Rodenticides comprising lithocholic acid derivatives

Abstract

An object of the present application is to provide a novel rodenticide. According to the present application, a rodenticide comprising a compound represented by the following general formula (I), a salt thereof, or a prodrug thereof is provided. In the formula, R 1 and R 2 each independently represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. n represents an integer of 1 to 3. R 3 , R 4 , R 5 and R 6 each independently represent a hydrogen atom or an alkyl group having 1 to 6 carbon atoms. X represents COOH, -C(=O)NH-Z, -CH(OH)-(Y) m -CH(OH)R7, -NH-CO-O-R 10 , -CO-O-R 10 or -NH-CO-N(R 11 )-R 10 . Z represents a hydrogen atom, -CN, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms or a hydroxyl group, Y represents -C(R8)(R9)-, -C(=O)- or -C(=CH2)-, and m represents an integer of 0 to 3. R7, R8 and R9 each independently represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. The alkyl group having 1 to 8 carbon atoms represented by Z, R7, R8 and R9 can have a substituent selected from a carboxyl group or a hydroxyl group. R 10 and R 11 each independently represent a hydrogen atom or an alkyl group having 1 to 8 carbon atom which can have a substituent.

Description

Technical Field

[0001] This invention relates to a rodenticide comprising a lithocholic acid derivative having vitamin D activity. Background Technology

[0002] The metabolic activator of vitamin D, 1α,25-dihydroxyvitamin D3, binds to the vitamin D receptor (VDR) and controls the expression of a specific gene. By controlling the expression of this gene, vitamin D plays important physiological roles such as maintaining blood calcium levels, bone formation, immune function, and controlling cell differentiation / proliferation. To date, various VDR ligands have been developed for the treatment of osteoporosis, psoriasis, and cancer, several of which are already in clinical use.

[0003] Lithocholic acid has been found to be an endogenous ligand for VDR. Patent document 1 describes lithocholic acid derivatives having a hydroxyalkyl group at the 3-position, wherein the lithocholic acid derivatives having two or more carbon atoms in the 3-position hydroxyalkyl backbone exhibit excellent vitamin D3 agonist activity.

[0004] On the other hand, rodenticides are agents used to eliminate rats. They are usually prepared in the form of poisoned bait, which rats ingest to achieve their killing effect. Rodenticides are classified into cumulative agents and acute agents. Cumulative agents exert their killing effect through repeated ingestion; examples include coumatetralyl, warfarin, and difethiarol. Acute agents include yellow phosphorus, arsenic trioxide, aluminum phosphide, zinc phosphide, norbormide, scilliroside, thallium, thallium sulfate, α-naphthiourea, and sodium monofluoroacetate, but these agents are highly toxic and difficult to handle.

[0005] Existing technical documents Patent documents Patent document 1: International Publication No. WO2017 / 131144. Summary of the Invention

[0006] The problem that the invention aims to solve The problem to be solved by the present invention is to provide a novel rodenticide.

[0007] Methods for solving problems To address the aforementioned issues, the inventors conducted in-depth research and discovered that a lithocholic acid derivative having a hydroxyalkyl group at the 3-position, wherein the 3-position hydroxyalkyl main chain has two or more carbon atoms, can be used as a rodenticide, thus completing this invention.

[0008] According to the present invention, the following invention is provided.

[0009] <1> A rodenticide comprising a compound represented by the following general formula (I), its salt, or a prodrug.

[0010] [Chemical Formula 1] In the formula, R 1 and R 2 Each can independently represent an alkyl group with 1 to 8 hydrogen atoms or carbon atoms. n represents an integer from 1 to 3.

[0011] R 3 R 4 R 5 and R 6 Each can be independently represented as an alkyl group having 1 to 6 hydrogen atoms or carbon atoms.

[0012] X represents COOH, -C(=O)NH-Z, and -CH(OH)-(Y). m -CH(OH)R7、-NH-CO-OR 10 -CO-OR 10 or -NH-CO-N(R) 11 )-R 10 Z represents a hydrogen atom, -CN, an alkyl group with 1 to 8 carbon atoms, an alkoxy group with 1 to 8 carbon atoms, or a hydroxyl group; Y represents -C(R8)(R9)-, -C(=O)-, or -C(=CH2)-; and m represents an integer from 0 to 3. R7, R8, and R9 each independently represent a hydrogen atom or an alkyl group with 1 to 8 carbon atoms. The alkyl groups with 1 to 8 carbon atoms represented by Z, R7, R8, and R9 may have substituents selected from carboxyl or hydroxyl groups. R 10 and R 11 Each can independently represent a hydrogen atom or an alkyl group with 1 to 8 carbon atoms that may have substituents.

