Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/16—Amides, e.g. hydroxamic acids
  • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
  • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
  • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• • A—HUMAN NECESSITIES
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  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
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  • A61P33/04—Amoebicides
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  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
  • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
  • A61P33/06—Antimalarials
• • A—HUMAN NECESSITIES
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  • A61P33/00—Antiparasitic agents
  • A61P33/10—Anthelmintics
• • A—HUMAN NECESSITIES
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  • A61P33/00—Antiparasitic agents
  • A61P33/10—Anthelmintics
  • A61P33/12—Schistosomicides
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  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C233/00—Carboxylic acid amides
  • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
  • C07C233/66—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
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  • C07C233/00—Carboxylic acid amides
  • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
  • C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
  • C07C233/68—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
  • C07C233/73—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
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  • C07—ORGANIC CHEMISTRY
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  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/61—Halogen atoms or nitro radicals
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  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/62—Oxygen or sulfur atoms
  • C07D213/63—One oxygen atom
  • C07D213/64—One oxygen atom attached in position 2 or 6
  • C07D213/643—2-Phenoxypyridines; Derivatives thereof
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
  • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
  • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D215/20—Oxygen atoms
  • C07D215/22—Oxygen atoms attached in position 2 or 4
  • C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
  • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
  • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D231/18—One oxygen or sulfur atom
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• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
  • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
  • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
  • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
  • C07D239/32—One oxygen, sulfur or nitrogen atom
  • C07D239/34—One oxygen atom
• • C—CHEMISTRY; METALLURGY
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  • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
  • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
  • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
  • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
  • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
  • C07D239/60—Three or more oxygen or sulfur atoms
• • C—CHEMISTRY; METALLURGY
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  • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
  • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
  • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
  • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D241/18—Oxygen or sulfur atoms
• • C—CHEMISTRY; METALLURGY
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  • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
  • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
  • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
  • C07D241/40—Benzopyrazines
  • C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
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  • C07—ORGANIC CHEMISTRY
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  • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
  • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
  • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
  • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
  • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
  • C07D277/62—Benzothiazoles
  • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2

Definitions

• the present invention relates an endoparasite control agent comprising a carboxamide derivative or a salt thereof as an active ingredient,, and a method for controlling endoparasites, comprising orally or parenterally administering the endoparasite control agent.
• Patent Literature 13 discloses certain kinds of carboxamide derivatives which are effective against endoparasites. However, there is no disclosure of the effects of the compounds of the present invention against endoparasites.
• parasitosis is caused by infestation of host animals with parasites such as unicellular protists (protozoa), multicellular helminths and arthropods. It is reported that the incidence of parasitosis in Japan has been remarkably decreased by improvement of environmental hygiene, but on a global scale, particularly in developing countries, parasitosis still widely prevails and causes tremendous damage. In recent years, there have been seen the introduction of infection sources via long- or short-term travelers having visited such countries; parasitic infection due to the consumption of food imports or raw meat and fish meat, which have become more available thanks to the advance in freezing and logistics technologies; and the transmission of parasitosis from pets. Under such circumstances, the incidence of parasitosis is on an upward trend again.
• parasites such as unicellular protists (protozoa), multicellular helminths and arthropods.
• Patent Literature 1 JP-A 01-151546
• Patent Literature 2 WO 2007/060162
• Patent Literature 3 JP-A 53-9739
• Patent Literature 4 WO 2007/108483
• Patent Literature 5 WO 2007/104496
• Patent Literature 6 WO 2008/101975
• Patent Literature 7 WO 2008/101976
• Patent Literature 8 WO 2008/003745
• Patent Literature 9 WO 2008/003746
• Patent Literature 10 WO 2009/012998
• Patent Literature 11 WO 2009/127718
• Patent Literature 12 WO 2010/106971
• Patent Literature 13 WO 2012/118139
• Non Patent Literature 1 Kiyoshi Kita, “Kansen (Infection)”, Winter 2010, Vol. 40-4, 310-319
• the present invention is mainly intended to provide a novel parasiticide, antiprotozoal or other endoparasite control agents which are effective for controlling animal endoparasites that have been impossible to control by conventional ones.
• the present inventors conducted extensive research to solve the above-described problems. As a result, the present inventors found that a carboxamide derivative represented by the general formula (I) of the present invention and a salt thereof are highly effective for controlling endoparasites. The present inventors further conducted a great deal of examination and then completed the present invention. That is, the present invention relates to the following.
