(THI)OXAZOLINE PESTICIDE

Abstract

The present invention relates to a compound of formula (I) [Formula 1] TIFF2024523269000071.tif51156 Compounds of formula (I) are provided that are useful for the long-term treatment and control of pests, such as fleas and ticks, in companion animals and livestock, and pharmaceutical compositions and methods of using the same.

Description

[Technical field]

[0001] This invention relates to medicinal chemistry, pharmacology, and veterinary and human healthcare. [Background technology]

[0002] Heteroarylisoxazolines are used in agriculture, forestry, turf, household, wood products, seedling crop protection, and veterinary medicine.Veterinary medicine includes companion animals and livestock, including fish.For example, such inhibitors are disclosed in WO 2005 / 085216, WO 2007 / 079162, US Patent Application Publication No. 2007 / 066617, US Patent Application Publication No. 20130131017, WO 2009 / 002809, WO 2009 / 112275, WO 2010 / 003923, WO 2010 / 070068, WO 2012 / 120399, WO 2013 / 079407, and WO 2021 / 127188.

[0003] In many applications, long-term effectiveness against pests is desirable. Long-lasting protection is particularly important in companion animals such as dogs and cats, as well as mice, guinea pigs, ferrets, and rabbits, and in large-scale grazing animals such as cattle, sheep, pigs, and fish, especially salmon and sea bass. Summary of the Invention

[0004] The present invention relates to compounds of formula (I) having long half-lives in companion animals and livestock, particularly warm-blooded animals, especially dogs, cats, and cattle, and their use in combating ectoparasites. In many cases, the compounds of formula (I) provide a long duration of action of several months after a single oral dose or injection.

[0005] The present invention also provides compounds of formula (I) that effectively treat and / or control ectoparasites in companion animals and livestock.

[0006] In one embodiment, the present invention provides a compound of formula (I): [ka] During the ceremony, A1 is selected from the group consisting of CF3, CHF2, CH2F, and CF2CF3; A2 is O or S; Z is N or CR2, preferably CR2; R1 is selected from the group consisting of hydrogen and halogen; R2 is selected from the group consisting of hydrogen, halogen, difluoromethyl, trifluoromethyl, and trifluoromethoxy, preferably selected from the group consisting of halogen, difluoromethyl, and trifluoromethyl, more preferably selected from the group consisting of fluorine, chlorine, difluoromethyl, and trifluoromethyl; R3 is selected from the group consisting of hydrogen, halogen and trifluoromethyl; R4 is selected from the group consisting of hydrogen, halogen, difluoromethyl, trifluoromethyl, hydroxy, methoxy, and trifluoromethoxy, preferably selected from the group consisting of halogen, difluoromethyl, and trifluoromethyl, more preferably selected from the group consisting of fluorine, chlorine, difluoromethyl, and trifluoromethyl; Q is selected from the group consisting of: [ka] During the ceremony, p is 0, 1, or 2; q is 0, 1, 2, or 3; r is 0 or 1; s is 0, 1, or 2; t is 0 or 1; R5 at each occurrence is independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, C2-C5-alkoxycarbonyl, C1-C6 alkyl, which is halogen, cyano, nitro, hydroxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, and -SO2C1-C4 alkyl. C1-C6 alkyl and C1-C6 alkoxy optionally substituted by 1 to 5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, and -SO2C1-C4 alkyl, -NR7C(O)(C1-C4 alkyl); -NR7C(O)(C1-C4 alkyl), -C(O)NR7(C1-C4 alkyl) which are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), and -N(C1-C4 alkyl)2, where R7 is independently selected from the group consisting of hydrogen and C1-C4 alkyl; -C(O)NR7(C1-C4 alkyl), where R7 is independently selected from the group consisting of hydrogen and C1-C4 alkyl, -C(O)NR7(C1-C4 alkyl), -SC1-C6 alkyl, where halogen, cyano, nitro, hydroxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), and -N(C1-C4 alkyl)2, each of which may be substituted with 1 to 5 substituents independently selected from the group consisting of C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), and -N(C1-C4 alkyl), where R7 is independently selected from the group consisting of hydrogen and C1-C4 alkyl;independently selected from the group consisting of -SC1-C6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of -NH(C1-C4 alkyl), and -N(C1-C4 alkyl)2, and -S(O)C1-C6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), and -N(C1-C4 alkyl)2; R6 at each occurrence is independently selected from the group consisting of oxo, C1-C4 alkyl, and C3-C6 cycloalkyl; A3 is O or S; A4 is CH or N; A5 is CH or N; A6 is CH or N; A7 is CH 2 O, S, a bond, or N; A8 is CH 2 O, S, a bond, or N; A9 is CH or N; A 10 is CH or N, A 11 is CH or N, A 12 is CH or N, A 13 is CH or N, A 14 is CH or N, A 15 is CH or N, A 16 is NR, O, or S, where R is selected from the group consisting of hydrogen, C1-C4 alkyl, and C3-C6 cycloalkyl; W1 is selected from the group consisting of -O-, -S-, -NR8-, -NC(O)R9-, -CH2-, and -C(O)-; W2 is selected from the group consisting of -O-, -S-, -NR8-, -NC(O)R9-, -CH2-, and -C(O)-; however, When W1 is -O-, -S-, -NR8-, or -NC(O)R9-, W2 is -CH2-, or -C(O)-; when W2 is -O-, -S-, -NR8-, or -NC(O)R9-, W1 is -CH2-, or -C(O)-; W3 is selected from the group consisting of nil, -O-, -S-, -S(O)-, -S(O)2-, -NR8-, -CH-, -N-, -CH2-, and -C(O)-; W4 is selected from the group consisting of nil, -O-, -S-, -S(O)-, -S(O)2-, -NR8-, -CH-, -N-, -CH2-, and -C(O)-; W5 is selected from the group consisting of nil, -O-, -S-, -S(O)-, -S(O)2-, -NR8-, -CH-, -N-, -CH2-, and -C(O)-; W6 is selected from the group consisting of nil, -O-, -S-, -S(O)-, -S(O)2-, -NR8-, -CH-, -N-, -CH2-, and -C(O)-; In the formula, the bond between W1, W2, W3, and W4 can be a single bond or a double bond; however, (i) Two or less of W1, W2, W3, and W4 are nil (none); (ii) no more than two of W1, W2, W3, and W4 are -O-, -S-, -S(O)-, -S(O)2-, -NR8-, or -C(O)-; (iii) when two of W1, W2, W3, and W4 are -O- and / or -S-, there is at least one carbon atom between them; and (iv) When W1, W2, W3, or W4 is -CH- and / or -NR8-, a double bond is formed in the ring formed by W1, W2, W3, and W4; R8 is independently selected at each occurrence from the group consisting of hydrogen and C1-C6 alkyl optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, and -SO2C1-C4 alkyl; R9 at each occurrence is independently selected from the group consisting of oxo, C1-C4 alkyl, and C3-C6 cycloalkyl; X is a 5-10 membered heteroaryl having 1 or 2 heteroatoms selected from the group of O, S, and N; The carbon of the 5-10 membered heteroaryl is halogen, cyano, nitro, hydroxyl, C1-C4 alkyl, which are selected from halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, and -C(O)NH-C1-C and optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, and -C(O)NH-C1-C6 haloalkyl, In the formula, any N of the heteroaryl is, if permitted by valence, hydrogen, C1-C4 alkyl optionally substituted by a substituent selected from the group consisting of halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, and -C(O)NH-C1-C6 haloalkyl, and C3-C6 cycloalkyl; or X is selected from the group consisting of: [ka] During the ceremony, R 10 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C2-C7 alkylcarbonyl, C2-C5 alkoxycarbonyl, C2-C6 alkenyl, and C2-C6 alkynyl; W is (i) hydrogen, (ii) C1-C6 alkyl, which may be substituted with 1 to 3 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, C3-C6 cycloalkyl, acetylenyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, which may be substituted with halogen, hydroxyl, cyano, and -C(O)NH-C3-C6 cycloalkyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of C1 to C4 alkyl which is optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C1 to C4 alkoxy, C3 to C6 cycloalkyl, and -NH2; -C(O)NH-C1 to C6 alkyl which is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C1 to C4 alkoxy, C3 to C6 cycloalkyl, and -NH2; -C(O)NH-C1-C6 alkyl which may be substituted by a substituent, -C(O)NH-C1-C6 cyanoalkyl which may be substituted by 1-3 halogens, -C(O)NH-C1-C6 haloalkyl, -C(O)-4-7 membered heterocycloalkyl which is bonded to a nitrogen atom and optionally has 1 or 2 other heteroatoms selected from the group consisting of O, S and N, wherein the carbon of the 4-7 membered heterocycloalkyl is selected from halogen, cyano, nitro, hydroxyl, oxo, - NH2, C1-C7 aminocarbonyl, C1-C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl;and C3-C6 cycloalkyl, wherein the other N in the 4- to 7-membered heterocycloalkyl is, if permitted by valence, hydrogen, -NH2, C1-C7 aminocarbonyl, -SO2C1-C4 alkyl, -SO2C1-C4 haloalkyl, and C1-C4 alkyl, which are halogen, cyano, hydroxyl, acetylenyl, C1-C4 alkoxy, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1 -C(O)-4-7 membered heterocycloalkyl, -C(O)-5-10 membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, and wherein the carbon of the 5-10 membered heteroaryl is selected from halogen, cyano, nitro, hydroxyl, C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl and -C(O)NH-C1-C6 haloalkyl. C1-C4 alkyl, C3-C6 cycloalkyl, C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl and -C(O)NH-C1-C6 haloalkyl; and optionally substituted by one, two or three substituents independently selected from the group consisting of 1-C4 haloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2 and -C(O)NH-C3-C6 cycloalkyl, wherein any N in the heteroaryl is, if permitted by the valence, hydrogen, C1-C4 alkyl which is halogen, cyano, hydroxyl, acetylenyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl,a 5-10 membered heteroaryl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl and -C(O)NH-C1-C6 alkyl, and a C1-C4 alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of C3-C6 cycloalkyl, wherein any S in the heteroaryl group is optionally substituted by 1 or 2 oxygen atoms; cycloalkyl which may be substituted with 1 to 3 groups selected from the group consisting of halogen, C1 to C4 alkyl, cyano, and hydroxyl; C3 to C6 cycloalkyl which may be substituted with 1 to 3 groups selected from the group consisting of halogen, cyano, hydroxyl, oxo, C1 to C4 alkoxy, C1 to C4 alkyl which may be substituted with 1 to 3 groups selected from the group consisting of halogen and cyano; C1 to C4 haloalkyl, -NH2, C1 to C7 aminocarbonyl, -NH(C1 to C4 alkyl), -N(C1 to C4 alkyl)2, -SC C3-C6 cycloalkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of 1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -C(O)NH-C1-C6 haloalkyl, C2-C6 alkenyl and C2-C6 alkynyl, and 4-7 membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S, B and N, wherein the heterocycloalkyl may be benzo-fused; The carbon of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused is halogen, cyano, nitro, hydroxyl, oxo, and C1-C4 alkyl, and examples thereof include halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, C3-C6 cycloalkyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl,and -C(O)NH-C1-C6 alkyl and -C(O)NH-C1-C6 haloalkyl, wherein any B in the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused is substituted with hydroxyl if permitted by the valence, and any N in the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused is substituted with hydrogen, -NH2, C1-C7 aminocarbonyl, -SO2C1- C1-C4 alkyl, -SO2C1-C4 haloalkyl, -C(O)-NH2, C1-C4 alkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, acetylenyl, C1-C4 alkoxy, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl and -C(O)NH-C1-C6 haloalkyl, C1-C4 alkyl, C3-C6 cycloalkyl, 5- to 6-membered heteroaryl, and phenyl which may be substituted with halogen, C1-C4 alkyl, cyano, and hydroxyl, wherein any S in the 4- to 7-membered heterocycloalkyl or the optionally benzo-fused 4- to 7-membered heterocycloalkyl is optionally substituted with 1 or 2 oxygen atoms; (iii) C3-C6 cycloalkyl which may be substituted by 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, oxo, carboxyl, C1-C4 alkoxy, C1-C4 alkyl which may be substituted by 1 to 3 groups selected from the group consisting of halogen and cyano, C1-C4 haloalkyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -C(O)NH-C1-C6 haloalkyl, C2-C6 alkenyl which may be substituted by 1 to 3 halogens, and C2-C6 alkynyl; (iv) a 6-membered aryl or a 5-10-membered heteroaryl having 1, 2 or 3 heteroatoms selected from the group consisting of O, S and N, wherein the carbon of the 6-membered aryl and the 5-10-membered heteroaryl is optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, C1-C4 alkyl, halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl and -C(O)NH-C1-C6 alkyl; a 6-membered aryl or a 5-10-membered heteroaryl, which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of -C(O)NH-C3-C6 cycloalkyl, (C1-C4 alkyl)2, and -C(O)NH-C3-C6 cycloalkyl, where any N of the heteroaryl is optionally substituted, if permitted by valence, by a substituent selected from the group consisting of hydrogen and C1-C4 alkyl which is optionally substituted by 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl; (v) A 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S, and N, wherein the heterocycloalkyl may be benzo-fused, and the carbon of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused is halogen, cyano, nitro, hydroxyl, oxo, C1-C4 alkoxy, C1-C4 alkyl, and the halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, C3-C6 cycloalkyl, -NH2, C1-C7 amino. and optionally substituted by 1 to 4 substituents independently selected from the group consisting of C1 to C4 alkyl optionally substituted by 1 to 5 substituents independently selected from the group consisting of -C(O)NH-C3 to C6 cycloalkyl, -C(O)NH-C1 to C6 alkyl and -C(O)NH-C1 to C6 haloalkyl, and 4 to 7 membered heterocycloalkyl or benzo-fused. Any N in the 4- to 7-membered heterocycloalkyl may be, if valence permits, hydrogen, -NH2, C1-C7 aminocarbonyl, -SO2C1-C4 alkyl, -SO2C1-C4 haloalkyl, -C(O)-NH2, C1-C4 alkyl which is halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, C3-C6 cycloalkyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -SON(C1- and phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C1 to C4 alkyl, cyano, and hydroxyl;4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl optionally benzofused with 4- to 7-membered heterocycloalkyl, in which any S is optionally substituted with 1 or 2 oxygen atoms, and (vi)-NR 11 R 12 is selected from the group consisting of During the ceremony, R 11 is selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C1-C7 alkylcarbonyl, C1-C7 aminocarbonyl, and C2-C5 alkoxycarbonyl; R 12is hydrogen, C1-C6 alkyl which may be substituted by 1 to 5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl and -SO2C1-C4 alkyl, and is C1-C6 alkyl, C3-C6 cycloalkyl, -C(O)-C1-C6 alkyl which may be substituted by 1 to 5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl and -SO2C1-C4 alkyl, and is -C(O)-C1-C6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of oxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl and -SO2C1-C4 alkyl, a 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, the heterocycloalkyl optionally being benzo-fused, and a compound represented by the formula Among these, the carbon of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused is halogen, cyano, nitro, hydroxyl, oxo, or C1-C4 alkyl, and the halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 a and -C(O)NH-C1-C6 haloalkyl, and any N in the 4-7 membered heterocycloalkyl or the 4-7 membered heterocycloalkyl which may be benzo-fused is, if permitted by the valence, hydrogen, C1-C4 alkyl which is halogen, cyano, hydroxyl, acetylenyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl,C1-C4 alkyl, C3-C6 cycloalkyl, 5-6 membered heteroaryl, and phenyl, which may be substituted with 1 to 5 substituents independently selected from the group consisting of -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, and which are substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4 alkyl, cyano, and hydroxyl. phenyl, optionally substituted with a substituent selected from the group consisting of 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl optionally fused with benzo, in which any S may be substituted with 1 or 2 oxygen atoms, and 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, in which the carbon of the 5- to 10-membered heteroaryl is selected from halogen, cyano, nitro, hydroxyl, C1-C4 alkyl, optionally substituted with halogen, cyano, hydroxyl, oxy, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, which may be substituted by 1 to 5 substituents independently selected from the group consisting of SO, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl. and optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -C(O)NH-C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, wherein any N of the heteroaryl is, if permitted by the valence, hydrogen, C1-C4 alkyl which is halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl,-SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, C1-C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of C3-C6 cycloalkyl, and 5-10 membered heteroaryl optionally substituted with a substituent selected from the group consisting of C3-C6 cycloalkyl; or R 10and W together with the nitrogen to which they are attached form a 4-7 membered ring which may contain 1-2 heteroatoms selected from the group consisting of N, S and O, wherein the carbons of the ring are cyano, hydroxyl, oxo, halogen, C1-C2 alkoxy, N,N-di-C1-C4-alkylaminocarboxyl, N-C1-C4-alkylaminocarboxyl, C1-C7 aminocarboxyl, C1-C4 alkyl which is halogen, cyano, hydroxyl, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl), C1-C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of -C(O)NH-C3-C6 cycloalkyl, C3-C6 cycloalkyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, cyano, hydroxyl and C1-C4 alkoxy, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -C(O)NH-C1-C6 haloalkyl, 5- to 6-membered heteroaryl, and phenyl optionally substituted with halogen, C1-C4 alkyl, cyano, hydroxyl, C1-C2 alkoxy, N,phenyl optionally substituted by 1 to 3 substituents independently selected from the group consisting of N-di-C1-C4-alkylaminocarboxyl, N—C1-C4-alkylaminocarboxyl, and C1-C7 aminocarboxyl; and wherein any N in the 4- to 7-membered ring is hydrogen, C1-C4 alkyl and substituted by 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, and -C(O)NH-C3-C6 cycloalkyl. and C1-C4 alkyl, C3-C6 cycloalkyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C1-C4 alkoxy, -C(O)NH-C3-C6 cycloalkyl and -C(O)NH-C1-C6 alkyl, 5- to 6-membered heteroaryl, and phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C1-C4 alkyl, cyano and hydroxyl, any S in the 4- to 7-membered ring may be substituted with 1 or 2 oxygen atoms, and Y is C1-C6 alkyl and is not limited to halogen, cyano, hydroxyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, acetylenyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -SON2NH(C1-C4 alkyl), -SON(C1-C4 alkyl)2, -SON2NH(C1-C4 haloalkyl), -C(O)NH-C3-C6 cycloalkyl and is not limited to halogen, hydantoyl, -NH, -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -SON2NH(C1-C4 alkyl), -SON2N(C1-C4 alkyl)2, -SON2NH(C1-C4 haloalkyl), -C(O)NH-C3-C6 cycloalkyl. -C(O)NH-C3-C6 cycloalkyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxyl, cyano, and C1 to C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C1 to C4 alkoxy, and -NH2, -C(O)NH-C1 to C6 alkyl, -C(O)NH-C1 to C6 cyanoalkyl optionally substituted with 1 to 3 halogens, -C(O)NH-C1 to C6 haloalkyl, phenyl and halogen , cyano, nitro, hydroxyl, C1-C4 alkyl which may be substituted by 1 to 3 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2 and -C(O)NH-C3-C6 cycloalkyl, and C3-C6 cycloalkyl which is halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 amino carbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, C3-C6 cycloalkyl optionally substituted by 1 to 5 substituents independently selected from the group consisting of C2-C6 alkenyl and C2-C6 alkynyl, phenyl optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of 5-10 membered heteroaryl which is O,and one or two heteroatoms selected from the group consisting of S and N, wherein the carbon of the 5-10 membered heteroaryl is halogen, cyano, nitro, hydroxyl, C1-C4 alkyl, selected from the group consisting of halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl. and optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -C(O)NH-C3-C6 cycloalkyl and -C(O)NH-C1-C6 alkyl, each of which is optionally substituted by 1 to 5 independently selected substituents, wherein any N in the heteroaryl is hydrogen, C1-C4 alkyl and is not halogen, sialic acid, if permitted by the valence. and C1-C4 alkyl optionally substituted by 1 to 5 substituents independently selected from the group consisting of no, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, and substituted by a substituent selected from the group consisting of C3-C6 cycloalkyl. 10-membered heteroaryl, and 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, wherein the heterocycloalkyl may be benzo-fused, and the carbon of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused is halogen, cyano, nitro, hydroxyl, oxo, or C1-C4 alkyl, and the halogen, cyano, hydroxyl, acetylenyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl),and C1-C4 alkyl and C3-C6 cycloalkyl which may be substituted by 1 to 5 substituents independently selected from the group consisting of -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, and any N in the 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl is, if permitted by the valence, hydrogen, C1-C4 alkyl which is halogen, cyano, hydroxyl, acetylenyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl ), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, and any S in the 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl which may be benzofused may be substituted with 1 or 2 oxygen atoms; A compound of formula (I), or a salt thereof, is provided:

[0007] In one embodiment, Z is CR2.

[0008] In another embodiment, Z is N.

[0009] In one embodiment, the present invention also provides a composition comprising a compound of formula (I) or a salt thereof, and at least one acceptable excipient, optionally further comprising at least one additional active compound.

[0010] In one embodiment, the present invention also provides a method for treating a pest, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (I) or a salt thereof, the method optionally further comprising an effective amount of at least one additional active compound.

[0011] In one embodiment, the present invention also provides a method for controlling pests, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (I) or a salt thereof, the method optionally further comprising an effective amount of at least one additional active compound.

[0012] In one embodiment, the present invention also provides a method for treating or controlling a pest, the method comprising contacting an environment of a subject with an effective amount of a compound of formula (I) or a salt thereof, the method optionally further comprising an effective amount of at least one additional active compound.

[0013] Thus, the present invention provides the use of a compound of the present invention as a medicament, including the manufacture of a medicament. In one embodiment, the present invention provides the manufacture of a medicament comprising a compound of formula (I) or a salt thereof for the treatment of parasites. In one embodiment, the present invention provides the manufacture of a medicament comprising a compound of formula (I) or a salt thereof for the control of pests, preferably fleas or ticks. In another embodiment, the present invention provides the use of a compound of formula (I) or a salt thereof in the manufacture of a medicament for the treatment or control of pests, preferably fleas or ticks.

[0014] The present invention also provides processes for making the compounds of the present invention and intermediates thereof. [Brief description of the drawings]

[0015] [Figure 1] FIG. 1 shows an alternative synthetic scheme for preparing the compounds of Examples 1.1 and 1.2 described herein. [Diagram 2] FIG. 2 shows an alternative synthetic scheme for preparing the compounds of Examples 3.1 and 3.2 described herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] The term "C1-C2 alkyl" refers to an alkyl chain having one to two carbon atoms, and includes methyl and ethyl.

[0017] The term "C1-C4 alkyl" refers to a straight or branched alkyl chain having one to four carbon atoms, and includes methyl, ethyl, propyl, isopropyl, butyl, and the like.

[0018] Similarly, the term "C1-C6 alkyl" refers to a straight or branched alkyl chain having one to six carbon atoms, and includes methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, and the like.

[0019] The terms "C1-C4 haloalkyl" and "C1-C4 halogenoalkyl" refer to straight or branched alkyl chains having one to four carbon atoms and one to five halogens, including fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 1,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, and the like.

[0020] The terms "C1-C6 haloalkyl" and "C1-C6 halogenoalkyl" refer to straight or branched alkyl chains having one to six carbon atoms and one to five halogens, including fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 1,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, and the like.

[0021] The term "C2-C6 alkenyl" refers to a straight or branched alkenyl chain having from two to four carbon atoms and one carbon-carbon double bond, including ethylene, propylene, iso-propylene, butylene, iso-butylene, sec-butylene, and the like.

[0022] The term "C2-C6 alkynyl" refers to a straight or branched alkynyl chain having from two to four carbon atoms and one carbon-carbon triple bond, and includes acetylene, propargyl, and the like.

[0023] The term "C1-C2 alkoxy" refers to a C1-C2 alkyl bonded through an oxygen atom, and includes methoxy and ethoxy.

[0024] The term "C1-C4 alkoxy" refers to a C1-C4 alkyl bonded through an oxygen atom, and includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, and the like.

[0025] The term "C1-C6 alkoxy" refers to a C1-C6 alkyl bonded through an oxygen atom, and includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, and the like.

[0026] The term "C3-C6 cycloalkyl" refers to alkyl rings of three to six carbon atoms, including cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. It is understood that the cycloalkyl rings can be fused, bridged, or spiro-fused.

[0027] The term "C4-C7 alkyl cycloalkyl" refers to a C1-C4 alkyl substituted with a C3-C6 cycloalkyl having a total of four to seven carbons, including cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, and the like.

[0028] The terms "halo", "halogen" and "halo" refer to a chloro, fluoro, bromo, or iodo atom.

[0029] The terms "4-7 membered heterocycloalkyl having one or two heteroatoms selected from the group O, S, N, which may be benzofused" and "4-7 membered heterocycloalkyl having one or two heteroatoms selected from the group O, S, B, N, which may be benzofused" refer to a 4-7 membered saturated or partially (but not completely) unsaturated ring having one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, or having one or two heteroatoms selected from the group consisting of nitrogen, oxygen, boron, and sulfur, and the ring optionally contains a carbonyl to form a lactam or lactone. It is understood that when sulfur is included, the sulfur can be either -S-, -SO-, or -SO2-. Heterocyclic rings may be monocyclic or bicyclic, and any bicyclic ring may be fused, bridged, or spiro-fused. This definition of 4-7 members excludes rings that may be benzo-fused. Also, as will be fully understood by those skilled in the art, the term saturated or partially (but not completely) unsaturated 4-7 membered heterocycloalkyl rings applies to heterocycloalkyl rings and not to any benzo-fused rings that, by their nature, would be fully unsaturated. It is further understood that the group may be attached as a substituent by either a heteroatom on the ring, a carbon atom of the heterocycloalkyl if the valence permits, or a carbon atom of the optionally benzo-fused ring. It is also understood that when an optionally benzo-fused 4-7 membered heterocycloalkyl is optionally substituted on carbon, the substituent may be on a carbon atom of the heterocycle and / or the benzo-fused ring.For example, but without limitation, this term includes azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, oxetanyl, thioxetanyl, dioxolanyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrofuryl, hexahydropyrimidinyl, tetrahydropyrimidinyl, 2,6-diazaspiro[3.3]heptanyl, isoxazolidine, dihydroimidazolyl, indolyl, isoindolyl, and the like.

[0030] The term "5- or 6-membered heteroaryl" refers to a 6-membered monocyclic fully unsaturated ring having one to five carbon atoms and one or more, typically one to four, heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur. For example, but not limited to, this term includes pyrrolyl, furyl, thienyl, imidazolyl, oxazoyl, isoxazoyl, thiazolyl, triazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidyl, etc. It will be appreciated that the 6-membered heteroaryl can be attached as a substituent via a ring carbon or ring nitrogen atom where such a binding mode is valid.