[0013] <2> according to <1> The rodenticide, wherein X is COOH.

[0014] <3> according to <1> or <2> The rodenticide, wherein R 1 and R 2 It can be methyl or ethyl.

[0015] <4> according to <1> or <2> The rodenticide, wherein R 3 R 4 R 5 and R 6 It is a hydrogen atom.

[0016] <5> according to <1> or <2> The rodenticide, wherein n is 1.

[0017] <6> A method of rat extermination, which uses <1> or <2> The aforementioned rodenticide.

[0018] According to the present invention, the following invention is further provided.

[0019] [A] A method of rodent control comprising administering to rodents a compound of general formula (I), its salt or a prodrug.

[0020] [B] Compounds of general formula (I), their salts or prodrugs used for rodent control.

[0021] [C] Compounds of general formula (I), their salts or prodrugs used in the manufacture of rodenticides.

[0022] Invention Effects The rodenticide of this invention has excellent rodent-killing effect. Detailed Implementation

[0023] The present invention will now be described in more detail.

[0024] The rodenticide of the present invention comprises a compound represented by the following general formula (I), its salt or its prodrug as an active ingredient.

[0025] [Chemical Formula 2] In the formula, R 1 and R 2 Each can independently represent an alkyl group with 1 to 8 hydrogen atoms or carbon atoms. n represents an integer from 1 to 3.

[0026] R 3 R 4 R 5 and R 6 Each can be independently represented as an alkyl group having 1 to 6 hydrogen atoms or carbon atoms.

[0027] X represents COOH, -C(=O)NH-Z, and -CH(OH)-(Y). m -CH(OH)R7、-NH-CO-OR 10 -CO-OR 10 or -NH-CO-N(R) 11 )-R 10 Z represents a hydrogen atom, -CN, an alkyl group with 1 to 8 carbon atoms, an alkoxy group with 1 to 8 carbon atoms, or a hydroxyl group; Y represents -C(R8)(R9)-, -C(=O)-, or -C(=CH2)-; and m represents an integer from 0 to 3. R7, R8, and R9 each independently represent a hydrogen atom or an alkyl group with 1 to 8 carbon atoms. The alkyl groups with 1 to 8 carbon atoms represented by Z, R7, R8, and R9 may have substituents selected from carboxyl or hydroxyl groups. R 10 and R 11Each can independently represent a hydrogen atom or an alkyl group with 1 to 8 carbon atoms that may have substituents.

[0028] Substituents at position 3 of the steroid skeleton (i.e., HOC(R)) 1 (R) 2 (CH2) n The stereoconfiguration of the group shown is not particularly limited; either α-substituted or β-substituted forms are acceptable.

[0029] The alkyl groups having 1 to 8 carbon atoms and alkyl groups having 1 to 6 carbon atoms in this specification can be any of straight-chain, branched, cyclic, or combinations thereof. There are no particular limitations on the alkyl groups having 1 to 8 carbon atoms and alkyl groups having 1 to 6 carbon atoms; examples include: methyl, ethyl, n-propyl, isopropyl, cyclopropylmethyl, n-butyl, sec-butyl, tert-butyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclohexyl, etc.

[0030] In this specification, alkoxy groups with 1 to 8 carbon atoms can be straight-chain, branched, cyclic, or a combination thereof. There are no particular limitations on alkoxy groups with 1 to 8 carbon atoms; examples include: methoxy, ethoxy, n-propoxy, isopropoxy, cyclopropylmethoxy, n-butoxy, sec-butoxy, tert-butoxy, cyclobutoxy, cyclobutylmethoxy, cyclopentoxy, cyclohexyloxy, etc.

[0031] In this specification, the alkyl portion of a carboxyalkyl group having 1 to 8 carbon atoms can be any of a straight-chain, branched, cyclic, or combination thereof, and is a divalent group obtained by removing one hydrogen atom from methyl, ethyl, n-propyl, isopropyl, cyclopropylmethyl, n-butyl, sec-butyl, tert-butyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, or cyclohexyl.

