Parasite- and hygienic pest-controlling agent

Abstract

There is provided a novel agent for controlling harmful arthropods or nematodes that are parasites and hygienic pests for animals. An ecto- or endo-parasiticide for mammals or the like comprising as active ingredient, one or more selected from substituted benzamide compounds of formula (1) or salts thereof: ##STR00001##
wherein A.sup.1 is CX.sup.3 or nitrogen atom, etc., A.sup.2 and A.sup.3 are CH, etc., A.sup.4 is CH or nitrogen atom, etc., G is G-2a, etc., W is oxygen atom or sulfur atom, X.sup.1 is halogen atom, trifluoromethyl, etc., X.sup.2 is hydrogen atom, halogen atom, trifluoromethyl, etc., X.sup.3 is hydrogen atom, halogen atom, etc., Y.sup.1 is hydrogen atom, halogen atom, methyl, etc., R.sup.1 is trifluoromethyl, etc., R.sup.2 is E-3a, etc., R.sup.3 is hydrogen atom, etc., p is an integer of 0 to 2.

Claims

1. A method for controlling parasites and hygienic pests comprising: administering to an animal a parasite- and hygienic pest-controlling composition comprising as active ingredient, a substituted benzamide compound of formula (1) or a salt thereof: ##STR00155## wherein A.sup.1 is CX.sup.3 or nitrogen atom, A.sup.2, A.sup.3 and A.sup.4 are independently of one another CY.sup.2 or nitrogen atom, G is a heterocyclic ring of following structural formulae G-2: ##STR00156## W is oxygen atom or sulfur atom, X.sup.1 is hydrogen atom, halogen atom, C.sub.1-C.sub.3haloalkyl, halocyclopropyl, OR.sup.4, SF.sub.5 or C.sub.1-C.sub.3haloalkylthio, X.sup.2 is hydrogen atom, halogen atom, cyano, nitro, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, OR.sup.4, S(O).sub.pR.sup.4 or NH.sub.2, X.sup.3 is hydrogen atom, halogen atom, cyano, methyl, methoxy, difluoromethoxy, methylthio, NH.sub.2 or dimethylamino, or X.sup.3 together with X.sup.1 optionally forms 5-membered or 6-membered ring together with carbon atoms to which each of X.sup.1 and X.sup.3 is bonded by forming CF.sub.2OCF.sub.2, OCF.sub.2O, CF.sub.2OCF.sub.2O or OCF.sub.2CF.sub.2O, Y.sup.1 is hydrogen atom, halogen atom, cyano, nitro, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, (C.sub.1-C.sub.2)alkyl substituted with R.sup.5, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3haloalkylthio, N(R.sup.7)R.sup.6, C(S)NH.sub.2, C.sub.2-C.sub.3alkynyl, trimethylsilylethynyl, phenyl, phenyl substituted with (Z).sub.n1 or D, D is an aromatic heterocyclic ring of following structural formulae D-1 to D-3, D-7, D-11 and D-19 to D-23: ##STR00157## Z is halogen atom, cyano, nitro, methyl, trifluoromethyl, methoxy, methylthio, methylsulfinyl, methylsulfonyl, NH.sub.2 or dimethylamino, when n1 to n4 are an integer of 2 or more, each Z may be identical with or different from each other, Y.sup.2 is hydrogen atom, halogen atom or methyl, or when two Y.sup.2s are adjacent, the adjacent two Y.sup.2s may form 5-membered or 6-membered ring together with carbon atoms to which the two Y.sup.2s are bonded by forming NSN or CHCHCHCH, in this case, hydrogen atoms bonded to each carbon atom forming the ring may be arbitrarily substituted with Z, further when it is substituted with two or more Zs, each Z may be identical with or different from each other, R.sup.1 is C.sub.1-C.sub.3haloalkyl or halocyclopropyl, R.sup.1a is hydrogen atom, halogen atom, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkylthiomethyl, C.sub.1-C.sub.3haloalkylthiomethyl, C.sub.1-C.sub.3alkylsulfinylmethyl, C.sub.1-C.sub.3haloalkylsulfinylmethyl, C.sub.1-C.sub.3alkylsulfonylmethyl, C.sub.1-C.sub.3haloalkylsulfonylmethyl, OH, C.sub.1-C.sub.3alkylthio or C.sub.1-C.sub.3alkylsulfonyl, R.sup.1b is hydrogen atom or halogen atom, or R.sup.1b together with R.sup.1a optionally forms C.sub.1-C.sub.4alkylidene, phenylmethylidene, hydroxyimino or C.sub.1-C.sub.3alkoxyimino, R.sup.2is a heterocyclic ring of following structural formulae E-6 or (C.sub.1-C.sub.3)alkyl Substituted with E-6: ##STR00158## R.sup.3 is hydrogen atom, C.sub.1-C.sub.4alkyl, (C.sub.1-C.sub.2)alkyl substituted with R.sup.11, C.sub.3-C.sub.4cycloalkyl, C.sub.3-C.sub.4alkenyl, C.sub.3-C.sub.4alkynyl, C(O)R.sup.12, C(O)OR.sup.13, C(O)C(O)OR.sup.13 or C.sub.1-C.sub.3haloalkylthio, R.sup.4 is C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl or C.sub.1-C.sub.2haloalkoxy (C.sub.1-C.sub.2)haloalkyl, R.sup.5 is OH, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio or C.sub.1-C.sub.3haloalkylthio, R.sup.6 is hydrogen atom, C.sub.1-C.sub.4alkyl, CHO, C.sub.1-C.sub.3alkylcarbonyl, C.sub.1-C.sub.3haloalkylcarbonyl, C.sub.3-C.sub.4cycloalkylcarbonyl, C.sub.1-C.sub.3alkoxycarbonyl, C.sub.1-C.sub.3alkylthiocarbonyl, C.sub.1-C.sub.3alkoxythiocarbonyl, C.sub.1-C.sub.3alkyldithiocarbonyl, C.sub.1-C.sub.3alkylsulfonyl or C.sub.1-C.sub.3haloalkylsulfonyl, R.sup.7 is hydrogen atom or C.sub.1-C.sub.3alkyl, R.sup.10 is hydrogen atom, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, hydroxy (C.sub.1-C.sub.2)alkyl, C.sub.1-C.sub.3alkoxy (C.sub.1-C.sub.2)alkyl, benzyl, C.sub.3-C.sub.4cycloalkyl, oxetan-3-yl, thietan-3-yl, C.sub.3-C.sub.4alkynyl, C.sub.3-C.sub.4alkenyl, phenyl or phenyl substituted with (Z).sub.n1, R.sup.11 is cyano, C.sub.3-C.sub.4cycloalkyl, OR.sup.14, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylsulfonyl, C.sub.1-C.sub.3alkoxycarbonyl, C(O)NH.sub.2, C(S)NH.sub.2, phenyl or D-23, R.sup.12 is hydrogen atom, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.3alkoxy (C.sub.1-C.sub.2)alkyl, C.sub.1-C.sub.3alkylthio (C.sub.1-C.sub.2)alkyl, C.sub.1-C.sub.3alkylsulfinyl (C.sub.1-C.sub.2)alkyl, C.sub.1-C.sub.3alkylsulfonyl (C.sub.1-C.sub.2)alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, phenyl, phenyl substituted with (Z).sub.n1, D-1, D-2 or D-23, R.sup.13 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.3alkoxy (C.sub.1-C.sub.2)alkyl, C.sub.3-C.sub.4alkenyl, C.sub.3-C.sub.4alkynyl or phenyl, R.sup.14 is hydrogen atom, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.4alkenyl, C.sub.3-C.sub.4alkynyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4haloalkylcarbonyl, C.sub.3-C.sub.6cycloalkylcarbonyl or C.sub.1-C.sub.4alkoxycarbonyl, n1 is an integer of 1 to 5, n2 is an integer of 0 to 3, n3 is an integer of 0 to 4, n4 is an integer of 0 to 2, n5 is an integer of 0 or 1, p is an integer of 0 to 2, and q is an integer of 0 or 1.

