Rodenticide comprising lithocholic acid derivative

Abstract

The present invention addresses the problem of providing a novel rodenticide. According to the present invention, there is provided a rodenticide comprising a compound represented by general formula (I), a salt thereof, or a prodrug thereof. (In the formula, R1 and R2 each independently represent a hydrogen atom or an alkyl group having 1-8 carbon atoms; n represents an integer of 1-3; R3, R4, R5, and R6 each independently represent a hydrogen atom or an alkyl group having 1-6 carbon atoms; X represents COOH, -C(=O)NH-Z, -CH(OH)-(Y)m-CH(OH)R7, -NH-CO-O-R10, -CO-O-R10 or -NH-CO-N(R11)-R10; Z represents a hydrogen atom, -CN, an alkyl group having 1-8 carbon atoms, an alkoxyl group having 1-8 carbon atoms, or a hydroxyl group; Y represents -C(R8)(R9)-, -C(=O)-, or -C(=CH2)-; m represents an integer of 0-3; R7, R8, and R9 each independently represent a hydrogen atom or an alkyl group having 1-8 carbon atoms; each of alkyl groups having 1-8 carbon atoms which are respectively represented by Z, R7, R8 and R9 may have a substituent selected from a carboxyl group and a hydroxyl group; and R10 and R11 each independently represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms which may have a substituent.)

Description

Rodenticides containing lithocholic acid derivatives

[0001] The present invention relates to rodenticides containing lithocholic acid derivatives having vitamin D activity.

[0002] Vitamin D binds to the vitamin D receptor (VDR) via its metabolically activated form, 1α,25-dihydroxyvitamin D3, and regulates the expression of specific genes. By regulating this gene expression, vitamin D plays important physiological roles, such as maintaining blood calcium levels, bone formation, immune function, and regulating cell differentiation and proliferation. To date, numerous VDR ligands have been developed with the aim of developing therapeutic drugs for osteoporosis, psoriasis, cancer, and other conditions, and some of these have been used clinically as pharmaceuticals.

[0003] Lithocholic acid has been found to be an endogenous ligand of VDR. Patent Document 1 describes that a lithocholic acid derivative having a hydroxyalkyl group at the 3-position, in which the main chain of the hydroxyalkyl group at the 3-position has two or more carbon atoms, has excellent vitamin D3 agonist activity.

[0004] On the other hand, rodenticides are chemicals used to exterminate rats. They are usually placed in the form of poison bait and consumed by rats to kill them. There are two types of rodenticides: cumulative poisons and acute poisons. Cumulative poisons are effective when taken continuously in several doses, and examples include coumatetralyl, warfarin, and diphethialol. Acute poisons include yellow phosphorus, arsenic trioxide, aluminum phosphide, zinc phosphide, norbormide, sciliroside, thallium, thallium sulfate, α-naphthylthiourea, and sodium monofluoroacetate, but these drugs are highly toxic and difficult to handle.

[0005] International Publication No. WO2017 / 131144

[0006] An object of the present invention is to provide a novel rodenticide.

[0007] As a result of intensive research to solve the above problems, the present inventors have found that lithocholic acid derivatives having a hydroxyalkyl group at the 3-position, wherein the hydroxyalkyl group at the 3-position has two or more carbon atoms in the main chain, are useful as rodenticides, and have thus completed the present invention.

[0008] According to the present invention, the following inventions are provided: <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 are each independently a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. n is an integer of 1 to 3. ３ , R ４ , R ５ and R ６ Each of the groups independently represents 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)R ７ , -NH-CO-OR 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, and Y represents —C(R ８ ) (R ９ )-, -C(=O)-, or -C(=CH ２ )-, and m represents an integer of 0 to 3. ７ , R ８ and R ９ each independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. ７ , R ８ and R ９ The alkyl group having 1 to 8 carbon atoms represented by R may have a substituent selected from a carboxyl group or a hydroxyl group. １０ and R １１ each independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms which may have a substituent.) <2> The rodenticide according to <1>, wherein X is COOH. <3> R１ and R ２ <4> The rodenticide according to <1> or <2>, wherein R is a methyl group or an ethyl group. ３ , R ４ , R ５ and R ６ <5> The rodenticide according to <1> or <2>, wherein n is a hydrogen atom. <6> The rodenticide according to <1> or <2>, wherein n is 1. <7> A method for killing rodents, using the rodenticide according to <1> or <2>.

