ANTHELMINTIC DEPSIPEPTIDE COMPOUNDS CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No. 62/163,997 filed on May 20, 2015, which is herein incorporated by reference.

FIELD OF THE INVENTION

The present invention is directed to new anthelmintic depsipeptides compounds with improved activity against endoparasites and ectoparasites. The invention is also directed to compositions comprising the compounds, methods and uses of the compounds for eradicating, controlling, and preventing a parasite infestation and/or infection in animals. The compounds of the invention may be administered to animals, particularly mammals, fish and birds, to prevent or treat parasitic infections. BACKGROUND OF THE INVENTION

Animals, such as mammals and birds, are often susceptible to parasite infestations. These parasites may be ectoparasites, such as fleas and ticks. Animals and humans also suffer from endoparasitic infections including, for example, helminthiasis which is most frequently caused by a group of parasitic worms described as nematodes or roundworms. These parasites cause severe economic losses in pigs, sheep, horses, and cattle as well as affecting companion animals (e.g. cats and dogs) and poultry. Other parasites include those which occur in the gastrointestinal tract of animals and humans include Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Toxocara, Toxascaris, Trichuris, Enterobius and parasites which are found in the blood or other tissues and organs such as filarial worms and the extra intestinal stages of Strongyloides, Toxocara and Trichinella.

One type of endoparasite which seriously harms mammals is Dirofilaria immitis, also known as Heartworm. Other filarial endoparasites include Dirofilaria repens and Dirofilaria honkongensis, which can also infect humans. The most common hosts are dogs and cats but other mammals such as ferrets and raccoons may also be infected. Heartworms go through several life stages before they become adults infecting the pulmonary artery of the host mammal. The worms require the mosquito as an intermediate host to complete their life cycle. The period between the initial infection when the dog is bitten by a mosquito and the maturation of the worms into adults living in the heart and pulmonary arteries is six to seven months in dogs and is known as the "prepatent period". L3 larvae migrate during blood feeding of the mosquito to the tip of the mosquito’s mouth parts (labium), leave the mosquito and are deposited on the skin of the dog where they then migrate through the bite wound into the host. Most L3 larvae molt to fourth-stage larvae (L4s) in canine subcutaneous tissues within 1-3 days after infection. Then, they migrate to the muscles of the chest and abdomen, and 45 to 60 days after infection, molt to the fifth stage (L5, immature adult). Between 75 and 120 days after infection, these immature heartworms then enter the bloodstream and are carried through the heart to reside in the pulmonary artery. Around seven months after infection, Dirofilaria immitis adults reach maturity and sexually reproduce in the pulmonary arteries and right ventricle. Adult males are around 15cm in length, and females are around 25cm in length and their normal life span as adults is calculated to be about 5 years.

Heartworm infection is a severe and life-threatening disease. Canine heartworm infection is preventable and prophylaxis treatment is a priority in heartworm endemic areas. Treatment of mature heartworm infection with an adulticide (e.g. melarsomine dihydrochloride) is costly and can cause serious adverse side effects, thus prevention by monthly administration of drugs that interrupt larvae development is widely used. The goal of marketed heartworm preventive therapies in dogs is to prevent the development of the parasite to adult heartworms by interrupting the Dirofilaria immitis life cycle post-infection.

The macrocyclic lactones (MLs, e.g. ivermectin, eprinomectin, milbemycin oxime, moxidectin, and selamectin) are the most commonly used chemoprophylaxis agents and are administered at monthly or six-month intervals. These drugs have been effective against Dirofilaria immitis infective third-stage larvae (L3) deposited by the mosquito as well as maturing fourth-stage larvae (L4). When administered monthly, MLs kill L3 and L4 larvae acquired within the previous 30 days, and thus prevent disease caused by adult worms. MLs can also be used monthly in infected dogs to suppress reproduction in adult worms and remove microfilariae, thereby reducing transmission and gradually causing the attrition of adult worms (Vet. Parasitol.2005 Oct 24133(2-3) 197-206).

In recent years, an increased number of lack of efficacy (LOE) cases have been reported, in which dogs develop mature heartworm infections despite receiving monthly prophylactic doses of macrocyclic lactones drugs. For example, Atkins et al., (Vet. Parasitol.206 (2014) 106– 113) recently reported that an increasing number of cases of dogs that tested heartworm antigen positive while receiving heartworm preventive medication which suggests that some populations of Dirofilaria immitis have developed selectional resistance to heartworm preventives (American Heartworm Society, 2010. Heartworm Preventive Resistance. Is it Possible, vol. 37. Bulletin of the American Heartworm Society, pp. 5.). Thus, there is an ongoing need to develop new anthelmintic agents with improved activity against Dirofilaria immitis and other endoparasites.

Various parasiticides exist in the art for treating endoparasites infections in animals. In addition to the macrocyclic lactones, cyclic depsipeptides with antiparasitic activity are known. PF1022A, a 24-membered cyclooctadepsipeptide isolated from the fungus Mycelia sterilia by Sasaki et al. (see J. Antibiotics 45: 692-697 (1992)), has been found to exhibit broad anthelmintic activity against a variety of endoparasites in vivo with low toxicity. These compounds are described, for example, in U.S. Patent Nos. 5,514,773; 5,747,448; 5,646,244; 5,874,530; among others, which are incorporated herein by reference. Emodepside is a semi synthetic analog of PF1022A containing a morpholine group at the para position of the aryl ring in the phenyl lactate groups. Emodepside is a potent anthelmintic used in combination with praziquantel in the product Profender ^® for the treatment of parasitic worms in cats and dogs. However, the anti- parasitic activity of PF1022A and emodepside is not satisfactory for the treatment of certain parasites, especially for the control of Dirofilaria immitis in mammals to prevent the establishment of heartworm disease. Thus, there is a need in the art for more effective antiparasitic agents for treatment and protection of animals, e.g. mammals, fish and birds against parasites, in particular internal parasites including nematodes and filarial worms such as heartworm.

It is expressly noted that 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. Any foregoing applications, and all documents cited therein or during their prosecution (“application cited documents”) and all documents cited or referenced in the application cited documents, and 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 incorporated herein by reference, and may be employed in the practice of the invention. SUMMARY OF THE INVENTION

The invention provides novel and inventive cyclic depsipeptide compounds with superior anthelmintic activity and also superior activity against ectoparasites. In addition the invention provides compositions comprising the novel depsipeptide compounds and methods and uses for the treatment and prevention of parasitic infection and possibly infestation of animals using the compounds.

In one embodiment, the present invention provides cyclic depsipeptide compounds of formula (I) shown below:

or a veterinarily acceptable salt thereof, wherein the meanings of variables R ¹ , R ² , R ³ , R ⁴ , Cy ¹ , Cy ² , R ^a , R ^b , R’, R’’, R’’’ and R’’’’ are as described below. The invention also provides veterinary compositions comprising the inventive compounds, or salts thereof, in combination with a pharmaceutically acceptable carrier or diluent.

The compounds of the invention are intended to encompass racemic mixtures, specific stereoisomers and tautomeric forms of the compound. Another aspect of the invention is a salt form of the compound of the invention. The inventive compounds and compositions comprising the compounds are highly effective for the treatment and prophylaxis of internal parasites in mammals, fish and birds, and in particular, cats, dogs, horses, chickens, pigs, sheep and cattle with the aim of ridding these hosts of all the endoparasites commonly encountered by mammals, fish and birds.

In one embodiment, the compounds and compositions of the invention are highly effective against endoparasites, such as filariae (e.g. heartworm), hookworms, whipworms and roundworms of the digestive tract of animals and humans. In certain embodiments, the compounds and compositions of the invention are effective against Dirofilaria immitis (heartworm) isolates that are less sensitive to treatment with macrocyclic lactones. In another embodiment, the novel and inventive depsipeptides of the invention are effective for treating and preventing infections of animals with nematodes that are less sensitive to treatment with commercially available or known macrocyclic lactone active agents.

In certain embodiments, the invention provides compositions comprising a combination of a novel depsipeptide of the invention in combination with at least a second active agent, which broadens the scope of protection afforded to animals against endoparasites and possibly also ectoparasites.

The present invention is also directed to methods for the treatment and prevention of a parasitic infection or infestation in an animal comprising administering at least one of the compounds of formula (I) of the invention to the animal. Also included in the present invention are uses of the compounds for the treatment and/or prevention of a parasitic infections and infestations in animals and the use of the compounds in the preparation of a medicament for the treatment and/or prevention of a parasitic infection in an animal.

It is an object of the invention to not encompass within the invention any previously known product, process of making the product, or method of using the product such that the Applicants reserve the right to this invention and hereby disclose a disclaimer of any previously known product, process, or method.

It is noted that in this disclosure and particularly in the claims and/or paragraphs, terms such as“comprises”,“comprised”,“comprising” and the like can have the meaning attributed to it in U.S. Patent law; e.g., they can mean“includes”,“included”,“including”, and the like; and that terms such as“consisting essentially of” and“consists essentially of” have the meaning ascribed to them in U.S. Patent law; e.g., they allow for elements not explicitly recited, but exclude elements that are found in the prior art or that affect a basic or novel characteristic of the invention.

These and other embodiments are disclosed or are obvious from, and encompassed by, the following Detailed Description. DETAILED DESCRIPTION

The present invention provides novel and inventive cyclic depsipeptide compounds of formula (I) having parasiticidal activity against endoparasites and also against ectoparasites in certain embodiments, or veterinarily salts thereof, and compositions comprising the compounds or salts for the treatment or prevention of parasitic infections and/or infestations in an animal Also provided are methods for the treatment or prevention of parasitic infestations and/or infection in animals, comprising administering an effective amount of the depsipeptide compound of the invention, or a salt thereof, to the animal.

The novel and inventive cyclic depsipeptide of formula (I) described herein and their veterinarily acceptable salts are particularly effective for controlling endoparasites. Endoparasites include, but are not limited to, nematodes (such as roundworms, hookworms, and whipworms) and filarial worms such as Dirofilaria immitis (heartworm). In certain embodiments, the novel cyclic depsipeptides of the invention have been found to have significantly higher efficacy against endoparasites compared with known cyclic depsipeptides including PF1022A and emodepside. Furthermore, it has been discovered that the novel cyclic depsipeptides of the invention are significantly more resistant to metabolic modification in the body of animals so that they maintain at a higher concentration in the host animal’s body and a higher level of activity against internal parasites for a longer duration of time.

In one embodiment, the cyclic depsipeptides of the invention have been found to be highly effective against filarial worms such as Dirofilaria immitis (microfilarial and larval stages), including isolates of the parasite that are resistant to macrocyclic lactones. In other embodiments, the compounds of the invention are effective against endoparasites that are not effectively controlled by the known cyclic depsipeptides such as PF1022A and emodepside.

In another embodiment, the cyclic depsipeptides of the invention have been found to have activity against ectoparasites such as fleas and ticks. Thus, in certain embodiments the cyclic depsipeptides may have endectocidal activity against both internal and external parasites. The invention includes at least the following features:

(a) In one embodiment, the invention provides novel cyclic depsipeptide compounds of formula (I), or pharmaceutically or veterinarily acceptable salts thereof, which are active endoparasites and in some cases also active against ectoparasites;

(b) veterinary compositions comprising a parasiticidally effective amount of the cyclic depsipeptide compounds of formula (I), or a pharmaceutically or veterinarily acceptable salt thereof, in combination with a pharmaceutically or veterinarily acceptable carrier or diluent;

(c) veterinary compositions comprising a parasiticidally effective amount of the cyclic depsipeptide compounds of the invention, or pharmaceutically or veterinarily acceptable salts thereof, in combination with one more other active agents and a pharmaceutically or veterinarily acceptable carrier or diluent;

(d) methods for treating a parasitic infestation/infection in or on an animal are provided comprising administering a parasiticidally effective amount of a cyclic depsipeptide compound of formula (I), or a pharmaceutically or veterinarily acceptable salts thereof, optionally with one or more additional active agents, to the animal in need thereof;

(e) methods for the prevention of a parasitic infestation/infection of an animal, which comprise administering a parasiticidally effective amount of a cyclic depsipeptide compound of formula (I), or pharmaceutically or veterinarily acceptable salts thereof, optionally with one or more additional active agents, to the animal in need thereof;

(f) uses of the cyclic depsipeptide compounds of formula (I), or pharmaceutically or veterinarily acceptable salts thereof, for the treatment or prevention of a parasitic infection and possibly also a parasitic infestation in an animal;

(g) uses of the cyclic depsipeptide compounds of formula (I), or pharmaceutically or veterinarily acceptable salts thereof, in the manufacture of a veterinary medicament for the treatment or prevention of a parasitic infection in an animal; and

(h) processes for the preparation of the compounds of formula (I).

