Dimeric 1-arylpyrazole derivatives for use against ectoparasites, agricultural pests, and household pests
This invention provides for dimeric1-arylpyrazole compounds, of formulas (I), (II), and (III): or salts thereof, and the use of these compounds against ectoparasites such as insects, arthropods and acarina. The resulting compounds may be used in veterinary formulations such as, for example, spot-on and pour-on formulations, which may be used for treatment, controlling and preventing of parasitic infections in warm-blooded animals and birds.
1. A compound of formula (I):
wherein:
R 1 and R 1a are independently selected from the group consisting of hydrogen, cyano, halogen, —C(═O)R 6 , —C(═O)R 8 , —C(═O)NR 11 R 12 , —CH(═NR 7 ), —CH(═NR 8 ), —C(═NR 7 )R 7 , —C(═NR 7 )R 8 , —C(═NR 8 )R 7 , —C(═NNR 7 )R 7 , —C(═NNR 7 )R 8 , —C(═NNR 8 )R 7 , and —C(S)NR 7 R 11 ;
R 3 and R 3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R 4 and R 4a are independently selected from the group consisting of halogen, cyano, nitro, R 7 , R 8 , —C(O)R 11 , —C(═O)NR 11 R 12 , —C(═NR 7 )R 7 , —C(═NR 7 )R 8 , —C(═NR 7 )NR 11 R 12 , —S(O) n R 11 , and SF 5 ;
R 5 and R 5a are independently selected from the group consisting of R 10 , R 11 , —C(═NR 7 )R 7 , —C(═NR 7 )R 8 , —C(═NR 8 )R 7 , —C(═NR 7 )NR 11 R 12 , —C(═S)NR 11 R 12 , —NR 11 R 12 , —NR 11 C(═O)R 8 , —NR 11 C(═O)R 11 , and —N═C(R 11 )NR 6 ;
Z and Z 1 are independently selected from the group consisting of nitrogen and C—R 3 ;
R 6 is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl, and heteroaryl, wherein said alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl, and heteroaryl groups are optionally substituted with one or more groups independently selected from the group consisting of R 8 , R 9 , and R 10 ;
R 7 is selected from the group consisting of hydrogen and R 6 ;
R 8 is selected from the group consisting of −OR 9 , —OR 11 , —SR 9 , —SR 11 , —NR 9 R 11 , and —NR 11 R 12 ;
R 9 is selected from the group consisting of aryl and heteroaryl, wherein said aryl and heteroaryl groups are optionally substituted with one or more groups independently selected from the group consisting of R 10 and R 11 ;
R 10 is selected from the group consisting of cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, —S(O) n R 11 , —S(O) n NR 11 R 12 , —NR 11 R 12 , —NR 11 (C═O)R 11 , —NR 11 (C═O)NR 11 R 12 , —NR 11 S(O) n R 11 , —NR 11 S(O) n NR 11 R 12 , —C(═O)R 11 , —C(═O)OR 11 , —C(═O)NR 11 R 12 , —C(═S)R 11 , and —C(═S)NR 11 R 12 ;
R 11 and R 12 are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R 13 and R 13a are independently selected from the group consisting of —NR 11 C(═S)—, —NR 11 SO 2 NR 11 , —NR 11 SO 2 —, —C(═NR 7 )—, —C(═NR 8 )—, —C(═S)NR 11 —, and —S(O) n NR 11 —;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxy aryl, heteroaryl, and any combination thereof, which may optionally contain one or more nitrogen, oxygen, sulfur, phosphorus, or silicon atoms; and
wherein said linker may optionally be substituted with one or more groups independently selected from cyano, nitro, hydroxy, halogen, oxygen, nitrogen, sulfur, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oximino, and alkoxyimino; and
n is independently 0, 1, or 2; or
a salt thereof.
