Amido-pyridyl ether compounds and compositions and their use against parasites

1. A compound of Formula I

wherein,

R a is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, alkylthiocarbonyl, haloalkyl, alkylthio, haloalkylthio, alkoxy, haloalkoxyalkyl, alkoxycarbonyl and haloalkoxycarbonyl;

R 1 is hydrogen or alkyl;

R 2 and R 3 are each independently selected from the group consisting of hydrogen, hydroxy, amino, alkyl, haloalkyl, alkoxyalkyl, alkenyl, alkynyl, alkylthio, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, and cyano,

or R 2 and R 3 taken together with the carbon to which both are bound form a substituted or unsubstituted 3- to 7-member cyclic, heterocyclic or heteroaromatic ring, wherein the substituents may each be independent of one another cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, alkoxy, haloalkoxy, amino, alkylamino, and dialkylamino;

a is an integer from zero to four,

b is an integer from zero to four,

d is an integer from zero to four,

R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are each independently hydrogen, halogen, alkyl, alkenyl, hydroxyalkyl, alkylthioalkyl, haloalkyl, alkyloxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkylsulfonyloxyalkyl, nitro, alkylthio, haloalkylthio, alkoxy, haloalkoxy, amino, alkylamino, and diamino;

R 10 and R 11 are each independently selected from the group consisting of hydrogen, hydroxy, amino, cyano, nitro, halogen, thiol, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, haloalkyl, alkylthio, haloalkylthio, arylthio, alkoxy, phenoxy, alkoxyalkoxy, cycloalkyloxy, haloalkoxy, formyl, alkylcarbonyl, alkoxycarbonyl, sulfonyl, sulfinyl, and unsubstituted or substituted phenyl, unsubstituted or substituted benzyl, unsubstituted or substituted arylthio, unsubstituted or substituted aryloxy, or unsubstituted or substituted heteroaryl, wherein the substituents, independent of one another, may be one or more of cyano, nitro, halogen, alkyl, haloalkyl, alkylthio, haloalkylthio, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, alkylaminoalkoxy, dialkylaminoalkoxy, and alkylaminoalkyl,

provided that,

at least one of b and d is other than zero, and

at least one of R 10 and R 11 is other than hydrogen.

2. The compound of claim 1 , wherein

b is one and d is zero,

b is two and d is zero,

b is one and d is one,

b is zero and d is one, or

b is zero and d is two.

3. The compound of claim 2 , wherein a is one or two.

4. The compound of claim 1 , wherein

a is zero,

provided that when R 10 and R 11 are both selected from the group consisting of chloro and methyl, then:

iii) d is other than zero, or

iv) R a is other than C 1-6 alkyl, or

iii) R 2 and R 3 when taken together with the carbon to which both are bound form a ring other than cyclopentyl or cyclohexyl.

5. The compound of claim 1 , wherein

R 10 and R 11 are each independently selected from the group consisting of hydrogen, halogen, branched or straight-chain C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, hydroxy(C 1-6 )alkyl, halo(C 1-6 )alkyl, C 1-6 alkoxy, halo(C 1-6 )alkoxy and unsubstituted or substituted phenyl, wherein the substituents, independent of one another, may be one or more of halogen, C 1-6 alkyl, halo(C 1-6 )alkyl, C 1-6 alkoxy, or halo(C 1-6 )alkoxy.

6. The compound of claim 5 , wherein

R 10 and R 11 are each independently selected from the group consisting of hydrogen, bromo, chloro, fluoro, methyl, ethyl, trifluoromethyl and trifluoromethoxy.

7. The compound of claim 1 , wherein

a is one,

R 4 and R 5 are both hydrogen,

b is zero, one or two, and

d is zero, one or two.

8. The compound of claim 7 , wherein

b is one or two,

d is zero, and

R 6 and R 7 in each instance are both hydrogen.

9. The compound of claim 7 , wherein

d is one or two,

b is zero, and

R 8 and R 9 in each instance are both hydrogen.

