Anthelmintic pyrrolopyridazine compounds

Abstract

The present invention relates to formula (I): JPEG2024540166000227.jpg4987(I) or salts thereof, compositions comprising these compounds, and methods for treating, controlling and / or preventing parasitic infestations and / or infections in an animal in need thereof by administering to said animal an effective amount of these compounds.

Description

[Technical field]

[0001] This patent application relates to novel antiparasitic compounds, compositions containing the compounds, and methods of using the compounds to prevent, treat and / or control parasites harmful to animals and humans. CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 263,367, filed November 1, 2021, which is incorporated by reference herein in its entirety. Incorporation by Reference All references cited herein are hereby incorporated by reference in their entirety. [Background technology]

[0002] Animals, such as mammals and birds, are often susceptible to external infestations of parasitic organisms. These parasites may be ectoparasites, such as fleas and ticks. Animals and humans also suffer from endoparasitic infections, including, for example, helminthiasis, most frequently caused by a group of parasitic worms called nematodes or roundworms. These parasites cause serious economic losses in pigs, sheep, horses, and cattle, and affect companion animals (such as cats and dogs) and poultry. Endoparasites occur in the gastrointestinal tract of animals and humans, for example those from the genera Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Toxocara, Toxascaris, Trichuris and Enterobius. Other parasites found in the blood or other tissues and organs include filarial worms and extraintestinal stages of Strongyloides and Trichinella.

[0003] A type of endoparasite that causes serious harm to mammals is Dirofilaria immitis (dog heartworm), also known as filaria. 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, can also be infected. Heartworms infect the pulmonary arteries of host mammals, where they go through several life stages before becoming adult worms. The worms require a mosquito as an intermediate host to complete their life cycle. The period between initial infection in a dog caused by a mosquito bite and the maturation of worms living in the heart and pulmonary arteries to adulthood is 6-7 months in dogs, and is called the "incubation period." L3 larvae migrate to the tip of the mosquito's mouthparts (lips) while the mosquito is feeding, detach from the mosquito, and are deposited on the dog's skin, where they then migrate to the host through the bite wound. Most L3 larvae molt into the fourth stage larvae (L4) in the dog's subcutaneous tissue within 1-3 days after infection. They then migrate to the chest and abdominal muscles, where they molt into the fifth stage (L5, immature adult) 45-60 days after infection. These immature filariae then invade the bloodstream and are transported through the heart to settle in the pulmonary artery between 75-120 days after infection. Approximately 7 months after infection, Dirofilaria immitis adult worms reach maturity and reproduce sexually in the pulmonary artery and right ventricle. Male adult worms are approximately 15 cm long, while female adult worms are approximately 25 cm long, and their normal life span as adults is calculated to be about 5 years.

[0004] Heartworm infection is a severe and life-threatening disease. Canine heartworm infection is preventable, and preventive treatment is a priority in heartworm-endemic areas. Treatment of mature heartworm infection with adulticides (e.g., melarsomine dihydrochloride) is costly and can have severe, harmful side effects, therefore prophylaxis by monthly administration of drugs that interrupt larval development is widely used. The goal of commercially available preventive treatments in dogs with heartworm disease is to prevent the parasite from developing into adult heartworms by interrupting the life cycle of Dirofilaria immitis after infection.

[0005] Macrocyclic lactones (MLs, e.g., ivermectin, eprinomectin, milbemycin oxime, moxidectin, and selamectin) are the most commonly used chemoprophylaxis agents, administered monthly or at 6-month intervals. These drugs have been shown to be effective against the third stage (L3) as well as the mature fourth stage (L4) of Dirofilaria immitis infections deposited by mosquitoes. When administered monthly, MLs kill L3 and L4 larvae acquired within the previous 30 days, thus preventing disease caused by adult worms. MLs may also be used monthly in infected dogs to inhibit reproduction in adult worms and eliminate microfilariae, thus reducing transmission and gradually reducing adult worms (Vet. Parasitol. 2005 Oct 24 133(2-3) 197-206).

[0006] In recent years, there have been reports of an increasing number of cases of lack of efficacy (LOE), where dogs have progressed to mature heartworm infection despite monthly prophylactic dosing with macrocyclic lactone drugs. For example, Atkins et al. (Vet. Parasitol. 206 (2014) 106-113) have reported a recent increase in the number of cases of dogs with positive heartworm antigen tests while receiving heartworm preventive drugs, suggesting that some populations of Dirofilaria immitis have evolved selective resistance to heartworm preventive drugs (Blagburn et al., “Evidence of genetic selection following treatment of heartworm-infected, microfilaremic dog with increasing dosages of ivermectin,” 58 thannual meeting of American Association of Veterinary Parasitologists, p. 64, 20-23 July, 2013 American Heartworm Society, 2010. Heartworm Preventive Resistance. Is it Possible, vol. 37. See also Bulletin of the American Heartworm Society, pp. 5.). Bowman also reviewed various studies from peer-reviewed journals in which LOE was observed for macrocyclic lactone treatments and reported to the Center for Veterinary Medicine (CVM) of the U.S. Food and Drug Administration (Bowman, Parasites & Vectors 2012, 5:138). Pulaski et al. described the establishment of macrocyclic lactone-resistant Dirofilaria immitis isolates in experimentally infected dogs (Pulaski et al., Parasites & Vectors 2014, 7:494). Similarly, Snyder et al. reported a controlled laboratory study with recent isolates of Dirofilaria immitis in which treatment with ivermectin and milbemycin oxime did not prevent maturation of inoculated L3 stage larvae. Blagburn et al. described a comparison of four commercially available prophylactic heartworm treatments against the MP3 laboratory strain of Dirofilaria immitis, with three of the four products failing to prevent infection with adult heartworms (Blagburn et al., Veterinary Parasitology, 2011, 176, 189-194).Further evidence of macrocyclic lactone-resistant isolates of Dirofilaria immits is reported in Bourguinat et al., Veterinary Parasitology, 2011, 181, 388-392; Geary et al., Topics in Companion Animal Medicine, 2011, vol. 26, no. 4, p. 187; Trends in Parasitology, October 2004, vol. 20, no. 10, p. 477; Bourguinat et al., Veterinary Parasitology, 2011, 176, p. 374-381. Furthermore, WO2016 / 161369 describes in the examples a study in which dogs infected with L3 stage Dirofilaria immitis of JYD-34 isolate were treated with ivermectin oral solution, Profender® tablets (emodepside + praziquantel) or a combination of ivermectin oral solution and Profender® tablets at two doses. The ivermectin and Profender® tablet groups had less than 50% efficacy, and the low dose ivermectin + Profender® tablet group had only 81% efficacy. Thus, there is a constant need to develop new anthelmintics with improved activity against Dirofilaria immitis and other endoparasites.

[0007] WO2017 / 178416A1 provides pyrazolopyrimidine derivatives for controlling, treating and / or preventing helminths. This publication describes anthelmintic compounds having different 5-6 fused nitrogen-containing heteroaryl cores. WO2018 / 197401A1 provides bicyclic pyrazole derivatives for controlling, treating and / or preventing helminths. WO2018 / 087036A1 provides quinolone-3-carboxamide derivatives for controlling, treating and / or preventing helminths. WO2019 / 025341 provides quinoline compounds for treating, controlling and / or preventing helminth infections, and WO2019 / 002132A1 describes azaquinoline derivatives for controlling, treating and / or preventing helminths. WO2019 / 215182A1 also describes quinoline derivatives for treating and controlling helminth infections.

[0008] WO2020 / 083971A2 describes additional carboxamide compounds substituted with bicyclic ring systems for treating and controlling parasitic infections. WO2021 / 204930 describes substituted fused azines containing bicyclic nitrogen-containing bicyclic ring systems that have anthelmintic properties. WO2021 / 018839A1 describes isoquinoline derivatives for use in the treatment of parasitic infections; WO2019 / 115768A1 describes methods for preparing anthelmintic 4-amino-quinoline-3-carboxamide derivatives. WO2020 / 131629A1, WO2020 / 131631A1 and WO2020 / 247747A1 describe bicyclic derivatives that are useful for controlling endoparasites, including filariasis, in warm-blooded animals. WO2021 / 122906A1 describes anthelmintic compounds including azaindole compounds, and WO2021 / 122911A1 describes quinoline compounds that are useful for treating diseases caused by helminths, such as Dirofilaria immitis.

[0009] WO2020 / 014068A1 describes anthelmintic heterocyclic compounds with a bicyclic pyrazolo[1,5-a]pyridine ring system core that have been found to be active against Dirofilaria immitis. The pyrazolo[1,5-a]pyridine ring system of the compounds described in this publication is a 5-6 fused ring system with two nitrogen atoms, one at the 5-6 ring junction and the other in a 5-membered ring. WO2020 / 191091A1 describes aza-benzothiophene and aza-benzofuran compounds that are useful for the control or prevention of parasitic infections, including infections by Dirofilaria immitis. WO2022 / 106469A2 describes N-(2,3-dihydro-1,4-benzoxazin-4-yl)-3-isopropyl-7-(2,3,5-trifluorophenyl)benzo-thiophene-2-carboxamide derivatives and similar compounds for treating filarial infections. WO2022 / 117783A1 describes bicyclic compounds of formula (I) and (I') disclosed for treating and / or controlling endoparasitic infections in warm-blooded animals.

[0010] WO2022 / 122987A1 describes anthelmintic compounds containing a pyridine structure for treating filarial disease caused by Dirofilaria immitis. WO2022 / 122988A1 describes anthelmintic compounds containing a thienopyridine structure for treating filarial disease caused by Dirofilaria immitis. WO2022 / 152918A1 describes azaquinazoline derivatives for use in the treatment or prevention of Dirofilaria immitis infection in a mammal. Summary of the Invention

[0011] The present application provides novel anthelmintic and antiparasitic pyrrolopyridazine heterocyclic compounds with improved activity against endoparasites. The present application is also directed to compositions comprising the compounds, methods and uses of the compounds for eradicating, controlling and / or preventing parasitic infections and / or infestations in animals, including humans. The compounds may be administered to animals, particularly mammals, fish and birds, to treat, control and / or prevent parasitic infections.

[0012] An embodiment of the present invention is a compound of formula (I): [ka] (I) or a salt thereof. 1 , R 1’ , R 2 , R 3 , R 4 , Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , L, Q, W, W 1 , Z and q are defined herein and the dashed bond ( [ka] ) indicates a single bond or a double bond)

[0013] The present invention also includes compositions comprising a compound of formula (I) or a salt thereof and a pharma- ceutically acceptable carrier. The compounds and compositions of the present invention may be administered to animals, particularly mammals, fish and birds, to prevent, control and / or treat parasitic infections in the animals. In particular, the compounds and compositions of the present invention may be administered to cats, dogs, horses, chickens, pigs, sheep and cows to substantially rid these hosts of endoparasites.

[0014] In certain embodiments, the compounds of formula (I) and compositions comprising the compounds are effective against endoparasites, such as filariae (e.g., Dirofilaria immitis), and nematodes, including but not limited to, hookworms, whipworms, and roundworms, of the gastrointestinal tract of animals and humans. In certain embodiments, the compounds of formula (I) and compositions comprising the compounds are effective against Dirofilaria immitis (filariasis) isolates that are less susceptible to treatment with macrocyclic lactones. In another embodiment, the compounds and compositions of the present invention are effective in treating, controlling, and / or preventing infection of animals with nematodes that are less susceptible to treatment with commercially available or known active agents.

[0015] In one embodiment, the present invention comprises a combination of a compound of formula (I) with at least a second active agent, which can provide expanded protection to animals against endoparasites and / or ectoparasites. Another embodiment includes a method for treating, controlling and / or preventing a parasitic infection in an animal, comprising administering to the animal a compound of formula (I). Another embodiment includes the use of a compound of formula (I) for treating, controlling and / or preventing a parasitic infection in an animal, and the use of a compound of formula (I) in the preparation of a medicament for treating, controlling and / or preventing a parasitic infection in an animal.

[0016] Thus, the present invention includes the following non-limiting embodiments: (a) a compound of formula (I) or a salt thereof which is an active endoparasiticide; (b) a veterinary composition comprising a parasiticidally effective amount of a compound of formula (I) or a salt thereof in combination with a pharma- ceutically acceptable carrier or diluent; (c) veterinary compositions comprising a parasitocidally effective amount of a compound of formula (I) or a salt thereof in combination with one or more additional active agents (i.e., active ingredients not encompassed by formula (I)) and a pharma- ceutically acceptable carrier or diluent; (d) a method for treating parasitic infections and / or infestations in or on an animal, comprising administering to an animal in need thereof a parasiticidally effective amount of a compound of formula (I) or a salt thereof, and optionally one or more additional active agents (i.e. active ingredients not encompassed by formula (I)); (e) a method for preventing parasitic infection and / or infestation in an animal, comprising administering to an animal in need thereof a parasiticidal effective amount of a compound of formula (I) or a salt thereof, and optionally one or more additional active agents (i.e. active ingredients not encompassed by formula (I)); (f) a compound of formula (I) or a salt thereof, and optionally one or more additional active agents (i.e. active ingredients not encompassed by formula (I)), for use in the treatment, control and / or prevention of parasitic infections and, optionally, parasitic infestations in animals; (g) the use of a compound of formula (I) or a salt thereof, optionally with one or more additional active agents (i.e. active ingredients not encompassed by formula (I)), for the manufacture of a veterinary medicament for the treatment, control and / or prevention of parasitic infections and / or infestations in animals; and (h) A process for preparing a compound of formula (I).

[0017] Definition: It should be noted that in this disclosure, and particularly in the claims and / or paragraphs, terms such as, for example, "comprises," "comprised," "comprising," etc., can be interpreted as "includes," "included," "including," etc.; for example, the terms "consisting essentially of" and "consists essentially of" are interpreted to contemplate elements not expressly recited, but to exclude elements found in the prior art or that affect a basic or novel characteristic of the invention.

[0018] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs at the time of filing. Terms not specifically defined herein should be given the meaning that would be given by one of ordinary skill in the art in light of this disclosure and context. The meaning and scope of the terms should be clear; however, in the event of any potential ambiguity, the definitions provided herein take precedence over any dictionary or external definitions. Furthermore, unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular. In this specification, the use of "or" means "and / or" unless otherwise stated. Furthermore, the use of the term "including," as well as other forms such as "includes" and "included," is not limiting. However, as used in the specification, unless otherwise specified, the following terms shall have the indicated meanings and the following conventions shall be followed.

[0019] In the groups, radicals, or moieties defined herein, the number of carbon atoms is often specified before the group, e.g., C 1-6 -Alkyl means an alkyl group or radical having 1 to 6 carbon atoms. Generally, HO, H 2 N, (O)S, (O) 2 S, NC (Cyano), HOOC, F 3 For groups such as aryl-C, one of ordinary skill in the art can recognize the point of radical attachment to the molecule from the free valence of the group itself. For combination groups containing two or more subgroups, the last named subgroup is the point of radical attachment, e.g., "aryl-C 1-3 The "-alkylene" substituent is 1-3 - means an aryl group bonded to an alkyl group, the latter of which is bonded to a core or to a group to which a substituent is bonded. When compounds of the invention are depicted in the form of a chemical name and a formula, the formula shall prevail in the event of any discrepancy. An asterisk may be used to indicate a bond that is attached to a core molecule defined in a subformula.

[0020] The numbering of the atoms of a substituent begins with the atom closest to the core or group to which the substituent is attached. For example, the term "3-carboxypropyl group" represents the following substituent: [ka] (wherein the carboxy group is attached to the third carbon atom of the propyl group) The terms "1-methylpropyl-", "2,2-dimethylpropyl-" or "cyclopropylmethyl-" represent the following groups: [ka]

[0021] The asterisk or "" indicates the core [ka] It may be used in subformulas to indicate the bond that is attached to a molecule.

[0022] The term "substituted," as used herein, means that one or more hydrogens on the specified atom are replaced with a group selected from the defined group of substituents, provided that the normal valence of the specified atom is not exceeded and the substitution results in a stable compound. Similarly, the term "substituted" may be used in conjunction with a chemical moiety, such as "substituted alkyl," "substituted aryl," etc., in place of a single atom.

[0023] Unless otherwise indicated with respect to a particular embodiment of the invention, the term "optionally substituted" as used herein means that a given group is selected from the following moieties: halogen, hydroxyl, oxo (C=O), alkyl, haloalkyl, cycloalkyl, cycloalkenyl, carboxyl, acyl, acyloxy, acetyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, haloalkylaminocarbonyl, dihaloalkylaminocarbonyl, amino, alkylamino or dialkylamino, amido, arylamino, alkoxy, haloalkoxy, aryloxy, alkylthio, haloalkylthio, nitro, cyano, azido, thiol, thioamide, imino, amidino, guanidino, carbonate, R 3 Si- or R 3 SiO- (wherein R is C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl or aryl), SF 5 , sulfate, alkylsulfonyl, haloalkylsulfonyl, alkoxysulfonyl, haloalkoxysulfonyl, arylsulfonyl, alkylsulfinyl, haloalkylsulfinyl, arylsulfinyl, sulfamoyl, sulfoximine, sulfinimine, sulfonimidamide, sulfondiimine, phosphonyl, phosphinyl, phosphoryl, phosphine, phosphonamidate, phosphinamidate, phosphinate, phosphine oxide, thioester, anhydride, oxime, hydrazine, carbamate, phosphate, phosphonate, aryl, heteroaryl, and heterocyclyl.

[0024] In some embodiments, unless otherwise indicated for a particular embodiment of the invention, the term "optionally substituted" refers to an alkyl group that is an aryl group selected from the group consisting of halogen (chloro, fluoro, bromo, iodo), hydroxyl, oxo, C 1 ~C 6- Alkyl, C 1~C 6 -Haloalkyl, 3-8 membered cycloalkyl, 5-8 membered cycloalkenyl, carboxyl, amino, amido, thioamido, imino, amidino, guanidino, carbonate, tri-C 1 ~C 6 -Alkylsilyl, tri-C 1 ~C 6 -Alkylsiloxy, sulfate, C 1 -C 6 -Alkylamino, C 1 -C 6 -Dialkylamino, phenylamino, C 1 -C 6 -Alkoxy, C 1 -C 6 -Haloalkoxy, phenoxy, cyano, azido, thiol, nitro, SF 5 , Acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Alkoxycarbonyloxy, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Alkylcarbonyloxy, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -Dialkylaminocarbonyl, aminocarbonyloxy, C 1 -C 6 -Alkylaminocarbonyloxy, C 1 -C 6 -dialkylaminocarbonyloxy, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6 -Alkylthio, C 1 -C 6-Alkyl sulfinyl, phenyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, phenyl sulfonyl, C 1 -C 6 -Alkoxysulfonyl, C 1 -C 6 -Haloalkylthio, C 1 -C 6 -Haloalkylsulfinyl, C 1 -C 6 -Haloalkylsulfonyl, C 1 -C 6 -including being substituted with haloalkoxysulfonyl, phenyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocyclyl, sulfamoyl, sulfoximine, sulfinimine, sulfonimidamide, sulfondiimine, phosphonyl, phosphinyl, phosphoryl, phosphine, phosphonamidate, phosphinamidate, phosphinate, phosphine oxide, thioester, anhydride, oxime, hydrazine, carbamate, phosphate or phosphonate.

[0025] In other embodiments, unless otherwise indicated for a particular embodiment of the invention, the term "optionally substituted" refers to any group in which the core group is substituted with halogen (chloro, fluoro, bromo, iodo), hydroxyl, C 1 ~C 3 -Alkyl, C 1 ~C 3 -haloalkyl, 3-8 membered cycloalkyl, 5-8 membered cycloalkenyl, amino, C 1 -C 3 -Alkylamino, C 1 -C 3 -dialkylamino, C 1 -C 3 -Alkoxy, C 1 -C 3 -Haloalkoxy, Cyano, Nitro, SF 5 , Acetyl, C 1 -C 3 -Alkoxycarbonyl, C 1 -C 3 -Haloalkoxycarbonyl, C 1 -C 3-Alkyl carbonyl, C 1 -C 3 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 3 -Alkylaminocarbonyl, C 1 -C 3 -dialkylaminocarbonyl, C 1 -C 3 -Haloalkylaminocarbonyl, C 1 -C 3 -dihaloalkylaminocarbonyl, C 1 -C 3 -Alkylthio, C 1 -C 3 -Alkyl sulfinyl, C 1 -C 3 -Alkyl sulfonyl, C 1 -C 3 -Haloalkylthio, C 1 -C 3 -Haloalkylsulfinyl, C 1 -C 3 -haloalkylsulfonyl, phenyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocyclyl.

[0026] In certain embodiments, unless otherwise indicated with respect to a particular embodiment of the invention, the term "optionally substituted" includes any of halogen (chloro, fluoro, bromo and iodo), methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, hydroxyl, thiol, amino, methylamino, ethylamino, propylamino, butylamino, dimethylamino, diethylamino, methoxy, ethoxy, propoxy, CF 3 , C.F. 2 CF 3 , -OCF 3 , -OCF 2 CF 3 , -SCH 3 , -SCF 3 , -S(O)CH 3 , -S(O)CF 3 , -S(O) 2 CH3 , -S(O) 2 CF 3 , aziridinyl, azetidinyl, morpholino, piperidinyl, pyridyl and phenyl.

[0027] Unless otherwise indicated, throughout the specification and the appended claims, a given chemical formula or name is intended to encompass tautomers and all stereo, optical and geometric isomers (e.g., enantiomers, diastereomers, E / Z isomers, etc.), and racemates thereof, as well as mixtures of unequal ratios of the individual enantiomers, diastereomeric mixtures, or mixtures of any of the foregoing forms, and solvates thereof, such as hydrates, where such isomers and enantiomers exist. Unless otherwise indicated, "pharmacologically acceptable salts", as defined in more detail below, are also intended to include solvates thereof, such as hydrates. In general, substantially pure stereoisomers can be obtained according to synthetic principles known to those skilled in the art, for example, by separating the corresponding mixtures, by using stereochemically pure starting materials, and / or by stereoselective synthesis. It is known in the art how to prepare optically active forms, for example, by separating racemates, or by synthesis starting from optically active starting materials, and / or by using chiral reagents.

[0028] Enantiomerically pure compounds or intermediates of the invention may be prepared by asymmetric synthesis, for example by preparing and then separating appropriate diastereomeric compounds or intermediates which can be separated by known methods (e.g. by chromatographic separation or crystallization), and / or by using chiral reagents, for example chiral starting materials, chiral catalysts or chiral auxiliaries.

[0029] Furthermore, methods are known to those skilled in the art for preparing enantiomerically pure compounds from corresponding racemic mixtures, for example by chromatographic separation of the corresponding racemic mixtures on chiral stationary phases; or by separation of the racemic mixtures using a suitable resolving agent, for example by formation of diastereomeric salts of the racemates with an optically active acid or base and subsequent separation of the salts and release of the desired compound from the salt; or by derivatization of the corresponding racemates with an optically active chiral auxiliary reagent and subsequent separation of the diastereomers and removal of the chiral auxiliary; or by kinetic separation of the racemates (for example by enzymatic separation); by enantioselective crystallization from a consortium of bipolar crystals under suitable conditions; or by (partial) crystallization from a suitable solvent in the presence of an optically active chiral auxiliary.

[0030] The phrase "pharmacologically acceptable" is used herein to refer to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of an animal without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. As used herein, "pharmaceutically acceptable salts" refers to derivatives of the disclosed compounds in which the parent compound is modified by making its acid or base salt. Examples of pharmaceutically acceptable salts include, but are not limited to, inorganic acid base or organic acid salts of basic residues, such as amines; alkali or organic salts of acidic residues, such as carboxylic acids; and the like.

[0031] For example, such salts include salts from benzenesulfonic acid, benzoic acid, citric acid, ethanesulfonic acid, fumaric acid, gentisic acid, hydrobromic acid, hydrochloric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, 4-methyl-benzenesulfonic acid, phosphoric acid, salicylic acid, succinic acid, sulfuric acid, and tartaric acid. Additionally, pharma- ceutically acceptable salts may be formed with cations from ammonia, L-arginine, calcium, 2,2'-iminobisethanol, L-lysine, magnesium, N-methyl-D-glucamine, potassium, sodium, and tris(hydroxymethyl)-aminomethane. The pharma- ceutically acceptable salts of the present invention may be synthesized from a parent compound that contains a basic or acidic moiety by conventional chemical methods. Generally, such salts may be prepared by reacting the free acid or base form of these compounds with a sufficient amount of the appropriate base or acid in water or in an organic diluent such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile, or a mixture thereof.

[0032] For example, salts of other acids than those mentioned above that are useful for purifying or isolating the compounds of the invention (eg, trifluoroacetates) also form part of the invention. The term "halogen" refers to fluorine, chlorine, bromine and iodine. "C 1-n The term "-alkyl" denotes, alone or in combination with other groups, an acyclic saturated branched or linear hydrocarbon group having 1 to n C atoms, where n is an integer selected from 2, 3, 4, 5 or 6, preferably 4, 5 or 6. For example, 1-5 The term -alkyl means H 3 C-, H 3 C-CH 2 -, H 3 C-CH 2 -CH 2 -, H 3 C-CH(CH 3 )-, H 3 C-CH 2 -CH 2 -CH 2 -, H 3 C-CH2 -CH(CH 3 )-, H 3 C-CH(CH 3 )-CH 2 -, H 3 CC(CH 3 ) 2 -, H 3 C-CH 2 -CH 2 -CH 2 -CH 2 -, H 3 C-CH 2 -CH 2 -CH(CH 3 )-, H 3 C-CH 2 -CH(CH 3 )-CH 2 -, H 3 C-CH(CH 3 )-CH 2 -CH 2 -, H 3 C-CH 2 -C(CH 3 ) 2 -, H 3 CC(CH 3 ) 2 -CH 2 -, H 3 C-CH(CH 3 )-CH(CH 3 )- and H 3 C-CH 2 -CH(CH 2 CH 3 )- groups.

[0033] "C 1-n The term "-alkylene" refers, alone or in combination with other groups, to an acyclic saturated branched or straight chain divalent alkyl group containing from 1 to n carbon atoms, where n is an integer selected from 2, 3, 4, 5 or 6, preferably 4, 5 or 6. For example, C 1-4 The term -alkylene means -CH 2 -, -CH 2 -CH 2 -, -CH(CH 3 )-, -CH 2 -CH 2 -CH 2-, -C(CH 3 ) 2 -, -CH(CH 2 CH 3 )-, -CH(CH 3 )-CH 2 -, -CH 2 -CH(CH 3 )-, -CH 2 -CH 2 -CH 2 -CH 2 -, -CH 2 -CH 2 -CH(CH 3 )-, -CH(CH 3 )-CH 2 -CH 2 -, -CH 2 -CH(CH 3 )-CH 2 -, -CH 2 -C(CH 3 ) 2 -, -C(CH 3 ) 2 -CH 2 -, -CH(CH 3 )-CH(CH 3 )-, -CH 2 -CH(CH 2 CH 3 )-, -CH(CH 2 CH 3 )-CH 2 -, -CH(CH 2 CH 2 CH 3 )-, -CH(CH(CH 3 )) 2 - and -C(CH 3 )(CH 2 CH 3 )-Includes.

[0034] "C 2-m The term "C-alkenyl" refers to a group in which m is an integer selected from 3, 4, 5 or 6, preferably 4, 5 or 6, and at least two carbon atoms of the group are bonded to each other by a double bond. 2-m -alkyl" groups. "C 2-mThe term "C-alkenylene" refers to "C-alkenylene", where m is an integer selected from 3, 4, 5 or 6, preferably 4, 5 or 6, and at least two carbon atoms of the group are bonded to each other by a double bond. 2-m -alkylene" groups. "C 2-m The term "C-alkynyl" refers to a group in which m is an integer selected from 3, 4, 5 or 6, preferably 4, 5 or 6, and at least two carbon atoms of the group are bonded together by a triple bond. 2-m -alkyl" groups. "C 2-m The term "C-alkynylene" refers to "C-alkynylene" where m is an integer selected from 3, 4, 5 or 6, preferably 4, 5 or 6, and at least two of the carbon atoms of said group are bonded together by a triple bond. 2-m -alkylene" groups.

