EP2299995A1 - Combinaison de dérivés d'amidine avec des depsipeptides cycliques - Google Patents

Combinaison de dérivés d'amidine avec des depsipeptides cycliques

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Publication number
EP2299995A1
EP2299995A1 EP09768920A EP09768920A EP2299995A1 EP 2299995 A1 EP2299995 A1 EP 2299995A1 EP 09768920 A EP09768920 A EP 09768920A EP 09768920 A EP09768920 A EP 09768920A EP 2299995 A1 EP2299995 A1 EP 2299995A1
Authority
EP
European Patent Office
Prior art keywords
spp
alkyl
products according
aminophenylamidine
sec
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP09768920A
Other languages
German (de)
English (en)
Inventor
Achim Harder
Dittmar Nerger
Thomas Bach
Venkata - Rangarao Kanikanti
Richard Kujanek
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Animal Health GmbH
Original Assignee
Bayer Animal Health GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Animal Health GmbH filed Critical Bayer Animal Health GmbH
Publication of EP2299995A1 publication Critical patent/EP2299995A1/fr
Withdrawn legal-status Critical Current

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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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/15—Depsipeptides; Derivatives thereof
    • 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
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to the combination of Aminophenylamidin derivatives with cyclic depsipeptides, products containing this combination and the use of these agents in combination for the control of endoparasites in humans and in animals.
  • Anthelmintisch effective aminophenylamidines and related compounds have long been known, see, for.
  • An important member of this class is the amidantel, which is known to be a potent anthelmintic for dogs (Wollweber H et al. Arzneistoffforschung / Drug Research 29 (1) 31-32; DE-OS-20 29 298). Human use against Ancylostoma duodenale is described in Rim HJ. et al. The Korean Journal of Parasitology 18 (1) 24-36.
  • Tribendimidine a symmetrical diamine derivative of amidine sheath
  • Tribendimidine a symmetrical diamine derivative of amidine sheath
  • the control of endoparasites in livestock is the subject of our co-pending patent application DE-Akz. 10 2007 061262.
  • PF 1022 and emodepside and their action against endoparasites are also already known, see e.g. EP-A 382 173, EP-A 634 408.
  • the subject of the present invention are:
  • Anthelmintisch effective aminophenylamidine derivatives are preferably compounds of formula (I), wherein
  • R, 1 is hydrogen or C i. 4- alkyl
  • R is preferably hydrogen, -COCH 2 (C 1-4 alkoxy) or, together with R, the radical
  • the anthelmintically effective Arninophenylamidin- derivative is the compound amide shell of the formula
  • the anthelmintic aminophenylamidine derivative is the compound Bay d 9216 of the formula
  • Tribendimidine and its synthesis are known.
  • a production method is described, for example, in Yao RH, Chen YQ (1986) "Synthesis of Tribendimidine and its substituted analogues as new anthelmintic agents.” Annual Report of Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, 1986, pp. 199-202 ,
  • Depsipeptides are similar to peptides and differ from them in that one or more ⁇ -amino acid building blocks are replaced by ⁇ -hydroxycarboxylic acid building blocks.
  • Preferably used according to the invention are cyclic depsipeptides having 18 to 24 ring atoms, in particular having 24 ring atoms (octadepsipeptides).
  • depsipeptides with 18 ring atoms include compounds of the general formula (IT):
  • R 2 , R 4 and R 6 independently represent hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms, hydroxyalkyl, mercaptoalkyl, alkanoyloxyalkyl, alkoxyalkyl, aryloxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, arylalkoxycarbonylalkyl, carbamoylalkyl, aminoalkyl, alkylaminoalkyl , Dialkylaminoalkyl, alkoxycarbonylaminoalkyl, alkenyl, cycloalkyl, cycloalkylalkyl optionally substituted aryl or arylalkyl wherein as substituents may be mentioned halogen, hydroxy, alkyl, alkoxy, and their optical isomers and racemates.
  • R 2 , R 4 and R 6 independently of one another represent straight-chain or branched C 1 -C 8 -alkyl, in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, sec Pentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, tert-heptyl, octyl, isooctyl, sec-octyl, hydroxy-Ci-C 6 -alkyl, in particular hydroxymethyl, 1 hydroxyethyl, C 1 -C 4 -Al- kanoyloxy-C ⁇ C ö alkyl, in particular acetoxymethyl, 1-acetoxyethyl, C 1 -C 4 -alkoxy-C 1
  • R ', R 3 and R 5 independently of one another represent straight-chain or branched C 1 -C 3 -alkyl, in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, sec-pentyl, hexyl, isohexyl , sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, isooctyl, sec-octyl, hydroxy-CrC ö alkyl, in particular hydroxymethyl, 1-hydroxyethyl, Ci-C 4 -AIkanoyIoxy-dC 6 - alkyl, in particular acetoxymethyl, 1-acetoxyethyl, C 1 -C 4 -alkoxy C 1 -C 6 -alkyl, in particular Methoxymethyl, 1-methoxyethyl
  • R 2 , R 4 and R 6 independently of one another represent straight-chain or branched Q-Cg-alkyl, in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, sec - pentyl, hexyl, isohexyl, sec-hexyl, heptyl, isoheptyl, sec-heptyl, tert-heptyl, octyl, isooctyl, sec-octyl, hydroxy-Ci-C 6 -alkyl, in particular hydroxymethyl, aryl-ci G t alkyloxy-Ci-Ce-alkyl, in particular benzyloxymethyl, 1-benzyloxyethyl, carboxy-Ci-C ß alkyl, in particular carboxymethyl, carboxyethyl