10. The compound of claim 7 , wherein

b is one or two,

R 6 and R 7 in each instance are both hydrogen,

d is one or two, and

R 8 and R 9 in each instance are both hydrogen.

11. The compound of claim 1 , wherein

R 1 is hydrogen or methyl,

R 2 and R 3 are each independently selected from the group consisting of hydrogen, C 1-6 alkenyl, cyano, C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino and C 1-6 alkylthio,

or R 2 and R 3 taken together with the carbon to which both are bound form a substituted or unsubstituted 3- to 7-member cyclic, heterocyclic or heteroaromatic ring.

12. The compound of claim 11 , wherein

R 2 and R 3 taken together with the carbon to which both are bound form a substituted or unsubstituted 3- to 7-member cyclic, heterocyclic or pyridine.

13. The compound of claim 12 , wherein

R 2 and R 3 taken together with the carbon to which both are bound form a substituted or unsubstituted pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, homopiperazinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, 2-pyrrolinyl, 3-pyrrolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, dithianyl, dithiolanyl and dihydrothienyl.

14. The compound of claim 13 , wherein

R 2 and R 3 taken together with the carbon to which both are bound form a substituted or unsubstituted cyclopropyl or 4-morpholinyl.

15. The compound of claim 11 , wherein

R 2 and R 3 are each independently selected from the group consisting of hydrogen, C 1-6 alkenyl, C 1-6 alkyl and C 1-6 alkylthio.

16. The compound of claim 1 , wherein R a is hydrogen.

17. The compound of claim 1 , wherein a is one or two.

18. The compound of claim 1 , having one of the following structures:

19. A paraciticidal composition comprising a compound of claim 1 and a carrier.

20. The composition of claim 19 , further comprising one or more additional active agents.

21. A method of treating or preventing infection or infestation of an animal by one or more parasites, said method comprising administering an effective amount of a compound of claim 1 .

22. The method of claim 21 , wherein said one or more parasites is selected from the group consisting of fleas, ticks, mites, mosquitoes, flies, fly larvae and lice and combinations thereof.

23. The method of claim 21 , wherein said one or more parasites is selected from the group consisting of fleas and ticks and combinations thereof.

24. The method of claim 21 , wherein said one or more parasites is an ectoparasite or an endoparasite or a combination thereof.

25. The method of claim 24 , wherein said ectoparasite is an arthropod.

26. The method of claim 25 , wherein said arthropod is selected from the group consisting of houseflies ( Musca domestica ), Musca hervei, Musca bezzi, Haematobia irritans, Simulium iwatens, Culicoides oxystoma, Tabanus chrysurus , common mosquito ( Culex pipiens ), Aedes albopictus ; lice pests (Anoplura), cattle lice ( Haematopinus eurysternus ), sheep lice ( Damalinia ovis ); tick pests (Acarina), Haemaphysalis longiconis, Boophilus microplus ; fleas (Siphonaptera), cat fleas ( Ctenocephalides felis ), dog fleas ( Ctenocephalides canis ) and oriental rat flea ( Xenopsylla cheopis ).

27. The method of claim 24 , wherein said endoparasite is a helminth.

28. The method of claim 24 , wherein said endoparasite is selected from the group consisting of Anaplocephala ( Anoplocephala ), Ancylostoma, Anecator, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Cyathostomum, Cylicocyclus, Cylicodontophorus, Cylicostephanus, Craterostomum, Dictyocaulus, Dipetalonema, Dipylidium, Dirofilaria, Dracunculus, Echinococcus, Enterobius, Fasciola, Filaroides, Habronema, Haemonchus, Metastrongylus, Moniezia, Necator, Nematodirus, Nippostrongylus, Oesophagostumum, Onchocerca, Ostertagia, Oxyuris, Paracaris, Schistosoma, Strongylus, Taenia, Toxocara, Strongyloides, Toxascaris, Trichinella, Trichuris, Trichostrongylus, Triodontophorous, Uncinaria, Wuchereria, Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia curticei, Nematodirus battus and combinations thereof.