[0031] R 10 and W taken together with the nitrogen to which they are attached, the term "4- to 7-membered ring optionally containing 1-2 heteroatoms selected from the group consisting of N, S and O" is understood to mean R 10 and W refers to a fully saturated or partially unsaturated (but not completely) ring having 4-7 members, including the nitrogen to which it is attached, including azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, oxetanyl, dioxolanyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrofuryl, hexahydropyrimidinyl, tetrahydropyrimidinyl, dihydroimidazolyl, and the like.

[0032] The term "5-10 membered heteroaryl having one or two heteroatoms selected from the group O, S, and N" refers to a 5-10 membered, monocyclic or polycyclic, fully unsaturated ring or ring system having one to nine carbon atoms and one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. For example, and without limitation, this term includes furyl, thienyl, pyrrolyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, thiazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidyl, azepinyl, diazepinyl, benzofuryl, benzothienyl, indolyl, isoindolyl, benzimidazolyl, benzisothiazolyl, benzisoxazolyl, benzoxazolyl, benzopyrazinyl, benzopyrazolyl, quinazolyl, thienopyridyl, quinolyl, isoquinolyl benzothiazolyl, and the like. Of course, a 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S, and N may be bonded as a substituent via a ring carbon or ring nitrogen atom where such a bonding mode is effective.

[0033] The term "oxo" refers to an oxygen atom that is double bonded to the carbon to which it is attached to form the carbonyl of an amide, ketone, or aldehyde. For example, the pryidone radical is considered to be an oxo-substituted 6-membered heteroaryl.

[0034] The term "carboxyl" refers to the following group: [ka]

[0035] The term "N,N-di-C1-C4-alkylaminocarboxyl" refers to the group immediately below, [ka] In the formula, the hydrogen on the nitrogen refers to a group that is substituted with two independently selected C1-C4 alkyl groups.

[0036] Similarly, the term "N-C1-C4-alkylaminocarboxyl" refers to the group immediately below: [ka] In the formula, one of the hydrogens on the nitrogen is substituted with a C1-C4 alkyl group.

[0037] The term "C2-C5 alkoxycarbonyl" refers to the following group: TIFF2024523269000008.tif19159In the formula, R refers to a group that is a C1 to C4 alkyl.

[0038] The term "C2-C7 alkylcarbonyl" refers to the group [ka] In the formula, R refers to a group that is a C1 to C6 alkyl.

[0039] Similarly, the term "C2-C7 haloalkylcarbonyl" refers to the group immediately above, where R is a C1-C6 haloalkyl.

[0040] The term "C1-C7 aminocarbonyl" refers to the group [ka] In the formula, R refers to a group that is hydrogen or C1-C4 alkyl.

[0041] The term "nil" as used herein with reference to groups, substituents, moieties, etc., indicates that the group, substituent, or moiety is absent, where a group, substituent, or moiety is originally bound to two or more other groups, substituents, or moieties, and the other groups are bound together in place of the groups, substituents, or moieties that are nil. For example, in a compound having the structure ABC, if B is nil, then the compound is AC because A is directly bound to C. As another example, in a compound having the structure ABC, if C is nil, then the compound is AB.

[0042] The terms "salt" and "salts" refer to veterinarily or pharma- ceutically acceptable salts of organic or inorganic acids and bases. Such salts are well known in the art and include those salts described in Journal of Science, 66, 2-19 (1977). One example is the hydrochloride salt.

[0043] The term "substituted", including the use of "optionally substituted" and "optionally substituted", refers to one or more hydrogen radicals of a group that are replaced with non-hydrogen radicals (substituents). It is understood that the substituents may be the same or different at each substituted position. The combinations of groups and substituents envisioned by the present invention are those that are stable or chemically feasible. With respect to the compounds described herein, the groups and substituents may be selected according to the allowed valences of the atoms and substituents, such that the selection and substitution result in a stable compound that does not spontaneously undergo transformation, for example, by rearrangement, cyclization, elimination, and the like.

[0044] The term "stable" refers to compounds that do not change substantially when subjected to conditions to enable their formation. In a non-limiting example, a stable compound or chemically viable compound is one that does not change substantially when kept at a temperature of 40° C. or less for about a week in the absence of moisture or other chemically reactive conditions.

[0045] When a term defined herein refers to a number of carbon atoms, it is understood that the number referred to refers to the group to which it is referred and does not include any carbons that may be present in optional substituents on that group or that may be present as part of a fused ring, including a benzo-fused ring.

[0046] Those of ordinary skill in the art will recognize that certain compounds of the present invention exist as isomers. All stereoisomers of the compounds of the present invention, including geometric isomers, enantiomers, and diastereomers, in all ratios, are contemplated as being within the scope of the present invention.

[0047] As used herein, the term "(RS)" in a chemical name refers to a racemic mixture at the indicated stereocenter.

[0048] As used herein, the terms "(R or S)" or "(S or R)" in a chemical name refer to one of the two possible configurations at the indicated stereocenter.

[0049] One of ordinary skill in the art will recognize that certain compounds of the invention exist as tautomers, and all tautomers of the compounds of the invention are contemplated as being within the scope of the invention.

[0050] The compounds of the present invention also include all isotopic variations in which at least one atom having the primary atomic mass is replaced by an atom having the same atomic number but an atomic mass different from the primary atomic mass. 2 The use of H) may result in greater metabolic stability. Additionally, certain isotopes of the compounds of the present invention may contain radioactive isotopes (e.g., tritium, 3 H, or 14 C), which may be useful in drug and / or substrate tissue distribution studies. 11 C. 18 F, 15 O, and 13Substitution with positron emitting isotopes, such as N, can be useful in Positron Emission Tomography (PET) studies.

[0051] The terms "this compound of the invention" and "a compound of the invention", as well as "a compound of the invention", include the embodiments of Formula (I), as well as the other more specific embodiments encompassed by Formula (I) described herein, as well as the exemplary compounds described herein, and salts of each of these embodiments.

[0052] In one embodiment of the compound of formula (I), R1 may be hydrogen only if R2 is trifluoromethyl, difluoromethyl, fluoro, chloro, or bromo; R3 may be hydrogen only if either R2 or R4 is trifluoromethyl, difluoromethyl, fluoro, chloro, or bromo; and At most three of R1, R2, R3, and R4 are hydrogen.

[0053] In one embodiment of the compound of formula (I) where Z is CR2, R1 may be hydrogen only if R2 is trifluoromethyl, difluoromethyl, fluoro, chloro, or bromo; R3 may be hydrogen only if either R2 or R4 is trifluoromethyl, difluoromethyl, fluoro, chloro, or bromo; and At most three of R1, R2, R3, and R4 are hydrogen.

[0054] In one embodiment of the compound of formula (I), R1 may be hydrogen only if R2 is trifluoromethyl, difluoromethyl, or bromo; R3 may be hydrogen only if either R2 or R4 is trifluoromethyl, difluoromethyl, or bromo; and At most three of R1, R2, R3, and R4 are hydrogen.

[0055] In one embodiment of the compound of formula (I) where Z is CR2, R1 may be hydrogen only if R2 is trifluoromethyl, difluoromethyl, or bromo; R3 may be hydrogen only if either R2 or R4 is trifluoromethyl, difluoromethyl, or bromo; and At most three of R1, R2, R3, and R4 are hydrogen.

[0056] Compounds of formula (I) in various embodiments are as follows:

[0057] Formula (I): [ka] TIFF2024523269000012.tif52154TIFF2024523269000013.tif158157TIFF2024523269000014.tif54163TIFF2024523269000015.tif59160

[0058] A4, A5, A6, A7, A9, A 10 , A 11 , A 12 , A 14 , and / or A 15 With respect to, it is understood that the substituent R5, when present, replaces the hydrogen of CH.

[0059] With respect to compounds of formula (Ig), it is further understood that the X group, if present, is attached by replacing the hydrogen of a -CH2- group or a -CH- group, or R of a -NR- group, at W3, W4, W5, or W6.

[0060] Further embodiments of the compounds of the invention are provided below: (1) One embodiment relates to a compound of formula (I) or a salt thereof:

[0061] (1.1) One embodiment relates to a compound of formula (I) or a salt thereof, wherein Z is CR2.

[0062] (1.2) One embodiment relates to a compound of formula (I) or a salt thereof, wherein Z is N.

[0063] (a) One embodiment relates to a compound of formula (Ia) or a salt thereof:

[0064] (a1) One embodiment relates to a compound of formula (Ia) or a salt thereof, wherein Z is CR2.

[0065] (a2) One embodiment relates to a compound of formula (Ia) wherein Z is N, or a salt thereof.

[0066] (b) One embodiment relates to a compound of formula (Ib) or a salt thereof:

[0067] (b1) One embodiment relates to a compound of formula (Ib) or a salt thereof, wherein Z is CR2.

[0068] (b2) One embodiment relates to a compound of formula (Ib) wherein Z is N, or a salt thereof.

[0069] (c) One embodiment relates to a compound of formula (Ic) or a salt thereof:

[0070] (c1) One embodiment relates to a compound of formula (Ic), wherein Z is CR2, or a salt thereof.

[0071] (c2) One embodiment relates to a compound of formula (Ic), wherein Z is N, or a salt thereof.

[0072] (d) One embodiment relates to a compound of formula (Id) or a salt thereof:

[0073] (d1) One embodiment relates to a compound of formula (Id), wherein Z is CR2, or a salt thereof.

[0074] (d2) One embodiment relates to a compound of formula (Id), wherein Z is N, or a salt thereof.

[0075] (e) One embodiment relates to a compound of formula (Ie) or a salt thereof:

[0076] (e1) One embodiment relates to a compound of formula (Ie) or a salt thereof, wherein Z is CR2.

[0077] (e2) One embodiment relates to a compound of formula (Ie) wherein Z is N, or a salt thereof.

[0078] (f) One embodiment relates to a compound of formula (If) or a salt thereof:

[0079] (f1) One embodiment relates to a compound of formula (If), wherein Z is CR2, or a salt thereof.

[0080] (f2) One embodiment relates to a compound of formula (If), wherein Z is N, or a salt thereof.

[0081] (g) One embodiment relates to a compound of formula (Ig) or a salt thereof:

[0082] (g1) One embodiment relates to a compound of formula (Ig) or a salt thereof, wherein Z is CR2.

[0083] (g2) One embodiment relates to a compound of formula (Ig), wherein Z is N, or a salt thereof.

[0084] (h) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is trifluoromethyl, R3 is hydrogen, and R4 is trifluoromethyl.

[0085] (i) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is trifluoromethyl, R3 is hydrogen, and R4 is bromo.

[0086] (j) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is trifluoromethyl, R3 is hydrogen, and R4 is fluoro.

[0087] (k) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is trifluoromethyl, R3 is hydrogen, and R4 is chloro.

[0088] (l) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is trifluoromethyl, R3 is hydrogen, and R4 is difluoromethyl.

[0089] (m) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is trifluoromethyl, R3 is hydrogen, and R4 is methoxy.

[0090] (n) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is chloro, R3 is hydrogen, and R4 is trifluoromethyl.

[0091] (o) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is chloro, R3 is hydrogen, and R4 is bromo.

[0092] (p) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is chloro, R3 is hydrogen, and R4 is fluoro.

[0093] (q) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is chloro, R3 is hydrogen, and R4 is chloro.

[0094] (r) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is chloro, R3 is hydrogen, and R4 is difluoromethyl.

[0095] (s) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is chloro, R3 is hydrogen, and R4 is methoxy.

[0096] (t) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is bromo, R3 is hydrogen, and R4 is trifluoromethyl.

[0097] (u) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is bromo, R3 is hydrogen, and R4 is bromo.

[0098] (v) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is bromo, R3 is hydrogen, and R4 is fluoro.

[0099] (w) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is bromo, R3 is hydrogen, and R4 is chloro.

[0100] (x) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is chloro, R3 is hydrogen, and R4 is difluoromethyl.

[0101] (y) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is chloro, R3 is hydrogen, and R4 is methoxy.

[0102] (z) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is fluoro, R3 is hydrogen, and R4 is trifluoromethyl.

[0103] (aa) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is fluoro, R3 is hydrogen, and R4 is bromo.

[0104] (ab) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is fluoro, R3 is hydrogen, and R4 is fluoro.

[0105] (ac) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is fluoro, R3 is hydrogen, and R4 is chloro.

[0106] (ad) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is fluoro, R3 is hydrogen, and R4 is difluoromethyl.

[0107] (ae) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is fluoro, R3 is hydrogen, and R4 is methoxy.

[0108] (af) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), and (g2), or a salt thereof, wherein R1 is hydrogen, R2 is trifluoromethoxy, R3 is hydrogen, and R4 is difluoromethyl.

[0109] (ag) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), (g2), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (y), (z), (aa), (ab), (ac), (ad), (ae), and (af), or a salt thereof, wherein A2 is O.

[0110] (ah) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), (g2), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (y), (z), (aa), (ab), (ac), (ad), (ae), (af), and (ag), or a salt thereof, wherein A1 is CF3.

[0111] (ai) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (b), (b1), (b2), (c), (c1), (c2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (g), (g1), (g2), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (y), (z), (aa), (ab), (ac), (ad), (ae), (af), and (ag), or a salt thereof, wherein A1 is CHF2.

[0112] (aj) One embodiment relates to embodiments (1), (1.1), (1.2), (a), (a1), (a2), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (y), (z), (aa), (ab), (ac), (ad), (ae), (af), (ag), (ah), and (ai) wherein A3 is S, or a salt thereof.

[0113] (ak) One embodiment relates to embodiments (1), (1.1), (1.2), (b), (b1), (b2), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (y), (z), (aa), (ab), (ac), (ad), (ae), (af), (ag), (ah), and (ai) or a salt thereof, wherein A4, A5 and A6 are CH.

