Anthelmintic compounds
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 6 , X 8 , Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , Q 6 , Ring A, Ring B, W, W′, R 2 , R 3 , R, R′, m, n and q 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.
1. An anthelmintic compound of formula (IA-1):
wherein:
Y is naphthyl, benzofuranyl, dihydrobenzofuranyl, quinolinyl, isoquinolinyl, tetrahydroquinolyl, tetrahydroisoquinolyl, indolyl, isoindolyl, benzothiophenyl, benzimidazolyl, benzoxazolyl or benzothiazolyl, which is optionally substituted by one or more of chloro, fluoro, bromo, CF 3 , OCF 3 , SCF 3 or SF 5 ;
Z is phenyl optionally substituted by one or more halogen, cyano, nitro, CF 3 , SF 5 , S(O)C 1-3 -alkyl, S(O) 2 —C 1-3 -alkyl, S(O)C 1-3 -haloalkyl or S(O) 2 C 1-3 -haloalkyl;
X 1 is a bond, —C(O)—, —(CH 2 )— where n is 1 to 3 or —NH—, wherein each CH 2 in —(CH 2 ) n and —NH— is optionally independently substituted with one or two substituents selected from the group consisting of halogen, C 1-3 alkyl, C 1-3 haloalkyl, hydroxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkyl, amino-C 1-3 alkyl, C 1-3 alkylamino-C 1-3 alkyl, C 1-3 dialkylamino-C 1-3 alkyl, C 1-3 alkoxycarbonyl, C 1-3 alkylcarbonyl and C 2-4 alkenylcarbonyl, each of which may be further independently substituted by hydroxy, hydroxy-C 1-3 alkyl, amino, C 1-3 alkylamino, C 1-3 dialkylamino or —COOH;
Ring A is L1, L2, L3, L13, L14, L15, L16, L17 or L18 wherein Q 5 and Q 6 are nitrogen; R 5 , R 6 , R 7 and R 8 are independently hydrogen, C 1-3 alkyl or C 1-3 haloalkyl:
Ring B is L4 wherein Q 1 is carbon and Q 2 is nitrogen:
W is O;
X 6 is a bond, —O—, —(CH 2 )— where n is 1 to 3 or —NH—;
X 8 is a bond, —(CH 2 ) n — where n is 1 to 3, —O— or —NH—, wherein each CH 2 in —(CH 2 ) n — and —NH— is optionally independently substituted with one or two substituents selected from the group consisting of halogen, C 1-3 alkyl, C 1-3 haloalkyl, hydroxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkyl, amino-C 1-3 alkyl, C 1-3 alkylamino-C 1-3 alkyl, C 1-3 dialkylamino-C 1-3 alkyl, C 1-3 alkoxycarbonyl, C 1-3 alkylcarbonyl and C 2-4 alkenylcarbonyl, each of which may be further independently substituted by hydroxy, hydroxy-C 1-3 alkyl, amino, C 1-3 alkylamino, C 1-3 dialkylamino or —COOH;
R 2 and R 3 are H;
n is 1 or 2; and
m and q are 0.
2. The anthelmintic compound of claim 1 , wherein Y is optionally substituted benzoxazolyl or benzothiazolyl.
3. The anthelmintic compound of claim 1 , wherein Z is phenyl substituted by halogen, cyano or CF 3 .
4. The anthelmintic compound of claim 1 , wherein X 1 is a bond.
5. The anthelmintic compound of claim 1 , wherein X 8 is a bond.
6. The anthelmintic compound of claim 1 , wherein X 1 and X 8 are each bonds.
7. The anthelmintic compound of claim 1 , wherein X 6 is —O— or —NH—.
8. The anthelmintic compound of claim 1 , wherein Y is optionally substituted benzoxazolyl or benzothiazolyl; and Z is phenyl substituted by halogen, cyano or CF 3 .
9. The anthelmintic compound of claim 1 , wherein Ring A is L1.
10. The anthelmintic compound of claim 1 , wherein:
Y is optionally substituted benzoxazolyl or benzothiazolyl;
Z is phenyl substituted by halogen, cyano or CF 3 ; and
Ring A is L1.
11. The anthelmintic compound of claim 10 , wherein X 1 is a bond.
12. The anthelmintic compound of claim 10 , wherein X 8 is a bond.
13. The anthelmintic compound of claim 10 , wherein X 6 is —O—.
14. The anthelmintic compound of claim 10 , wherein:
X 1 and X 8 are each bonds;
X 6 is —O—; and
n is 1.
15. The anthelmintic compound of claim 14 , wherein Y is benzoxazolyl or benzothiazolyl substituted by CF 3 , SCF 3 or OCF 3 .
16. The anthelmintic compound of claim 15 , wherein Z is phenyl substituted by cyano, CF 3 or fluoro.
17. The anthelmintic compound of claim 1 , wherein the compound has the structure
18. A composition for the treatment and prevention 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.
19. The composition of claim 18 , wherein the composition comprises an additional parasiticidal active agent.
20. A method for the treatment and prevention of a parasitic infection or infestation in an animal, comprising administering an effective amount of the compound of claim 1 to the animal.