[0032] R 1 and R 2 Each group can be the same or different groups, but is preferably the same group. R is particularly preferred. 1 and R 2 All are methyl or ethyl.

[0033] R 3 R 4 R 5 and R 6 Each group can be the same or different groups, independently. R is particularly preferred. 3 R 4 R 5 and R 6 It consists entirely of hydrogen atoms.

[0034] n represents an integer from 1 to 3, preferably 1 or 2, and more preferably 1.

[0035] X represents COOH, -C(=O)NH-Z, and -CH(OH)-(Y). m -CH(OH)R7、-NH-CO-OR 10 -CO-OR 10 or -NH-CO-N(R) 11 )-R 10 Of the above, COOH is preferred.

[0036] Z represents a hydrogen atom, -CN, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, or a hydroxyl group. Preferably, Z is -CN or an alkyl group having 1 to 8 carbon atoms that may have a carboxyl group. As an alkyl group having 1 to 8 carbon atoms that may have a carboxyl group, -(CH2)3COOH is particularly preferred.

[0037] Y represents -C(R8)(R9)-, -C(=O)-, or -C(=CH2)-, preferably -C(R8)(R9)-, and more preferably -CH2-.

[0038] m represents an integer from 0 to 3, preferably 0 or 1.

[0039] R7, R8, and R9 each independently represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. R7 is preferably a hydrogen atom or a methyl group.

[0040] The alkyl groups represented by R7, R8, and R9, having 1 to 8 carbon atoms, may or may not have substituents selected from carboxyl or hydroxyl groups. When the alkyl group has a carboxyl group, a carboxylalkyl group having 1 to 8 carbon atoms is preferred.

[0041] R 10 and R 11 Each can independently represent a hydrogen atom or an alkyl group with 1 to 8 carbon atoms that may have substituents. The alkyl group with 1 to 8 carbon atoms in "alkyl group with 1 to 8 carbon atoms that may have substituents" may have substituents. Examples of substituents include: halogens (fluorine, chlorine, bromine, or iodine, etc.), ethers, aromatic rings, etc. It should be noted that ethers or aromatic rings may exist within the alkyl chain.

[0042] In X is -NH-CO-OR 10 In the case of R, it is preferred 10 It indicates methyl or ethyl.

[0043] When X is -NH-CO-N(R) 11 )-R 10 In the case of R, it is preferred 10 and R 11 Each can be used independently to represent a hydrogen atom or a methyl group.

[0044] In X is -CO-OR 10 In the case of R, it is preferred10 It indicates methyl, ethyl, n-propyl, or isopropyl.

[0045] The compounds represented by general formula (I) sometimes have one or more asymmetric carbons. Any optically active organisms, diastereomers, stereoisomers, any mixtures of stereoisomers, racemates, etc., based on asymmetric carbons are included within the scope of this invention.

[0046] The compounds represented by general formula (I) sometimes exist in the form of salts such as acid addition salts or base addition salts, which are also included within the scope of this invention. Examples of acid addition salts include inorganic acid salts such as hydrochlorides, hydrobroms, sulfates, and nitrates, and organic acid salts such as p-toluenesulfonates, methanesulfonates, oxalates, tartrates, and maleates. Examples of base addition salts include metal salts such as sodium salts, potassium salts, magnesium salts, and calcium salts, and organic amine salts such as ammonium salts, triethylamine salts, and ethanolamine salts. In addition to these, amino acid salts such as glycine salts are also included within the scope of this invention.

[0047] The compounds represented by general formula (I) can be formulated as prodrugs. After administration to an organism, the prodrug forms a pharmaceutically active compound through enzymatic action or metabolic hydrolysis. Prodrugs can be acid derivatives known to those skilled in the art, such as esters obtained by reacting the compound represented by general formula (I) with a suitable alcohol, amides obtained by reacting the compound represented by general formula (I) with a suitable amine, 2,4-ols as carboxyl reductions, etc., but without particular limitation.