[0114] (al) One embodiment relates to embodiment (ak), or a salt thereof, wherein p is 1 and R5 is C1-C6 alkyl.

[0115] (am) One embodiment relates to the embodiment (al), or a salt thereof, wherein R5 is methyl.

[0116] (an) In one embodiment, A7, A8, A9, A 10 , A 11and A 12 is CH; or a salt thereof.

[0117] (ao) In one embodiment, 13 , A 14 and A 15 is CH; or a salt thereof.

[0118] (ap) One embodiment relates to the embodiment (ao), or a salt thereof, in which W1 is -CH2- and W2 is O.

[0119] (aq) In one embodiment, X is [ka] where R 10 is hydrogen, or a salt thereof.

[0120] (ar) One embodiment is embodiment (aq), wherein W is C1-C6 alkyl; halogen, Cyano, Hydroxyl, Oxo, C1-C4 alkoxy, C3-C6 cycloalkyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen and cyano; Acetylenyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl halogen, Hydroxyl, Cyano and C1-C4 alkyl halogen, Cyano, Hydroxyl, C1-C4 alkoxy, C3-C6 cycloalkyl, and -C(O)NH-C3-C6 cycloalkyl optionally substituted by 1 to 3 substituents independently selected from the group consisting of: -C1 to C4 alkyl optionally substituted by 1 to 5 substituents independently selected from the group consisting of: -NH2; -C(O)NH-C1-C6 alkyl, halogen, Cyano, Hydroxyl, C1-C4 alkoxy, C3-C6 cycloalkyl, and -NH2, -C(O)NH-C1-C6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of; -C(O)NH-C1-C6 cyanoalkyl optionally substituted with 1 to 3 halogens; -C(O)NH-C1-C6 haloalkyl, -C(O)-4-7 membered heterocycloalkyl having a nitrogen atom attached thereto and optionally one or two other heteroatoms selected from the group O, S, N, wherein the carbon of the 4-7 membered heterocycloalkyl is halogen, Cyano, Nitro, Hydroxyl, Oxo, -NH2, C1-C7 aminocarbonyl, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, Oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, and C3-C6 cycloalkyl, In addition, if the valence allows, the other N of the 4- to 7-membered heterocycloalkyl is hydrogen, -NH2, C1-C7 aminocarbonyl, -SO2C1-C4 alkyl, -SO2C1-C4 haloalkyl, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, C1-C4 alkoxy, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -C(O)-4 to 7 membered heterocycloalkyl, -C(O)-C1 to C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of -C(O)NH-C1 to C6 haloalkyl, A 5-10 membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, wherein the carbon of the 5-10 membered heteroaryl is halogen, Cyano, Nitro, Hydroxyl, C1-C4 alkyl halogen, Cyano, Hydroxyl, Oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, and -C(O)NH-C1-C6 haloalkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, and -C(O)NH-C3-C6 cycloalkyl, Any N in the heteroaryl may be, if the valence permits, hydrogen, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, Oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl, and C3-C6 cycloalkyl, and a 5- to 10-membered heteroaryl, any S in the heteroaryl being substituted with 1 or 2 oxygen atoms. Phenyl halogen, C1-C4 alkyl, Cyano, or phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxyl; C3-C6 cycloalkyl halogen, Cyano, Hydroxyl, Oxo, C1-C4 alkoxy, C1-C4 alkyl optionally substituted with 1 to 3 groups selected from the group consisting of halogen and cyano; C1-C4 haloalkyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -C(O)NH-C1-C6 haloalkyl, C2-C6 alkenyl, and C3-C6 cycloalkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of C2-C6 alkynyl, and A 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S, B, and N, wherein the heterocycloalkyl is optionally benzo-fused, and the carbon of the 4- to 7-membered heterocycloalkyl or the optionally benzo-fused 4- to 7-membered heterocycloalkyl is halogen, Cyano, Nitro, Hydroxyl, Oxo, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, Oxo, C1-C4 alkoxy, C3-C6 cycloalkyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, and -C(O)NH-C1-C6 haloalkyl; Any B in the 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl is substituted with hydroxyl if the valence permits; In addition, any N in the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused can be, if the valence allows, hydrogen, -NH2, C1-C7 aminocarbonyl, -SO2C1-C4 alkyl, -SO2C1~C4 haloalkyl, -C(O)-NH2, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, C1-C4 alkoxy, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 haloalkyl, C3-C6 cycloalkyl, 5-6 membered heteroaryl, and Phenyl halogen, C1-C4 alkyl, Cyano and phenyl, optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxyl; Any S in the 4- to 7-membered heterocycloalkyl or the optionally benzo-fused 4- to 7-membered heterocycloalkyl is substituted with 1 or 2 oxygen atoms; and C1-C6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of 4- to 7-membered heterocycloalkyl. The embodiment (aq), or a salt thereof.

[0121] (as) One embodiment is embodiment (ar), wherein W is C1-C6 alkyl; -C(O)NH-C1-C6 alkyl, halogen, Cyano, Hydroxyl, C1-C4 alkoxy, C3-C6 cycloalkyl, and -NH2, -C(O)NH-C1-C6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of; -C(O)NH-C1-C6 cyanoalkyl optionally substituted with 1 to 3 halogens; -C(O)NH-C1-C6 haloalkyl, and -C(O)-4-7 membered heterocycloalkyl having a nitrogen atom attached thereto and optionally one or two other heteroatoms selected from the group O, S, N, wherein the carbon of the 4-7 membered heterocycloalkyl is halogen, Cyano, Nitro, Hydroxyl, Oxo, -NH2, C1-C7 aminocarbonyl, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, Oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and C1-C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of -C(O)NH-C1-C6 alkyl, and C3-C6 cycloalkyl, In addition, if the valence allows, the other N of the 4- to 7-membered heterocycloalkyl is hydrogen, -NH2, C1-C7 aminocarbonyl, -SO2C1-C4 alkyl, -SO2C1~C4 haloalkyl, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, C1-C4 alkoxy, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -C(O)NH-C1-C6 haloalkyl; -C1-C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of -C(O)-4 to 7 membered heterocycloalkyl; The embodiment relates to (ar), or a salt thereof.

[0122] (at) One embodiment is embodiment (as), wherein W is [ka] or a salt thereof.

[0123] (au) One embodiment is embodiment (aq), wherein W is C1-C6 alkyl and not halogen. 、 and C1-C6 alkyl substituted with -C(O)NH-C3-C6 cycloalkyl optionally substituted with 1-3 substituents independently selected from the group consisting of: hydroxyl, cyano, and C1-C4 alkyl optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C1-C4 alkoxy, and -NH2, or a salt thereof.

[0124] (av) One embodiment is embodiment (aq), wherein W is C1-C6 alkyl; halogen, Cyano, Hydroxyl, C1-C4 alkoxy, C3-C6 cycloalkyl, and -NH2, C1-C6 alkyl substituted with -C(O)NH-C1-C6 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of; The embodiment (aq), or a salt thereof.

[0125] (av1) One embodiment is embodiment (av), in which W is [ka] or a salt thereof.

[0126] (av2) One embodiment is embodiment (av), wherein W is [ka] or a salt thereof.

[0127] (aw) One embodiment is embodiment (aq) in which W is C1-C6 alkyl substituted with a 5-10 membered heteroaryl having 1 or 2 heteroatoms selected from the group of O, S, B, and N, and the carbon of the 5-10 membered heteroaryl is selected from halogen, cyano, nitro, hydroxyl, C1-C4 alkyl having halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 amino. C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, -NH2, optionally substituted by 1 to 5 substituents independently selected from the group consisting of -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 alkyl; and any B of said heteroaryl is substituted with hydroxyl, and any N of said heteroaryl is substituted with hydrogen, C1-C4 alkyl, halogen, cyano, hydroxyl, acetylenyl, oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, and any S of the heteroaryl is substituted by 1 or 2 oxygen atoms, or a salt thereof.

[0128] (aw1) One embodiment is embodiment (aq) in which W is C1-C6 alkyl with halogen, cyano, nitro, hydroxyl, C1-C4 alkyl with halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH or a salt thereof.

[0129] (aw2) One embodiment is embodiment (aq) in which W is C1-C6 alkyl with halogen, cyano, nitro, hydroxyl, C1-C4 alkyl with halogen, cyano, hydroxyl, oxo, C1-C4 alkoxy, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH- or a salt thereof.

[0130] (ax) One embodiment is embodiment (aq) in which W is a 4-7 membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group O, S, and N, which heterocycloalkyl is optionally benzo-fused, and the carbons of the 4-7 membered heterocycloalkyl or optionally benzo-fused 4-7 membered heterocycloalkyl are halogen, Cyano, Nitro, Hydroxyl, Oxo, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, Oxo, C1-C4 alkoxy, C3-C6 cycloalkyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, and -C(O)NH-C1-C6 haloalkyl, optionally substituted with 1 to 5 substituents independently selected from the group consisting of C1 to C4 alkyl, and In addition, any N in the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused can be, if the valence allows, hydrogen, -NH2, C1-C7 aminocarbonyl, -SO2C1-C4 alkyl, -SO2C1~C4 haloalkyl, -C(O)-NH2, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, C1-C4 alkoxy, C3-C6 cycloalkyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and -C(O)NH-C1-C6 haloalkyl, C3-C6 cycloalkyl, 5-6 membered heteroaryl, and Phenyl halogen, C1-C4 alkyl, Cyano and phenyl, optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxyl; Any S in the 4- to 7-membered heterocycloalkyl or optionally benzofused 4- to 7-membered heterocycloalkyl is substituted with 1 or 2 oxygen atoms. The embodiment (aq), or a salt thereof.

[0131] (ax1) One embodiment is embodiment (ax), wherein W is a 4-7 membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group O, S, N, and is selected from the group consisting of pyrrolyl, azetidinyl, 2-oxoazetidinyl, isoxazolidinyl, 2,6-diazaspiro[3.3]heptanyl, and 1,6-diazaspiro[3.3]heptanyl, and the carbons of the 4-7 membered heterocycloalkyl are halogen, Cyano, Nitro, Hydroxyl, Oxo, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, Oxo, C1-C4 alkoxy, C3-C6 cycloalkyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, and -C(O)NH-C1-C6 haloalkyl; In addition, any N in the 4- to 7-membered heterocycloalkyl4- to 7-membered heterocycloalkyl is, if the valence allows, hydrogen, -SO2C1-C4 alkyl, -SO2C1~C4 haloalkyl, -C(O)-NH2, C1-C4 alkyl halogen, Cyano, Hydroxyl, Acetylenyl, C1-C4 alkoxy, C3-C6 cycloalkyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, and C1-C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of -C(O)NH-C1-C6 haloalkyl, and C3-C6 cycloalkyl;

[0033] The present invention relates to embodiment (ax), or a salt thereof.

[0132] (ay) One embodiment is embodiment (ax) and (ax1), in which the carbons of the 4-7 membered heterocycloalkyl are optionally substituted with 1-2 substituents independently selected from the group consisting of oxo and C1-C4 alkyl; Also relates to embodiments (ax) and (ax1), or a salt thereof, wherein any N in the 4-7 membered heterocycloalkyl is substituted, if valence permits, with hydrogen and C1-C4 alkyl optionally substituted with 1-3 halogen, cyano, acetylenyl, or C3-C6 cycloalkyl.

[0133] (az) One embodiment relates to embodiments (ax), (ax1), and (ay), or a salt thereof, in which a carbon of the 4-7 membered heterocycloalkyl is substituted with one oxo, and any N of the 4-7 membered heterocycloalkyl is substituted, if valence permits, with a C1-C4 alkyl substituted with one cyano.

[0134] (ba) One embodiment relates to embodiments (ax), (ax1), and (ay) in which a carbon of the 4-7 membered heterocycloalkyl is substituted with one oxo and any N of the 4-7 membered heterocycloalkyl is substituted, if valences permit, with a C1-C4 alkyl substituted with 1-3 halogens, or a salt thereof.

[0135] (bb) One embodiment relates to embodiments (ax), (ax1), and (ay), or a salt thereof, in which a carbon of the 4-7 membered heterocycloalkyl is substituted with one oxo, and any N of the 4-7 membered heterocycloalkyl is substituted, if valence permits, with a C1-C4 alkyl substituted with one C3-C6 cycloalkyl.

[0136] (bc) One embodiment relates to embodiments (ax), (ax1), and (ay) in which any N in the 4-7 membered heterocycloalkyl is substituted, if valence allows, with a C1-C4 alkyl substituted with one cyano, or a salt thereof.

[0137] (bd) One embodiment relates to embodiments (ax), (ax1), and (ay) in which any N in the 4-7 membered heterocycloalkyl is substituted, if valence allows, with C1-C4 alkyl substituted with 1-3 halogens, or a salt thereof.

[0138] (be) One embodiment relates to embodiments (ax), (ax1) and (ay) in which any N in the 4-7 membered heterocycloalkyl is substituted, if valence permits, with C1-C4 alkyl substituted with one C3-C6 cycloalkyl, or a salt thereof.

[0139] (be1) One embodiment is embodiment (aq), in which W is C3-C6 cycloalkyl; halogen, Cyano, Hydroxyl, Oxo, C1-C4 alkoxy, C1-C4 alkyl optionally substituted with 1 to 3 groups selected from the group consisting of halogen and cyano; C1-C4 haloalkyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl, -C(O)NH-C1-C6 alkyl, -C(O)NH-C1-C6 haloalkyl, C2-C6 alkenyl optionally substituted with 1 to 3 halogens, and C2-C6 alkynyl, and C3-C6 cycloalkyl optionally substituted by 1 to 5 substituents independently selected from the group consisting of: The embodiment (aq), or a salt thereof.