  • R 1 , R 3 and R 5 independently of one another represent straight-chain or branched C 1 -C 8 -alkyl, in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, sec-pentyl, hexyl, isohexyl , sec-hexyl, heptyl, isoheptyl, sec-heptyl, octyl, isooctyl, sec-octyl, C 2 -C 8 -alkenyl, especially allyl, C 3 -C 7 -cycloalkyl-Ci-C 4 -alkyl, in particular Cyclohexylmethyl, phenyl-C r C 4 -alkyl, in particular phenylmethyl,
  • R ', R 2 , R 3 , R 4 independently of one another represent hydrogen, Q-Cio-alkyl or aryl, in particular
  • Phenyl which are optionally substituted by hydroxy, C] -C ] 0 -alkoxy or halogen.
  • R a, R 2a, R l la and R 12a independently of one another
  • Ci -8 - alkyl, C ,. 8 -haloalkyl, C 3-6 -cycloalkyl, aralkyl, aryl, R 3a , R 5a , R 7a , R 9a independently of one another represent hydrogen or straight-chain or branched C 1-8 -
  • R 3a, R 5a, R 7a, R 9a is hydrogen, straight or branched Ci -8 alkyl, especially methyl, ethyl, propyl, i-propyl, n-, s-, t-butyl, optionally substituted by Ci ⁇ - Alkoxy, especially methoxy,
  • R 4a , R 6a , R 8a , R 10a independently of one another represent hydrogen, methyl, ethyl, n-propyl, n-butyl,
  • the compounds of the formula (IIId) can also be prepared according to the methods described in EP-A-382 173, DE-A 4 317432, DE-A 4 317457, DE-A 4 317 458, EP-A-634 408, EP-A-718 293, EP-A-872481, EP-A-685 469, EP-A-626 375, EP-A-664 297, EP-A-669 343, EP-A-787 141, EP-A-865 498, Obtained by EP-A-903 347.
  • Very particularly preferred depilatory puffs according to the invention are PF 1022 A (see formula (IIIa) and emodepside (PF 1022-221, compound of the formula (IIIb) in which both Z radicals are the morpholinyl radical.)
  • the INN emodepside stands for the compound with systematic name: Cyclo [(R) -lactoyl-N-methyl-L-leucyl- (R) -3- (p-monopholinophenyl) lactoyl-N-methyl-L-leucyl (i) -lactoyl-N-methyl -L-leucyl- (i?) - 3- (p-mo ⁇ hohnophenyl) lactoyl-N-methyl-L-leucyl.
  • 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.
  • 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 present invention also encompasses the use of the tautomeric forms.
  • the active compounds may also be used in the form of their salts, solvates and solvates of the salts
  • salts physiologically acceptable salts of the active ingredients are preferred in the context of the present invention.
  • Physiologically acceptable salts of the active compounds comprise, depending on the structure of the active substance, acid addition salts of maleic acids, carboxylic acids and sulfonic acids, for example salts of chlorine.
  • 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.
  • 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
  • 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.
  • the present invention also includes prodrugs of the active ingredients.
  • 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 products 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 species.
  • pathogenic endoparasites it is intended to reduce disease, fatalities and impairments (for example in the production of meat, milk, wool, hides, eggs, honey, etc.) so that the use of the active substances makes it possible to achieve more economical and easier animal husbandry.
  • the pathogenic endoparasites include cestodes, trematodes, nematodes, acantocephalen in particular:
  • Cyclophyllidea eg: Mesocestoides spp., Anoplocephala spp., Paranoplocuspala 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., Hymenolepis spp., Echinolepis spp., Echinocotyle spp., Diorchis spp., Dipylidium spp., Joyeuxiella spp., Diplopylidium 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
  • Strongylus spp. Triodontophorus spp., Oesophagodontus spp., Trichonema spp., Gyalocephalus spp., Cylindropharynx spp., Poteriostromum spp., Cyclococercus spp., Cylicostephanus spp., Oesophagostomum spp., Chabertia spp.
  • Stephanurus spp. Ancylostoma spp., Uncinaria spp., Bunostomum spp., Globocephalus spp., Syngamus spp., Cyathostomum spp., Metastrongylus spp., Dictyocaulus spp., Muellerius spp., Protostrongylus spp., Neostrongylus spp., Cystocaulus Spp., Pneumostrongylus spp., Spicocaulus spp., Elaphostrongylus spp., Parelaphostrongylus spp., Crenosoma spp., Paracrenosoma spp., Angiostrongylus spp., Aelurostrongylus spp., Filaroides spp., Paraflaroids spp., Trichostrongylus spp., Haemonchus spp.
  • Oxyuris spp. Enterobius spp., Passaluras spp., Syphacia spp., Aspiculuris spp., Heterakis spp.
  • Ascaridia for example: Ascaris spp., Toxascaris spp., Toxocara spp., Parascaris spp., Anisakis spp., Ascaridia spp.
  • Spirurida Gnathostoma spp., Physaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp.
  • tapeworms e.g. Taenia spp.
  • nematodes such. B .:
  • Spirurida for example: Gnathostoma spp., Physaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp.
  • the livestock include in particular mammals such as e.g. Cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur animals such as e.g. Mink, Chinchilla, Raccoon.
  • cattle are preferably sheep and pigs.
  • non-mammal species but which are also livestock: birds, e.g. Chickens, geese, turkeys, ducks; Freshwater and saltwater fish such as Trout, carp, eels, reptiles; Insects such as e.g. Honeybee and silkworm.
  • Hobby animals include dogs and cats.
  • preferred are Toxoscaris spp., Toxocara spp., Trichuris spp., Trichinella spp. and the hookworms Ancylostoma spp. and Uncinaria spp. fought.
  • the products can also be used in humans.
  • Ascaris spp. Ancylostoma spp, Necator spp., Trichuris spp., Strongyloides spp. and Enterobius spp. fought.