• An endoparasite control agent comprising, as an active ingredient, a carboxamide derivative represented by the general formula (I):
• A represents a nitrogen atom or a C—Y 5 group (wherein Y 5 is a hydrogen atom or a (C 1 -C 6 ) alkyl group),
• X 1 and X 2 may be the same or different, and each represent
• R 1 and R 2 may be the same or different, and are selected from the group consisting of
• R 3 and R 4 may be the same or different, and are selected from the group consisting of
• Y 1 represents
• Y 2 and Y 4 may be the same or different, and each represent
• A represents a nitrogen atom or a C—H group
• X 1 and X 2 may be the same or different, and each represent
• R 1 and R 2 each represent (b1) a hydrogen atom
• Y 1 represents (d2) a halogen atom
• Y 2 and Y 4 each represent (e1) a hydrogen atom
• Y 3 is selected from the group consisting of
• a pyridyloxy group having, on the ring, 1 to 4 substituting groups which may be the same or different and are selected from the group consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a (C 1 -C 6 ) alkyl group, (e) a halo (C 1 -C 6 ) alkyl group, (f) a (C 1 -C 6 ) alkoxy group and (g) a halo (C 1 -C 6 ) alkoxy group;
• A represents a C—H group
• X 1 and X 2 may be the same or different, and are selected from the group consisting of
• R 1 and R 2 each represent (b1) a hydrogen atom
• R 3 and R 4 may be the same or different, and are selected from the group consisting of
• Y 1 represents (d2) a halogen atom
• Y 2 and Y 4 each represent (e1) a hydrogen atom
• A represents a nitrogen atom
• X 1 and X 2 may be the same or different, and are selected from the group consisting of
• R 1 and R 2 each represent (b1) a hydrogen atom
• Y 1 represents
• Y 2 and Y 4 each represent (e1) a hydrogen atom
• Y 3 is selected from the group consisting of
• [5] A method for controlling endoparasites, comprising orally or parenterally administering an effective amount of the endoparasite control agent according to any one of the above [1] to [4] to a non-human mammal or a bird.
• a method for controlling endoparasites comprising orally or parenterally administering an effective amount of the endoparasite control agent according to any one of the above [1] to [4] to a non-human mammal.
• a method for controlling endoparasites comprising orally or parenterally administering an effective amount of the endoparasite control agent according to any one of the above [1] to [4] to a human.
• the present invention provides an endoparasite control agent having better performance in the disinfection or control of endoparasites as compared with the conventional art.
• halogen atom refers to a chlorine atom, a bromine atom, an iodine atom or a fluorine atom.
• the “(C 1 -C 6 ) alkyl group” refers to a straight-chain or branched-chain alkyl group of 1 to 6 carbon atoms, for example, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, a neopentyl group, a n-hexyl group or the like.
• the “(C 1 -C 6 ) alkoxy group” refers to a straight-chain or branched-chain alkoxy group of 1 to 6 carbon atoms, for example, a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, a sec-butoxy group, a tert-butoxy group, a n-pentyloxy group, an isopentyloxy group, a neopentyloxy group, a n-hexyloxy group or the like.
• halo (C 1 -C 6 ) alkyl group refers to a straight-chain or branched-chain alkyl group of 1 to 6 carbon atoms substituted with one or more halogen atoms which may be the same or different from each other, for example, a trifluoromethyl group, a difluoromethyl group, a perfluoroethyl group, a hexafluoroisopropyl group, a perfluoroisopropyl group, a chloromethyl group, a bromomethyl group, a 1-bromoethyl group, a 2,3-dibromopropyl group or the like.
• halo (C 1 -C 6 ) alkoxy group refers to a straight-chain or branched-chain alkoxy group of 1 to 6 carbon atoms substituted with one or more halogen atoms which may be the same or different from each other, for example, a trifluoromethoxy group, a difluoromethoxy group, a perfluoroethoxy group, a perfluoroisopropoxy group, a chloromethoxy group, a bromomethoxy group, a 1-bromoethoxy group, a 2,3-dibromopropoxy group or the like.
• the “(C 3 -C 6 ) cycloalkane” formed of R 1 and R 2 together with the carbon atom bound to R 1 and R 2 is, for example, cyclopropane, cyclobutane, cyclopentane, cyclohexane or the like.