[0140] (bf) One embodiment is any of embodiments (1), (1.1), (1.2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (y), (z), (aa), (ab), (ac), (ad), (ae), (af), (ag), (ah), (aj), (ak), (ao), and (ap), wherein Y is C1-C6 alkyl; halogen, Cyano, Hydroxyl, Oxo, C3-C6 cycloalkyl, C1-C4 alkoxy, Acetylenyl, -NH2, C1-C7 aminocarbonyl, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -SC1-C4 alkyl, -S(O)C1-C4 alkyl, -SO2C1-C4 alkyl, -C(O)NH-C3-C6 cycloalkyl halogen, Hydroxyl, Cyano and C1-C4 alkyl halogen, Cyano, Hydroxyl, C1-C4 alkoxy, and -NH2, C1-C4 alkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of; -C(O)NH-C3-C6 cycloalkyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of; -C(O)NH-C1-C6 alkyl, -C(O)NH-C1-C6 cyanoalkyl optionally substituted with 1 to 3 halogens; -C(O)NH-C1-C6 haloalkyl, Regarding embodiments (1), (1.1), (1.2), (d), (d1), (d2), (e), (e1), (e2), (f), (f1), (f2), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (y), (z), (aa), (ab), (ac), (ad), (ae), (af), (ag), (ah), (aj), (ak), (ao), and (ap), or a salt thereof.

[0141] (bg) One embodiment relates to embodiment (bf), or a salt thereof, wherein Y is C1-C6 alkyl substituted with one -SO2C1-C4 alkyl.

[0142] (bh) One embodiment relates to embodiment (bf), or a salt thereof, wherein Y is C1-C6 alkyl substituted with one -SO2CH3.

[0143] (bi) One embodiment is embodiment (w), wherein W is [ka] The present invention relates to embodiment (w),

[0144] (xa) Another embodiment relates to each of the exemplified compounds or a salt thereof.

[0145] (xb) Another embodiment relates to each stereoisomer of each of the exemplified, depicted or named compounds, or a salt thereof.

[0146] (xc) Another embodiment relates to salts of each of the exemplified compounds.

[0147] The compounds of the present invention can be prepared by various procedures, many of which have already been described in the art.See, for example, WO 2005 / 085216, WO 2007 / 079162, US Patent Application Publication No. 2007 / 066617, US Patent Application Publication No. 20130131017, WO 2009 / 002809, WO 2009 / 112275, WO 2010 / 003923, WO 2010 / 070068, WO 2012 / 120399, WO 2013 / 079407 and WO 2021 / 127188.

[0148] The following examples are intended to be illustrative and non-limiting and represent specific embodiments of the present invention. [ka] TIFF2024523269000022.tif236161TIFF2024523269000023.tif250162TIFF2024523269000024.tif253163TIFF2024523269000025.tif61163 and each stereoisomer of the above compounds.

[0149] In another aspect, there is disclosed a compound of formula (II) or a salt thereof: [ka] During the ceremony, A1 is -CF3, -CHF2, -CH2F, or -CF2CF3; Cy1 is [ka] is selected from Cy2 is [ka] are selected from T1 is [ka] Selected from TIFF2024523269000030.tif136160.

[0150] In one embodiment, a compound of formula (IIa) or a salt thereof is disclosed: [ka] wherein A1, Cy1, Cy2, and T1 are as defined above.

[0151] In another embodiment, a compound of formula (IIb) or a salt thereof is disclosed: [ka] wherein A1, Cy1, Cy2, and T1 are as defined above.

[0152] Further embodiments of the present invention are provided below: (2) One embodiment relates to a compound of formula (II) or a salt thereof:

[0153] (2a) One embodiment relates to a compound of formula (IIa) or a salt thereof:

[0154] (2b) One embodiment relates to a compound of formula (IIb) or a salt thereof:

[0155] (2c) One embodiment relates to embodiments (2), (2a), and (2b) wherein A1 is -CF3.

[0156] (2d) One embodiment relates to embodiments (2), (2a), and (2b) wherein A1 is -CHF2.

[0157] (2e) One embodiment relates to embodiments (2), (2a), and (2b) wherein A1 is -CH2F.

[0158] (2f) One embodiment relates to embodiments (2), (2a), and (2b) wherein A1 is -CF2CF3.

[0159] (2g) In one embodiment, Cy1 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), and (2f), wherein

[0160] (2h) In one embodiment, Cy1 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), and (2f), wherein

[0161] (2i) In one embodiment, Cy1 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), and (2f), wherein

[0162] (2j) In one embodiment, Cy1 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), and (2f), wherein

[0163] (2k) In one embodiment, Cy1 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), and (2f), wherein

[0164] (2l) In one embodiment, Cy2 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), (2f), (2g), (2h), (2i), (2j), and (2k), wherein

[0165] (2m) In one embodiment, Cy2 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), (2f), (2g), (2h), (2i), (2j), and (2k), wherein

[0166] (2n) In one embodiment, Cy2 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), (2f), (2g), (2h), (2i), (2j), and (2k), wherein

[0167] (2o) In one embodiment, T1 is [ka] This relates to embodiments (2), (2a), (2b), (2c), (2d), (2e), (2f), (2g), (2h), (2i), (2j), (2k), (2l), (2m), and (2n), wherein

[0168] In another aspect, there is disclosed a compound of formula (III) or a salt thereof: [ka] During the ceremony, A1 is -CF3 or -CHF2, Cy3 is [ka] is selected from Cy4 is [ka] and T2 is [ka] is selected from.

[0169] In one embodiment, a compound of formula (IIIa) or a salt thereof is disclosed: [ka] wherein A1, Cy3, Cy4, and T2 are as defined above.

[0170] In another embodiment, a compound of formula (IIIb) or a salt thereof is disclosed: [ka] wherein A1, Cy3, Cy4, and T2 are as defined above.

[0171] Further embodiments of the present invention are provided below: (3) One embodiment relates to a compound of formula (III) or a salt thereof:

[0172] (3a) One embodiment relates to a compound of formula (IIa) or a salt thereof:

[0173] (3b) One embodiment relates to a compound of formula (IIb) or a salt thereof:

[0174] (3c) One embodiment relates to embodiments (3), (3a), and (3b) wherein A1 is -CF3.

[0175] (3d) One embodiment relates to embodiments (3), (3a), and (3b) wherein A1 is -CHF2.

[0176] (3e) One embodiment relates to embodiments (3), (3a), and (3b) wherein A1 is -CH2F.

[0177] (3f) One embodiment relates to embodiments (3), (3a), and (3b) wherein A1 is -CF2CF3.

[0178] (3g) In one embodiment, Cy3 is [ka] This relates to embodiments (3), (3a), (3b), (3c), (3d), (3e), and (3f), wherein

[0179] (3h) In one embodiment, Cy3 is [ka] This relates to embodiments (3), (3a), (3b), (3c), (3d), (3e), and (3f), wherein

[0180] (3i) In one embodiment, Cy3 is TIFF2024523269000050.tif26158, relating to embodiments (3), (3a), (3b), (3c), (3d), (3e), and (3f).

[0181] (3j) In one embodiment, Cy3 is [ka] This relates to embodiments (3), (3a), (3b), (3c), (3d), (3e), and (3f), wherein

[0182] (3k) In one embodiment, Cy3 is [ka] In an embodiment (3), Concerning (3a), (3b), (3c), (3d), (3e), and (3f).

[0183] (3l) In one embodiment, Cy4 is [ka] This relates to embodiments (3), (3a), (3b), (3c), (3d), (3e), (3f), (3g), (3h), (3i), (3j), and (3k), wherein

[0184] (3m) In one embodiment, T2 is [ka] This relates to embodiments (3), (3a), (3b), (3c), (3d), (3e), (3f), (3g), (3h), (3i), (3j), (3k), and (3l), wherein

[0185] (3n) In one embodiment, T2 is [ka] This relates to embodiments (3), (3a), (3b), (3c), (3d), (3e), (3f), (3g), (3h), (3i), (3j), (3k), and (3l), wherein

[0186] (3o) In one embodiment, T2 is [ka] This relates to embodiments (3), (3a), (3b), (3c), (3d), (3e), (3f), (3g), (3h), (3i), (3j), (3k), and (3l), wherein

[0187] (3p) In one embodiment, T2 is [ka] This relates to embodiments (3), (3a), (3b), (3c), (3d), (3e), (3f), (3g), (3h), (3i), (3j), (3k), and (3l), wherein

[0188] The following examples are intended to be illustrative and non-limiting and represent specific embodiments of the present invention.

[0189] The analysis was carried out using a liquid chromatography (LC) system coupled with a quadrupole mass spectrometry (MS) detector. UV (DAD) acquisition was performed with a scan range of 200–400 nm.

[0190] LC-MS, analysis method A: Instrument: Waters Acquity UPLC LC system - Waters SQ detector 2; Column: Acquity UPLC BEH C18 column with length 50 mm, inner diameter 2.1 mm, and particle size 1.7 μm; Eluent A: water with 0.1% formic acid; Eluent B: CH3CN.

[0191] LC-MS, analysis method B: Instrument: SHIMADZU LCMS-UFLC 20-AD -LCMS 2020 MS detector; Column: Kinetex EVO C18 2.6 μm, 50 × 3.0 mm; Eluent A: water / 6.5 mM NH4HCO3; Eluent B: CH3CN.

[0192] LC-MS, analysis method C: Instrument: SHIMADZU LCMS-UFLC 20-AD -LCMS 2020 MS detector, column: CORTECS C18 2.7 μm, 50 × 2.1 mm, eluent A: water + 0.1% by volume formic acid, eluent B: CH3CN + 0.10% by volume formic acid.

[0193] LC-MS, analytical method D: Instrument: SHIMADZU LCMS-UFLC 20-AD -LCMS 2020 MS detector; Column: Kinetex EVO C18 2.6 μm, 50 × 3.0 mm; Eluent A: water + 0.05% NH4HCO3 by volume; Eluent B: CH3CN.

[0194] As used herein, aq. means aqueous solution, br means broad, CH3CN means acetonitrile, d means doublet, dd means doublet, DCM means dichloromethane, DIPEA means N-diisopropylethylamine, DMF means N,N-dimethylformamide, DMSO means dimethylsulfoxide, ee means enantiomeric excess, ES means electrospray ionization, EtOAc means ethyl acetate, h means hours (~hours), and HATU means 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, HPLC means high performance liquid chromatography, iPrOH means isopropanol, J means coupling constant, LCMS means liquid chromatography-mass spectrometry, m / z means mass-to-charge ratio, M means molar concentration, m means multiplet, MeOH means methanol, min means minutes, NaHCO3 means sodium bicarbonate, Na2CO3 means sodium carbonate, NEt3 means triethylamine, NMR means nuclear magnetic resonance, q means quartet, quint means quintet, rt means room temperature, R t means retention time, s means singlet, sat. means saturated, T means temperature, t means triplet, td means triple doublet, THF means tetrahydrofuran, wt means weight, and δ means chemical shift.

[0195] rel-(R)-4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide (Example 1.1) and rel-(S)-4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide (Example 1.2) [ka]

[0196] Pd(dppf)Cl2 (4.55 g, 6.22 mmol) and NEt3 (28.0 mL, 187 mmol) were added to a degassed solution of 2-bromo-4-(trifluoromethyl)pyridine (14.0 g, 62.2 mmol) in MeOH (200 mL) under nitrogen atmosphere. The resulting solution was stirred at 80 °C under CO gas (150 psi) for 3 h. After the reaction was complete, the mixture was filtered through Celite® and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel (10% EtOAc in hexane) to give methyl 4-(trifluoromethyl)picolinate. LC-MS: m / z = 205.9 [M + H] + .

[0197] To a stirred solution of methyl 4-(trifluoromethyl)picolinate (11.0 g, 53.6 mmol) in CHCl3 (120 mL) was added mCPBA (27.7 g, 161 mmol) and the resulting mixture was heated at 60 °C for 16 h. After completion of the reaction, the mixture was allowed to cool to room temperature, diluted with DCM and filtered through Celite®. The filtrate was washed with saturated NaHCO3 solution and extracted with DCM (3x). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0-15% EtOAc / petroleum ether) to give the desired product as a yellowish oil. LC-MS: m / z=222.1 [M+H] + .

[0198] A solution of 2-(methoxycarbonyl)-4-(trifluoromethyl)pyridine 1-oxide (8.00 g, 36.2 mmol) in POCl3 (80 mL) was heated at 90 °C for 2 h. After completion of the reaction, the mixture was concentrated under reduced pressure. Ice water was added to the residue and the mixture was extracted with EtOAc (3x). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-15% EtOAc / petroleum ether) to give methyl 6-chloro-4-(trifluoromethyl)picolinate as a yellowish solid. LC-MS: m / z=239.9 [M+H] + .

[0199] To a stirred solution of 6-chloro-4-(trifluoromethyl)methylpicolinate (5.90 g, 24.6 mmol) in MeOH (8 mL) was added NaOMe (64.0 mg, 1.23 mmol) at 0° C. Then NaBH4 (1.86 g, 49.3 mmol) was added and the resulting reaction mixture was stirred at room temperature for 2 h. After completion of the reaction, the mixture was concentrated under reduced pressure. DCM was added and the solution was filtered. The filtrate was concentrated under reduced pressure to give (6-chloro-4-(trifluoromethyl)pyridin-2-yl)methanol. The product was used in the next synthetic step without further purification. LC-MS: m / z=212.1 [M+H] + .

