EP4580627A1 - Traitement de la fasciolose - Google Patents

Traitement de la fasciolose

Info

Publication number
EP4580627A1
EP4580627A1 EP23764889.4A EP23764889A EP4580627A1 EP 4580627 A1 EP4580627 A1 EP 4580627A1 EP 23764889 A EP23764889 A EP 23764889A EP 4580627 A1 EP4580627 A1 EP 4580627A1
Authority
EP
European Patent Office
Prior art keywords
compound
fasciolosis
use according
mammal
compounds
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.)
Pending
Application number
EP23764889.4A
Other languages
German (de)
English (en)
Inventor
Michael Berger
Ulrich Sondern
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.)
Intervet International BV
Original Assignee
Intervet International BV
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 Intervet International BV filed Critical Intervet International BV
Publication of EP4580627A1 publication Critical patent/EP4580627A1/fr
Pending legal-status Critical Current

Links

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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • 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

Definitions

  • Fasciolosis can result from the migration of large numbers of immature fluke larvae through the liver, from the presence of adult flukes in the bile ducts, or both. Fasciolosis occurs in three main clinical forms - acute, subacute and chronic fasciolosis. Which form occurs depends on the numbers of infective metacercariae ingested and the period over which they are ingested.
  • fasciolosis The primary impact of fasciolosis is on farmed ruminants, however, they are not selective regarding the final host and successfully infect a wide range of mammals, including humans. Among the farmed ruminants, fasciolosis may cause annual economic losses of several billions of dollars world-wide.
  • Mature F. hepatica are large, leaf-shaped trematodes; about 3 to 5 cm in length and 1 cm in width. Both the immature and the mature stages of the parasite feed by secreting enzymes, most notably cysteine proteases, which break down blood and the liver tissue. The parasites irritate the walls of the bile ducts causing hyperplasia of the bile duct epithelium.
  • triclabendazole (TCBZ)
  • TABZ triclabendazole
  • immature stages i.e. early immature larvae (1 to 6 weeks old) and immature larvae (6 to 9 weeks old).
  • it is the only flukicide effective against all early immature liver fluke larvae.
  • Isoxazoline compounds are known in the art and these compounds are described, for example, in US patent application US 2007/0066617, and international patent applications WO 2005/085216, WO 2007/079162, WO 2009/002809, WO 2009/024541, WO 2009/003075, WO 2009/080250, WO 2010/070068 and WO 2010/079077.
  • the Applicant has addressed the problems of the prior art by identifying compounds that are effective at treating fasciolosis.
  • X is O or S, preferably O
  • Y is selected from
  • - denotes the bond to the carbonyl group for use in the treatment of fasciolosis of mammals.
  • Another aspect of the current invention is a composition comprising such compound and a pharmaceutically acceptable carrier for use in the treatment of fasciolosis of mammals.
  • Fasciolosis refers to a clinical or subclinical disease of mammals in connection with an infection of a mammal with Fasciola hepatica or Fasciola gigantica.
  • Fascioliosis ranges in severity from a devastating disease in sheep, and pseudo-ruminants such as alpacas, and llamas to a subclinical infection that is more common in cattle.
  • Chronic fascioliosis can occur in any season, but it manifests primarily in late fall and winter. It occurs as a result of ingesting moderate numbers of metacercariae over much longer periods of time.
  • Chronic fasciolosis is the most common form of liver fluke infection in sheep, goats and cattle - and particularly in more resistant hosts, such as horses and pigs. It occurs when the parasites reach the bile ducts in the liver. The fluke ingests blood, which produces severe anemia and chronic inflammation and enlargement of the bile ducts. The clinical signs develop slowly. The animals become increasingly anemic, appetite is lowered, the mucous membranes of the mouth and eyes become pale, and some animals develop oedema under the jaw ('bottle jaw'). Affected animals are reluctant to travel.