• the “(C 3 -C 6 ) cycloalkane” formed of R 3 and R 4 together with the carbon atom bound to R 3 and R 4 is, for example, cyclopropane, cyclobutane, cyclopentane, cyclohexane or the like.
• Examples of the salt of the carboxamide derivative represented by the general formula (I) of the present invention include inorganic acid salts, such as hydrochlorides, sulfates, nitrates and phosphates; organic acid salts, such as acetates, fumarates, maleates, oxalates, methanesulfonates, benzenesulfonates and p-toluenesulfonates; and salts with an inorganic or organic base such as a sodium ion, a potassium ion, a calcium ion and a trimethylammonium ion.
• inorganic acid salts such as hydrochlorides, sulfates, nitrates and phosphates
• organic acid salts such as acetates, fumarates, maleates, oxalates, methanesulfonates, benzenesulfonates and p-toluenesulfonates
• carboxamide derivative of the present invention preferred is a compound of the general formula (I) in which
• A represents a nitrogen atom or a C—H group
• X 1 and X 2 may be the same or different, and each represent
• R 1 and R 2 each represent (b1) a hydrogen atom
• R 3 and R 4 may be the same or different, and are selected from the group consisting of
• Y 1 represents (d2) a halogen atom
• Y 2 and Y 4 each represent (e1) a hydrogen atom
• Y 3 is selected from the group consisting of
• carboxamide derivative of the present invention further preferred is a compound of the general formula (I) in which
• A represents a C—H group
• X 1 and X 2 may be the same or different, and are selected from the group consisting of
• R 1 and R 2 each represent (b1) a hydrogen atom
• R 3 and R 4 may be the same or different, and are selected from the group consisting of
• Y 1 represents (d2) a halogen atom
• Y 2 and Y 4 each represent (e1) a hydrogen atom
• Y 3 is selected from the group consisting of
• a benzothiazolyloxy group having, on the ring, 1 to 4 substituting groups which may be the same or different and are selected from the group consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a (C 1 -C 6 ) alkyl group, (e) a halo (C 1 -C 6 ) alkyl group, (f) a (C 1 -C 6 ) alkoxy group and (g) a halo (C 1 -C 6 ) alkoxy group, or a salt thereof.
• A represents a nitrogen atom
• X 1 and X 2 may be the same or different, and are selected from the group consisting of
• R 1 and R 2 each represent (b1) a hydrogen atom
• R 3 and R 4 may be the same or different, and are selected from the group consisting of
• Y 1 represents
• Y 2 and Y 4 each represent (e1) a hydrogen atom
• Y 3 is selected from the group consisting of
• the compound represented by the general formula (I) of the present invention can be produced by any of the production methods described in JP-A 01-151546, WO 2007/060162, JP-A 53-9739, WO 2007/108483, WO 2008/101975, WO 2008/101976, WO 2008/003745, WO 2008/003746, WO 2009/012998, WO 2009/127718, WO 2010/106971 and WO 2012/113139, the method described in Shin-Jikken Kagaku Kouza 14 (Maruzen, Dec. 20, 1977), a modified method of the foregoing, or the like.
• Q1 to Q19 represent the following structures.
• the black circle in each of the formulae Q1 to Q19 represents a binding site.
• the endoparasite control agent of the present invention has excellent anti-endoparasite effect, and exerts appropriate control effect against endoparasites.
• the animal for which the endoparasite control agent of the present invention can be used is a human and an animal of non-human mammalian or avian species.
• Exemplary members of the non-human mammalian species include domestic animals, such as pigs, horses, cattle, sheep, goats, rabbits, camels, water buffalos, deer, mink and chinchillas; pet animals, such as dogs, cats, little birds and monkeys; and experimental animals, such as rats, mice, golden hamsters and guinea pigs.
• Exemplary members of the avian species include domestic fowls, such as chickens, ducks, aigamo ducks (crossbreeds of wild and domestic ducks), quails, domestic ducks, geese and turkeys.
• domestic fowls such as chickens, ducks, aigamo ducks (crossbreeds of wild and domestic ducks), quails, domestic ducks, geese and turkeys.
• domestic fowls such as chickens, ducks, aigamo ducks (crossbreeds of wild and domestic ducks), quails, domestic ducks, geese and turkeys.
• protozoa Human endoparasites against which the endoparasite control agent of the present invention is effective are roughly classified into protozoa and helminths.
