Anthelmintic depsipeptide compounds

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:
• Cy1 and Cy2 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, SF5, R5S(O)—, R5S(O)2—, R5C(O)—, R5R6NC(O)—, R5R6NC(O)NR5—, R5OC(O)—, R5C(O)O—, R5C(O)NR6—, —CN, —NO2, cycloalkyl, heteroalkyl, heterocyclyl, aryl and heteroaryl, wherein each cycloalkyl, heteroalkyl, heterocyclyl, aryl or heteroaryl substituents of Cy1 and Cy2 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, SF5, R5S(O)—, R5S(O)2—, R5C(O)—, R5R6NC(O)—, R5OC(O)—, R5C(O)O—, R5C(O)NR6—, —CN and —NO2;
• R5 and R6 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthio, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl, or the group —CH2C(O)NHCH2CF3;
• or R5 and R6 together with the atom(s) to which they are bonded form a C3-C6 cyclic group;
• R′, R″, R′″ and R″″ are each independently hydrogen or C1-C3alkyl;
• Ra and Rb are independently hydrogen, C1-C3alkyl or C1-C3haloalkyl;
• and
• (a) R1 is C1-C3 alkyl or C1-C3 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 C1-C3alkyl;
• or
• R1 and R1″ together form a 2-4-membered carbon chain to form a ring;
• and
• R2, R2′, R3, R3′, R4 and R4′ are each independently hydrogen or C1-C8 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) R2 is C1-C3 alkyl or C1-C3 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 R2′ is hydrogen or C1-C3alkyl;
• or
• R2 and R2′ together form a 2-4-membered carbon chain to form a ring;
• and
• R1, R1″, R3, R3′, R4 and R4′ are each independently hydrogen or C1-C8 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) R3 is C1-C3 alkyl or C1-C3 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 R3′ is hydrogen or C1-C3alkyl;
• or
• R3 and R3′ together form a 2-4-membered carbon chain to form a ring;
• and
• R1, R1′, R2, R2′, R4 and R4′ are each independently hydrogen or C1-C8 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) R4 is C1-C3 alkyl or C1-C3 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 R4′ is hydrogen or C1-C3alkyl;
• or
• R4 and R4′ together form a 2-4-membered carbon chain to form a ring;
• and
• R1, R1′, R2, R2′, R3 and R3′ are each independently hydrogen or C1-C8 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) R1 and R2 are each independently C1-C3 alkyl or C1-C3 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 R1′ and R2′ are independently hydrogen or C1-C3alkyl;
• or
• R1 and R1′ together and/or R2 and R2′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R3, R3′, R4 and R4′ are each independently hydrogen or C1-C8 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) R1 and R3 are each independently C1-C3 alkyl or C1-C3 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 R1′ and R3′ are independently hydrogen or C1-C3alkyl;
• or
• R1 and R1″ together and/or R3 and R3′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R2, R2′, R4 and R4′ are each independently hydrogen or C1-C8 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
• (g) R1 and R4 are each independently C1-C3 alkyl or C1-C3 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 R1′ and R4′ are independently hydrogen or C1-C3alkyl;
• or
• R1 and R1′ together and/or R4 and R4′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R2, R2′, R3 and R3′ are each independently hydrogen or C1-C8 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
• (h) R2 and R4 are each independently C1-C3 alkyl or C1-C3 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 R2′ and R4′ are independently hydrogen or C1-C3alkyl;
• or
• R2 and R2′ together and/or R4 and R4′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R1, R1′, R3 and R3′ are each independently hydrogen or C1-C8 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
• (i) R2 and R3 are each independently C1-C3 alkyl or C1-C3 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 R2′ and R3′ are independently hydrogen or C1-C3alkyl;
• or
• R2 and R2′ together and/or R3 and R3′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R1, R1′, R4 and R4′ are each independently hydrogen or C1-C8 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
• (j) R3 and R4 are each independently C1-C3 alkyl or C1-C3 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 R3′ and R4′ are independently hydrogen or C1-C3alkyl;
• or
• R3 and R3′ together and/or R4 and R4′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R1, R1′, R2 and R2′ are each independently hydrogen or C1-C8 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
• (k) R1, R2 and R3 are each independently C1-C3 alkyl or C1-C3 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 R1′, R2′ and R3′ are independently hydrogen or C1-C3alkyl;
• or
• R1 and R1′ together and/or R2 and R2′ together and/or R3 and R3′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R4 and R4′ are independently hydrogen or C1-C8 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
• (1) R2, R3 and R4 are each independently C1-C3 alkyl or C1-C3 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 R2′, R3′ and R4′ are independently hydrogen or C1-C3alkyl;
• or
• R2 and R2′ together and/or R3 and R3′ together and/or R4 and R4′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R1 and R1′ are independently hydrogen or C1-C8 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
• (m) R1, R3 and R4 are each independently C1-C3 alkyl or C1-C3 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″, R3′ and R4′ are independently hydrogen or C1-C3alkyl;
• or
• R1 and R1″ together and/or R3 and R3′ together and/or R4 and R4′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R2 and R2′ are independently hydrogen or C1-C8 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
• (n) R1, R2 and R4 are each independently C1-C3 alkyl or C1-C3 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 R1′, R2′ and R4′ are independently hydrogen or C1-C3alkyl;
• or
• R1 and R1″ together and/or R2 and R2′ together and/or R4 and R4′ together independently form a 2-4-membered carbon chain to form a ring;
• and
• R3 and R3′ are independently hydrogen or C1-C8 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
• (o) R1, R2, R3 and R4 are each independently C1-C3 alkyl or C1-C3 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 R1′, R2′, R3′ and R4′ are independently hydrogen or C1-C3alkyl;
• or
• R1 and R1″ together and/or R2 and R2′ together and/or R3 and R3′ together and/or R4 and R4′ together independently form a 2-4-membered carbon chain to form a ring.