2. The method according to claim 1, wherein in the parasite- and hygienic pest-controlling composition, A.sup.2 is CH, A.sup.3 and A.sup.4 are independently of one another CY.sup.2 or nitrogen atom, X.sup.1 is halogen atom, trifluoromethyl, pentafluoroethyl, trifluoromethoxy, SF.sub.5 or trifluoromethylthio, X.sup.2 is hydrogen atom, halogen atom, cyano, methyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, difluoromethylthio or trifluoromethylthio, X.sup.3 is hydrogen atom, fluorine atom, chlorine atom, bromine atom, cyano or difluoromethoxy, Y.sup.1 is hydrogen atom, halogen atom, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxymethyl, cyclopropyl, difluoromethoxy, methylthio, N(R.sup.7)R.sup.6, C(S)NH.sub.2 or ethynyl, Y.sup.2 is hydrogen atom, or when two Y.sup.2s are adjacent, the adjacent two Y.sup.2s may form 6-membered ring together with carbon atoms to which the two Y.sup.2s are bonded by forming CHCHCHCH, R.sup.1 is difluoromethyl, trifluoromethyl or chlorodifluoromethyl, R.sup.1a is hydrogen atom, halogen atom, methyl, methylthiomethyl, methylsulfinylmethyl or methylsulfonylmethyl, R.sup.1b is hydrogen atom, or R.sup.1b together with R.sup.1a optionally forms C.sub.2-C.sub.3alkylidene, R.sup.2 is E-6, R.sup.3 is hydrogen atom, C.sub.1-C.sub.3alkyl, methyl substituted with R.sup.11, cyclopropyl, allyl, propargyl, C(O)R.sup.12 or C(O)OR.sup.13, R.sup.6 is hydrogen atom, methyl, C.sub.1-C.sub.3alkylcarbonyl or cyclopropylcarbonyl, R.sup.7 is hydrogen atom or methyl, R.sup.10 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.3alkoxy (C.sub.1-C.sub.2)alkyl, oxetan-3-yl or C.sub.3-C.sub.4alkynyl, R.sup.11 is cyano, methoxy, ethoxy or C(S)NH.sub.2, R.sup.12 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.3alkoxy (C.sub.1-C.sub.2)alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.2-C.sub.4alkenyl or C.sub.2-C.sub.4alkynyl, R.sup.13 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.3alkoxy (C.sub.1-C.sub.2)alkyl, C.sub.3-C.sub.4alkenyl or C.sub.3-C.sub.4alkynyl, and q is 1.

