EP2782572A1

EP2782572A1 - Use of fluopyram for controlling endoparasites

Info

Publication number: EP2782572A1
Application number: EP12788574.7A
Authority: EP
Inventors: Achim Harder; Ulrich Görgens
Original assignee: Bayer Intellectual Property GmbH
Current assignee: Bayer Intellectual Property GmbH
Priority date: 2011-11-25
Filing date: 2012-11-23
Publication date: 2014-10-01
Also published as: WO2013076231A1

Abstract

The invention relates to the use of fluopyram for controlling endoparasites in humans and animals, to drugs containing fluopyram, to a method for producing drugs and to a method for treating humans and animals to control endoparasites, especially nematodes.

Description

Use of fluopyram to combat endoparasites

The invention relates to the use of fluopyram for the control of endoparasites in humans and animals and to a method for the treatment of humans and in animals for the control of endoparasites. Endoparasites or especially helminthic nematodes such as e.g. Haemonchus contortus, Cooperia spp., Trichostrongylus spp. et al cause significant economic damage in the livestock of livestock. Other nematodes affect the health of pets, such as dogs and cats.

There is therefore an urgent need for anthelmintics, in particular nematicides, which enable a sufficient control of endoparasites in humans and in animals. It is already known that certain pyridylethylbenzamides have fungicidal, insecticidal and acaricidal and nematicidal properties.

Fluopyram is defined as compound according to formula (I)

Respiratory chain by blocking the electron transport of the respiratory chain of the succinate dehydrogenase complex.

Fluopyram, with the chemical name N - {[3-chloro-5- (trifluoromethyl) -2-pyridinyl] ethyl} -2- (trifluoromethyl) -benzamide, and suitable processes for its preparation, starting from commercially available starting materials, in EP -A- 1 531 675. WO 2004/016088 describes pyridylethylbenzamides and their use as fungicides. The possibility of combining one or more of the disclosed pyridylethylbenzamide derivatives with other known fungicides, insecticides, nematicides or acaricides to broaden the spectrum of activity is also described. WO 2005/077901 teaches fungicidal compositions comprising at least one pyridylethylbenzamide and an inhibitor of electron transport in the respiratory chain of fungi. However, the patent application does not mention mixtures of pyridylethylbenzamides with insecticides. WO 2008/003738 teaches fungicidal compositions comprising at least one pyridylethylbenzamide and an insecticide. A possible nematicidal effect of the compositions is described in the application, but not explicitly for mixtures comprising N- {2- [3-chloro-5- (trifluoromethyl) -2-pyridinyl] ethyl} -2-trifluoromethylbenzamide. The general nematicidal effect of fluopyram is described in WO-A 2008/126922.

Surprisingly, it has now been found that fluopyram, is outstandingly suitable for controlling endoparasites, in particular of helminthic nematodes in humans and in animals. Accordingly, the subject of the present invention is the use of fluopyram for the control of endoparasites in humans and in animals

In the context of the present invention, "control of endoparasites" means a significant reduction of infestation by endoparasites compared to the untreated human or animal, preferably a substantial reduction (by 40-79%) compared to the untreated human or animal (100%). Particularly preferably, the infection is completely suppressed by endoparasites (by 70-100%) .The control can be curative, ie for the treatment of already infected humans or animals or protective, ie for the protection of hitherto uninfected humans or animals.

Combinations of fluopyram with other drugs, including other endoparasiticides, may also be used in the control of endoparasites in the present invention.

Depending on the structure, active compounds can be present in stereoisomeric forms or as stereoisomer mixtures, e.g. as enantiomers or racemates. Both the stereoisomer mixtures and the pure stereoisomers can be used according to the invention. It is also possible to use, where appropriate, salts of the active compounds with pharmaceutically acceptable acids or bases and also solvates, in particular hydrates, of the active substances or their salts.

The active substances used in the products according to the invention may, depending on their structure, exist in stereoisomeric forms (enantiomers, diastereomers). According to the invention, the enantiomers or diastereomers and their respective mixtures can be used.

If the active compounds can occur in tautomeric forms, the present invention also encompasses the use of the tautomeric forms.

If appropriate, the active compounds can also be used in the form of their salts, solvates and solvates of the salts. Salts which are preferred in the context of the present invention are physiologically acceptable salts of the active compounds. Physiologically acceptable salts of the active compounds comprise acid addition salts of mineral acids, carboxylic acids and sulfonic acids, for example salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid, naphthalenedisulfonic acid, acetic acid, trifluoroacetic acid, propionic acid, depending on the structure of the active substance. Lactic acid, tartaric acid, malic acid, citric acid, fumaric acid, maleic acid and benzoic acid.

Physiologically acceptable salts of the active compounds optionally also include salts of customary bases, such as, by way of example and by way of preference, alkali metal salts (for example sodium and potassium salts), alkaline earth salts (for example calcium and magnesium salts) and ammonium salts derived from ammonia or organic amines having 1 to 16 carbon atoms, such as, by way of example and by way of preference, ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, procaine, dibenzylamine, N-methylmorpholine, arginine, lysine, ethylenediamine, N-methylpiperidine and choline.