  • herbivores are preferred for the application of the abovementioned combinations, ie animals which mainly feed on plants.
  • ruminants such as sheep, goats, cattle.
  • Strongyhda in particular Haemonchus spp., T ⁇ chostrongylus spp., Coope ⁇ a spp. and Ostertagia spp. be fought.
  • sheep are particularly preferably treated.
  • cattle are treated according to the invention.
  • the application can be both prophylactic and therapeutic.
  • the application of the active ingredient is carried out directly or in the form of suitable preparations enteral, parenteral, dermal, nasal, by treatment of the environment or with the aid of active ingredient-containing moldings such.
  • suitable preparations enteral, parenteral, dermal, nasal, by treatment of the environment or with the aid of active ingredient-containing moldings such.
  • active ingredient-containing moldings such as strips, plates, ligaments, collars, ear tags, limb bands, marking devices.
  • Enteral administration of the active ingredient is e.g. oral form of powder, suppositories, tablets, capsules, fasting, potions, granules, drenches, boii, medicated feed or drinking water.
  • the dermal application is e.g. in the form of dipping, spraying, bathing, washing, pour-on and spot-on, and empowering.
  • Parenteral administration is, for example, in the form of injection (mtramuscular, subcutaneous, intravenous, intrape ⁇ toneal) or by implants.
  • Suitable preparations are:
  • Solutions such as injection solutions, other solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, infusion formulations, gels; Emulsions and suspensions for oral or dermal use and for injection; semi-solid preparations;
  • Solid preparations such as powders, premixes or concentrates, granules, pellets, tablets, tablets, capsules; Aerosols and inhalants, active substance-containing moldings.
  • Injection solutions are administered intravenously, intramuscularly and subcutaneously.
  • Concentrates are applied directly. Concentrates are administered orally after prior dilution to the concentration of use.
  • Solutions for use on the skin are dripped, brushed, rubbed, sprayed on, sprayed on or applied by dipping (dipping, bathing or washing).
  • Gels are applied to the skin or brushed or incorporated into body cavities.
  • Pour-on formulations are infused or sprayed onto limited areas of the skin, whereby the active ingredient either penetrates the skin and acts systemically or spreads on the body surface.
  • Emulsions can be administered orally, dermally or as an injection. Emulsions are either water-in-oil type or oil-in-water type.
  • Suspensions may be administered orally, dermally or as an injection.
  • Semi-solid preparations may be administered orally or dermally.
  • the active compound is mixed with suitable excipients, if appropriate with the addition of auxiliaries, and brought into the desired form.
  • the products according to the invention may optionally contain further active ingredients.
  • the use in combination means either that the anthelmintic aminophenylamidine derivatives and the cyclic depsipeptides in a common preparation formulated and applied together accordingly.
  • the products may also comprise separate preparations for each active substance. If more than two active substances can be used, corresponding to all active ingredients in a common preparation, all active ingredients are formulated in separate formulations, conceivable are also mixed forms in which a part of the active ingredients together and a part of the active ingredients is formulated separately.
  • the products contain the active ingredients in each case in concentrations of 10 ppm to 90 weight percent, preferably 0.1 to 50 weight percent.
  • Ready-to-use preparations usually contain the active compounds in concentrations of 10 ppm to 20 percent by weight, preferably from 0.1 to 10 percent by weight.
  • Preparations which are diluted before use contain the active compounds in concentrations of 0.5-90 wt .-%, preferably from 5 to 50 weight percent.
  • the weight ratio of aminophenylamidine to cyclodepsipeptide in the products according to the invention depends on various factors, but is generally in the range of 10:90 to 50:50, preferably 20:80 to 30:70.
  • Usual dosages of Aminophenylamidine per day are 1 to 100 mg / kg body weight, preferably 2 to 60 mg / kg body weight.
  • Usual dosages of depsipeptides per day are 0.1 to 100 mg / kg, preferably 0.5 to 50 mg / kg, more preferably 1 to 50 mg / kg of body weight per day.
  • the active ingredients are filled in the amounts given below as a powder in a gelatin capsules:
  • the compounds were dissolved in DMSO and added to the incubation medium so that final concentrations of 100, 10, 1, 0.1, 0.01, 0.001 and 0.0001 ⁇ g / ml were present.
  • the controls contained only DMSO.
  • the acetylcholinesterase activity was determined according to the above publication.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne la combinaison de dérivés d'aminophénylamidine avec des depsipeptides cycliques, des produits renfermant cette combinaison, ainsi que l'utilisation de ces principes actifs en combinaison pour lutter contre les endoparasites chez l'homme et chez l'animal.
EP09768920A 2008-06-28 2009-06-16 Combinaison de dérivés d'amidine avec des depsipeptides cycliques Withdrawn EP2299995A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102008030764A DE102008030764A1 (de) 2008-06-28 2008-06-28 Kombination von Amidin-Derivaten mit cyclischen Depsipeptiden
PCT/EP2009/004304 WO2009156071A1 (fr) 2008-06-28 2009-06-16 Combinaison de dérivés d'amidine avec des depsipeptides cycliques