[0035] "C 3-k The term "cycloalkyl" denotes, alone or in combination with other groups, a cyclic saturated unbranched hydrocarbon group containing 3 to k C atoms, where k is an integer selected from 4, 5, 6, 7 or 8, preferably 4, 5 or 6. For example, 3-7 The term -cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. "C 3-k The term "cycloalkenyl" refers, alone or in combination with other groups, to a cyclic, unsaturated but non-aromatic, unbranched hydrocarbon group containing from 3 to k C atoms, at least two of which are linked to each other by a double bond, where k is an integer selected from 4, 5, 6, 7 or 8, preferably 4, 5 or 6. For example, 3-7 The term -cycloalkenyl includes cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl and cycloheptatrienyl.

[0036] The term "halo" appended to an "alkyl", "alkylene", "alkenyl", "alkenylene", "alkynyl", "alkynylene", "cycloalkyl", "cycloalkenyl" or "alkoxy" group defines an alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloalkenyl or alkoxy group in which one or more hydrogen atoms have been replaced with a halogen atom selected from among fluorine, chlorine, bromine or iodine, preferably from among fluorine and chlorine, with fluorine being particularly preferred. 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 have been replaced by a fluorine atom, for example, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl or pentafluoroethyl.

[0037] The term "alkoxy" refers to alkyl-O-, where alkyl is as defined above. Similarly, the terms "alkenyloxy", "alkynyloxy", "haloalkoxy", "haloalkenyloxy", "haloalkynyloxy", "cycloalkoxy", "cycloalkenyloxy", "halocycloalkoxy", and "halocycloalkenyloxy" refer to alkenyl-O-, alkynyl-O-, haloalkyl-O-, haloalkenyl-O-, haloalkynyl-O-, cycloalkyl-O-, cycloalkenyl-O-, halocycloalkyl-O-, and halocycloalkenyl-O- groups, respectively, where alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, halocycloalkyl, and halocycloalkenyl are as defined herein. 1 ~C 6 Examples of -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 , O.C.H. 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, and 1-ethyl-2-methylpropoxy.

[0038] The term "carbocyclyl" or "carbocycle", alone or in combination with another group, means a monocyclic, bicyclic, or tricyclic ring structure of 3 to 14 carbon atoms. The term "carbocyclyl" or "carbocycle" refers to fully saturated, partially saturated, and aromatic ring systems. The term "carbocyclyl" or "carbocycle" includes fused, bridged, and spirocyclic systems. Examples include:

[0039] [ka] There is.

[0040] The term "aryl", alone or in combination with another group, denotes an aromatic, fully saturated or partially saturated, carbocyclic aromatic monocyclic group containing 6 carbon atoms, which may be further fused to a second 5- or 6-membered carbocyclic group. The term "aryl" includes, but is not limited to, phenyl, indanyl, indenyl, naphthyl, anthracenyl, phenanthrenyl, tetrahydronaphthyl, and dihydronaphthyl.

[0041] The term "aralkyl" refers to a diradical alkylene bridge, (-CH 2 -) n wherein n is 1 to 6 and "aryl" is as defined herein.

[0042] The term "heterocyclyl" or "heterocycle" may include aromatic rings, and may be N, O, S, S(O) or S(O) 2means a saturated or unsaturated monocyclic or polycyclic ring system, consisting of 3 to 14 ring atoms, containing one or more heteroatoms selected from the following, and none of the heteroatoms are part of an aromatic ring. The term "heterocyclyl" or "heterocycle" is intended to include all possible isomeric forms. Thus, the term "heterocyclyl" or "heterocycle" includes the following exemplary structures (not shown as groups, since each form may be attached to any atom via a covalent bond, as long as the appropriate valence is maintained):

[0043] [ka] JPEG2024540166000009.jpg190170

[0044] The term "heteroaryl" refers to a heteroaryl group that contains at least one aromatic ring and is selected from the group consisting of N, O, S, S(O) or S(O). 2 and 5 to 14 ring atoms, with at least one of the heteroatoms being part of an aromatic ring. The term "heteroaryl" is intended to include all possible isomeric forms. Thus, the term "heteroaryl" includes the following exemplary structures (not shown as groups, since each form may be bonded to any atom via a covalent bond, as long as the appropriate valence is maintained):

[0045] [ka]

[0046] Many of the terms given in this specification may be used repeatedly in the definitions of formulae or groups and in each case have, independently of one of the meanings given in this specification.

[0047] The term "bicyclic ring system" means a group consisting of two linked cyclic moieties, including spirocyclic, fused, and bridged ring systems.

[0048] The term "tricyclic ring system" means a group consisting of three linked cyclic moieties, including spirocyclic, fused and bridged ring systems.

[0049] As used herein, the term "control" in relation to "parasitic infection and / or infestation in an animal" means that the parasitic infection and / or infestation is cured or ameliorated, its incidence is persistently reduced, and / or its worsening is prevented in relation to the animal. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0050] Detailed Description: An embodiment of the present invention is a compound of formula (I): [ka] (I) or a salt thereof, wherein: L is L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, or L17; [ka] R ’ is hydrogen, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted aryl, or two R' of the same L group may join together to form a 2-4 membered carbon chain to form a heterocycle; R 1is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p (optionally substituted alkyl or haloalkyl), -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, alkyl or haloalkyl; R 2is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl; optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, -SO p (optionally substituted alkyl or haloalkyl), -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 3is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl; optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, -SO p (optionally substituted alkyl or haloalkyl), -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 4 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, -S(O) p (optionally substituted alkyl), -SF 5, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted 5- to 10-membered heteroaryl, a spirocyclic heterocyclyl-carbocyclyl group, a spirocyclic heterocyclyl-heterocyclyl group, a spirocyclic carbocyclyl-carbocyclyl group, a spirocyclic carbocyclyl-heterocyclyl group, or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5’ is independently, at each occurrence, hydrogen, halogen, cyano, nitro, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkoxy, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted di(alkyl)aminocarbonyl, optionally substituted alkylcarbonyloxy, optionally substituted alkylcarbonylamino, optionally substituted aryl, optionally substituted heteroaryl, -SF 5 , -SO p (optionally substituted alkyl or haloalkyl); or R 5 is R 5’together with -NR c R d and R c and R d is independently H or optionally substituted alkyl; or R c and R d may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 6 and R 7 are independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted alkoxy, or optionally substituted cycloalkoxy; or R 6 is R 7 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, and the carbon or nitrogen atoms in the chain may be substituted; R 8 is hydrogen or C 1 ~C 4 - alkyl; R 9 is hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, alkenyl, or alkynyl; Q is CR 9 or N; X is O, S or N-R'; Y 1 and Y 6 are each independently N, C, or -CR 5 - and; Y 2 , Y 3 , Y 4 and Y5 are each independently N, NR ’ ,S,O,-CR 5 - or CR 5 R 5’ and; W is for CR 6 , C.R. 6 R 7 , O, SO p , N or NR 8 or W is absent; W 1 CR 6 , C.R. 6 R 7 , O, SO p , N or NR 8 and; Z is CR 7 , C.R. 6 R 7 , O, SO p , N or NR 8 and Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 at most three of which are heteroatoms; q is 0 or 1; p is independently, at each occurrence, 0, 1, or 2; The dashed bonds (

[0051] [ka] ) indicates a single or double bond; or a salt thereof; "Optionally substituted" means that the recited group is selected from the group consisting of halogen, hydroxyl, oxo, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, carboxyl, acyl, acyloxy, acetyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, haloalkylaminocarbonyl, dihaloalkylaminocarbonyl, amino, alkylamino or dialkylamino, amido, arylamino, alkoxy, haloalkoxy, alkylthio, haloalkylthio, aryloxy, nitro, cyano, azido, thiol, thioamide, imino, amidino, guanidino, carbonate, R 3 Si- or R 3 SiO- (wherein R is alkyl, haloalkyl or aryl), SF 5 , sulfate, alkylsulfonyl, haloalkylsulfonyl, alkoxysulfonyl, alkylsulfinyl, haloalkylsulfinyl, sulfamoyl, sulfoximine, sulfinimine, sulfonimidamide, sulfondiimine, phosphonyl, phosphinyl, phosphoryl, phosphine, phosphonamidate, phosphineamidate, phosphinate, phosphine oxide, thioester, anhydride, oxime, hydrazine, carbamate, phosphate, phosphonate, aryl, heteroaryl, and heterocyclyl).

[0052] In another embodiment, the present invention includes a compound of formula (I) as described above or a salt thereof, wherein R 1’ , R 2 , R 3 , R 4 , L, Q, W, W 1 , Z, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 and q have the same definition as described above for formula (I); [ka] ) indicates a single or double bond; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p (optionally substituted alkyl or haloalkyl), -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, or 5-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" indicates that the recited group is optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (I) above.

[0053] In another embodiment, the present invention includes a compound of formula (I) as described above or a salt thereof, wherein R1’ , R 2 , R 3 , R 4 , L, Q, W, W 1 , Z, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 and q have the same definition as described above for formula (I); [ka] ) indicates a single or double bond; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p (optionally substituted alkyl or haloalkyl), -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R bmay, together with the nitrogen to which they are attached, form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (I) above.

[0054] In another embodiment, the present invention provides a compound of formula (I) or a salt thereof: (In the formula: R' is hydrogen, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, optionally substituted C 3 ~C 8 -cycloalkyl, or optionally substituted phenyl; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 -C 6 -Haloalkyl, Hydroxy-C 1 -C 6 -Alkyl, Hydroxy-C 1 -C 6 -Haloalkyl, C 1 -C 6 -Alkoxy-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkoxy-C 1 -C 6 -Alkyl, Amino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkylamino-C 1 -C6 -Alkyl, Di-C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkoxy, C 2 -C 6 -Alkenyloxy, C 2 -C 6 -haloalkenyloxy, C 2 -C 6 -Alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 1 -C 6 -Haloalkoxy, C 2 -C 6 -Alkenyl, C 2 -C 6 -Haloalkenyl, C 2 -C 6 -Alkynyl, C 2 -C 6 -Haloalkynyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, di-C 1 -C 6 -Alkylaminocarbonyl, di-C 1 -C 6 -haloalkylaminocarbonyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8-cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl, -SF 5 , Tri-C 1 ~C 6 -Alkylsilyl, tri-C 1 ~C 6 -Alkylsilyloxy, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), or -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 6 -alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, C 1 ~C 3 -Alkyl or C 1 ~C 3 - haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl; optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), SF 5 , or -NR a R b and R a and Rb are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 3 is hydrogen, cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl; optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S, C 1~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 4 is C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6-Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -Cycloalkenyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, di-C 1 -C 6 -Alkylaminocarbonyl, di-C 1 -C 6 -Haloalkylaminocarbonyl, -SF 5 , -S(O) p (C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O and S; optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, a 5- to 11-membered spirocyclic heterocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic heterocyclyl-heterocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-heterocyclyl group, or -NR a R b and R a and R b are independently H, C 1~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5’ is independently, at each occurrence, hydrogen, halogen, cyano, nitro, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted C 1 ~C 6 -Alkylcarbonyl, optionally substituted C 1 ~C 6 -Alkoxycarbonyl, aminocarbonyl, optionally substituted C 1 ~C 6 -Alkylaminocarbonyl, di(C1 ~C 6 -alkyl)aminocarbonyl, optionally substituted C 1 ~C 6 -Alkylcarbonyloxy, optionally substituted C 1 ~C 6 -alkylcarbonylamino, optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, -SF 5 , -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl); or R 5 is R 5’ together with -NR c R d and R c and R d are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R c and R d may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 9 is hydrogen, halogen, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 3 ~C 8 -Cycloalkyl, C 2 ~C 6 -alkenyl or C 2 ~C 6 -alkynyl; L, Q, X, Y 1 , Y2 , Y 3 , Y 4 , Y 5 , Y 6 , W, W 1 , Z, R 6 , R 7 , R 8 , q, p and the dashed bond (

[0055] [ka] ) is as defined above for compounds of formula (I); The term "optionally substituted" means that the recited group is optionally substituted with one or more halogens (chloro, fluoro, bromo, iodo), C 1 ~C 6- Alkyl, C 1 ~C 6 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 -C 6 -Alkylamino, C 1 -C 6 -Haloalkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -dihaloalkylamino, C 1 -C 6 -Alkoxy, C 1 -C 6 -Haloalkoxy, Cyano, Nitro, SF 5 , C 1 -C 6 -Trialkylsilyl, C 1 -C 6 -Trialkylsiloxy, acyl, acyloxy, acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C1 -C 6 -dialkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6 -Alkylthio, C 1 -C 6 -Alkyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, C 1 -C 6 -Haloalkylthio, C 1 -C 6 -Haloalkylsulfinyl, C 1 -C 6 -haloalkylsulfonyl, phenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclyl

[0056] In another embodiment, the present invention provides a compound of formula (I) or a salt thereof, wherein: R' is hydrogen, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, optionally substituted C 3 ~C 8 -cycloalkyl, or optionally substituted phenyl; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl C 1 -C 6 -Haloalkyl, Hydroxy-C 1 -C 6 -Alkyl, Hydroxy-C 1 -C 6 -Haloalkyl, C 1 -C 6 -Alkoxy-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkoxy-C1 -C 6 -Alkyl, Amino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkoxy, C 2 -C 6 -Alkenyloxy, C 2 -C 6 -haloalkenyloxy, C 2 -C 6 -Alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 1 -C 6 -Haloalkoxy, C 2 -C 6 -Alkenyl, C 2 -C 6 -Haloalkenyl, C 2 -C 6 -Alkynyl, C 2 -C 6 -Haloalkynyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6-Haloalkylaminocarbonyl, di-C 1 -C 6 -Alkylaminocarbonyl, di-C 1 -C 6 -haloalkylaminocarbonyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl, -SF 5 , Tri-C 1 ~C 6 -Alkylsilyl, tri-C 1 ~C 6 -Alkylsilyloxy, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), or -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 6 -alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, or 5-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, C 1 ~C 3 -Alkyl or C 1 ~C 3 - haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl; optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 3 is hydrogen, cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6-alkyl, optionally substituted phenyl; optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, di-C 1 -C 6 -Alkylaminocarbonyl, di-C 1 -C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R bmay together with the nitrogen to which they are attached form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 4 is C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -Cycloalkenyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, di-C 1 -C 6 -Alkylaminocarbonyl, di-C 1 -C 6 -Haloalkylaminocarbonyl, -SF 5 , -S(O) p (C1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O and S; optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, a 5- to 11-membered spirocyclic heterocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic heterocyclyl-heterocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-heterocyclyl group, or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may together with the nitrogen to which they are attached form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5’ is independently, at each occurrence, hydrogen, halogen, cyano, nitro, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 1 ~C 6 -Alkoxy-C 1 ~C6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted C 1 ~C 6 -Alkylcarbonyl, optionally substituted C 1 ~C 6 -Alkoxycarbonyl, aminocarbonyl, optionally substituted C 1 ~C 6 -Alkylaminocarbonyl, di(C 1 ~C 6 -alkyl)aminocarbonyl, optionally substituted C 1 ~C 6 -Alkylcarbonyloxy, optionally substituted C 1 ~C 6 -alkylcarbonylamino, optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, -SF 5 , -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl); or R 5 is R 5’ together with -NR c R d and R c and R d are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R c and R dmay together with the nitrogen to which they are attached form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 9 is hydrogen, halogen, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 3 ~C 8 -Cycloalkyl, C 2 ~C 6 -alkenyl or C 2 ~C 6 -alkynyl; L, Q, X, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , W, W 1 , Z, R 6 , R 7 , R 8 , q, p and the dashed bond (

[0057] [ka] ) is as defined above for compounds of formula (I); The term "optionally substituted" means that the recited group is optionally substituted with one or more halogens (chloro, fluoro, bromo, iodo), C 1 ~C 6- Alkyl, C 1 ~C 6 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 -C 6 -Alkylamino, C 1 -C 6 -Haloalkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -dihaloalkylamino, C 1 -C 6 -Alkoxy, C1 -C 6 -Haloalkoxy, cyano, nitro, C 1 -C 6 -Trialkylsilyl, C 1 -C 6 -Trialkylsiloxy, SF 5 , acyl, acyloxy, acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -dialkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6 -Alkylthio, C 1 -C 6 -Alkyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, C 1 -C 6 -Haloalkylthio, C 1 -C 6 -Haloalkylsulfinyl, C 1 -C 6 -haloalkylsulfonyl, phenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclyl

[0058] In yet another embodiment, the present invention provides a compound of formula (I) or a salt thereof, wherein: R' is hydrogen, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, optionally substituted C3 ~C 8 -cycloalkyl, or optionally substituted phenyl; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 -C 6 -Haloalkyl, Hydroxy-C 1 -C 6 -Alkyl, Hydroxy-C 1 -C 6 -Haloalkyl, C 1 -C 6 -Alkoxy-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkoxy-C 1 -C 6 -Alkyl, Amino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkoxy, C 2 -C 6 -Alkenyloxy, C 2 -C 6 -haloalkenyloxy, C 2 -C 6 -Alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 1 -C 6 -Haloalkoxy, C 2-C 6 -Alkenyl, C 2 -C 6 -Haloalkenyl, C 2 -C 6 -Alkynyl, C 2 -C 6 -Haloalkynyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, di-C 1 -C 6 -Alkylaminocarbonyl, di-C 1 -C 6 -haloalkylaminocarbonyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl, -SF 5 , Tri-C 1 ~C 6 -Alkylsilyl, tri-C 1 ~C 6 -Alkylsilyloxy, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), or -NR a R b and R a and R bare independently H or optionally substituted C 1 ~C 6 -alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, C 1 ~C 3 -Alkyl or C 1 ~C 3 - haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl; optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8-cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 3 is hydrogen, cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl; optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, di-C 1 -C 6 -Alkylaminocarbonyl, di-C 1 -C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6-Alkyl or C 1 ~C 6 -haloalkyl), SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 4 is C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -Cycloalkenyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, di-C 1 -C 6 -Alkylaminocarbonyl, di-C 1 -C 6 -Haloalkylaminocarbonyl, -SF 5 , -S(O) p (C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O and S; optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, a 5- to 11-membered spirocyclic heterocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic heterocyclyl-heterocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-heterocyclyl group, or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5’ is independently, at each occurrence, hydrogen, halogen, cyano, nitro, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted C 1 ~C 6 -Alkylcarbonyl, optionally substituted C 1 ~C 6 -Alkoxycarbonyl, aminocarbonyl, optionally substituted C 1 ~C 6 -Alkylaminocarbonyl, di(C 1 ~C 6 -alkyl)aminocarbonyl, optionally substituted C 1 ~C 6 -Alkylcarbonyloxy, optionally substituted C 1 ~C 6 -alkylcarbonylamino, optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, -SF 5 , -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl); or R 5 is R 5’together with -NR c R d and R c and R d are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R c and R d may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 9 is hydrogen, halogen, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 3 ~C 8 -Cycloalkyl, C 2 ~C 6 -alkenyl or C 2 ~C 6 -alkynyl; L, Q, X, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , W, W 1 , Z, R 6 , R 7 , R 8 , q, p and the dashed bond (

[0059] [ka] ) is as defined above for compounds of formula (I); The term "optionally substituted" means that the recited group is optionally substituted with one or more halogens (chloro, fluoro, bromo, iodo), C1 ~C 6- Alkyl, C 1 ~C 6 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 -C 6 -Alkylamino, C 1 -C 6 -Haloalkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -dihaloalkylamino, C 1 -C 6 -Alkoxy, C 1 -C 6 -Haloalkoxy, cyano, nitro, C 1 -C 6 -Trialkylsilyl, C 1 -C 6 -Trialkylsiloxy, SF 5 , acyl, acyloxy, acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -dialkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6 -Alkylthio, C 1 -C 6 -Alkyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, C 1 -C 6 -Haloalkylthio, C 1 -C 6 -Haloalkylsulfinyl, C1 -C 6 -haloalkylsulfonyl, phenyl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclyl

[0060] In another embodiment, the present invention comprises a compound of formula (I) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R 4 , L, Q, W, W 1 , Z, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 and q have the same definition as described above for formula (I); [ka] ) indicates a single or double bond; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p(optionally substituted alkyl or haloalkyl), -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (I) above); with the exception of the following compounds:

[0061] [ka]

[0062] An embodiment of the present invention is a compound of formula (IA): [ka] (IA) or a salt thereof (wherein: L is L1, L2, L6, L7, L16 or L17;

[0063] [ka] R ’ is hydrogen, optionally substituted alkyl, optionally substituted haloalkyl or optionally substituted aralkyl; R 1is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, optionally substituted alkyl or haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted alkenyl or optionally substituted alkynyl; R 3 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted alkenyl or optionally substituted alkynyl; R 4is optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted spirocyclic heterocyclyl-carbocyclyl group, optionally substituted spirocyclic heterocyclyl-heterocyclyl group, optionally substituted spirocyclic carbocyclyl-carbocyclyl group, optionally substituted spirocyclic carbocyclyl-heterocyclyl group, optionally substituted spirocyclic carbocyclyl-heterocyclyl group, optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, or -NR a R b and R a and R b is independently H, alkyl, or haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5’ is independently at each occurrence hydrogen, halogen, cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy; R 9 is hydrogen, halogen, alkyl or haloalkyl; R 6 and R 7 are independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, or R 6 is R 7 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, and the carbon or nitrogen atoms in the chain may be substituted; Q is CR 9 or N; X is O, S or N-R'; Y 1 and Y 6 is independently C or N; Y 2 , Y 3 , Y 4 and Y 5 are each independently N or -CR 5 and; W is for CR 6 , C.R. 6 R 7 or W is absent; W 1 CR 6 or CR 6 R 7 and; Z is CR 6 , C.R. 6 R 7 or O; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 at most three of are N; The dashed bonds (

[0064] [ka] ) indicates a single or double bond; "Optionally substituted" means that the recited group is selected from the group consisting of halogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, carboxyl, acyl, acyloxy, acetyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, haloalkylaminocarbonyl, dihaloalkylaminocarbonyl, amino, alkylamino or dialkylamino, amido, alkoxy, haloalkoxy, alkylthio, haloalkylthio, cyano, thiol, thioamide, aryl, heteroaryl, aryloxy, arylamino, heterocyclyl, SF 5, trialkylsilyl, trialkylsiloxy, alkylsulfonyl, alkoxysulfonyl or alkylsulfinyl), This includes stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts thereof.

[0065] In another embodiment, the present invention includes a compound of formula (IA) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R 4 , L, Q, W, W 1 , Z, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 has the same definition as for formula (IA); the dashed bond ( [ka] ) indicates a single or double bond; R 1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, or 5-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same substituents defined under "optionally substituted" with respect to the broadest embodiment of the compounds of formula (IA) above.

[0066] In yet another embodiment, the present invention comprises a compound of formula (IA) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R 4 , L, Q, W, W 1 , Z, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 has the same definition as for formula (IA); the dashed bond ( [ka] ) indicates a single or double bond; R 1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may together with the nitrogen to which they are attached form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as "optionally substituted" defined with respect to the broadest embodiment of formula (IA) above.

[0067] In another embodiment, the present invention provides a compound of formula (IA) or a salt thereof: (In the formula: R' is hydrogen, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, or optionally substituted benzyl; R 1 is hydrogen, halogen, or optionally substituted C 1 ~C 6 -Alkyl, C 1 -C 6 -Haloalkyl, Hydroxy-C 1 -C 6 -Alkyl, Hydroxy-C 1 -C 6 -Haloalkyl, C 1 -C 6 -Alkoxy-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkoxy-C 1 -C 6 -Alkyl, Amino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, C 1 -C6 -Alkoxy, C 2 -C 6 -Alkenyloxy, C 2 -C 6 -haloalkenyloxy, C 2 -C 6 -Alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 1 -C 6 -Haloalkoxy, C 2 -C 6 -Alkenyl, C 2 -C 6 -Haloalkenyl, C 2 -C 6 -Alkynyl, C 2 -C 6 -haloalkynyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted 3- to 7-membered heterocyclyl, or -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 6 -alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, or optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 - haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6-Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; R 3 is hydrogen, cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; R 4 is optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8-cycloalkenyl, an optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S; an optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl, a 5- to 11-membered spirocyclic heterocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic heterocyclyl-heterocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-heterocyclyl group, or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5’ is independently, at each occurrence, hydrogen, halogen, cyano, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 - haloalkoxy; R 6 and R 7 are independently hydrogen, halogen, C 1 ~C 6 -Alkyl, C 1 ~C 6-Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Alkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -haloalkoxy or R 6 is R 7 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, and the carbon or nitrogen atoms in the chain may be substituted; R 9 is hydrogen, halogen, C 1 ~C 6 -Alkyl or C 1 ~C 6 - haloalkyl; L, Q, X, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , W, W 1 , Z and the dashed bond (

[0068] [ka] ) is as defined above for compounds of formula (IA); The term "optionally substituted" means that the recited group is optionally substituted with one or more of halogen (chloro, fluoro, bromo, iodo), hydroxyl, C 1 ~C 6- Alkyl, C 1 ~C 6 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 -C 6 -Alkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -Alkoxy, C 1 -C 6 -Haloalkoxy, Cyano, SF5 , C 1 -C 6 -Trialkylsilyl, C 1 -C 6 -Trialkylsiloxy, acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -dialkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6 -Alkylthio, C 1 -C 6 -Alkyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, C 1 -C 6 -Haloalkylthio, C 1 ~C 6 -haloalkylsulfinyl or C 1 ~C 6 -haloalkylsulfonyl)

[0069] In another embodiment, the present invention provides a compound of formula (IA) or a salt thereof, wherein: R' is hydrogen, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, or optionally substituted benzyl; R 1 is hydrogen, halogen, or optionally substituted C 1 ~C 6 -Alkyl, C1 -C 6 -Haloalkyl, Hydroxy-C 1 -C 6 -Alkyl, Hydroxy-C 1 -C 6 -Haloalkyl, C 1 -C 6 -Alkoxy-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkoxy-C 1 -C 6 -Alkyl, Amino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkoxy, C 2 -C 6 -Alkenyloxy, C 2 -C 6 -haloalkenyloxy, C 2 -C 6 -Alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 1 -C 6 -Haloalkoxy, C 2 -C 6 -Alkenyl, C 2 -C 6 -Haloalkenyl, C 2 -C 6 -Alkynyl, C 2 -C 6 -haloalkynyl, optionally substituted C3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted 3- to 7-membered heterocyclyl, or -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 6 -alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, or 5-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, or optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 - haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; R 3 is hydrogen, cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; R 4 is an optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, an optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S; an optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl, a 5- to 11-membered spirocyclic heterocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic heterocyclyl-heterocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-heterocyclyl group, or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R bmay, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5’ is independently, at each occurrence, hydrogen, halogen, cyano, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 - haloalkoxy; R 6 and R 7 are independently hydrogen, halogen, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Alkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -haloalkoxy or R 6 is R 7 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, and the carbon or nitrogen atoms in the chain may be substituted; R 9 is hydrogen, halogen, C 1 ~C 6 -Alkyl or C 1 ~C6 - haloalkyl; L, Q, X, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , W, W 1 , Z and the dashed bond (

[0070] [ka] ) is as defined above for compounds of formula (IA); The term "optionally substituted" means that the recited group is optionally substituted with one or more of halogen (chloro, fluoro, bromo, iodo), hydroxyl, C 1 ~C 6- Alkyl, C 1 ~C 6 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 -C 6 -Alkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -Alkoxy, C 1 -C 6 -Haloalkoxy, Cyano, SF 5 , Acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -dialkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6-Alkylthio, C 1 -C 6 -Alkyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, C 1 -C 6 -Haloalkylthio, C 1 ~C 6 -haloalkylsulfinyl or C 1 ~C 6 -haloalkylsulfonyl)

[0071] In another embodiment, the present invention provides a compound of formula (IA) or a salt thereof, wherein: R' is hydrogen, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, or optionally substituted benzyl; R 1 is hydrogen, halogen, or optionally substituted C 1 ~C 6 -Alkyl, C 1 -C 6 -Haloalkyl, Hydroxy-C 1 -C 6 -Alkyl, Hydroxy-C 1 -C 6 -Haloalkyl, C 1 -C 6 -Alkoxy-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkoxy-C 1 -C 6 -Alkyl, Amino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6-Alkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkoxy, C 2 -C 6 -Alkenyloxy, C 2 -C 6 -haloalkenyloxy, C 2 -C 6 -Alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 1 -C 6 -Haloalkoxy, C 2 -C 6 -Alkenyl, C 2 -C 6 -Haloalkenyl, C 2 -C 6 -Alkynyl, C 2 -C 6 -haloalkynyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted 3- to 7-membered heterocyclyl, or -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 6 -alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, or optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6- haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; R 3 is hydrogen, cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; R 4 is optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, an optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S; an optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl, a 5- to 11-membered spirocyclic heterocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic heterocyclyl-heterocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-carbocyclyl group, a 5- to 11-membered spirocyclic carbocyclyl-heterocyclyl group, or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5’ is independently, at each occurrence, hydrogen, halogen, cyano, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 - haloalkoxy; R 6 and R 7 are independently hydrogen, halogen, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Alkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -haloalkoxy or R 6 is R 7 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, and the carbon or nitrogen atoms in the chain may be substituted; R 9 is hydrogen, halogen, C 1 ~C 6 -Alkyl or C 1 ~C 6 - haloalkyl; L, Q, X, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , W, W 1 , Z and the dashed bond (

[0072] [ka] ) is as defined above for compounds of formula (IA); The term "optionally substituted" means that the recited group is optionally substituted with one or more of halogen (chloro, fluoro, bromo, iodo), hydroxyl, C 1 ~C 6- Alkyl, C 1 ~C 6 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 -C 6 -Alkylamino, C1 -C 6 -dialkylamino, C 1 -C 6 -Alkoxy, C 1 -C 6 -Haloalkoxy, Cyano, SF 5 , Acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -dialkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6 -Alkylthio, C 1 -C 6 -Alkyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, C 1 -C 6 -Haloalkylthio, C 1 ~C 6 -haloalkylsulfinyl or C 1 ~C 6 -haloalkylsulfonyl)

[0073] In some embodiments of formula (IA): R 1 is optionally substituted C 1 ~C 4 -alkyl, optionally substituted C 1 ~C 4 -alkoxy, optionally substituted C 2 ~C 4 -alkenyl, optionally substituted C 2 ~C4 -alkynyl, an optionally substituted saturated or partially unsaturated 5-, 6-, or 7-membered heterocyclyl group, an optionally substituted heteroaryl, or -NR a R b and R a and R b is independently optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, and S, and which may be substituted; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 4 - alkyl; R 2 is hydrogen, halogen, or optionally substituted C 1 ~C 4 -alkyl or optionally substituted C 1 ~C 4 -alkoxy; R 3 is hydrogen, halogen, or optionally substituted C 1 ~C 4 -alkyl or optionally substituted C 1 ~C 4 -alkoxy; R 4 is phenyl optionally substituted with 1, 2 or 3 substituents; R 5 and R 5’ are independently hydrogen, halogen, cyano, C 1 ~C 4 -Alkyl or C 1 ~C 4 Haloalkyl, "optionally substituted" refers to the recited group being optionally substituted with the same groups as "optionally substituted" defined for the broadest embodiment of formula (IA) above.