Definitions

Terms used herein will have their customary meanings in the art unless specified. The organic moieties mentioned in the definitions of the variables of the cyclic depsipeptide formula (I) are like the term halogen– i.e., collective terms for individual listings of the individual group members– fluoro, chloro, bromo and iodo with respect to halogen. The prefix C _n -C _m indicates in each case the possible number of carbon atoms in the group.

The term“alkyl” refers to saturated straight, branched, primary, secondary or tertiary hydrocarbons, including those having 1 to 12 atoms. In some embodiments, alkyl groups will include C ₁ -C ₁₀ , C ₁ -C ₈ , C ₁ -C ₆ , C ₁ -C ₄ or C ₁ -C ₃ alkyl groups. Examples of C ₁ -C ₁₀ alkyl include, but are not limited to, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1- ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3- methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2- dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2- trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, heptyl, octyl, 2-ethylhexyl, nonyl and decyl and their isomers. C ₁ -C ₄ -alkyl means for example methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl.

Cyclic alkyl groups, may be referred to as“cycloalkyl” and include those with 3 to 10 carbon atoms having single or multiple fused rings. Non-limiting examples of cycloalkyl groups include adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.

Carbocyclic groups are cyclic groups composed exclusively of carbon. The carbocyclic groups include both aromatic rings such as phenyl and non-aromatic rings such cyclohexyl and include those with 3 to 14 carbon atoms having single or multiple fused rings.

The alkyl and cycloalkyl and carbocyclic groups described herein can be unsubstituted or substituted with one or more moieties selected from the group consisting of alkyl, halo, haloalkyl, hydroxyl, carboxyl, acyl, acyloxy, amino, alkyl- or dialkylamino, amido, arylamino, alkoxy, aryloxy, nitro, cyano, azido, thiol, imino, sulfonic acid, sulfate, sulfonyl, sulfanyl, sulfinyl, sulfamoyl, ester, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrazine, carbamate, phosphonic acid, phosphate, phosphonate, or any other viable functional group that does not inhibit the biological activity of the compounds of the invention, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in Greene and Wuts, Protective Groups in Organic Synthesis, John Wiley and Sons, Third Edition, 1999, hereby incorporated by reference. The term“alkenyl” refers to both straight and branched carbon chains which have at least one carbon-carbon double bond. In some embodiments, alkenyl groups may include C ₂ -C ₁₂ alkenyl groups. In other embodiments, alkenyl includes C ₂ -C ₁₀ , C ₂ -C ₈ , C ₂ -C ₆ or C ₂ -C ₄ alkenyl groups. In one embodiment of alkenyl, the number of double bonds is 1-3; in another embodiment of alkenyl, the number of double bonds is one. Other ranges of carbon-carbon double bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule.“C ₂ -C ₁₀ -alkenyl” groups may include more than one double bond in the chain. Examples include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl, 1- methyl-ethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1- methyl-2-propenyl, 2-methyl-2-propenyl; 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1- methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2- butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1- dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1- ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl- 2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3- pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2- dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2- ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1- propenyl and 1-ethyl-2-methyl-2-propenyl.

“Cycloalkenyl” refers to monovalent cyclic alkenyl groups of from 4 to 10 carbon atoms, preferably 5 to 8 carbon atoms, having single or multiple fused rings which fused rings may or may not be cycloalkenyl provided that the point of attachment is to a cycloalkenyl ring atom. Examples of cycloalkenyl groups include, by way of example, cyclopenten-4-yl, cyclooctene-5- yl and the like. Alkenyl and cycloalkenyl groups may be unsubstituted or substituted with one or more substituents as described for alkyl above. “Alkynyl” refers to both straight and branched carbon chains which have at least one carbon-carbon triple bond. In one embodiment of alkynyl, the number of triple bonds is 1-3; in another embodiment of alkynyl, the number of triple bonds is one. In some embodiments, alkynyl groups include from 2 to 12 carbon atoms. In other embodiments, alkynyl groups may include C ₂ -C ₁₀ , C ₂ -C ₈ , C ₂ -C ₆ or C ₂ -C ₄ alkynyl groups. Other ranges of carbon-carbon triple bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule. For example, the term”C ₂ -C ₁₀ -alkynyl” as used herein refers to a straight-chain or branched unsaturated hydrocarbon group having 2 to 10 carbon atoms and containing at least one triple bond, such as ethynyl, prop-1-yn-1-yl, prop-2-yn-1-yl, n-but-1-yn- 1-yl, n-but-1-yn-3-yl, n-but-1-yn-4-yl, n-but-2-yn-1-yl, n-pent-1-yn-1-yl, n-pent-1-yn-3-yl, n- pent-1-yn-4-yl, n-pent-1-yn-5-yl, n-pent-2-yn-1-yl, n-pent-2-yn-4-yl, n-pent-2-yn-5-yl, 3- methylbut-1-yn-3-yl, 3-methylbut-1-yn-4-yl, n-hex-1-yn-1-yl, n-hex-1-yn-3-yl, n-hex-1-yn-4-yl, n-hex-1-yn-5-yl, n-hex-1-yn-6-yl, n-hex-2-yn-1-yl, n-hex-2-yn-4-yl, n-hex-2-yn-5-yl, n-hex-2- yn-6-yl, n-hex-3-yn-1-yl, n-hex-3-yn-2-yl, 3-methylpent-1-yn-1-yl, 3-methylpent-1-yn-3-yl, 3- methylpent-1-yn-4-yl, 3-methylpent-1-yn-5-yl, 4-methylpent-1-yn-1-yl, 4-methylpent-2-yn-4-yl or 4-methylpent-2-yn-5-yl and the like.

The term“haloalkyl” refers to an alkyl group, as defined herein, which is substituted by one or more halogen atoms. For example C ₁ -C ₄ -haloalkyl includes, but is not limited to, chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and the like.

The term "fluoroalkyl" as used herein refers to an alkyl in which one or more of the hydrogen atoms is replaced with fluorine atoms, for example difluoromethyl, trifluoromethyl, 1- fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl or pentafluoroethyl.

The term“haloalkenyl” refers to an alkenyl group, as defined herein, which is substituted by one or more halogen atoms.

The term“haloalkynyl” refers to an alkynyl group, as defined herein, which is substituted by one or more halogen atoms. “Alkoxy” refers to alkyl-O-, wherein alkyl is as defined above. Similarly, the terms “alkenyloxy,”“alkynyloxy,”“haloalkoxy,”“haloal kenyloxy,”“haloalkynyloxy,”“cycloalkoxy,” “cycloalkenyloxy,”“halocycloalkoxy,” and“halocycloalkenyloxy” refer to the groups alkenyl- O-, alkynyl-O-, haloalkyl-O-, haloalkenyl-O-, haloalkynyl-O-, cycloalkyl-O-, cycloalkenyl-O-, halocycloalkyl-O-, and halocycloalkenyl-O-, respectively, wherein alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, halocycloalkyl, and halocycloalkenyl are as defined above. Examples of C ₁ -C ₆ -alkoxy include, but are not limited to, methoxy, ethoxy, OCH ₂ -C ₂ H ₅ , OCH(CH ₃ ) ₂ , n-butoxy, OCH(CH ₃ )-C ₂ H ₅ , OCH ₂ –CH(CH ₃ ) _2, OC(CH ₃ ) ₃ , n-pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethyl-propoxy, 1-ethylpropoxy, n-hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3- methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy, 1-ethyl-2- methylpropoxy and the like.

“Aryl” refers to a monovalent aromatic carbocyclic group of from 6 to 14 carbon atoms having a single ring or multiple fused rings. Aryl groups include, but are not limited to, phenyl, biphenyl, and naphthyl. In some embodiments aryl includes tetrahydronaphthyl, phenylcyclopropyl and indanyl. Aryl groups may be unsubstituted or substituted by one or more moieties selected from halogen, cyano, nitro, hydroxy, mercapto, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, cycloalkoxy, cycloalkenyloxy, halocycloalkoxy, halocycloalkenyloxy, alkylthio, haloalkylthio, cycloalkylthio, halocycloalkylthio, alkylsulfinyl, alkenylsulfinyl, alkynyl-sulfinyl, haloalkylsulfinyl, haloalkenylsulfinyl, haloalkynylsulfinyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, haloalkyl-sulfonyl, haloalkenylsulfonyl, haloalkynylsulfonyl, -SF ₅ , alkylamino, alkenylamino, alkynylamino, di(alkyl)amino, di(alkenyl)-amino, di(alkynyl)amino, or trialkylsilyl.

The term“aralkyl” refers to an aryl group that is bonded to the parent compound through a diradical alkylene bridge, (-CH ₂ -) _n , where n is 1-12 and where“aryl” is as defined above.

“Heteroaryl” refers to a monovalent aromatic group of from 1 to 15 carbon atoms, preferably from 1 to 10 carbon atoms, having one or more oxygen, nitrogen, and sulfur heteroatoms within the ring, preferably 1 to 4 heteroatoms, or 1 to 3 heteroatoms. The nitrogen and sulfur heteroatoms may optionally be oxidized. Such heteroaryl groups can have a single ring (e.g., pyridyl or furyl) or multiple fused rings provided that the point of attachment is through a heteroaryl ring atom. Examples of heteroaryls include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinnyl, furanyl, thiophenyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, pyrazolyl benzofuranyl, benzothiophenyl, imidazopyridyl, imidazopyrimidyl, or pyrrolopyrimidyl. Heteroaryl rings may be unsubstituted or substituted by one or more moieties as described for aryl above.

“Heterocyclyl,”“heterocyclic” or“heterocyclo” refers to fully saturated or unsaturated, cyclic groups, for example, 3 to 7 membered monocyclic, 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic ring systems, which have one or more oxygen, sulfur or nitrogen heteroatoms in ring, preferably 1 to 4 or 1 to 3 heteroatoms. The nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be attached at any heteroatom or carbon atom of the ring or ring system and may be unsubstituted or substituted by one or more moieties as described for aryl groups above.

Exemplary monocyclic heterocyclic groups include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2- oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl, triazinyl, and the like.

Exemplary bicyclic heterocyclic groups include, but are not limited to, indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetra- hydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuryl, chromonyl, coumarinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl]or furo[2,3-b]pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), tetrahydroquinolinyl and the like. The term "alkylthio” refers to alkyl-S-, where“alkyl” is as defined above. In some embodiments, the alkyl component of the alkylthio group will include C ₁ -C ₁₀ , C ₁ -C ₈ , C ₁ -C ₆ C ₁ - C ₄ or C ₁ -C ₃ alkyl groups. For example, C ₁ -C ₄ -alkylthio include, but are not limited to, methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2- methylpropylthio or 1,1-dimethylethylthio.

Similarly, the terms“haloalkylthio,”“cycloalkylthio,”“halocycloal kylthio” refer to the groups–S-haloalkyl, -S-cycloalkyl, and–S-halocycloalkyl, respectively, where the terms “haloalkyl,”“cycloalkyl,” and“halocycloalkyl” are as defined above.

The term“alkylsulfinyl" refers to the group alkyl-S(=O)-, where“alkyl” is as defined above. In some embodiments, the alkyl component in alkylsulfinyl groups will include C ₁ -C ₁₂ , C ₁ -C ₁₀ , C ₁ -C ₈ , C ₁ -C ₆ , C ₁ -C ₄ or C ₁ -C ₃ alkyl groups. Examples include, but are not limited to, - SO–CH ₃ , -SO–C ₂ H ₅ , n-propylsulfinyl, 1-methylethylsulfinyl, n-butylsulfinyl, 1- methylpropylsulfinyl, 2-methylpropylsulfinyl, 1,1-dimethylethylsulfinyl, n-pentylsulfinyl, 1- methylbutylsulfinyl, 2-methylbutylsulfinyl, 3-methylbutylsulfinyl, 1,1-dimethylpropylsulfinyl, 1,2-dimethylpropylsulfinyl, 2,2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl, n-hexylsulfinyl, 1-methylpentylsulfinyl, 2-methylpentylsulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl, 1,2-dimethylbutylsulfinyl, 1,3-dimethylbutylsulfinyl, 2,2- dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl, 3,3-dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl, 1-ethyl-1- methylpropylsulfinyl or 1-ethyl-2-methylpropylsulfinyl.

Similarly, the terms “alkenylsulfinyl,” “alkynylsulfinyl,” “haloalkylsulfinyl,” “haloalkenylsulfinyl,” and“haloalkynylsulfinyl” refer to the groups alkenyl-S(=O)-, alkynyl- S(=O)-, and haloalkyl-S(=O)-, haloalkenyl-S(=O)-, and haloalkynyl-S(=O)-, where the terms “alkenyl,”“alkynyl,”“haloalkyl,”“haloalkenyl,� �� and“haloalkynyl” are as defined above.