[0048] Compounds represented by general formula (I), their salts, and their prodrugs sometimes exist as adducts (hydrates or solvates) with water or various solvents, and these adducts are also within the scope of this invention. Examples of solvents in solvates include methanol, ethanol, acetonitrile, etc., without particular limitation. The adducts (hydrates or solvates) can be single substances or mixtures of multiple substances.

[0049] The compounds represented by general formula (I), their salts, and any crystal form of their prodrugs are also within the scope of this invention.

[0050] The following compounds can be listed as specific examples of compounds represented by general formula (I).

[0051] [Chemical Formula 3] [Chemical Formula 4] [Chemical Formula 5] .

[0052] The compound represented by general formula (I) is described in International Publication No. WO2017 / 131144, International Publication No. WO2021 / 033766, and Japanese Patent Application Publication No. 2023-111289, and can be prepared according to the methods described in the above publications.

[0053] The compound represented by general formula (I) has excellent rodenticidal activity and can therefore be used as an active ingredient in rodenticides. According to the present invention, a method for rodent control using the rodenticide of the present invention is provided.

[0054] The compound represented by general formula (I) has rodenticidal activity, which can be verified by administering the compound represented by general formula (I) to mice and evaluating the survival rate of the mice.

[0055] The rodenticide of the present invention comprises a compound of general formula (I) as an active ingredient.

[0056] The rodenticide of the present invention can be in any form suitable for controlling harmful rodents, for example, it can be provided as a formulation suitable for oral administration. In particular, the rodenticide of the present invention can be in the form of a concentrated liquid, powder, grain, gel, paste, or extruded bait such as granules or blocks.

[0057] In addition to the compound represented by general formula (I) as the active ingredient, the rodenticide of the present invention may also contain one or more excipients. Examples of excipients include mineral oil, sugars such as dextrin, inorganic substances such as clay, other organic solvents such as glycol (ethylene glycol) and DMSO, water, grain raw materials such as barley, wheat, corn or rice, and binders such as paraffin wax.

[0058] The mixing of the compound represented by general formula (I) with the excipient can be carried out by conventional methods (e.g., convection, dispersion, shearing, etc.).

[0059] The rodenticide of this invention can be used to eradicate rodents (especially harmful rodents). Examples of rodents include mice, rats, voles, brown rats, black rats, and house mice. Examples include black rats (Rattus rattus), brown rats (Rattus norvegicus), house mice (Mus musculus), and voles (Microtus montebelli, Japanese voles).

[0060] The rodenticide of the present invention can be used to eliminate rodents in home environments, rural environments, business environments, urban environments, public catering or hospitality service shops, or agricultural product processing industries.

[0061] The rodenticide of the present invention can be used as a preventative measure in areas where rodent attacks should be prevented. The rodenticide of the present invention can also be formulated or fixed in bait boxes suitable for eliminating rodents.

[0062] The amount of the compound represented by general formula (I) used can be appropriately set according to the target rodent, preferably 1 mg / kg to 500 mg / kg, more preferably 2 mg / kg to 100 mg / kg, and more preferably 5 mg / kg to 50 mg / kg, depending on the target rodent.

[0063] The present invention is specifically illustrated by the following embodiments, but the present invention is not limited to the embodiments. Example

[0064] <Synthesis of Compound 2> [Chemical Formula 6] Under an argon atmosphere, 14.2 mg (0.030 mmol) of compound 1 in 2.5 mL of diethyl ether solution was cooled to 0 °C, and 0.20 mL of 0.5 M ethyl lithium (0.10 mmol) in benzene / cyclohexane solution was added. The mixture was stirred at 0 °C for 2 hours and 30 minutes. 2 M hydrochloric acid was added to the reaction solution, and the mixture was stirred at room temperature for 30 minutes. 28% ammonia was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine. After drying with anhydrous magnesium sulfate, the solvent was distilled off to obtain the crude product. Purification by rapid column chromatography (AcOEt / n-hexane = 1 / 12) yielded 4.3 mg of colorless oily compound 2 (28%).

[0065] 1 H NMR (400 MHz, CDCl3) δ 7.34 (d, J=4.1 Hz, 4H), 7.31-7.27 (m, 1H), 4.50 (s, 2H), 3.44 (t, J=6.6 Hz, 2H), 2.40 (q, J=7.3 Hz, 2H), 2.30 (d, J=6.9Hz, 2H), 1.95 (d, J=11.9 Hz, 1H), 1.88-1.60 (m, 5H), 1.60-0.86 (m, 23 H), 1.04 (t, J=7.3 Hz, 3H), 0.92 (s, 3 H), 0.91 (d, J=5.0 Hz, 3H), 0.63 (s, 3H).