3. The method according to claim 2, wherein in the parasite- and hygienic pest-controlling composition, A.sup.3 is CY.sup.2, X.sup.1 is halogen atom, trifluoromethyl, trifluoromethoxy or trifluoromethylthio, X.sup.2 is hydrogen atom, halogen atom, cyano or trifluoromethyl, X.sup.3 is hydrogen atom, fluorine atom, chlorine atom or difluoromethoxy, Y.sup.1 is hydrogen atom, halogen atom, nitro, methyl, ethyl, trifluoromethyl, methoxymethyl or N(R.sup.7)R.sup.6, R.sup.1 is trifluoromethyl or chlorodifluoromethyl, R.sup.1a is hydrogen atom or halogen atom, R.sup.1b is hydrogen atom, R.sup.3 is hydrogen atom, ethyl, cyanomethyl, methoxymethyl, propargyl, C(O)R.sup.12 or methoxycarbonyl, R.sup.6 is hydrogen atom, methyl or acetyl, R.sup.10 is C.sub.1-C.sub.3alkyl or C.sub.2-C.sub.3haloalkyl, and R.sup.12 is C.sub.1-C.sub.4alkyl or cyclopropyl.

4. The method according to claim 3, wherein in the parasite- and hygienic pest-controlling composition, A.sup.3 and A.sup.4 are CH, W is oxygen atom, X.sup.1 is chlorine atom, bromine atom, iodine atom or trifluoromethyl, X.sup.2 is hydrogen atom, halogen atom or trifluoromethyl, X.sup.3 is hydrogen atom, fluorine atom or chlorine atom, Y.sup.1 is halogen atom, nitro, methyl, ethyl or trifluoromethyl, R.sup.1 is trifluoromethyl, R.sup.1a is hydrogen atom, and R.sup.3 is hydrogen atom.

5. The method according to claim 4, wherein in the parasite- and hygienic pest-controlling composition, A.sup.1 is CX.sup.3, X.sup.1 is chlorine atom, bromine atom or trifluoromethyl, X.sup.2 is chlorine atom, bromine atom or trifluoromethyl, X.sup.3 is hydrogen atom or fluorine atom, and Y.sup.1 is chlorine atom, bromine atom or methyl.

6. The method according to claim 1, wherein in the parasite- and hygienic pest-controlling composition, R.sup.2 is E-6.

7. The method according to claim 1, wherein in the parasite- and hygienic pest-controlling composition, R.sup.1a and R.sup.1b are hydrogen atom, and R.sup.2 is E-6.

8. The method according to claim 1, wherein in the parasite- and hygienic pest-controlling composition, R.sup.1a is halogen atom, R.sup.1b are hydrogen atom, and R.sup.2 is E-6.

9. The method according to claim 1, wherein administering the compound is an oral administration.

10. The method according to claim 1, wherein administering the compound is a parenteral administration.

11. The method according to claim 10, wherein the parenteral administration is a transdermal administration.

12. The method according to claim 9, wherein in the parasite- and hygienic pest-controlling composition, the animals are mammals.

13. The method according to claim 12, wherein in the parasite- and hygienic pest-controlling composition, the mammals are rabbit, guinea pig, hamster, Mongolian gerbil, mouse, rat, squirrel, monkey, dog, ferret, cat, yak, cattle, buffalo, goat, sheep, antelope, deer, reindeer, swine, pig, camel, alpaca, llama, donkey, horse or kangaroo.

14. The method according to claim 13, wherein in the parasite-and and hygienic pest-controlling composition, the mammals are dog or cat.

15. The method according to claim 1, wherein in the parasite- and hygienic pest-controlling composition, the parasite is ecto-parasitic invertebrates for animals.

16. The method according to claim 15, wherein in the parasite- and hygienic pest-controlling composition, the ecto-parasitic invertebrates for animals are flea, biting louse, louse, feather mite, itch mite, Cheyletidae, face mite, soft tick, hard tick, Dermanyssidae or Macronyssidae.

17. The method according to claim 16, wherein in the parasite- and hygienic pest-controlling composition, the ecto-parasitic invertebrate for animals is flea, itch mite, Cheyletidae, face mite, soft tick or hard tick.

Description

EXAMPLES

(1) Hereinafter, the present invention will be explained in more detail by specifically referring to Synthetic Examples and Test Examples of the substituted benzamide compound of formula (1) used as the active ingredient of the present invention, but the present invention is not limited to these Examples.

(2) In the meantime, physical property (melting point) described in Synthetic Examples was measured with a micromelting point system (MP-J3) manufactured by Yanaco Laboratory instrument development Co., LTD., and spectral data (.sup.1H NMR) were measured with a nuclear magnetic resonance spectrometer (ECX-300 or ECP-300) manufactured by JEOL Ltd.

Synthetic Examples

Synthetic Example 1

4-[5-(3,5-Dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(thietan-3-yl)benzoic acid amide (Compound No. 1-001)

(3) To a solution of 3.08 g of 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methylbenzoyl chloride (WO 2007/026965; Step 4 of Synthetic Example 1) in 5 mL of dichloromethane, 1.00 g of thietan-3-yl amine hydrobromide and 1.78 g of triethylamine were added under cooling with ice and with stirring, and stirred at room temperature for 18 hours. After the completion of the reaction, 50 mL of water was added to the reaction mixture, was extracted with chloroform (50 mL1), the organic phase was washed with water, and dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluted with ethyl acetate-hexane (1:9 to 1:1 gradient), and 2.10 g of the aimed product was obtained as white crystal. Melting point: 158.0-159.0 C.

