Antiparisitic dihydroazole compounds and compositions comprising same
The present invention relates to novel dihydroazole of formula (I) and salts thereof: Wherein R 1 , A 1 , A 2 , G, X and Y are as defined in the description, compositions thereof, processes for their preparation and their uses to prevent or treat parasitic infections or infestations in animals and as pesticides.
1. A dihydroazole compound of formula (I), or a pharmaceutically or agriculturally acceptable salt thereof:
wherein:
R 1 is halogen, —CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R 7 S(O)—, R 7 S(O) 2 —, R 7 C(O)—, R 7 R 8 NC(O)—, R 7 OC(O)—, R 7 C(O)O—, R 7 C(O)NR 8 —, —CN or —NO 2 ;
X is aryl or heteroaryl, which may be unsubstituted or substituted by one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R 7 S(O)—, R 7 S(O) 2 —, R 7 C(O)—, R 7 R 8 NC(O)—, R 7 OC(O)—, R 7 C(O)O—, R 7 C(O)NR 8 —, —CN or —NO 2 ;
A 1 is oxygen;
A 2 is oxygen, NR 2 or CR 7 R 8 ;
G is G-1;
B 1 , B 2 , B 3 , B 4 and B 5 are independently N or C—R 9 ;
Y is hydrogen, halogen, —CN; or Y is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, aryl, or heterocyclyl or heteroaryl each of which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R 7 S(O)—, R 7 S(O) 2 —, R 7 C(O)—, R 7 R 8 NC(O)—, R 7 OC(O)—, R 7 C(O)O—, R 7 C(O)NR 8 —, —CN or —NO 2 ; or Y is Y-1, Y-2, Y-3, Y-4, Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13;
R 2 , R 3 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxylakyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, R 10 S(O)—, R 10 S(O) 2 —, R 10 C(O)—, R 10 C(S)—, R 10 R 11 NC(O)—, R 10 R 11 NC(S)—R 10 OC(O)—;
R 4 , R 5 and R 6 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxylakyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, aryl or heteroaryl;
R 7 and R 8 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxylakyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;
R 9 is hydrogen, halogen, —CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R 7 S(O)—, R 7 S(O) 2 —, R 7 C(O)—, R 7 R 8 NC(O)—, R 7 OC(O)—, R 7 C(O)O—, R 7 C(O)NR 8 —, —CN or —NO 2 ;
R 10 , R 11 , R 12 and R 13 are each independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxylakyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; or
R 10 together with R 11 form ═O, ═S or ═NR 2 ; or
R 12 together with R 13 form ═O, ═S or ═NR 2 ;
W is O, S or NR 2 ;
n is 1-4; and
m is 0, 1 or 2.
2. The compound of claim 1 , wherein:
X is optionally substituted aryl.
3. The compound of claim 1 , wherein:
X is optionally substituted aryl;
R 1 is halogen, alkyl or haloalkyl; and
Y is Y-1, Y-2, Y-3, Y-4, Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13.
4. The compound of claim 1 , wherein:
X is optionally substituted aryl;
R 1 is halogen, alkyl or haloalkyl; and
Y is pyrazolyl or triazolyl.
5. The compound of claim 1 , wherein:
B 1 , B 2 , B 3 , B 4 and B 5 are each C—R 9 ;
R 1 is C 1 -C 4 alkyl or C 1 -C 4 haloalkyl;
X is phenyl, which may be unsubstituted or substituted by one or more halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl;
A 2 is CR 7 R 8 ;
Y is Y-1, Y-4, Y-5, Y-6;
R 3 and R 4 are independently hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 akoxy-C 1 -C 4 alkyl or C 1 -C 4 alkylthio-C 1 -C 4 alkyl; and
R 2 and R 9 are independently hydrogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.
6. The compound of claim 1 , wherein:
B 1 , B 2 , B 4 and B 5 are each C—R 9 ;
B 3 is N;
R 1 is C 1 -C 4 alkyl or C 1 -C 4 haloalkyl;
X is phenyl, which may be unsubstituted or substituted by one or more halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl;
A 1 is oxygen;
A 2 is CR 7 R 8 ;
Y is Y-1, Y-4, Y-5, Y-6;
R 3 and R 4 are independently hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 akoxy-C 1 -C 4 alkyl or C 1 -C 4 alkylthio-C 1 -C 4 alkyl; and
R 2 and R 9 are independently hydrogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.
7. The compound of claim 5 , wherein:
A 2 is CH 2 ,
R 9 is hydrogen;
R 10 together with R 11 form ═O, ═S or ═NR 2 ;
R 3 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkylthio-C 1 -C 4 -alkyl;
R 2 , R 7 and R 8 are each hydrogen; and
Y is Y-1 or Y-4.
8. The compound of claim 5 , wherein:
A 2 is CH 2 , R 9 is hydrogen;
R 10 together with R 11 form ═O, ═S or ═NR 2 ;
R 12 together with R 13 form ═O, ═S or ═NR 2 ;
R 3 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkylthio-C 1 -C 4 -alkyl;
R 2 , R 7 and R 8 are each hydrogen; and
Y is Y-1 or Y-4.