[0009] The present invention further provides the following: [A] A method for killing rodents, which comprises administering a compound represented by general formula (I), a salt thereof, or a prodrug thereof to rodents. [B] A compound represented by general formula (I), a salt thereof, or a prodrug thereof for use in killing rodents. [C] Use of a compound represented by general formula (I), a salt thereof, or a prodrug thereof for the manufacture of a rodenticide.

[0010] The rodenticide of the present invention has excellent rodenticidal activity.

[0011] The present invention will be described in more detail below. The rodenticide of the present invention contains, as an active ingredient, a compound represented by the following general formula (I), a salt thereof, or a prodrug thereof. (In the formula, R １ and R ２ are each independently a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. n is an integer of 1 to 3. ３ , R ４ , R ５ and R ６ Each of the groups independently represents 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)R ７ , -NH-CO-OR 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, and Y represents —C(R ８ ) (R ９)-, -C(=O)-, or -C(=CH ２ )-, and m represents an integer of 0 to 3. ７ , R ８ and R ９ each independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. ７ , R ８ and R ９ The alkyl group having 1 to 8 carbon atoms represented by R may have a substituent selected from a carboxyl group or a hydroxyl group. １０ and R １１ each independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms which may have a substituent.

[0012] The substituent at the 3-position of the steroid skeleton (i.e., HOC(R １ ) (R ２ ) (CH ２ ) ｎ The configuration of the aryl group (group represented by -) is not particularly limited, and may be either an α-substituted or β-substituted form.

[0013] In this specification, the alkyl group having 1 to 8 carbon atoms and the alkyl group having 1 to 6 carbon atoms may be linear, branched, cyclic, or a combination thereof. The alkyl group having 1 to 8 carbon atoms and the alkyl group having 1 to 6 carbon atoms are not particularly limited, and examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropylmethyl group, an n-butyl group, a sec-butyl group, a tert-butyl group, a cyclobutyl group, a cyclobutylmethyl group, a cyclopentyl group, and a cyclohexyl group.

[0014] In this specification, the alkoxyl group having 1 to 8 carbon atoms may be linear, branched, cyclic, or a combination thereof. The alkoxyl group having 1 to 8 carbon atoms is not particularly limited, and examples thereof include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, a cyclopropylmethyloxy group, an n-butoxy group, a sec-butoxy group, a tert-butoxy group, a cyclobutyloxy group, a cyclobutylmethoxy group, a cyclopentyloxy group, and a cyclohexyloxy group.

[0015] In this specification, the alkyl moiety in the carboxyalkyl group having 1 to 8 carbon atoms may be linear, branched, or cyclic, or a combination thereof, and is a divalent group in which one hydrogen atom has been removed from a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropylmethyl group, an n-butyl group, a sec-butyl group, a tert-butyl group, a cyclobutyl group, a cyclobutylmethyl group, a cyclopentyl group, or a cyclohexyl group.

[0016] R １ and R ２ may each independently be the same group or different groups, but preferably be the same group. １ and R ２ It is particularly preferred that both R are methyl groups or ethyl groups. ３ , R ４ , R ５ and R ６ may each independently be the same group or different groups. ３ , R ４ , R ５ and R ６ are particularly preferably all hydrogen atoms. n represents an integer of 1 to 3, preferably 1 or 2, and more preferably 1.

[0017] X is COOH, -C(=O)NH-Z, -CH(OH)-(Y) ｍ -CH(OH)R ７ , -NH-CO-OR １０ , -CO-O-R １０ or —NH—CO—N(R １１ )-R １０ Among the above, COOH is preferred.

[0018] Z represents a hydrogen atom, -CN, an alkyl group having 1 to 8 carbon atoms, an alkoxyl 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 which may have a carboxyl group. Examples of the alkyl group having 1 to 8 carbon atoms which may have a carboxyl group include -(CH ２ ) ３ COOH is particularly preferred.

[0019] Y is -C(R８ ) (R ９ )-, -C(=O)-, or -C(=CH ２ )-, preferably -C(R ８ ) (R ９ )—, more preferably —CH ２ m represents an integer of 0 to 3, preferably 0 or 1. ７ , R ８ and R ９ R each independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. ７ is preferably a hydrogen atom or a methyl group. ７ , R ８ and R ９ The alkyl group having 1 to 8 carbon atoms represented by may have a substituent selected from a carboxyl group or a hydroxyl group, or may not have the above substituent. When the alkyl group has a carboxyl group, it is preferably a carboxyalkyl group having 1 to 8 carbon atoms.

