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WO1989000992A1 - Acylhydrazones anthelmintiques, procede d'utilisation et compositions - Google Patents

Acylhydrazones anthelmintiques, procede d'utilisation et compositions Download PDF

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Publication number
WO1989000992A1
WO1989000992A1 PCT/US1988/002367 US8802367W WO8900992A1 WO 1989000992 A1 WO1989000992 A1 WO 1989000992A1 US 8802367 W US8802367 W US 8802367W WO 8900992 A1 WO8900992 A1 WO 8900992A1
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WIPO (PCT)
Prior art keywords
alkyl
pyrazinyl
cpd
ethylidene
hydrazide
Prior art date
Application number
PCT/US1988/002367
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English (en)
Inventor
Douglas C. Rector
George A. Conder
Sylvester D. Folz
Original Assignee
The Upjohn Company
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Filing date
Publication date
Application filed by The Upjohn Company filed Critical The Upjohn Company
Publication of WO1989000992A1 publication Critical patent/WO1989000992A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D241/12—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/28—Radicals substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/20—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hydrogen atoms and substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention pertains to a new method for killing and controlling worms (Helminths), and new formulations for killing and controlling worms in animals, and new chemical compounds.
  • the invention is more particularly directed to a new method for killing and controlling parasitic worms in animals with certain acylhydrazones, to new anthelmintic formulations comprising the same, and to new acylhydrazones.
  • the anthelmintic acylhydrazones have the general structural formula I. BACKGROUND OF THE INVENTION
  • helminthiasis The diseases or groups of diseases described generally as helminthiasis are due to infection of the animal with parasitic worms known as helminths. Helminthiasis and helminthosis are prevalent and may lead to serious economic problems in valuable domestic warmblooded animals such as sheep, swine, cattle, goats, dogs, cats, horses, poultry and man. Among the helminths, the groups of worms known as nematodes, trematodes and cestodes cause widespread and often-times serious infections in various species of animals including man.
  • the most common genera of nematodes, trematodes and cestodes infecting the animals referred to above are Dictvocaulus, Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Bunostomum, Oesophagostomum, Chabertia, Strongyloides, Trichuris, Fasciola, Dicrocoelium, Enterobius, Ascaris, Toxascaris, Toxocara, Ascaridia, Capillaria, Heterakis, Ancylostoma, Uncinaria, Dirofilaria, Onchocerca, Taenia, Moniezia, Dipylidium, Metastrongylus, Triodontophorus, Macracanthorhvnchus, Hyostrongylus, and Strongylus.
  • acylhydrazones of this invention including hydrates or pharmaceutically acceptable salts thereof, are represented by Formula I wherein W is selected from the group consisting of (1) pyrazinyl (A); (2) pyranyl (B); or (3) thiazolyl (C); wherein, the variable substituents (1)-(3) are optionally substituted with one or two C 1 -C 4 alkyl, preferably C 1 -C 3 alkyl; C 1 -
  • X is (a) hydrogen; (b) C 1 -C 10 alkyl; (c) C 2 -C 6 alkenyl, preferably C 2 -C 4 alkenyl; (d) C 2 -C 6 alkynyl; (e) cyclo(C 3 -C 10 )alkyl optionally substituted with one, 2 or 3 C 1 -C 4 alkyl, or C 2 -C 4 alkenyl; (g) 1-methylpyrrolidinyl; (h) 1-methylpiperidinyl; (i) C 2 -C 6 alkoxyalkyl; (j) cyclo(C 3 -C 10 )alkyl(C 1 -C 4 )alkyl; (k) phenyl(C 1 - C 4 )
  • C____ - C___ means the carbon content of various hydrocarbon-containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety.
  • (C 1 -C 3 ) alkyl refers to alkyl of one to 3 carbon atoms, inclusive or methyl, ethyl, propyl, and isopropyl.
  • Halogen atom refers to a bromo, chloro, iodo or fluoro atom.
  • Heteroaromatic refers to an aromatic heterocycle of 5 to 10 members, containing one or two heteroatoms selected from the group consisting of oxygen, nitrogen or sulfur and includes quinoline, pyrrole, indole, benzofuran, benzothiophene, quinazoline, quinoxaline, imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, pyridazine, pyrimidine, pyrazine, benzimidazole, benzothiazole, benzoxazole, pyridine, thiophene or furan, as well as the N-oxides, hydrates and pharmaceutically acceptable salts thereof.
  • compositions and/or substances which are acceptable to the patient from a pharmacologically-toxicological point of view and to the manufacturing pharmaceutical chemist from a physical-chemical point of view regarding composition, formulation, stability, patient acceptance and bioavailability.