The term "alkylsulfonyl" refers to the group alkyl-S(=O) ₂ -, where the term“alkyl” is as defined above. In some embodiments, the alkyl component in alkylsulfonyl groups will include C ₁ -C ₁₂ , C ₁ -C ₁₀ , C ₁ -C ₈ , C ₁ -C ₆ or C ₁ -C ₄ alkyl groups. Examples include, but are not limited to, - SO ₂ –CH ₃ , -SO ₂ –C ₂ H ₅ , n-propylsulfonyl, -SO ₂ –CH(CH ₃ ) ₂ , n-butylsulfonyl, 1- methylpropylsulfonyl, 2-methylpropylsulfonyl, -SO ₂ –C(CH ₃ ) ₃ , n-pentylsulfonyl, 1- methylbutylsulfonyl, 2-methylbutylsulfonyl, 3-methylbutylsulfonyl, 1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl, 2,2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, n-hexylsulfonyl, 1-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl, 4- methylpentylsulfonyl, 1,1-dimethylbutylsulfonyl, 1,2-dimethylbutylsulfonyl, 1,3- dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3- dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1,1,2-trimethylpropylsulfonyl, 1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropylsulfonyl or 1-ethyl-2- methylpropylsulfonyl and the like.

The terms “alkenylfulfonyl,” “alkynylsulfonyl,” “haloalkylsulfonyl,” “haloalkenylsulfonyl,” and“haloalkynylsulfonyl” refer to the groups alkenyl-S(=O) ₂ -, alkynyl- S(=O) ₂ -, and haloalkyl-S(=O) ₂ -, haloalkenyl-S(=O) ₂ -, and haloalkynyl-S(=O) ₂ -, where the terms “alkenyl,”“alkynyl,”“haloalkyl,”“haloalkenyl,� �� and“haloalkynyl” are as defined above.

The terms “alkylamino,” “dialkylamino,” “alkenylamino,” “alkynylamino,” “di(alkenyl)amino,” and“di(alkynyl)amino” refer to the groups -NH(alkyl), -N(alkyl) ₂ , - NH(alkenyl), -NH(alkynyl), -N(alkenyl) ₂ and -N(alkynyl) ₂ , where the terms“alkyl,”“alkenyl,” and“alkynyl” are as defined above. In some embodiments, the alkyl component in alkylamino or dialkylamino groups will include C ₁ -C ₁₂ , C ₁ -C ₁₀ , C ₁ -C ₈ , C ₁ -C ₆ or C ₁ -C ₄ alkyl groups.

Compounds of the Invention:

The compounds of the invention are 24-membered cyclic depsipeptide compounds which have potent activity against endoparasites such as nematodes and filarial worms (microfilarial and larval stages) and also in some cases against ectoparasites such as fleas and ticks. In one embodiment the invention provides cyclic depsipeptide compounds of formula (I), or a pharmaceutically or veterinarily acceptable salt thereof:

(I)

wherein:

Cy ¹ and Cy ² are independently aryl, carbocyclic, heteroaryl or heterocyclic optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O- heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ ;

R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, or the group -CH ₂ C(O)NHCH ₂ CF ₃ ; or R ⁵ and R ⁶ together with the atom(s) to which they are bonded form a C ₃ -C ₆ cyclic group;

R’, R’’, R’’’ and R’’’’ are each independently hydrogen or C ₁ -C ₃ alkyl; R ^a and R ^b are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl; and

(a) R ¹ is C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ² , R ³ and R ⁴ are each independently C ₁ -C ₈ alkyl; or

(b) R ² is C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ¹ , R ³ and R ⁴ are each independently C ₁ -C ₈ alkyl; or

(c) R ³ is C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ¹ , R ² and R ⁴ are each independently C ₁ -C ₈ alkyl; or

(d) R ⁴ is C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ¹ , R ² and R ³ are each independently C ₁ -C ₈ alkyl; or

(e) R ¹ and R ² are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ³ and R ⁴ are each independently C ₁ -C ₈ alkyl; or

(f) R ¹ and R ³ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ² and R ⁴ are each independently C ₁ -C ₈ alkyl; or (g) R ¹ and R ⁴ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ² and R ³ are each independently C ₁ -C ₈ alkyl; or

(h) R ² and R ⁴ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ¹ and R ³ are each independently C ₁ -C ₈ alkyl; or

(i) R ² and R ³ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ¹ and R ⁴ are each independently C ₁ -C ₈ alkyl; or

(j) R ³ and R ⁴ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ¹ and R ² are each independently C ₁ -C ₈ alkyl; or

(k) R ¹ , R ² and R ³ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ⁴ is C ₁ -C ₈ alkyl; or

(l) R ² , R ³ and R ⁴ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and R ¹ is C ₁ -C ₈ alkyl; or

(m) R ¹ , R ³ and R ⁴ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino; and

R ² is C ₁ -C ₈ alkyl; or

(n) R ¹ , R ² and R ⁴ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino and alkylamino, dialkylamino; and

R ³ is C ₁ -C ₈ alkyl; or

(o) R ¹ , R ² , R ³ and R ⁴ are each independently C ₁ -C ₈ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino.

Cy ¹ and Cy ² Groups

In one embodiment, Cy ¹ and Cy ² are independently phenyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S- heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I). In another embodiment, Cy ¹ and Cy ² are independently phenyl, heteroaryl or heterocyclyl optionally independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In another embodiment, Cy ¹ and Cy ² are independently 6-12 membered bicyclic aryl or heteroaryl groups optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In another embodiment, Cy ¹ and Cy ² are independently bicyclic heterocyclic groups optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O- heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In another embodiment, Cy ¹ and Cy ² are independently phenyl, biphenyl, naphthyl, tetrahydronaphthyl, phenylcyclopropyl, biphenylene, fluorene, anthracene, acenaphthene, phenanthrene or indanyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In yet another embodiment, Cy ¹ and Cy ² are independently pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, furanyl, thiophenyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, pyrazolyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, imidazopyridyl, imidazopyrimidyl or pyrrolopyrimidyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In another embodiment, Cy ¹ and Cy ² are independently pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuranyl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2- oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl or triazinyl optionally independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In another embodiment, Cy ¹ and Cy ² are independently indolyl, isoindolyl, benzothiazolyl, benzoxazolyl, benz[d]isoxazolyl, benzotriazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuranyl, dihydrobenzofuranyl, chromonyl, coumarinyl, cinnolinyl, indazolyl, pyrrolopyridyl, phthalazinyl, 1,2,3-benzotriazinyl, 1,2,4-benzotriazinyl, furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl]or furo[2,3-b]pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), tetrahydroquinolinyl or tetrahydroisoquinolinyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In one embodiment, Cy ¹ and Cy ² are independently phenyl substituted with heterocyclyl. In yet another embodiment, Cy ¹ and Cy ² are independently a 6-membered heteroaryl group substituted with heterocyclyl. In still another embodiment, Cy ¹ and Cy ² are independently heterocyclyl substituted with a heterocyclyl group. In yet another embodiment, Cy ¹ and Cy ² are independently phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or tetrazinyl substituted with heterocyclyl.

In one embodiment, Cy ¹ and Cy ² are independently phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or tetrazinyl substituted with morpholino, tetrahydropyran, tetrahydrofuran, pyrrolidino or piperidino.

In one embodiment, Cy ¹ and Cy ² are independently phenyl, a 5-membered or a 6- membered heteroaryl ring optionally substituted with halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, -SF ₅ , amino, alkylamino or dialkylamino.

In another embodiment, Cy ¹ and Cy ² are independently phenyl, a 5-membered or a 6- membered heteroaryl ring optionally substituted with alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl.

In another embodiment, Cy ¹ and Cy ² are independently phenyl, a 5-membered or a 6- membered heteroaryl ring optionally substituted with C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₂ -C ₄ alkenyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ alkynyl, C ₂ -C ₄ haloalkynyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, C ₁ -C ₃ alkylamino or C ₁ -C ₃ dialkylamino.

In another embodiment, Cy ¹ and Cy ² are independently phenyl, a 5-membered or a 6- membered heteroaryl ring optionally substituted with methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, CF ₃ , -CH ₂ CF ₃ , -CHFCF ₃ or -CF ₂ CF ₃ . In another embodiment, Cy ¹ and Cy ² are independently phenyl, a 5-membered or a 6- membered heteroaryl ring optionally substituted with fluoro, chloro, bromo or iodo.

In another embodiment, Cy ¹ and Cy ² are independently phenyl, a 5-membered or a 6- membered heteroaryl ring optionally substituted with hydroxy, methoxy, trifluoromethoxy, - OCH ₂ CF ₃ , -OCHFCF ₃ , -OCF ₂ CF ₃ , -SCH ₃ , -SCF ₃ , -SCH ₂ CF ₃ , -SCHFCF ₃ , -SCF ₂ CF ₃ , -S(O)CH ₃ , -S(O)CF ₃ , -S(O)CH ₂ CF ₃ , -S(O)CHFCF ₃ ,–S(O)CF ₂ CF ₃ , -S(O) ₂ CH ₃ , -S(O) ₂ CF ₃ , -S(O) ₂ CH ₂ CF ₃ , - S(O) ₂ CHFCF ₃ ,–S(O) ₂ CF ₂ CF ₃ or SF ₅ .

In yet another embodiment, Cy ¹ and Cy ² are independently phenyl, thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or tetrazinyl optionally substituted with halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino or dialkylamino.

In yet another embodiment, Cy ¹ and Cy ² are independently phenyl, thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or tetrazinyl optionally substituted with alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl.

In yet another embodiment, Cy ¹ and Cy ² are independently phenyl, thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or tetrazinyl optionally substituted with C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₂ - C ₄ alkenyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ alkynyl, C ₂ -C ₄ haloalkynyl, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, C ₁ -C ₃ alkylamino or C ₁ -C ₃ dialkylamino.

In another embodiment, Cy ¹ and Cy ² are independently phenyl, a 5-membered or a 6- membered heteroaryl ring optionally substituted with methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, CF ₃ , -CH ₂ CF ₃ , -CHFCF ₃ or -CF ₂ CF ₃ .

In yet another embodiment, Cy ¹ and Cy ² are independently phenyl, thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or tetrazinyl optionally substituted with fluoro, chloro, bromo or iodo.

In yet another embodiment, Cy ¹ and Cy ² are independently phenyl, thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or tetrazinyl optionally substituted with hydroxy, methoxy, trifluoromethoxy, -OCH ₂ CF ₃ , -OCHFCF ₃ , -OCF ₂ CF ₃ , -SCH ₃ , -SCF ₃ , -SCH ₂ CF ₃ , -SCHFCF ₃ or -SCF ₂ CF ₃ , -S(O)CH ₃ , -S(O)CF ₃ , -S(O)CH ₂ CF ₃ , -S(O)CHFCF ₃ ,–S(O)CF ₂ CF ₃ , -S(O) ₂ CH ₃ , - S(O) ₂ CF ₃ , -S(O) ₂ CH ₂ CF ₃ , -S(O) ₂ CHFCF ₃ ,–S(O) ₂ CF ₂ CF ₃ or SF ₅ .

In another embodiment, Cy ¹ and Cy ² are independently one of R1 to R8 shown below:

wherein Y ¹ , Y ² , Y ³ , Y ⁴ , Y ⁵ , Y ⁶ , Y ⁷ , Y ⁸ and Y ⁹ are each independently C, CH or N; and X ¹ , X ² , X ⁵ , X ⁶ and X ⁷ are independently hydrogen, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, heteroaryl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In one embodiment, Cy ¹ and Cy ² are independently R1 to R8 wherein Y ¹ , Y ² , Y ³ , Y ⁴ , Y ⁵ , Y ⁶ , Y ⁷ , Y ⁸ and Y ⁹ are each independently C, CH or N; and X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ and X ⁷ are independently hydrogen, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, thioamido, amino, alkylamino or dialkylamino. In another embodiment, Cy ¹ and Cy ² are independently R1 to R8 wherein Y ¹ , Y ² , Y ³ , Y ⁴ , Y ⁵ , Y ⁶ , Y ⁷ , Y ⁸ and Y ⁹ are each independently C, CH or N; and X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ and X ⁷ are independently hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl.

In another embodiment, Cy ¹ and Cy ² are independently R1 to R8 wherein Y ¹ , Y ² , Y ³ , Y ⁴ , Y ⁵ , Y ⁶ , Y ⁷ , Y ⁸ and Y ⁹ are each independently C, CH or N; and X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ and X ⁷ are independently hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, CF ₃ , - CH ₂ CF ₃ , -CHFCF ₃ or CF ₂ CF ₃ .