[0020] R １０ and R １１ each independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms which may have a substituent. The alkyl group having 1 to 8 carbon atoms in the "alkyl group having 1 to 8 carbon atoms which may have a substituent" may have a substituent, and examples of the substituent include halogen (fluorine, chlorine, bromine, iodine, etc.), ether, and aromatic ring. The ether or aromatic ring may be present in the middle of the alkyl chain.

[0021] X is -NH-CO-OR １０ When R １０ represents methyl or ethyl. X is —NH—CO—N(R １１ )-R １０ When R １０ and R １１ each independently represents a hydrogen atom or a methyl group. １０ When R １０ represents a methyl group, an ethyl group, an n-propyl group, or an isopropyl group.

[0022] The compound represented by general formula (I) may have one or more asymmetric carbon atoms, and any optically active substance based on the asymmetric carbon atoms, stereoisomers such as diastereoisomers, any mixture of stereoisomers, racemates, etc. are all included in the scope of the present invention.

[0023] The compound represented by general formula (I) may exist in the form of a salt such as an acid addition salt or a base addition salt, and these salts are also included within the scope of the present invention. Examples of acid addition salts include mineral acid salts such as hydrochloride, hydrobromide, sulfate, and nitrate, and organic acid salts such as p-toluenesulfonate, methanesulfonate, oxalate, tartrate, and maleate. Examples of base addition salts include metal salts such as sodium salt, potassium salt, magnesium salt, and calcium salt, and organic amine salts such as ammonium salt, triethylamine salt, and ethanolamine salt. In addition to these, amino acid salts such as glycine salts are also included within the scope of the present invention.

[0024] The compound represented by general formula (I) may be made into a prodrug. After administration to a living body, the prodrug becomes a pharmaceutically active compound through the action of an enzyme, metabolic hydrolysis, or the like. The prodrug may be an acid derivative known to those skilled in the art, and examples thereof include, but are not limited to, esters produced by reacting the compound represented by general formula (I) with an appropriate alcohol, amides produced by reacting the compound represented by general formula (I) with an appropriate amine, and 2,4-alcohols as reduced forms of carboxyl groups.

[0025] The compound represented by general formula (I), its salt, and its prodrug may exist in the form of an adduct (hydrate or solvate) with water or various solvents, and these adducts are also within the scope of the present invention. Examples of the solvent in the solvate include, but are not limited to, methanol, ethanol, acetonitrile, etc. The adduct (hydrate or solvate) may be a single one or a mixture of multiple types.

[0026] Any crystalline form of the compound represented by formula (I), its salts and prodrugs thereof are also within the scope of the present invention.

[0027] Specific examples of the compound represented by formula (I) include the following compounds.

[0028]

[0029]

[0030] The compound represented by the general formula (I) is described in International Publication No. WO2017 / 131144, International Publication No. WO2021 / 033766, and JP-A-2023-111289, and can be produced by the method described in the above publications.

[0031] The compound represented by formula (I) has excellent rodenticidal activity and can be used as an active ingredient in rodenticides. According to the present invention, there is provided a method for killing rodents using the rodenticide of the present invention.

[0032] The rodenticidal activity of the compound represented by general formula (I) can be verified by administering the compound represented by general formula (I) to mice and evaluating the survival rate of the mice.

[0033] The rodenticide of the present invention contains a compound represented by general formula (I) as an active ingredient. The rodenticide of the present invention can be in any form suitable for repelling harmful rodents, for example, it can be provided in a formulation suitable for oral administration. The rodenticide of the present invention can be in the form of a concentrated liquid, powder, grain, gel, paste, or extruded bait such as pellets or blocks.

[0034] The rodenticide of the present invention may contain one or more excipients in addition to the compound represented by general formula (I) as an active ingredient, such as mineral oil, carbohydrates such as dextrin, inorganic substances such as clay, other organic solvents such as glycol and DMSO, water, grain raw materials such as barley, wheat, corn, or rice, and binders such as paraffin.

[0035] The compound represented by formula (I) can be mixed with an excipient by a conventional method (for example, convection, dispersion, shear, etc.).