[0066] <Synthesis of Compound 3> [Chemical Formula 7] Under an argon atmosphere, 9.8 mg (0.019 mmol) of compound 2 in 5.0 mL of diethyl ether solution was cooled to −69 °C, and 0.25 mL of 0.5 M ethyl lithium (0.13 mmol) in benzene / cyclohexane solution was added. The mixture was stirred at −69 °C for 4 hours and 15 minutes. A saturated aqueous solution of ammonium chloride was added to the reaction solution, and after reaching room temperature, water was added, followed by extraction with ethyl acetate. The organic layer was washed with brine. After drying with anhydrous magnesium sulfate, the solvent was distilled off to obtain the crude product. Purification by rapid column chromatography (AcOEt / n-hexane = 1 / 10) yielded 3.1 mg of colorless oily compound 3 (30%).

[0067] 1 H NMR (400 MHz, CDCl3) δ 7.35 (d, J=4.1 Hz, 4H), 7.31-7.28 (m, 1H), 4.51 (s, 2H), 3.44 (t, J=6.9 Hz, 2H), 1.96 (d, J=11.4 Hz, 1H), 0.64 (s, 3H).

[0068] <Synthesis of Compound 4> [Chemical Formula 8] 3.5 mg of palladium hydroxide was added to a 2.5 mL methanol solution containing 6.3 mg (0.012 mmol) of compound 3, followed by hydrogen exchange. The mixture was stirred at room temperature for 2 hours and 30 minutes. The reaction solution was filtered through diatomaceous earth and the solvent was distilled off to obtain 6.1 mg (quantitative) of a white solid, compound 4.

[0069] 1 H NMR (400 MHz, CDCl3) δ 3.66-3.58 (m, 2H), 1.95 (dd, J=11.5, 3.2 Hz,1H), 1.88-0.79 (m, 31H), 1.74 (d, J =13.3 Hz, 1H), 1.47 (q, J=7.6 Hz, 4H), 0.92 (d, J=6.9 Hz, 3H), 0.91 (s, 3H), 0.85 (t, J=7.6 Hz, 6H), 0.64 (s, 3H).

[0070] <Synthesis of Compound II> [Chemical Formula 9] Jones' reagent was prepared by dissolving 265.6 mg of chromium oxide (VI) in 0.77 mL of water and adding 0.23 mL of concentrated sulfuric acid under ice-cooling. 0.1 mL of Jones' reagent was added to 2.0 mL of anhydrous acetone solution containing 5.8 mg (0.013 mmol) of compound 4, and the mixture was stirred at room temperature for 40 minutes. Water was added to the reaction solution, the acetone was distilled off, and the mixture was extracted with diethyl ether. The organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off to obtain the crude product. Purification by GPC (CHCl3) yielded 4.0 mg of white solid compound II (67%).

[0071] 1 ¹H NMR (400 MHz, CDCl₃) δ 2.44–2.36 (m, 1H), 2.30–2.22 (m, 1H) 1.94 (d, J=11.0 Hz, 1H), 1.83–0.95 (m, 29H), 1.74 (d, J=13.3 Hz, 1H), 1.47 (q, J=7.3 Hz, 4H), 0.92 (d, J=6.4 Hz, 3H), 0.91 (s, 3H), 0.85 (t, J=7.3 Hz, 6H), 0.64 (s, 3H); HRMS calculated values, for C 30 H 52 NaO3(M + Na) + 483.3809, measured value 483.3815.

[0072] <Synthesis of Compound 5> [Chemical Formula 10] Under an argon atmosphere, 300.0 mg (0.651 mmol) of compound II, 200.0 mg (1.302 mmol) of methyl 4-aminobutyrate hydrochloride, and 197.8 mg (1.956 mmol) of N-methylmorpholine were dissolved in dichloromethane. Then, 250.0 mg (1.304 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added, and the mixture was stirred at room temperature for 7 hours. The solution was diluted with chloroform, washed with 1 M hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off to give the crude product. Purification by silica gel column chromatography (AcOEt / n-hexane = 1 / 1) yielded 274.7 mg of a colorless oily compound 5 (75%).

