthesis, was normalized to ribosomal protein 49 (rp49) to calculate relative fold changes.

[0131] (Cells and cell cultures) Two types of cultured cells were used: Hep G2 cell line (human hepatoma cell line) and RAW 264.7 cell line (mouse macrophage cell line). These cells were seeded and cultured in 96-well plates containing MEMα medium consisting of 10% FBS, 2% glutamine, and 100 U / mL penicillin / streptomycin and a predetermined concentration of test compound. After a predetermined period of culture, the number of viable and dead cells was recorded. Based on the dose-response curve, the 50% killing concentration (LD 50 ) was calculated.

[0132] [IV-2. Results] (Effects of test compounds on mosquito larvae) The results of compounds that showed high insecticidal activity against Culex mosquito larvae are shown in Table 2. In the table, the LD 50 Values ​​are presented as the mean and standard deviation (SD) of at least three replicates.

[0133] [Table 2]

[0134] As shown in Table 2, these compounds had LD of 5 ppm or less against Culex mosquito larvae. 50 In contrast, desmethylglycitein (DMG), known to have insecticidal activity against Culex mosquito larvae (Inaba, K. et al., 2022, BMC Biology, 20, 43), showed an LD of 9.39 ppm in the same assay. 50 These results demonstrate that these compounds have high insecticidal activity against Culex mosquito larvae.

[0135] The developmental stage of Culex mosquito larvae can be determined by measuring the head diameter. Therefore, the developmental stage of Culex mosquito larvae was examined 24 hours after treatment with the test compound. The results are shown in Figure 4. In the figure, A is a photograph of an individual from the untreated control group and an individual from the 1 ppm compound R-022-treated group. The scale bar represents 1 mm. B is a graph showing the head diameter of individuals from the untreated control group and an individual from the 1 ppm compound R-022-treated group. The vertical axis represents the head diameter (mm) of individuals in each group. ** indicates a significant difference from the control group in Student's t-test (**: p<0.01). n = 79 (control group), n = 56 (compound R-022-treated group). Error bars indicate standard deviation.

[0136] As shown in Figure 4, the head diameter of Culex mosquito larvae treated with compound R-022 was significantly smaller than that of larvae in the untreated control group. This result demonstrated that compound R-022 can retard the growth of Culex mosquito larvae.

[0137] The expression levels of downstream genes involved in ecdysteroid biosynthesis in Culex mosquito larvae treated with compound R-022 were investigated using RT-qPCR. The results are shown in Figure 5. In the figure, the vertical axis represents the relative expression level of the E74B gene normalized to the expression level of rp49 mRNA. * and ** indicate significant differences compared to the control group in Student's t-test (*: p<0.05, **: p<0.01). Error bars indicate standard deviation.

[0138] As shown in Figure 5, the expression level of the E74B gene was reduced in a concentration-dependent manner in the compound R-022-treated group. These results suggest that the compound of the present invention induces insecticidal development by inhibiting ecdysteroid biosynthesis.

[0139] The test compounds were added to cultured mouse and human cells to confirm their effect on growth. As a result, compound R-022 had an LD of 310.33 ± 82.38 μM against the mouse RAW 264.7 cell line. 50 The value was calculated as an LD of more than 350 μM for the human Hep G2 cell line.50 The compound R-010 had an LD of 84.27 ± 1.15 μM against the mouse RAW 264.7 cell line. 50 The value was calculated as an LD of more than 350 μM for the human Hep G2 cell line. 50 These results demonstrate that the test compounds do not substantially inhibit the growth of cultured mammalian cells.

[0140] The present invention is not limited to the above-described embodiments, but includes various modifications. For example, the above-described embodiments have been described in detail to clearly explain the present invention, and the present invention is not necessarily limited to those including all of the described configurations. Furthermore, it is possible to add, delete, and / or replace part of the configuration of each embodiment with other configurations.