Solvates in the context of the invention are those forms of the active ingredients which form a complex in the solid or liquid state by coordination with solvent molecules. Hydrates are a special form of solvates that coordinate with water.

In addition, the present invention also includes prodrugs of the active ingredients. The term "prodrugs" includes compounds which may themselves be biologically active or inactive, but are converted to the actual active ingredient during their residence time in the body (for example metabolically or hydrolytically).

The agents according to the invention are suitable in the case of favorable warm-blooded toxicity for controlling pathogenic endoparasites which occur in humans and in animal husbandry and animal breeding in productive, breeding, zoo, laboratory, experimental and hobby animals. They are effective against all or individual stages of development of the pests and against resistant and normally sensitive endoparasite isolates. By controlling the pathogenic Endoparasiten disease, deaths and reductions in performance (eg in the production of meat, milk, wool, hides, eggs, honey, etc.) to be reduced, so that through the use of active ingredients more economical and easier animal husbandry is possible. Pathogenic endoparasites include platyhelmintha (eg monogenea, cestodes and trematodes), nematodes, pentastoma and acanthocephala: Monogenea: eg: Gyrodactylus spp., Dactylogyrus spp., Polystoma spp.

Cestodes: From the order of Pseudophyllidea, for example: Diphyllobothrium spp., Spirometra spp., Schistocephalus spp., Ligula spp., Bothridium spp., Diphlogonoporus spp.

From the order of the Cyclophyllida eg: Mesocestoides spp., Anoplocephala spp., Paranoplocephala spp., Moniezia spp., Thysanosoma spp., Thysaniezia spp., Avitellina spp., Stilesia spp., Cittotaenia spp., Andyra spp., Bertiella spp. , Taenia spp., Echinococcus spp., Hydatigera spp., Davainea spp., Raillietina spp., Hymenolepis spp., Echinolepis spp., Echinocotyle spp., Diorchis spp., Dipylidium spp., Joyeuxiella spp., Diplopylidium spp.

Trematodes: From the genus Digenea e.g. : Diplostomum spp. , Posthodiplostomum spp., Schistosoma spp., Trichobilharzia spp., Ornithobilharzia spp., Austrobilharzia spp., Gigantobilharzia spp., Leucochloridium spp., Brachylaima spp., Echinostoma spp., Echinoparyphium spp., Echinochasmus spp., Hypoderaeum spp., Fasciola Spp., Fasciolides spp., Fasciolopsis spp., Cyclocoelum spp., Typhlocoelum spp., Paramphistomum spp., Calicophoron spp, Cotylophoron spp., Gigantocotyle spp., Fischoederius spp., Gastrothylacus spp., Notocotylus spp., Catatropis spp. , Plagiorchis spp., Prosthogonimus spp., Dicrocoelium spp., Eurytrema spp., Troglotrema spp., Paragonimus spp., Collyriclum spp., Nanophyetus spp., Opisthorchis spp., Clonorchis spp. Metorchis spp., Heterophyes spp., Metagonimus spp.

Nematodes: From the order of Trichinellida, for example: Trichuris spp., Capillaria spp., Trichomosoides spp., Trichinella spp. From the order of Tylenchida, for example: Micronema spp., Strongyloides spp.

From the order of Rhabditina, 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., Uncinaria spp., Bunostomum spp. , Globocephalus spp., Syngamus spp., Cyathostoma spp., Metastrongylus spp., Dictyocaulus spp., Muellerius spp., Protostrongylus spp., Neostrongylus spp., Cystocaulus spp., Pneumostrongylus spp., Spicocaulus spp., Elapho strongylus spp. Parelaphostrongylus spp., Crenosoma spp., Paracrenosoma spp., Angiostrongylus spp., Aelurostrongylus spp., Filaroides spp., Parafilaroides spp., Trichostrongylus spp., Haemonchus spp., Ostertagia spp., Marshallagia spp., Cooperia spp., Nematodirus spp , Hyostrongylus spp., Obeliscoides spp., Amidostomum spp., Ollulanus spp. From the order of Spirurida, for example: Oxyuris spp., Enterobius spp., Passalurus spp., Syphacia spp., Aspiculuris spp., Heterakis spp .; Ascaris spp., Toxascaris spp., Toxocara spp., Baylisascaris spp., Parascaris spp., Anisakis spp., Ascaridia spp .; Gnathostoma spp., Physaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp .; Stephanofüaria spp., Parafüaria spp., Setaria spp., Loa spp., Dirofilaria spp., Litomosoides spp., Brugia spp., Wuchereria spp., Onchocerca spp.

Acantocephala: From the order of Oligacanthorhynchida, for example: Macracanthorhynchus spp., Prosthenorchis spp .; from the order of Polymorphida, for example: Filicollis spp .; from the order of Moniliformida, for example: Moniliformis spp.,

From the order of Echinorhynchida e.g. Acanthocephalus spp., Echinorhynchus spp., Leptorhynchoides spp.

Pentastoma: From the order of porocephalis e.g. Linguatula spp. In a preferred embodiment, fluopyram is used to control cestodes (tapeworms) as listed above (e.g., Taenia spp.).