  • Significant production losses caused by (especially subcl inical) fasciolosis in livestock include reduced production and quality of wool, reduced lambing percentages, poor growth rate of lambs and/or increased costs for replacement stock in sheep; reduced calving percentages, poor growth rate of calves and/or increased costs for replacement stock in cattle; reduced production and quality of milk in dairy cattle and lower growth rates and lower feed conversion rates in fattening cattle.
  • live fluke infection refers to infestation of a mammal with Fasciola hepatica or Fasciola gigantica parasites. Unless otherwise indicated the term includes infestation or infection by flukes at any stage of maturity and mixtures of stages of maturity.
  • the fasciolosis is due to liver fluke infection by early immature stage liver fluke i.e., by early immature larvae (1 to 6 weeks old).
  • the fasciolosis is due to liver fluke infection by immature stage liver fluke i.e., by immature larvae (6 to 9 weeks old).
  • the fasciolosis is due to liver fluke infection by mature stage liver fluke i.e., by mature flukes (>9 weeks old).
  • the compound for use according to the invention is effective against all stages of liver flukes.
  • This compound is also known as a 4-[5-(5-chloro-a,a,a-trifluoro-m-tolyl)-4,5-dihydro-5-(trifluoromethyl)-l,2-oxazol- 3yl]-/V-[2-oxo-2-[(2,2,2-trifluoroethylamino]ethyl]naphthalene-l-or afoxolaner.
  • Afoxolaner is for example disclosed in WO 2007/079162.
  • the isoxazoline compound is Esafoxolaner.
  • a compound used as alternative is 2-chloro-/V-(l-cyanocyclopropyl)-5-[l-[2-methyl-5-(l,l,2,2,2-pentafluoroethyl)-4- (trifluoromethyl)pyrazol-3-yl]pyrazol-4-yl]benzamide (CAS RN 1621436) This compound is known as tigolaner.
  • the compound is 4H- Cyclopenta[c]thiophene-l-carboxamide, 3-[(5S)-5-(3,5-dichloro-4- fluorophenyl)-4,5-dihydro-5- (trifluoromethyl)-3-isoxazolyl]-N-[2-[(2,2- difluoroethyl)amino]-2-oxoethyl]-5,6-dihydro- (CAS 1414642-93-5). This compound is known as mivorilaner.
  • the compound of Formula (I) is (Z)-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-N-[(methoxy- imino)methyl]-2-methylbenzamide (CAS RN 928789-76-8).
  • the compound is 4-[5- (3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-yl) benzamide (CAS RN 1164267-94-0) that was disclosed in WO 2009/0080250.
  • the compound is 5-[5- (3,5-dDichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-3-methyl-N-[2-oxo-2-[(2,2,2- trifluoroethyl) amino] ethyl]- 2-thiophenecarboxamide (CAS RN 1231754-09-8) that was disclosed in WO 2010/070068.
  • the compound of Formula (I) is selected from fluralaner (including (S) fluralaner), afoxolaner (including esafoxolaner), sarolaner, or lotilaner.
  • fluralaner corresponding to 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5- dihydroisoxazol-3-yl]-2-methyl-/ ⁇ /-[(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide
  • systemic insecticide and/or acaricide a) which is represented by Formula (II)
  • the compounds for use according to the current invention may exist in various isomeric forms.
  • a reference to a compound always includes all possible isomeric forms of such a compound.
  • a compound structure that does not indicate a particular conformation is intended to encompass compositions of all the possible conformational isomers of the compound, as well as compositions comprising fewer than all the possible conformational isomers.
  • Compounds of Formula (I) can be prepared according to one or other of the processes described e.g., in patent applications US 2007/0066617, WO 2007/079162, WO 2009/002809, WO 2009/080250, WO 2010/070068, WO 2010/079077, WO 2011/075591 and WO 2011/124998 or any other process coming within the competence of a person skilled in the art who is an expert in chemical synthesis.
  • composition for use according to the invention comprising more than one pharmaceutically active ingredient, i.e. wherein the composition for oral administration comprises another active pharmaceutical ingredient.
  • the term “comprise,” or variations thereof such as “comprises” or “comprising,” are to be read to indicate the inclusion of any recited integer (e.g., a feature, element, characteristic, property, method/process step or limitation) or group of integers (e.g., features, element, characteristics, properties, method/process steps or limitations) but not the exclusion of any other integer or group of integers.
