Anthelmintic compounds and compositions and method of using thereof

Patent metadata

Field	Value
Publication number	US-10155725-B2
Application number	US-201514981847-A
Country	US
Kind code	B2
Filing date	Dec 28, 2015
Priority date	Nov 20, 2012
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

The present invention relates to novel anthelmintic compounds of formula (I) below:

wherein
Y and Z are independently a bicyclic carbocyclic or a bicyclic heterocyclic group, or one of Y or Z is a bicyclic carbocyclic or a bicyclic heterocyclic group and the other of Y or Z is alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclyl or heteroaryl, and variables X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 and X 8 are as defined herein. The invention also provides for veterinary compositions comprising the anthelmintic compounds of the invention, and their uses for the treatment and prevention of parasitic infections in animals.

First claim

What is claimed is:

1. An anthelmintic compound of formula (IA-2):

wherein Y is a bicyclic carbocyclic or a bicyclic heterocyclic group selected from the group consisting of naphthyl, indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, indolizinyl, benzofuranyl, dihydrobenzofuranyl, chromonyl, coumarinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl, dihydroisoindolyl, dihydroquinazolinyl and tetrahydroquinolinyl optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, SF 5 , haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkyl sulfonyl or haloalkylsulfonyl;
Z is phenyl optionally substituted with one or more halogen, nitro, cyano, or haloalkyl;
X 1 is a bond,
X 8 is —O—, or —NH—, which is optionally substituted with alkyl;
Ring A is L1:

W is O or S;
R 2 and R 3 are independently hydrogen or alkyl;
n is 1, 2 or 3; and
r is 0 to 5.

2. A composition for the treatment of a parasitic infection or infestation in an animal, comprising an effective amount of at least one anthelmintic compound of claim 1 in combination with a pharmaceutically acceptable carrier.

3. The composition of claim 2 , wherein the composition comprises an additional parasiticidal active agent.

4. A method for the treatment of a parasitic infection or infestation in an animal, comprising administering an effective amount of the anthelmintic compound of claim 1 to the animal.

5. The compound of claim 1 , wherein X 8 is —O—, —NH— or —N(CH 3 )—.

6. The compound of claim 5 , wherein:
R 2 and R 3 are independently hydrogen or C 1 -C 3 alkyl; and
X 8 is —NH— or —N(CH 3 )—.

7. The compound of claim 6 , wherein Y is naphthyl, benzothiazolyl, benzoxazolyl, benzothienyl, quinolinyl, isoquinolinyl, indolizinyl, benzofuranyl or dihydrobenzofuranyl optionally substituted by one or more halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, alkoxy, haloalkoxy, SF 5 , alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl or haloalkylsulfonyl; and Z is phenyl optionally substituted with one or more halogen, nitro, cyano or CF 3 .

8. The compound of claim 7 , wherein Y is naphthyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, indolizinyl, benzofuranyl or dihydrobenzofuranyl optionally substituted with one or more halogen, haloalkyl, haloalkylthio, SF 5 or haloalkoxy; and Z is phenyl substituted with one or more fluoro, nitro or CF 3 .

9. The compound of claim 7 , wherein Y is naphthyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, indolizinyl, benzofuranyl or dihydrobenzofuranyl optionally substituted with one or more halogen haloalkyl, haloalkoxy, SF 5 or haloalkylthio; and Z is phenyl substituted with one or more fluoro, cyano or CF 3 .

10. The compound of claim 8 , wherein Y is naphthyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, indolizinyl, benzofuranyl or dihydrobenzofuranyl optionally substituted with one or more halogen, CF 3 , —OCF 3 , —SCF 3 or SF 5 ; and Z is phenyl substituted with nitro and CF 3 .

11. The compound of claim 9 , wherein Y is naphthyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl benzofuranyl or dihydrobenzofuranyl, optionally substituted with one or more halogen, CF 3 , —OCF 3 , —SCF 3 or —SF 5 ; and Z is phenyl substituted with cyano and CF 3 .

12. The compound of claim 8 , wherein:
Y is naphthyl, quinolinyl, benzothiazolyl or benzoxazolyl optionally substituted with one or more halogen, or C 1 -C 3 haloalkyl;
X 8 is —NH—;
R 2 and R 3 are each independently hydrogen or C 1 -C 3 alkyl;
Z is phenyl optionally substituted with one or more of F, nitro, cyano or CF 3 ; and
n is 2 or 3.

13. The compound of claim 12 , wherein:
Y is naphthyl optionally substituted with one or more F, Cl or CF 3 ;
R 2 and R 3 are independently hydrogen or CH 3 ;
Z is phenyl substituted with one or more nitro, cyano or CF 3 .

14. The compound of claim 12 , wherein:
Y is quinolinyl optionally substituted with one or more F, Cl or CF 3 ;
R 2 and R 3 are independently hydrogen or CH 3 ;
Z is phenyl substituted with one or more nitro, cyano or CF 3 .

15. The compound of claim 12 , wherein:
Y is benzothiazole optionally substituted with one or more F, Cl or CF 3 ;
R 2 and R 3 are independently hydrogen or CH 3 ;
Z is phenyl substituted with one or more nitro, cyano or CF 3 .

16. The compound of claim 12 , wherein:
Y is benzoxazole optionally substituted with one or more F, Cl or CF 3 ;
R 2 and R 3 are independently hydrogen or CH 3 ;
Z is phenyl substituted with one or more nitro, cyano or CF 3 .

Assignees

• Merial Inc

Inventors

• Meng Charles Q
• Long Alan
• Huber Scot
• Gurrala Srinivas Reddy
• Wilkinson Douglas Edward
• Pacofsky Gregory

Classifications

• A61P33/10

  Anthelmintics · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• C07D295/15

  to an acyclic saturated chain · CPC title

• A61K31/4704

  2-Quinolinones, e.g. carbostyril · CPC title

• C07D295/16

  acylated on ring nitrogen atoms · CPC title