• protozoa include, but are not limited thereto, Rhizopoda, such as Entamoeba histolytica ; Mastigophora, such as Leishmania, Trypanosoma and Trichomonas ; Sporozoea, such as Plasmodium and Toxoplasma ; and Ciliophora, such as Balantidium coli .
• helminths include, but are not limited thereto, Nematoda, such as Ascaris lumbricoides, Anisakis, Toxocara canis, Trichostrongylus spp., Enterobius vemicularis , hookworms (for example, Ancylostoma duodenale, Necator americanus, Ancylostoma braziliense , etc.), Angiostrongylus spp., Gnathostoma spp., filarial worms (filaria, Wuchereria bancrofti, Brugia malayi , etc.), Onchocerca volvulus, Dracunculus medinensis, Trichinella spiralis and Strongyloides stercoralis ; Acanthocephala, such as Macracanthorhynchus hirudinaceus ; Gordiacea, such as Gordioidea; Hirudinea, such as Hirudo nipponia ; Tremato
• Cestoda such as Diphyllobothrium latum, Sparganum mansoni, Sparganum proliferum, Diplogonoporus grandis , Taeniidae for example, Taeniarhynchus saginatus, Taenia solium, Echinococcus , etc.
• Hymenolepis spp. Dipylidium caninum, Mesocestoides lineatus, Bertiella spp. and Nybelinia surmenicola.
• Non-human mammalian or avian endoparasites against which the endoparasite control agent of the present invention is effective are roughly classified into protozoa and helminths.
• the protozoa include, hut are not limited thereto, Apicomplexa, such as Cocoidia (for example, Eimeria, Isospora, Toxoplasma, Neospora, Sarcocystis, Besnoitia, Hammondia, Cryptosporidium, Caryospora , etc.), Haemosporina (for example, Leucocytozoon, Plasmodium , etc.), Piroplasma (for example, Theileria, Anaplasma, Eperythrozoon, Haemobartonella, Ehrlichia , etc.), and others (for example, Hepatozoon, Haemogregarina , etc.); Microspora, such as Encephalitozoon and Nosema ; Mastigophora, such as Trypano
• helminths include, but are not limited thereto, Nentatoda, such as Ascaridida (for example, Ascaris suum ( Ascaris ), Toxocara canis and Toxocara cati ( Toxocara ), Toxascaris leonina ( Toxascaris ), Parascaris equorum ( Parascaris ), Ascaridia galli ( Ascaridia ), Heterakis gallinarum ( Heterakis ), Anisakis , etc.), Oxyurida (for example, Oxyuris equi ( Qxyuris ), Passalurus ambiguus ( Passalurus , etc.), Strongylida (for example, Strongylus vulgaris (Strongylus), Haemonchus contortus ( Haemonchus ), Ostertagia ostertagi ( Ostertagia ), Trichostrongylus colubriformis ( Trichostrongylus ), Cooperia punctata ( Cooperi
• examples of the helminths include, but are not limited to, Nematoda, such as Enoplida (for example, Trichuris spp., Capillaria spp., Trichomosoides spp., Trichinella spp., etc.), Rhabditia (for example, Micronema spp., Strongyloides spp., etc.), Strongylida (for example, Strongylus spp., Triodontophorus spp., Oesophagodontus spp., Trichonema spp., Gyalocephalus spp., Cylindropharynx spp., Poteriostomum spp., Cyclococercus spp., Cylicostephanus spp., Oesophagostomum spp., Chabertia spp., Stephanurus spp., Ancylostoma spp.
• Cestoda such as Pseudophyllidea (for example, Diphyllobothrium spp., Spirometra spp., Schistocephalus spp., Ligula spp., Bothridium spp., Diplogonoporus spp., etc.), and Cyclophyllidea (for example, Mesocestoides spp., Anoplocephala spp., Paranoplocehala spp., Moniezia spp., Thysanosomsa spp., Thysaniezia spp., Avitellina spp., Stilesia spp., Cittotaenia spp., Andyra spp., Bertiella spp., Taenia spp., Echinococcus spp., Hydatigera spp., Davainea spp., Raillietina spp., Hymenolep
• the endoparasite control agent of the present invention is effective for controlling not only parasites that live in the body of an intermediate or final host, but also parasites that live in the body of a reservoir host.
• the compound represented by the general formula (I) of the present invention is effective for controlling parasites at their every developmental stage.
• the compound in the case of protozoa, the compound is effective against their cysts, precystic forms and trophozoites; schizonts and amoeboid forms at the asexual stage; gametocytes, gametes and zygotes at the sexual stage; sporozoites; etc.