[0073] 1H NMR (600 MHz, CDCl3) δ 5.72 (s, 1H), 3.69 (s, 3H), 3.30 (dd, J=12.7, 6.6 Hz, 2H), 2.38 (t, J=7.1 Hz, 2H), 2.28-2.20 (m, 1H), 2.10-2.02 (m,1H) 1.98-1.90 (m, 1H), 1.90-0.95 (m, 35H), 0.91 (d, J=6.6 Hz, 3H), 0.91 (s,3H), 0.85 (t, J=7.5 Hz, 6H), 0.63 (s, 3H).

[0074] <Synthesis of Compound IV> [Chemical Formula 11] 250.0 mg (0.447 mmol) of compound 5 was dissolved in 10 mL of ethanol, and 2.0 mL of 15% (w / w) potassium hydroxide aqueous solution was added. The mixture was stirred overnight at room temperature. The solvent was distilled off, 1 M hydrochloric acid was added, and the solution was filtered and washed with water. The solution was dissolved in diethyl ether, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off to give 207.6 mg of white solid compound IV (85%).

[0075] 1 ¹H NMR (600 MHz, CDCl₃) δ 5.89 (m, 2H), 3.34 (dd, J=12.5, 6.2 Hz, 2H), 2.40 (t, J=6.9 Hz, 2H), 2.32–2.22 (m, 1H), 2.14–2.04 (m, 1H) 1.98–1.90 (m, 1H), 1.90–0.95 (m, 35H), 0.92 (d, J=6.5 Hz, 3H), 0.91 (s, 3H), 0.85 (t, J=7.5 Hz, 6H), 0.63 (s, 3H); HRMS calculated values, for C 34 H 59 NNaO4(M + Na) + 568.4333, measured value 568.4336.

[0076] <Synthesis of Compound XII> [Chemical Formula 12] Under an argon atmosphere, 200.0 mg (0.462 mmol) of compound 6 was dissolved in 10 mL of ethanol, and 0.033 mL (0.462 mmol) of acetyl chloride was added. The mixture was stirred at room temperature for 2 hours, followed by the addition of 0.30 mL (4.204 mmol) of acetyl chloride, and stirred overnight. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine. After drying with anhydrous magnesium sulfate, the solvent was distilled off to obtain the crude product. Purification by silica gel column chromatography (AcOEt / n-hexane = 10 / 1, 5 / 1) yielded 179.4 mg of a colorless oily compound XII (α:β = 80:20) (84%).

[0077] 1 ¹H NMR (600 MHz, CDCl₃) δ 4.12 (dd, J=14.0, 6.9 Hz, 2H), 2.38–2.30 (m, 1H), 2.24–2.14 (m, 1H), 2.05–0.93 (m, 30H), 1.25 (t, J=7.1 Hz, 3H), 1.24–1.21 (m, 6H), 0.93–0.89 (m, 6H), 0.64 (s, 3H); HRMS calculated values, for C 30 H 52 NaO3(M + Na) + 483.3810, measured value 483.3809.

[0078] <Synthesis of Compound XIII> [Chemical Formula 13] Under an argon atmosphere, 200.0 mg (0.462 mmol) of compound 6 was dissolved in 10 mL of 1-propanol, and 0.33 mL (4.624 mmol) of acetyl chloride was added. The mixture was stirred overnight at room temperature. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off to give the crude product. Purification by silica gel column chromatography (AcOEt / n-hexane = 10 / 1, 5 / 1) yielded 190.3 mg of a colorless oily compound XIII (α:β = 80:20) (87%).

[0079] 1¹H NMR (600 MHz, CDCl₃) δ 4.02 (t, J=6.8 Hz, 2H), 2.38–2.30 (m, 1H), 2.26–2.16 (m, 1H), 2.08–0.86 (m, 30H), 1.69–1.61 (m, 2H), 1.25–1.20 (m, 6H), 0.95 (t, J=7.3 Hz, 3H), 0.93–0.89 (m, 6H), 0.64 (s, 3H); HRMS calculated values, for C 31 H 54 NaO3(M + Na) + 497.3966, measured value 497.3965.