In another embodiment, Cy ¹ and Cy ² are independently R1 to R8 wherein Y ¹ , Y ² , Y ³ , Y ⁴ , Y ⁵ , Y ⁶ , Y ⁷ , Y ⁸ and Y ⁹ are each independently C, CH or N; and X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ and X ⁷ are independently hydrogen, fluoro, chloro, bromo or iodo.

In another embodiment, Cy ¹ and Cy ² are independently R1 to R8, wherein Y ¹ , Y ² , Y ³ , Y ⁴ , Y ⁵ , Y ⁶ , Y ⁷ , Y ⁸ and Y ⁹ are each independently C, CH or N; and X ¹ , X ² , X ³ , X ⁴ , X ⁵ , X ⁶ and X ⁷ are independently hydrogen, hydroxy, methoxy, trifluoromethoxy, -OCH ₂ CF ₃ , -OCHFCF ₃ , - OCF ₂ CF ₃ , methylthio, trifluoromethylthio, -SCH ₂ CF ₃ , -SCHFCF ₃ , -SCF ₂ CF ₃ or SF ₅ .

In another embodiment, Cy ¹ and Cy ² are independently R9 to R11 shown below:

wherein X ¹ , X ² and X ³ are independently hydrogen, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, heteroaryl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ , wherein R ⁵ and R ⁶ are as defined above for formula (I).

In one embodiment, Cy ¹ and Cy ² are independently R9 to R11, wherein X ¹ , X ² and X ³ are independently hydrogen, halogen, alkyl or haloalkyl. In another embodiment, Cy ¹ and Cy ² are independently R9 to R11, wherein X ¹ , X ² and X ³ are independently hydrogen, fluoro, chloro, bromo or iodo. In another embodiment, Cy ¹ and Cy ² are independently R9 to R11, wherein X ¹ , X ² and X ³ are independently hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert- butyl, CF ₃ , -CH ₂ CF ₃ , -CHFCF ₃ or CF ₂ CF ₃ . In yet another embodiment, Cy ¹ and Cy ² are independently R9 to R11, wherein X ¹ , X ² and X ³ are independently hydrogen, hydroxy, methoxy, trifluoromethoxy, -OCH ₂ CF ₃ , -OCHFCF ₃ , -OCF ₂ CF ₃ , methylthio, trifluoromethylthio, -SCH ₂ CF ₃ , -SCHFCF ₃ , -SCF ₂ CF ₃ or SF ₅ .

In another embodiment, Cy ¹ and/or Cy ² are independently phenyl, p-morpholinophenyl, p-fluorophenyl, p-OCF ₃ -phenyl, p-CF ₃ -phenyl, 3,4,5-trifluoro-phenyl, p-tetrahydropyranyl-4-yl- phenyl, 2-(morpholin-4-yl)pyridine-5-yl, 5-(morpholin-4-yl)pridin-2-yl, p- thiosulfonylmorpholin-4-yl-phenyl, p-NH ₂ -phenyl, p-(1-Me-1H-tetrazole-5-thiolyl)phenyl, p- NH ₂ - phenyl, 2,3-dihydrobenzofuran-5-yl, 4-(morpholin-4-yl)cyclylhexanyl, p-iodophenyl, p- bromophenyl, p-nitrophenyl and p-tert-butylphenyl.

In another embodiment, Cy ¹ and Cy ² are the groups shown in Table 1 below:

Table 1:

R ^a and R ^b

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl. In one embodiment, R ^a and R ^b are independently hydrogen or methyl. In another embodiment, R ^a and R ^b are independently hydrogen, methyl, ethyl or propyl. In another embodiment, R ^a and R ^b are independently hydrogen, methyl or CF ₃ . In still another embodiment, R ^a and R ^b are both methyl. In yet another embodiment, R ^a and R ^b are both hydrogen.

R', R'', R''' and R''''

In one embodiment, each of R', R'', R''' and R'''' are independently hydrogen or C ₁ -C ₃ alkyl. In another embodiment, each of R', R'', R''' and R'''' are independently hydrogen or methyl. In another embodiment, each of R', R'', R''' and R'''' are independently hydrogen, methyl or ethyl. R ¹ , R ² , R ³ and R ⁴

It will be understood that the invention includes compounds wherein the various groups Cy ¹ and Cy ² described in the above embodiments are combined with any combination of R ¹ , R ² , R ³ and R ⁴ described above for formula (I) and in the embodiments described below.

In one embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₈ alkyl group substituted by one or more of the substituents for these variables described above for formula (I) while the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₈ alkyl. In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more of the substituents for these variables described above for formula (I) while the other two of R ¹ to R ⁴ are unsubstituted C ₁ -C ₈ alkyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more of the substituents for these variables described above for formula (I) while the other of R ¹ to R ⁴ is unsubstituted C ₁ -C ₈ alkyl.

In still another embodiment, all four of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more of the substituents for these variables described above for formula (I).

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by one or more of the substituents for these variables described above for formula (I) while the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more of the substituents for these variables described above for formula (I) while the other two of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more of the substituents for these variables described above for formula (I) while the other of R ¹ to R ⁴ is unsubstituted C ₁ -C ₆ alkyl.

In still another embodiment, all four of R ¹ to R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more of the substituents for these variables described above for formula (I).

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by one or more of the substituents for these variables described above for formula (I) while the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more of the substituents for these variables described above for formula (I) while the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more of the substituents for these variables described above for formula (I) while the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₈ alkyl group substituted by one or more halogen while the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₈ alkyl. In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more halogen while the other two of R ¹ to R ⁴ are unsubstituted C ₁ -C ₈ alkyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more halogen while the other of R ¹ to R ⁴ is unsubstituted C ₁ -C ₈ alkyl.

In still another embodiment, all four of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted one or more halogen.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by one or more halogen while the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more halogen while the other two of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more halogen while the other of R ¹ to R ⁴ is unsubstituted C ₁ -C ₆ alkyl.

In still another embodiment, all four of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted one or more halogen.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by one or more halogen while the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more halogen while the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2- dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more halogen while the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2- dimethylpropyl.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₈ alkyl group substituted by one or more fluoro while the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₈ alkyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more fluoro while the other two of R ¹ to R ⁴ are unsubstituted C ₁ -C ₈ alkyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more fluoro while the other of R ¹ to R ⁴ is unsubstituted C ₁ -C ₈ alkyl.

In still another embodiment, all four of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted one or more fluoro. In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by one or more fluoro while the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more fluoro while the other two of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more fluoro while the other of R ¹ to R ⁴ is unsubstituted C ₁ -C ₆ alkyl.

In still another embodiment, all four of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted one or more fluoro.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by one or more fluoro while the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more fluoro while the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2- dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more fluoro while the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2- dimethylpropyl.

In one embodiment of the invention, one of R ¹ to R ⁴ is CH ₂ F, CHF ₂ or CF ₃ ; and the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are CH ₂ F, CHF ₂ or CF ₃ ; and the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are CH ₂ F, CHF ₂ or CF ₃ ; and the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, all four of R ¹ to R ⁴ are CH ₂ F, CHF ₂ or CF ₃ .

In one embodiment of the invention, one of R ¹ to R ⁴ is -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, all four of R ¹ to R ⁴ are -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen. In one embodiment of the invention, one of R ¹ to R ⁴ is -CH ₂ CF(CH ₃ ) ₂ ; and the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, all four of R ¹ to R ⁴ are -CH ₂ CF(CH ₃ ) ₂ .

In another embodiment of the invention, one of R ¹ to R ⁴ is -CH ₂ CX(CH ₃ ) ₂ wherein X is CH ₂ F, CHF ₂ or CF ₃ ; and the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2- dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are -CH ₂ CX(CH ₃ ) ₂ wherein X is CH ₂ F, CHF ₂ or CF ₃ ; and the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are -CH ₂ CX(CH ₃ ) ₂ wherein X is CH ₂ F, CHF ₂ or CF ₃ ; and the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, all four of R ¹ to R ⁴ are -CH ₂ CX(CH ₃ ) ₂ wherein X is CH ₂ F, CHF ₂ or CF ₃ .

In one embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₈ alkyl group substituted by one or more aryl or heteroaryl groups while the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₈ alkyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more aryl or heteroaryl groups while the other two of R ¹ to R ⁴ are unsubstituted C ₁ -C ₈ alkyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted by one or more aryl or heteroaryl groups while the other of R ¹ to R ⁴ is unsubstituted C ₁ -C ₈ alkyl.

In still another embodiment, all four of R ¹ to R ⁴ are C ₁ -C ₈ alkyl independently substituted one or more aryl or heteroaryl groups.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by one or more aryl or heteroaryl groups while the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more aryl or heteroaryl groups while the other two of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more aryl or heteroaryl groups while the other of R ¹ to R ⁴ is unsubstituted C ₁ -C ₆ alkyl. In still another embodiment, all four of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted one or more aryl or heteroaryl groups.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by one or more aryl or heteroaryl groups while the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more aryl or heteroaryl groups while the other two of R ¹ to R ⁴ are unsubstituted 2- methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are C ₁ -C ₆ alkyl independently substituted by one or more aryl or heteroaryl groups while the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by an optionally substituted phenyl while the others of R ¹ to R ⁴ are unsubstituted 2- methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are independently C ₁ -C ₆ alkyl substituted by an optionally substituted phenyl while the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are independently C ₁ -C ₆ alkyl substituted by an optionally substituted phenyl while the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, all four of R ¹ to R ⁴ are independently C ₁ -C ₆ alkyl substituted by an optionally substituted phenyl.

In another embodiment of the invention, one of R ¹ to R ⁴ is a C ₁ -C ₆ alkyl group substituted by an optionally substituted heteroaryl group selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl while the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are independently C ₁ -C ₆ alkyl substituted by an optionally substituted heteroaryl group selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl while the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are independently C ₁ -C ₆ alkyl substituted by an optionally substituted heteroaryl group selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl while the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, all four of R ¹ to R ⁴ are independently C ₁ -C ₆ alkyl substituted by an optionally substituted heteroaryl group selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl.

In another embodiment of the invention, one, two, three or all four of R ¹ to R ⁴ is the group G-1:

G-1;

wherein R ^1A , R ^1B , R ^1C , R ^1D and R ^1E are independently hydrogen, halogen, alkyl or haloalkyl; and the others of R ¹ to R ⁴ , if applicable, are unsubstituted C ₁ -C ₈ alkyl.

In one embodiment of the invention, one of R ¹ to R ⁴ is G-1; and the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, two of R ¹ to R ⁴ are G-1; and the other two of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, three of R ¹ to R ⁴ are G-1; and the other of R ¹ to R ⁴ is unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, all four of R ¹ to R ⁴ are G-1.

In one embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A , R ^1B , R ^1C , R ^1D and R ^1E are independently hydrogen, fluoro,C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl and the others of R ¹ to R ⁴ are unsubstituted C ₁ -C ₆ alkyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A , R ^1B , R ^1C , R ^1D and R ^1E are independently hydrogen, fluoro,C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl and the others of R ¹ to R ⁴ are unsubstituted 2-methylpropyl or 2,2-dimethylpropyl.

In one embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1D and R ^1E are independently H or halogen. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1D and R ^1E are independently C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is H or halogen. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is halogen, and R ^1B and R ^1C are independently C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl. In yet another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1D and R ^1E are H, R ^1A is halogen, and R ^1B and R ^1C are independently C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In one embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1D and R ^1E are independently H or F. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1D and R ^1E are independently methyl or trifluoromethyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is H or F. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is methyl or trifluoromethyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl. In yet another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1D and R ^1E are H, R ^1A is F, R ^1B and R ^1C are methyl or trifluoromethyl.

In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is C ₁ - C ₃ alkyl or C ₁ -C ₃ haloalkyl; and the other of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is halogen, and R ^1B and R ^1C are independently C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl; and the other of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In yet another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1D and R ^1E are H, R ^1A is halogen, and R ^1B and R ^1C are independently C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl; and the other of R ¹ to R ⁴ are 2-methylpropyl or 2,2- dimethylpropyl.

In one embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein one of R ^1D and R ^1E is F; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein one of R ^1D and R ^1E is methyl or trifluoromethyl; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is F; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is methyl or trifluoromethyl; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In yet another embodiment, one, two, three or all four of R ¹ to R ⁴ are G-1, wherein R ^1D and R ^1E are H, R ^1A is F, R ^1B and R ^1C are methyl or trifluoromethyl; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, one of R ¹ to R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, two of R ¹ to R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, three of R ¹ to R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and the others of R ¹ to R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, all four of R ¹ to R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl. In one embodiment, R ¹ is G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ² , R ³ and R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, R ² is G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ² , R ³ and R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In yet another embodiment, R ³ is G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ¹ , R ² and R ⁴ are 2- methylpropyl or 2,2-dimethylpropyl. In another embodiment, R ⁴ is G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ¹ , R ² and R ³ are 2-methylpropyl or 2,2- dimethylpropyl.