• the compound is effective against their eggs, larvae and adults.
• the compound of the present invention is capable of not only disinfecting parasites in the living body, but also even preventing parasitic infection by application to the environment as a route of infection.
• soil-borne infection i.e., infection from soil of crop fields and parks; percutaneous infection from water in rivers, lakes, marshes, paddy fields, etc.; oral infection from feces of animals such as dogs and cats; oral infection from saltwater fish, freshwater fish, crustaceans, shellfish, raw meat of domestic animals, etc.; infection from mosquitoes, gadflies, flies, cockroaches, mites and ticks, fleas, lice, assassin bugs, trombiculid mites, etc.; and the like can be prevented from occurring.
• the endoparasite control agent of the present invention can be administered as a pharmaceutical for treatment or prevention of parasitosis in humans and animals of non-human mammalian or avian species.
• the mode of administration may be oral or parenteral administration.
• the endoparasite control agent of the present invention can be administered, for example, as a capsule, a tablet, a pill, a powder, a granule, a fine granule, a powder, a syrup, an enteric-coated preparation, a suspension or a paste, or after blended in a liquid drink or feed for animals.
• the endoparasite control agent of the present invention can be administored, for example, as an injection, an infusion, a suppository, an emulsion, a suspension, a drop, an ointment, a cream, a solution, a lotion, a spray, an aerosol, a cataplasm or a tape, or in a dosage form which allows sustained mucosal or percutaneous absorption.
• the optimum amount (effective amount) of the active ingredient varies with the purpose (treatment or prevention), the kind of infectious parasite, the type and severity of infection, the dosage form, etc., but in general, the oral daily dose is in the range of about 0.0001 to 10000 mg/kg body weight and the parenteral daily dose is in the range of about 0.0001 to 10000 mg/kg body weight.
• Such a dose may be given as a single dose or divided into multiple doses.
• the concentration of the active ingredient in the endoparasite control agent of the present invention is generally about 0.001 to 100% by mass, preferably about 0.001 to 99% by mass, and more preferably about 0.005 to 20% by mass.
• the endoparasite control agent of the present invention may be a composition that can be directly administered, or a highly concentrated composition that needs to be diluted to a suitable concentration before use.
• the endoparasite control agent of the present invention can be used in combination with any existing endoparasite control agent for the purpose of reinforcing or complementing its effect.
• two or more active ingredients may be mixed and formulated into a single preparation before administration, or two or more different preparations may be administered separately.
• part means a part by mass
• a carboxamide derivative represented by the general formula (I) of the present invention 50 parts of white beeswax, and 43 parts of white petrolatum are well mixed to give an ointment.
• a carboxamide derivative represented by the general formula (I) of the present invention 10 parts of vegetable oil (olive oil), 3 parts of crystalline cellulose, 20 parts of white carbon, and 65 parts of kaolin are well mixed and compressed into a tablet.
• a carboxamide derivative represented by the general formula (I) of the present invention Five parts of a carboxamide derivative represented by the general formula (I) of the present invention, 20 parts of a surfactant for ordinary use as a dissolution or suspension aid, and 75 parts of ion exchanged water are well mixed to give a solution.
• the compound of the present invention was prepared as solutions in 100% DMSO at the final concentrations of 50 ppm, 5 ppm, 0.5 ppm, 0.05 ppm and 0.005ppm.
• DMSO stands for dimethyl sulfoxide.
• a larval suspension containing 1st-stage larvae of Haemonchus contortus harvested by the Baermann technique was placed at a density of 20 larvae per well in a test plate, and 0.5 ⁇ L/well of the test solution containing the compound of the present invention diluted to a predetermined concentration was added to the test plate.
• the plate was kept under the conditions of 27° C./95% RH for 4 days.
• ivermectin was used for the positive control and DMSO was used for the negative control.
• the motor ability of the larvae was examined with an automatic analyzer equipped with an LCD camera.
• the inhibitory effect on the motion of the larvae in each treatment plot was corrected based on the inhibitory effect in the plot treated with DMSO only for the negative control.
• the EC 50 value was calculated from the data on the corrected inhibitory effect on the motion of the larvae, and graded according to the criteria shown below.
• the compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-45, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-56, 1-57,1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 2-1, 2-2, 2-3, 2-4 and 2-5 of the present invention showed the activity level graded as C or higher.

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