  • C 1 -C 4 alkyl are methyl, ethyl, propyl, butyl and isomeric forms thereof.
  • Examples of C 1 -C 3 alkoxy are methoxy, ethoxy, propoxy and isomeric forms thereof.
  • phenoxy substituted with one, 2 or 3 C 1 -C 4 alkyl are (o-, m-, or p-)tolyl, (o-, m-, or p-)ethylphenyl, p-tert-butylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 2,4-dimethylphenyl, (2,3,4-, 2,3,5-, 2,3,6-, 2,4,6- or 2,4,5-)trimethylphenyl.
  • C 2 -C 6 dialkylamino examples are dimethylamino, diethylamino, methylethylamino, dipropylamino and ethylpropylamino.
  • phenyl(C 1 -C 3 )alkyl examples include benzyl, phenylethyl and phenylpropyl.
  • phenyl(C 1 -C 3 )alkyl substituted with one, 2 or 3 C 1 -C 4 alkoxy, halo or trifluoromethyl examples include 4-chlorobenzyl, 2- chlorophenylethyl, p-tolylethyl, 2-methylbenzyl, 4-methoxybenzyl.
  • C 1 -C 3 alkylthio examples include methylthio, ethylthio, and n- propylthio.
  • Examples of substituted cyclo(C 3 -C 10 )alkyl are chrysanthemyl, 1-methylcyclopropyl and 2-methyleyelopropyl.
  • Examples of cyclo(C 3 -C- 10 )alkyl(C 1 -C 4 )alkyl are 2-cyclohexylethyl and cyclohexylmethyl.
  • An example of substituted cyclo(C 3 -C 6 )alkyloxy is menthyl.
  • Examples of naphthyl(C 1 -C 3 )alkyl include 2-naphthylmethyl and 1-naphthylethyl.
  • substituted naphthyl (C 1 -C 3 )alkyl is (3,8-dichloro-1-naphthyl)methyl; (4-chloro-1-naphthyl)methyl; and (4-methoxy-1-naphthyl)methyl.
  • substituted naphthyl include 3,6-dichloro-1-naphthyl; 3,5-dichloro-2-naphthyl; 6-methyl-2- naphthyl; and 4,6-dichloro-1-naphthyl.
  • bridged polycyclic hydrocarbon substituents of six to 10 nuclear carbons, optionally substituted with one, 2 or 3 (C 1 -C 3 ) alkyl groups include exo or endo-2-norbonyl, bicyclo[2,2,2]- oct-1-yl, and 1-adamanty1.
  • perhalo (C 1 -C 7 ) alkyl examples include trifluoromethyl, n-heptafluoropropyl and n-undecafluoropentyl.
  • Preferred acylhydrazones of Formula I are 2-pyrazinyl acylhydrazones (IA), 2-pyranyl acylhydrazones (IB) or 5-thiazolyl acylhydrazones (IC).
  • Preferred Y and Z of IA, IB and IC include hydrogen, methyl, or a chloro atom.
  • Preferred R 1 includes hydrogen, methyl or ethyl.
  • Preferred X include hydrogen; C 1 -C 4 alkyl; cyclohexylethyl; phenyl optionally substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 2 alkoxy, trifluoromethyl and chloro; C 1 -C 4 alkoxy; phenoxy optionally substituted with one, 2 or 3 C 1 -C 2 alkyl, C 1 -C 2 alkoxy, trifluoromethyl and chloro; cyclo(C 3 -C 6 )alkyl; pyridinyl; thienyl; furyl; benzyloxy optionally substituted with one or 2 C 1 -C 2 alkoxy; di(C 1 - C 2 )alkoxyphenylmethyl; N-morpholinylethyl; or 1-menthylo.
  • A is pyrazinyl (including pyrazinyl N-oxide and pyrazinyl N,N'- dioxide) optionally substituted with one or two C 1 -C 4 alkyl, preferably C 1 -C 3 alkyl; C 1 -C 3 alkoxy; C 1 -C 3 alkylthio; halo; trifluoromethyl; or hydroxy.
  • B is pyranyl optionally substituted with one or two C 1 -C 4 alkyl, preferably C 1 -C 3 alkyl; C 1 -C 3 alkoxy; C 1 -C 3 alkylthio; halo; trifluoromethyl; or hydroxy.
  • C is thiazolyl optionally substituted with one or two C 1 -C 4 alkyl, preferably C 1 -C 3 alkyl; C 1 -C 3 alkoxy; C 1 -C 3 alkylthio; halo; trifluoromethyl; or hydroxy.
  • Preferred compounds of this invention are the compounds of Table A represented by compound nos . : 1-14, 16-23, 26, 28, 29, 31, 38, 39, 40, 42-45.
  • acylhydrazones of formula IA pyrazinealdehyde isonicotinoylhydrazone; isonicotinic acid (2- pyrazinylmethylene) hydrazide pyrazinealdehyde nicotinoylhydrazone; nicotinic acid (2-pyrazinylmethylene) hydrazide pyrazinealdehyde picolinoylhydrazone; picolinic acid (2- pyrazinylmethylene) hydrazide are known. See K.
  • One embodiment of this invention includes, of course, the anthelmintic use and anthelmintic compositions of compounds of Formula I, IA, IB, or IC hydrates thereof or pharmaceutically acceptable salts thereof.
  • Still another embodiment of this invention are the novel compounds, hydrates thereof or pharmaceutically acceptable salts thereof according to Formula I, IA, IB, and IC.
  • acylhydrazones of this invention are readily prepared by reacting the appropriate ketone (II) with the acylhydrazide/carbazate (III) (Chart A, Scheme A) or by heating the pyridyl ketone (II) with hydrazine (IV) to form the hydrazone intermediate (V) which is then acylated with the halide or anhydride (VI) to form the acylhydrazone (I) (Chart A, Scheme B).
  • the reaction of Scheme A is carried out in the presence of a suitable solvent, for example, water, alcohols, ethers, halogenated hydrocarbons, hydrocarbons and include methanol, ethanol, isopropanol, propanol, hexane, tetrahydrofuran, dioxane, methylene chloride, preferably ethanol.