In another embodiment, R ¹ and R ³ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ² and R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, R ² and R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ¹ and R ³ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, R ¹ and R ² are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ³ and R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In yet another embodiment, R ² and R ³ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ¹ and R ⁴ are 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, R ¹ and R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ² and R ³ are 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, R ¹ , R ² and R ³ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ⁴ is 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, R ¹ , R ² and R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ³ is 2-methylpropyl or 2,2-dimethylpropyl. In another embodiment, R ¹ , R ³ and R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ² is 2- methylpropyl or 2,2-dimethylpropyl. In another embodiment, R ² , R ³ and R ⁴ are G-1, wherein R ^1A is F, and R ^1B and R ^1C are methyl or trifluoromethyl; and R ¹ is 2-methylpropyl or 2,2- dimethylpropyl.

In one embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or naphthyl substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ ;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or C ₁ -C ₃ alkyl;

R ¹ and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino;

R ² and R ⁴ are independently unsubstituted C ₁ -C ₆ alkyl; and R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, or the group -CH ₂ C(O)NHCH ₂ CF ₃ ; or R ⁵ and R ⁶ together with the atom(s) to which they are bonded form a C ₃ -C ₆ cyclic group.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or naphthyl substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, alkyl, haloalkyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heterocyclyl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S- heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ - C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or C ₁ -C ₃ alkyl; and

R ¹ and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ² and R ⁴ are independently unsubstituted C ₁ -C ₆ alkyl; and

R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl or the group -CH ₂ C(O)NHCH ₂ CF ₃ .

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ - C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ - C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, R ⁵ R ⁶ NC(O)-, phenyl, C ₃ - C ₆ cycloalkyl, C ₄ -C ₆ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, -O- C ₄ -C ₆ heterocyclyl or -S-C ₄ -C ₆ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, CN, NO ₂ , SF ₅ , alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ and R ³ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen;

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, CN, NO ₂ , SF ₅ , C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₃ - C ₆ cycloalkyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino, wherein each C ₃ -C ₆ cycloalkyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl; R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ and R ³ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl, -S- tetrazolyl or pyrrolidinyl, wherein each cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ and R ³ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ and R ³ are independently -CH ₂ CF(CH ₃ ) ₂ ; and

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In one embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or naphthyl substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ ;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or C ₁ -C ₃ alkyl;

R ² and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino;

R ¹ and R ³ are independently unsubstituted C ₁ -C ₆ alkyl; and

R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, or the group -CH ₂ C(O)NHCH ₂ CF ₃ ; or R ⁵ and R ⁶ together with the atom(s) to which they are bonded form a C ₃ -C ₆ cyclic group.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or naphthyl substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, alkyl, haloalkyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heterocyclyl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S- heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ - C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or C ₁ -C ₃ alkyl;

R ² and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ¹ and R ³ are independently unsubstituted C ₁ -C ₆ alkyl; and

R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl or the group -CH ₂ C(O)NHCH ₂ CF ₃ .

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ - C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ - C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ² and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, R ⁵ R ⁶ NC(O)-, phenyl, C ₃ - C ₆ cycloalkyl, C ₄ -C ₆ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, -O- C ₄ -C ₆ heterocyclyl or -S-C ₄ -C ₆ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, CN, NO ₂ , SF ₅ , alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ² and R ⁴ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen;

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, CN, NO ₂ , SF ₅ , C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₃ - C ₆ cycloalkyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino, wherein each C ₃ -C ₆ cycloalkyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ² and R ⁴ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen;

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl, -S- tetrazolyl or pyrrolidinyl, wherein each cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² and R ⁴ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ² and R ⁴ are independently -CH ₂ CF(CH ₃ ) ₂ ; and

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In one embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ ; R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or C ₁ -C ₃ alkyl; and

R ¹ and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino;

R ² and R ⁴ are independently unsubstituted C ₁ -C ₆ alkyl; and

R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, or the group -CH ₂ C(O)NHCH ₂ CF ₃ ; or R ⁵ and R ⁶ together with the atom(s) to which they are bonded form a C ₃ -C ₆ cyclic group.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, alkyl, haloalkyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heterocyclyl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ - C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or C ₁ -C ₃ alkyl;

R ¹ and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more aryl, heteroaryl, heterocyclyl or halogen;

R ² and R ⁴ are independently unsubstituted C ₁ -C ₆ alkyl; and

R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl or the group -CH ₂ C(O)NHCH ₂ CF ₃ .

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl or tetrazinyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ - C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more halogen , optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl or tetrazinyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, R ⁵ R ⁶ NC(O)-, phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₆ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, -O-C ₄ -C ₆ heterocyclyl or -S-C ₄ - C ₆ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, CN, NO ₂ , SF ₅ , alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ³ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen;

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl. In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently pyridinyl, pyrimidinyl, pyridazinyl, or pyrazinyl substituted with one or more substituents selected from the group consisting of halogen, CN, NO ₂ , SF ₅ , C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₃ -C ₆ cycloalkyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino, wherein each C ₃ -C ₆ cycloalkyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ and R ³ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl, -S- tetrazolyl or pyrrolidinyl, wherein each cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ³ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ and R ³ are independently -CH ₂ CF(CH ₃ ) ₂ ; and

R ² and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In one embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, thioamido, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN and -NO ₂ ;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or C ₁ -C ₃ alkyl;

R ² and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, halogen, hydroxy, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkoxyalkoxy, oxo, cyano, amino, alkylamino and dialkylamino;

R ¹ and R ³ are independently unsubstituted C ₁ -C ₆ alkyl; and

R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, or the group -CH ₂ C(O)NHCH ₂ CF ₃ ; or R ⁵ and R ⁶ together with the atom(s) to which they are bonded form a C ₃ -C ₆ cyclic group.

In another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, alkyl, haloalkyl, SF ₅ , R ⁵ S(O)-, R ⁵ S(O) ₂ -, R ⁵ C(O)-, R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , cycloalkyl, heterocyclyl, heteroaryl, -O-heteroaryl, -S-heteroaryl, -O-heterocyclyl or -S-heterocyclyl, wherein each cycloalkyl, heteroalkyl, aryl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ - C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or C ₁ -C ₃ alkyl;

R ² and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more aryl, heteroaryl, heterocyclyl or halogen;

R ¹ and R ³ are independently unsubstituted C ₁ -C ₆ alkyl; and

R ⁵ and R ⁶ are independently hydrogen, alkyl, haloalkyl or the group -CH ₂ C(O)NHCH ₂ CF ₃ .

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl or tetrazinyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ - C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and R ² and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen , optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl or tetrazinyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, R ⁵ R ⁶ NC(O)-, phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₆ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, -O-C ₄ -C ₆ heterocyclyl or -S-C ₄ - C ₆ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, CN, NO ₂ , SF ₅ , alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² and R ⁴ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen;

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently pyridinyl, pyrimidinyl, pyridazinyl, or pyrazinyl substituted with one or more substituents selected from the group consisting of halogen, CN, NO ₂ , SF ₅ , C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, C ₃ -C ₆ cycloalkyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino, wherein each C ₃ -C ₆ cycloalkyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² and R ⁴ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl, -S- tetrazolyl or pyrrolidinyl, wherein each cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholino, tetrahydropyran, tetrahydrofuran, piperidino or pyrrolidino is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ² and R ⁴ are independently -CH ₂ CX(CH ₃ ) ₂ wherein X is halogen; and

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ - C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² and R ⁴ are independently -CH ₂ CF(CH ₃ ) ₂ ; and

R ¹ and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ² are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl;

R ³ and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ³ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl;

R ¹ and R ² are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl;

R ¹ and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl;

R ² and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ² are -CH ₂ CF(CH ₃ ) ₂ ; and

R ³ and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ³ and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ¹ and R ² are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and R ² and R ³ -CH ₂ CF(CH ₃ ) ₂ ; and

R ¹ and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ² and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ , R ² and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl;

R ⁴ is 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ² and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl;

R ³ is 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ³ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl;

R ² is 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl. In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² , R ³ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl;

R ¹ is 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ² and R ³ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ⁴ is 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ² and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ³ is 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ³ and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ² is 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; R ² , R ³ and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ¹ is 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, -NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ -C ₆ heteroaryl, - O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ , R ² , R ³ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, aryl, heteroaryl or heterocyclyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently heteroaryl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ , R ² , R ³ and R ⁴ are each -CH ₂ CF(CH ₃ ) ₂ .

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ² are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ³ and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ³ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl; R ¹ and R ² are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ¹ and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl; R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ² and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R ² are -CH ₂ CF(CH ₃ ) ₂ ; and

R ³ and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ³ and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ¹ and R ² are independently 2-methylpropyl or 2,2-dimethylpropyl. In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² and R ³ -CH ₂ CF(CH ₃ ) ₂ ; and

R ¹ and R ⁴ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ and R4 -CH ₂ CF(CH ₃ ) ₂ ; and

R ² and R ³ are independently 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ² and R ³ are independently C ₁ -C ₆ alkyl substituted by one or more halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ⁴ is 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O- C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ² and R ⁴ are independently C ₁ -C ₆ alkyl substituted by halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ³ is 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O-C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ³ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ² is 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O-C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² , R ³ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl;

R ¹ is 2-methylpropyl or 2,2-dimethylpropyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuryl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ² and R ³ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ⁴ is 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ² and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ³ is 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ³ and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ² is 2-methylpropyl or 2,2-dimethylpropyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ² , R ³ and R ⁴ are -CH ₂ CF(CH ₃ ) ₂ ; and

R ¹ is 2-methylpropyl or 2,2-dimethylpropyl.

In another embodiment, the invention provides compounds of formula (I) wherein:

Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ - C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl, C ₁ - C ₃ haloalkyl, SF ₅ , R ⁵ R ⁶ NC(O)-, R ⁵ R ⁶ NC(O)NR ⁵ -, R ⁵ OC(O)-, R ⁵ C(O)O-, R ⁵ C(O)NR ⁶ -, -CN, - NO ₂ , phenyl, C ₃ -C ₆ cycloalkyl, C ₄ -C ₇ heterocyclyl, C ₅ -C ₆ heteroaryl, -O-C ₅ -C ₆ heteroaryl, -S-C ₅ - C ₆ heteroaryl, -O-C ₄ -C ₇ heterocyclyl or -S-C ₄ -C ₇ heterocyclyl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl; R ^a and R ^b may independently be hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R', R'', R''' and R'''' are each independently hydrogen or methyl;

R ¹ , R ² , R ³ and R ⁴ are independently C ₁ -C ₆ alkyl substituted by halogen, optionally substituted phenyl or an optionally substituted heteroaryl selected from the group consisting of thienyl, oxazolyl, isothiazolyl, 1,3-4-thiadazolyl, pyrazolyl, furyl, imidazolyl, pyrrolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and tetrazinyl; and

R ⁵ and R ⁶ are independently hydrogen, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl.

In yet another embodiment, the invention provides compounds of formula (I) wherein: Cy ¹ and Cy ² are independently phenyl or pyridyl substituted with one or more substituents selected from the group consisting of halogen, NO ₂ , SF ₅ , methyl, CF ₃ , OCF ₃ , cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl or pyrrolidinyl, wherein each cyclohexyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl or pyrrolidinyl is optionally further independently substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkoxy, C ₁ -C ₃ haloalkoxy, C ₁ -C ₃ alkylthio, C ₁ -C ₃ haloalkylthio, amino, C ₁ -C ₃ alkylamino, C ₁ -C ₃ dialkylamino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl;

R ^a and R ^b may independently be hydrogen, methyl or CF ₃ ;

R', R'', R''' and R'''' are each independently hydrogen or methyl; and

R ¹ , R ² , R ³ and R ⁴ are each -CH ₂ CF(CH ₃ ) ₂ .

In one embodiment, the invention provides compounds of formula (I) shown in Tables 2 to 39 below, wherein R’, R’’, R’’’ and R’’’’ are each independently hydrogen or C ₁ -C ₃ alkyl; and Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Tables 2 to 39 below. In the tables, Me indicates methyl.

Table 2: Compounds of formula (I), wherein Cy ¹ and Cy ² are unsubstituted phenyl and R ^a , R ^b , R ¹ to R ⁴ are as shown.