(4) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.35-7.6 (m, 6H), 6.30 (d, J=7.9 Hz, 1H), 5.40 (sxt, J=8.3 Hz, 1H), 4.08 (d, J=18.2 Hz, 1H), 3.69 (d, J=18.2 Hz, 1H), 3.35-3.55 (m, 4H), 2.45 (s, 3H).

Synthetic Example 2

4-[5-(3,5-Dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(1-oxothietan-3-yl)benzoic acid amide (Compound No. 1-002) and 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(1,1-dioxothietan-3-yl)benzoic acid amide (Compound No. 1-003)

(5) To a solution of 1.46 g of 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(thietan-3-yl)benzoic acid amide (Compound No. 1-001) in 5 mL of dichloromethane, a solution of 0.44 g of 3-chloro perbenzoic acid (75%) in 5 mL of dichloromethane was added dropwise at 0 C. with stirring, and after the completion of dropwise addition, the mixture was stirred at room temperature for 2 hours. After the completion of the reaction, 50 mL of saturated sodium hydrogen carbonate aqueous solution was added to the reaction mixture, was extracted with chloroform (50 mL1), the organic phase was washed with water, and dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluted with ethyl acetate-hexane (1:9 to 10:0 gradient), and then with methanol-ethyl acetate (1:4), and 0.25 g of 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(1-oxothietan-3-yl)benzoic acid amide and 0.162 g of 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(1,1-dioxothietan-3-yl)benzoic acid amide were obtained as white crystal respectively.

4-[5-(3,5-Dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(1-oxothietan-3-yl)benzoic acid amide

(6) Melting point: 106.0-108.0 C.

(7) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.5-7.6 (m, 4H), 7.4-7.45 (m, 2H), 6.49 (d, J=7.6 Hz, 1H), 4.69 (sxt, J=7.9 Hz, 1H), 4.15-4.25 (m, 2H), 4.08 (d, J=17.5 Hz, 1H), 3.69 (d, J=17.5 Hz, 1H), 3.26 (dt, J=12.4, 3.1 Hz, 2H), 2.46 (s, 3H).

4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(1,1-dioxothietan-3-yl)benzoic acid amide

(8) Melting point: 189.0-191.0 C.

(9) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.5-7.55 (m, 4H), 7.4-7.45 (m, 2H), 6.61 (d, J=7.2 Hz, 1H), 4.8-4.95 (m, 1H), 4.55-4.65 (m, 2H), 4.08 (d, J=17.5 Hz, 1H), 4.0-4.05 (m, 2H), 3.70 (d, J=17.5 Hz, 1H), 2.47 (s, 6H).

Synthetic Example 3

4-[5-(3,5-Dibromo-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methyl-N-(thietan-3-yl)benzoic acid amide (Compound No. 1-004)

Step 1: Production of 3,5-dibromo-4-fluoro-1-(1-trifluoromethylethenyl)benzene

(10) To a solution of 6.12 g of methyltriphenylphosphonium bromide in 60 mL of tetrahydrofuran, 1.93 g of potassium tert-butoxide was added, and stirred at 0 C. for 1 hour. Then, to the reaction mixture, under cooling with ice and with stirring, 3.00 g of 1-(3,5-dibromo-4-fluorophenyl)-2,2,2-trifluoroethanone (WO 2011/027051; Synthetic Example 17) was added, and continued to stir at room temperature for 18 hours. After the completion of the reaction, precipitated solid was removed through filtration with Celite, and the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluted with ethyl acetate-hexane (0:10 to 2:8 gradient), and 1.92 g of the aimed product was obtained as colorless oily substance.

(11) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.59 (d, J=7.5 Hz, 2H), 6.04 (d, J=1.5 Hz, 1H), 5.78 (d, J=1.5 Hz, 1H).

Step 2: Production of methyl 4-[5-(3,5-dibromo-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl benzoate

(12) To a solution of 180 mg of methyl 4-(hydroxyiminomethyl)-2-methyl benzoate in 5 mL of 1,2-dimethoxyethane, 124 mg of N-chlorosuccinimide was added, and stirred at 80 C. for 2 hours. Then, the reaction mixture was cooled to 0 C., 296 mg of 3,5-dibromo-4-fluoro-1-(1-trifluoromethylethenyl)benzene and 186 mg of potassium hydrogen carbonate were added, and continued to stir at room temperature further for 18 hours. After the completion of the reaction, the reaction mixture was poured to 50 mL of ice water, extracted with ethyl acetate (25 mL2), the organic phase was washed with water, and dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluted with ethyl acetate-hexane (1:9 to 1:1 gradient), and 341 mg of the aimed product was obtained as pale yellow resinous substance.

(13) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.96 (d, J=9.0 Hz, 1H), 7.77 (d, J=5.9 Hz, 2H), 7.45-7.55 (m, 2H), 4.10 (d, J=17.9 Hz, 1H), 3.91 (s, 3H), 3.72 (d, J=17.9 Hz, 1H), 2.62 (s, 3H).

Step 3: Production of 4-[5-(3,5-dibromo-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl benzoic acid

(14) To a solution of 341 mg of methyl 4-[5-(3,5-dibromo-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl benzoate in 10 mL of ethanol and 3 mL of tetrahydrofuran, 1.27 mL of 1N potassium hydroxide aqueous solution was added, and stirred at room temperature for 2 hours. After the completion of the reaction, the solvent was distilled off under reduced pressure, 10 mL of water was added to the residue, and concentrated hydrochloric acid was added under cooling with ice and with stirring. After the reaction mixture was adjusted to pH 2, it was extracted with chloroform (10 mL2). The combined organic phase was washed with 20 mL of water, and then dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure, and 330 mg of the aimed product was obtained as pale yellow resinous substance.