  • a catalyst such as glacial acetic acid, hydrochloric acid, sulfuric acid or p-toluenesulfonic acid can be utilized to enhance the yield/rate of the reaction, particularly when R 1 is alkyl of 3 or more atoms, arylalkyl arylalkenyl or aryl.
  • the acylation reaction of Scheme B is carried out in the presence of a suitable base such as a tertiary amine, for example, triethylamine or preferably, pyridine.
  • a suitable base such as a tertiary amine, for example, triethylamine or preferably, pyridine.
  • the base may also be the solvent.
  • the starting compounds are known or can be readily prepared by known methods. R. L. Frank and C. Weatherbee, J. Am. Chem. Soc, 70, 3482-3 (1948); N. B. Mahishi, et al., J. Indian Chem. Soc, 42, 67-74 (1965) and M. Ogata and H. Kano, Chem. Pharm. Bull (Tokyo), 11, 32 (1963).
  • acylhydrazones of this invention are effective against parasitic worms, particularly those of valuable domestic warm-blooded animals and more particularly helminth parasites in ovines (sheep) and bovines (cattle).
  • the sheep are sacrificed 7-12 days after treatment (days 35-49 PI), and the abomasum is ligated and removed from each sheep. Each abomasum is longitudinally sectioned and rinsed into an 80 mesh sieve. Sieve contents are collected in individual containers and fixed in formol-alcohol. Later each sample is transferred to a 1000 or 2000 ml beaker and the volume brought to 400-1000 ml with tap water. The total number of worms in a 40-100 ml aliquot (10%) is determined. When no worms are found in the 10% aliquot, the entire sample is examined. Total worm number/sheep and percentage clearance for each treatment are calculated.
  • acylhydrazones of Formula I can be used as the pure compounds or as mixtures of pure compounds but for practical reasons the compounds are preferably formulated as anthelmintic compositions and administered as a single or multiple dose, alone or in combination with other anthelmintics (e.g. avermectins, benzimidazoles, levamisole, praziquantel, etc.).
  • anthelmintics e.g. avermectins, benzimidazoles, levamisole, praziquantel, etc.
  • aqueous or oil suspensions can be administered orally, or the compounds can be formulated with a solid carrier for feeding.
  • an oil suspension can be converted into an aqueous emulsion by mixing with water and injecting the emulsion intramuscularly, subcutaneously or into the peritoneal cavity.
  • the active compound(s) can be administered topically to the animal in a conventional pour-on formulation.
  • Pure compounds, mixtures of the active compounds, or combinations thereof with a solid carrier can be administered in the animal's food, or administered in the form of tablets, pills, boluses, wafers, pastes, and other conventional unit dosage forms, as well as sustained release dosage forms which deliver the active compound over an extended period of days, weeks or months. All of these various forms of the active compounds of this invention can be prepared using physiologically acceptable carriers and known methods of formulation and manufacture.
  • Solid carriers conveniently available and satisfactory for physiologically acceptable, unit dosage formulations include corn starch, powdered lactose, powdered sucrose, talc, stearic acid, magnesium stearate, finely divided bentonite, and the like.
  • the active agent can be mixed with a carrier in varying proportions from, for example, about 0.001 percent by weight in animal feed to about 90 or 95 percent or more in a pill or capsule. In the latter form, one might use no more carrier than sufficient to bind the particles of active compound.
  • the compounds can be formulated in stable powders or granules for mixing in an amount of feed for a single feeding or enough feed for one day and thus obtain therapeutic efficacy without complication. It is the prepared and stored feeds or feed premixes that require care. A recommended practice is to coat a granular formulation to protect and preserve the active ingredient. A prepared hog-feed containing about 0.2 percent of the active compound will provide a dosage of about 100 mg per kg body weight for each 100 lb pig in its daily ration.
  • a solid diluent carrier need not be a homogeneous entity, but mixtures of different diluent carriers can include small proportions of adjuvants such as water; alcohols; protein solutions and suspensions like skimmed milk; edible oils; solutions, e.g., syrups; and organic adjuvants such as propylene glycols, sorbitol, glycerol, diethyl carbonate, and the like.
  • solid carrier formulations of the inventions are conveniently prepared in unit dosage forms, to facilitate administration to animals. Accordingly, several large boluses (about