_38-42 ^{H CH} ₂ ^CMe ₂ ^{F CH} ₂ ^{-tBu CH} ₂ ^CMe ₂ ^{F CH} ₂ ^-tBu 3 _8-43 ^CH ₃ ^CH ₂ ^CMe ₂ ^{F iPr CH} ₂ ^CMe ₂ ^{F iPr}

3 _8-44 ^CH ₃ ^CH ₂ ^CMe ₂ ^{F nPr CH} ₂ ^CMe ₂ ^{F nPr}

3 _8-45 ^CH ₃ ^CH ₂ ^CMe ₂ ^{F sBu CH} ₂ ^CMe ₂ ^{F sBu}

3 _8-46 ^CH ₃ ^CH ₂ ^CMe ₂ ^{F tBu CH} ₂ ^CMe ₂ ^{F tBu}

CH ₂ -p- CH ₂ -p- 3 _8-47 ^CH ₃ ^CH ₂ ^CMe ₂ ^{F CH2CMe2F}

b _iphenyl biphenyl 3 _8-48 ^CH ₃ ^CH ₂ ^CMe ₂ ^{F CH} ₂ ^{-p-tBuPh CH} ₂ ^CMe ₂ ^{F CH} ₂ ^-p-tBuPh 3 _8-49 ^CH ₃ ^CH ₂ ^CMe ₂ ^{F CH} ₃ ^CH ₂ ^CMe ₂ ^{F CH} ₃

3 _8-50 ^{H CH} ₂ ^CMe ₂ ^{F iPr CH} ₂ ^CMe ₂ ^{F iPr}

38-51 CH ₃ CH ₂ CMe ₂ F CH ₂ CH ₂ CMe ₃ CH ₂ CMe ₂ F CH ₂ CH ₂ CMe ₃ 38-52 CH ₃ CH ₂ CMe ₂ F CH ₂ CH ₂ -iPr CH ₂ CMe ₂ F CH ₂ CH ₂ -iPr 38-53 CH ₃ CH ₂ -p-pyridyl CH ₂ -iPr CH ₂ -p-pyridyl CH ₂ -iPr 38-54 CH ₃ CH ₂ -p-pyridyl CH ₂ -tBu CH ₂ -p-pyridyl CH ₂ -tBu Particular embodiments of the compounds of the invention are further described in Tables 39-112 wherein the meaning of the variables Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as described for Tables 2-38, respectively, with the exception that R’, R’’, R’’’ and R’’’’ are each specifically defined below.

Table 39: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 2, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 40: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 3, and R’, R’’, R’’’ and R’’’ are each methyl.

Table 41: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 4, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 42: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 5, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 43: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 6, and R’, R’’, R’’’ and R’’’’ are each methyl. Table 44: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 7, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 45: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 8, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 46: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 9, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 47: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 10, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 48: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 11, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 49: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 12, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 50: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 13, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 51: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 14, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 52: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 15, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 53: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 16, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 54: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 17, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 55: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 18, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 56: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 19, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 57: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 20, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 58: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 21, and R’, R’’, R’’’ and R’’’’ are each methyl. Table 59: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 22, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 60: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 23, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 61: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 24, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 62: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 25, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 63: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 26, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 64: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 27, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 65: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 28, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 66: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 29, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 67: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 30, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 68: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 31, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 69: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 32, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 70: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 33, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 71: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 34, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 72: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 35, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 73: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 36, and R’, R’’, R’’’ and R’’’’ are each methyl. Table 74: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 37, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 75: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 38, and R’, R’’, R’’’ and R’’’’ are each methyl.

Table 76: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 2, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 77: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 3, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 78: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 4, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 79: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 5, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 80: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 6, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 81: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 7, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 82: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 8, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 83: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 9, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 84: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 10, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 85: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ² , R ³ and R ⁴ are as shown in Table 11, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 86: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 12, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 87: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 13, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 88: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 14, and R’, R’’, R’’’ and R’’’’ are each hydrogen. Table 89: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 15, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 90: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 16, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 91: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 17, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 92: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 18, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 93: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 19, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 94: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 20, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 95: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 21, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 96: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 22, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 97: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 23, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 98: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 24, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 99: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 25, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 100: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 26, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 101: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 27, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 102: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 28, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 103: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 29, and R’, R’’, R’’’ and R’’’’ are each hydrogen. Table 104: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 30, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 105: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 31, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 106: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 32, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 107: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 33, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 108: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 34, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 109: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 35, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 110: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 36, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 111: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 37, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Table 112: Compounds of formula (I), wherein Cy ¹ , Cy ² , R ^a , R ^b , R ¹ , R ² , R ³ and R ⁴ are as shown in Table 38, and R’, R’’, R’’’ and R’’’’ are each hydrogen.

Surprisingly, it has been found that substitution of the alkyl groups R ¹ , R ² , R ³ and R ⁴ , which are 2-methylpropyl groups in the parent cyclic depsipeptide PF1022 and also in emodepside, with certain groups improve the in vitro metabolic stability of the compounds and may also improve the activity of the compounds against endoparasites and ectoparasites. Furthermore, it has been surprisingly found that substitution of the compounds of formula (I) with certain Cy ¹ and/or Cy ² groups also significantly improves the in vitro metabolic stability of the compounds of the invention compared with PF1022 and emodepside. Thus, the compounds of the invention where the groups Cy ¹ and/or Cy ² and at least one of R ¹ , R ² , R ³ and R ⁴ are substituted with certain substituents have been found to have significantly improved metabolic stability and equal or significantly improved efficacy against endoparasites including Dirofilaria immitis microfilaria and/or L3 and L4 larvae and/or Haemonchus contortus larvae. In embodiments, the compounds of formula (I) with certain substituents will also exhibit improved activity against ectoparasites. It has also been surprisingly found that the spatial order of substitution of R ¹ to R ⁴ also has a significant impact on the activity of the compounds. For example it has been found that when the naturally-occurring 2-methylpropyl groups of PF1022A and emodepside represented by positions identified as R ¹ and R ³ in the compound of formula (I) are modified the activity of the compounds is significantly improved over compounds where the 2-methylpropyl groups at the positions R ² and R ⁴ are substituted.

The influence of certain substituents on one or more of R ¹ , R ² , R ³ and R ⁴ is also surprising. Thus, substitution of one or more of R ¹ , R ² , R ³ and R ⁴ with fluoro has been found to significantly improve the in vitro activity of the compounds of formula (I) on the motility of Haemonchus contortus larvae and Dirofilaria immitis microfilaria compared with unsubstituted compounds (e.g. PF1022 or analogs where Cy ¹ and/or Cy ² are substituted phenyl but R ¹ to R ⁴ are 2-methylpropyl) or compounds in which the naturally-occurring 2-methylpropyl groups of PF1022A and emodepside, represented by positions identified as R ¹ and R ³ in the compound of formula (I), are substituted with a methyl group. In addition, the substitution of R ¹ and R ³ groups with fluoro has been found to result in significantly improved in vitro activity against H. contortus larvae and D. immitis microfilaria compared with compounds substituted with fluoro at R ² or other combinations. It is apparent that the type of substitution in groups R ¹ , R ² , R ³ and R ⁴ as well as which of R ¹ , R ² , R ³ and R ⁴ are substituted have a significant influence on the activity of the compounds.

Scherkenbeck et al. (Bioorg. Med. Chem. Lett. 8 (1998), 1035-1040) described that the replacement of the N-methyl leucine residues for a series of related N-methylated amino acids such as isoleucine, valine, norvaline, alanine and phenylalanine resulted in nearly complete loss of anthelmintic efficacy following oral administration in sheep. Furthermore, the publication reported that modification of half of the N-methyl leucine residues with either methyl or n-propyl side chains also surprisingly resulted in significantly reduced activity. It was concluded that the (L)-N-methyl leucine residues in the cyclic depsipeptide PF1022A were a critical part of the pharmacophore and essential for in vivo activity.

Thus, it is surprising and unexpected that modification of the groups R ¹ to R ⁴ in the compound of formula (I), which correspond to the N-methyl leucine residues in PF1022A or emodepside, result in enhanced in vitro metabolic stability and/or improved activity compared with the compounds containing unmodified N-methyl leucine residues. It is also very surprising and unexpected that the compounds of formula (I) in which the alkyl groups represented by R ¹ and R ³ are substituted with certain groups exhibit significantly improved efficacy against endoparasites compared to compounds that are substituted with the same groups at R ² and R ⁴ or in other combinations. In addition, the inclusion of certain substituents in groups R ¹ to R ⁴ and Cy ¹ and Cy ² result in improved in vitro metabolic stability compared with unsubstituted compounds. It follows that an appropriate combination of the substitution at Cy ¹ and Cy ² and R ¹ to R ⁴ in the compounds of formula (I) results in significantly improved activity against endoparasites and improved metabolic stability in animals.

Furthermore, the substitution of the naturally-occurring 2-methylpropyl groups of PF1022A and emodepside, represented by positions R ¹ and R ³ in the compound of formula (I), with certain substituents, including fluoro and methyl, has been found to improve the in vitro permeability of the compounds. For example, compounds of formula (I) wherein Cy ¹ and Cy ² are either both unsubstituted phenyl or p-fluorophenyl groups and R ² and R ⁴ , respectively, are2- methylpropyl fluoro-substituted were found to have significantly improved permeability compared with the compounds where R ² and R ⁴ are unsubstituted 2-methylpropyl. Further, compounds where Cy ¹ and Cy ² are p-morpholino phenyl and R ² and R ⁴ are methyl-substituted 2- methylpropyl were found to have significantly improved permeability compared with emodepside (R ² and R ⁴ = 2-methylpropyl).

The characteristics described above for the compounds of formula (I) are expected to result in compounds with superior antiparasitic efficacy against endoparasites and ectoparasites in or on animals.

Stereoisomers and polymorphic forms

It will be appreciated by those of skill in the art that the compounds of the invention may exist and be isolated as optically active and racemic forms. Compounds having one or more chiral centers, including that at a sulfur atom, may be present as single enantiomers or diastereomers or as mixtures of enantiomers and/or diastereomers. For example, it is well known in the art that sulfoxide compounds may be optically active and may exist as single enantiomers or racemic mixtures. In addition, compounds of the invention may include one or more chiral centers, which results in a theoretical number of optically active isomers. Where compounds of the invention include n chiral centers, the compounds may comprise up to 2 ⁿ optical isomers. The present invention encompasses the specific enantiomers or diastereomers of each compound as well as mixtures of different enantiomers and/or diastereomers of the compounds of the invention that possess the useful properties described herein. The optically active forms can be prepared by, for example, resolution of the racemic forms by selective crystallization techniques, by synthesis from optically active precursors, by chiral synthesis, by chromatographic separation using a chiral stationary phase or by enzymatic resolution.

The compounds of present invention may also be present in different solid forms such as different crystalline forms or in the form of an amorphous solid. The present invention encompasses different crystalline forms as well as amorphous forms of the inventive compounds.

In addition, the compounds of the invention may exist as hydrates or solvates, in which a certain stoichiometric amount of water or a solvent is associated with the molecule in the crystalline form. The hydrates and solvates of the compounds of formula (I) are also the subject of the invention.

Salts

In addition to the neutral compounds of formula (I), salt forms of the compounds are also active against endoparasites. The term "veterinarily acceptable salt" is used throughout the specification to describe any salts of the compounds that are acceptable for administration for veterinary applications, and which provides the active compound upon administration.

In cases where compounds are sufficiently basic or acidic to form stable non-toxic acid or base salts, the compounds may be in the form of a veterinarily or agriculturally acceptable salt. Veterinarily acceptable salts include those derived from veterinarily or agriculturally acceptable inorganic or organic bases and acids. Suitable salts include those comprising alkali metals such as lithium, sodium or potassium, alkaline earth metals such as calcium, magnesium and barium. Salts comprising transition metals including, but not limited to, manganese, copper, zinc and iron are also suitable. In addition, salts comprising ammonium cations (NH ⁺

4 ) as well as substituted ammonium cations, in which one or more of the hydrogen atoms are replaced by alkyl or aryl groups are encompassed by the invention.

Salts derived from inorganic acids including, but not limited to, hydrohalide acids (HCl, HBr, HF, HI), sulfuric acid, nitric acid, phosphoric acid, and the like are particularly suitable. Suitable inorganic salts also include, but not limited to, bicarbonate, and carbonate salts. In some embodiments, examples of veterinarily and agriculturally acceptable salts are organic acid addition salts formed with organic acids including, but not limited to, maleate, dimaleate, fumarate, tosylate, methanesulfonate, acetate, citrate, malonate, tartarate, succinate, benzoate, ascorbate, ^-ketoglutarate, and ^-glycerophosphate. Of course, other acceptable organic acids may be used.

Alkali metal (for example, sodium, potassium or lithium) or alkaline earth metal (for example calcium) salts of the compounds can also be made by reacting a sufficiently acidic residue on the compounds with a hydroxide of the alkali metal or alkaline earth metal.

Veterinarily acceptable salts may be obtained using standard procedures well known in the art, for example by reacting a sufficiently basic compound such as an amine with a suitably acid functional group present in the compound, or by reacting a suitable acid with a suitably basic functional group on the compound of the invention.