[0074] In some embodiments of formula (IA): R 1 is an optionally substituted C 1 ~C 4 -alkyl, optionally substituted C 1 ~C 4 -alkoxy, optionally substituted C 2 ~C 4 -alkenyl, optionally substituted C 2 ~C 4 -alkynyl, an optionally substituted saturated or partially unsaturated 5-, 6-, or 7-membered heterocyclyl group, an optionally substituted heteroaryl, or -NR a R b and R a and R b is independently optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, or 5-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, and S, and which may be substituted; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 4 - alkyl; R 2 is hydrogen, halogen, or optionally substituted C 1 ~C 4 -alkyl or optionally substituted C 1 ~C 4 -alkoxy; R 3 is hydrogen, halogen, or optionally substituted C 1 ~C 4 -alkyl or optionally substituted C 1 ~C 4 -alkoxy; R 4 is phenyl optionally substituted with 1, 2 or 3 substituents; R 5 and R 5’ are independently hydrogen, halogen, cyano, C1 ~C 4 -Alkyl or C 1 ~C 4 Haloalkyl, "optionally substituted" refers to the recited group being optionally substituted with the same groups as "optionally substituted" defined for the broadest embodiment of formula (IA) above.

[0075] In another embodiment of formula (IA): R 1 is optionally substituted C 1 ~C 4 -alkyl, optionally substituted C 1 ~C 4 -alkoxy, optionally substituted C 2 ~C 4 -alkenyl, optionally substituted C 2 ~C 4 -alkynyl, an optionally substituted saturated or partially unsaturated 5-, 6-, or 7-membered heterocyclyl group, an optionally substituted heteroaryl, or -NR a R b and R a and R b is independently optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, and S, and which may be substituted; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 4 - alkyl; R 2 is hydrogen, halogen, or optionally substituted C 1 ~C 4 -alkyl or optionally substituted C 1 ~C 4 -alkoxy; R 3 is hydrogen, halogen, or optionally substituted C 1 ~C4 -alkyl or optionally substituted C 1 ~C 4 -alkoxy; R 4 is phenyl optionally substituted with 1, 2 or 3 substituents; R 5 and R 5’ are independently hydrogen, halogen, cyano, C 1 ~C 4 -Alkyl or C 1 ~C 4 Haloalkyl, "optionally substituted" refers to the recited group being optionally substituted with the same groups as "optionally substituted" defined for the broadest embodiment of formula (IA) above.

[0076] In yet another embodiment, the present invention comprises a compound of formula (IA) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R 4 , L, Q, W, W 1 , Z, Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 has the same definition as for formula (IA); the dashed bond ( [ka] ) indicates a single or double bond; R 1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl or -NRa R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may together with the nitrogen to which they are attached form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as "optionally substituted" defined for the broadest embodiment of formula (IA) above; with the exception of the following compounds:

[0077] [ka]

[0078] In one embodiment, L is L1. In another embodiment, L is L2. In another embodiment, L is L3. In another embodiment, L is L4. In another embodiment, L is L5. In another embodiment, L is L6. In another embodiment, L is L7. In another embodiment, L is L8. In another embodiment, L is L9. In another embodiment, L is L10. In another embodiment, L is L11. In another embodiment, L is L12. In another embodiment, L is L13. In another embodiment, L is L14. In another embodiment, L is L15. In another embodiment, L is L16. In another embodiment, L is L17.

[0079] In some embodiments of Formula (I) or Formula (IA), R 1 is hydrogen. In some embodiments, R 1 is C 1 ~C 4 -Alkyl, C 1 ~C 4 -Haloalkyl, C 1 ~C 4-Haloalkyl, Amino, C 1 ~C 4 -Alkylamino, or di-(C 1 ~C 4 -alkyl)amino. In some embodiments, R 1 is dimethylamino. In some embodiments, R 1 is C 1 ~C 4 -Alkyl or C 1 ~C 4 -haloalkyl. In another embodiment, R 1 is a halogen. In another embodiment, R 1 is chloro or fluoro. In another embodiment, R 1 is C 1 ~C 4 -Alkyl-SO p -, C 1 ~C 4 -Haloalkyl-SO p -or-SF 5 It is.

[0080] In other embodiments, R 1 is hydroxy-C 1 ~C 4 -Alkyl, C 1 ~C 4 -Alkoxy-C 1 ~C 4 -Alkyl, C 1 ~C 4 -Haloalkoxy-C 1 ~C 4 -Alkyl or C 1 ~C 4 -Haloalkoxy-C 1 ~C 4 -haloalkyl. In another embodiment, R 1 is hydroxy-C 1 ~C 3 -alkyl. In another embodiment, R 1 -C(CH 3 ) 2It is OH. In another embodiment, R 1 is methyl, ethyl, propyl, butyl, pentyl, isopropyl (i-Pr), tert-butyl (t-butyl), prop-1-en-2-yl, 2-fluoroprop-2-yl, 1,1-difluoroethyl or 2-hydroxyprop-2-yl. In some embodiments, R 1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl.

[0081] In other embodiments, R 1 is isopropyl or tert-butyl. In one embodiment, R 1 is tert-butyl. In another embodiment, R 1 is C 1 ~C 3 -Alkoxy or C 1 ~C 3 -haloalkoxy. In another embodiment, R 1 is OCH 3 or OCH 2 CH 3 It is. In another embodiment, R 1 is OCF 3 or SCF 3 It is. In another embodiment, R 1 CF 3 , -CH 2 CF 3 , -CHFCF 3 or -CF 2 CF 3 It is. In some embodiments, R 1 is C 2 ~C 4 -alkenyl or C 2 ~C 4 -haloalkenyl. In some embodiments, R 1is optionally substituted cyclopentyl or optionally substituted cyclohexyl. In other embodiments, R 1 is optionally substituted cyclopropyl or optionally substituted cyclobutyl. In another embodiment, R 1 is optionally substituted cyclopropyl. In one embodiment, R 1 is one or more C 1 ~C 6 -Alkyl or C 1 ~C 6 -cyclopropyl substituted with a haloalkyl group.

[0082] In another embodiment, R 1 is one or more methyl or CF 3 Group-substituted cyclopropyl. In some embodiments, R 1 is an optionally substituted saturated or unsaturated 6-membered heterocyclyl group. In one embodiment, R 1 -NR a R b and R a and R b are independently hydrogen or C 1 ~C 6 In another embodiment, R 1 -NR a R b and R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, and S, and which may be substituted.

[0083] In another embodiment, R 1 -NR a R b and R a and R bmay together with the nitrogen to which they are attached form a 3- or 4-membered heterocyclyl group, which heterocyclyl group may include one or more C 1 ~C 4 -Alkyl, C 1 ~C 4 -Optionally substituted with haloalkyl or halogen. In another embodiment, R 1 -NR a R b and R a and R b may together with the nitrogen to which they are attached form a four-membered azetidinyl group, which is optionally substituted with one or more halogens.

[0084] In another embodiment, R 1 -NR a R b and R a and R b may, together with the nitrogen to which they are attached, form a 4-membered heterocyclyl group, which is substituted with 1 or 2 halogen atoms. 1 -NR a R b and R a and R b may together with the nitrogen to which they are attached form a 4-membered heterocyclyl group, which is substituted with 1 or 2 fluoro atoms. In another embodiment, R 1 is C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -haloalkylaminocarbonyl.

[0085] In some embodiments, R 1 is optionally substituted tetrahydrofuryl, dihydrofuryl, morpholino, pyranyl, dihydropyranyl, piperidinyl, dihydropiperidinyl, dihydrothiophene, or tetrahydrothiophene. In some embodiments, R 1 is optionally substituted phenyl. In some embodiments, R 1 is an aryl group consisting of 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, nyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyranyl, dihydropyranyl, tetrahydropyranyl, thiopyranyl, dihydrothiopyranyl, tetrahydrothiopyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl or triazinyl. In some embodiments, R 1 is aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl or pyrrolyl, all of which are represented by one or more C 1 ~C 4 -Alkyl, C 1 ~C 4 - optionally substituted by haloalkyl or halogen. In some embodiments, R 1is morpholinyl, piperidinyl or piperazinyl, each of which is represented by one or more C 1 ~C 4 -Alkyl, C 1 ~C 4 - optionally substituted by haloalkyl or halogen.

[0086] In some embodiments, R 1 is one or more C 1 ~C 4 -Alkyl, C 1 ~C 4 -aziridinyl or azetidinyl optionally substituted by haloalkyl or halogen.

[0087] In other embodiments, R 1 is one or more C 1 ~C 3 -Alkyl, C 1 ~C 3 - aziridinyl or azetidinyl optionally substituted by haloalkyl, chloro or fluoro. In other embodiments, R 1 is one or more of methyl, ethyl, trifluoromethyl, -CH 2 CF 3 , -CF 2 CF 3 , aziridinyl or azetidinyl optionally substituted by chloro or fluoro. In other embodiments, R 1 is aziridinyl or azetidinyl optionally substituted by one or more methyl or fluoro. In another embodiment, R 1 is azetidinyl substituted by one or more fluoro.

[0088] In yet another embodiment, R 1 is an azetidinyl substituted by two fluoro. In another embodiment, R 1 is azetidinyl substituted by one or more methyl groups. In another embodiment, R 1 is azetidinyl substituted by one or more fluoro and one or more methyl groups.

[0089] In yet another embodiment, R 1 is an azetidinyl selected from the following groups: [ka] In some embodiments, R 1 is one or more C 1 ~C 4 -Alkyl, C 1 ~C 4 -pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, each of which may be substituted by haloalkyl or halogen. In other embodiments, R 1 is one or more C 1 ~C 4 -Alkyl, C 1 ~C 4 -morpholinyl, piperidinyl or piperazinyl, optionally substituted by haloalkyl or halogen. In other embodiments, R 1 is one or more C 1 ~C 3 -Alkyl, C 1 ~C 3 -haloalkyl, morpholinyl, piperidinyl or piperazinyl, optionally substituted with chloro or fluoro. In other embodiments, R 1 is one or more of methyl, ethyl, trifluoromethyl, -CH 2 CF 3 , -CF 2 CF 3 , morpholinyl, piperidinyl or piperazinyl, optionally substituted by chloro or fluoro. In another embodiment, R 1 is morpholinyl. In one embodiment, R 1’is hydrogen. In another embodiment, R 1’ is C 1 ~C 3 -alkyl. In another embodiment, R 1’ is methyl.

[0090] In another embodiment, R 1’ is C 1 ~C 3 -haloalkyl.

[0091] In another embodiment, R 1’ CF 3 It is. In another embodiment, R 1’ is a halogen. In some embodiments, R 2 is hydrogen, C 1 ~C 4 -Alkyl, C 1 ~C 4 -Haloalkyl, Amino, C 1 ~C 4 -Alkylamino, or di-(C 1 ~C 4 alkyl)amino. In some embodiments, R 2 is methyl. In another embodiment, R 2 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl. In another embodiment, R 2 is hydrogen, CF 3 , -CH 2 CF 3 , -CHFCF 3 or -CF 2 CF 3 It is.

[0092] In one embodiment, R 2 CF 3 It is. In some embodiments, R 2 is hydrogen. In some embodiments, R2 is a halogen. In another embodiment, R 2 is fluoro, bromo or chloro. In another embodiment, R 2 is hydrogen, halogen, C 1 ~C 4 Alkyl or C 1 ~C 4 It is haloalkyl. In another embodiment, R 2 is hydrogen, chloro, fluoro, bromo, methyl or CF 3 It is. In another embodiment, R 2 is hydrogen, C 1 ~C 4 -Alkoxy, C 1 ~C 4 -haloalkoxy or S(O) p (C 1 ~C 4 -Alkyl or C 1 ~C 4 -haloalkyl) (wherein p is 0, 1 or 2). In another embodiment, R 2 is methoxy, ethoxy, propoxy or butoxy. In another embodiment, R 2 is methylthio, ethylthio, propylthio or butylthio. In another embodiment, R 2 -OCF 3 or -SCF 3 It is. In some embodiments, R 2 is C 2 ~C 4 -alkenyl or C 2 ~C 4 -haloalkenyl. In some embodiments, R 2 is optionally substituted cyclopentyl or optionally substituted cyclohexyl. In some embodiments, R 2 is an optionally substituted saturated or unsaturated 6-membered heterocyclyl group.

[0093] In some embodiments, R 2 is optionally substituted tetrahydrofuryl, dihydrofuryl, morpholino, pyranyl, dihydropyranyl, piperidinyl, dihydropiperidinyl, dihydrothiophene, or tetrahydrothiophene. In some embodiments, R 2 is optionally substituted phenyl. In other embodiments, R 2 is phenyl substituted with 1, 2, or 3 substituents which are independently halo, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkoxy, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0094] In another embodiment, R 2 is a 5- or 6-membered heteroaryl having one or two substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0095] In one embodiment, R 2 is halogen, cyano, nitro, C 1 ~C 3 -Alkyl, C 1 ~C 3 -Haloalkyl, C 1 ~C 3 -Alkoxy, C 1 ~C 3 -haloalkoxy or (C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl)S(O)p and pyridinyl optionally substituted with In some embodiments, R 2 is an optionally substituted 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 or triazinyl.

[0096] In some embodiments, R 2 is aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolyl, or morpholinyl, all of which may be substituted by one or more halogens. In some embodiments, R 3 is hydrogen, C 1 ~C 4 -Alkyl, C 1 ~C 4 -Haloalkyl, Amino, C 1 ~C 4 -Alkylamino, or di-(C 1 ~C 4 alkyl)amino. In another embodiment, R 3 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl. In certain embodiments, R 3 is methyl. In another embodiment, R 3 is hydrogen, CF3 , -CH 2 CF 3 , -CHFCF 3 or -CF 2 CF 3 It is.

[0097] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a halogen. In another embodiment, R 3 is fluoro, bromo or chloro. In certain embodiments, R 3 is chloro. In another embodiment, R 3 is hydrogen, halogen, C 1 ~C 4 Alkyl or C 1 ~C 4 It is haloalkyl. In another embodiment, R 3 is hydrogen, chloro, fluoro, bromo, methyl or CF 3 It is. In another embodiment, R 3 is hydrogen, C 1 ~C 4 -Alkoxy, C 1 ~C 4 -haloalkoxy or S(O) p (C 1 ~C 4 -Alkyl or C 1 ~C 4 -haloalkyl) (wherein p is 0, 1 or 2).

[0098] In another embodiment, R 3 is methoxy, ethoxy, propoxy or butoxy. In another embodiment, R 3 is methylthio, ethylthio, propylthio or butylthio. In another embodiment, R 3 -OCF 3 or -SCF 3 It is. In some embodiments, R3 is C 1 ~C 4 -alkenyl or C 1 ~C 4 -haloalkenyl. In some embodiments, R 3 is optionally substituted cyclopentyl or optionally substituted cyclohexyl.

[0099] In some embodiments, R 3 is an optionally substituted saturated or unsaturated 6-membered heterocyclyl group. In some embodiments, R 3 is optionally substituted tetrahydrofuryl, dihydrofuryl, morpholino, pyranyl, dihydropyranyl, piperidinyl, dihydropiperidinyl, dihydrothiophene, or tetrahydrothiophene. In some embodiments, R 3 is optionally substituted phenyl. In other embodiments, R 3 is phenyl substituted with 1, 2, or 3 substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkoxy, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0100] In another embodiment, R 3 is a 5- or 6-membered heteroaryl having one or two substituents which are independently halo, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy. In one embodiment, R 3are halo, cyano, nitro, C 1 ~C 3 -Alkyl, C 1 ~C 3 -Haloalkyl, C 1 ~C 3 -Alkoxy, C 1 ~C 3 -haloalkoxy or (C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl)S(O) p and pyridinyl optionally substituted with In some embodiments, R 3 is an optionally substituted 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 or triazinyl.

[0101] In some embodiments, R 3 is aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolyl, or morpholinyl, all of which may be substituted by one or more halogens. In some embodiments, R 4 is a 6- to 10-membered aryl optionally substituted with 1, 2, 3, 4, or 5 substituents. In some embodiments, R 4 is C 1 ~C 4-Alkyl or C 1 ~C 4 -haloalkyl. In some embodiments, R 4 is methyl, ethyl, n-propyl, n-butyl, isopropyl, tert-butyl, sec-butyl or isobutyl. In other embodiments, R 4 CF 3 , -CH 2 CF 3 , -CHFCF 3 or -CF 2 CF 3 It is.

[0102] In some embodiments, R 4 is an optionally substituted C 3 ~C 8 -cycloalkyl. In yet another embodiment, R 4 is an optionally substituted C 3 ~C 6 -cycloalkyl. In yet another embodiment, R 4 is an optionally substituted C 3 ~C 8 -cycloalkenyl or C 3 ~C 6 -cycloalkenyl. In some embodiments, R 4 is optionally substituted cyclopentyl or cyclohexyl. In other embodiments, R 4 is optionally substituted cyclopropyl or cyclobutyl.

[0103] In one embodiment, R 4 is one or more halo, C 1 ~C 3 -Alkyl or C 1 ~C 3 -cyclohexyl optionally substituted by haloalkyl. 4 is one or two fluoro, chloro or CF 3 and cyclohexyl substituted with . In some embodiments, R 4is optionally substituted piperidinyl, morpholinyl, tetrahydrofuranyl, or dihydrofuranyl. 4 is one or more halogens, C 1 ~C 6 -Alkyl or C 1 ~C 6 In another embodiment, R is a piperidinyl, morpholinyl, tetrahydrofuranyl, or dihydrofuranyl substituted with -haloalkyl. 4 is piperidinyl, morpholinyl, tetrahydrofuranyl or dihydrofuranyl substituted with one or more methyl, chloro or fluoro.

[0104] In some embodiments, R 4 is a 5-10 membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 substituents. In one embodiment, the 5-10 membered heteroaryl is pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, furanyl, thiophenyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, pyrazolylbenzofuranyl, benzothiophenyl, imidazopyridyl, imidazopyrimidyl or pyrrolopyrimidyl. In other embodiments, R 4 is an optionally substituted spirocyclic heterocyclyl-carbocyclyl group, an optionally substituted spirocyclic heterocyclyl-heterocyclyl group, an optionally substituted spirocyclic carbocyclyl-carbocyclyl group or an optionally substituted spirocyclic carbocyclyl-heterocyclyl group. 4is a 5- to 11-membered optionally substituted spirocyclic heterocyclyl-carbocyclyl group, a 5- to 11-membered optionally substituted spirocyclic heterocyclyl-heterocyclyl group, a 5- to 11-membered optionally substituted spirocyclic carbocyclyl-carbocyclyl group or a 5- to 11-membered optionally substituted spirocyclic carbocyclyl-heterocyclyl group. Non-limiting examples of spirocyclic carbocyclyl-carbocyclyl, spirocyclic carbocyclyl-heterocyclyl and spirocyclic heterocyclyl-heterocyclyl groups are shown in the following figures.

[0105] [ka]

[0106] However, it will be clear to those skilled in the art that the second ring of the spirocyclic group may be attached at any available carbon of the first ring. It will also be understood that the first ring of the spirocyclic group may be attached to the molecule at any available atom. Thus, the present invention includes 3-, 4-, 5-, 6- and 7-membered carbocyclic or heterocyclic rings as defined herein that are attached to the second 3-, 4-, 5-, 6- and 7-membered carbocyclic or heterocyclic ring at any available carbon atom of the first ring. In some embodiments, R 4 is phenyl substituted with 1 to 4 substituents. 4 is phenyl substituted with 1 to 3 substituents. 4 is phenyl substituted with 1 or 2 substituents. In some embodiments, R 4 is phenyl substituted with 1, 2, 3, or 4 substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, phenyl, substituted phenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0107] In some embodiments, R 4 is a para-substituted phenyl. In some embodiments, R 4 is a meta substituted phenyl. In some embodiments, R 4 is an ortho-substituted phenyl. In some embodiments, R 4 is halophenyl. In some embodiments, R 4 is haloalkylphenyl. In some embodiments, R 4 is haloalkoxyphenyl.

[0108] In some embodiments, R 4 is phenyl substituted with two substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0109] In some embodiments, R 4 is a 2,3-disubstituted phenyl. In some embodiments, R 4 is a 2,4-disubstituted phenyl. In some embodiments, R 4 is a 2,5-disubstituted phenyl. In some embodiments, R 4 is a 2,6-disubstituted phenyl. In some embodiments, R 4 is a 3,5-disubstituted phenyl.

[0110] In other embodiments, R 4 is a 3,4-disubstituted phenyl. In other embodiments, R 4is a 3,6-disubstituted phenyl. In some embodiments, R 4 is dihalophenyl, for example dichlorophenyl; difluorophenyl; or chlorophenyl, fluorophenyl. In some embodiments, R 4 is 2,3-dihalophenyl. In other embodiments, R 4 is 2,3-dichlorophenyl or 2,3-difluorophenyl. In another embodiment, R 4 is 3,5-dichlorophenyl or 2,3-difluorophenyl. In some embodiments, R 4 is chlorophenyl. In another embodiment, R 4 is fluorophenyl. In another embodiment, R 4 is dichlorophenyl. In another embodiment, R 4 is difluorophenyl. In yet another embodiment, R 4 is 3,5-dichlorophenyl. In another embodiment, R 4 is 3,5-difluorophenyl. In another embodiment, R 4 is 2,6-dichlorophenyl. In another embodiment, R 4 is 2,6-difluorophenyl. In some embodiments, R 4 is phenyl substituted with three substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0111] In some embodiments, R 4 is trihalophenyl, for example trichlorophenyl; trifluorophenyl; or chloro-, chloro-, fluorophenyl, or fluoro-, fluoro-, chlorophenyl. In another embodiment, R 4 is 2,3,5-trihalophenyl. In another embodiment, R 4 is 2,4,6-trihalophenyl. In one embodiment, R 4 is 2,5-dichloro-4-fluorophenyl. 4 is 2,4,6-trifluorophenyl. In another embodiment, R 4 is 2,4,6-trichlorophenyl. In one embodiment, R 4 is 2,6-dichloro-4-fluorophenyl. In another embodiment, R 4 is 2,3,5-trifluorophenyl. In another embodiment, R 4 is 2,3,5-trichlorophenyl. In another embodiment, R 4 is 2,3-difluoro-5-chlorophenyl. In another embodiment, R 4 is 2,3-dichloro-5-fluorophenyl.

[0112] In some embodiments, R 4 is phenyl substituted with halogen and haloalkyl. In some embodiments, R 4 is phenyl substituted with halogen and haloalkoxy. In some embodiments, R 4 is phenyl substituted with haloalkyl and haloalkoxy. In some embodiments, R 4 is phenyl substituted with 2 halogens and haloalkyl. In some embodiments, R 4 is phenyl substituted with 2 halogen and haloalkoxy. In some embodiments, R 4 is phenyl substituted with one haloalkyl, one halogen, and one haloalkoxy.

[0113] In some embodiments, R 4 is phenyl substituted with one halogen and two haloalkyl. In some embodiments, R 4 is a 5-membered heteroaryl optionally substituted by one or two substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy. In some embodiments, R 4 is a 6-membered heteroaryl optionally substituted by one or two substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0114] In some embodiments, R 4 is 2-pyridyl optionally substituted by one or two substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy. In some embodiments, R 4is 3-pyridyl optionally substituted by one or two substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0115] In some embodiments, R 4 is 4-pyridyl optionally substituted by one or two substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0116] In another embodiment, R 4 is 4-pyridyl which is unsubstituted or substituted with one or two chloro or fluoro. In yet another embodiment, R 4 is 3-pyridyl which is unsubstituted or substituted by one or two chloro or fluoro. In other embodiments, R 4 is an optionally substituted 3- to 7-membered heterocycle. 4is an optionally substituted 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 or triazinyl.

[0117] In another embodiment, R 4 may be an optionally substituted heterocyclic bridged bicyclic group. In some embodiments, R 5 and / or R 5’ is hydrogen. In some embodiments, each R 5 and / or R 5’ are independently hydrogen, C 1 ~C 4 -Alkyl, C 1 ~C 4 -Haloalkyl, Amino, C 1 ~C 4 -Alkylamino, or di-(C 1 ~C 4 alkyl)amino. In another embodiment, each R 5 and / or R 5’ are independently hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, or tert-butyl. In another embodiment, R 5 and / or R 5’ are independently hydrogen, CF 3 , -CH 2CF 3 , -CHFCF 3 or -CF 2 CF 3 It is. In some embodiments, R 5 and / or R 5’ is independently hydrogen or halogen. In another embodiment, R 5 and / or R 5’ is independently hydrogen, fluoro or chloro. In another embodiment, R 5 and / or R 5’ are independently hydrogen, C 1 ~C 4 -Alkoxy, C 1 ~C 4 -haloalkoxy or S(O) p (C 1 ~C 4 -Alkyl or C 1 ~C 4 -haloalkyl), where p is 0, 1 or 2.