(15) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 8.02 (d, J=9.0 Hz, 1H), 7.77 (d, J=5.5 Hz, 2H), 7.54 (s, 1H), 7.53 (d, J=9.0 Hz, 1H), 4.11 (d, J=17.9 Hz, 1H), 3.71 (d, J=17.9 Hz, 1H), 2.65 (s, 3H).

Step 4: Production of 4-[5-(3,5-dibromo-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethy)isoxazol-3-yl]-2-methyl-N-(thietan-3-yl)benzoic acid amide

(16) To a solution of 330 mg of 4-[5-(3,5-dibromo-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl benzoic acid in 5 mL of dichloromethane, 129 mg of thietan-3-yl amine hydrobromide, 154 mg of triethylamine, 5 mg of 1-hydroxybenzotriazole and 146 mg of 1-[3-(diethylamino)propyl]-3-ethylcarbodiimide hydrochloride were added, and stirred at room temperature for 18 hours. After the completion of the reaction, 20 mL of chloroform was added to the reaction mixture, washed with water (20 mL1), and the organic phase was dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluted with ethyl acetate-hexane (1:9 to 1:1 gradient), and 160 mg of the aimed product was obtained as white crystal.

(17) Melting point: 179.0-181.0 C.

(18) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.78 (d, J=8.4 Hz, 2H), 7.47 (s, 2H), 7.35-7.4 (m, 1H), 6.50 (bs, 1H), 5.3-5.45 (m, 1H), 4.09 (d, J=17.5 Hz, 1H), 3.71 (d, J=17.5 Hz, 1H), 3.45-3.5 (m, 4H), 2.44 and 2.42 (s, 3H).

Synthetic Example 4

4-[4-(2,6-dichloropyridin-4-yl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-N-(thietan-3-yl)benzoic acid amide (Compound No. 5-001)

Step 1: Production of ethyl 2-methyl-4-[N[(trimethylsilyl)methyl]carbamoyl]benzoate

(19) To a solution of 443 mg of 4-ethoxycarbonyl-3-methyl benzoic acid and 0.1 mL of N,N-dimethylforamide in 4.0 mL of dichloromethane, 324 mg of oxalyl chloride was added dropwise, and after the completion of the dropwise addition, the mixture was stirred at room temperature for 1 hour. After the completion of the reaction, the solvent was distilled off under reduced pressure, the residue was dissolved in 4.0 ml of dichloromethane, then 215 mg of triethylamine and 264 mg of (trimethylsilyl)methylamine were added, and stirred at room temperature for 1 hour. After the completion of the reaction, 5.0 mL of water was added to the reaction mixture, and extracted with chloroform (10 mL1), and the organic phase was washed with 5.0 mL of water, then dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure. The residue was washed with diisopropylether-hexane mixed solvent, and 535 mg of the aimed product was obtained as white crystal.

(20) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.93 (d, J=8.1 Hz, 1H), 7.60 (s, 1H), 7.53 (d, J=8.1 Hz, 1H), 5.95 (bs, 1H), 4.37 (q, J=7.2 Hz, 2H), 2.97 (d, J=5.8 Hz, 2H), 2.63 (s, 3H), 1.40 (t, J=7.2 Hz, 3H), 0.14 (s, 9H).

Step 2: Production of ethyl 2-methyl-4-[N[(trimethylsilyl)methyl]thiocarbamoyl]benzoate

(21) To a suspension of 535 mg of ethyl 2-methyl-4-[N[(trimethylsilyl)methyl]carbamoyl]benzoate in 10 mL of toluene, 850 mg of Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphethane-2,4-disulfide) was added, and stirred under reflux with heat for 3 hours. After the completion of the reaction, the reaction mixture was cooled to room temperature, poured in 10 ml of water, extracted with ethyl acetate (10 ml2). The combined organic phase was washed with 10 mL of water, and dehydrated and dried with saturated sodium chloride aqueous solution and then with anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluted with ethyl acetate-hexane (1:3 to 1:1 gradient), and 670 mg of the aimed product was obtained as pale yellow oily substance.

(22) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.72 (d, J=8.1 Hz, 1H), 7.38 (s, 1H), 7.29 (d, J=8.1 Hz, 1H), 4.18 (q, J=6.9 Hz, 2H), 3.34 (d, J=6.0 Hz, 2H), 2.44 (s, 3H), 1.21 (t, J=6.9 Hz, 3H), 0.19 (s, 9H).

Step 3: Production of ethyl 2-methyl-4-[methylthio [(trimethylsilyl)methylimino]methyl]benzoate

(23) To a solution of 670 mg of ethyl 2-methyl-4-[N[(trimethylsilyl)methy]lthiocarbamoyl]benzoate in 10 mL of tetrahydrofuran, 257 mg of potassium tert-butoxide was added dropwise under cooling with ice and with stirring, and stirred at room temperature for 15 minutes. Then, 325 mg of methyl iodide was added to the reaction mixture, and continued to stir at the same temperature further for 12 hours. After the completion of the reaction, 20 mL of water was added to the reaction mixture, and extracted with ethyl acetate (15 ml2). The combined organic phase was washed with 10 mL of water, and dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure, and 320 mg of the aimed product was obtained as pale yellow oily substance. The resulting product was used as such without further purification for the next step.