[0036] The rodenticide of the present invention can be used to exterminate rodents (especially harmful rodents). Rodents include mice, rats, voles, brown rats, roof rats, and house mice. Examples include roof rats (Rattus rattus), brown rats (Rattus norvegicus), house mice (Mus musculus), and field mice (Microtus montebelli).

[0037] The rodenticides of the present invention can be used to control rodents in domestic, rural, commercial, or urban environments, in public food service or hospitality establishments, or in agricultural processing industries. The rodenticides of the present invention may also be used as a preventative measure in areas that should be protected from rodent attack. The rodenticides of the present invention may be placed or secured within bait boxes adapted for rodent control.

[0038] The dose of the compound represented by general formula (I) used can be appropriately determined depending on the target rodent, and is preferably 1 mg / kg to 500 mg / kg, preferably 2 mg / kg to 100 mg / kg, more preferably 5 mg / kg to 50 mg / kg, depending on the target rodent.

[0039] The present invention will be specifically explained by the following examples, but the present invention is not limited to these examples.

[0040] <Synthesis of Compound 2>

[0041] Under an argon atmosphere, a solution of compound 1 (14.2 mg, 0.030 mmol) in diethyl ether (2.5 mL) was cooled to 0°C, and 0.5 M ethyllithium (benzene / cyclohexane solution, 0.20 mL, 0.10 mmol) 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% aqueous ammonia 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 evaporated to give a crude product. Purification by flash column chromatography (AcOEt / n-hexane = 1 / 12) gave compound 2 (4.3 mg, 28%) as a colorless oil. 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 = 6.9 Hz, 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, 3 H).

[0042] <Synthesis of Compound 3>

[0043] Under an argon atmosphere, a solution of compound 2 (9.8 mg, 0.019 mmol) in diethyl ether (5.0 mL) was cooled to -69°C, and 0.5 M ethyllithium (benzene / cyclohexane solution, 0.25 mL, 0.13 mmol) 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 the temperature was returned to room temperature, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated to obtain a crude product. Purification by flash column chromatography (AcOEt / n-hexane = 1 / 10) yielded compound 3 (3.1 mg, 30%) as a colorless oil. 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), 1.93-1.60 (m, 5H), 1.60-0.79 (m, 26 H), 1.48 (q, J = 7.3 Hz, 4H), 0.92 (d, J = 5.0 Hz, 3H), 0.91 (s, 3H), 0.86 (t, J = 7.6 Hz, 6H), 0.64 (s, 3H).

[0044] <Synthesis of Compound 4>

[0045] Palladium hydroxide (3.5 mg) was added to a solution of compound 3 (6.3 mg, 0.012 mmol) in methanol (2.5 mL), and the mixture was stirred at room temperature for 2 hours and 30 minutes after purging with hydrogen. The reaction solution was filtered through Celite, and the solvent was evaporated to give compound 4 (6.1 mg, quant.) as a white solid. 1H 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).

[0046] <Synthesis of Compound II>

[0047] Chromium(VI) oxide (265.6 mg) was dissolved in water (0.77 mL) and concentrated sulfuric acid (0.23 mL) was added under ice cooling to prepare the Jones reagent. To a solution of compound 4 (5.8 mg, 0.013 mmol) in anhydrous acetone (2.0 mL), Jones reagent (0.1 mL) was added and stirred at room temperature for 40 minutes. Water was added to the reaction solution, and the acetone was evaporated. The mixture was then extracted with diethyl ether, and the organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated to give the crude product. Purification by GPC (CHCl3) afforded compound II (4.0 mg, 67%) as a white solid. 1 H 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 calcd for C 30 H 52 NaO3 (M + Na) + 483.3809, found 483.3815.

[0048] <Synthesis of Compound 5>

[0049] Under an argon atmosphere, compound II (300.0 mg, 0.651 mmol), methyl 4-aminobutyrate hydrochloride (200.0 mg, 1.302 mmol), and N-methylmorpholine (197.8 mg, 1.956 mmol) were dissolved in dichloromethane, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (250.0 mg, 1.304 mmol) was added. The mixture was stirred at room temperature for 7 hours. The mixture was diluted with chloroform, washed with 1 M hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated to give a crude product. Purification by silica gel column chromatography (AcOEt / n-hexane = 1 / 1) afforded compound 5 (274.7 mg, 75%) as a colorless oil. 1 H 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).