[0118] In another embodiment, R 5 and / or R 5’ is independently hydrogen, methoxy, ethoxy, propoxy, or butoxy.

[0119] In another embodiment, R 5 and / or R 5’ is independently hydrogen, methylthio, ethylthio, propylthio, or butylthio. In another embodiment, R 5 and / or R 5’ are independently hydrogen, -OCF 3 or -SCF 3 It is. In some embodiments, R 5 and / or R 5’ are independently hydrogen, C 1 ~C 4 -alkenyl or C 1 ~C 4 -haloalkenyl. In some embodiments, R 5and / or R 5’ are independently hydrogen, C 1 ~C 4 -Alkylcarbonyl or C 1 ~C 4 -alkoxycarbonyl.

[0120] In other embodiments, R 5 and / or R 5’ are independently hydrogen, C 1 ~C 4 -alkylcarbonylamino. In some embodiments, R 5 and / or R 5’ is independently hydrogen, optionally substituted cyclopentyl, or optionally substituted cyclohexyl. In some embodiments, R 5 and / or R 5’ are independently hydrogen, optionally substituted tetrahydrofuryl, dihydrofuryl, morpholino, pyranyl, dihydropyranyl, piperidinyl, dihydropiperidinyl, dihydrothiophene, or tetrahydrothiophene. In some embodiments, R 5 and / or R 5’ are independently hydrogen or optionally substituted phenyl.

[0121] In other embodiments, R 5 and / or R 5’ is independently hydrogen, phenyl substituted with 1, 2, or 3 substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkoxy, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy. In other embodiments, R 5 and / or R 5’is independently hydrogen, a 5- or 6-membered heteroaryl having one or two substituents which are independently halogen, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, or haloalkenyloxy.

[0122] In some embodiments, R 5 and / or R 5’ are independently hydrogen, optionally substituted aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, oxadiazolyl, piperi thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl or triazinyl. In some embodiments, R 5 and R 5’ is independently hydrogen, aziridinyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolyl, or morpholinyl, all of which are optionally substituted by one or more halogens.

[0123] In some embodiments, R 6 and R 7 is independently, in each occurrence, hydrogen, halogen, C 1 ~C 4 -Alkyl, C 1 ~C4 -haloalkyl. In another embodiment, R 6 and R 7 are independently hydrogen, halogen or C 1 ~C 4 -alkyl. In another embodiment, R 6 and R 7 Each is hydrogen. In one embodiment, R 6 and R 7 are carbonyl groups (C=O) together with the carbon to which they are attached. In another embodiment, R 6 and R 7 are, together with the carbon to which they are attached, a thiocarbonyl group (C=S). In yet another embodiment, R 6 and R 7 are imino groups (C=NR') together with the carbon to which they are attached. In one embodiment, R 9 is H. In another embodiment, R 9 is C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl. In some embodiments, Q is N. In another embodiment, Q is CR 9 It is. In some embodiments, X is O. In some embodiments, X is S. In some embodiments, X is NR'.

[0124] In some embodiments, W is CH 2 It is. In another embodiment, W is CH, CC 1 ~C 3 -Alkyl or CC 1 ~C 3 In another embodiment, W is CH 2 , C(C 1 ~C 3 -alkyl) 2 Or C(C 1 ~C 3 -haloalkyl)2 It is. In other embodiments, W is CH 2 , C(CH 3 ) 2 , C(C 2 H 5 ) 2 or C(CF 3 ) 2 It is. In some embodiments, W is absent. In some embodiments, W 1 CH 2 It is. In another embodiment, W 1 , C.H., C.C. 1 ~C 3 -Alkyl or CC 1 ~C 3 -haloalkyl. In another embodiment, W 1 is CH 2 , C(C 1 ~C 3 -alkyl) 2 Or C(C 1 ~C 3 -haloalkyl) 2 It is.

[0125] In another embodiment, W 1 is CH 2 , C(CH 3 ) 2 , C(C 2 H 5 ) 2 or C(CF 3 ) 2 It is. In some embodiments, Z is CH 2 It is. In another embodiment, Z is CH, CC 1 ~C 3 -Alkyl or CC 1 ~C 3 -haloalkyl. In other embodiments, Z is C(C 1 ~C 3 -alkyl) 2 Or C(C 1 ~C 3 -haloalkyl)2 It is. In some embodiments, Z is O.

[0126] In some embodiments, the compound of formula (I) or a salt thereof is a compound of formula (I-1). [ka] (I-1) (In the formula, L, R 1 , R 1’ , R 2 , R 3 , R 4 , Y 1 , Y 3 , Y 4 , Y 5 , Y 6 , Q, W, W 1 and Z are as defined in any of the above Formula (I) embodiments;

[0127] [ka] ) indicates a single bond or a double bond) In another embodiment, a compound of formula (I-1) is provided, wherein L, R 1 , R 1’ , R 2 , R 3 , R 4 , Y 1 , Y 3 , Y 4 , Y 5 , Y 6 , Q, W, W 1 and Z are as defined in any of the embodiments of formula (IA) above; the dashed bond ( [ka] ) indicates a single bond or a double bond)

[0128] In one embodiment of formula (I-1), Z is O. In one embodiment of formula (I-1), W is CH 2and Z is O. In one embodiment, W is absent. In another embodiment, W is absent and Z is CH 2 In one embodiment, Q is N. In another embodiment, Q is CR 9 In another embodiment of formula (I-1), Q is CH. In another embodiment of formula (I-1), W is CH 2 And W 1 CH 2 and Z is CH 2 In another embodiment of formula (I-1), W and W1 are independently CR 6 R 7 and R 6 and R 7 , H, C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl and Z is O. In another embodiment, W and W 1 are CH 2 and Z is O. In one embodiment of formula (I-1), Y 3 is S. In another embodiment of formula (I-1), Y 5 is S. In another embodiment, Y 3 is N. In another embodiment, Y 5 is N. In another embodiment of formula (I-1), Y 5 is N and Y 3 is S. In yet another embodiment of formula (I-1), Y 5 is S and Y 3 is N. In another embodiment of formula (I-1), Y 6 and Y 3 Each is N. In another embodiment of formula (I-1), Y 6 is N and Y 4 is N. In another embodiment, Y 1 is N and Y 5 is N. In another embodiment, Y 3 is N and Y 5 is N. In another embodiment, Y 3 is N and Y 4 is N. In another embodiment, Y 3is NR' and Y 4 is N. In another embodiment, Y 3 is NR', R' is hydrogen or C 1 ~C 3 -alkyl, and Y 4 is N.

[0129] In some embodiments, the compound of formula (I) or a salt thereof is a compound of formula (I-2). [ka] (I-2) (In the formula, R 1 , R 1’ , R 2 , R 3 , R 4 , R', Y 2 , Y 3 , Y 4 , Y 5 , X, Q, W, W 1 and Z are as defined in any of the above Formula (I) embodiments;

[0130] [ka] ) indicates a single bond or a double bond) In another embodiment, a compound of formula (I-2) is provided, wherein R 1 , R 1’ , R 2 , R 3 , R 4 , R', Y 2 , Y 3 , Y 4 , Y 5 , X, Q, W, W 1 and Z is as defined in any of the embodiments of formula (IA) above. In one embodiment of formula (I-2), Q is CR 9 In another embodiment of formula (I-2), Q is CH. In another embodiment of formula (I-2), Q is N.

[0131] In one embodiment of formula (I-2), Z is O. In one embodiment of formula (I-2), W is CH 2 and Z is O. In one embodiment, W is absent. In another embodiment, W is absent and Z is CH 2 In another embodiment, W is absent and Z is CH 2 and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment, W is absent and Z is CH 2 and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment, W is absent and Z is CH 2 and Y 2 is N. In another embodiment, W is absent and Z is CH 2 and Y 4 is N. In another embodiment, W is absent and Z is CH 2 and Y 5 is N. In another embodiment, W is absent and Z is O.

[0132] In another embodiment of formula (I-2), W is CH 2 And W 1 CH 2 and Z is CH 2 In another embodiment of formula (I-2), W and W1 are independently CR 6 R 7 and R 6 and R 7 , H, C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl and Z is O. In some embodiments, W and W 1 Independently, CR 6 R 7 and R 6 and R 7 is H or methyl and Z is O. In another embodiment, W and W 1 are CH 2and Z is O. In one embodiment of formula (I-2), each Y 2 , Y 3 , Y 4 and Y 5 Independently, CR 5 In one embodiment, each Y 2 , Y 3 , Y 4 and Y 5 are independently CH. In another embodiment, Z is O and W is CR 6 R 7 and R 6 and R 7 together with the carbon atom to which they are attached form C=O. In another embodiment of formula (I-2), W 1 is CR 6 R 7 and R 6 and R 7 may together form a 2-5 membered chain which may contain one or two N, O, Si or S atoms to form a carbocyclic or heterocyclic ring. 1 is CR 6 R 7 and R 6 and R 7 may be taken together to form a 3-, 4- or 5-membered chain to form a cyclobutyl, cyclopentyl or cyclohexyl ring.

[0133] In another embodiment, the compound of formula (I) or a salt thereof is a compound of formula (I-3): [ka] (I-3) (In the formula, R 1 , R 1’ , R 2 , R 3 , R 4 , R', Y 2 , Y 3 , Y 4 , Y 5 , X, Q, W, W 1and Z are as defined in any of the above Formula (I) embodiments;

[0134] [ka] ) indicates a single bond or a double bond) In another embodiment, a compound of formula (I-3) is provided, wherein R 1 , R 1’ , R 2 , R 3 , R 4 , R', Y 2 , Y 3 , Y 4 , Y 5 , X, Q, W, W 1 and Z is as defined in any of the embodiments of formula (IA) above.

[0135] In one embodiment of formula (I-3), Q is CR 9 In another embodiment of formula (I-3), Q is CH. In another embodiment of formula (I-3), Q is N. In one embodiment of formula (I-3), Z is O. In one embodiment of formula (I-3), W is CH 2 and Z is O. In one embodiment, W is absent. In another embodiment, W is absent and Z is CH 2 In another embodiment, W is absent and Z is CH 2 and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment, W is absent and Z is CH 2 and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment, W is absent and Z is CH 2 and Y 2 is N. In another embodiment, W is absent and Z is CH 2 and Y 4 is N. In another embodiment, W is absent and Z is CH 2and Y 5 is N. In another embodiment, W is absent and Z is O.

[0136] In another embodiment of formula (I-3), W is CH 2 And W 1 CH 2 and Z is CH 2 In another embodiment of formula (I-3), W and W1 are independently CR 6 R 7 and R 6 and R 7 , H, C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl and Z is O. In some embodiments, W and W 1 Independently, CR 6 R 7 and R 6 and R 7 is H or methyl and Z is O. In another embodiment, W and W 1 are CH 2 and Z is O. In one embodiment of formula (I-3), each Y 2 , Y 3 , Y 4 and Y 5 Independently, CR 5 In one embodiment, each Y 2 , Y 3 , Y 4 and Y 5 are independently CH. In another embodiment, Z is O and W is CR 6 R 7 and R 6 and R 7 together with the carbon atom to which they are attached form C=O. In another embodiment of formula (I-3), W 1 is CR 6 R 7 and R 6 and R 7may together form a 2-5 membered chain which may contain one or two N, O, Si or S atoms to form a carbocyclic or heterocyclic ring. 1 is CR 6 R 7 and R 6 and R 7 may be taken together to form a 3-, 4- or 5-membered chain to form a cyclobutyl, cyclopentyl or cyclohexyl ring.

[0137] In some embodiments, the compound of formula (I) or a salt thereof is a compound of formula (Ia). [ka] (Ia) (In the formula, R 1 , R 1’ , R 2 , R 3 , R 4 , R', R 9 , W 1 , Z, Y 2 , Y 3 , Y 4 and Y 5 is as defined in any of the above Formula (I) embodiments; W is absent or -CR 6 R 7 -, -NR 8 -, -O-, or -S(O) P -; and dashed bonds ( [ka] ) indicates a single bond or a double bond)

[0138] In another embodiment, a compound of formula (Ia) is provided, wherein R 1 , R 1’ , R 2 , R 3 , R 4 , R', R 9 , W 1 , Z, Y 2 , Y 3 , Y 4 and Y 5is as defined in any of the embodiments of formula (IA) above; W is absent or CR 6 R 7 -; and dashed bonds ( [ka] ) indicates a single bond or a double bond)

[0139] In one embodiment of Formula (Ia), R 9 In another embodiment of formula (Ia), R' is H. In another embodiment, W and W 1 CH 2 In another embodiment, R 1’ is H. In one embodiment of Formula (Ia), Z is O. In one embodiment of Formula (Ia), W is CH 2 and Z is O. In one embodiment, W is absent. In another embodiment, W is absent and Z is CH 2 In another embodiment, W is absent and Z is CH 2 and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment, W is absent and Z is CH 2 and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment, W is absent and Z is CH 2 and Y 2 is N. In another embodiment, W is absent and Z is CH 2 and Y 4 is N. In another embodiment, W is absent and Z is CH 2 and Y 5 is N. In another embodiment, W is absent and Z is O.

[0140] In another embodiment of formula (Ia), W is CH 2 And W 1 CH 2 and Z is CH 2In another embodiment of formula (Ia), W and W1 are independently CR 6 R 7 and R 6 and R 7 , H, C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl and Z is O. In some embodiments, W and W 1 Independently, CR 6 R 7 and R 6 and R 7 is H or methyl and Z is O. In another embodiment, W and W 1 are CH 2 and Z is O. In one embodiment of Formula (Ia), each Y 2 , Y 3 , Y 4 and Y 5 Independently, CR 5 In one embodiment, each Y 2 , Y 3 , Y 4 and Y 5 are independently CH. In another embodiment, Z is O and W is CR 6 R 7 and R 6 and R 7 together with the carbon atom to which they are attached form C=O.

[0141] In another embodiment of formula (Ia), W 1 is CR 6 R 7 and R 6 and R 7 may together form a 2-5 membered chain which may contain one or two N, O, Si or S atoms to form a carbocyclic or heterocyclic ring. 1 is CR 6 R 7 and R 6 and R 7may be taken together to form a 3-, 4- or 5-membered chain to form a cyclobutyl, cyclopentyl or cyclohexyl ring.

[0142] In some embodiments, the compound of Formula (I) or a salt thereof is a compound of Formula (Ib). [ka] (Ib) (In the formula, R 1 , R 1’ , R 2 , R 3 , R 4 , R', R 9 , Y 2 , Y 3 , Y 4 , Y 5 , W 1 and Z are as defined in any of the above Formula (I) embodiments; W is absent or CR 6 R 7 -, -NR 8 -, -O-, or -S(O) P -; and dashed bonds ( [ka] ) indicates a single bond or a double bond)

[0143] In another embodiment, a compound of formula (Ib) is provided, wherein R 1 , R 1’ , R 2 , R 3 , R 4 , R', R 9 , W, W 1 , Z, Y 2 , Y 3 , Y 4 and Y 5 is as defined in any of the embodiments of formula (IA) above; W is absent or CR 6 R 7 -; and dashed bonds ( [ka] ) indicates a single bond or a double bond)

[0144] In one embodiment of Formula (Ib), R 9 In another embodiment of formula (Ib), R' is H. In another embodiment, W and W 1 are CH 2 In another embodiment, R 1’ is H.

[0145] In one embodiment of Formula (Ib), Z is O. In one embodiment of Formula (Ib), W is CH 2 and Z is O. In one embodiment, W is absent. In another embodiment, W is absent and Z is CH 2 In another embodiment, W is absent and Z is CH 2 and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment, W is absent and Z is CH 2 and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment, W is absent and Z is CH 2 and Y 2 is N. In another embodiment, W is absent and Z is CH 2 and Y 4 is N. In another embodiment, W is absent and Z is CH 2 and Y 5 is N. In another embodiment, W is absent and Z is O. In another embodiment of formula (Ib), W is CH 2 And W 1 CH 2 and Z is CH 2 In another embodiment of formula (Ib), W and W1 are independently CR 6 R 7 and R 6 and R 7 , H, C 1 ~C 3 -Alkyl or C 1 ~C3 -haloalkyl and Z is O. In some embodiments, W and W 1 Independently, CR 6 R 7 and R 6 and R 7 is H or methyl and Z is O. In another embodiment, W and W 1 are CH 2 and Z is O.

[0146] In one embodiment of Formula (Ib), each Y 2 , Y 3 , Y 4 and Y 5 Independently, CR 5 In one embodiment, each Y 2 , Y 3 , Y 4 and Y 5 are independently CH. In another embodiment, Z is O and W is CR 6 R 7 and R 6 and R 7 together with the carbon atom to which they are attached form C=O. In another embodiment of formula (Ib), W 1 is CR 6 R 7 and R 6 and R 7 may together form a 2-5 membered chain which may contain one or two N, O, Si or S atoms to form a carbocyclic or heterocyclic ring. 1 is CR 6 R 7 and R 6 and R 7 may be taken together to form a 3-, 4- or 5-membered chain to form a cyclobutyl, cyclopentyl or cyclohexyl ring.

[0147] In some embodiments, the compound of Formula (I) or a salt thereof is a compound of Formula (Ic). [ka] (I C) (In the formula, R 1 , R 1’ , R 2 , R 3 , R 4 , R', R 9 , R 5 , W 1 and Z are as defined in any of the above Formula (I) embodiments; W is absent or CR 6 R 7 -, -NR 8 -, -O-, or -S(O) P -; o is 0, 1, 2, 3 or 4; dashed bond (

[0148] [ka] ) indicates a single bond or a double bond) In another embodiment, a compound of formula (Ic) is provided, wherein R 1 , R 1’ , R 2 , R 3 , R 4 , R', R 9 , R 5 , W 1 and Z are as defined in any of the embodiments of formula (IA) above; W is absent or CR 6 R 7 -; o is 0, 1, 2, 3 or 4; dashed bond ( [ka] ) indicates a single bond or a double bond) In one embodiment of Formula (Ic), R 9 In another embodiment of formula (Ic), R' is H. In another embodiment, W and W 1 are CH 2 In another embodiment, R 1’ is H. In one embodiment of Formula (Ic), Z is O. In one embodiment of Formula (Ic), W is CH 2 and Z is O. In one embodiment, W is absent. In another embodiment, W is absent and Z is CH2 In another embodiment, W is absent and Z is O.

[0149] In another embodiment of formula (Ic), W is CH 2 And W 1 CH 2 and Z is CH 2 In another embodiment of formula (Ic), W and W1 are independently CR 6 R 7 and R 6 and R 7 , H, C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl and Z is O. In some embodiments, W and W 1 Independently, CR 6 R 7 and R 6 and R 7 is H or methyl and Z is O. In another embodiment, W and W 1 are CH 2 and Z is O. In one embodiment of Formula (Ic), o is 1. In another embodiment, o is 2. In yet another embodiment, o is 3. In one embodiment, R 5 is halogen. In another embodiment, R 5 In another embodiment, o is 1 or 2 and R 5 is chloro or fluoro.

[0150] In another embodiment, the compound of formula (I) or a salt thereof is a compound of formula (Id). [ka] (Id) (In the formula, R 1 , R 1’ , R 2 , R 3 , R 4 , R ’ , R 9 , R 5 , W 1and Z is as defined in any of the above embodiments of formula (I); W is absent or -CR 6 R 7 -, -NR 8 -, -O-, or -S(O) P -; o is 0, 1, 2, 3 or 4; dashed bond (

[0151] [ka] ) indicates a single bond or a double bond) In another embodiment, a compound of formula (Id) is provided, wherein R 1 , R 1’ , R 2 , R 3 , R 4 , R', R 9 , R 5 , W 1 and Z is as defined in any of the embodiments of formula (IA) above; W is absent or -CR 6 R 7 -; o is 0, 1, 2, 3 or 4; dashed bond ( [ka] ) indicates a single bond or a double bond)

[0152] In one embodiment of Formula (Id), R 9 In another embodiment of formula (Id), R' is H. In another embodiment, W and W 1 are CH 2 In another embodiment, R 1’ is H. In one embodiment of Formula (Id), Z is O. In one embodiment of Formula (Id), W is CH 2 and Z is O. In one embodiment, W is absent. In another embodiment, W is absent and Z is CH 2 In another embodiment, W is absent and Z is O.

[0153] In another embodiment of formula (Id), W is CH 2 And W1 CH 2 and Z is CH 2 In another embodiment of formula (Id), W and W1 are independently CR 6 R 7 and R 6 and R 7 , H, C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl and Z is O. In some embodiments, W and W 1 Independently, CR 6 R 7 and R 6 and R 7 is H or methyl and Z is O. In another embodiment, W and W 1 are CH 2 and Z is O.

[0154] In one embodiment of Formula (Id), o is 1. In another embodiment, o is 2. In yet another embodiment, o is 3. In one embodiment, R 5 is halogen. In another embodiment, R 5 In another embodiment, o is 1 or 2 and R 5 is chloro or fluoro.

[0155] In another embodiment, the compound of formula (I) or a salt thereof is a compound of formula (Ie). [ka] (Ie) (In the formula, R 1 , R 1’ , R 2 , R 3 , R', R 9 , Y 2 , Y 3 , Y 4 , Y 5 , W 1 and Z are as defined for formula (I); W is absent or -CR 6 R 7 -, -NR8 -, -O-, or -S(O) P m is 0, 1, 2, 3, 4, or 5; each R 10 is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6-Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2); SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and may be optionally substituted, where "optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (I) above.

[0156] In another embodiment, the present invention includes a compound of formula (Ie) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R', R 9 , Y 2 , Y 3 , Y 4 , Y 5 , W 1 and Z is as defined for (I); W is absent or -CR 6 R 7 -, -NR 8 -, -O-, or -S(O) P m is 0, 1, 2, 3, 4, or 5; each R 10is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2); SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p(optionally substituted alkyl or haloalkyl) (wherein p is 0, 1 or 2); -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, or 5-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (I) above.

[0157] In another embodiment, the present invention includes a compound of formula (Ie) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R', R 9 , Y 2 , Y 3 , Y 4 , Y 5 , W 1 and Z are as defined for formula (I); W is absent or -CR 6 R 7 -, -NR 8 -, -O-, or -S(O) P m is 0, 1, 2, 3, 4, or 5; each R 10 is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2); SF 5 , or -NR a R b and R a and R b are independently H, C1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p (optionally substituted alkyl or haloalkyl) (wherein p is 0, 1 or 2); -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R bmay, together with the nitrogen to which they are attached, form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (I) above.

[0158] In another embodiment, a compound of formula (Ie) is provided, wherein R 1 , R 1’ , R 2 , R 3 , R', R 9 , W 1 , Z, Y 2 , Y 3 , Y 4 and Y 5 is as defined for formula (IA); W is absent or -CR 6 R 7 m is 0, 1, 2, 3, 4, or 5; each R 10 is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6-alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl), (wherein p is 0, 1 or 2), SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R bmay, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and may be optionally substituted, where "optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" in relation to the broadest embodiment of formula (IA) above.

[0159] In another embodiment, the present invention includes a compound of formula (Ie) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R', R 9 , Y 2 , Y 3 , Y 4 , Y 5 , W 1 and Z is as defined for formula (IA); W is absent or -CR 6 R 7 m is 0, 1, 2, 3, 4, or 5; each R 10 is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6-alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2); SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R bmay, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p (optionally substituted alkyl or haloalkyl) (wherein p is 0, 1 or 2); -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, or 5-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (IA) above.

[0160] In another embodiment, the present invention includes a compound of formula (Ie) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R', R 9 , Y 2 , Y 3 , Y 4 , Y 5 , W 1 and Z is as defined for formula (IA); W is absent or -CR 6 R 7 m is 0, 1, 2, 3, 4, or 5; each R 10 is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8-cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2); SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p (optionally substituted alkyl or haloalkyl) (wherein p is 0, 1 or 2); -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (IA) above.

[0161] In another embodiment, the present invention provides a compound of formula (Ie) as above, wherein: R' is hydrogen, optionally substituted C 1~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, or optionally substituted benzyl; R 1 is an optionally substituted C 1 ~C 6 -Alkyl, C 1 -C 6 -Haloalkyl, Hydroxy-C 1 -C 6 -Alkyl, Hydroxy-C 1 -C 6 -Haloalkyl, C 1 -C 6 -Alkoxy-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkoxy-C 1 -C 6 -Alkyl, Amino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkoxy, C 2 -C 6 -Alkenyl, C 2 -C 6 -Haloalkenyl, C 2 -C 6 -Alkynyl, C 2 -C 6 -Haloalkynyl, C 2 -C 6 -Alkenyloxy, C 2 -C6 -haloalkenyloxy, C 2 -C 6 -Alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 1 -C 6 -haloalkoxy, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted 3- to 7-membered heterocyclyl, or -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 6 -alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, or 5-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, or optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 - haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6-Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; R 3 is hydrogen, cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; Each R 5 is independently, at each occurrence, hydrogen, halogen, cyano, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 - haloalkoxy; R 6 and R 7 are independently hydrogen, halogen, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Alkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -haloalkoxy or R 6 is R 7 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, and the carbon or nitrogen atoms in the chain may be substituted; R 9 is hydrogen, halogen, C 1 ~C 6 -Alkyl or C 1 ~C 6 - haloalkyl; Each R 10 is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1~C 6 -alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2); SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R bmay, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; m is 0, 1, 2, 3, 4 or 5; Y 2 , Y 3 , Y 4 , Y 5 , W 1 , Z, X and the dashed bond (

[0162] [ka] ) is as defined above for compounds of formula (IA); and W is absent or -CR 6 R 7 -; The term "optionally substituted" means that the recited group is optionally substituted with one or more of halogen (chloro, fluoro, bromo, iodo), hydroxyl, C 1 ~C 6- Alkyl, C 1 ~C 6 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 -C 6 -Alkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -Alkoxy, C 1 -C 6 -Haloalkoxy, Cyano, SF 5 , Acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6-dialkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6 -Alkylthio, C 1 -C 6 -Alkyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, C 1 -C 6 -Haloalkylthio, C 1 ~C 6 -haloalkylsulfinyl or C 1 ~C 6 -haloalkylsulfonyl)

[0163] In another embodiment, the present invention provides a compound of formula (Ie) as above, wherein: R' is hydrogen, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl, or optionally substituted benzyl; R 1 is an optionally substituted C 1 ~C 6 -Alkyl, C 1 -C 6 -Haloalkyl, Hydroxy-C 1 -C 6 -Alkyl, Hydroxy-C 1 -C 6 -Haloalkyl, C 1 -C 6 -Alkoxy-C 1 -C 6 -Alkyl, C 1 -C 6 -Haloalkoxy-C 1 -C 6 -Alkyl, Amino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkylamino-C 1 -C6 -Alkyl, C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Alkylamino-C 1 -C 6 -Alkyl, Di-C 1 -C 6 -Haloalkylamino-C 1 -C 6 -Alkyl, C 1 -C 6 -Alkoxy, C 2 -C 6 -Alkenyl, C 2 -C 6 -Haloalkenyl, C 2 -C 6 -Alkynyl, C 2 -C 6 -Haloalkynyl, C 2 -C 6 -Alkenyloxy, C 2 -C 6 -haloalkenyloxy, C 2 -C 6 -Alkynyloxy, C 2 -C 6 -haloalkynyloxy, C 1 -C 6 -haloalkoxy, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkenyl, optionally substituted 3- to 7-membered heterocyclyl, or -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 6 -alkyl; or R a and R bmay together with the nitrogen to which they are attached form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1-3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, or optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 - haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; R 3 is hydrogen, cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl or C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 - alkyl; Each R 5 is independently, at each occurrence, hydrogen, halogen, cyano, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 - haloalkoxy; R 6 and R 7 are independently hydrogen, halogen, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Alkynyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -haloalkoxy or R 6 is R 7 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, and the carbon or nitrogen atoms in the chain may be substituted; R 9 is hydrogen, halogen, C 1 ~C 6 -Alkyl or C 1 ~C 6 - haloalkyl; Each R 10 is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6 -Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2); SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; m is 0, 1, 2, 3, 4 or 5; Y 2 , Y 3 , Y 4 , Y 5 , W 1 , Z, X and the dashed bond (

[0164] [ka] ) is as defined above for compounds of formula (IA); and W is absent or -CR 6 R 7 -; The term "optionally substituted" means that the recited group is optionally substituted with one or more of halogen (chloro, fluoro, bromo, iodo), hydroxyl, C 1 ~C 6-Alkyl, C 1 ~C 6 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 -C 6 -Alkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -Alkoxy, C 1 -C 6 -Haloalkoxy, Cyano, SF 5 , Acetyl, C 1 -C 6 -Alkoxycarbonyl, C 1 -C 6 -Haloalkoxycarbonyl, C 1 -C 6 -Alkyl carbonyl, C 1 -C 6 -Haloalkylcarbonyl, aminocarbonyl, C 1 -C 6 -Alkylaminocarbonyl, C 1 -C 6 -dialkylaminocarbonyl, C 1 -C 6 -Haloalkylaminocarbonyl, C 1 -C 6 -dihaloalkylaminocarbonyl, C 1 -C 6 -Alkylthio, C 1 -C 6 -Alkyl sulfinyl, C 1 -C 6 -Alkyl sulfonyl, C 1 -C 6 -Haloalkylthio, C 1 ~C 6 -haloalkylsulfinyl or C 1 ~C 6 -haloalkylsulfonyl)

[0165] In another embodiment, the present invention comprises a compound of formula (Ie) or a salt thereof as described above, wherein R 1’ , R 2 , R 3 , R', R 9 , Y2 , Y 3 , Y 4 , Y 5 , W 1 and Z is as defined for formula (IA); W is absent or -CR 6 R 7 m is 0, 1, 2, 3, 4, or 5; each R 10 is cyano, halogen, hydroxyl, C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkyl, C 1 ~C 6 -Alkoxy, C 1 ~C 6 -Haloalkoxy, C 2 ~C 6 -Alkenyl, C 2 ~C 6 -Haloalkenyl, C 2 ~C 6 -Alkynyl, C 2 ~C 6 -Haloalkynyl, C 1 ~C 6 -Alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -Haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si, and S, C 1 ~C 6 -Alkyl carbonyl, C 1 ~C 6 -Haloalkylcarbonyl, C 1 ~C 6 -Alkoxycarbonyl, C 1 ~C 6-Haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 -Alkylaminocarbonyl, C 1 ~C 6 -Haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -Haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2); SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p (optionally substituted alkyl or haloalkyl) (wherein p is 0, 1 or 2); -SF 5 , or -NR a R b and R a and R b is independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; "Optionally substituted" refers to the recited group being optionally substituted with the same groups as defined under "optionally substituted" with respect to the broadest embodiment of formula (IA) above); with the exception of the following compounds:

[0166] [ka]

[0167] In one embodiment of formula (Ie), R 10 is halogen. In another embodiment, R 10 is chloro. In yet another embodiment, R 10 is fluoro. In another embodiment, R 10 is chloro or fluoro and m is 1, 2 or 3. In yet another embodiment, R 10 is fluoro and m is 2. In another embodiment, R 10 is chloro and m is 2. In another embodiment, R 10 is fluoro or chloro, m is 2, and the fluoro or chloro is substituted at the 3 and 5 positions of the phenyl ring. 10 is fluoro or chloro, m is 2, and the fluoro or chloro is substituted at the 2- and 6-positions. In another embodiment of formula (Ie), R 10 is fluoro or chloro and m is 3. In another embodiment, R 10 In another embodiment of formula (Ie), R 10 is fluoro or chloro, m is 3, chloro is substituted at the 2- and 3-positions, and fluoro is substituted at the 5-position of the phenyl ring. 10 is fluoro, m is 3, and the fluoro is substituted at the 2-, 3-, and 5-positions of the phenyl ring. 10 is chloro, m is 3, and fluoro is substituted at the 2-, 3-, and 5-positions of the phenyl ring.