  • combination with as well as “combination” and “synergistic combination” as used herein are taken to mean that a compound different from a compound of Formula (I) or another compound of Formula (I) is administered prior to, during, or after the administration of an compound of Formula (I). That is, in these are administered either sequentially or simultaneously to the mammal.
  • the combination is with a compound different from a compound of Formula (I).
  • sequentially administration means administration of within three days of administration of the other.
  • the compounds for use of the current invention are administered together with the combination compound within a day of each other and even more typically on the same day.
  • Sequential administration also means administration of such compounds within an hour, or even minutes, of administration of the othe compound.
  • Simultaneous administration includes preferably the presence of such compounds in the same veterinary product.
  • active ingredients which may include, without limitation antiparasitics such as endoparasiticides (including anthelmintics) and ecto-parasiticides, hormones and/or derivatives thereof, anti-inflammatory compounds and minerals and vitamins.
  • antiparasitics such as endoparasiticides (including anthelmintics) and ecto-parasiticides, hormones and/or derivatives thereof, anti-inflammatory compounds and minerals and vitamins.
  • a combination with selenium especially as sodium selenate.
  • the active ingredients are preferably antiparasitics, more preferably endoparasiticides, preferably anthelmintics and are preferably selected from the group consisting of avermectins (e.g., ivermectin, doramectin, abamectin, eprinomectin); milbemycins (moxidectin and milbemycin oxime); probenzimidazoles (e.g., febantel, netobimin, and thiophanate); benzimidazole derivatives, such as a thiazole benzimidazole derivatives (e.g., thiabendazole and cambendazole), carbamate benzimidazole derivatives (e.g., fenbendazole, albendazole (oxide), mebendazole, oxfendazole, parbendazole, oxibendazole, flubendazole, and triclabendazole); imidazothi
  • ivermectin eprinomectin
  • moxidectin levamisole
  • fenbendazole abamectin, monepantel, derquantel, oxfendazole, albendazole, closantel and combinations thereof.
  • An effective amount of the compound for use according to the current invention is administered to the mammal orally or parenterally.
  • an effective amount is administered orally to the mammal.
  • an effective amount is administered parenterally to the mammal.
  • the compounds are administered to an animal in need thereof in the form of a pharmaceutical or veterinary composition.
  • compositions for oral administration include components conventionally used in the art of formulation and may therefore be processed in a known manner to give, for example, solutions, emulsions, soluble powders, powder mixtures, granules or microencapsulation in polymeric substances.
  • Such formulations, preparations or compositions optionally include a solid or liquid adjuvant, and are produced in a manner well-known in the art, for example by intimately mixing and/or grinding the active ingredients with the adjuvants, for example with solvents, solid carriers, etc.
  • Oral administration can also be accomplished by drench, gavage, tablet, capsule, or in feed.
  • compositions are known to be suitable for oral administration to animals, but they vary for the different animal species.
  • Oral administration can be accomplished by conventional dosage forms, such as e.g. drench, gavage, tablet, capsule, or in feed.
  • Drenching means that a liquid, potentially slightly viscous pharmaceutical composition comprising the active pharmaceutical ingredient and excipients is applied via the mouth with a specific drenching gun that dispenses the composition into the sheep's throat.
  • Oral drench compositions are in general solutions or suspensions and generally not more than 20 ml, preferably not more than 15 ml of such drench are applied per sheep.
  • a concentrated solution is used to administer the compound for use according to the invention via drench application to sheep.
  • a suspension formulation is used for the drench application.