Step 4: Production of ethyl 4-[4-(2,6-dichloropyridin-4-yl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl benzoate

(24) To a solution of 320 mg of ethyl 2-methyl-4-[methylthio[(trimethylsilyl)methylimino]methyl]benzoate and 359 mg of 2,6-dichloro-4-[1-(trifluoromethyl)ethenyl]pyridine in 10 mL of tetrahydrofuran, 0.25 mL of 1M tetrahydrofuran solution of tetrabutyl ammonium fluoride was added dropwise under cooling with ice and with stirring, and after the completion of the dropwise addition, the mixture was stirred at room temperature for 12 hours. After the completion of the reaction, 10 mL of water was added to the reaction mixture, and extracted with ethyl acetate (10 ml2). The combined organic phase was washed with 5 mL of water, and dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluted with ethyl acetate-hexane (1:20 to 1:3 gradient), and 320 mg of the aimed product was obtained as pale yellow oily substance.

(25) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.97 (d, J=8.1 Hz, 1H), 7.73 (s, 1H), 7.69 (d, J=8.1 Hz, 1H), 7.29 (s, 2H), 4.91 (d, J=17.1 Hz, 1H), 4.45 (d, J=17.1 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 3.83 (d, J=17.4 Hz, 1H), 3.46 (d, J=17.4 Hz, 1H), 2.65 (s, 3H), 1.41 (t, J=7.2 Hz, 3H).

Step 5: Production of 4-[4-(2,6-dichloropyridin-4-yl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl benzoic acid

(26) To a solution of 320 mg of ethyl 4-[4-(2,6-dichloropyridin-4-yl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl benzoate in 5 mL of tetrahydrofuran, 5 mL of 10% sodium hydroxide acqueous solution and 50 mg of tetrabutyl ammonium bromide were added, and stirred at room temperature for 6 hours. After the completion of the reaction, concentrated hydrochloric acid was added dropwise to the reaction mixture under cooling with ice and with stirring, and the reaction mixture was adjusted to pH 2, and then extracted with ethyl acetate (15 ml1). The organic phase was dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure, and 240 mg of the aimed product was obtained as blown solid. The resulting product was used as such without further purification for the next step.

Step 6: Production of 4-[4-(2,6-dichloropyridin-4-yl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-N-(thietan-3-yl)benzoic acid amide

(27) To a solution of 40.0 mg of 4-[4-(2,6-dichloropyridin-4-yl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl benzoic acid in 2 mL of N,N-dimethylformamide, 57.0 mg of O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate, 26.0 mg of N,N-diisopropylethylamine and 34.0 mg of thietan-3-yl amine hydrochloride were added, and stirred at room temperature for 12 hours. After the completion of the reaction, 5 mL of water was added to the reaction mixture, and extracted with ethyl acetate (10 ml1). The organic phase was washed with 5 mL of water, and dehydrated and dried with saturated sodium chloride aqueous solution and anhydrous sodium sulfate in that order, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluted with ethyl acetate-hexane (1:3 to 1:2 gradient), and 23.3 mg of the aimed product was obtained as colorless resinous substance.

(28) .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 7.72 (s, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.28 (s, 2H), 6.27 (d, J=7.8 Hz, 1H), 5.35-5.5 (m, 1H), 4.90 (d, J=17.1 Hz, 1H), 4.44 (d, J=17.1 Hz, 1H), 3.81 (d, J=17.4 Hz, 1H), 3.35-3.55 (m, 5H), 2.49 (s, 3H).

(29) The substituted benzamide compounds of formula (1) that are used as the active ingredient of the present invention can be produced according to the production methods described in the above-mentioned patent documents and the above-mentioned synthetic examples. The examples of the substituted benzamide compounds produced similarly to Synthetic Examples 1 to 4 are shown in Tables 4 to 8 to which the substituted benzamide compounds of formula (1) that are used as the active ingredient of the present invention are not limited.

(30) In Tables, the indication Et means ethyl, and in Tables, heterocyclic rings of E-3a-1, E-3a-2, E-3a-3 and E-6-1 are the following structures, respectively

(31) ##STR00149##

(32) For example, the indication of [(E-6-1)Et] means (R)-2-ethyl-3-oxo-2,3,4,5-tetrahydroisoxazol-4-yl.

(33) In addition, the indication of *1 in the Tables means that the physical property of the compound was resinous.

(34) TABLE-US-00025 TABLE 4 0 No. X.sup.1 X.sup.3 X.sup.2 Y.sup.1 R.sup.3 R.sup.2 m.p. ( C.) 1-001 Cl H Cl CH.sub.3 H E-3a-1 158.0-159.0 1-002 Cl H Cl CH.sub.3 H E-3a-2 106.0-108.0 1-003 Cl H Cl CH.sub.3 H E-3a-3 189.0-191.0 1-004 Br F Br CH.sub.3 H E-3a-1 179.0-181.0 1-005 Br F Br CH.sub.3 H E-3a-2 128.0-130.0 1-006 Br F Br CH.sub.3 H E-3a-3 113.0-115.0 1-007 CF.sub.3 H Cl CH.sub.3 H E-3a-1 170.0-172.0 1-008 CF.sub.3 H Cl CH.sub.3 H E-3a-2 108.0-110.0 1-009 CF.sub.3 H Cl CH.sub.3 H E-3a-3 74.0-76.0 1-010 CF.sub.3 H Br CH.sub.3 H E-3a-1 131.0-133.0 1-011 CF.sub.3 H Br CH.sub.3 H E-3a-2 108.0-110.0 1-012 CF.sub.3 H Br CH.sub.3 H E-3a-3 104.0-106.0 1-013 Cl H Cl CH.sub.3 H (E-6-1)Et 197.0-200.0 1-014 Cl H Cl CH.sub.3 H (E-6-1)CH.sub.2CF.sub.3 205.0-218.0