[0168] In one embodiment of formula (Ie), R 9 is H. In another embodiment of formula (Ie), R' is H. In another embodiment, R 1’ is H. In another embodiment, W and W 1 are CH 2 It is. In another embodiment of formula (Ie), W is CH 2 And W 1 CH 2 and Z is CH 2 In another embodiment of formula (Ie), W and W1 are independently CR 6 R 7 and R 6 and R 7 is H and C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl and Z are O. In another embodiment, W and W 1 are CH 2 and Z is O.

[0169] In one embodiment of formula (Ie), R 1 is optionally substituted C 1 ~C 6 -alkyl, optionally substituted C 3 ~C 6 -cycloalkyl, -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 3 -alkyl or R a and R b together with the nitrogen form an optionally substituted 3-, 4-, 5- or 6-membered heterocycle, which may contain one additional heteroatom selected from O or N; R 2 is hydrogen or optionally substituted C 1 ~C 3 -alkyl; R 3 is hydrogen, optionally substituted C 1 ~C 3 - alkyl or halogen; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is halogen, m is 2 or 3; W is CH 2is or is not present; W 1 CH 2 and Z is CH 2 or O, and Y 2 , Y 3 , Y 4 and Y 5 are each independently N, CH or C-halogen; the optional substituents are one or more of halogen, hydroxy, cyano, C 1 ~C 3- Alkyl, C 1 ~C 3 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 ~C 3 -Alkylamino, C 1 ~C 3 -dialkylamino, C 1 ~C 3 -Alkoxy and C 1 ~C 3 -haloalkoxy.

[0170] In another embodiment of formula (Ie), R 1 is C 1 ~C 4 -Alkyl, -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 3 -alkyl or R a and R b together with the nitrogen form an optionally substituted 3- or 4-membered heterocycle; R 2 is hydrogen; R 3 is hydrogen, optionally substituted C 1 ~C 3 -alkyl, chloro or fluoro; R 1’ is hydrogen; R' is hydrogen; R 9 is hydrogen; R 10 is chloro or fluoro, m is 2 or 3; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y4 and Y 5 are each independently CH or C-halogen; the optional substituents are one or more of halogen, hydroxy, C 1 ~C 3- Alkyl, C 1 ~C 3 -Haloalkyl, C 1 ~C 3 -Alkoxy or C 1 ~C 3 -haloalkoxy.

[0171] In another embodiment of formula (Ie), R 1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 3 -alkyl or R a and R b together with the nitrogen form an aziridine, azetidine or pyrrolidinyl ring, each of which may be substituted by one or more fluoro or methyl; R 2 is hydrogen; R 3 is hydrogen, optionally substituted C 1 ~C 3 -alkyl, chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is chloro or fluoro, m is 2 or 3; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are each independently CH or C-halogen; the optional substituents are one or more of chloro, fluoro, hydroxy, C 1 ~C3- Alkyl or C 1 ~C 3 -haloalkyl.

[0172] In another embodiment of formula (Ie), R 1 isopropyl, tert-butyl, -N(CH 3 ) 2 , azetidinyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is chloro or fluoro, m is 2 or 3; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are CH, respectively. In another embodiment of formula (Ie), R 1 isopropyl, tert-butyl, -N(CH 3 ) 2 , azetidinyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is chloro or fluoro, m is 3, and the chloro or fluoro substituents are located at the 2-, 3-, and 5-positions of the phenyl ring; W and W 1 are CH2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are CH, respectively.

[0173] In another embodiment of formula (Ie), R 1 isopropyl, tert-butyl, -N(CH 3 ) 2 , azetidinyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is chloro, m is 3, and the chloro substituents are substituted at the 2-, 3-, and 5-positions of the phenyl ring; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are CH, respectively.

[0174] In another embodiment of formula (Ie), R 1 isopropyl, tert-butyl, -N(CH 3 ) 2 , azetidinyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10is fluoro, m is 3 and the fluoro substituents are substituted at the 2-, 3- and 5-positions of the phenyl ring; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are CH, respectively.

[0175] In another embodiment of formula (Ie), R 1 is morpholinyl, piperidinyl or piperazinyl, optionally substituted by one or more fluoro or methyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is chloro or fluoro, m is 2 or 3; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are CH, respectively. In another embodiment of formula (Ie), R 1 is morpholinyl, piperidinyl or piperazinyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is chloro or fluoro, m is 3, and the chloro or fluoro substituents are located at the 2-, 3-, and 5-positions of the phenyl ring; W and W1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are CH, respectively.

[0176] In another embodiment of formula (Ie), R 1 is morpholinyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is chloro, m is 3, and the chloro substituents are substituted at the 2-, 3-, and 5-positions of the phenyl ring; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are CH, respectively. In another embodiment of formula (Ie), R 1 is morpholinyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; R 10 is fluoro, m is 3, and the fluoro substituents are substituted at the 2-, 3-, and 5-positions of the phenyl ring; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5are CH, respectively.

[0177] In another embodiment, the compound of formula (I) is a compound of formula (If). [ka] (If) (In the formula, R 1 , R 1’ , R 2 , R 3 , R', R 9 , Y 2 , Y 3 , Y 4 , Y 5 , W 1 and Z is as defined in any of the embodiments of formula (I); W is absent or -CR 6 R 7 -, -NR 8 -, -O-, or -S(O) P -;R 10 and m are as defined above for formula (Ie); b is 0 or 1; and the dashed bond (

[0178] [ka] ) represents a single or double bond; D represents N, SiR 11 and R 11 is C 1 ~C 6 Alkyl or C 1 ~C 6 Haloalkyl, C or CR 5 ;D 1 is N-R', O, SiR 11 R 12 and R 11 and R 12 is independently 1 ~C 6 Alkyl or C 1 ~C 6 Haloalkyl, -CR 5 R 5’ , S(O) p and p is 0, 1 or 2, or D 1 is CR5 R 5’ and R 5 and R 5’ form a spirocyclic group together with a 2- to 5-membered chain which may be substituted with one heteroatom in the chain.

[0179] In another embodiment, a compound of formula (If) is provided, wherein R 1 , R 1’ , R 2 , R 3 , R', R 9 , W 1 , Z, Y 2 , Y 3 , Y 4 and Y 5 is as defined in any of the embodiments of formula (IA) above; W is absent or -CR 6 R 7 -;R 10 and m are as defined for formula (Ie); b is 0 or 1; and the dashed bond ( [ka] ) represents a single or double bond; D represents N, SiR 11 and R 11 is C 1 ~C 6 Alkyl or C 1 ~C 6 Haloalkyl, C or CR 5 ;D 1 is N-R', O, SiR 11 R 12 and R 11 and R 12 is independently 1 ~C 6 Alkyl or C 1 ~C 6 Haloalkyl, -CR 5 R 5’ , S(O) p where p is 0, 1 or 2, or D 1 is CR 5 R 5’ and R 5 and R 5’form a spirocyclic group together with a 2- to 5-membered chain which may be substituted with one heteroatom in the chain.

[0180] In one embodiment of formula (If), R 9 In another embodiment of formula (If), R' is CH. In another embodiment, R 1’ is H. In another embodiment, W and W 1 are CH 2 It is.

[0181] In one embodiment of formula (If), R 1 is an optionally substituted C 1 ~C 6 -alkyl, optionally substituted C 3 ~C 6 -cycloalkyl, -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 3 -alkyl or R a and R b R together with the nitrogen forms an optionally substituted 3-, 4-, 5- or 6-membered heterocycle, which may contain one additional heteroatom selected from O or N; 2 is hydrogen or optionally substituted C 1 ~C 3 -alkyl; R 3 is hydrogen, optionally substituted C 1 ~C 3 - alkyl or halogen; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; D is N or CH; D 1 CH 2 , C.F. 2 , N or O; R 10 is halogen or C 1 ~C 3 -alkyl, m is 1 or 2; W is CH2 is or is not present; W 1 CH 2 Z is CH 2 or O, and Y 2 , Y 3 , Y 4 and Y 5 are each independently N, CH or C-halogen; the optional substituents are one or more of halogen, hydroxy, cyano, C 1 ~C 3- Alkyl, C 1 ~C 3 -Haloalkyl, 3-8 membered cycloalkyl, amino, C 1 ~C 3 -Alkylamino, C 1 ~C 3 -dialkylamino, C 1 ~C 3 -Alkoxy and C 1 ~C 3 -haloalkoxy.

[0182] In another embodiment of formula (If), R 1 is C 1 ~C 4 -Alkyl, -NR a R b and R a and R b are independently H or optionally substituted C 1 ~C 3 -alkyl or R a and R b together with the nitrogen form an optionally substituted 3- or 4-membered heterocycle; R 2 is hydrogen; R 3 is hydrogen, optionally substituted C 1 ~C 3 -alkyl, chloro or fluoro; R 1’ is hydrogen; R' is hydrogen; R 9 is hydrogen; D is N; D 1 is CH 2 , C.F. 2 or O;R 10 is fluoro or methyl, m is 1 or 2; W and W1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 are each independently CH or C-halogen; the optional substituents are one or more of halogen, hydroxy, C 1 ~C 3- Alkyl, C 1 ~C 3 -Haloalkyl, C 1 ~C 3 -Alkoxy or C 1 ~C 3 -haloalkoxy.

[0183] In another embodiment of formula (If), R 1 isopropyl, tert-butyl, -N(CH 3 ) 2 , azetidinyl, or morpholinyl; R 2 is hydrogen; R 3 is hydrogen, methyl, -CF 3 , -CH 2 F, -CHF 2 , chloro or fluoro; R 1’ is hydrogen; R' is hydrogen or C 1 ~C 3 -alkyl; R 9 is hydrogen; D is N; D 1 CH 2 , C.F. 2 or O;R 10 is fluoro or methyl, m is 1 or 2; W and W 1 are CH 2 Z is O and Y 2 , Y 3 , Y 4 and Y 5 In another embodiment of formula (If), W is CH 2 And W 1 CH 2 and Z is CH 2In another embodiment of formula (If), W and W1 are independently CR 6 R 7 and R 6 and R 7 is H and C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl and Z are O. In another embodiment, W and W 1 are CH 2 and Z is O.

[0184] In some embodiments, the invention provides a compound of formula (If): wherein the dashed bond is a single bond. In some embodiments, the invention provides a compound of formula (If): where the dashed bond is a d double bond. In the above formulae (Ic) and (Id), the variable group R 5 However, the substituents on the aromatic ring, e.g. (R 5 ) o When shown to be present as a group, where o is 0, 1, 2, 3, or 4, in embodiments where o is 0, R 5 It will be understood by those skilled in the art that since the aryl groups will not be present, they will represent non-hydrogen substituents. The same principle applies to the variable R in compounds of formula (Ie) and (If). 11 applies to. In another embodiment, the present invention provides a compound of formula (IA), 1 , R 1’ , R 2 , R 3 , R 4 , R', R 5 , R 9 , W 1 and Z are as defined for formula (I) above, and W is absent or -CR 6 R 7 -, -NR 8 -, -O-, or -S(O) P - and Y 2 , Y 3 , Y 4 and Y 5 are shown in Table 1):

[0185] In another embodiment, the present invention provides a compound of formula (Ia), 1 , R 1’ , R 2 , R 3 , R 4 , R', R 5 , R 9 , W 1 and Z is as defined in any of the embodiments of formula (IA) above, and W is absent or -CR 6 R 7 - and Y 2 , Y 3 , Y 4 and Y 5 are shown in Table 1): [ka] (Ia)

[0186] JPEG2024540166000060.jpg73144

[0187] In another embodiment, the present invention provides a compound of formula (Ib), 1 , R 1’ , R 2 , R 3 , R 4 , R 5 , R', R 9 , W 1 and Z is as defined in any of the embodiments of formula (IA) above, and W is absent or -CR 6 R 7 - and Y 2 , Y 3 , Y 4 and Y 5 are shown in Table 2): [ka] (Ib)

[0188] JPEG2024540166000062.jpg73144

[0189] In another embodiment, the present invention provides compounds of formula (IA-1) as shown in Table 3 below, where L, R 1 , R 1’ , R 2 , R 3 and R 4 is defined in the Table; L1, L2 and L3 are as defined for formula (I); X is O unless otherwise noted in the Table, and R' is hydrogen unless otherwise noted in the Table; [ka] is one of the following ring systems:

[0190] [ka] Ring system A; [ka] Ring system B; [ka] Ring system C; [ka] ring system D; [ka] Ring system E; [ka] ring system F; [ka] ring system G; [ka] Ring system H; [ka] Ring system I; [Chemistry] Ring system J; [Chemistry] Ring system K; [Chemistry] Ring system L; [Chemistry] Ring system M; [Chemistry] Ring system N; [Chemistry] Ring system O; [Chemistry] Ring system P; [Chemistry] Ring system Q; [Chemistry] Ring system R; [Chemistry] Ring system S; [Chemistry] Ring system T; [Chemistry] Ring system U; [Chemistry] Ring system V; [Chemistry] ring system W; [ka] ring system X; [ka] ring system Y; [ka] ring system Z; [ka] ring system AA; [ka] ring system AB; [ka] ring system AC; [ka] ring system AD; [ka] Ring system AE.

[0191] In Table 3, "Me" stands for methyl, "i-Pr" stands for isopropyl, "t-Bu" stands for tert-butyl; the expression "3,5-di-Cl-Ph" stands for 3,5-dichlorophenyl group; "2,6-di-Cl-4-F-Ph" stands for 2,6-dichloro-4-fluorophenyl; "2,4,6-tri-F-Ph" stands for 2,4,6-trifluorophenyl; "2,3,5-tri-F-Ph" stands for 2,3,5-trifluorophenyl; "2,3,5-tri-Cl-Ph" stands for 2,3,5-trichlorophenyl; "2,3-di-Cl-5-F-Ph" stands for 2,3-dichloro-5-fluorophenyl, and so forth.

[0192] [ka] Formula (IA-1) [Table A] JPEG2024540166000097.jpg248170 JPEG2024540166000098.jpg227170 JPEG2024540166000099.jpg249170 JPEG2024540166000100.jpg237170 JPEG2024540166000101.jpg237170 JPEG2024540166000102.jpg245170 JPEG2024540166000103.jpg238170 JPEG2024540166000104.jpg192170To avoid any concerns, each compound shown in Table 3 has been prepared and characterized.

[0193] Veterinary Compositions A composition of the present invention comprising an effective amount of a compound of the present invention, including compounds of formula (I), (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) and (IA-1), or a salt thereof, in combination with an acceptable carrier or diluent.

[0194] In another embodiment, the invention comprises an effective amount of a compound of the invention, or a pharma- ceutically acceptable salt thereof, in combination with one or more additional active agents and an acceptable carrier or diluent. The compositions may be in a variety of solid and liquid forms suitable for various methods of application or administration to animals. For example, veterinary compositions containing the compounds may be compositions suitable for oral administration, injectable administration, including subcutaneous and parenteral administration, as well as topical administration (e.g., spot-on or pour-on), transdermal or subcutaneous administration. The compositions are intended to be administered to animals, including, but not limited to, mammals, birds and fish. Examples of mammals include, but are not limited to, humans, cows, 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 to protect companion animals, such as dogs and cats, from internal parasites is particularly useful.

[0195] In some embodiments, the composition of the present invention may be in a form suitable for oral use.Suitable dosage forms for oral administration include dietary supplements, troches, candies, chewable tablets, tablets, hard or soft capsules, boluses, emulsions, aqueous or oily suspensions, aqueous or oily solutions, oral drench compositions, dispersible powders or granules, premixes, syrups or elixirs, enteric compositions or pastes.Compositions intended for oral use can be prepared according to any method known in the art for producing pharmaceutical compositions. Suitable tablets may, for example, be obtained by mixing one or more compounds of formula (I) with known excipients, such as inert diluents, carriers, disintegrants, adjuvants, surfactants, binders and / or lubricants.

[0196] In one embodiment of the present invention, there is provided a soft chewable veterinary composition comprising an effective amount of at least one compound of formula (I), optionally in combination with an effective amount of at least one second active agent, in a pharma- ceutically acceptable carrier. In another embodiment, the oral composition comprises a tablet or capsule, hi yet another embodiment, the oral composition comprises a chewable tablet.

[0197] Treatment As discussed above, the compounds of the present invention are effective against endoparasites and can be used to treat, control and / or prevent parasitic infections in animals. In one embodiment, the present invention provides a method for treating, controlling and / or preventing endoparasitic infections in animals (e.g., mammals or birds), comprising administering to the animal an effective amount of a compound of the present invention, comprising a compound of formula (I), (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) or (IA-1), or a pharma- ceutically acceptable salt thereof, or a composition comprising the compound. In some embodiments, the animal that can be treated is a mammal, including, but not limited to, humans, cats, dogs, cows, chickens, dairy cows, bison, deer, goats, horses, llamas, camels, pigs, sheep and yaks. In one embodiment of the present invention, the mammal to be treated is a human, cat or dog. In another embodiment, the invention provides a method for treating or preventing endoparasitic infections in horses. In another embodiment, the mammal being treated is a livestock animal, such as a cow or sheep. In another embodiment, the compounds of the invention may be used to treat fish.

[0198] The invention also provides the use of a compound of formula (I), (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) or (IA-1) in the preparation of a medicament for treating, controlling and / or preventing a parasitic infection in an animal. The invention also provides a compound of the invention for use in the treatment, control and / or prevention of a parasitic infection in an animal. In another embodiment, the compounds of formula (I), (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) or (IA-1) may be used in combination with at least a second active agent having activity against ectoparasites (e.g., fleas and ticks) for use in the treatment, control and / or prevention of endoparasitic infections and ectoparasitic infestations in and on animals. In another embodiment, the present invention provides a method for treating, controlling and / or preventing endoparasitic infections and ectoparasitic infestations in and on an animal, comprising administering to the animal an effective amount of a compound of formula (I), (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) or (IA-1) in combination with at least one additional active agent having activity against ectoparasites. Further, the present invention provides the use of a compound of the present invention in combination with at least a second active agent for the preparation of a medicament for treating, controlling and / or preventing endoparasitic infections and ectoparasitic infestations.

[0199] In yet another embodiment of the invention, there is provided a method for treating, controlling and / or preventing parasitic infestation in a locus, comprising administering or applying to the locus an effective amount of a compound of Formula (I), Formula (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) or (IA-1), or a pharma- ceutically acceptable salt thereof. With respect to animal health applications, "locus" is intended to mean a habitat, farm, land, area, material or environment in which or in which a parasite may grow or grow, other than within or on an animal.

[0200] In one embodiment of the present invention, the compounds of formula (I), formula (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) or (IA-1) have been found to have excellent efficacy against endoparasites, particularly against endoparasites that are resistant to the macrocyclic lactone class of active agents. In one embodiment, the present invention provides a method for treating and / or preventing parasitic infections of endoparasites that are resistant to treatment with macrocyclic lactones. In another embodiment, the present invention provides a method for treating, controlling and / or preventing parasitic infestations and / or infections in an animal, comprising administering to an animal in need thereof an effective amount of an anthelmintic compound of the present invention in combination with an effective amount of another antiparasitic active agent.

[0201] In one embodiment, the compounds and compositions of the invention are directed to parasitic worms of the following genera: Anaplocephala (Anoplocephala), Ankylostomum, Necator, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Cyathostomum, Cylicocyclus, Cylicodont ophorus, Cylicostephanus, Craterostomum, Dictyocaulus, Dipetalonema, Dipylidium, Dirofilaria, Dracunculus, Echinococcus, Enterobius, Fasciola, Filaroides Filaroides, Habronema, Haemonchus, Metastrongylus, Moniezia, Necator, Nematodirus, Nippostrongylus, Oesophagostomum, Onchocerca, Ostertagia, Oxyuris, Paraascaris, Parascaris, Schistosoma, Strongylus, Taenia, Toxocara, Strongyloides, Toxascaris, Trichinella, Trichuris, Trichostrongylus, Triodontophorus, Uncinaria, Wuchereria, and combinations thereof.

[0202] In a particularly preferred embodiment of the present invention, the compounds and compositions of the present invention are used to treat, control and / or prevent infection by Dirofilaria immitis. The compounds have been found to be highly effective against D. immitis microfilariae and L4 larvae, including isolates of D. immitis that are resistant to macrocyclic lactone therapy. Thus, the compounds can be used to protect animals from developing filarial disease by killing immature stages of D. immitis before they can develop into adult worms, including those that are resistant to macrocyclic lactones and other active agents. In one embodiment, the compounds and compositions comprising the compounds can be used to prevent the development of filarial disease by killing immature stages of D. immitis that are resistant to macrocyclic lactones. In another embodiment, the compounds and compositions of the present invention are used to treat, control and / or prevent infection by Dirofilaria repens or Dirofilaria hongkongensis.

[0203] In another embodiment, the compounds of Formula (I), Formula (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) or (IA-1) can be used to treat, control and / or prevent a parasitic infection by a parasite selected from Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia curticei, Nematodirus battu, and combinations thereof.

[0204] In another embodiment for treating both endoparasites and ectoparasites, when used in combination with an ectoparasiticide, the ectoparasites are selected from the group consisting of Ctenocephalides, Rhipicephalus, Dermacentor, Ixodes, Boophilus, Amblyomma, Haemaphysalis, Hyalomma, Sarcoptes, Cyprinoides ... One or more insects or arachnids including those of the genera Psoroptes, Otodectes, Chorioptes, Hypoderma, Damalinia, Linognathus, Haematopinus, Solenoptes, Trichodectes, and / or Felicola.

[0205] In another embodiment for treating against ectoparasites, the ectoparasite is from the genera of Ctenocephalides, Rhizobia, Dermacentor, Ixodes and / or Rheum. Ectoparasites to be treated include, but are not limited to, fleas, ticks, mites, mosquitoes, flies, lice, blowflies and combinations thereof. Specific examples include, but are not limited to, cat and dog fleas (Ctenocephalides felis, Dolicococcus spp., etc.), ticks (Ixodes spp., Ixodes spp., Dermacentor spp., Amblyomma spp., etc.), and mites (Demodex spp., Sarcoptes spp., Otodectes spp., etc.), lice (Anas spp., Cheyletiella spp., Anas spp., etc.), mosquitoes (Aedes spp., Culex spp., Anopheles spp., etc.), and flies (Haematobia spp., Musca spp., Stomoxys spp., Dermatobia spp., Cochliomyia spp., etc.). In yet another embodiment for treating against ectoparasites, the ectoparasites are fleas and / or ticks.

[0206] Additional examples of ectoparasites include, but are not limited to, the tick genus Ixodes bovis, in particular the species Boophilus microplus (cattle tick), Boophilus decoloratus and Boophilus annulatus; myiasis, such as Dermatobia hominis (known as Berne in Brazil) and Cochliomyia hominivorax (blowfly); sheep myiasis, such as Lucilia sericata, Lucilia cuprina (known as blowfly myiasis in Australia, New Zealand and South Africa). Flies, i.e., adult parasites, such as Haematobia irritans (horn fly) and Stomoxys calcitrans (stable fly); lice, such as Linognathus vitulorum; mites, such as Sarcoptes scabiei and Psoroptes ovis. The above list is not exhaustive and other ectoparasites are well known in the art to be harmful to animals and humans. These include, for example, migratory dipteran larvae. In each aspect of the present invention, the compounds and compositions of the present invention may be applied to a single pest or a combination thereof.

[0207] Mixtures with other activators In another embodiment, compositions comprising compounds of the invention, including those of formula (I), (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If), and (IA-1), may also include other veterinary medicinal agents. Veterinary medicinal agents that may be included in compositions of the invention are well known in the art (e.g., Plumb's Veterinary Drug Handbook, 5 thEdition, ed. Donald C. Plumb, Blackwell Publishing, (2005) or The Merck Veterinary Manual, 9th Edition, (January 2005).

[0208] In one embodiment of the present invention, arylpyrazole compounds known in the art, such as phenylpyrazoles, may be used in combination with compounds of formula (I) or formula (IA) in the compositions of the present invention. In another embodiment of the invention, one or more macrocyclic lactones that act as acaricides, anthelmintics and / or insecticides may be added to the compositions of the invention. Macrocyclic lactones include both avermectins and milbemycin active agents.