Publications (1)

Publication Number Publication Date
EP2299995A1 true EP2299995A1 (fr) 2011-03-30

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EP09768920A Withdrawn EP2299995A1 (fr) 2008-06-28 2009-06-16 Combinaison de dérivés d'amidine avec des depsipeptides cycliques

Country Status (13)

Country Link
US (1) US20110201550A1 (fr)
EP (1) EP2299995A1 (fr)
JP (1) JP2011526262A (fr)
AR (1) AR073180A1 (fr)
AU (1) AU2009262581A1 (fr)
BR (1) BRPI0913996A2 (fr)
CA (1) CA2729420A1 (fr)
DE (1) DE102008030764A1 (fr)
MX (1) MX2010014442A (fr)
TW (1) TW201012471A (fr)
UY (1) UY31921A (fr)
WO (1) WO2009156071A1 (fr)
ZA (1) ZA201009064B (fr)

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CN102344391B (zh) * 2011-07-28 2013-12-25 山东新华制药股份有限公司 N-(4-乙酰氨基苯基)-n′，n′-二甲基乙脒的合成方法
ES2916216T3 (es) 2015-05-20 2022-06-29 Boehringer Ingelheim Animal Health Usa Inc Compuestos de depsipéptidos antihelmínticos
CN108699052B (zh) 2015-12-28 2022-04-29 勃林格殷格翰动物保健美国公司 驱虫缩酚酸肽化合物
EP3541789A1 (fr) 2016-11-16 2019-09-25 Boehringer Ingelheim Animal Health USA Inc. Composés depsipeptidiques anthelminthiques
US11643438B2 (en) 2018-07-20 2023-05-09 The Board Of Regents Of The University Of Oklahoma Antimicrobial peptides and methods of use
CN114146074B (zh) * 2020-09-08 2024-03-01 中国疾病预防控制中心寄生虫病预防控制所(国家热带病研究中心) 抗寄生虫的药物组合及其应用、制备方法

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DE102008030764A1 (de) 2009-12-31
US20110201550A1 (en) 2011-08-18
ZA201009064B (en) 2012-02-29
AU2009262581A1 (en) 2009-12-30
TW201012471A (en) 2010-04-01
MX2010014442A (es) 2011-01-21
CA2729420A1 (fr) 2009-12-30
JP2011526262A (ja) 2011-10-06
WO2009156071A1 (fr) 2009-12-30
AR073180A1 (es) 2010-10-20
WO2009156071A8 (fr) 2010-12-29
UY31921A (es) 2010-01-29
BRPI0913996A2 (pt) 2015-10-20

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