Processes for the Preparation of Compounds of Formula (I):

The compounds of formula (I) may be prepared by processes adapted from those described in US Patent Nos. 5,514,773; 5,747,448; 5,874,530; 5,856,436; 6,033,879; 5,763,221; 6,329,338, 5,116,815; 6,468,966; 6,369,028; 5,777,075; and 5,646,244, all which are hereby incorporated by reference in their entirety. In addition, various synthetic methods for cyclic depsipeptides have been reported in the chemical literature (see Luttenberg et al., Tetrahedron 68 (2012), 2068-2073; Byung H. Lee, Tetrahedron Letters, 1997, 38 (5), 757-760; Scherkenbeck et al., Eur. J. Org. Chem., 2012, 1546-1553; Biosci. Biotech. Biochem., 1994, 58(6), 1193-1194; and Scherkenbeck et al., Tetrahedron, 1995, 51(31), 8459-8470) It will be understood by those skilled in the art that certain functional groups in the compounds and intermediates may be unprotected or protected by suitable protecting groups, as taught by Greene and Wuts, Protective Groups in Organic Synthesis, John Wiley and Sons, Inc., 4 ^th edition 2006. Further, it will be apparent to those skilled in the art that the compounds and intermediates may be isolated by standard aqueous work-up conditions and optionally purified. For example, the compounds or intermediates may be purified by chromatographic methods or crystallized to yield the desired product in suitable purity.

In one embodiment, the compounds of formula (I) where R ¹ , R ² , R ³ , R ⁴ , Cy ¹ and Cy ² are as defined above and R’, R’’, R’’’ and R’’’’ are methyl are prepared according to the general process described in Scheme 1 below: Scheme 1

1-7

1-8 P ₁ and P ₂ are amine and carboxylic acid protecting groups, respectively, commonly used in the art (see, for example, Greene and Wuts, Protective Groups in Organic Synthesis, John Wiley and Sons, Inc., 4th edition 2006) and R ¹ , R ² , R ³ , R ⁴ , Cy ¹ and Cy ² are as defined above.

Furthermore, the coupling of amines with carboxylic acids to form amides is well known in the art and standard reagents may be used in the coupling of a fragment with an unprotected amine with a second fragment having a free carboxylic acid group (see for example, Peptide Synthesis by Miklos Bodanszky and Miguel Ondetti, Interscience Publishers, 1966; Amino Acid and Peptide Synthesis, 2 ^nd Ed. By John Jones, Oxford University Press, 2002). The compounds may be prepared by solution phase synthesis or using solid-phase synthesis with polymeric supports. For example, the formation of amide bonds may be mediated by activating reagents such as carbodiimide reagents (e.g. dicyclohexyldiimide, diisopropyldiimide and (N-(3- Dimethylaminopropyl)-N’-ethylcarbodiimide · HCl) in combination with additives such as N- hydroxybenzotriazole (HOBt) and the like. In addition, the formation of amide bonds in the synthesis may be accomplished by using phosphonium reagents such as BOP (Benzotriazol-1- yloxy-tris (dimethylamino)- phosphonium hexafluorophosphate), PyBOP (Benzotriazol-1-yloxy- tripyrrolidino-phosphonium hexafluorophosphate), PyBrOP (Bromo-tripyrrolidino-phosphonium hexa- fluorophosphate) and the like. Other useful reagents for forming the amide bonds of the compounds of the invention are the so called aminium/uronium-imonium reagents such as TBTU/HBTU (2-(1H-Benzotriazol-1-yl)-N,N,N’,N’- tetramethylaminium tetrafluoroborate/ hexafluorophosphate), HATU (2-(7-Aza-1H-benzotriazol-1-yl)-N,N,N’,N’- tetramethylaminium hexafluorophosphate) and the like. These reagents and the methods employing these reagents for the preparation of amide bonds are well known in the art.

Veterinary compositions:

The compounds of formula (I) and compositions comprising the compounds are useful for the prevention and treatment of parasitic infestations/infections in animals. The compositions of the invention comprise an effective amount of at least one cyclic depsipeptide compound of formula (I), or a veterinarily acceptable salt thereof, in combination with a veterinarily acceptable carrier or diluent and optionally other non-active excipients. The compositions may be in a variety of solid and liquid forms which are suitable for various forms of application or administration to an animal. For example, the veterinary compositions comprising the inventive compounds may be in formulations suitable for oral administration, injectable administration, including subcutaneous and parenteral administration, and topical administration (e.g. spot-on or pour-on), dermal or subdermal administration. The formulations are intended to be administered to an animal including, but not limited to, mammals, birds and fish. Examples of mammals include but are not limited to humans, cattle, sheep, goats, llamas, alpacas, pigs, horses, donkeys, dogs, cats and other livestock or domestic mammals. Examples of birds include turkeys, chickens, ostriches and other livestock or domestic birds. The use of the compounds of formula (I) to protect companion animals such as dogs and cats from endoparasites is particularly useful.

As discussed above, the compositions of the invention may be in a form suitable for oral use (see, e.g., U.S. Patent No. 4,564,631, which is hereby incorporated by reference in its entirety), dietary supplements, troches, lozenges, chewables, tablets, hard or soft capsules, bolus, emulsions, aqueous or oily suspensions, aqueous or oily solutions, oral drench formulations, dispersible powders or granules, premixes, syrups or elixirs, enteric formulations or pastes. Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more sweetening agents, bittering agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations.

Tablets may contain the active ingredient in admixture with non-toxic, pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be, for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example, magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated by the technique described in U.S. Patent Nos. 4,256,108; 4,166,452; and 4,265,874 (all incorporated herein by reference in their entirety) to form osmotic therapeutic tablets for controlled release.

Oral formulations include hard gelatin capsules, wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin. Capsules may also be soft gelatin capsules, wherein the active ingredient is mixed with water or miscible solvents such as propylene glycol, PEGs and ethanol, or an oil medium, for example peanut oil, liquid paraffin, or olive oil.

In one embodiment, the compounds of formula (I) may be administered in chewable tablet compositions or soft chewable compositions such as those described in US 2013/0203692 A1, US 2010/0087492, US 2006/0222684, US 2004/0151759, US 7955632, all incorporated herein by reference. The veterinary compositions may be in the form of a soft chewable formulation (“soft chew”) which is palatable and acceptable to the animal. In addition to the active ingredient(s), the soft chews of the invention may include one or more of the following components: a solvent or mixture of solvents, one or more fillers, one or more binders, one or more surfactants, one or more humectants, one or more lubricants, one or more disintegrants, one or more colorants, one or more antimicrobial agents, one or more antioxidants, one or more pH modifiers and one or more flavoring agents.

Solvents that may be used in the compositions of the invention include, but are not limited to, various grades of liquid polyethylene glycol (PEG) including PEG 200, PEG 300, PEG 400 and PEG 540; propylene carbonate; propylene glycol; triglycerides including, but not limited to caprylic/capric triglyceride, caprylic/capric/linoleic triglyceride (e.g. MIGLYOL ^® 810 and 812, caprylic/capric/succinic triglyceride, propylene glycol dicaprylate/dicaprate, and the like; water, sorbitol solution, glycerol caprylate/caprate and polyglycolized glycerides (GELUCIRE ^® ), or a combination thereof.

Various fillers known in the art may be used in the soft chewable compositions of the invention. Fillers include, but are not limited to, corn starch, pre-gelatinized corn starch, soy protein fines, corn cob, and corn gluten meal, and the like. In some embodiments, a combination of two or more fillers may be used in the compositions.

Binders that may be used in the compositions of the invention include, but are not limited to, polyvinylpyrrolidone (e.g. Povidone), cross-linked polyvinylpyrrolidone (Crospovidone), polyethylene glycols of various grades including PEG 3350, PEG 4000, PEG 6000, PEG 8000 and even PEG 20,000, and the like; co-polymers of vinylpyrrolidone and vinyl acetate (e.g. Copovidone) such as the product sold by BASF by the tradename Kollidon ^® VA 64 and the like; starch such as potato starch, tapioca starch or corn starch; molasses, corn syrup, honey, maple syrup and sugars of various types; or a combination of two or more binders. Humectants that may be used in the compositions include, but are not limited to, glycerol (also referred to herein as glycerin), propylene glycol, cetyl alcohol and glycerol monostearate, and the like. Polyethylene glycols of various grades may also be used as humectants.

Surfactants may be present in the composition to improve their solubility and absorption after ingestion. Surfactants are typically present in a concentration of about 1 to 10% (w/w), more typically about 1 to about 5% (w/w). Examples of surfactants that may be used in the compositions include, but are not limited to, glyceryl monooleate, polyoxyethylene sorbitan fatty acid esters, sorbitan esters including sorbitan monooleate (Span ^® 20), polyvinyl alcohol, polysorbates including polysorbate 20 and polysorbate 80, d- ^-tocopheryl polyethylene glycol 1000 succinate (TPGS), sodium lauryl sulfate, co-polymers of ethylene oxide and propylene oxide (e.g. poloxamers such as LUTROL ^® F87 and the like), polyethylene glycol castor oil derivatives including polyoxyl 35 castor oil (Cremophor ^® EL), polyoxyl 40 hydrogenated castor oil (Cremophor ^® RH 40), polyoxyl 60 hydrogenated castor oil (Cremophor ^® RH60); propylene glycol monolaurate (LAUROGLYCOL ^® ); glyceride esters including glycerol caprylate/caprate (CAPMUL ^® MCM), polyglycolized glycerides (GELUCIRE ^® ), PEG 300 caprylic/capric glycerides (Softigen ^® 767), PEG 400 caprylic/capric glycerides (Labrasol ^® ), PEG 300 oleic glycerides (Labrafil ^® M-1944CS), PEG 300 linoleic glycerides (Labrafil ^® M-2125CS); polyethylene glycol stearates and polyethylene glycol hydroxy stearates including polyoxyl 8 stearate (PEG 400 monostearate), polyoxyl 40 stearate (PEG 1750 monostearate, and the like.

The inventive formulations may contain other inert ingredients such as antioxidants, preservatives, or pH stabilizers. These compounds are well known in the formulation art. Antioxidants may be added to the compositions of the invention to inhibit degradation of the active agents. Suitable antioxidants include, but are not limited to, alpha tocopherol, ascorbic acid, ascrobyl palmitate, fumaric acid, malic acid, sodium ascorbate, sodium metabisulfate, n- propyl gallate, BHA (butylated hydroxy anisole), BHT (butylated hydroxy toluene) monothioglycerol and the like.

The compositions of the invention may also include one or more lubricants and/or processing aids. In some cases, the lubricant/processing aid may also behave as a solvent, and accordingly, there some of the components of the inventive compositions may have dual functions. Lubricants/processing aids include, but are not limited to polyethylene glycols of various molecular weight ranges including PEG 3350 (Dow Chemical) and PEG 4000, corn oil, mineral oil, hydrogenated vegetable oils (STEROTEX or LUBRITAB), peanut oil and/or castor oil.

Many flavoring agents may be used in the compositions of the invention to improve the palatability of the oral veterinary formulations. Preferred flavoring agents are those that are not derived from animal sources. In various embodiments, flavoring components derived from fruit, meat (including, but not limited to pork, beef, chicken, fish, poultry, and the like), vegetable, cheese, bacon, cheese-bacon and/or artificial flavorings may be used. A flavoring component is typically chosen based upon consideration related to the organism that will be ingesting the soft chew. For example, a horse may prefer an apple flavoring component, while a dog may prefer a meat flavoring component. Although flavoring components derived from non-animal sources are preferred, in some embodiments, natural flavors containing beef or liver extracts, etc., may be used such as braised beef flavor artificial powdered beef flavor, roast beef flavor and corned beef flavor among others.

In another embodiment of the invention, the active composition may be administered via a drench, and may be administered either topically or orally. Drench formulations are those in which the liquid-containing compositions of the invention are administered to the mouth or throat of the animal, or poured onto the skin or coat of the animal.

The compositions of the invention may also be in the form of oil-in-water or water-in-oil emulsions. The oily phase maybe a vegetable oil, for example, olive oil or arachis oil, or a mineral oil, for example, liquid paraffin or mixtures of these. Suitable emulsifying agents include naturally-occurring phosphatides, for example, soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, for example, sorbitan monoleate, and condensation products of the said partial esters with ethylene oxide, for example, polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening agents, bittering agents, flavoring agents, and/or preservatives.

In one embodiment, the composition of the invention may be in the form of a microemulsion. Microemulsions are well suited as the liquid carrier vehicle. Microemulsions are quaternary systems comprising an aqueous phase, an oily phase, a surfactant and a cosurfactant. They are translucent and isotropic liquids.

Microemulsions are composed of stable dispersions of microdroplets of the aqueous phase in the oily phase or conversely of microdroplets of the oily phase in the aqueous phase. The size of these microdroplets may be less than 200 nm (1000 to 100,000 nm for emulsions). The interfacial film may be composed of an alternation of surface-active (SA) and co-surface- active (Co-SA) molecules which, by lowering the interfacial tension, allows the microemulsion to be formed spontaneously.