Landscapes

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

Abstract

La présente invention concerne des composés et des compositions de formule (I) pour le traitement d'une fasciolose chez un mammifère.
EP23764889.4A 2022-09-02 2023-09-01 Traitement de la fasciolose Pending EP4580627A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP22193586 2022-09-02
PCT/EP2023/074068 WO2024047241A1 (fr) 2022-09-02 2023-09-01 Traitement de la fasciolose

Publications (1)

Publication Number Publication Date
EP4580627A1 true EP4580627A1 (fr) 2025-07-09

Family

ID=83191797

Family Applications (1)

Application Number Title Priority Date Filing Date
EP23764889.4A Pending EP4580627A1 (fr) 2022-09-02 2023-09-01 Traitement de la fasciolose

Country Status (6)

Country Link
EP (1) EP4580627A1 (fr)
JP (1) JP2025527799A (fr)
AU (1) AU2023332216A1 (fr)
CA (1) CA3264674A1 (fr)
MX (1) MX2025002490A (fr)
WO (1) WO2024047241A1 (fr)

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101768129B (zh) 2004-03-05 2012-05-23 日产化学工业株式会社 异*唑啉取代苯甲酰胺化合物的制备中间体
TWI412322B (zh) 2005-12-30 2013-10-21 Du Pont 控制無脊椎害蟲之異唑啉
TWI430995B (zh) 2007-06-26 2014-03-21 Du Pont 萘異唑啉無脊椎有害動物控制劑
TWI411395B (zh) 2007-12-24 2013-10-11 Syngenta Participations Ag 殺蟲化合物
EP2379544B1 (fr) 2008-12-18 2013-10-16 Novartis AG Dérivés d'isoxazoline et leur utilisation en tant que pesticide
PL2379537T3 (pl) 2008-12-19 2013-03-29 Elanco Tiergesundheit Ag Pochodne izooksazoliny i ich zastosowanie jako pestycydów
ME02432B (fr) 2009-12-17 2016-09-20 Merial Inc Dihydroazoles antiparasitaires et compositions les incluant
WO2011124998A1 (fr) 2010-04-08 2011-10-13 Pfizer Inc. Dérivés de 3,5-diphényl-isoxazoline substitués comme insecticides et acaricides

Also Published As

Publication number Publication date
CA3264674A1 (fr) 2024-03-07
MX2025002490A (es) 2025-04-02
WO2024047241A1 (fr) 2024-03-07
JP2025527799A (ja) 2025-08-22
AU2023332216A1 (en) 2025-02-20

Similar Documents

Publication Publication Date Title
AU2021266292B2 (en) Soft chewable pharmaceutical products
KR101787917B1 (ko) 구충제 경구 투여에 의한 흡혈 및 혈 소모 기생충의 전신 치료
CN113038937A (zh) 可口的抗寄生虫制剂
AU2023219972B2 (en) Use of isoxazoline compounds for treating demodicosis
RU2673723C1 (ru) Применение содержащих изоксазолин соединений в качестве противопаразитарных средств
CN113134008A (zh) 宠物用伊维菌素吡喹酮咀嚼片及其制备方法
AU2023332216A1 (en) Treatment of fasciolosis
JP2003514834A (ja) 寄生虫を防除するためのｎ−フェニル−ｎ’−ベンゾイル尿素誘導体とネクチン化合物の組合せ
JPH06211792A (ja) 寄生生物の全身的駆除
US20080249153A1 (en) Anthelmintic formulations
Taylor Use of anthelmintics in sheep
US11903962B1 (en) Isoxazoline complexes and compositions thereof
RU2773154C1 (ru) Противопаразитарные составы с привлекательным вкусом
US20240366572A1 (en) Isoxazoline complexes and compositions thereof
CN101987108A (zh) 一种驱除动物体内外寄生虫的复方注射剂及其制备方法
Craig Current Approaches to Internal Parasite Control in Food Animals
RU2772279C2 (ru) Твердые фармацевтические композиции для перорального введения на основе изоксазолиновых соединений
Harikrishnan Dewormers and Dewormer Resistance in Sheep and Goats
Schilliger How i use the anthelmintic profender in reptiles.
JPS5817444B2 (ja) 抗コクシジウム剤

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20250402

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC ME MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)