Claims

1. Formula (I) or (II): 【Chemistry 1】 [In the formula, n is 0 or 1, R 1 and R 2 are, independently of one another, hydrogen, halogen (fluorine, chlorine, bromine or iodine) or hydroxy, A is represented by formula (A-1), (A-2) or (A-3): 【Chemistry 2】 is a monovalent group represented by * indicates the bonding position to the nitrogen atom, X is a carbon atom or a nitrogen atom, R A1 , R A2 and R A4 are, independently of each other, hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryl aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted acylamino; R A3 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, oxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted acylamino; R A5 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted aryloxy, oxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylalkenyloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted heteroarylalkyloxy, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted cycloalkoxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted arylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted arylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted acylamino. or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof, as an active ingredient.

2. R A1 , R A2 and R A4 are independently hydrogen, halogen (fluorine, chlorine, bromine or iodine), hydroxy, substituted or unsubstituted C 1 ~C 9 Alkyl, substituted or unsubstituted C 2 ~C 9 Alkenyl, substituted or unsubstituted C 2 ~C 9 Alkynyl, substituted or unsubstituted C 1 ~C 9 Alkoxy, substituted or unsubstituted C 1 ~C 9 Alkoxycarbonyl, substituted or unsubstituted C 1 ~C 20 Acyl, substituted or unsubstituted C 1 ~C 9 Alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C 1 ~C 9 Alkyl sulfonyl, substituted or unsubstituted amino sulfonyl, substituted or unsubstituted C 1 ~C 9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C 1 ~C 20 2. The insecticide of claim 1, which is an acylamino.

3. R A3 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C 1 ~C 9 Alkyl, substituted or unsubstituted C 2 ~C 9 Alkenyl, substituted or unsubstituted C 2 ~C 9 Alkynyl, substituted or unsubstituted C 1 ~C 9 Alkoxy, substituted or unsubstituted C 1 ~C 9 Alkoxycarbonyl, substituted or unsubstituted C 1 ~C 20 Acyl, substituted or unsubstituted C 1 ~C 9 Alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C 1 ~C 9 Alkyl sulfonyl, substituted or unsubstituted amino sulfonyl, substituted or unsubstituted C 1 ~C 9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C 1 ~C 20 is acylamino, R A5 is hydrogen, halogen (fluorine, chlorine, bromine or iodine), nitro, hydroxy, substituted or unsubstituted C 1 ~C 9 Alkyl, substituted or unsubstituted C 2 ~C 9 Alkenyl, substituted or unsubstituted C 2 ~C 9 Alkynyl, substituted or unsubstituted C 1 ~C 9 Alkoxy, substituted or unsubstituted C 1 ~C 9 Alkoxycarbonyl, substituted or unsubstituted C 1 ~C 20 Acyl, substituted or unsubstituted C 1 ~C 9 Alkylcarbonyloxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted C 1 ~C 9 Alkyl sulfonyl, substituted or unsubstituted amino sulfonyl, substituted or unsubstituted C 1 ~C 9 alkylsulfanyl, substituted or unsubstituted amino, or substituted or unsubstituted C 1 ~C 20 acylamino, The insecticide of claim 1.

4. Conditions (i) and (ii): Condition (i) n is 0, A is a monovalent group represented by formula (A-1), X is a carbon atom, R A1 , R A2 and R A4 are both hydrogen, and R A3 is nitro, or Condition (ii) n is 1, R A1 , R A2 and R A4 are, independently of one another, hydrogen, halogen (fluorine, chlorine, bromine or iodine), or substituted or unsubstituted C 1 ~C 9 is alkyl, R A3 is hydrogen, nitro, substituted or unsubstituted C 1 ~C 9 Alkyl, substituted or unsubstituted C 1 ~C 9 Alkoxycarbonyl, substituted or unsubstituted C 1 ~C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C 1 ~C 20 is acylamino, R A5 is hydrogen, nitro, substituted or unsubstituted C 1 ~C 9 Alkyl, substituted or unsubstituted C 1 ~C 9 Alkoxycarbonyl, substituted or unsubstituted C 1 ~C 20 Acyl, substituted or unsubstituted aminosulfonyl, or substituted or unsubstituted C 1 ~C 20 acylamino, The insecticide according to claim 1, which satisfies any one of the conditions.