In one embodiment of the oily phase, the oily phase may be formed from mineral or vegetable oils, from unsaturated polyglycosylated glycerides or from triglycerides, or alternatively from mixtures of such compounds. In one embodiment of the oily phase, the oily phase may be comprised of triglycerides; in another embodiment of the oily phase, the triglycerides are medium-chain triglycerides, for example C ₈ -C ₁₀ caprylic/capric triglyceride. In another embodiment of the oily phase may represent a % v/v range of about 2 to about 15%; about 7 to about 10%; and about 8 to about 9% v/v of the microemulsion.

The aqueous phase may include, for example water or glycol derivatives, such as propylene glycol, glycol ethers, polyethylene glycols or glycerol. In one embodiment, the glycol may be propylene glycol, diethylene glycol monoethyl ether, dipropylene glycol monoethyl ether or mixtures thereof. Generally, the aqueous phase will represent a proportion from about 1 to about 4% v/v in the microemulsion.

Surfactants for the microemulsion may include diethylene glycol monoethyl ether, dipropyelene glycol monomethyl ether, polyglycolyzed C ₈ -C ₁₀ glycerides or polyglyceryl-6 dioleate. In addition to these surfactants, the cosurfactants may include short-chain alcohols, such as ethanol and propanol.

Some compounds are common to the three components discussed above, i.e., aqueous phase, surfactant and cosurfactant. However, it is well within the skill level of the practitioner to use different compounds for each component of the same formulation. In one embodiment for the amount of surfactant/cosurfactant, the cosurfactant to surfactant ratio will be from about 1/7 to about 1/2. In another embodiment for the amount of cosurfactant, there will be from about 25 to about 75% v/v of surfactant and from about 10 to about 55% v/v of cosurfactant in the microemulsion.

Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example, atachis oil, olive oil, sesame oil or coconut oil, or in mineral oil such as liquid paraffin. The oily suspensions may contain a thickening agent, for example, beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as sucrose, saccharin or aspartame, bittering agents, and flavoring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid, or other known preservatives.

Aqueous suspensions may contain the active material in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients include suspending agents, for example, sodium carboxymethylcellulose, methylcellulose, hydroxy-propylmethylcellulose, sodium alginate, polvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents include naturally-occurring phosphatide, for example lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example, heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide, with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl, p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents and/or bittering agents, such as those set forth above.

Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water may provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example, sweetening, bittering, flavoring and coloring agents, may also be present.

Syrups and elixirs may be formulated with sweetening agents, for example, glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative, flavoring agent(s) and/or coloring agent(s).

In another embodiment of the invention, the composition may be in paste form. Examples of embodiments in a paste form include, but are not limited to, those described in U.S. Patent Nos. 6,787,342 and 7,001,889 (each of which are incorporated herein by reference). In addition to the compounds of the invention, the paste may further contain fumed silica; a viscosity modifier; a carrier; optionally, an absorbent; and optionally, a colorant, stabilizer, surfactant, or preservative. In one embodiment of the formulation, the formulation may be a paste containing the compounds of the invention, fumed silica, a viscosity modifier, an absorbent, a colorant; and a hydrophilic carrier which is triacetin, a monoglyceride, a diglyceride, or a triglyceride.

The paste may also include a viscosity modifier. Suitable viscosity modifiers include, but are not limited to, polyethylene glycols (PEG) including, but not limited to, PEG 200, PEG 300, PEG 400, PEG 600; monoethanolamine, triethanolamine, glycerol, propylene glycol, polyoxyethylene (20) sorbitan mono-oleate (polysorbate 80 or Tween 80), or poloxamers (e.g., Pluronic L 81); an absorbent such as magnesium carbonate, calcium carbonate, starch, and cellulose and its derivatives; and a colorant including, but not limited to, titanium dioxide iron oxide, or FD&C Blue #1 Aluminum Lake.

In some embodiments, the compositions may be in the form of a sterile injectable aqueous or oleagenous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example, as a solution in 1,3-butane diol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. Cosolvents such as ethanol, propylene glycol, glycerol formal or polyethylene glycols may also be used. Preservatives, such as phenol or benzyl alcohol, may be used.

In addition, sterile, fixed oils may be conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

Topical, dermal and subdermal formulations may include, by way of non-limiting example, emulsions, creams, ointments, gels, pastes, powders, shampoos, pour-on formulations, ready-to-use formulations, spot-on solutions and suspensions, dips and sprays. Topical application of an inventive compound or of a composition including at least one inventive compound among active agent(s) therein, in the form of a spot-on, spray-on or pour-on composition, may allow for the inventive composition to be absorbed through the skin to achieve systemic levels, distributed through the sebaceous glands or on the surface of the skin achieving levels throughout the coat. When the compound is distributed through the sebaceous glands, they may act as a reservoir, whereby there may be a long-lasting effect (up to several months) effect. Spot-on formulations are typically applied in a localized region which refers to an area other than the entire animal. In one embodiment, the location may be between the shoulders. In another embodiment it may be a stripe, e.g. a stripe from head to tail of the animal.

Pour-on formulations are described in U.S. Patent No. 6,010,710, also incorporated herein by reference. Pour-on formulations may be advantageously oily, and generally comprise a diluent or vehicle and also a solvent (e.g. an organic solvent) for the active ingredient if the latter is not soluble in the diluent.

Organic solvents that can be used in the invention include, but are not limited to, acetyltributyl citrate, fatty acid esters such as the dimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzyl alcohol, ethyl alcohol, butyl diglycol, dimethylacetamide, dimethylformamide, dimethyl sulfoxide, dipropylene glycol n-butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol, 2-pyrrolidone (e.g. N-methylpyrrolidone), diethylene glycol monoethyl ether, ethylene glycol, triacetin, C ₁ -C ₁₀ esters of carboxylic acids such as butyl or octyl acetate, and diethyl phthalate, or a mixture of at least two of these solvents.

The solvent will be used in proportion with the concentration of the active agent compound and its solubility in this solvent. It will be sought to have the lowest possible volume. The vehicle makes up the difference to 100%.

A vehicle or diluent for the formulations may include dimethyl sulfoxide (DMSO), glycol derivatives such as, for example, propylene glycol, glycol ethers, polyethylene glycols or glycerol. As vehicle or diluent, mention may also be made of plant oils such as, but not limited to soybean oil, groundnut oil, castor oil, corn oil, cotton oil, olive oil, grape seed oil, sunflower oil, etc.; mineral oils such as, but not limited to, petrolatum, paraffin, silicone, etc.; aliphatic or cyclic hydrocarbons or alternatively, for example, medium-chain (such as C ₈ to C ₁₂ ) triglycerides.

In another embodiment of the invention, an emollient and/or spreading and/or film- forming agent may be added. In one embodiment, the emollient and/or spreading and/or film- forming agent may be:

(a) polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinyl acetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol, polyoxyethylenated sorbitan esters; lecithin, sodium carboxymethylcellulose, silicone oils, polydiorganosiloxane oils (such as polydimethylsiloxane (PDMS) oils), for example those containing silanol functionalities, or a 45V2 oil,

(b) anionic surfactants such as alkaline stearates, sodium, potassium or ammonium stearates; calcium stearate, triethanolamine stearate; sodium abietate; alkyl sulphates (e.g. sodium lauryl sulphate and sodium cetyl sulphate); sodium dodecylbenzenesulphonate, sodium dioctylsulphosuccinate; fatty acids (e.g. those derived from coconut oil),

(c) cationic surfactants include water-soluble quaternary ammonium salts of formula N ⁺ R'R"R"'R"", Y- in which the radicals R are optionally hydroxylated hydrocarbon radicals and Y- is an anion of a strong acid such as the halide, sulphate and sulphonate anions; cetyltrimethylammonium bromide is among the cationic surfactants which can be used,

(d) amine salts of formula N ⁺ HR'R"R'" in which the radicals R are optionally hydroxylated hydrocarbon radicals; octadecylamine hydrochloride is among the cationic surfactants which can be used,

(e) nonionic surfactants such as sorbitan esters, which are optionally polyoxyethylenated (e.g. polysorbate 80), polyoxyethylenated alkyl ethers; polyoxypropylated fatty alcohols such as polyoxypropylene-styrol ether; polyethylene glycol stearate, polyoxyethylenated derivatives of castor oil, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids, copolymers of ethylene oxide and propylene oxide, (f) amphoteric surfactants such as the substituted lauryl compounds of betaine; or (g) a mixture of at least two of these agents.

In one embodiment of the amount of emollient, the emollient used may be in a proportion of from about 0.1 to 50% or 0.25 to 5%, by volume. In another embodiment, the emollient used may be in a proportion of from about 0.1% to about 30%, about 1% to about 30%, about 1% to about 20%, or about 5% to about 20% by volume.

In another embodiment of the invention, the composition may be in ready-to-use solution form as is described in U.S. Patent No.6,395,765, incorporated herein by reference. In addition to the compounds of the invention, the ready-to-use solution may contain a crystallization inhibitor and an organic solvent or a mixture of organic solvents. In some embodiments, water may be included with the organic solvent. In various embodiments of the invention, the compositions may include a crystallization inhibitor in an amount of about 1 to about 50% (w/v) or about 5 to about 40% (w/v) based on the total weight of the formulation. In other embodiments, the amount of crystallization inhibitor in the inventive formulations may be about 1% to about 30%, about 5% to about 20%, about 1% to about 15%, or about 1% to about 10% (w/w). The type of crystallization inhibitor used in the inventive formulations is not limited as long as it functions to inhibit crystallization of the active or inactive agents from the formulation. For example, in certain embodiments of the invention, a solvent or co-solvent of the formulation may also function as a crystallization inhibitor if it sufficiently inhibits the formation of crystals from forming over time when the formulation is administered.

Crystallization inhibitors which are useful for the invention include, but are not limited to:

(a) polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinyl acetate and vinylpyrrolidone, polyethylene glycols, benzyl alcohol, dimethylformamide, dimethylacetamide, dimethylsulfoxide, 2-pyrrolidone, N-methylpyrrolidone, mannitol, glycerol, sorbitol or polyoxyethylenated esters of sorbitan; lecithin or sodium carboxymethylcellulose; or acrylic derivatives, such as acrylates or methacrylates or polymers or copolymers thereof, polyethyleneglycols (PEG) or polymers containing polyethyleneglycols, such as glycofurol and the like, and others;

(b) anionic surfactants, such as alkaline stearates (e.g. sodium, potassium or ammonium stearate); calcium stearate or triethanolamine stearate; sodium abietate; alkyl sulphates, which include but are not limited to sodium lauryl sulphate and sodium cetyl sulphate; sodium dodecylbenzenesulphonate or sodium dioctyl sulphosuccinate; or fatty acids (e.g. coconut oil);

(c) cationic surfactants, such as water-soluble quaternary ammonium salts of formula N ⁺ R'R''R'"R""Y¯, in which the R radicals are identical or different optionally hydroxylated hydrocarbon radicals and Y¯ is an anion of a strong acid, such as halide, sulphate and sulphonate anions; cetyltrimethylammonium bromide is one of the cationic surfactants which can be used;

(d) amine salts of formula N ⁺ HR'R''R'", in which the R radicals are identical or different optionally hydroxylated hydrocarbon radicals; octadecylamine hydrochloride is one of the cationic surfactants which can be used; (e) non-ionic surfactants, such as optionally polyoxyethylenated esters of sorbitan, e.g. Polysorbate 80, or polyoxyethylenated alkyl ethers; polyethylene glycol stearate, polyoxyethylenated derivatives of castor oil, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids or copolymers of ethylene oxide and of propylene oxide;

(f) amphoteric surfactants, such as substituted lauryl compounds of betaine;

(g) a mixture of at least two of the compounds listed in (a)-(f) above; or

(h) an organic solvent or mixture of solvents which inhibit the formation of crystals or amorphous solid after the formulation is administered.

In one embodiment of the crystallization inhibitor, a crystallization inhibitor pair will be used. Such pairs include, for example, the combination of a film-forming agent of polymeric type and of a surface-active agent. These agents will be selected from the compounds mentioned above as crystallization inhibitor.

In some embodiments, the organic solvent(s) may have a dielectric constant of between about 10 and about 35 or between about 20 and about 30. In other embodiments, the organic solvent may have a dielectric constant of between about 10 and about 40 or between about 20 and about 30. The content of this organic solvent or mixture of solvents in the overall composition is not limited and will be present in an amount sufficient to dissolve the desired components to a desired concentration. As discussed above, the organic solvent may also function as a crystallization inhibitor in the formulation.