[0050] <Synthesis of Compound IV>

[0051] Compound 5 (250.0 mg, 0.447 mmol) was dissolved in ethanol (10 mL), and 15% (w / w) aqueous potassium hydroxide solution (2.0 mL) was added. The mixture was stirred at room temperature overnight. The solvent was evaporated, and 1 M hydrochloric acid was added. The residue was collected by filtration and washed with water. The residue was dissolved in diethyl ether, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and then evaporated to give compound IV (207.6 mg, 85%) as a white solid. 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 calcd for C 34 H 59 NNaO4 (M + Na) + 568.4333, found 568.4336.

[0052] <Synthesis of Compound XII>

[0053] Under an argon atmosphere, compound 6 (200.0 mg, 0.462 mmol) was dissolved in ethanol (10 mL), acetyl chloride (0.033 mL, 0.462 mmol) was added, and the mixture was stirred at room temperature for 2 hours. Further acetyl chloride (0.30 mL, 4.204 mmol) was added, and the mixture was stirred overnight. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated to give the crude product. Purification by silica gel column chromatography (AcOEt / n-hexane = 10 / 1, 5 / 1) afforded compound XII (α:β=80:20) (179.4 mg, 84%) as a colorless oil. 1 H 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 calcd for C 30 H 52 NaO3 (M + Na)+ 483.3810, found 483.3809.

[0054] <Synthesis of Compound XIII>

[0055] Under an argon atmosphere, compound 6 (200.0 mg, 0.462 mmol) was dissolved in 1-propanol (10 mL), acetyl chloride (0.33 mL, 4.624 mmol) was added, and the mixture was stirred overnight at room temperature. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated to give the crude product. Purification by silica gel column chromatography (AcOEt / n-hexane = 10 / 1, 5 / 1) afforded compound XIII (α:β=80:20) (190.3 mg, 87%) as a colorless oil. 1 H 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 calcd for C 31 H 54 NaO3 (M + Na) + 497.3966, found 497.3965.

[0056] <Synthesis of Compound XIV>

[0057] Under an argon atmosphere, compound 6 (200.0 mg, 0.462 mmol) was dissolved in isopropanol (10 mL), acetyl chloride (0.033 mL, 0.462 mmol) was added, and the mixture was stirred at room temperature for 2 hours. Further acetyl chloride (0.30 mL, 4.204 mmol) was added, and the mixture was stirred overnight. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated to give the crude product. Purification by silica gel column chromatography (AcOEt / n-hexane = 10 / 1, 5 / 1) afforded compound XIV (α:β=80:20) (117.9 mg, 54%) as a colorless oil. 1 H NMR (600 MHz, CDCl3) δ 5.00 (quin, 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 calcd for C 31 H 54 NaO3 (M + Na) + 497.3968, found 497.3965.

[0058] <Test Example> Cholecalciferol (150 mg / kg, 100 mg / kg, or 50 mg / kg) or compounds I to IV, VI, VII, XII to XIV (50 mg / kg, 25 mg / kg, or 20 mg / kg, 10 mg / kg) were orally administered by gavage in a single dose to male rats (Slc:Wistar / ST, 7 weeks old) (N=3 per group). Corn oil (10 mL / kg) was also orally administered by gavage in a single dose as a vehicle control (N=2). Observation was carried out for 14 days after administration.

[0059] As a result, the number of animals confirmed dead or moribund during the observation period was 3 / 3 in the cholesterol calciferol 150 mg / kg 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 to IV, VI, VII, and XII to XIV are shown in the table below.

[0060]

[0061] *N=3 for each group *-: Not performed

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 independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms; and n represents an integer of 1 to 3. ３ , R ４ , R ５ and R ６ are each independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and X is COOH, —C(═O)NH-Z, —CH(OH)—(Y). ｍ -CH(OH)R ７ , -NH-CO-OR 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, and Y represents —C(R ８ ) (R ９ )-, -C(=O)-, or -C(=CH ２ )-, and m represents an integer of 0 to 3. ７ , R ８ and R ９ each independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. ７ , R ８ and R ９ The alkyl group having 1 to 8 carbon atoms represented by R may have a substituent selected from a carboxyl group or a hydroxyl group. １０ and R １１ each independently represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms which may have a substituent.

2. The rodenticide of claim 1, wherein X is COOH.

3. R １ and R ２ 3. The rodenticide according to claim 1, wherein is a methyl group or an ethyl group.

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

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

6. A method for killing rodents, which uses the rodenticide according to claim 1 or 2.

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