USE OF HALOARYLPYRAZOLE COMPOUNDS IN THE CONTROL OF PARASITE INFESTATION ON ANIMALS
The present invention relates to the use of haloarylpyrazoles as tick-repellent compositions, and to an administration regimen of specific haloarylpyrazoles for controlling ticks on animals.
1 ) A method for deterring ticks from infesting an animal, wherein:
the method comprises administering a haloarylpyrazole to the animal;
the haloarylpyrazole corresponds in structure to formula (I):
Ar is 2,6-dichloro-4-trifluoromethylphenyl or 2-nitro-4-trifluoromethylphenyl;
A is S(O) m , CH═CH, O, or NH;
as to W and Z:
W is N, and Z is CR 5 ; or
W is CR 1 , and Z is N or CR 5 ;
R 1 is hydrogen, optionally substituted alkyl, halogen, or R 20 S(O) q ;
R 2 and R 3 are hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, aryl, cyano, halogen, nitro, YR 20 , S(O) 2 NR 8 R 9 , CHO, NR 8 R 9 , or CYNR 8 R 9 ;
R 4 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acyl, or optionally substituted alkoxycarbonyl;
R 5 is hydrogen, alkyl, optionally substituted amino, or halogen;
R 8 and R 9 are independently hydrogen, optionally substituted alkyl, acyl, or aryl;
R 20 is optionally substituted alkyl;
Y is O or S;
m is zero, 1, or 2;
p is zero or 1;
n is zero, 1, or 2;
q is zero, 1, or 2;
any alkyl, alkoxy, or alkylthio comprises 1 to 4 carbon atoms;
any alkenyl or alkynyl comprises 2 to 5 carbon atoms;
any alkyl, alkoxy, alkylthio, alkenyl, or alkynyl portion of a substituted alkyl, alkoxy, alkylthio, alkenyl, or alkynyl is substituted by one or more substituents independently selected from the group consisting of halogen, YR 20 , dihalocyclopropyl, cyano, nitro, optionally substituted amino, acyloxy, and aryl;
any aryl is phenyl optionally substituted by halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, haloalkylsulphonyl, cyano, or nitro;
any acyl is alkanoyl comprising 1 to 4 carbon atoms, alkylsulphonyl, or haloalkylsulphonyl;
any optionally substituted amino is NR 8 R 9 ; and
R 4 is not alkyl when:
W is CR 1 ,
Z is CR 5 , and
n and p are both zero.
2 ) The method according to claim 1 , wherein the haloarylpyrazole is 5-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano-1H-imidazol-2-yl-3-methyl-1-H pyrazole.
3 ) The method according to claim 1 , wherein the haloarylpyrazole is applied systemically to the animal.
4 ) The method according to claim 3 , wherein the haloarylpyrazole is applied orally to the animal.
5 ) The method according to claim 1 , wherein the haloarylpyrazole is applied as a tablet to the animal.
6 ) The method according to claim 1 , wherein the animal is a dog or cat.
7 ) The method according to claim 1 , wherein the haloarylpyrazole is applied in an initial dose of 4 mg/kg bodyweight of the animal, followed by weekly administration of doses of 2 mg/kg bodyweight of the animal.
8 ) A method for deterring ticks from infesting an animal, wherein the method comprises orally administering an initial dose of 4 mg of 5-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano-1H-imidazol-2-yl-3-methyl-1-H pyrazole per kg bodyweight of the animal, followed by weekly oral administration of 2 mg doses of 5-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano-1H-imidazol-2-yl-3-methyl-1H pyrazole per kg bodyweight of the animal.
9 ) The method according to claim 8 , wherein 5-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano-1H-imidazol-2-yl-3-methyl-1-H pyrazole is administered as a tablet.
10 ) The method according to claim 8 , wherein the animal is a dog.
11 ) The method according to claim 2 , wherein the 5-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano-1H-imidazol-2-yl-3-methyl-1-H pyrazole is applied systemically to the animal.
12 ) The method according to claim 11 , wherein the 5-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano-1H-imidazol-2-yl-3-methyl-1-H pyrazole is applied orally to the animal.
13 ) The method according to claim 2 , wherein the animal is a dog or cat.
14 ) The method according to claim 2 , wherein the 5-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano-1H-imidazol-2-yl-3-methyl-1-H pyrazole is applied in an initial dose of 4 mg/kg bodyweight of the animal, followed by weekly administration of doses of 2 mg/kg bodyweight of the animal.
15 ) The method according to claim 3 , wherein the animal is a dog or cat.
16 ) The method according to claim 3 , wherein the haloarylpyrazole is applied in an initial dose of 4 mg/kg bodyweight of the animal, followed by weekly administration of doses of 2 mg/kg bodyweight of the animal.
17 ) The method according to claim 4 , wherein the animal is a dog or cat.
18 ) The method according to claim 5 , wherein the animal is a dog or cat.
19 ) The method according to claim 9 , wherein the animal is a dog.
20 ) A use of a haloarylpyrazole for making a medicament to deter ticks from infesting an animal, wherein:
the haloarylpyrazole corresponds in structure to formula (I):
Ar is 2,6-dichloro-4-trifluoromethylphenyl or 2-nitro-4-trifluoromethylphenyl;
A is S(O) m , CH═CH, O, or NH;
as to W and Z:
W is N, and Z is CR 5 ; or
W is CR 1 , and Z is N or CR 5 ;
R 1 is hydrogen, optionally substituted alkyl, halogen, or R 20 S(O) q ;
R 2 and R 3 are hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, aryl, cyano, halogen, nitro, YR 20 , S(O) 2 NR 8 R 9 , CHO, NR 8 R 9 , or CYNR 8 R 9 ;
R 4 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, acyl, or optionally substituted alkoxycarbonyl;
R 5 is hydrogen, alkyl, optionally substituted amino, or halogen;
R 8 and R 9 are independently hydrogen, optionally substituted alkyl, acyl, or aryl;
R 20 is optionally substituted alkyl;
Y is O or S;
m is zero, 1, or 2;
p is zero or 1;
n is zero, 1, or 2;
q is zero, 1, or 2;
any alkyl, alkoxy, or alkylthio comprises 1 to 4 carbon atoms;
any alkenyl or alkynyl comprises 2 to 5 carbon atoms;
any alkyl, alkoxy, alkylthio, alkenyl, or alkynyl portion of a substituted alkyl, alkoxy, alkylthio, alkenyl, or alkynyl is substituted by one or more substituents independently selected from the group consisting of halogen, YR 20 , dihalocyclopropyl, cyano, nitro, optionally substituted amino, acyloxy, and aryl;
any aryl is phenyl optionally substituted by halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, haloalkylsulphonyl, cyano, or nitro;
any acyl is alkanoyl comprising 1 to 4 carbon atoms, alkylsulphonyl, or haloalkylsulphonyl;
any optionally substituted amino is NR 8 R 9 ; and
R 4 is not alkyl when:
W is CR 1 ,
Z is CR 5 , and
n and p are both zero.