  • the solid, unit dosage forms can be conveniently prepared in various sizes and concentrations of active ingredient, to accommodate treatment of the various sizes of animals that are parasitized by worms.
  • Liquid formulations can also be used.
  • Representative liquid formulations include aqueous (including isotonic saline) suspensions, oil solutions and suspensions, and oil in water emulsions.
  • Aqueous suspensions are obtained by dispersing the active compound in water, preferably including a suitable surface-active dispersing agent such as cationic, anionic, or non-ionic surface-active agents.
  • suitable ones are polyoxyalkylene derivatives of fatty alcohols and of sorbitan esters, and glycerol and sorbitan esters of fatty acids.
  • dispersing or suspending agents can be included and representative ones are synthetic and natural gums, tragacanth, acacia, alginate, dextran, gelatin, sodium carboxymethylcellulose, methylcellulose, sodium polyvinylpyrrolidone, and the like.
  • the proportion of the active compound in the aqueous suspensions of the invention can vary from about 1 percent to about 20 percent or more.
  • Oil solutions are prepared by mixing the active compound and an oil, e.g. an edible oil such as cottonseed oil, peanut oil, coconut oil, modified soybean oil, and sesame oil. Usually, solubility in oil will be limited and oil suspensions can be prepared by mixing additional, finely divided compound in the oil.
  • an oil e.g. an edible oil such as cottonseed oil, peanut oil, coconut oil, modified soybean oil, and sesame oil.
  • solubility in oil will be limited and oil suspensions can be prepared by mixing additional, finely divided compound in the oil.
  • Oil in water emulsions are prepared by mixing and dispersing an oil solution or suspension of the active compound in water preferably aided by surface-active agents and dispersing or suspending agents as indicated above.
  • the formulations of this invention are administered to animals so as to achieve therapeutic or prophylactic levels of the active compound.
  • a dose of 100 mg/kg of body weight in sheep of an acylhydrazone of this invention will effectively combat a wide variety of parasites.
  • Much lower effective dosages of various compounds are contemplated, e.g., in the range of 1 to 75 mg/kg of body weight.
  • dosage rates of about 1 mg to about 800 mg/kg of body weight.
  • a preferred, contemplated range of dosage rates is from about 5 mg to about 400 mg/kg of body weight.
  • concentration of active compound in the formulation selected for administration is in many situations not critical.
  • One can also administer a sustained release dosage system (protracted delivery formulation) so as to provide therapeutic and/or prophylactic dosage amounts over an extended period.
  • Unit dosage forms in accordance with this invention can have anywhere from less than 1 mg to 500 g of active compound per unit.
  • the anthelmintic agents of this invention will find their primary use in the treatment and/or prevention of helminth parasitisms in valuable warm-blooded domesticated animals such as sheep, cattle, horses, dogs, swine, goats and poultry, they are also effective in treatment that occurs in other warm blooded animals including man.
  • the optimum amount to be employed for best results will, of course, depend upon the particular compound employed, species of animal to be treated, the regimen of treatment and the type and severity of helminth infection.
  • compounds of Formula I by the oral or parenteral route of administration of about 1 to 300 mg/kg of animal bodyweight (such total dose being given at one time, in a protracted manner or in divided doses over a short period of time such as 1-4 days).
  • the technique for administering these materials to animals are known to those skilled in the veterinary and medical fields.
  • acylhydrazones of Formula I can be used to treat various helminth diseases in humans, including those caused by Ascaris, Enterobius, Ancylostoma, Trichuris, Strongyloides, Fasciola, Taenia, and/or Onchocerca or other filariae at a dose of from 1 mg/kg to 300 mg/kg of body weight upon oral and/or parenteral administration.
  • helminth diseases including those caused by Ascaris, Enterobius, Ancylostoma, Trichuris, Strongyloides, Fasciola, Taenia, and/or Onchocerca or other filariae at a dose of from 1 mg/kg to 300 mg/kg of body weight upon oral and/or parenteral administration.
  • TLC thin-layer chromatography
  • Brine aqueous saturated sodium chloride solution
  • the ratio of solvents used are volume/volume (v/v).
  • Q is a halogen atom or other activating group, for example, an anhydride