[0209] In another embodiment of the present invention, compositions are provided that include a compound of the present invention in combination with certain acaricides or insecticides known as insect growth regulators (IGRs). Compounds belonging to this group are well known to practitioners and represent a wide variety of chemical classes. All of these compounds act by interfering with the development or growth of pests. In one embodiment, the IGR is a compound that mimics a juvenile hormone. In another embodiment, the IGR compound is a chitin synthesis inhibitor. In yet another embodiment of the present invention, adulticides, insecticides and acaricides may also be added to the compositions of the present invention. In some embodiments, the compositions of the present invention may include one or more nematocides. In other embodiments, the compositions of the present invention may include an antitrematodal agent. Anti-tasteworm compounds may also be advantageously used in the compositions of the present invention.

[0210] In yet other embodiments, the compositions of the present invention may contain other active agents that are effective against arthropod parasites. Antiparasitic agents that may be combined with the compounds of the present invention to form compositions may be biologically active peptides or proteins, including, but not limited to, cyclic depsipeptides that act at the neuromuscular junction by stimulating presynaptic receptors belonging to the secretin receptor family, resulting in complete paralysis and death of the parasite. In another embodiment, the compositions of the present invention may include an active agent from the neonicotinoid class of pesticides. Neonicotinoids bind to and inhibit insect-specific nicotinic acetylcholine receptors. In another embodiment, the compositions of the present invention may advantageously include one or more isoxazoline active agents known in the art that are highly effective against ectoparasites, such as fleas and ticks. In another embodiment of the present invention, nodulisporic acid and its derivatives (certain known acaricides, anthelmintics, antiparasitic agents and insecticides) may be added to the compositions of the present invention.

[0211] In another embodiment, an anthelmintic compound of the aminoacetonitrile class (AAD) of compounds may be added to the compositions of the present invention. In another embodiment, an aryloazol-2-yl cyanoethylamino compound may be included in the composition. The compositions of the present invention may be used in combination with paraherquamide compounds and derivatives of the compounds.The paraherquamide family of compounds is a known class of compounds that contain a spirodioxepinoindole core that has activity against certain parasites.In addition, the structurally related marcfortine family of compounds is also known and may be used in combination with the formulations of the present invention. In another embodiment of the invention, the compositions may include a spinosyn active agent or a semi-synthetic spinosoid active agent produced by the soil actinomycete Saccharopolyspora spirosa. Spinosyns are typically referred to as factors or components A, B, C, D, E, F, G, H, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, or Y, any of these components or combinations thereof may be used in the compositions of the invention. The invention will be further described by the following non-limiting examples.

[0212] Synthesis method Compounds of the present invention, including compounds of formula (I), formula (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) and (IA-1) or salts thereof as described herein, may be prepared according to the processes set forth in Schemes 1 and 2 shown below. One skilled in the art will be able to prepare various compounds of the present invention by adapting the processes described below using alternative starting materials and / or reagents known in the art.

[0213] Scheme 1 [ka]

[0214] Scheme 2 [ka] EXAMPLES

[0215] Preparation Example The following examples are intended to merely illustrate the present invention, but are not limiting thereof. Compounds of the present invention, including those of formula (I), (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) and (IA-1) or salts thereof, may be prepared by employing one of the following reaction schemes. The starting materials for their preparation may be commercially available or known to those skilled in the art and may be prepared by methods as described in the literature or may be intermediates in other schemes described herein. It will be understood that the following procedures may be modified by those skilled in the art to prepare additional compounds according to the present invention. For example, those skilled in the art will understand that the substitution of certain starting materials or the use of different intermediates will allow the preparation of different compounds of formula (I), formula (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) and (IA-1).

[0216] The terms "ambient temperature" and "room temperature" are used interchangeably and refer to a temperature of about 20° C. Although the subject matter of the following invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be understood by those skilled in the art that certain changes and modifications may be made within the scope of the examples.

[0217] JPEG2024540166000107.jpg255160 JPEG2024540166000108.jpg253158

[0218] Some examples of formula (I), formula (IA), (I-1), (I-2), (I-3), (Ia), (Ib), (Ic), (Id), (Ie), (If) and (IA-1) or salts thereof are produced after separation of the racemic mixtures and obtained as enantiomerically pure products. Stereochemical structures are sometimes arbitrarily assigned and each compound is characterized by analytical methods.

[0219] Preparation Example 1 Compound A465. Compound A465 was prepared according to general Scheme 1 shown above, as described below. In addition, the following compounds of the present invention can be prepared by applying the reactions described below for the synthesis of general scheme 1 and example A465, as well as by using and modifying known reactions in the literature (see, for example, WO2021030379, WO2012125886, and WO2012125893): A461, A462, A463, A464, A469, A466, A467, A468, A470, A471, A473, A474, A475, A476, A483, A484, A486, A487, A488, A489, A492, A494, A495, A496, A497, A498, A500.

[0220] 1. Synthesis of 1-(3,5-dichlorophenyl)-4-hydroxy-2-methylbutan-1-one [ka] A mixture of 3.0 g (13.3 mmol) of 1-bromo-3,5-dichlorobenzene in 50 mL of anhydrous THF was cooled to -95°C with a MeOH / nitrogen bath and 10.8 mL (17.3 mmol) of tert-butyllithium was added dropwise, followed by the dropwise addition of 1.99 g (19.9 mmol) of alpha-methyl-gamma-butyrolactone in 10 mL of anhydrous THF. The reaction mixture was stirred at -85°C for 1 h. The reaction mixture was diluted with saturated NH 4 Quenched with Cl solution at -90°C, the solution was warmed to room temperature and extracted twice with EE, the organic layers were collected, dried, filtered and the filtrate was evaporated to give 3.6 g (27%) of crude product as a yellow oil.

[0221] 2. Synthesis of 4-(3,5-dichlorophenyl)-3-methyl-4-oxobutanal [ka] A mixture of 2.59 mL (26.42 mL) DMSO in 25 mL DCM was cooled to -78°C. 1.6 mL (18.9 mmol) oxalyl chloride was added dropwise and the solution was stirred for 15 min. 3.6 g (3.6 mmol) 1-(3,5-dichlorophenyl)-4-hydroxy-2-methylbutan-1-one in 8 mL DCM was added and the reaction mixture was stirred at -78°C for 1 h. 11.67 mL (83.76 mmol) TEA was added and the solution was allowed to warm to room temperature and stirred at room temperature for 1.5 h. The reaction mixture was quenched with water and extracted with DCM. The organic layer was collected, dried, filtered and the filtrate was evaporated. The residue was purified by column chromatography (silica gel, PE / EtOAc) and the solvent was removed in vacuo to give 1.10 g (92.0%) of the product as a yellow oil.

[0222] 3. Synthesis of 2-[2-(3,5-dichlorophenyl)-3-methyl-1H-pyrrol-1-yl]-2,3-dihydro-1H-isoindole-1,3-dione [ka] A mixture of 1.10 g (3.36 mmol) of 4-(3,5-dichlorophenyl)-3-methyl-4-oxobutanal, 600 mg (3.7 mmol) of N-aminophthalimide, and 9.26 mL (37.0 mmol) was stirred for 1 h at 100° C. The reaction mixture was evaporated and the crude residue was crystallized with PE / EE to give 720 mg (57.0%) of 2-[2-(3,5-dichlorophenyl)-3-methyl-1H-pyrrol-1-yl]-2,3-dihydro-1H-isoindole-1,3-dione as a white solid.

[0223] 4. Synthesis of 2-(3,5-dichlorophenyl)-3-methyl-1H-pyrrol-1-amine [ka] A mixture of 1.1 g (3.0 mmol) of 2-[2-(3,5-dichlorophenyl)-3-methyl-1H-pyrrol-1-yl]-2,3-dihydro-1H-isoindole-1,3-dione and 0.2 mL (7.4 mmol) of hydrazine monohydrate in 12 mL of EtOH was stirred at reflux for 2 h. The reaction mixture was filtered and the filtrate was evaporated. The crude residue was purified by column chromatography (silica gel, PE / EtOAc) and the solvent was removed in vacuo to give 650 mg (91%) of the product as a white solid.

[0224] 5. Synthesis of methyl 7-(3,5-dichlorophenyl)-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate [ka] To a mixture of 1.1 g (4.6 mmol) of 2-(3,5-dichlorophenyl)-3-methyl-1H-pyrrol-1-amine in 40 mL of methanol, 820.0 mg (4.1 mmol) of methyl (2Z)-2-(dimethylamino)-methylidene]-4-methyl-3-oxopentanoate and 1.2 mL of 4 M HCl in dioxane were added and the mixture was stirred for 3 h at 80° C. After evaporation of the solvent, the crude residue was purified by column chromatography (silica gel, cyclohexane / EtOAc) and the solvent was removed in vacuo to give 380 mg (24%) of the product as a solid.

[0225] 6. Synthesis of 7-(3,5-dichlorophenyl)-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylic acid [ka] To a mixture of 94.5 mg (0.2 mmol) of methyl 7-(3,5-dichlorophenyl)-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate and 1.5 mL of a solution of LiOH (1 M) was added 1.5 mL of THF. After stirring at 40° C. for 2 h, the reaction mixture was heated to 60° C. overnight. The solution was then acidified with 4 M HCl at room temperature, and the resulting residue was filtered off and washed with 2 mL of H 2 The mixture was washed with O. After drying the residue, 84 mg (93.0%) of 7-(3,5-dichlorophenyl)-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylic acid was obtained as a yellow solid.

[0226] 7. Synthesis of 7-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (A465) [ka] A solution of 350 mg (0.9 mmol) of 7-(3,5-dichlorophenyl)-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylic acid in 8 mL of DMF was treated with 650 μl of DIPEA and 410 mg (1.7 mmol) of HATU and stirred for 10 min. After adding 200 mg (1.1 mmol) of (S)-chroman-4-amine hydrochloride, the mixture was stirred at room temperature for 16 h. The solvent was removed in vacuo and the residue was purified by column chromatography (silica gel, PE / EtOAc). After removing the solvent in vacuum, 310 mg (65.0%) of 7-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (A465) was obtained as a white solid. (ESI, m / z): 495 [M+H] +

[0227] Preparation Example 2 Synthesis of 3,4-dihydro-2H-1,4-benzoxazin-4-amine 3,4-Dihydro-2H-1,4-benzoxazin-4-amines are used in the synthesis of compounds of the invention containing ring system D (see Table 3 above), such as A479, A482, A494, A495, A496, A497, A498, A516 and A565, and are prepared according to the methods described below.

[0228] 1. Synthesis of 4-nitroso-3,4-dihydro-2H-1,4-benzoxazine [ka] In a 500 mL round-bottom flask, 3,4-dihydro-2H-1,4-benzoxazine (3.0 g, 22.2 mmol) and HCl (300 ml, 3 M) were added and NaNO 2 (1.8 g, 26.1 mmol) was added portionwise over 2 h at 0° C. under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE / EA (10:1) to give 4-nitroso-3,4-dihydro-2H-1,4-benzoxazine (2.7 g, 75%) as a yellow oil.

[0229] 2. Synthesis of 3,4-dihydro-2H-1,4-benzoxazin-4-amine [ka] In a 500 mL round bottom flask, 4-nitroso-3,4-dihydro-2H-1,4-benzoxazine (2.7 g, 19.2 mmol) and THF (300 ml) were added, and LAH (1.35 g, 1.9 mmol) was added portionwise over 2 h at 0° C. under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (10:1) to give 3,4-dihydro-2H-1,4-benzoxazin-4-amine (2.2 g, 45%) as a yellow oil.

[0230] Preparation Example 3 Scheme 3 below illustrates the synthesis of intermediate compounds INT-1, INT-2, and INT-3, which are each formed from compound 2-1 (wherein R 1’ and R 2 is hydrogen) and compound 2-4 (wherein R 1 is tert-butyl, R 2 and R 1’ are hydrogen and compounds, and R 3 is chloro) and compound 2-5 (wherein R 1 is tert-butyl, R 2 and R 1’ are hydrogen and compounds, and R 3 These intermediates are used to prepare various compounds of the invention as depicted in Scheme 2 and described in detail below.

[0231] Scheme 3 [ka]

[0232] 1. Synthesis of 2,2,2-trichloro-1-(4-chloro-1H-pyrrol-2-yl)ethanone (3-2) [ka] In a 5.0 L three-neck round bottom flask was placed 2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethanone (3-1, 600 g, 2824.2 mmol) in DCM (4.0 L). 2 Cl 2 (419.30 g, 3106.6 mmol) was added dropwise at 0° C. The reaction mixture was stirred at 20° C. for 12 h. The resulting mixture was diluted with Na 2 CO 3 The pH was adjusted to 8 with aqueous solution (2M). The resulting mixture was extracted with DCM (2.0 L x 3). The combined organic layer was washed with anhydrous Na 2 SO 4Drying at rt and concentration under reduced pressure gave 2,2,2-trichloro-1-(4-chloro-1H-pyrrol-2-yl)ethanone (3-2, 730 g, crude) as a black solid which was used directly in the next step.

[0233] 2. Synthesis of methyl 4-chloro-1H-pyrrole-2-carboxylate (3-3) [ka] In a 3.0 L three-neck round bottom flask, 2,2,2-trichloro-1-(4-chloro-1H-pyrrole-2-yl)ethanone (3-2, 730 g, crude), MeOH (2.5 L) and DMAP (72.34 g, 592.1 mmol) were charged. The reaction mixture was stirred at 70° C. for 1 h. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (10 / 1) to give methyl 4-chloro-1H-pyrrole-2-carboxylate (3-3, 330 g, 73% 2 steps) as a white solid.

[0234] 3. Synthesis of methyl 1-amino-4-chloropyrrole-2-carboxylate (3-4) [ka] In a 5 L 3-neck round-bottom flask, add NH 4 Cl (80 g, 1495.6 mmol), ethyl ether (1.5 L) and NH 3 .H 2 20 mL of 120 O was added. To this was added NaClO (1.7 L) dropwise at -10°C. The reaction mixture was stirred at -10°C for 2 hours. The aqueous phase was then removed by separatory funnel. The organic layer was washed with 1.0 L of chilled brine. The organic layer (1.5 L) was diluted with anhydrous Na 2 SO 4The mixture was dried at 40° C. and stored at −40° C. for 1 h. In a separate 2.0 L 3-neck round bottom flask, methyl 4-chloro-1H-pyrrole-2-carboxylate (3-3, 80 g, 501.3 mmol) in DMF (800 mL) was charged. This was followed by the addition of NaH (30.08 g, 752.0 mmol, 60%) in portions at 0° C. The reaction mixture was stirred at 0° C. for 30 min. Then the above organic layer (1.5 L) was added. The combined reaction mixture was stirred at 20° C. for 2 h. The reaction was then diluted with 600 mL of Na 2 S 2 O 4 It was quenched by the addition of saturated aqueous solution and the reaction mixture was stirred for 15 min. The resulting mixture was extracted with EA (3×1.0 L). The combined organic layers were washed with anhydrous Na 2 SO 4 The reaction was repeated once more and the combined residue was purified by silica gel column chromatography eluting with PE / EA (20 / 1) to give methyl 1-amino-4-chloropyrrole-2-carboxylate (3-4, 188 g, 71%) as a white solid.

[0235] 4. Synthesis of ethyl 6-chloro-4-hydroxypyrrolo[1,2-b]pyridazine-3-carboxylate (INT-1) [ka] In a 3.0 L round bottom flask was charged methyl 1-amino-4-chloropyrrole-2-carboxylate (3-4, 150 g, 859.2 mmol) and ethyl 3,3-diethoxypropanoate (196.15 g, 1031.0 mmol) in DMF (1.5 L) and PTSA (22.19 g, 128.9 mmol) was added. The reaction mixture was stirred at 90° C. for 2 h. The mixture was cooled to 60° C. Then DBU (261.61 g, 1718.4 mmol) was added at 60° C. The reaction mixture was stirred at 60° C. for 1 h. The mixture was cooled to room temperature. The resulting mixture was diluted with EA (4.0 L) and washed with 3×1.0 L water. The resulting solution was diluted with Na 2 SO 4The crude product was stirred as a slurry with EtOH / water (3 / 1) to give ethyl 6-chloro-4-hydroxypyrrolo[1,2-b]pyridazine-3-carboxylate (INT-1, 127 g, 61%) as a white solid after filtration. (ES, m / z): 239 [MH] - ; 1 H NMR (300 MHz, CDCl 3 , ppm): δ12.28 (s, 1H), 8.30 (s, 1H), 7.69 (d, J = 2.0 Hz, 1H), 6.89 (d, J = 1.6 Hz, 1H), 4.44 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H).

[0236] 5. Synthesis of ethyl 6-chloro-4-(trifluoromethanesulfonyloxy)pyrrolo[1,2-b]pyridazine-3-carboxylate (3-5) [ka] In a 2.0 L round bottom flask was charged ethyl 6-chloro-4-hydroxypyrrolo[1,2-b]pyridazine-3-carboxylate (INT-1, 82 g, 340.8 mmol), DCM (800 mL), and TEA (103.44 g, 1022.3 mmol). To this was added triflic anhydride (153.82 g, 545.2 mmol) dropwise at 0° C. The reaction mixture was stirred at 20° C. for 2 h. The resulting mixture was diluted with DCM (1.0 L) and washed with 3×500 mL of water. The organic phase was collected and diluted with Na 2 SO 4 The mixture was dried at 40° C. and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE / EA (50 / 1) to give ethyl 6-chloro-4-(trifluoromethanesulfonyloxy)pyrrolo[1,2-b]pyridazine-3-carboxylate (3-5, 90.5 g, 71%) as a yellow solid.

[0237] 6. Synthesis of ethyl 4-tert-butyl-6-chloropyrrolo[1,2-b]pyridazine-3-carboxylate (INT-2) [ka] In a 2.0 L three-neck round bottom flask was charged ethyl 6-chloro-4-(trifluoromethanesulfonyloxy)pyrrolo[1,2-b]pyridazine-3-carboxylate (3-5, 62 g, 166.3 mmol), THF (1.2 L). LiBr (108.35 g, 1247.6 mmol) and CuI (237.62 g, 1247.6 mmol) were added to it at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes. Following this, tert-butylmagnesium chloride (38.88 g, 332.7 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes. NH 4 Cl(H 2 The reaction was quenched at 0° C. by the addition of 4M in 203O, 1.0 L). The mixture was extracted with EA (3×500 mL). The organic phase was collected and washed with Na 2 SO 4 The mixture was dried at 40° C. and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE / EA (25 / 1) to give ethyl 4-tert-butyl-6-chloropyrrolo[1,2-b]pyridazine-3-carboxylate (INT-2, 42.5 g, 91%) as a yellow oil.

[0238] 7. Synthesis of ethyl 4-tert-butyl-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (INT-3) [ka] In a 1.0 L round-bottom flask, add ethyl 4-tert-butyl-6-chloropyrrolo[1,2-b]pyridazine-3-carboxylate (INT-2, 42 g, 149.6 mmol), dioxane (500 mL), H 2 O (25 mL, 1387.7 mmol), Na 2 CO 3(39.64 g, 374.0 mmol), trimethylboroxine (65.73 g, 524.0 mmol), X-Phos (7.13 g, 14.7 mmol) and Pd(DtBPF)Cl 2 (9.75 g, 14.9 mmol) was charged under nitrogen atmosphere. The reaction mixture was stirred at 100° C. for 4 h. The mixture was cooled to room temperature. The resulting mixture was diluted with EA (1.5 L) and washed with 3×500 mL of water. The organic phase was collected and diluted with Na 2 SO 4 The mixture was dried at 40° C. and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with PE / EA (20 / 1) to give ethyl 4-tert-butyl-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (INT-3, 31 g, 79%) as a yellow oil. (ES, m / z): 261 [M+H] + ; 1 H NMR (300 MHz, CDCl 3 , ppm): δ7.75 (s, 1H), 7.54 (s, 1H), 6.68 (s, 1H), 4.36 (q, J = 7.2 Hz, 2H), 2.37 (s, 3H), 1.58 (s, 9H), 1.40 (t, J = 7.2 Hz, 3H).

[0239] By utilizing the above intermediates INT-1, INT-2 and INT-3 and applying the method shown in Scheme 2, the following compounds of the present invention can be obtained: A477, A478, A479, A480, A481, A482, A490, A491, A493, A499, A501, A502, A503, A504, A505, A506, A507, A508, A509, A510, A511, A512, A513, A514, A515, A516, A517, A518, A519, A520, A521, A522, A523, A524, A525, A526, A527, A528, A529, A530, A531, A532, A533, A534, A535, A536, A537, A538, A539, ​​A540, A541, A542, A543, A544, A545, A546, A547, A548, A549, A550, A551, A552, A553, A554, A555, A556, A557, A558, A559, A560, A561, A562, A563, A564, A565, A566, A567, A568, A569, A570, A571, A572, A573, A574, A575, A576, A577, A578, A579, A580, A581, A582, A583, A58 21, A522, A523, A524; A525, A526, A527, A528, A529, A530, A531, A532, A533, A534, A535, A536a, A536b, A538, A540, A541, A542, A544, A5 45, A546, A547, A548, A549, A550, A551, A552, A553, A554, A556, A557, A558, A559, A560, A561, A562, A563, A564, A565, A566, A567, A568.

[0240] It is understood by those skilled in the art that the order of reactions shown in the chemical schemes described herein can be changed depending on the reactivity of the substituents.In addition, it will be understood that known reactants in the literature can be prepared according to published procedures.In addition, it is understood that when the chemical reactions described herein result in racemic mixtures, only the desired enantiomer can be isolated by known purification methods known in the art, including but not limited to chiral HPLC methods.

[0241] Preparation Example 4 7-(2,3-Dichloro-5-fluorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxamide (A493) Compound A493 was prepared according to the general method described in Scheme 2. Specific synthetic details are provided below.

[0242] 1. Synthesis of ethyl 6-chloro-4-(trifluoromethanesulfonyloxy)pyrrolo[1,2-b]pyridazine-3-carboxylate (3-5) [ka] To a solution of 613.0 mg (2.5 mmol) of ethyl 6-chloro-4-hydroxypyrrolo[1,2-b]pyridazine-3-carboxylate (INT-1) and 776 μL (5.6 mmol) of triethylamine in 5 mL of dichloromethane, 471 μL (2.8 mmol) of anhydrous trifluoromethane was added at 0° C. The solution was stirred at room temperature overnight. Water was then added and the layers were separated by a phase transfer cartridge. The organic layer was washed with Na 2 SO 4 Drying at 40° C. and evaporating the solvent under reduced pressure gave 1.2 g of crude product as a brown oil. (3-5, ESI, m / z): 373 [M+H] +

[0243] 2. Synthesis of ethyl 6-chloro-4-(dimethylamino)pyrrolo[1,2-b]pyridazine-3-carboxylate (4-1) [ka] A solution of 31.0 g (83.1 mmol) of ethyl 6-chloro-4-(trifluoromethanesulfonyloxy)pyrrolo[1,2-b]pyridazine-3-carboxylate (3-5) in 300 mL of ethanol was added to 40 mL (0.22 mol) of dimethylamine in ethanol (5.6 mol / L) and the solution was heated to reflux for 15 min. After cooling to room temperature, the solution was diluted with ethyl acetate and diluted with 1 N HCl, 10% Na 2 CO 3 The mixture was washed with hexane and brine. After filtration through Celite, the solvent was evaporated under reduced pressure. Silica gel chromatography (CH / EA 9:1 to 2:8) afforded 22.3 g (70%) of 4-1 as a yellow solid. (ESI, m / z): 268 [M+H] +

[0244] 3. Synthesis of ethyl 4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (4-2) [ka] A solution of 7.4 g (27.6 mmol) of ethyl 6-chloro-4-(dimethylamino)pyrrolo[1,2-b]pyridazine-3-carboxylate (4-1) in 50 mL of dioxane in a three-neck flask was added with 10 mL of trimethylboroxine and 80 mL of 1 M Na 2 CO 3 The mixture was purged with argon for 5 min, then heated to 50° C. and treated with 3.0 g (3.5 mmol) of XPHOS Pd G3 under argon and stirred at 90° C. for 1 h. After cooling to room temperature, the solution was diluted with ethyl acetate and diluted with 10% Na 2 CO 3 The mixture was washed with hexanes and brine. After filtration through Celite, the solvent was evaporated under reduced pressure. Silica gel chromatography (CH / EA 95:5 to 1:9) afforded 5.6 g (81%) of the title compound (4-2) as a yellow oil that solidified on standing. (ESI, m / z): 248 [M+H] +

[0245] 4. Synthesis of ethyl 7-bromo-4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (4-3) [ka] To a solution of 5.6 g (22.6 mmol) of ethyl 4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (4-2) in 120 mL of DMF, 3.9 g (21.9 mmol) of NBS was added at 0° C. and the mixture was stirred at room temperature for 1 h. The solution was diluted with ethyl acetate and diluted with 10% Na 2 CO 3The mixture was washed with ethyl acetate and brine. After filtration through Celite, the solvent was evaporated under reduced pressure. Silica gel chromatography (CH / EA 95:5 to 2:8) afforded 6.4 g (86%) of the title compound (4-3) as a yellow solid. (ESI, m / z): 327 [M+H] +

[0246] 5. Synthesis of potassium 7-bromo-4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (4-4) [ka] To a solution of 14.6 g (44.7 mmol) of ethyl 7-bromo-4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (4-3) in 400 mL of THF, 12.7 g (89.0 mmol) of TMSOK was added and the mixture was stirred at 70° C. for 7 h. After evaporation of the volatiles, 15 g of crude product (4-4) was obtained and used directly in the next step. (ESI, m / z): 337 [M+H] +

[0247] 6. Synthesis of 7-bromo-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxamide (4-5) [ka] To a solution of 15 g (35.6 mmol) of potassium 7-bromo-4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (4-4) in 400 mL of DMF, 28 mL (159.9 mmol) of DIPEA and 24.0 g (63.1 mmol) of HATU were added at room temperature. After stirring for 5 min at room temperature, 13 g (70.0 mmol) of (S)-chroman-4-amine hydrochloride was added and the mixture was stirred at 50° C. for 30 min. After cooling to room temperature, the solution was diluted with ethyl acetate and washed with 1N HCl, 10% Na 2 CO 3The mixture was washed with ethyl acetate and brine. After filtration through Celite, the solvent was evaporated under reduced pressure to about 200 mL and the product was crystallized. The filtered solid was washed with a little EA and dried to give 10.6 g of product, which was combined with the remaining mother liquor that was purified by silica gel chromatography (CH / EA 85:15 to 3:7) to give a total of 11.9 g (77%) of the title compound (4-5) as a beige solid. (ESI,m / z):430[M+H] +

[0248] 7. Synthesis of 7-(2,3-dichloro-5-fluorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxamide (A493) [ka] To a solution of 720 mg (1.5 mmol) of 7-bromo-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-4-(dimethylamino)-6-methylpyrrolo[1,2-b]pyridazine-3-carboxamide (4-5) in 25 mL of dioxane was added 430 mg (2.0 mmol) of 2,3-dichloro-5-fluorophenylboronic acid under argon, followed by 200 mg (0.3 mmol) of 1,1'-bis-(di-tert-butylphosphino)ferrocene-palladium dichloride and 3 mL of Na 2 CO 3 Solution (2 mol / L) was added. The mixture was stirred in a sealed vessel at 80° C. for 2 h. After cooling to room temperature, the solution was diluted with water and extracted with EA. The organic layers were combined and the solvent was evaporated under reduced pressure. Silica gel chromatography (CH vs. CH / EA 8:2) afforded 680 mg (51%) of the title compound (A493) as a brown solid. (ESI, m / z): 514 [M+H] +

[0249] Preparation Example 5 Synthesis of 4-tert-butyl-6-chloro-7-(2,3-dichloro-5-fluorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]pyrrolo[1,2-b]pyridazine-3-carboxamide (A502) Compound A502 was prepared according to the general method described in Scheme 2. Specific synthetic details are provided below.