9. The compound of claim 5 , wherein:
A 2 is CH 2 ;
R 9 is hydrogen;
R 10 together with R 11 form ═O;
R 12 together with R 13 form ═O;
R 3 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkylthio-C 1 -C 4 -alkyl;
R 2 , R 7 and R 8 are hydrogen; and
Y is Y-1 or Y-4.
10. The compound of claim 6 , wherein:
A 2 is CH 2 ;
R 9 is hydrogen;
R 10 together with R 11 form ═O, ═S or ═NR 2 ;
R 3 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkylthio-C 1 -C 4 -alkyl;
R 2 , R 7 and R 8 are each hydrogen; and
Y is Y-1 or Y-4.
11. The compound of claim 6 , wherein:
A 2 is CH 2 ;
R 9 is hydrogen;
R 10 together with R 11 form ═O, ═S or ═NR 2 ;
R 12 together with R 13 form ═O, ═S or ═NR 2 ;
R 3 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkylthio-C 1 -C 4 -alkyl;
R 2 , R 7 and R 8 are each hydrogen; and
Y is Y-1 or Y-4.
12. The compound of claim 6 , wherein:
A 2 is CH 2 ;
R 9 is hydrogen;
R 10 together with R 11 form ═O;
R 12 together with R 13 form ═O;
R 3 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkylthio-C 1 -C 4 -alkyl;
R 2 , R 7 and R 8 are hydrogen; and
Y is Y-1 or Y-4.
13. A parasiticidal veterinary composition comprising an effective amount of a compound of formula (I) of claim 1 in combination with a pharmaceutically acceptable carrier.
14. A pesticidal composition comprising a pesticidally effective amount of a compound of formula (I) of claim 1 in combination with an agriculturally acceptable carrier or diluent.
15. The composition of claim 13 , wherein the composition comprises an additional active agent.
16. The composition of claim 15 , wherein the additional active agent is an arylpyrazole compound, an amino acetonitrile active agent, another isoxazoline active agent, a paraherquamide active agent, a benzimidazole, an imidazothiazole, a tetrahydropyrimidine active agent, an antitrematodal active agent, a macrocyclic lactone, an insect growth regulator, a neonicotinoid active agent, a pyrethroid, a formamidine or a spinosyn active agent.
17. The composition of claim 16 , wherein the macrocyclic lactone is abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin, milbemectin, milbemycin D, moxidectin, nemadectin or milbemycin oxime.
18. The compound of claim 9 , wherein:
Y is Y-1; and
R 3 is —CH 2 CH 2 SCH 3 .
19. The compound of claim 10 , wherein:
Y is Y-4; and
R 3 is —CH 2 CF 3 .
20. A dihydroazole compound of the formula:
or a pharmaceutically acceptable or agriculturally acceptable salt thereof, wherein Z, B 1 , B 2 , B 3 , B 4 , B 5 , R 15 , R 16 and p are selected from:
Compound
No.
(Z) p
B 5
B 4
B 3
B 2
B 1
R 15
R 16
2.001
3,5-Cl 2
C—H
C—H
N
C—H
C—H
H
CH 2 C(O)NHCH 2 CF 3
2.002
3,5-Cl 2
C—H
C—H
N
C—H
C—H
H
CH 2 CF 3
2.003
3,5-Cl 2
C—H
C—H
N
C—H
C—H
H
CH 2 CH 2 SCH 3
2.004
3,5-(CF 3 ) 2
C—H
C—H
N
C—H
C—H
H
CH 2 C(O)NHCH 2 CF 3
2.005
3,5-(CF 3 ) 2
C—H
C—H
N
C—H
C—H
H
CH 2 CF 3
2.006
3,5-(CF 3 ) 2
C—H
C—H
N
C—H
C—H
H
CH 2 CH 2 SCH 3
2.007
3-Cl,5-CF 3
C—H
C—H
N
C—H
C—H
H
CH 2 C(O)NHCH 2 CF 3
2.008
3-Cl,5-CF 3
C—H
C—H
N
C—H
C—H
H
CH 2 CF 3
2.009
3-Cl,5-CF 3
C—H
C—H
N
C—H
C—H
H
CH 2 CH 2 SCH 3
2.010
3,5-Cl 2
C—H
C—H
C—H
C—H
C—H
H
CH 2 C(O)NHCH 2 CF 3
2.011
3,5-Cl 2
C—H
C—H
C—H
C—H
C—H
H
CH 2 CF 3
2.012
3,5-Cl 2
C—H
C—H
C—H
C—H
C—H
H
CH 2 CH 2 SCH 3
2.013
3,5-(CF 3 ) 2
C—H
C—H
C—H
C—H
C—H
H
CH 2 C(O)NHCH 2 CF 3
2.014
3,5-(CF 3 ) 2
C—H
C—H
C—H
C—H
C—H
H
CH 2 CF 3
2.015
3,5-(CF 3 ) 2
C—H
C—H
C—H
C—H
C—H
H
CH 2 CH 2 SCH 3
2.016
3-Cl,5-CF 3
C—H
C—H
C—H
C—H
C—H
H
CH 2 C(O)NHCH 2 CF 3
2.017
3-Cl,5-CF 3
C—H
C—H
C—H
C—H
C—H
H
CH 2 CF 3
2.018
3-Cl,5-CF 3
C—H
C—H
C—H
C—H
C—H
H
CH 2 CH 2 SCH 3 .