Anthelmintic depsipeptide compounds

Patent metadata

Field	Value
Publication number	US-10793604-B2
Application number	US-201816111027-A
Country	US
Kind code	B2
Filing date	Aug 23, 2018
Priority date	May 20, 2015
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

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

First claim

What is claimed is:

1. A method for the treatment or prevention of a parasitic infection or infestation in an animal comprising administering a parasiticidally effective amount of an anthelmintic cyclic depsipeptide of formula (I), or a pharmaceutically or veterinarily acceptable salt thereof, to the animal:

wherein:
Cy 1 and Cy 2 are independently aryl, carbocyclic, heteroaryl or heterocyclic 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, heteroaryl, —O-heteroaryl, —S-heteroaryl, —O— heterocyclyl and —S-heterocyclyl, wherein each cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally further 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, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, 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 8 alkyl substituted by one or more halogen; and
R 2 , R 3 and R 4 are each independently C 1 -C 8 alkyl; or
(b) R 2 is C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 , R 3 and R 4 are each independently C 1 -C 8 alkyl; or
(c) R 3 is C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 , R 2 and R 4 are each independently C 1 -C 8 alkyl; or
(d) R 4 is C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 , R 2 and R 3 are each independently C 1 -C 8 alkyl; or
(e) R 1 and R 2 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 3 and R 4 are each independently C 1 -C 8 alkyl; or
(f) R 1 and R 3 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 2 and R 4 are each independently C 1 -C 8 alkyl; or
(g) R 1 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 2 and R 3 are each independently C 1 -C 8 alkyl; or
(h) R 2 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 and R 3 are each independently C 1 -C 8 alkyl; or
(i) R 2 and R 3 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 and R 4 are each independently C 1 -C 8 alkyl; or
(j) R 3 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 and R 2 are each independently C 1 -C 8 alkyl; or
(k) R 1 , R 2 and R 3 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 4 is C 1 -C 8 alkyl; or
(l) R 2 , R 3 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 is C 1 -C 8 alkyl; or
(m) R 1 , R 3 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 2 is C 1 -C 8 alkyl; or
(n) R 1 , R 2 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 3 is C 1 -C 8 alkyl; or
(o) R 1 , R 2 , R 3 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen.

2. The method of claim 1 , wherein:
(f) R 1 and R 3 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 2 and R 4 are each independently C 1 -C 8 alkyl; or
(h) R 2 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 and R 3 are each independently C 1 -C 8 alkyl; or
(e) R 1 and R 2 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 3 and R 4 are each independently C 1 -C 8 alkyl; or
(g) R 1 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 2 and R 3 are each independently C 1 -C 8 alkyl; or
(i) R 2 and R 3 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 and R 4 are each independently C 1 -C 8 alkyl; or
(j) R 3 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 and R 2 are each independently C 1 -C 8 alkyl.

3. The method of claim 1 , wherein:
(a) R 1 is C 1 -C 8 alkyl substituted by one or more halogen; and
R 2 , R 3 and R 4 are each independently C 1 -C 8 alkyl; or
(b) R 2 is C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 , R 3 and R 4 are each independently C 1 -C 8 alkyl; or
(c) R 3 is C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 , R 2 and R 4 are each independently C 1 -C 8 alkyl; or
(d) R 4 is C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 , R 2 and R 3 are each independently C 1 -C 8 alkyl.

4. The method of claim 1 , wherein:
(k) R 1 , R 2 and R 3 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 4 is C 1 -C 8 alkyl; or
(l) R 2 , R 3 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 1 is C 1 -C 8 alkyl; or
(m) R 1 , R 3 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 2 is C 1 -C 8 alkyl; or
(n) R 1 , R 2 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen; and
R 3 is C 1 -C 8 alkyl.

5. The method of claim 1 , wherein:
(o) R 1 , R 2 , R 3 and R 4 are each independently C 1 -C 8 alkyl substituted by one or more halogen.

6. The method of claim 1 , wherein at least one of R 1 , R 2 , R 3 and R 4 is C 1 -C 8 alkyl substituted by halogen.

7. The method of claim 6 , wherein one of R 1 , R 2 , R 3 and R 4 is C 1 -C 8 alkyl substituted by halogen.

8. The method of claim 6 , wherein three of R 1 , R 2 , R 3 and R 4 is C 1 -C 8 alkyl substituted by halogen.

9. The method of claim 6 , wherein each of R 1 , R 2 , R 3 and R 4 are C 1 -C 8 alkyl substituted by halogen.

10. The method of claim 6 , wherein two of R 1 , R 2 , R 3 and R 4 is C 1 -C 8 alkyl substituted by halogen.

11. The method of claim 10 , wherein R 1 and R 3 are C 1 -C 8 alkyl substituted by halogen.

12. The method of claim 11 , wherein halogen is fluoro.

13. The method of claim 10 , wherein R 2 and R 4 are C 1 -C 8 alkyl substituted by halogen.

14. The method of claim 13 , wherein halogen is fluoro.

15. The method of claim 1 , wherein Cy 1 and Cy 2 are independently phenyl, a 5-membered heteroaryl or a 6-membered heteroaryl, wherein said phenyl, 5-membered heteroaryl or 6-membered heteroaryl is optionally subst

Assignees

• Boehringer Ingelheim Animal Health Usa Inc

Inventors

• Le Hir De Fallois Loic
• Pacofsky Greg
• Long Alan
• Meng Charles
• Lee Hyoung Ik
• Ogbu Cyprian O

Classifications

• C07K11/02 Primary

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

• A61P33/10

  Anthelmintics · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A01P17/00

  Pest repellants · CPC title

• A01N43/90

  having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system · CPC title