[0250] 1. Synthesis of ethyl 7-bromo-4-tert-butyl-6-chloropyrrolo[1,2-b]pyridazine-3-carboxylate (5-1) [ka] To a solution of 325 mg (1.0 mmol) of ethyl 4-tert-butyl-6-chloropyrrolo[1,2-b]pyridazine-3-carboxylate (INT-2) in 5 mL of DMF, 166 mg (0.9 mmol) of NBS was added at room temperature, and the mixture was stirred at room temperature for 1 h. The solution was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with Na 2 SO 4 The mixture was dried at 40° C. and the solvent was evaporated under reduced pressure. 2 O / TFA) to give 323 mg (86%) of the title compound (5-1) as a yellow solid. (5-1, ESI, m / z): 360 [M+H] +

[0251] 2. Synthesis of ethyl 4-tert-butyl-6-chloro-7-(2,3-dichloro-5-fluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxylate (5-2) [ka] To a solution of 100 mg (0.27 mmol) of ethyl 7-bromo-4-tert-butyl-6-chloropyrrolo[1,2-b]pyridazine-3-carboxylate (5-1) in 3 mL of dioxane was added 63 mg (0.3 mmol) of 2,3-dichloro-5-fluorophenylboronic acid under argon, followed by 0.5 mL of Na 2 CO3 Solution (2 mol / L) and 45 mg (0.05 mmol) of 1,1'-bis-(di-tert-butylphosphino)ferrocene-palladium dichloride were added. The mixture was stirred in a sealed vessel at 80° C. for 2 h. After cooling to room temperature, the solution was diluted with water and extracted with EA. The organic layers were combined and diluted with Na 2 SO 4 After drying at 40°C, the solvent was evaporated under reduced pressure. 2 O / TFA) to give 45 mg (37%) of the title compound (5-2) as a brown solid. (ESI, m / z): 444 [M+H] +

[0252] 3. Synthesis of 4-tert-butyl-6-chloro-7-(2,3-dichloro-5-fluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxylic acid (5-3) [ka] To a solution of 45 mg (0.1 mmol) of ethyl 4-tert-butyl-6-chloro-7-(2,3-dichloro-5-fluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxylate (5-2) in 1 mL of dioxane / ethanol, 0.5 mL of NaOH solution (4 mol / L) was added at room temperature and the mixture was stirred at 90° C. for 12 h. After cooling to room temperature, the solution was treated with HCl (4 mol / L) at 0° C. until acidic pH and diluted with DCM. After filtration through a phase separation cartridge, the organic phase was evaporated under reduced pressure and the crude title product (5-3) was used directly in the subsequent step. (ESI, m / z): 416 [M+H] +

[0253] 4. Synthesis of 4-tert-butyl-6-chloro-7-(2,3-dichloro-5-fluorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]pyrrolo[1,2-b]pyridazine-3-carboxamide (A502) [ka] To a solution of 42 mg (0.1 mmol) of 4-tert-butyl-6-chloro-7-(2,3-dichloro-5-fluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxylic acid (5-3) in 1.5 mL of DMF, 51 μL (0.3 mmol) of DIPEA and 38 mg (0.1 mmol) of HATU were added at room temperature. After stirring for 5 min at room temperature, 28 mg (0.15 mmol) of (S)-chroman-4-amine hydrochloride was added and the mixture was stirred at room temperature for 2 h. After acidification with TFA, the mixture was analyzed by preparative HPLC (ACN / H 2 O / TFA) to give 10 mg (18%) of the title compound (A502) as a yellow solid. (ESI, m / z): 547 [M+H] +

[0254] Preparation Example 6 Synthesis of N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methyl-4-(propan-2-yl)-7-(2,3,5-trifluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxamide (A513) 1. Synthesis of ethyl 6-chloro-4-(prop-1-en-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-1) [ka] A solution of 1.55 g (8.1 mmol) of ethyl 6-chloro-4-(trifluoromethanesulfonyloxy)pyrrolo[1,2-b]pyridazine-3-carboxylate (3-5) in 25 mL of 1,2-dimethoxyethane was dissolved in 9.24 g (28.3 mmol) of Cs 2 CO 3 The solution was treated under argon with 5 mL of water in which was dissolved 1,2-dichlorophenylboronic acid, followed by the addition of 2.59 mL (13.7 mmol) of isopropenylboronic acid pinacol ester. After degassing for 5 min, 794 mg (1.0 mmol) of 1,1'-bis-(di-tert-butylphosphino)ferrocene-palladium dichloride was added under argon and the sealed vessel was stirred at 80°C for 3 h. After cooling to room temperature, the solution was diluted with ethyl acetate and diluted with 10% Na 2 CO3 The solvent was removed and washed with Na 2 SO 4 The mixture was dried over 1000 ml of ethyl acetate and evaporated under reduced pressure. 2 O / TFA) to give 578 mg (27%) of the title compound (6-1) as a solid. (ESI, m / z): 265 [M+H] +

[0255] 2. Synthesis of ethyl 6-chloro-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-2) [ka] A solution of 578 mg (2.1 mmol) of ethyl 6-chloro-4-(prop-1-en-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-1) in 25 mL of acetic acid was dissolved in 50 mg of PtO 2 The crude mixture was filtered and the filtrate was evaporated. 2 O / TFA) to give 337 mg (57%) of the title compound (6-2) as a solid. (ESI, m / z): 267 [M+H] +

[0256] 3. Synthesis of ethyl 6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-3) [ka] To a solution of 2.0 g (7.5 mmol) of ethyl 6-chloro-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-2) in 22 mL of dioxane in a vial, 505 mg (0.75 mmol) of XPHOSPd G3 was added under argon, followed by 3.5 mL (24.7 mmol) of trimethylboroxine and 11.2 mL of 2 M Na 2 CO 3The solution was added. The mixture was purged with argon for 5 minutes and then heated at 80° C. for 6 hours. After cooling to room temperature, the solution was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with Na 2 SO 4 The mixture was dried at 40° C. and the solvent was evaporated under reduced pressure. Silica gel chromatography (CH / EA 9:1) afforded 1.43 g (69%) of the title compound (6-3) as a solid. (ESI, m / z): 247 [M+H] +

[0257] 4. Synthesis of ethyl 7-bromo-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-4) [ka] To a solution of 1.43 g (5.2 mmol) of ethyl 6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-3) in 14 mL of DMF, 837 mg (4.7 mmol) of NBS was added at room temperature, and the mixture was stirred at room temperature for 30 min. After acidification with TFA, the mixture was analyzed by preparative HPLC (ACN / H 2 O / TFA) to give a total of 1.14 g (67%) of the title compound (6-4) as a yellow oil. (ESI, m / z): 326 [M+H] +

[0258] 5. Synthesis of ethyl 6-methyl-4-(propan-2-yl)-7-(2,3,5-trifluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-5) [ka] To a solution of 25 mg (0.1 mmol) of ethyl 7-bromo-6-methyl-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-4) in 1 mL of dioxane was added 20 mg (0.1 mmol) of 2,3-dichloro-5-fluorophenylboronic acid under argon, followed by 153 μL of Na 2 CO3 solution (2 mol / L) and 10 mg (0.015 mmol) of 1,1'-bis-(di-tert-butylphosphino)ferrocene-palladium dichloride were added. The mixture was stirred in a sealed vessel at 80° C. for 1 h. After cooling to room temperature, the solution was diluted with DCM and brine. After filtration through a phase separation cartridge, the organic phase was evaporated under reduced pressure and the mixture was purified by preparative HPLC (ACN / H 2 O / TFA) to give 10 mg (34%) of the title compound (6-5) as a brown solid. (ESI, m / z): 377 [M+H] +

[0259] 6. Synthesis of 6-methyl-4-(propan-2-yl)-7-(2,3,5-trifluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxylic acid (6-6) [ka] To a solution of 10 mg (0.02 mmol) of ethyl 6-methyl-4-(propan-2-yl)-7-(2,3,5-trifluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxylate (6-5) in 2 mL of ethanol, 0.13 mL of NaOH solution (4 mol / L) was added at room temperature and the mixture was stirred at 90° C. for 2 h. After cooling to room temperature, the solution was treated with HCl (4 mol / L) at 0° C. until acidic pH and diluted with DCM. After filtration through a phase separation cartridge, the organic phase was evaporated under reduced pressure and the crude title product (6-6) was used directly in the subsequent step. (ESI, m / z): 349 [M+H] +

[0260] 7. Synthesis of N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methyl-4-(propan-2-yl)-7-(2,3,5-trifluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxamide (A513) [ka] To a solution of 9 mg (0.02 mmol) of 6-methyl-4-(propan-2-yl)-7-(2,3,5-trifluorophenyl)pyrrolo[1,2-b]pyridazine-3-carboxylic acid (6-6) in 1 mL of DMF, 13 μL (0.078 mmol) of DIPEA and 9.8 mg (0.026 mmol) of HATU were added at room temperature. After stirring for 10 min at room temperature, 5.7 mg (0.03 mmol) of (S)-chroman-4-amine hydrochloride was added and the mixture was stirred at room temperature overnight. After dilution with ACN and acidification with TFA, the mixture was analyzed by preparative HPLC (ACN / H 2 O / TFA) to give 9 mg (72%) of the title compound (A513) as a solid. (ESI, m / z): 480 [M+H] +

[0261] Preparation Example 7 Synthesis of 4-tert-butyl-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methyl-7-(piperidin-1-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (A524) 1. Synthesis of ethyl 7-bromo-4-tert-butyl-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (7-1) [ka] To a solution of 680 mg (2.6 mmol) of ethyl 4-tert-butyl-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (INT-3) in 10 mL of DMF, 360 mg (2.0 mmol) of NBS was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. The solution was diluted with ethyl acetate and diluted with 10% Na 2 CO 3 The combined organic layers were filtered through Celite and the solvent was evaporated under reduced pressure. Silica gel chromatography (CH / EA gradient) afforded 730 mg (74%) of the title compound (7-1) as a yellow oil. (ESI, m / z): 340 [M+H] +

[0262] 2. Synthesis of potassium 7-bromo-4-tert-butyl-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (7-2) [ka] To a solution of 3 g (7.0 mmol) of ethyl 7-bromo-4-tert-butyl-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate (7-1) in 100 mL of THF, 3.0 g (21.2 mmol) of TMSOK was added and the mixture was stirred at 70° C. for 7 h. After evaporation of the volatiles, 2.2 g of crude product (7-2) was obtained and used directly in the next step. (ESI, m / z): 350 [M+H] +

[0263] 3. Synthesis of 7-bromo-4-tert-butyl-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methylpyrrolo[1,2-b]pyridazine-3-carboxamide (7-3) [ka] To a solution of 2.2 g (6.8 mmol) of 7-bromo-4-tert-butyl-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methylpyrrolo[1,2-b]pyridazine-3-carboxylate potassium (7-2) in 85 mL of DMF, 4.2 mL (24.7 mmol) of DIPEA and 3.78 g (9.9 mmol) of HATU were added at room temperature. After stirring for 5 minutes at room temperature, 2.0 g (11.0 mmol) of (S)-chroman-4-amine hydrochloride was added and the mixture was stirred at 50° C. for 1 hour. The mixture was diluted with ethyl acetate and washed with 1N HCl, 10% Na 2 CO 3 The organic layer was washed with NaCl and brine. 2 SO 4 The mixture was dried at 40° C. and the solvent was evaporated under reduced pressure. Silica gel chromatography (CH / EA gradient) afforded 2.0 g (68%) of the title compound (7-3) as a solid. (ESI, m / z): 443 [M+H] +

[0264] 4. Synthesis of 4-tert-butyl-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methyl-7-(piperidin-1-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (A524) [ka] A 5 mL vial was charged with 50 mg (0.1 mmol) of 7-bromo-4-tert-butyl-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methylpyrrolo[1,2-b]pyridazine-3-carboxamide (7-3), 1 mL of dioxane, and 11 μL (0.1 mmol) of piperidine and degassed with argon. 43 mg (0.45 mmol) of t-BuONa was added, and after further degassing with argon, 1.45 mg (0.002 mmol) of Pd-PEPPSI-IPent Cl was added and the sealed vial was heated to 80 °C overnight. After cooling to room temperature, the mixture was diluted with MeOH and purified by preparative HPLC (ACN / H 2 O / TFA) to give 3 mg (6%) of the title compound (A524) as a solid. (ESI, m / z): 447 [M+H] +

[0265] Preparation Example 8 Synthesis of 6-chloro-7-(2,3-dichloro-5-fluorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carbothioamide (A539) [ka] To a solution of 48 mg (0.1 mmol) of 6-chloro-7-(2,3-dichloro-5-fluorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-4-(propan-2-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (A523) in 3 mL of THF was added 54 mg (0.14 mmol) of Lawesson's reagent. The mixture was stirred at room temperature for 3 h and then heated to 50° C. overnight. After cooling to room temperature the mixture was acidified with TFA and purified by preparative HPLC (ACN / H 2 O / TFA) to give 16.5 mg (33%) of the title compound (A539) as a yellow solid. (ESI, m / z): 549 [M+H] +

[0266] Preparation Example 9 Synthesis of 4-tert-butyl-7-(2,3-dichloro-5-fluorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-N,6-dimethylpyrrolo[1,2-b]pyridazine-3-carboxamide (A543) [ka] To a solution of 20 mg (0.03 mmol) of 4-tert-butyl-7-(2,3-dichloro-5-fluorophenyl)-N-[(4S)-3,4-dihydro-2H-1-benzopyran-4-yl]-6-methylpyrrolo[1,2-b]pyridazine-3-carboxamide (A481) in 3 mL of DMF, 3.3 mg (0.077 mmol) of NaH was added. After adding 2.6 μL (0.042 mmol) of MeI, the mixture was stirred at room temperature for 1 h and then analyzed by preparative HPLC (ACN / H 2 O / TFA) to give 9.5 mg (41%) of the title compound (A543) as a yellow solid. (ESI, m / z): 541 [M+H] +

[0267] Preparation Example 10 Synthesis of 5H,6H,7H-pyrano[3,2-d][1,3]thiazol-7-amine (11-9) The amine group (11-9) used in the preparation of ring system U in compound A550 is synthesized from commercially available starting materials by the following reaction method.

[0268] 1. Synthesis of 3-[(tert-butyldimethylsilyl)oxy]-1-(2,5-dibromo-1,3-thiazol-4-yl)propan-1-ol (10-2) [ka] In a 250 mL three-neck round bottom flask, LDA (2M) (15.50 mL, 30.9 mmol) in THF (20.00 mL) was charged. The resulting solution was cooled to -78 °C. Then, a solution of 2,5-dibromo-1,3-thiazole (10-1, 5.00 g, 20.6 mmol) in 15 mL of THF was added. The resulting solution was stirred at -78 °C for 30 min. A solution of 3-[(tert-butyldimethylsilyl)oxy]propanal (3.88 g, 20.6 mmol) in 15 mL of THF was added. The resulting solution was stirred at -78 °C for 1 h. The resulting solution was further reacted at room temperature for 15 h under stirring. The pH value of the solution was adjusted to 6-7 with HCl (1 mol / L). The resulting solution was extracted with 2 x 100 mL of ethyl acetate and the organic layers were combined. The organic layers were washed with 100 ml of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:15). This gave 4.00 g (45%) of 3-[(tert-butyldimethylsilyl)oxy]-1-(2,5-dibromo-1,3-thiazol-4-yl)propan-1-ol (10-2) as a yellow oil.

[0269] 2. Synthesis of 2,5-dibromo-4-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (10-3) [ka] Into a 250 mL round bottom flask was charged 3-[(tert-butyldimethylsilyl)oxy]-1-(2,5-dibromo-1,3-thiazol-4-yl)propan-1-ol (10-2, 4.0 g, 9.3 mmol), DCM (40.00 mL), DHP (3.90 g, 46.4 mmol), and PPTS (0.23 g, 0.9 mmol). The resulting solution was stirred at 40° C. for 3 h. The resulting mixture was diluted with 30 mL of H 2 The mixture was washed with 30 mL of 0 and 30 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:10). This gave 3.62 g (75%) of 2,5-dibromo-4-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (10-3) as a yellow oil.

[0270] 3. Synthesis of 5-bromo-4-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (10-4) [ka] Into a 100 mL 3-neck round bottom flask was charged 2,5-dibromo-4-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (10-3, 3.60 g, 7.0 mmol) in 40 mL of THF. The resulting solution was cooled to -10 °C. i-PrMgCl (2M) (3.70 mL, 7.3 mmol) was added. The resulting solution was stirred at -10 °C for 1 h. The reaction was then quenched with 100 mL of NH 4 The reaction was quenched by the addition of saturated aqueous Cl. The resulting solution was extracted with 2×50 mL of ethyl acetate and the organic layers were combined. The organic layer was washed with 50 ml of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. This gave 2.60 g (85%) of 5-bromo-4-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (10-4) as a yellow oil.

[0271] 4. Synthesis of 3-(5-bromo-1,3-thiazol-4-yl)-3-(oxan-2-yloxy)propan-1-ol (10-5) [ka] In a 250 mL round bottom flask was charged 5-bromo-4-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (10-4, 2.60 g, 6.0 mmol), THF (30.00 mL), and TBAF (1 M) (7.20 mL, 7.2 mmol). The resulting solution was stirred at room temperature for 2 h. The resulting mixture was diluted with 30 mL of H 2 The mixture was washed with 30 mL of 0 and 30 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:1). This gave 1.55 g (81%) of 3-(5-bromo-1,3-thiazol-4-yl)-3-(oxan-2-yloxy)propan-1-ol (10-5) as a yellow oil.

[0272] 5. Synthesis of 7-(oxan-2-yloxy)-5H,6H,7H-pyrano[3,2-d][1,3]thiazole (10-6) [ka] In a 40 mL vial, 3-(5-bromo-1,3-thiazol-4-yl)-3-(oxan-2-yloxy)propan-1-ol (10-5, 1.55 g, 4.8 mmol), toluene (16.00 mL), Cs 2 CO 3(2.35 g, 7.2 mmol) and t-BuBrettPhos Pd G3 (0.33 g, 0.4 mmol) were charged. The resulting solution was stirred at 120° C. for 15 h. The solid was filtered off and washed with 20 mL of EA. The filtrate was concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:4). This gave 0.60 g (52%) of 7-(oxan-2-yloxy)-5H,6H,7H-pyrano[3,2-d][1,3]thiazole (10-6) as a yellow oil.

[0273] 6. Synthesis of 5H,6H,7H-pyrano[3,2-d][1,3]thiazol-7-ol (10-7) [ka] In a 20 mL vial, 7-(oxan-2-yloxy)-5H,6H,7H-pyrano[3,2-d][1,3]thiazole (10-6, 0.60 g, 2.5 mmol), THF (3.00 mL), H 2 2H2O (3.00 mL) and PTSA (85.63 mg, 0.35 mmol) were added. The resulting solution was stirred at room temperature for 2 hours. The resulting solution was diluted with 10 mL of H2O. 2 The mixture was diluted with 0.05% water. The resulting solution was extracted with 3×15 mL of ethyl acetate and the organic layers were combined. The organic layers were washed with 30 mL of brine. The organic layers were dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:1). This gave 0.20 g (51%) of 5H,6H,7H-pyrano[3,2-d][1,3]thiazol-7-ol (10-7) as a yellow oil.

[0274] 7. Synthesis of 7-azido-5H,6H,7H-pyrano[3,2-d][1,3]thiazole (10-8) [ka] In a 20 mL vial, 5H,6H,7H-pyrano[3,2-d][1,3]thiazol-7-ol (10-7, 200 mg, 1.3 mmol), THF (4.00 mL), and DPPA (420 mg, 1.5 mmol) were added. The resulting solution was cooled to 0° C. and DBU (232 mg, 1.5 mmol) was added. The resulting solution was stirred at room temperature for 15 h. To the resulting solution was added 10 mL of 10% HCl. The resulting solution was extracted with 2×10 mL of ethyl acetate and the organic layers were combined. The organic layer was washed with 20 ml of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:4). This afforded 110 mg (47%) of 7-azido-5H,6H,7H-pyrano[3,2-d][1,3]thiazole (10-8) as a yellow oil.

[0275] 8. Synthesis of 5H,6H,7H-pyrano[3,2-d][1,3]thiazol-7-amine (10-9) [ka] In a 50 mL pressure vessel reactor, 7-azido-5H,6H,7H-pyrano[3,2-d][1,3]thiazole (10-8, 0.30 g, 1.65 mmol), EtOH (9.00 mL), and Pd / C (30 mg, 10 wt%) were charged. The resulting solution was stirred at 40° C. under 10 atm hydrogen pressure for 6 h. The solids were filtered off and washed with 10 mL of EtOH. The filtrate was concentrated. The crude product was purified by flash preparative HPLC under the following conditions (IntelFlash-1): column, C18 silica gel; mobile phase, H 2 O:ACN=100:0~H 2 O:ACN increased to 70:30 within 15 min; detector, 254 nm. This gave 206.2 mg (80%) of 5H,6H,7H-pyrano[3,2-d][1,3]thiazol-7-amine (10-9) as a yellow solid. MS (ES, m / z): 157 [M+H] + ; 1 H NMR (300 MHz, CDCl 3, ppm) δ: 8.53 (s, 1H), 4.44-4.28 (m, 2H), 4.21 (t, J = 5.4 Hz, 1H), 2.23 (m, 1H), 1.86 (m, 1H).

[0276] Preparation Example 11 Synthesis of 5H,6H,7H-pyrano[2,3-d][1,3]thiazol-7-amine The amine group used in the preparation of ring system V in compound A551 is synthesized from commercially available starting materials by the following reaction methodology.

[0277] 1. Synthesis of 3-[(tert-butyldimethylsilyl)oxy]-1-(2,4-dibromo-1,3-thiazol-5-yl)propan-1-ol (11-2) [ka] In a 250 mL three-neck round bottom flask, LDA (2M, 15.50 mL, 30.9 mmol), THF (20 mL) were charged. The resulting solution was cooled to -78 °C. Then, a solution of 2,4-dibromo-1,3-thiazole (11-1, 5.00 g, 20.6 mmol) in THF (15 mL) was added. The resulting solution was stirred at -78 °C for 30 min. To the above solution, 3-[(tert-butyldimethylsilyl)oxy]propanal (3.88 g, 20.6 mmol) in THF (15.00 mL) was added. The resulting solution was stirred at -78 °C for 1 h. The resulting solution was reacted at room temperature for another 15 h with stirring. The pH value of the solution was adjusted to 6-7 with HCl (1 mol / L). The resulting solution was extracted with 2 x 100 mL of ethyl acetate and the organic layers were combined. The organic layer was washed with 100 ml of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:12). This gave 5.00 g (56%) of 3-[(tert-butyldimethylsilyl)oxy]-1-(2,4-dibromo-1,3-thiazol-5-yl)propan-1-ol (11-2) as a yellow oil.

[0278] 2. Synthesis of 2,4-dibromo-5-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (11-3) [ka] Into a 250 mL round bottom flask was charged 3-[(tert-butyldimethylsilyl)oxy]-1-(2,4-dibromo-1,3-thiazol-5-yl)propan-1-ol (11-2, 4.00 g, 9.3 mmol), DCM (60 mL), DHP (3.90 g, 46.4 mmol), PPTS (0.23 g, 0.9 mmol). The resulting solution was stirred at 40° C. for 2 h. The resulting mixture was diluted with 1×50 mL of H 2 The mixture was washed with 1×50 mL of 0 and 1×50 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:15). This gave 4.30 g (90%) of 2,4-dibromo-5-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (11-3) as a yellow oil.

[0279] 3. Synthesis of 4-bromo-5-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (11-4) [ka] Into a 100 mL 3-neck round bottom flask was charged 2,4-dibromo-4-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (11-3, 5.46 g, 10.6 mmol) and THF (50.0 mL). The resulting solution was cooled to -10 °C and i-PrMgCl (2M) (5.60 mL, 11.1 mmol) was added. The resulting solution was stirred at -10 °C for 1 h. The reaction was then quenched with 100 mL of NH 4The reaction was quenched by the addition of saturated aqueous Cl. The resulting solution was extracted with 2×50 mL of ethyl acetate and the organic layers were combined. The organic layer was washed with 50 ml of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. This gave 4.00 g (86%) of 4-bromo-5-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (11-4) as a yellow oil.

[0280] 4. Synthesis of 3-(4-bromo-1,3-thiazol-5-yl)-3-(oxan-2-yloxy)propan-1-ol (11-5) [ka] Into a 250 mL round bottom flask was charged 4-bromo-5-[3-[(tert-butyldimethylsilyl)oxy]-1-(oxan-2-yloxy)propyl]-1,3-thiazole (11-4, 4.00 g, 9.2 mmol), THF (40 mL), and TBAF (1M) (11 mL, 11.1 mmol). The resulting solution was stirred at room temperature for 2 h. The resulting mixture was diluted with 30 mL of H 2 The mixture was washed with 30 mL of 0 and 30 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:1). This gave 2.75 g (93%) of 3-(4-bromo-1,3-thiazol-5-yl)-3-(oxan-2-yloxy)propan-1-ol (11-5) as a yellow oil.

[0281] 5. Synthesis of 7-(oxan-2-yloxy)-5H,6H,7H-pyrano[2,3-d][1,3]thiazole (11-6) [ka] In a 40 mL vial, 3-(4-bromo-1,3-thiazol-5-yl)-3-(oxan-2-yloxy)propan-1-ol (11-5, 2.75 g, 8.5 mmol), toluene (25.00 mL), Cs 2 CO3 (4.17 g, 12.8 mmol) and t-BuBrettPhos Pd G3 (0.58 g, 0.7 mmol) were charged. The resulting solution was stirred at 100 °C for 15 h. The solid was filtered off and washed with 20 mL of EA. The filtrate was concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:4). This gave 1.20 g (58%) of 7-(oxan-2-yloxy)-5H,6H,7H-pyrano[2,3-d][1,3]thiazole (11-6) as a yellow oil.

[0282] 6. Synthesis of 5H,6H,7H-pyrano[2,3-d][1,3]thiazol-7-ol (11-7) [ka] In a 20 mL vial, 7-(oxan-2-yloxy)-5H,6H,7H-pyrano[2,3-d][1,3]thiazole (11-6, 1.20 g, 5.0 mmol), THF (4 mL), H 2 2H2O (4 mL) and PTSA (0.17 g, 1.0 mmol) were added. The resulting solution was stirred at room temperature for 15 hours. The resulting solution was diluted with 10 mL of H2O. 2 The mixture was diluted with 0.05% water. The resulting solution was extracted with 3×15 mL of ethyl acetate and the organic layers were combined. The organic layers were washed with 30 mL of brine. The organic layers were dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (9:1). This afforded 0.40 g (51%) of 5H,6H,7H-pyrano[2,3-d][1,3]thiazol-7-ol (11-7) as a yellow oil.

[0283] 7. 7-Azido-5H,6H,7H-pyrano[2,3-d][1,3]thiazole (11-8) [ka] In a 40 mL vial, 5H,6H,7H-pyrano[2,3-d][1,3]thiazol-7-ol (11-7, 400 mg, 2.5 mmol), THF (8 mL), and DBU (465 mg, 3.0 mmol) were charged. The resulting solution was cooled to 0° C. Then, DPPA (840 mg, 3.0 mmol) was added. The resulting solution was stirred at room temperature for 2 h. The resulting solution was added to 20 mL of 10% HCl. The resulting solution was extracted with 2×20 mL of ethyl acetate and the organic layers were combined. The organic layer was washed with 20 ml of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:3). This gave 0.22 g (47%) of 7-azido-5H,6H,7H-pyrano[2,3-d][1,3]thiazole (11-8) as a yellow oil.

[0284] 8. Synthesis of 5H,6H,7H-pyrano[2,3-d][1,3]thiazol-7-amine (11-9) [ka] In a 30 mL pressure vessel reactor, 7-azido-5H,6H,7H-pyrano[2,3-d][1,3]thiazole (11-8, 300 mg, 1.65 mmol), EtOH (6 mL), and Pd / C (30 mg, 0.3 mmol) were charged. The resulting solution was stirred at room temperature under 5 atm hydrogen pressure for 15 h. The solids were filtered off and washed with 20 mL of EtOH. The filtrate was concentrated. The crude product was purified by flash preparative HPLC with the following conditions (IntelFlash-1): column, C18 silica gel; mobile phase, H 2 O:ACN=80:20~H 2 O:ACN increased to 40:60 within 15 min; detector, 254 nm. This gave 210.6 mg (82%) of 5H,6H,7H-pyrano[2,3-d][1,3]thiazol-7-amine (11-9) as a pale yellow solid. MS (ES, m / z): 157 [M+H] + ; 1 H NMR (300 MHz, CDCl 3, ppm) δ: 8.47 (s, 1H), 4.41-4.29 (m, 2H), 4.21 (t, J = 5.4 Hz, 1H), 2.23 (m, 1H), 1.83(m, 1H).