2. The compound of claim 1 , wherein:
R 1 and R 1a are independently selected from the group consisting of hydrogen, cyano, halogen, —C(═O)R 6 , —C(═O)R 8 , —C(═O)NR 11 R 12 , —CH(═NR 7 ), —CH(═NR 8 ), —C(═NR 7 )R 7 , —C(═NR 7 )R 8 , —C(═NR 8 )R 7 , and —C(S)NR 7 R 11 ;
R 3 and R 3a are independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R 4 and R 4a are independently selected from the group consisting of halogen, R 7 , R 8 , —S(O) n R 11 , and SF 5 ;
R 5 and R 5a are independently selected from the group consisting of R 10 , R 11 , —C(═NR 7 )R 7 , —C(═NR 7 )R 8 , —C(═NR 8 )R 7 , —C(═NR 7 )NR 11 R 12 , —C(═S)NR 11 R 12 , —NR 11 R 12 , and —N═C(R 11 )NR 6 ;
Z and Z 1 are C—R 3 ; and
R 13 and R 13a are independently selected from the group consisting of a —C(═NR 7 )—, —C(═NR 8 )—, —C(═S)NR 11 —, and —S(O) n NR 11 —.
3. The compound of claim 1 , wherein:
R 1 and R 1a are independently selected from the group consisting of cyano, halogen, and —C(S)NR 7 R 11 ;
R 3 and R 3a are halogen;
R 4 and R 4a are independently selected from the group consisting of halogen, haloalkyl, —S(O) n R 11 , and SF 5 ;
R 5 and R 5a are independently selected from the group consisting of alkyl, haloalkyl, —NR 11 R 12 , and —N═C(R 11 )NR 6 ;
Z and Z 1 are C—R 3 ;
R 7 is selected from the group consisting of hydrogen and alkyl;
R 11 and R 12 are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl; and
R 13 and R 13a are independently selected from the group consisting of a —C(═NR 7 )—, —C(═NR 8 )—, —C(═S)NR 11 —, and —S(O) n NR 11 —.
4. The compound of claim 1 , wherein:
R 1 and R 1a are independently selected from the group consisting of cyano and —C(S)NR 7 R 11 ;
R 3 and R 3a are halogen;
R 4 and R 4a are haloalkyl;
R 5 and R 5a are independently selected from the group consisting of alkyl and —NR 11 R 12 ;
Z and Z 1 are C—R 3 ;
R 7 is selected from the group consisting of hydrogen and alkyl;
R 11 and R 12 are hydrogen; and
R 13 and R 13a are —S(O) n NR 11 .
5. The compound of claim 1 , wherein:
R 1 and R 1a are cyano;
R 3 and R 3a are halogen;
R 4 and R 4a are haloalkyl;
R 5 and R 5a are independently selected from the group consisting of alkyl and —NR 11 R 12 ;
Z and Z 1 are C—R 3 ;
R 11 and R 12 are hydrogen;
R 13 and R 13a are —S(O) n NR 11 —;
L is alkyl or haloalkyl; and
n is 2.
6. A composition comprising: (A) an effective amount of the compound of claim 1 to treat or prevent a parasite infestation or infection in an animal; and (B) a veterinarily acceptable carrier.
7. The composition of claim 6 , wherein the composition is a topical, dermal, or subdermal formulation.
8. The composition of claim 6 , wherein the composition is a microemulsion, a paste, a pour-on formulation, a ready-to-use formulation, a spot-on formulation, an oral solution, an emulsion, an injectable solution, a suspension, or an enteric formulation.
9. The composition of claim 6 , further comprising an additional pesticidally active ingredient.
10. The composition of claim 9 , wherein the additional pesticidally active ingredient is selected from the group consisting of arylpyrazoles, nodulisporic acid or derivatives thereof, macrocyclic lactones, formamidines, pyrethroids, insect growth regulators, benzenedisulfonamide compounds, anti-cestodal agents, pyridylmethyl derivatives, depsipeptides, and mixtures thereof.
11. An insecticidal composition comprising: (A) an effective amount of the compound of claim 1 to treat or prevent an insect infestation or infection in an animal; and (B) an acceptable carrier.
12. A method for the preparation of pesticidal compositions, comprising mixing an effective amount of the compound of claim 1 to treat or prevent an insect infestation or infection in an animal with extenders or surface-active substances.
13. A method of controlling pests, comprising applying an effective amount of the compound of claim 1 to treat or prevent an insect infestation or infection in an animal to the pests or their environment, or on the plants, plant parts, seeds, soils, areas, materials, or spaces to be kept free from them.
14. A method for the treatment or prevention of a parasitic infestation or infestation in an animal comprising administering an effective amount of the compound of claim 1 to treat or prevent an insect infestation or infection in an animal to the animal in need thereof.