(35) TABLE-US-00026 TABLE 5 No. X.sup.1 X.sup.3 X.sup.2 Y.sup.1 R.sup.3 R.sup.2 m.p. ( C.) 2-001 Cl H Cl CH.sub.3 H (E-6-1)Et *1

(36) TABLE-US-00027 TABLE 6 No. X.sup.1 X.sup.3 X.sup.2 Y.sup.1 R.sup.3 R.sup.2 m.p. ( C.) 3-001 Cl H Cl CH.sub.3 H (E-6-1)Et 213.0-217.0

(37) TABLE-US-00028 TABLE 7 No. X.sup.1 X.sup.2 Y.sup.1 R.sup.3 R.sup.2 m.p. ( C.) 4-001 Cl Cl CH.sub.3 H E-3a-1 *1

(38) TABLE-US-00029 TABLE 8 No. X.sup.1 X.sup.2 Y.sup.1 R.sup.3 R.sup.2 m.p. ( C.) 5-001 Cl Cl CH.sub.3 H E-3a-1 *1

(39) .sup.1H NMR data of the substituted benzamide compounds of formula (1) described in 5 and 7 are shown in Table 9.

(40) TABLE-US-00030 TABLE 9 No. .sup.1H NMR (CDCl.sub.3, Me.sub.4Si, 300 MHz) 2-001 92.2% d.e. 7.3-7.55 (m, 6H), 6.55 (s, 1H), 4.96 (t, J = 8.1 Hz, 1H), 4.84 (td, J = 10.5, 8.1 Hz, 1H), 3.95-4.15 (m, 2H), 3.55-3.75 (m, 3H), 2.48 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H), 4-001 7.98 (s, 1H), 7.84 (s, 1H), 7.81 (s, 1H) 7.67 and 7.63 (d, J = 8.1 Hz, 2H), 7.39 and 7.33 (d, J = 8.1 Hz, 2H), 6.02 and 5.07 (q, J = 6.9 HZ, 1H) 4.14 and 4.13 (d, J = 17.4 Hz, 1H), 3.71 (d, J = 17.4 Hz, 1H), 2.85-3.5 (m, 2H), 2.20 and 2.17 (s, 3H), 1.66 and 1.54 (d, J = 7.2 Hz, 3H), 1.02 and 0.99 (t, J = 7.2 Hz, 3H).

TEST EXAMPLES

(41) Next, usefulness of the parasite-controlling agents of the present invention is specifically explained in the following Test Examples to which the present invention is not limited.

Test Example 1

Insecticidal Test Against Cat Flea

(42) A chemical solution having a concentration of 100 ppm was prepared by dissolving 3.5 mg of a substituted benzamide compound in 35 mL of acetone. The chemical solution was diluted to one-tenth concentration to obtain an acetone solution (a concentration of 10 ppm), 350 L of the acetone solution was coated on the bottom face and the lateral face of a glass container having an inner wall surface area of 35 cm.sup.2, and then thin film of the substituted benzamide compound was formed in the inner wall of the glass container by vaporizing acetone. As the inner wall surface area of the glass container used is 35 cm.sup.2, a treated dosage is 0.1 g/cm.sup.2. In the glass container, 5-cat flea (Ctenocephalides felis) in the adult stage (male and female) were released, and the glass container was covered with a lid and placed at a thermostat chamber at 25 C. A number of dead insect(s) after 4 days was counted and a rate of dead insects was calculated by the following calculation equation. Incidentally, the test was carried out with two districts.
Rate of dead insects(%)=(Number of dead insects/Number of released insects)100 As a result, the following compounds showed a rate of dead insects of 80% or more among the compounds tested. Substituted benzamide compounds: No. 1-001*, 1-002, 1-003, 1-004*, 1-005*, 1-006, 1-007*, 1-008*, 1-009*, 1-010*, 1-011*, 1-012*, 1-013*, 2-001*, 4-001*, 5-001.

(43) In the above, the indication of * shows that the insecticidal test was carried out at a treated dosage of 0.01 g/cm.sup.2.

Test Example 2

Insecticidal Test Against American Dog Tick

(44) A chemical solution having a concentration of 100 ppm was prepared by dissolving 3.5 mg of a substituted benzamide compound in 35 mL of acetone. The chemical solution was diluted to one-one hundredth concentration to obtain an acetone solution (a concentration of 1 ppm), 350 L of the acetone solution was coated on the bottom face and the lateral face of a glass container having an inner wall surface area of 35 cm.sup.2, and then thin film of the substituted benzamide compound was formed in the inner wall of the glass container by vaporizing acetone. As the inner wall surface area of the glass container used is 35 cm.sup.2, a treated dosage is 0.01 g/cm.sup.2. In the glass container, 5-American dog tick (Dermacentor variabilis) in the first nymph stage (male and female) were released, and the glass container was covered with a lid and contained at a thermostat chamber at 25 C. A number of dead insect(s) after 4 days was counted and a rate of dead insects was calculated by the calculation equation similar to that in Test Example 1. Incidentally, the test was carried out with two districts.