[0080] <Synthesis of Compound XIV> [Chemical Formula 14] Under an argon atmosphere, 200.0 mg (0.462 mmol) of compound 6 was dissolved in 10 mL of isopropanol, and 0.033 mL (0.462 mmol) of acetyl chloride was added. The mixture was stirred at room temperature for 2 hours, followed by the addition of 0.30 mL (4.204 mmol) of acetyl chloride, and stirred overnight. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off to obtain the crude product. Purification by silica gel column chromatography (AcOEt / n-hexane = 10 / 1, 5 / 1) yielded 117.9 mg of a colorless oily compound XIV (α:β = 80:20) (54%).

[0081] 1 ¹H NMR (600 MHz, CDCl₃) δ 5.00 (quintet, J=6.3 Hz, 1H), 2.35–2.25 (m, 1H), 2.21–2.14 (m, 1H), 2.06–0.70 (m, 30H), 1.57 (s, 6H), 1.25–1.19 (m, 6H), 0.93–0.84 (m, 6H), 0.64 (s, 3H); HRMS calculated values, for C 31 H 54 NaO3(M + Na) + 497.3968, measured value 497.3965.

[0082] <Experimental Example> Male rats (Slc: Wistar / ST, 7 weeks old) were administered cholecalciferol (150 mg / kg, 100 mg / kg, or 50 mg / kg) or compounds I-IV, VI, VII, XII-XIV (50 mg / kg, 25 mg / kg, 20 mg / kg, or 10 mg / kg) orally once, at N=3 per group. As a solvent control, corn oil (10 mL / kg) was administered orally once, at N=2 per group. Patients were observed for 14 days after administration.

[0083] The results showed that the number of individuals confirmed to have died or be near death during the observation period was as follows: 3 / 3 in the 150 mg / kg cholecalciferol group, 1 / 3 in the 100 mg / kg group, 0 / 3 in the 50 mg / kg group, and 0 / 2 in the corn oil group. The results for compounds I–IV, VI, VII, and XII–XIV are shown in the table below.

[0084] [Table 1] compound Ⅰ Ⅱ Ⅲ Ⅳ Ⅵ Ⅶ XII XⅢ XⅣ 50mg / kg 3 - - - 3 3 3 3 1 25mg / kg 3 3 - 3 3 1 3 1 0 20mg / kg - - 3 - - - - - - 10mg / kg 3 3 2 3 0 0 0 0 - *N=3 for each group; *-: Not implemented.

Claims

1. A rodenticide comprising a compound represented by the following general formula (I), a salt thereof, or a prodrug thereof: In the formula, R 1 and R 2 Each can independently represent an alkyl group with 1 to 8 hydrogen atoms or carbon atoms, where n represents an integer from 1 to 3. R 3 R 4 R 5 and R 6 Each can independently represent an alkyl group having 1 to 6 hydrogen atoms or carbon atoms. X represents COOH, -C(=O)NH-Z, and -CH(OH)-(Y). m -CH(OH)R7、-NH-CO-OR 10 -CO-OR 10 or -NH-CO-N(R) 11 )-R 10 Z represents a hydrogen atom, -CN, an alkyl group with 1 to 8 carbon atoms, an alkoxy group with 1 to 8 carbon atoms, or a hydroxyl group; Y represents -C(R8)(R9)-, -C(=O)-, or -C(=CH2)-; m represents an integer from 0 to 3; R7, R8, and R9 each independently represent a hydrogen atom or an alkyl group with 1 to 8 carbon atoms; the alkyl groups with 1 to 8 carbon atoms represented by Z, R7, R8, and R9 may have substituents selected from carboxyl or hydroxyl groups; R 10 and R 11 Each can independently represent a hydrogen atom or an alkyl group with 1 to 8 carbon atoms that may have substituents.

2. The rodenticide according to claim 1, wherein, X is COOH.

3. The rodenticide according to claim 1 or 2, wherein, R 1 and R 2 It can be methyl or ethyl.

4. The rodenticide according to claim 1 or 2, wherein, R 3 R 4 R 5 and R 6 It is a hydrogen atom.

5. The rodenticide according to claim 1 or 2, wherein, n is 1.

6. A method for rodent control, wherein the rodenticide described in claim 1 or 2 is used.

Images