Animals such as mammals and birds are often susceptible to parasite infestations. These parasites may be ectoparasites such as insects, and endoparasites such as filariae and worms.
Domesticated animals, such as cats and dogs, are often infested with one or more of the following ectoparasites:                fleas (Ctenocephalides felis, Ctenocephalides sp. and the like),        ticks (Rhipicephalus sp., Ixodes sp., Dermacentor sp., Amblyomma sp. and the like),        mites (Demodex sp., Sarcoptes sp., Otodectes sp. and the like),        lice (Trichodectes sp., Cheyletiella sp., Linognathus sp., and the like), and        flies (Hematobia sp., Musca sp., Stomoxys sp., Dermatobia sp., Cochliomyia sp.,        mosquitoes (family Culicidae), and the like.        
Fleas are a particular problem because not only do they adversely affect the health of the animal or human, but they also cause a great deal of psychological stress. Moreover, fleas are also vectors of pathogenic agents in animals, such as dog tapeworm (Dipylidium caninum), and may also transmit pathogens to humans.
Similarly, ticks are also harmful to the physical and psychological health of the animal or human. However, the most serious problem associated with ticks is that they are the vector of pathogenic agents, which cause diseases in both humans and animals Major diseases which are caused by ticks include borreliosis (Lyme disease caused by Borrelia burgdorferi), babesiosis (or piroplasmosis caused by Babesia sp.) and rickettsiosis (also known as Rocky Mountain spotted fever). Ticks also release toxins which cause inflammation or paralysis in the host. Occasionally, these toxins are fatal to the host, such as in the case of the Australian paralysis tick, Ixodes holocyclus. 
Moreover, mites and lice are particularly difficult to combat since there are very few active substances which act on these parasites and they require frequent treatment.
Likewise, farm animals are also susceptible to parasite infestations. For example, cattle are affected by a large number of parasites. Likewise, arthropod pests, such as fleas, lice and ticks, and mites infest poultry. A parasite that is very prevalent among farm animals is the tick genus Boophilus, especially those of the species microplus (cattle tick), decoloratus and anulatus. Ticks, such as Boophilus microplus, are particularly difficult to control because they live in the pasture where the farm animals graze. Other important parasites of cattle and sheep are listed as follows in order of decreasing importance:
(a) myiases-causing flies such as Dermatobia hominis (known as Berne in Brazil), Hypoderma, and Cochlyomia hominivorax (greenbottle); sheep myiases-causing flies such as Lucilia sericata, Lucilia cuprina (known as blowfly strike in Australia, New Zealand and South Africa). These are flies whose larva constitutes the animal parasite;(b) flies proper, namely those whose adult constitutes the parasite, such as Haematobia irritans (horn fly);(c) lice such as Linognathus vituli etc.; and(d) mites such as Sarcoptes scabiei and Psoroptes ovis. 
The compounds of the invention may also be useful against household pests including, but not limited to, cockroach, Blatella sp., clothes moth, Tineola sp., carpet beetle, Attagenus sp. and the housefly Musca domestica and against Solenopsis invicta (imported fire ants), termites, and the like.
These compounds may further be useful against agricultural pests such as aphids (Acyrthiosiphon sp.), locusts, and boll weevils as well as against insect pests that attack stored grains, such as Tribolium sp., and against immature stages of insects living on plant tissue.
The above list is not exhaustive and other ectoparasites are well known in the art to be harmful to animals, humans and crops.
Compounds that exhibit a degree of activity against a wide range of ectoparasites including arthopods and insects are known in the art. One such class of compounds is the arylpyrazoles which are referred to, for example, in U.S. Pat. Nos. 4,963,575; 5,232,940; 5,547,974; 5,608,077; 5,714,191; 5,817,688; 5,885,607; 5,916,618; 5,922,885; 5,965,491; 5,994,386; 6,010,710; 6,069,157; 6,083,519; 6,096,329; 6,124,339; 6,160,002; 6,180,798; 6,350,771; 6,372,774; 6,395,906; 6,531,501; 6,630,499; 6,685,954; 7,067,548; and U.S. application Ser. No. 11/825,050, all of which are incorporated herein by reference in their entirety. Arylpyrazoles are also referred to, for example, in EP 0 234 119, EP 0 295 117, EP 0 352 944; EP 0 780 378; EP 0 846 686; and EP 0 948 485, all of which are incorporeated herein by reference.
The arylpyrazoles are known to possess excellent activity against insects, such as fleas and ticks. Fipronil is a specific type of 1-N-arylpyrazole that is particularly effective against fleas and ticks and is the active ingredient in Frontline® and Frontline Plus®.
Bis-1-arylpyrazoles containing a disulfide linkage at the 4-position of the pyrazole are used as synthetic intermediates en route to monomeric 1-arylpyrazoles in EP 0 295 117, however these derivatives themselves are not disclosed as pesticidal agents therein. Bis-N-phenylpyrazole derivatives linked through the 5-position of the pyrazole are described in U.S. application Ser. No. 11/615,668.
However, ectoparasiticidal agents can vary in their effectiveness to a particular parasite as well as vary in their cost of production. Moreover, the results of ectoparasiticidal agents may not always be satisfactory because of, for example, the development of resistance by the parasite to the therapeutic agent, as is the case, for example, with carbamates, organophosphorus compounds and pyrethroids. In conjunction with developing resistance issues, modern pesticidal research must also consider spectrum of action, side effect profiles with respect to animal hosts, and convenience of dosing regimen.
Thus, there remains a need in the art for more effective and rapidly acting novel antiparasitic compositions for the treatment and protection of animals, e.g. mammals, fish and birds, from a wide range of parasites. There is a need in the art for an antiparasitic formulation which is easy to use on any type of domestic animal, irrespective of its size and the nature of its coat and which does not require administration over the entire body of the mammal, fish or bird. Further, the formulation should be of prolonged efficacy thereby reducing the number of applications.
All documents cited or referenced herein (“herein cited documents”), and all documents cited or referenced in herein cited documents, together with any manufacturer's instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby explicitly incorporated herein by reference, and may be employed in the practice of the invention.
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.
USPTO Backgrounds
USPTO Backgrounds