[0200] Dess-Martin periodinane (22.5 g, 53.1 mmol) was added to a solution of (6-chloro-4-(trifluoromethyl)pyridin-2-yl)methanol (5.6 g, 26.5 mmol) in DCM (100 mL) at 0 °C in an ice bath. The resulting reaction mixture was stirred for 2 h and allowed to warm to room temperature. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (10% EtOAc in hexanes) to give 6-chloro-4-(trifluoromethyl)picolinaldehyde. LC-MS: m / z=209.9 [M+H] + .

[0201] To a stirred solution of 6-chloro-4-(trifluoromethyl)picolinaldehyde (2.80 g, 13.4 mmol) in DCM (100 mL) was added DAST (7.8 g, 20.0 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 h. After this time, the reaction was quenched by the addition of ice water and the resulting aqueous layer was extracted with DCM (2×). The solvent was removed under reduced pressure to give the desired product. 2-Chloro-6-(difluoromethyl)-4-(trifluoromethyl)pyridine was used in the next synthetic step without further purification.

[0202] Cs2CO3 (6.30 g, 194 mmol) was added to a degassed solution of 2-chloro-6-(difluoromethyl)-4-(trifluoromethyl)pyridine (1.50 g, 6.47 mmol) in THF (10 mL) and water (5 mL) under nitrogen atmosphere. Pd(OAc)2 (217 mg, 323 μmol), PPh3 (203 mg, 777 μmol), and potassium trifluoro(3,3,3-trifluoroprop-1-en-2-yl)borate (1.96 g, 9.71 mmol) were then added and the reaction mixture was heated at 80 °C for 16 h. After this time, the mixture was diluted with water and extracted with Et2O (3x). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0-3% EtOAc / petroleum ether) to give 2-(difluoromethyl)-4-(trifluoromethyl)-6-(3,3,3-trifluoroprop-1-en-2-yl)pyridine as a brownish oil.

[0203] To a stirred solution of methyl 4-((hydroxyimino)methyl)-2-methylbenzoate (334 mg, 1.73 mmol) in DMF (3 mL) was added NCS (275 mg, 2.06 mmol) and the reaction mixture was stirred at 40° C. for 10 min. After this time, the mixture was cooled to 0° C. in an ice bath. 2-(difluoromethyl)-4-(trifluoromethyl)-6-(3,3,3-trifluoroprop-1-en-2-yl)pyridine (600 mg, 2.06 mmol) and NEt3 (417 mg, 4.12 mmol) in DMF (3.0 mL) were then added and the resulting reaction mixture was allowed to stir at room temperature for 16 h. The mixture was then diluted with water and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-5% EtOAc / petroleum ether) to give methyl 4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate. LC-MS: m / z=483.1[M+H] + .

[0204] A mixture of methyl 4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate (200 mg, 0.414 mmol) and LiOH·H2O (520 mg, 1.24 mmol) in dioxane (2 mL) and water (2 mL) was heated at 90 °C for 6 h. The reaction was quenched by the addition of aqueous HCl (1 M). The resulting precipitate was filtered, washed with water and dried under reduced pressure. The desired product, 4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was obtained as a yellowish solid and used in the next synthetic step without further purification. LC-MS: m / z=469.1 [M+H] + .

[0205] To a stirred solution of compound 4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (130 mg, 277 μmol), 2-amino-N-(2,2,2-trifluoroethyl)acetamide (80.1 mg, 416 μmol) and HATU (158 mg, 416 μmol) in DMF (4 mL) was added DIPEA (107 mL, 832 μmol) and the resulting reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched by addition of water and extracted with EtOAc (3×). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-10% EtOAc / petroleum ether) to give racemic 4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide as a colorless solid. LC-MS (Method A)R t =2.22 min, m / z=607.4[M+H] + . 1 H NMR(DMSO-d6,400MHz)δ8.61(t,J=6.0Hz,2H),8.26(s,1H),8.18(s,1H),7.68-7.62(m,2H),7.49(d,J=8. 0Hz,1H), 7.16(t,J=54Hz,1H),4.50(d,J=18Hz,1H),4.35(d,J=18Hz,1H),4.00-4.87(m,4H),2.39(s,3H).

[0206] The two enantiomers were separated by SFC. The separation was carried out on a CHIRALPAK-AD-H with column dimensions of 250 mm x 30 mm (5 μm), a flow rate of 100 g / min, and a CO2-based mobile phase with 10% iPrOH containing 0.2% N,N-dimethylethylamine as additive, to obtain Example 1.1: rel-(R)-4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl. Example 1.2: rel-(S)-4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide.

[0207] An alternative synthetic scheme for preparing Examples 1.1 and 1.2 can be seen in FIG.

[0208] The following compounds were similarly prepared by the methodology of Examples 1.1 and 1.2. [Table 1] TIFF2024523269000060.tif227170TIFF2024523269000061.tif77170

[0209] 4-((R*)-5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((trans)-3-(trifluoromethyl)cyclobutyl)benzamide (Example 2.1) and 4-((S*)-5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((trans)-3-(trifluoromethyl)cyclobutyl)benzamide (Example 2.2) [ka]

[0210] A mixture of 2,4-bis(chloranil)-6-[tris(fluoranyl)methyl]pyridine (2.00 g, 9.26 mmol), trifluoro(3,3,3-trifluoroprop-1-en-2-yl)-14-borane, potassium salt (3.74 g, 18.5 mmol), Cs2CO3 (9.05 g, 27.8 mmol), and Pd(dppf)Cl2 (672 mg, 926 μmol) in THF (15 mL) and water (6 mL) was stirred at 80 °C under nitrogen atmosphere for 4 h. After cooling to room temperature, water was added and the resulting mixture was extracted with petroleum ether. The combined organic layer was dried over anhydrous Na2SO4, filtered, and used directly in the next step. GC-MS: R t =2.43 min, m / z=275(M) + .

[0211] To a solution of methyl (E)-4-((hydroxyimino)methyl)-2-methylbenzoate (2.10 g, 10.9 mmol) in DMF, NCS (1.45 g, 10.9 mmol) was added at room temperature, and the resulting mixture was stirred at room temperature for 30 min. Then, a solution of 4-chloro-2-(trifluoromethyl)-6-(3,3,3-trifluoroprop-1-en-2-yl)pyridine in petroleum ether (10.9 mmol) was added. The mixture was stirred for 10 min, and then NEt3 (2.20 g, 21.8 mmol) was added. After 1 h, the reaction mixture was poured into ice-cold water. The precipitate was collected, washed with water, and then purified by column chromatography on silica gel (0-10% EtOAc in petroleum ether) to give methyl 4-(5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate as a yellow solid. LC-MS (Method C): R t =1.12 min, m / z=467(M+H) + .

[0212] A solution of methyl 4-(5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate (1.00 g, 2.14 mmol) and LiOH (256.54 mg, 10.71 mmol) in THF (15 mL) and water (15 mL) was stirred at room temperature for 16 h. The mixture was acidified with HCl (6 M) until the pH value reached 3. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give 4-(5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid as a yellow solid. LC-MS (Method C): R t = 1.01 min, m / z = 451 (MH) - .

[0213] A reaction mixture of rac-4-(5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (214 mg, 472 μmol), trans-3-(trifluoromethyl)cyclobutan-1-amine·HCl (83.0 mg, 473 μmol), HATU (217 mg, 570 μmol), and diisopropylethylamine (367 mg, 2.84 mmol, 494 μL) was stirred at room temperature for 1.5 h. The resulting mixture was poured into water and then extracted with EtOAc. The combined organic layer was dried over anhydrous Na2SO4 and then concentrated under reduced pressure. The residue was purified by preparative TLC (PE / EA=2:1) ​​to give racemic 4-(5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((trans)-3-(trifluoromethyl)cyclobutyl)benzamide. LC-MS (Method D): Rt=1.42 min, m / z=574 (M+H). + . 1 H-NMR (400MHz, DMSO-D6): δ8.78(d,1H),8.34(s,1H),8.17(s,1H),8.67-8.64(m,2H),7.44(d, 1H),4.50-4.25(m,2H),3.25-3.05(m,2H),2.49-2.40(m,2H),2.36(s,3H),2.30-2.20(m,2H).

[0214] The two enantiomers were separated by preparative chiral-HPLC (column: CHIRALPAK IE, 2×25 cm, 5 μm, mobile phase A: hexane (0.5% 2M NH3-MeOH), mobile phase B: IPA) to give Example 2.1: 4-((R*)-5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((trans)-3-(trifluoromethyl)cyclobutyl)benzamide, and Example 2.2: 4-((S*)-5-(4-chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((trans)-3-(trifluoromethyl)cyclobutyl)benzamide.

[0215] The following compounds were similarly prepared by the methodology of Examples 2.1 and 2.2. [Table 2]

[0216] rel-(S)-2-Methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzamide Example 3.1 and rel-(R)-2-Methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzamide Example 3.2 [ka]

[0217] To a solution of 2-chloranyl-6-[tris(fluoranyl)methyl]pyrazine (1.90 g, 10.4 mmol) in THF (30 mL) and water (7.5 mL) was added trifluoro(3,3,3-trifluoroprop-1-en-2-yl)-14-borane, potassium salt (3.15 g, 15.61 mmol), Cs2CO3 (10.2 g, 31.2 mmol), and Pd(dppf)Cl2 (755 mg, 1.04 mmol). The reaction mixture was stirred at 80 °C in a sealed tube under nitrogen atmosphere for 24 h. The reaction mixture was quenched with water and extracted with petroleum ether. The combined organic layer was dried over anhydrous Na2SO4 and filtered through a pad of celite. The filtrate was concentrated under reduced pressure in an ice bath (to about 20 mL). The solution was used in the next step without further purification. GC-MS: m / z=242(M) + .

[0218] To a solution of methyl 2-methyl-4-[(E)-oxydanyliminomethyl]benzoate (1.76 g, 9.09 mmol) in DMF (30 mL) was added NCS (1.10 g, 8.26 mmol, 668 μL). The reaction mixture was stirred at 30° C. for 2 h. To the above solution was added 2-[tris(fluoranyl)methyl]-6-[1-[tris(fluoranyl)methyl]vinyl]pyrazine (8.26 mmol, solution in 20 mL petroleum ether) at 0° C. The resulting mixture was stirred at 0° C. for 5 min, then NEt3 (836 mg, 8.26 mmol, 1.15 mL) was added. The reaction mixture was allowed to warm to room temperature and stirred for an additional 2 h. The mixture was quenched with water and extracted with EtOAc. The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (PE / EA=4:1) to give methyl 2-methyl-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzoate as a yellow oil. GC-MS: m / z=433(M). + .

[0219] To a solution of methyl 2-methyl-4-[(5-(trifluoromethyl)-5-[6-(trifluoromethyl)pyrazin-2-yl]-4H-isoxazol-3-yl]benzoate (400 mg, 923 μmol) in THF (4 mL) and water (4 mL) was added LiOH (111 mg, 4.62 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with water and acidified with HCl (2 M) until the pH value reached 4. The mixture was extracted with EtOAc. The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to give 2-methyl-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzoic acid as a yellow oil. LC-MS (Method C): R t =0.94min;m / z=420(M+H) + .

[0220] To a solution of 2-methyl-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzoic acid (280 mg, 668 μmol) in DMF (6 mL) was added HATU (330 mg, 868 μmol), N,N-diisopropylethylamine (345 mg, 2.67 mmol, 465 μL), and 2-azanyl-N-[2,2,2-tris(fluoranyl)ethyl]acetamide (156 mg, 1.00 mmol). The reaction mixture was stirred at room temperature for 1 h. The mixture was quenched with water and extracted with EtOAc. The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC (PE / EA=2:1) ​​and preparative HPLC to give rac-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzamide. LC-MS (Method D): R t =1.412 min, MS(ESIpos):m / z=558(M+H) + . 1H NMR(400MHz,DMSO-d6):δ9.39-9.36(d,2H),8.63-8.60(m,2H),7.68-7.66(d,2H),7.5 0-7.48(d,1H),4.54-4.50(d,1H),4.36-4.31(d,1H),3.99-3.91(m,4H),2.40(s,3H).

[0221] The two enantiomers were separated by preparative chiral HPLC (column: CHIRALPAK IF, 2 × 25 cm, 5 μm, mobile phase A: hexane (0.5% of 2M NH3-MeOH), mobile phase B: EtOH) to give Example 3.1: rel-(S)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzamide, and Example 3.2: rel-(R)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzamide.

[0222] An alternative synthetic scheme for preparing Examples 3.1 and 3.2 can be seen in FIG. [Table 3] TIFF2024523269000066.tif251168

[0223] The compounds of the present invention are valuable active ingredients for use in pest control.The term "pest" includes ectoparasites and endoparasites on and in animals and in the field of hygiene.Specific pests are fleas, ticks, mites, flies, worms, and lice.Even more specific pests are fleas and ticks.

[0224] Animals in the context of the present invention are understood to include vertebrates. The term vertebrates in this context is understood to include mammals, including fish, amphibians, reptiles, birds, and humans. One preferred group of vertebrates according to the present invention includes domestic animals, such as cows, horses, pigs, sheep, and goats, poultry, such as chickens, turkeys, guinea fowl, and geese, fur animals, such as minks, foxes, chinchillas, rabbits, and the like, as well as companion animals, such as ferrets, guinea pigs, rats, hamsters, cats, and dogs, and warm-blooded animals, including humans. Another preferred group of vertebrates according to the present invention includes fish, including salmon.