According to a further preferred embodiment, fluopyram is used for controlling the nematodes listed above, in particular Oxyuris spp., Enterobius spp., Passalurus spp., Syphacia spp., Aspiculuris spp., Heterakis spp., Toxascaris spp., Toxocara spp. Baylisascaris spp., Parascaris spp., Ascaridia spp .; Gnathostoma spp., Physaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp .; Stephanofüaria spp., Parafüaria spp., Setaria spp., Loa spp., Dirofilaria spp., Litomosoides spp., Brugia spp., Wuchereria spp (except Wuchereria bancrofti)., Onchocerca spp. (except Onchocerca volvulus). The following nematodes are particularly preferably controlled: Trichinellida, Tylenchida, Rhabditina or the following Spirurida: Physaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp.

The subject of a further particularly preferred embodiment is the use of fluopyram for the control of strongylida, in particular Haemonchus spp. (eg Haemonchus contortus), Trichostrongylus spp. (eg Trichostrongylus colubriformis), Cooperia spp., Ostertagia spp or Teladorsagia spp ..

The subject of a further particularly preferred embodiment is the use of fluopyram for controlling Parascaris spp.

Animals can be fish, reptiles, birds or especially mammals.

The livestock include in particular mammals such as cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur animals such as mink, chinchilla, raccoon. Of the livestock mammals preferred are cattle sheep and pigs Also included in the use according to the invention are the following species other than mammals but which are also farm animals: birds such as chickens, geese, turkeys, ducks, ostriches; Fresh and saltwater fish such as salmon, trout, carp, perch, pike, eels; reptiles; Insects such as honeybee and silkworm. Laboratory and experimental animals include, among others, mice, rats, guinea pigs, golden hamsters.

Hobby animals include horses, preferably dogs or cats. In dogs or cats, Toxoscaris spp., Toxocara spp., Trichuris spp., Trichinella spp. and the hookworms Ancylostoma spp. and Uncinaria spp. fought.

According to another embodiment, the products can also be used in humans. Preferably, in humans, Ancylostoma spp, Necator spp., Trichuris spp., Strongyloides spp. and Enterobius spp. fought.

Among mammals, according to one embodiment, herbivores (herbivores) are preferred for the application of the above-mentioned combinations, ie animals which mainly feed on plants. Particularly preferred is the treatment of ruminants (such as sheep, goats, cattle).

As non-ruminant herbivores, which are mammals, the horses are mentioned as a preferred example. There, the above combinations may be preferred z. B. for controlling Strongylida or in particular roundworms (Ascaridia), such as. B. Parascaris equorum used. In ruminants strongylida, in particular Haemonchus spp., Trichostrongylus spp., Cooperia spp. and Ostertagia spp. be fought.

According to the invention, sheep are particularly preferably treated.

Also particularly preferred according to the invention cattle are treated.

The application can be both prophylactic and therapeutic. The application of the active ingredient is carried out in a conventional manner directly or in the form of suitable preparations.

Usual doses of fluopyram per day are 1 to 100 mg / kg body weight, preferably 2 to 60 mg / kg body weight.

The following example serves to illustrate the invention without, however, limiting it. Biological Example Example A

After oral administration of fluopyram in sheep, the following efficacy against Haemonchus contortus was determined.

Claims

claims:

1. Fluopyram according to formula (I)

and its salts, N-oxides and tautomeric forms

for use in the control of endoparasites in humans or animals.

2. Fluopyram according to claim 1, wherein the endoparasites are platyhelmintha, pentastoma or acanthocephala.

3. Fluopyram according to claim 2, wherein the endoparasites are cestodes.

4. Fluopyram according to claim 1, wherein the endoparasites nematodes selected from Oxyuris spp., Enterobius spp., Passalurus spp., Syphacia spp., Aspiculuris spp., Heterakis spp., Toxascaris spp.

Toxocara spp., Baylisascaris spp., Parascaris spp., Ascaridia spp .; Gnathostoma spp., Physaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp .; Stephanofilaria spp., Parafilaria spp., Setaria spp., Loa spp., Dirofilaria spp., Litomosoides spp., Brugia spp., Wuchereria spp (except Wuchereria bancrofti)., Onchocerca spp. (except Onchocerca volvulus).

5. The fluopyram according to claim 1, wherein the endoparasites are nematodes selected from Trichinellida, Tylenchida, Rhabditina or the following Spirurida: Physaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp. ,

6. Fluopyram according to claim 1, wherein the endoparasites nematodes selected from Haemonchus spp. (eg Haemonchus contortus), Trichostrongylus spp. (eg Trichostrongylus colubriformis), Cooperia spp., Ostertagia spp or Teladorsagia spp. are.

7. Fluopyram according to claim 1, wherein the endoparasites Parascaris spp. are.

8. Fluopyram according to any one of claims 1 to 7, wherein the animals are ruminants.

9. Medicaments containing fluopyram according to claim 1 for combating endoparasites in humans or in animals

10. Use of fluopyram according to claim 1 for the preparation of medicaments for the control of endoparasites in humans or in animals.

11. A method for combating endoparasites in humans and in animals, characterized in that the humans or animals are treated with fluopyram.