[0285] Preparation Example 12 Synthesis of 2H,3H,4H-pyrano[3,2-c]pyridin-4-amine (12-2) The bicyclic amines used in the preparation of the ring systems AF present in compound A569 (see Table 3) are prepared from commercially available materials according to the method shown below.

[0286] [ka]

[0287] To a solution of 400 mg (2.6 mmol) of 2H-pyrano[3,2-c]pyridin-4(3H)-one (12-1) and 1.35 g (21.4 mmol) of ammonium formate in 13.4 mL of methanol, 887 mg (13.4 mmol) of sodium cyanoborohydride was added at room temperature, and the mixture was then stirred at 60° C. overnight. After further addition of the same amount of ammonium formate and sodium cyanoborohydride and stirring at 60° C. for 3 h, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, and quenched with water. After phase separation, the organic phase was washed with anhydrous Na 2 SO 4 Drying at 40° C. and evaporation of the solvent afforded 120 mg (23%) of the title compound (12-2) as a crude oil. The crude material was used without further purification. (ESI, m / z): 151 [M+H] +

[0288] Table 4 below relates to certain compounds shown in Table 3 and prepared according to the methods outlined in Schemes 1, 2 and 3, and the preparative examples set forth above. 1 H NMR data included.

[0289] JPEG2024540166000167.jpg242168 JPEG2024540166000168.jpg244155 JPEG2024540166000169.jpg244155 JPEG2024540166000170.jpg243154 JPEG2024540166000171.jpg244154 JPEG2024540166000172.jpg244156 JPEG2024540166000173.jpg245155 JPEG2024540166000174.jpg243154 JPEG2024540166000175.jpg212170

[0290] Biological Examples The present disclosure is further illustrated by the following biological examples, which should not be construed as limiting the disclosure in scope or spirit to the specific procedures described herein. It should be understood that the examples are provided to illustrate certain embodiments, and that no limitations on the scope of the present disclosure are intended thereby. It should be further understood that various other embodiments, modifications, and equivalents thereof can be used, and may suggest themselves to those skilled in the art, without departing from the spirit of the present disclosure and / or the scope of the appended claims.

[0291] Biological Example 1 A screening method for testing the activity of compounds against microfilariae of Dirofilaria immitis (dog heartworm). 400-600 Dirofilaria immitis microfilariae were added to wells of a microtiter plate containing RPMI medium and test compound formulated in 100% DMSO. Incubate at 37°C and 5% CO 2 Plates were kept at RT for 3 days. Compound efficacy was determined based on the motility of microfilariae compared to the average motility of control wells containing DMSO only. Dose-response assays were performed to determine the EC 50Compounds A468, A470, A480, A482, A508, A510, A514, A529, A536b, A538, A543, A547, A548, A552, A556, A561, A562, A563, A564 and A567 were determined to have EC 50 Compounds A465, A467, A475, A509, A527, A524, A549, A554 and A560 exhibited EC values ​​of 100-1000 nM. 50 Compounds A518, A497, A494, A481, A479, A478, A473, A487, A476, A483, A469, A466, A462, A492, A528, A532, A533, A539, ​​A544, A550, A551, A555, and A559 exhibited EC 50 The values ​​ranged from 10 nM to 100 nM. Compounds A463, A464, A484, A485, A486, A499, A471, A472, A474, A477, A488, A489, A490, A491, A492, A493, A495, A496, A498, A501, A502, A503, A504, A505, A506, A507, A513, A516, A517, A519, A522, A523, A525, A526, A530, A534, A536a, A537, A540, A541, A553, A557, A558, A565, A566, A568 and A569 have an EC 50 It presented value.

[0292] Biological Example 2 A screening method for testing the activity of compounds against Haemonchus contortus. Twenty L1 larval bodies of Haemonchus contortus were added to wells of a microtiter plate containing culture medium and test compound in DMSO. Assays were performed over 4 days to determine the extent of development of L1-L3 larval bodies. Larval bodies exposed to DMSO alone served as controls. Dose-response assays were performed to determine the EC 50 Compounds A512, A515, A535, A549, A554, A563, A564 and A567 had EC values ​​of 1000 nM to 10000 nM.50 Compounds A462, A466, A479, A492, A482, A527, A528, A524, A532, A533, A544, and A560 exhibited EC values ​​ranging from 100 nM to 1000 nM. 50 Compounds A463, A465, A483, A476, A487, A475, A474, A477, A478, A488, A481, A494, A496, A497, A498, A499, A501, A503, A504, A505, A506, A513, A516, A517, A518, A525, A526, A536a, A540, A541, A550, A551, A555, A559 and A565 had an EC value of 10 nM to 100 nM. 50 Compounds A484, A485, A486, A472, A471, A473, A493, A495, A502, A507, A523, A522, A530, A534, A553, A557, A558, A566 and A568 exhibited EC values ​​of less than 10 nM. 50 It presented value.

[0293] Biological Example 3 A screening method for testing the activity of compounds against L4 stage larval bodies of Dirofilaria immitis. Four to six L4 stage Dirofilaria immitis larvae were added to wells of a microtiter plate containing maintenance culture medium and test compound formulated in 100% DMSO. The wells were incubated at 37 °C and 5% CO. 2 The plates were kept at 5°C for 3 days and then evaluated to determine motility of larvae. Compound efficacy is determined by comparing the motility of treated L4 with the average motility of larvae in control wells containing DMSO only. Dose-response assays were performed to determine the EC 50 Compounds 536b, 538, A543, A545, A546, A547, A548, A552, A556, A561, A562, A563 and A564 have an EC value of 1000 nM to 10000 nM. 50Compounds A467, A478, A479, A480, A521, A524, A529, A532, A533, A539, ​​A544, A549, A554 and A567 exhibited EC values ​​ranging from 100 nM to 1000 nM. 50 Compounds A462, A463, A465, A466, A469, A482, A488, A496, A527, A528, A536a, A537, A540, A550, A551, A555, and A559 exhibited EC values ​​ranging from 10 nM to 100 nM. 50 Compounds A464, A483, A484, A485, A486, A471, A473, A474, A476, A477, A487, A489, A482, A499, A491, A481, A490, A493, A494, A495, A498, A501, A502, A503, A504, A505, A506, A507, A513, A516, A519, A522, A523, A525, A526, A530, A534, A541, A553, A557, A558, A565 and A566 were found to have an EC 50 It presented value.

[0294] Biological Example 4 In vivo efficacy against the resistant JYD-34 isolate of Dirofilaria immitis in immunodeficient (NOD-scid-gamma, NSG) mice. The efficacy of the compounds of the invention against resistant isolates of Dirofilaria immitis (JYD-34 isolate) was evaluated in immunodeficient mice (NOD-scid-gamma, NSG) as intermediate hosts of the parasite (see WO2018 / 148392). Mice were infected with approximately 50 third stage Dirofilaria immitis (JYD-34 isolate) by subcutaneous injection on day 0. Mice were treated orally with placebo and test substance at a dose of 25 mg / kg body weight on days 1, 15 and 30. A dose of 25 mg / kg in rodent models is considered to be equivalent to a dose of 5 mg / kg in dogs. Mice were euthanized on day 45 after treatment, 15 days after the last dose, and live Dirofilaria immitis larvae were collected from tissues and counted.

[0295] In this model, compound A491 exhibited less than 50% efficacy, compounds A465, A484 and A495 exhibited 50%-70% efficacy, compounds A464, A486, A471, A481, A489, A501, A502 and A566 exhibited 70%-90% efficacy, and compounds A472, A473, A493, A504, A507, A522 and A530 exhibited greater than 90% efficacy. Mice treated with the macrocyclic lactone ivermectin orally at a dose of 0.2 mg / kg exhibited less than 50% efficacy. For the commercially available HEARTGARD® Plus (ivermectin / pyrantel), the minimum recommended dosage level of ivermectin for dogs is 6 μg / kg.

[0296] Biological Example 5 Comparison of in vivo efficacy against the resistant JYD-34 isolate of Dirofilaria immitis in immunodeficient (NOD-scid-gamma, NSG) mice with the closest prior art compound. The compounds of the present invention having a bicyclic pyrrolopyridazine core structure have been found to be highly efficacious against immature stages of Dirofilaria immitis, such as microfilariae and L4 stage larvae, including isolates of Dirofilaria immitis that have been shown to be resistant to macrocyclic lactone treatments. Such resistant isolates of Dirofilaria immitis include isolate JYD34 and the like. Importantly, the compounds of the present invention having a 5-6 fused bicyclic pyrrolopyridazine core structure have demonstrated surprising and unexpected superior efficacy against immature stages of Dirofilaria immitis, as compared to compounds having the same substituents around the bicyclic core, but different 5-6 fused nitrogen-containing bicyclic cores. The efficacy of compound A465 of the present invention and prior art compound 156 described in WO2020 / 014068 (see page 124) was evaluated using the in vivo protocol described in Biological Example 4 above. The compounds described in WO2020 / 014068 contain a different 5-6 fused bicyclic ring core (pyrazolo[1,5-a]pyridine) compared to the pyrrolopyridazine core ring system of the compounds of the present invention. Except for the different core ring systems, compound A465 and prior art compound 156 contain the same substituents around the bicyclic ring. The structures of compound A465 of the present invention and prior art compound 156 are illustrated below.

[0297] [ka]

[0298] In this in vivo model system, at a dose of 25 mg / kg, compound A465 exhibited 68% efficacy, whereas compound 156 exhibited 29% efficacy. The difference in efficacy is significant in this model. This example clearly demonstrates the importance of the pyrrolopyridazine bicyclic ring for the in vivo efficacy of compounds against resistant isolates of Dirofilaria immitis. As illustrated by the two structures above, apart from the bicyclic ring system, the substitution patterns of these compounds are identical.

[0299] Biological Example 6 In vivo efficacy against resistant JYD-34 isolates of Dirofilaria immitis in dogs. Beagles were tested for microfilaria and heartworm antigens and underwent a complete physical examination prior to inclusion in the study. On day -30, each dog was inoculated with 50 infective third stage D. immitis larvae using the JYD-34 isolate, which has demonstrated resistance to macrocyclic lactones. Antigen testing performed on blood collected on day 90 confirmed that the animals had not been exposed to D. immitis prior to the induced infection. The dogs were ranked by ascending weight within sex to form groups of 8 dogs each with approximately equal numbers of each sex, and randomly assigned to each treatment group. Each study group contained 5 dogs. In the negative control group (group 1), the dogs were untreated. Group 2 dogs were orally treated 4 times at monthly intervals with the commercial product Interceptor™ (milbemycin oxime) according to the product label. Groups 3 and 4 dogs were orally treated 4 times at monthly intervals (days 0, 27, 55, and 84) with capsules containing an oral solution of compounds A471 and A464, respectively, at a dose of 5 mg / kg body weight. On study day 120, the dogs were euthanized and necropsied to assess for the presence of adult heartworms. The results of the study are shown in Table 5 below.

[0300] JPEG2024540166000177.jpg52132

[0301] As shown in Table 5, compounds A471 and A464 of the present invention were found to be more effective than the commercial Interceptor™ when administered according to the labeled dosage against the resistant JYD-34 isolate of Dirofilaria immitis.

[0302] Biological Example 7 In vivo efficacy at two doses against resistant JYD-34 isolates of Dirofilaria immitis in dogs. In a further in vivo study conducted according to the procedure described in Biological Example 6 above, the efficacy of compounds A481 and A493 against a resistant heartworm isolate (JYD-34) in beagles was tested at two different dose rates, compared to a negative control group (group 1) and a positive control group (group 2) treated with Interceptor™ (milbemycin oxime). The purpose of administering the test compounds daily at a higher dose rate was to evaluate the effect of increased exposure to the compounds on efficacy against heartworm. Considering the length of the heartworm life cycle of the target L4 stage larvae (see, for example, page 1, line 25 to page 2, line 10) and the duration of the study, it is believed that splitting the total dose into two daily administrations would not adversely affect the study outcome. In this study, group 3 was treated with compound A481 at a dose of 5 mg / kg body weight on days 0, 27, 55 and 84. Dogs in group 4 were treated with compound A481 at a dose of 5 mg / kg body weight on days -1, 0, 26, 27, 54, 55, 83 and 84. Similarly, dogs in group 5 were treated with compound A493 at a dose of 5 mg / kg body weight on days 0, 27, 55 and 84, and dogs in group 6 were treated with compound A493 at a dose of 5 mg / kg body weight on days -1, 0, 26, 27, 54, 55, 83 and 84. The results of the study are shown in Table 6 below.

[0303] JPEG2024540166000178.jpg73146

[0304] As shown in Table 6, compounds A481 and A493 are highly efficacious against resistant JYD-34 isolates of Dirofilaria immitis compared to the positive control. It is important to note that the Interceptor™ group (group 2) was dosed monthly according to the product label, but the optimal dose of the test compound has yet to be determined. It is also noted that the efficacy of the Interceptor™ group (group 2) in this study was significantly higher than that observed in the studies described in Biological Example 6 and Biological Example 9 (below). When administered at a dose of 5 mg / kg two consecutive days per month for four months, compounds A481 and A493 exhibited approximately 98% and 100% efficacy against resistant JYD-34 isolates of Dirofilaria immitis, while compound A493 exhibited 99% efficacy when administered at a single dose of 5 mg / kg once per month for four months. These results for resistant isolates of Dirofilaria immitis are significant and surprising.

[0305] Biological Example 8 In vivo efficacy against resistant JYD-34 isolates of Dirofilaria immitis in dogs. In a further in vivo study, the efficacy of compound A472 was tested against a resistant heartworm isolate (JYD-34) in beagles, compared to a negative control group (group 1) and a positive control group (group 2) treated with Interceptor™ (milbemycin oxime), using the procedure described in Biological Example 6. In this study, compound A472 was found to be 100% effective in preventing adult heartworm infections when administered monthly for four months at a dose of 5 mg / kg body weight. In comparison, the milbemycin oxime control group was found to only be 16.6% effective. The results of the study are summarized in Table 7 below.

[0306] JPEG2024540166000179.jpg52160

[0307] The superior in vivo efficacy of the compounds of the present invention against resistant isolates of Dirofilaria immitis, as shown above in comparison to the commercially available Interceptor™ (milbemycin oxime), is noteworthy and demonstrates the inventive step of the compounds described herein.

[0308] Having thus described preferred embodiments of the invention in detail, it is to be understood that the invention as defined by the above paragraphs is not limited to the specific details set forth in the above specification, but rather is capable of many apparent variations therein without departing from the spirit or scope of the invention.

Claims

1. Compounds of Formula I: 【Chemical 1】 （I） (In the formula: L is L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16 or L17; 【Chemistry 2】 R' is hydrogen, optionally substituted alkyl, optionally substituted haloalkyl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted aryl, or two R's of the same L group may join together to form a 2- to 4-membered carbon chain, resulting in a heterocycle; R 1 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, optionally substituted trialkylsilyl, optionally substituted trialkylsilyloxy, -SO p (optionally substituted alkyl or haloalkyl), —SF 5 , or -NR a R b and R a and R b are independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1 ' is hydrogen, halogen, alkyl or haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl; optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, -SO p (optionally substituted alkyl or haloalkyl), —SF 5 , or -NR a R b and R a and R b are independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 3 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl; optionally substituted aryloxy, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkoxy, optionally substituted heterocyclyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, -SO p (optionally substituted alkyl or haloalkyl), —SF 5 , or -NR a R b and R a and R b are independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 4 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylaminocarbonyl, -S(O) p (optionally substituted alkyl), —SF 5 , optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted 5- to 10-membered heteroaryl, spirocyclic heterocyclyl-carbocyclyl group, spirocyclic heterocyclyl-heterocyclyl group, spirocyclic carbocyclyl-carbocyclyl group, spirocyclic carbocyclyl-heterocyclyl group or -NR a R b and R a and R b are independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 5 and R 5 ' is independently, at each occurrence, hydrogen, halogen, cyano, nitro, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkoxy, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted di(alkyl)aminocarbonyl, optionally substituted alkylcarbonyloxy, optionally substituted alkylcarbonylamino, optionally substituted aryl, optionally substituted heteroaryl, -SF 5 , -SO p (optionally substituted alkyl or haloalkyl); or R 5 is R 5 together with —NR′ form a 2- to 6-membered chain which may contain one or two heteroatoms selected from the group consisting of N, O, Si and S, forming a carbocyclic or heterocyclic ring together with the carbon atom to which they are attached; or —NR c R d and R c and R d are independently H or optionally substituted alkyl; or R c and R d may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 9 is hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, alkenyl or alkynyl; R 6 and R 7 are independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted alkoxy, or optionally substituted cycloalkoxy, or R 6 is R 7 together with form a 2-6 membered chain which may contain 1 or 2 heteroatoms selected from the group consisting of N, O, Si and S to form a carbocyclic or heterocyclic ring together with the carbon atoms to which they are attached, and any carbon or nitrogen atom in the chain may be substituted; Q is C-R 9 or N; X is O, S or N—R′; Y 1 and Y 6 are each independently N, C, or —CR 5 and Y 2 , Y 3 , Y 4 and Y 5 are each independently N, NR′, S, O, or —CR 5 - or CR 5 R 5 ' and; W is CR 6 , C.R. 6 R 7 , O, SO p , N or N-R 8 or W is absent; W 1 is CR 6 , C.R. 6 R 7 , O, SO p , N or N-R 8 and Z is CR 7 , C.R. 6 R 7 , O, SO p , N or N-R 8 and R 8 is hydrogen or C 1 ~C 4 - alkyl; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 at most three of which are heteroatoms; q is 0 or 1; p is independently, in each occurrence, 0, 1, or 2; The dashed bond ( 【Chemistry 3】 ) represents a single or double bond; "Optionally substituted" means that the listed group is selected from the group consisting of halogen, hydroxyl, oxo, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, carboxyl, acyl, acyloxy, acetyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, haloalkylaminocarbonyl, dihaloalkylaminocarbonyl, amino, alkylamino or dialkylamino, amido, arylamino, alkoxy, haloalkoxy, alkylthio, haloalkylthio, aryloxy, nitro, cyano, azido, thiol, thioamide, imino, amidino, guanidino, carbonate, silyl, silyl ether, SF 5 , R 3 Si- or R 3 SiO— (wherein R is alkyl, haloalkyl, or aryl), SF 5 , sulfate, alkylsulfonyl, haloalkylsulfonyl, sulfate, alkylsulfonyl, haloalkylsulfonyl, alkoxysulfonyl, alkylsulfinyl, haloalkylsulfinyl, sulfamoyl, sulfoximine, sulfinimine, sulfonimidamide, sulfondiimine, phosphonyl, phosphinyl, phosphoryl, phosphine, phosphonamidate, phosphinamidate, phosphinate, phosphine oxide, thioester, anhydride, oxime, hydrazine, carbamate, phosphate, phosphonate, aryl, heteroaryl, or heterocyclyl) Or its salt.

2. The compound of formula (I) of claim 1 having the structure of formula (IA): 【Chemistry 4】 (IA) (In the formula: L is L1, L2, L6, L7, L16 or L17; 【Chemistry 5】 R ’ is hydrogen, optionally substituted alkyl, optionally substituted haloalkyl or optionally substituted aralkyl; R 1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl or -NR a R b and R a and R b are independently H or optionally substituted alkyl; or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; R 1’ is hydrogen, halogen, alkyl or haloalkyl; R 2 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted alkenyl or optionally substituted alkynyl; R 3 is hydrogen, cyano, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted alkenyl or optionally substituted alkynyl; R 4 is optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted phenyl or optionally substituted 5- or 6-membered heteroaryl; R 5 and R 5’ is independently at each occurrence hydrogen, halogen, cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted alkoxy; R 9 is hydrogen, halogen, alkyl or haloalkyl; R 6 and R 7 are independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, or R 6 is R 7 together with form a 2-6 membered chain which may contain 1 or 2 heteroatoms selected from the group consisting of N, O, Si and S to form a carbocyclic or heterocyclic ring together with the carbon atoms to which they are attached, and any carbon or nitrogen atom in the chain may be substituted; Q is C-R 9 or N; X is O, S or N—R′; Y 1 and Y 6 is independently N or C; Y 2 , Y 3 , Y 4 and Y 5 are each independently N or —CR 5 and W is CR 6 or CR 6 R 7 or W is absent; W 1 is CR 6 or CR 6 R 7 and Z is CR 6 , C.R. 6 R 7 or O; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 at most three of are N; The dashed bond ( 【Chemistry 6】 ) represents a single or double bond; "Optionally substituted" means that the listed group is substituted with one or more of halogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, carboxyl, acyl, acyloxy, acetyl, R 3 Si- or R 3 SiO— (wherein R is alkyl, haloalkyl, or aryl), SF 5 , sulfate, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonyl, haloalkylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, haloalkylaminocarbonyl, dihaloalkylaminocarbonyl, amino, alkylamino or dialkylamino, amido, alkoxy, haloalkoxy, alkylthio, haloalkylthio, cyano, thiol, thioamide, SF 5 , alkylsulfonyl, alkoxysulfonyl, or alkylsulfinyl) Or its salt.

3. 3. A compound of formula (I) or formula (IA) according to claim 1 or 2, wherein Q is N.

4. Q is C-R 9 3. A compound of formula (I) or formula (IA) according to claim 1 or 2, wherein:

5. 2. The compound of formula (I) or formula (IA) according to claim 1, wherein X is O or S.

6. 2. The compound of formula (I) or formula (IA) according to claim 1, wherein L is L1 or L2.

7. W and W 1 But independently, CR 6 R 7 and Z is O.

8. 3. A compound of formula (I) or formula (IA) according to claim 1 or 2, represented by a compound of formula (Ie): 【Chemistry 7】 (Ie) (In the formula: Each R 10 are independently halogen, cyano, hydroxyl, optionally substituted C 3 ~C 8 -cycloalkyl, optionally substituted C 3 ~C 8 -cycloalkyloxy, C 1 ~C 4 -Alkyl, C 1 ~C 4 -haloalkyl, C 3 ~C 8 -halocycloalkyl, C 1 ~C 4 -alkoxy, C 1 ~C 4 -haloalkoxy, C 2 ~C 6 -alkenyl, C 2 ~C 6 -haloalkenyl, C 2 ~C 6 -alkynyl, C 2 ~C 6 -haloalkynyl, C 1 ~C 6 -alkoxy-C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkoxy-C 1 ~C 6 -alkyl, optionally substituted phenyl, optionally substituted phenyloxy, optionally substituted 5- or 6-membered heteroaryl, optionally substituted 3- to 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from the group consisting of N, O, Si and S, C 1 ~C 6 - alkylcarbonyl, C 1 ~C 6 -haloalkylcarbonyl, C 1 ~C 6 -alkoxycarbonyl, C 1 ~C 6 -haloalkoxycarbonyl, aminocarbonyl, C 1 ~C 6 - alkylaminocarbonyl, C 1 ~C 6 -haloalkylaminocarbonyl, di-C 1 ~C 6 -Alkylaminocarbonyl, di-C 1 ~C 6 -haloalkylaminocarbonyl, -SO p (Optionally substituted C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl) (wherein p is 0, 1 or 2), SF 5 , or -NR a R b and R a and R b are independently H, C 1 ~C 6 -Alkyl or C 1 ~C 6 -haloalkyl); or R a and R b may, together with the nitrogen to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclyl group, which may contain 1 to 3 additional heteroatoms selected from the group consisting of N, O, Si, and S, and which may be substituted; m is 0, 1, 2, 3, 4 or 5.

9. Each R 10 The compound of claim 8 , wherein: is independently a halogen; and m is 2 or 3.

10. Each R 10 is independently chloro or fluoro; m is 2 or 3; R 1 But C 1 ~C 4 -alkyl or -NR a R b and R 1’ is hydrogen; R 2 But hydrogen, halogen, C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl; R 3 But hydrogen, halogen, C 1 ~C 3 -Alkyl or C 1 ~C 3 -haloalkyl; W is CH 2 and W 1 is CH 2 and Z is O; The compound of claim 8.

11. R 10 is chloro or fluoro, the chloro or fluoro substituents being located at positions 2, 3 and 5 of the phenyl ring; R 2 is hydrogen; R 3 But C 1 ~C 3 - alkyl or halogen, The compound of claim 10.

12. R 1 isopropyl, tert-butyl, -N(CH 3 ) 2 or azetidinyl, which may be substituted by one or more methyl or fluoro; The compound of claim 11.

13. Each Y 2 , Y 3 , Y 4 and Y 5 But independently, -C-R 5 2. The compound of claim 1, wherein:

14. Y 2 is N and Y 3 , Y 4 and Y 5 But independently, -C-R 5 or Y 3 is N and Y 2 , Y 4 and Y 5 But independently, -CR 5 or Y 4 is N and Y 2 , Y 3 and Y 5 But independently, -CR 5 or Y 5 is N and Y 2 , Y 3 and Y 4 But independently, -CR 5 or Y 2 and Y 3 is N; Y 4 and Y 5 But independently, -CR 5 or Y 3 and Y 4 is N; Y 2 and Y 5 But independently, -CR 5 or Y 4 and Y 5 is N; Y 2 and Y 3 But independently, -CR 5 or Y 2 and Y 4 is N; Y 3 and Y 5 But independently, -CR 5 or Y 3 and Y 5 is N; Y 2 and Y 4 But independently, -CR 5 or Y 3 and Y 4 is N; Y 2 and Y 5 But independently, -CR 5 2. The compound of claim 1, wherein:

15. The compound of claim 1 having the formula (IA-1): 【Chemistry 8】 Formula (IA-1) (In the formula, L, R 1 , R 1’ , R 2 , R 3 and R 4 is as defined in the table below; X is oxygen unless otherwise noted in the table, and R' is hydrogen unless otherwise noted in the table; base 【Chemistry 9】 represents the following ring system: 【Chemistry 10】 Ring system A; 【Chemistry 11】 Ring system B; 【Chemistry 12】 Ring system C; 【Chemistry 13】 Ring system D; 【Chemistry 14】 Ring system E; 【Chemistry 15】 Ring system F; 【Chemistry 16】 Ring system G; 【Chemistry 17】 Ring system H; 【Chemistry 18】 Ring system I; 【Chemistry 19】 Ring system J; 【Chemistry 20】 Ring system K; 【Chemical 21】 Ring system L; 【Chemical Formula 22】 Ring system M; 【Chemical 23】 Ring system N; 【Chemistry 24】 Ring system O; 【Chemistry 25】 Ring system P; 【Chemical 26】 Ring system Q; 【Chemical 27】 Ring system R; 【Chemical formula 28】 Ring system S; 【Chemical 29】 Ring system T; 【Chemistry 30】 Ring system U; 【Chemical 31】 Ring system V; 【Chemical 32】 Ring system W; 【Chemical 33】 Ring system X; 【Chemical 34】 Ring system Y; 【Chemical 35】 Ring system Z; 【Chemical 36】 Ring system AA; 【Chemical 37】 Ring system AB; 【Chemical 38】 Ring system AC; 【Chemical Formula 39】 Ring system AD; 【Chemistry 40】 Ring system AE; 【change】 【change】 【change】 【change】 【change】 【change】 【change】

16. 10. A veterinary composition comprising a compound of claim 1 or a salt thereof and a pharmaceutically acceptable carrier.

17. 10. A veterinary composition comprising a compound of claim 1 or a salt thereof, one or more additional active agents, and a pharmaceutically acceptable carrier.

18. 10. A method for treating, controlling and / or preventing parasitic infection and / or infestation in a non-human animal in need thereof, comprising administering to said non-human animal an effective amount of a compound according to claim 1 or a salt thereof.

19. 10. Use of a compound according to claim 1 in the preparation of a medicament for treating, controlling and / or preventing parasitic infections and / or infestations in animals.

20. 10. A compound of formula (I) according to claim 1 for use in a method for treating, controlling and / or preventing parasitic infections and / or infestations in animals.

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