[0225] In the context of the present invention, ectoparasites are understood to be in particular insects, acarids (mites and ticks) and crustaceans (sea lice). These include insects of the following orders: Lepidoptera, Coleoptera, Homoptera, Hemiptera, Heteroptera, Diptera, Dictyoptera, Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera, Psocoptera and Hymenoptera. However, ectoparasites which may be mentioned in particular are those which annoy humans or animals and which carry pathogens, such as the house fly Musca domestica, the Australian house fly Musca vetustissima, the European house fly Musca autumnalis, the little house fly Fannia canicularis, the flesh fly Sarcophaga carnaria, the sheep blow fly Lucilia cuprina, the broad-banded blow fly Lucilia sericata, the cow fly Hypoderma bovis, the cow fly Hypoderma lineatum, the flies of the genus Chrysomyia chloropyga, the human dung fly Dermatobia hominis, the screwworm fly Cochliomyia hominivorax, the horse fly Gasterophilus intestinalis, flies such as the sheep fly (Oestrus ovis), stable flies such as the horn fly (Haematobia irritans irritans), a subspecies of the horn fly (Haematobia irritans exigua), and the stable fly (Stomoxys calcitrans), horse flies (hors flies) such as the various species of the genus Haematopota (Haematopota spp.) (e.g. Haematopota pluvialis) and the subfamilies Tabanidae (e.g. Tabanus spp.) (e.g. Tabanus nigrovittatus) as well as the subfamilies Chrysops spp.bot flies, including subfamilies such as the Chrysopsinae (e.g. the deer fly Chrysops caecutiens), Hippoboscid flies, e.g. Melophagus ovinus (sheep ked), tsetse flies, e.g. Glossinia spp., midges, e.g. Ceratopogonidae (biting midges), Simuliidae (black flies), Psychodidae (sand flies), as well as other biting insects such as Anopheles spp., Aedes spp. and Culex spp. blood-sucking insects, such as mosquitoes, e.g. Ctenocephalides felis and Ctenocephalides canis (cat and dog fleas), Xenopsylla cheopis, Pulex irritans, Ceratophyllus gallinae, fleas, e.g. Dermatophilus penetrans, e.g. Linognathus spp, Haematopinus spp, Solenopotes spp, Pediculus spp, Lice (order Anoplura) such as blood-sucking lice (Anoplura) such as Bovicola (Damalinia) ovis, Bovicola (Damalinia) bovis and other Bovicola species, as well as lice (order Mallophaga) such as Bovicola (Damalinia) ovis, Bovicola (Damalinia) bovis and other Bovicola species. Ectoparasites are also included, for example mites (e.g. Chorioptes bovis, Cheyletiella spp., Dermanyssus gallinae, Ortnithonyssus spp.Representative ticks include members of the order Acarina, such as Demodex canis, Sarcoptes scabiei, Psoroptes ovis and Psorergates spp., and ticks. Representative ticks include the genera Boophilus, Amblyomma, and Vexillaria, which preferably infest vertebrates, including warm-blooded animals, including livestock, such as cattle, horses, pigs, sheep and goats, poultry, such as chickens, turkeys, guinea fowl and geese, fur animals, such as mink, foxes, chinchillas, rabbits and companion animals, such as ferrets, guinea pigs, rats, hamsters, cats and dogs, as well as humans and fish. a), Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius and Ornithodoros.

[0226] The compounds of the invention according to the invention are also active against all or individual developmental stages of animal pests that show normal sensitivity as well as resistance to widely used parasiticides. This is particularly true for resistant insects and members of the order Acarina. The insecticidal, ovicidal and / or acaricidal effect of the active substances of the invention can manifest itself directly, i.e. by killing the pests or destroying their eggs, either immediately or after some time has elapsed, for example when molting occurs, or indirectly, for example by reducing the number of laid eggs and / or the hatching rate, with a good efficacy corresponding to a killing rate (mortality rate) of at least 50-60%.

[0227] The compounds of the invention may also be used against sanitary pests, particularly those of the orders Diptera, Orthoptera, Dictyoptera (e.g. Blattidae (cockroaches), e.g. Blatella germanica, Blatta orientalis, Periplaneta americana) of the families Muscidae, Sarcophagidae, Anophilidae, and Culicidae, and Hymenoptera (e.g. Formicidae (ants) and Vespidae (wasps).

[0228] The compounds of formula (I) are also effective against ectoparasites of fish, particularly the subclass of Copepoda (eg, Siphonostomatoida (sea lice)), whilst being well tolerated by fish.

[0229] The compounds of formula (I) may also be used against worms of the class Cestoda, which includes the subclasses Eucestoda and Cestodaria.

[0230] The compounds of the invention also have a sustainable efficacy against plant parasitic mites and insect parasites. In the case of Acarina spider mites, they are effective against eggs, nymphs and adults of the family Tetranychidae (Tetranychus spp. and Panonychus spp.).

[0231] They have high activity against sap-sucking insects of the suborder Homoptera, in particular pests of the families Aphididae, Delphacidae, Cicadellidae, Psyllidae, Loccidae, Diaspididae and Eriophydidae (e.g. citrus rust mites), pests of the orders Hemiptera, Heteroptera and Thysanoptera, as well as herbivorous insects of the orders Lepidoptera, Coleoptera, Diptera and Orthoptera.

[0232] They are likewise suitable as soil pesticides against harmful organisms in the soil.

[0233] Thus, the compounds of formula (I) are effective against all developmental stages of sap-sucking and crop-feeding insects in crops such as, for example, cereals, cotton, rice, corn, soybeans, potatoes, vegetables, fruits, tobacco, hops, citrus, avocado, and other crops.

[0234] The compounds of formula I are also effective against plant parasitic nematodes such as species of the genera Meloidogyne, Heterodera, Pratylenchus, Ditylenchus, Radopholus and Rizoglyphus.

[0235] The compounds of the present invention are effective against helminths.Helminths are commercially important because they cause serious diseases in mammals and poultry, such as sheep, pigs, goats, cattle, horses, donkeys, camels, dogs, cats, rabbits, guinea pigs, hamsters, chickens, turkeys, guinea fowl, and other domestic birds, as well as exotic birds.Typical nematodes include Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostonum, Oesophagostonum, Charbertia, Trichuris, Strongylus, and the like. ), Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. The trematodes include in particular the Fasciolideae, in particular Fasciola hepatica.

[0236] The insecticidal action of the compounds of formula (I) according to the invention corresponds to a mortality rate of about 50-60% of the pests mentioned, more preferably a mortality rate of more than 90%, most preferably 95-100%. The compounds of formula (I) are preferably used internally and externally in raw form or, preferably, together with adjuvants conventionally used in the technical field of formulations and thus may be processed in known manner to give, for example, liquid formulations (e.g., spot-ons, pour-ons, spray-ons, emulsions, suspensions, solutions, emulsifiable concentrates, solution concentrates), semisolid formulations (e.g., creams, ointments, pastes, gels, liposomal preparations) and solid preparations (e.g., capsules, powders including soluble powders, food additive tablets including granules, etc., or embedding the active ingredient in polymeric substances such as implants or microparticles). As with the compositions, the application method is selected depending on the intended purpose and the prevailing situation.

[0237] The compounds of the present invention can be administered alone or in the form of a composition.In practice, the compounds of the present invention are usually administered in the form of a composition, i.e., in admixture with at least one acceptable excipient.The proportion and nature of any acceptable excipient will be determined by the properties of the selected compound of the present invention, the selected route of administration, and standard practice in the veterinary and pharmaceutical fields.

[0238] In one embodiment, the present invention provides a composition comprising a compound of the present invention and at least one acceptable excipient.

[0239] To achieve such treatment and / or eradication, the compound of the present invention can be administered in any form and route that allows the compound to be bioavailable.The compound of the present invention can be administered by various routes, including oral, particularly by tablets and capsules.The compound of the present invention can be administered more specifically by parenteral route, such as inhalation, subcutaneous, intramuscular, intravenous, intraarterial, transdermal, intranasal, rectal, vaginal, intraocular, topical, sublingual, and buccal, intraperitoneal, intraadiposally, intrathecal, and via local delivery, for example, by catheter or stent.

[0240] Those skilled in the art can easily select the appropriate form and administration route depending on the specific characteristics of the selected compound, the disorder or condition to be treated, the stage of the disorder or condition, and other relevant circumstances.The pharmaceutical composition of the present invention can be administered to a subject in the form of, for example, tablets, including chewable tablets, capsules, cachets, papers, lozenges, oblates, elixirs, boli, ointments, transdermal patches, aerosols, inhalants, suppositories, solutions, solutions, injections, and suspensions.

[0241] The term "acceptable excipient" refers to those excipients typically used in the preparation of veterinary and pharmaceutical compositions, and should be pure and non-toxic in the amount used. They are generally solid, semi-solid, or liquid substances that can function as a vehicle or medium for the active ingredient in the aggregate. Some examples of acceptable excipients are identified in Remington's Pharmaceutical Sciences and Handbook of Pharmaceutical, and include diluents, vehicles, carriers, ointment bases, binders, disintegrants, lubricants, glidants, sweeteners, flavorings, gel bases, sustained release matrices, stabilizers, preservatives, solvents, suspending agents, buffers, emulsifiers, dyes, propellants, coatings, and others.

[0242] In one embodiment, the composition is adapted for oral administration, such as a tablet or capsule, or a liquid formulation adapted for oral administration, such as a solution or suspension. In one embodiment, the composition is adapted for oral administration, such as a chewable formulation adapted for oral administration. In yet another embodiment, the composition is a liquid or semi-solid formulation, such as a solution or suspension or paste, adapted for parenteral administration.

[0243] In one embodiment, the composition is adapted for injectable administration, such as a solution or suspension adapted for injectable administration.

[0244] Particular compositions for use in a subject in the treatment and / or control of nematodes / helminths include solutions, injections, typical emulsions, such as water-free organic compositions, preferably oil-based compositions, which form an emulsion with bodily fluids when added to the subject's body, emulsions, including microemulsions and self-emulsifying compositions, suspensions (water solutions), pour-on formulations, food additives, powders, tablets, including effervescent tablets, boli, capsules, including microcapsules, and chewable treats. In particular, the composition form is a tablet, capsule, food additive, or chewable treat.

[0245] The compositions of the present invention are prepared in a manner well known in the veterinary and pharmaceutical arts and comprise at least one of the compounds of the present invention as the active ingredient.

[0246] The amount of the compound of the present invention may vary depending on its particular form, and may conveniently be from 1% to about 50% of the weight of the unit dosage form. The pharmaceutical composition is preferably formulated in a unit dosage form, with each dosage typically containing from about 0.5 mg to about 100 mg of the compound of the present invention.

[0247] One or more unit dosage forms may be incorporated to affect the therapeutic dosage.

[0248] In one embodiment, the present invention also provides a method for treating a pest, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (I) or a salt thereof, the method optionally further comprising an effective amount of at least one additional active compound.

[0249] In one embodiment, the present invention also provides a method for controlling pests, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (I) or a salt thereof, the method optionally further comprising an effective amount of at least one additional active compound.

[0250] In one embodiment, the present invention also provides a method for treating or controlling a pest, the method comprising contacting an environment of a subject with an effective amount of a compound of formula (I) or a salt thereof, the method optionally further comprising an effective amount of at least one additional active compound.

[0251] Thus, the present invention provides the use of a compound of the present invention as a medicament, including the manufacture of a medicament. In one embodiment, the present invention provides the manufacture of a medicament comprising a compound of formula (I) or a salt thereof for treating a pest. In one embodiment, the present invention provides the manufacture of a medicament comprising a compound of the present invention or a salt thereof for combating a pest.

[0252] The terms "treating," "to treat," "treated," or "treatment" include, but are not limited to, inhibiting, slowing, halting, reducing, ameliorating, reversing the progression or severity of existing symptoms, or preventing a disorder, condition, or disease. For example, an adult heartworm infection would be treated by administering a compound of the invention. Treatment may be applied or administered therapeutically.

[0253] The terms "control", "controlling" or "controlled" refer to, but are not limited to, lowering, reducing or ameliorating the risk of a symptom, disorder, condition or disease, and protecting an animal from a symptom, disorder, condition or disease. Controlling can refer to therapeutic, prophylactic or preventative administration. For example, larvae or immature pests may be asymptomatic, but are controlled by acting on the larvae or immature pests to prevent the infection from progressing to a symptomatic or debilitating infection by mature pests.

[0254] Thus, the use of the compounds of the invention to treat and / or control pests, particularly endoparasitic nematodes and trematode helminths, refers to the use of the compounds of the invention to act on various forms of pests throughout their life cycle, regardless of whether the subject is symptomatic, including diseased or mortal, and regardless of the stage of challenge.

[0255] As used herein, "administering to a subject" includes, but is not limited to, administration to the skin, subcutaneously, intramuscularly, mucosally, submucosally, transdermally, orally, or intranasally. Administration can include injection or local administration, such as pour-on or spot-on administration. The pour-on or spot-on method is particularly advantageous for use with herd animals, such as cattle, horses, sheep, or pigs, where it is difficult or time-consuming to treat all animals orally or by injection. Due to its simplicity, this method can of course also be used with all other animals, including individual livestock or pet animals, and is highly favored by animal breeders, as it can often be performed without the presence of a veterinary specialist.

[0256] The terms "subject" and "patient" refer to vertebrates as described herein, including humans and non-human mammals and fish, such as dogs, cats, mice, rats, guinea pigs, rabbits, ferrets, cows, horses, sheep, goats, and pigs. Particular subjects are pet or companion animals that are mammals, such as dogs and cats, as well as mice, guinea pigs, ferrets, and rabbits.

[0257] The term "effective amount" means an amount that provides the desired benefit to the subject, and includes both therapeutic and curative administrations. The amount will vary from subject to subject and will depend on several factors, including the subject's overall physical condition and the severity of the underlying cause of the condition being treated, concurrent treatments, and the amount of the compound of the invention used to maintain the desired response at a beneficial level.

