Anthelmintic depsipeptide compounds

Patent metadata

Field	Value
Publication number	US-11230571-B2
Application number	US-201916392412-A
Country	US
Kind code	B2
Filing date	Apr 23, 2019
Priority date	Dec 28, 2015
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

Abstract

The present invention provides cyclic depsipeptide compounds of formula (I) and compositions comprising the compounds that are effective against parasites that harm animals, including humans. The compounds and compositions may be used for combating parasites in or on animals including mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in animals, including birds and mammals.

First claim

What is claimed is:

1. A method for the treatment of a parasitic infection in a mammal caused by an endoparasite selected from group consisting of Anaplocephala, Ancylostoma, Necator, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Cyathostomum, Cylicocyclus, Cylicodontophorus, Cylicostephanus, Craterostomum, Dictyocaulus, Dipetalonema, Dipylidium, Dracunculus, Echinococcus, Enterobius, Fasciola, Filaroides, Habronema, Haemonchus, Metastrongylus, Moniezia, Nematodirus, Nippostrongylus, Oesophagostomum, Onchocerca, Ostertagia, Oxyuris, Parascaris, Schistosoma, Strongylus, Taenia, Toxocara, Strongyloides, Toxascaris, Trichinella, Trichuris, Trichostrongylus, Triodontophorus, Uncinaria and Wuchereria comprising administering a parasiticidally effective amount of an anthelmintic cyclic depsipeptide of Formula (I) to the animal:

wherein:
Cy 1 and Cy 2 are independently aryl or heteroaryl, each of which is optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF 5 , R 5 S(O)—, R 5 S(O) 2 —, R 5 C(O)—, R 5 R 6 NC(O)—, R 5 R 6 NC(O)NR 5 —, R 5 OC(O)—, R 5 C(O)O—, R 5 C(O)NR 6 —, —CN, —NO 2 , cycloalkyl, heteroalkyl, heterocyclyl, aryl and heteroaryl, wherein each cycloalkyl, heteroalkyl, heterocyclyl, aryl or heteroaryl substituents of Cy 1 and Cy 2 is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF 5 , R 5 S(O)—, R 5 S(O) 2 —, R 5 C(O)—, R 5 R 6 NC(O)—, R 5 OC(O)—, R 5 C(O)O—, R 5 C(O)NR 6 —, —CN and —NO 2 ;
R 5 and R 6 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthio, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl, or the group —CH 2 C(O)NHCH 2 CF 3 ; or R 5 and R 6 together with the atom(s) to which they are bonded form a C 3 -C 6 cyclic group;
R′, R″, R′″ and R″″ are each independently hydrogen or C 1 -C 3 alkyl;
R a and R b are independently hydrogen, C 1 -C 3 alkyl or C 1 -C 3 haloalkyl; and
(a) R 1 is C 1 -C 3 alkyl or C 1 -C 3 haloalkyl substituted by a 3- to 6-membered non-aromatic carbocyclic ring; wherein said 3- to 6-membered non-aromatic carbocyclic ring may be further substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and R″ is hydrogen or C 1 -C 3 alkyl; or
R 1 and R 1″ together form a 2-4-membered carbon chain to form a ring; and
R 2 , R 2′ , R 3 , R 3′ , R 4 and R 4′ are each independently hydrogen or C 1 -C 8 alkyl, optionally substituted by one or more halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino or dialkylamino; or
(b) R 2 is C 1 -C 3 alkyl or C 1 -C 3 haloalkyl substituted by a 3- to 6-membered non-aromatic carbocyclic ring; wherein said 3- to 6-membered non-aromatic carbocyclic ring may be further substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and R 2′ is hydrogen or C 1 -C 3 alkyl; or
R 2 and R 2′ together form a 2-4-membered carbon chain to form a ring; and
R 1 , R 1″ , R 3 , R 3′ , R 4 and R 4′ are each independently hydrogen or C 1 -C 8 alkyl, optionally substituted by one or more halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino or dialkylamino; or
(c) R 3 is C 1 -C 3 alkyl or C 1 -C 3 haloalkyl substituted by a 3- to 6-membered non-aromatic carbocyclic ring; wherein said 3- to 6-membered non-aromatic carbocyclic ring may be further substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and R 3′ is hydrogen or C 1 -C 3 alkyl; or
R 3 and R 3′ together form a 2-4-membered carbon chain to form a ring; and
R 1 , R 1′ , R 2 , R 2′ , R 4 and R 4′ are each independently hydrogen or C 1 -C 8 alkyl, optionally substituted by one or more halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino or dialkylamino; or
(d) R 4 is C 1 -C 3 alkyl or C 1 -C 3 haloalkyl substituted by a 3- to 6-membered non-aromatic carbocyclic ring; wherein said 3- to 6-membered non-aromatic carbocyclic ring may be further substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and R 4′ is hydrogen or C 1 -C 3 alkyl; or
R 4 and R 4′ together form a 2-4-membered carbon chain to form a ring; and
R 1 , R 1′ , R 2 , R 2′ , R 3 and R 3′ are each independently hydrogen or C 1 -C 8 alkyl, optionally substituted by one or more halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino or dialkylamino; or
(e) R 1 and R 2 are each independently C 1 -C 3 alkyl or C 1 -C 3 haloalkyl substituted by a 3- to 6-membered non-aromatic carbocyclic ring; wherein said 3- to 6-membered non-aromatic carbocyclic rings may be further independently substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and R 1′ and R 2′ are independently hydrogen or C 1 -C 3 alkyl; or
R 1 and R 1′ together and/or R 2 and R 2′ together independently form a 2-4-membered carbon chain to form a ring; and
R 3 , R 3′ , R 4 and R 4′ are each independently hydrogen or C 1 -C 8 alkyl, optionally substituted by one or more halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, halothio, alkylsulfinyl, haloalkylsulfinyl, alkyl sulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino or dialkylamino; or
(f) R 1 and R 3 are each independently C 1 -C 3 alkyl or C 1 -C 3 haloalkyl substituted by a 3- to 6-membered non-aromatic carbocyclic ring; wherein said 3- to 6-membered non-aromatic carbocyclic rings may be further independently substituted by one or more

Assignees

• Boehringer Ingelheim Animal Health Usa Inc

Inventors

• Le Hir De Fallois Loic
• Pacofsky Greg
• Long Alan
• Meng Charles Q
• Lee Hyoung Ik

Classifications

• A01N43/72 Primary

  having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms · CPC title

• C07K11/02 Primary

  cyclic, e.g. valinomycins {; Derivatives thereof} · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• A61K38/15

  Depsipeptides; Derivatives thereof · CPC title

• C07D273/00 Primary

  Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 · CPC title