(45) As a result, the following compounds showed a rate of dead insects of 80% or more among the compounds tested. Substituted benzamide compounds: No. 1-001*, 1-002, 1-003, 1-004*, 1-005, 1-006, 1-007, 1-008, 1-009, 1-010*, 1-011, 1-013*, 2-001, 4-001, 5-001.

(46) In the above, the indication of * shows that the insecticidal test was carried out at a treated dosage of 0.001 g/cm.sup.2.

Test Example 3

Insecticidal Test Against Housefly

(47) A chemical solution having a concentration of 0.01 g/L was prepared by diluting a substituted benzamide compound with acetone. The chemical solution was coated on the thoracic dorsal region of female adults of housefly (Musca domestica) in an amount of 1 L per fly, and the treated flies were placed at a thermostat chamber at 25 C. A number of dead insect(s) after 3 days was counted and a rate of dead insects was calculated by the calculation equation similar to that in Test Example 1. Incidentally, the test was carried out with two districts.

(48) As a result, the following compounds showed an insecticidal rate of 90% or more among the compounds tested. Substituted benzamide compounds: No. 1-001, 1-002, 1-003*, 1-004, 1-009, 1-010, 1-011, 1-012, 1-013.

(49) In the above, the indication of * shows that the insecticidal test was carried out by use of the chemical solution having a concentration of 0.1 g/L.

Test Example 4

Insecticidal Test Against Mosquito

(50) In a plastic test container of 1.9 mL (Cellstar 24 well plate, GREINER), 0.9 mL of distilled water in which 10 or more of larvas of Culex pipiens molestus Forskal of 1-day after hatching and a suitable amount of feed for ornamental fishes (TetraMin, Tetra Japan & Spectrum Brands, Inc.) were added was placed.

(51) 1% DMSO solution of a substituted benzamide compound was prepared, and diluted with distilled water to a concentration of 0.0001%. 0.1 mL of the diluted solution was added to the test container in which Culex pipiens molestus Forskal was placed (final concentration of the compound: 0.1 ppm), stirred and then placed at a thermostat chamber at 25 C. A number of dead insect(s) after 1 day was counted and a rate of dead insects was calculated by the calculation equation similar to that in Test Example 1. Incidentally, the test was carried out with two districts.

(52) As a result, the following compounds showed a rate of dead insects of 90% or more among the compounds tested. Substituted benzamide compounds: No. 1-001, 1-002, 1-003, 1-004, 1-008, 1-009, 1-010, 1-011, 1-012, 1-013, 4-001.

Test Example 5

Insecticidal Test Against German Cockroach

(53) A chemical solution having a concentration of 10 g/L was prepared by diluting a substituted benzamide compound with acetone. The chemical solution was coated on the abdominal region of male adults of German cockroach (Blattella germanica) in an amount of 1 L per cockroach, and the treated cockroaches were placed at a thermostat chamber at 25 C. A number of dead insect(s) after 2 days was counted and a rate of dead insects was calculated by the calculation equation similar to that in Test Example 1. Incidentally, the test was carried out with five districts. As a result, the following compounds showed a rate of dead insects of 90% or more among the compounds tested. The compounds of the present invention: No. 1-001*, 1-002*, 1-003*, 1-004*, 1-009*, 1-010*, 1-011, 1-012, 1-013*, 4-001.

(54) In the above, the indication of * shows that the insecticidal test was carried out by use of the chemical solution having a concentration of 1 g/L, and the indication of ** shows that the insecticidal test was carried out by use of the chemical solution having a concentration of 0.1 g/L.

Test Example 6

Insecticidal Test Against Termite

(55) A 10% emulsifiable concentrate of a substituted benzamide compound was diluted with water to prepare a chemical solution with a concentration of 10 ppm. 0.5 ml of the chemical solution was added dropwise in 10 g of sand and mixed. A filter paper and the sand treated with the chemical solution were placed in a laboratory dish in which 1% agar was laid. 10-termite (Reticulitermes flavipes) per dish was left and placed at a thermostat chamber at 25 C. A number of dead insect(s) after 10 days was counted and a rate of dead insects was calculated by the calculation equation similar to that in Test Example 1. Incidentally, the test was carried out with two districts. As a result, the following compounds showed a rate of dead insects of 90% or more among the compounds tested. The compounds of the present invention: No. 1-001, 1-002, 1-003, 1-004, 1-009, 1-010, 1-011, 1-012, 1-013, 4-001*.

(56) In the above, the indication of * shows that the insecticidal test was carried out by use of the chemical solution having a concentration of 100 ppm.

INDUSTRIAL APPLICABILITY

(57) The parasite- and hygienic pest-controlling agent of the present invention can effectively control ecto- or endo-parasites and hygienic pests belonging to insects such as Hymenoptera, Diptera, Siphonaptera, Hemiptera, Psocodea, Blattaria, and Isoptera, etc., mites such as Astigmata, Oribatida, Prostigmata, Metastigmata and Mesostigmata, etc., nematodes such as Enoplida, Rhabditida, Strongylida, Oxyurida, Ascaridida and Spirurida, etc. that have developed in resistance to existing parasite- or hygienic pest-controlling agents such as organic phosphorus compounds, carbamate compounds or pyrethroides compounds with causing little adverse effect against animals to be protected such as mammals, birds and like.