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention concerne un procédé permettant de tuer des parasites internes, en particulier des nématodes, des trématodes et des cestodes affectant les animaux à sang chaud tels que les moutons, le bétail à cornes, les porcs, les chèvres, les chiens, les chats, et les êtres humains ainsi que la volaille en leur administrant une quantité efficace d'un composé de formule (I). Les composés sont préparés aisément par des réactions chimiques classiques.
PCT/US1988/002367 1987-07-31 1988-07-19 Acylhydrazones anthelmintiques, procede d'utilisation et compositions WO1989000992A1 (fr)

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US080,522 1987-07-31

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JP (1) JPH03500769A (fr)
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2325932A (en) * 1997-06-04 1998-12-09 Bayer Agrochem Kk Isonicotinic Acid Hydrazide Derivatives
WO2022040747A1 (fr) * 2020-08-27 2022-03-03 Alterity Therapeutics Limited Composés et méthodes de traitement de maladies

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1479239A (en) * 1974-11-21 1977-07-06 Egyt Gyogyszervegyeszeti Gyar Acylated 2-hydrazono formyl quinoxaline-1,4-dioxides
WO1986004582A1 (fr) * 1985-02-11 1986-08-14 The Upjohn Company Acylhydrazones de pyridinyle anthelmintiques, procede d'utilisation et compositions
WO1987006132A1 (fr) * 1986-04-07 1987-10-22 The Upjohn Company Acylhydrazones d'alkyle quaternaire anthelmintiques, procede d'utilisation et compositions

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1479239A (en) * 1974-11-21 1977-07-06 Egyt Gyogyszervegyeszeti Gyar Acylated 2-hydrazono formyl quinoxaline-1,4-dioxides
WO1986004582A1 (fr) * 1985-02-11 1986-08-14 The Upjohn Company Acylhydrazones de pyridinyle anthelmintiques, procede d'utilisation et compositions
WO1987006132A1 (fr) * 1986-04-07 1987-10-22 The Upjohn Company Acylhydrazones d'alkyle quaternaire anthelmintiques, procede d'utilisation et compositions

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2325932A (en) * 1997-06-04 1998-12-09 Bayer Agrochem Kk Isonicotinic Acid Hydrazide Derivatives
FR2764290A1 (fr) * 1997-06-04 1998-12-11 Nihon Bayer Agrochem Kk Derives d'hydrazide d'acide isonicotinique
GB2325932B (en) * 1997-06-04 2001-06-06 Bayer Agrochem Kk Isonicotinic acid hydrazide derivatives
WO2022040747A1 (fr) * 2020-08-27 2022-03-03 Alterity Therapeutics Limited Composés et méthodes de traitement de maladies

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EP0370065A1 (fr) 1990-05-30
AU2314488A (en) 1989-03-01
JPH03500769A (ja) 1991-02-21

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