5. A compound represented by formula (I) or (II) or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof, 2-[5-(trifluoromethyl)-2-pyridinyl]-1,2,3,4-tetrahydroisoquinoline (compound R-010); 6-(3,4-dihydro-2(1H)-isoquinolinyl)-N,N-diethyl-3-pyrimidinesulfonamide (compound R-018); 6-(3,4-dihydro-2(1H)-isoquinolinyl)-N,N-diisopropyl-3-pyrimidinesulfonamide (compound R-021); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinoline (compound R-022); 2-(3,4-dihydro-1H-isoquinolin-2-yl)-4-methyl-pyrimidine-5-carboxylate ethyl (compound R-025); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-6-ol (compound R-093); 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-094); 2-(5-nitro-2-pyridinyl)-2,3-dihydro-1H-isoindol-5-ol (compound R-096); N-[6-(6,7-dihydrothieno[3,2-c]-5(4H)-pyridinyl)-3-pyridinyl]-2-(methylsulfonyl)acetamide (compound R-097); 2-(3-chloro-5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-098); 2-(2-chloro-5-nitro-4-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-099); 6-(1,2,3,4-tetrahydro-2-isoquinolyl)-1H,3H-furo[3,4-c]pyridin-3-one (compound R-102); 6-Fluoro-2-(5-nitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline (compound R-104); [6-(1,2,3,4-tetrahydroisoquinolin-2-yl)pyridin-3-yl]methanamide (compound K-068); 2-[4-methyl-6-(trifluoromethyl)pyridin-2-yl]-1,2,3,4-tetrahydroisoquinoline (compound K-076); or 1-[4-methyl-2-(1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidin-5-yl]ethan-1-one (compound K-080); or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof.

6. 10. The insecticide of claim 1 for controlling mosquitoes.

7. 1. An agricultural chemical composition comprising a compound represented by formula (I) or (II) as defined in claim 1 or an agriculturally acceptable salt thereof, or an agriculturally acceptable solvate thereof, and one or more agriculturally acceptable carriers.

8. 8. The agrochemical composition of claim 7 for controlling mosquitoes.

9. Formula (Ia): 【Transformation 3】 [In the formula, n is 0 or 1, When n is 0, R 1 is hydroxy and R 2 is hydrogen, When n is 1, R 1 is hydrogen and R 2 is hydrogen or hydroxy, A is a member of the formula (Aa-1), (Aa-2) or (Aa-3): 【Chemistry 4】 is a monovalent group represented by * indicates the bonding position to the nitrogen atom, R A1 is hydrogen or a halogen (fluorine, chlorine, bromine or iodine), R A2 is a halogen (fluorine, chlorine, bromine or iodine), However, when A is a monovalent group represented by formula (Aa-1) or (Aa-2), R 1 , R 2 , R A1 and R A2 Neither of the is hydrogen. or a salt thereof, or a solvate thereof.

10. 10. The compound according to claim 9, or a salt thereof, or a solvate thereof, wherein n is 1.

11. 2-(5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-6-ol (compound R-093); 2-(5-nitro-2-pyridinyl)-2,3-dihydro-1H-isoindol-5-ol (compound R-096); 2-(3-chloro-5-nitro-2-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-098); 2-(2-chloro-5-nitro-4-pyridinyl)-1,2,3,4-tetrahydroisoquinolin-7-ol (compound R-099); 6-(1,2,3,4-tetrahydro-2-isoquinolyl)-1H,3H-furo[3,4-c]pyridin-3-one (compound R-102); or 6-Fluoro-2-(5-nitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline (compound R-104); 10. The compound according to claim 9, or a salt thereof, or a solvate thereof,

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