Parasiticidal compositions comprising indole derivatives, methods and uses thereof

Patent metadata

Field	Value
Publication number	US-9776986-B2
Application number	US-201514744166-A
Country	US
Kind code	B2
Filing date	Jun 19, 2015
Priority date	Jun 19, 2014
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

The invention relates to oral, topical or injectable compositions for combating liver fluke parasites in mammals, comprising at least one indole derivative active agent. The invention also provides for an improved method for eradicating and controlling liver fluke parasite infections and infestations in a mammal comprising administering the compositions of the invention to the mammal in need thereof.

First claim

What is claimed is:

1. A compound of formula:

wherein:
R 1 is (C 1 -C 6 )-alkyl substituted with one or more halogens;
R 2 is H, halogen, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl;
R 3 is biphenyl, naphthyl, aryl, aryl ether, or (C 3 -C 6 ) cycloalkyl;
wherein the last three substituents may be unsubstituted or substituted with one or more of halogen, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-haloalkoxy, aminoalkyl, cyano or carboxyl;
R 4 is halogen;
R 5 is H, halogen, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-haloalkyl; and
R 6 is H, halogen, (C 1 -C 6 )-alkyl, (C 2 -C 5 )-alkenyl, or (C 2 -C 5 )-alkynyl, wherein each of (C 1 -C 6 )-alkyl, (C 2 -C 5 )-alkenyl, or (C 2 -C 5 )-alkynyl is independently unsubstituted or substituted with one or more halogens.

2. A compound according to claim 1 wherein R 1 is (C 1 -C 4 )-alkyl substituted with fluorine.

3. A compound according to claim 1 wherein R 2 is Cl.

4. A compound according to claim 1 wherein R 3 is a mono- or bi-halogen substituted phenyl ether.

5. A compound according to claim 1 wherein R 3 is a bi- or tri-halogen substituted phenyl.

6. A compound according to claim 4 wherein the halogen is chlorine, bromine or fluorine.

7. A compound according to claim 5 wherein the halogen is chlorine, bromine or fluorine.

8. A compound according to claim 1 wherein R 4 is chlorine.

9. A compound according to claim 1 wherein R 5 is hydrogen.

10. A composition for treating helminth infestation comprising an anthelmintically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

11. A composition for treating helminth infestation according to claim 10 wherein the compound of formula (I) is combined with an additional active agent selected from the group consisting of acaricides, anthelmintics, anti-parasitics and insecticides.

12. A composition for treating helminth infestation according to claim 11 wherein the active agent is a macrocyclic lactone.

13. A composition for treating helminth infestation according to claim 12 wherein the macrocyclic lactone is selected from the group consisting of abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin or ML-1,694,554.

14. A composition for treating helminth infestation according to claim 10 wherein the compound of formula (I) is combined with verapamil.

15. A method for treating helminth infestation comprising administration of an anthelmintically effective amount of the compound of claim 1 to an animal in need thereof.

16. A method according to claim 15 in which the helminths are trematodes.

17. A method according to claim 16 in which the helminths are Fasciola hepatica.

18. A compound of formula:

wherein:
R 1 is CF 3 ;
R 2 is H;
R 3 is phenyl or heteroaryl;
wherein the phenyl or heteroaryl is unsubstituted or substituted with one or more of halogen, (C 1 -C 3 )-haloalkyl or cyano;
R 4 is halogen;
R 5 is H; and
R 6 is H.

19. A compound according to claim 18 wherein the heteroaryl is a pyridine.

20. A composition for treating helminth infestation comprising an anthelmintically effective amount of the compound of claim 18 and a pharmaceutically acceptable carrier.

21. A composition for treating helminth infestation according to claim 20 wherein the compound of formula (I) is combined with an additional active agent selected from the group consisting of acaricides, anthelmintics, anti-parasitics and insecticides.

22. A composition for treating helminth infestation according to claim 21 wherein the active agent is a macrocyclic lactone.

23. A composition for treating helminth infestation according to claim 22 wherein the macrocyclic lactone is selected from the group consisting of abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin or ML-1,694,554.

24. A composition for treating helminth infestation according to claim 20 wherein the compound of formula (I) is combined with verapamil.

25. A method for treating helminth infestation comprising administration of an anthelmintically effective amount of the compound of claim 18 to an animal in need thereof.

26. A method according to claim 25 in which the helminths are trematodes.

27. A method according to claim 26 in which the helminths are Fasciola hepatica.

Assignees

• Merial Inc
• Merial Inc

Inventors

• Meng Charles
• Le Hir De Fallois Loïc

Classifications

• A61P33/14

  Ectoparasiticides, e.g. scabicides · CPC title

• A61P33/10

  Anthelmintics · CPC title

• H03K7/00

  Modulating pulses with a continuously-variable modulating signal · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D209/08

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title