[0258] An effective amount can be readily determined by the attending physician as one of ordinary skill in the art by the use of known techniques and by observing results obtained under similar circumstances. In determining an effective amount, dosage, many factors are considered by the attending physician, including, but not limited to, the species of the patient, the size, age, and overall health of the patient, the particular condition, disorder, infection or disease involved, the degree of severity of the condition, disorder or disease involved, the response of the individual patient, the particular compound administered, the mode of administration, the bioavailability characteristics of the preparation administered, the administration regimen selected, the use of concomitant medications, and other relevant circumstances. An effective amount, therapeutic dosage of the present invention is expected to be in the range of 0.5 mg to 100 mg. The specific amount can be determined by one of ordinary skill in the art. These dosages are based on subjects weighing about 1 kg to about 20 kg, although a diagnostician can determine appropriate dosages for subjects weighing outside this weight range. An effective amount, therapeutic dosage of the present invention is expected to be in the range of 0.1 mg to 10 mg / kg for a subject. Dosing regimens are expected to be monthly, quarterly, semi-annually, or annually.

[0259] The compounds of the present invention may be combined with one or more other active compounds or therapies for the treatment of one or more disorders, diseases, or conditions, including treating pests for which they are indicated. The compounds of the present invention may be administered in combination with one or more compounds or therapies for treating pests and other disorders, either simultaneously, sequentially, or separately.

[0260] It is therefore understood that the compositions and methods of the present invention include, optionally, the inclusion of an effective amount of at least one additional active compound. Additional active compounds useful in the present invention include those used to treat fleas, ticks, flies, and mosquitoes, and include macrocyclic lactones such as milbemycin oxime, imidacloprid, spinosad, pyriproxyfen, premethrin, S-methoprene, praziquantel, and moxidectin. Further exemplary additional active compounds include, but are not limited to, afoxolaner, broflanilide, fluralaner, fluxamethamide, isocycloceram, lotilaner, modoflaner, nicofluprole, sarolaner, tigolaner, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, parabendazole, thiabendazole, triclabendazole, amitraz, demiditraz, clorsulon, closantel, oxyclonazide, lafoxanide, cyphenothrin, flumethrin, permethrin, cyromazine, delcantel, dimethicone, tetracycline ... Examples of such inhibitors include amphenetide, dicyclanil, dinotefuran, imidacloprid, nitenpyram, thiamethoxam, abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin, selamectin, milbemycin oxime, emodepside, epsiprantel, fipronil, fluazuron, fluhexafon, indoxacarb, levamisole, lufenuron, metaflumizone, methoprene, monepantel, morantel, niclosamide, nitroscanate, nitroxynil, novaluron, oxantel, praziquantel, pyrantel, pyriprole, pyriproxyfen, sisapronil, spinosad, spinetoram, and triflumezopyrim, or a salt of any of the foregoing.

[0261] The activity of the compounds of the present invention may be determined by a variety of methods, including in vitro and in vivo methods.

[0262] Example A: In vitro evaluation of anti-adult cat flea activity following ingestion To prepare the test blood mixture for feeding the fleas, the test substance is dissolved in dimethyl sulfoxide and diluted to the desired concentration with citrated bovine blood. To construct the test set-up, about 20 unfed male and female adult cat fleas (Ctenocephalides felis) are placed into a chamber that is closed at the top and bottom with gauze. A metal cylinder is placed in the chamber with one end sealed with a parafilm membrane and the base sealed, and filled with the test blood mixture, which can be absorbed by the fleas through the parafilm membrane. The blood cylinder part of the constructed test set-up is housed at about 37°C in an isolated air-heated container on an isolation carrier plate that holds the flea chamber. The flea chamber part is kept at room temperature. After 48 hours, the insecticidal activity against the fleas is determined. 100% means that all fleas are dead or moribund, and 0% means that no fleas are affected by the administered dose. From the dose-response curves, the respective EC50s were calculated (four-parameter logistic curve fitting). EC 50 When the applied dose is below 20 ppm, this substance shows good insecticidal activity against the cat flea (Ctenocephalides felis).

[0263] For example, in this test, the following compounds from the preparation examples were 50 Showed <1 ppm: Examples 1.1, 1.3, 1.5, 1.7, 1.9, 1.11, 1.13, 1.15, 2.1, 2.3, and 3.1.

[0264] For example, in this test, the following compounds from the preparation examples were 50Showed <20 ppm: Examples 1.1, 1.2, 1.3, 1.5, 1.7, 1.8, 1.9, 1.11, 1.12, 1.13, 1.14, 1.15, 1.16, 2.1, 2.2, 2.3, and 3.1.

[0265] With regard to the above data, if a single isomer was tested without knowing the absolute configuration of the isomer, the data will indicate whether the test substance is one isomer or the other isomer, e.g., Example 1.1 or its enantiomer.

[0266] Example B In vitro evaluation of contact activity against adult Rhipicephalus sanguineus In vitro tick contact tests are performed on male and female adult Rhipicephalus sanguineus ticks. Test substances are dissolved in acetone and diluted to the desired concentration for coating into test vials. The solution is then applied evenly to the inside walls and bottom of the glass vial by rolling and rocking on an orbital shaker until the solvent is completely evaporated. For example, a 900 ppm test substance solution will have a concentration of 5 μg / cm 2 After the solvent has completely evaporated, 5-10 adult ticks are placed in each coated test vial, which is then sealed with a perforated plastic lid and incubated horizontally in the dark at room temperature and ambient humidity. The acaricidal activity is determined after 48 hours. For this, the ticks are moved to the bottom of the test vial by gentle rocking, which is then incubated on a hot plate at 45-50°C for no more than 5 minutes. Ticks that remain motionless at the bottom of the test vial or that behave chaotically without intentionally climbing to avoid the heat are considered dead or moribund, respectively. 100% acaricidal activity means that all ticks were dead or moribund. 0% acaricidal activity means that none of the ticks were found dead or moribund. From the dose-response curves, the respective EC50s were calculated (four-parameter logistic curve fitting). EC 50 is 5μg / cm2 When the application rate is below 100 mg / kg, this substance exhibits good acaricidal activity against brown dog ticks (Rhipicephalus sanguineus).

[0267] For example, in this test, the following compounds from the preparation examples were 50 <0.04μg / cm 2 Examples 1.1, 1.11, 1.12, and 1.13 were given.

[0268] For example, in this test, the following compounds from the preparation examples were 50 <0.25 μg / cm 2 Examples 1.1, 1.3, 1.5, 1.11, 1.12, and 1.13 were shown.

[0269] For example, in this test, the following compounds from the preparation examples were 50 <5 μg / cm 2 Examples 1.1, 1.2, 1.3, 1.5, 1.6, 1.7, 1.8, 1.10, 1.11, 1.12, and 1.13 were shown.

[0270] With regard to the above data, if a single isomer was tested without knowing the absolute configuration of the isomer, the data will indicate whether the test substance is one isomer or the other isomer, e.g., Example 1.1 or its enantiomer.

[0271] Example C In vitro evaluation of contact activity against adult cat fleas In vitro tick contact tests are performed on male and female adult cat fleas (Ctenocephalides felis). The test substance is dissolved in acetone and diluted to the desired concentration for coating into the test vials. The solution is then applied evenly to the inside walls and bottom of the glass vial by rolling and rocking on an orbital shaker until the solvent is completely evaporated. For example, a 900 ppm test substance solution will have a concentration of 5 μg / cm 2 An area-based dose of is achieved.

[0272] After the solvent has completely evaporated, approximately 10 adult fleas are placed in each coated test vial, which is then sealed with a perforated plastic lid and incubated horizontally in the dark at room temperature and ambient humidity. Insecticidal activity is determined after 48 hours. Fleas that remain motionless at the bottom of the test vial or move chaotically without occasional hopping or walking in a straight line are considered dead or moribund, respectively. 100% insecticidal activity means that all fleas were dead or moribund. 0% insecticidal activity means that no fleas were affected. From the dose-response curves, the respective EC50s were calculated (four-parameter logistic curve fitting). EC50s of 5 μg / cm 2 When applied at a dose below this amount, this substance exhibits good insecticidal activity against the cat flea (Ctenocephalides felis).

[0273] For example, in this test, the following compounds from the preparation examples were 50 <0.05μg / cm 2 Examples 1.1, 1.7, 1.11, 1.12, and 1.13 were shown.

[0274] For example, in this test, the following compounds from the preparation examples were 50 <5 μg / cm 2 Examples 1.1, 1.3, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, 1.12, and 1.13 were shown.

[0275] With regard to the above data, if a single isomer was tested without knowing the absolute configuration of the isomer, the data will indicate whether the test substance is one isomer or the other isomer, e.g., Example 1.1 or its enantiomer.

[0276] Example D In vitro evaluation of systemic anti-female engorged bullfrog activity To prepare the test compound mixture for injection into the ticks, the test substances are dissolved in dimethyl sulfoxide and diluted to the desired concentration with the same solvent. 1 μl of this test mixture is injected into each abdomen of five engorged adult female bull ticks (Rhipicephalus (Boophilus) microplus). The ticks are transferred individually into a single compartment of a 5×5 replicate plate and kept in a temperature- and humidity-controlled chamber (28° C., 85% relative humidity). The acaricidal activity against bull ticks is evaluated after 7 days by evaluation of the fertilized eggs laid. Eggs that appear abnormal can be stored in a temperature- and humidity-controlled cabinet [28° C., 85% relative humidity] until the larvae hatch after 42 days. 100% acaricidal activity means that none of the ticks laid eggs or the eggs laid were infertile. 0% means that all eggs are fertilized. From the dose-response curves, the respective EC50s were calculated (four-parameter logistic curve fitting). Substances with EC50s below an applied dose of 10 μg per tick (μg / tick) exhibit good systemic acaricidal activity against Rhipicephalus microplus.

[0277] For example, in this test, the following compounds from the preparation examples were 50 Showed <0.5 μg / tick: Examples 1.1, 1.3, 1.5, 1.7, 1.8, 1.9, 1.11, and 1.13.

[0278] With regard to the above data, if a single isomer was tested without knowing the absolute configuration of the isomer, the data will indicate whether the test substance is one isomer or the other isomer, e.g., Example 1.1 or its enantiomer.

[0279] Example E In vitro evaluation of anti-Hexamethus bovis larval activity by contact This in vitro contact test is performed using larvae of the bullfrog tick (Rhipicephalus microplus). The test substance is dissolved in acetone pa and diluted to the desired concentration for coating into the test vials. The solution is then applied evenly to the inside walls and bottom of the glass vial by rolling and rocking on an orbital shaker until the solvent is completely evaporated. For example, a 900 ppm test substance solution will have a concentration of 5 μg / cm 2 After complete evaporation of the solvent, 10-20 tick larvae are placed in each coated test vial, which is then sealed with a perforated plastic lid and incubated horizontally in a tray maintained in a temperature- and humidity-controlled chamber (28°C, 85% relative humidity). The acaricidal activity is determined after 48 hours. For this, the vials are placed vertically and the effect is evaluated using the natural negatively gravitactic behavior of the bovis tick larvae. Tick larvae that remain motionless at the bottom of the test vial or that behave chaotically without intentionally climbing are considered dead or moribund, respectively. 100% acaricidal activity means that all tick larvae were dead or moribund. 0% acaricidal activity means that no tick larvae were affected. From the dose-response curve, the respective EC50 was calculated (four-parameter logistic curve fitting). EC50 of 5 μg / cm 2 When the application rate is below 100 mg / kg, this substance exhibits good acaricidal activity against brown dog ticks (Rhipicephalus sanguineus).

[0280] For example, in this test, the following compounds from the preparation examples were 50 <0.05μg / cm 2 Examples 1.1, 1.3, 1.5, 1.7, 1.9, 1.11, and 1.13 were shown.

[0281] With regard to the above data, if a single isomer was tested without knowing the absolute configuration of the isomer, the data will indicate whether the test substance is one isomer or the other isomer, e.g., Example 1.1 or its enantiomer.

Claims

1. A compound of formula (I), 【Chemical Formula 1】 wherein, A １ is selected from the group consisting of CF ３ , CHF ２ , CH ２ F, and CF ２ CF ３ and is selected from the group consisting of, A ２ is O or S, Z is N or CR ２ and, R １ is selected from the group consisting of hydrogen and halogen, R ２ is selected from the group consisting of hydrogen, halogen, difluoromethyl, trifluoromethyl and trifluoromethoxy, R ３ is selected from the group consisting of hydrogen, halogen and trifluoromethyl, R ４ is selected from the group consisting of hydrogen, halogen, difluoromethyl, trifluoromethyl, hydroxy, methoxy and trifluoromethoxy, Q is selected from the group consisting of the following, 【Chemical Formula 2】 wherein, p is 0, 1, or 2, q is 0, 1, 2, or 3, r is 0 or 1, s is 0, 1, or 2, t is 0 or 1, R ５ is, each occurrence, halogen, cyano, nitro, hydroxyl, -NH ２ , -NH(C １ ~ C ４ alkyl), -N(C １ ~ C ４ alkyl) ２ , C ２ ~ C ５ - alkoxycarbonyl, C １ to C ６ alkyl which is halogen, cyano, nitro, hydroxyl, oxo, C ３ to C ６ cycloalkyl, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ , -SC １ to C ４ alkyl, -S(O)C １ to C ４ alkyl, and -SO ２ C １ to C ４ alkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, oxo, C １ to C ６ alkyl, C １ to C ６ alkoxy which is halogen, cyano, nitro, hydroxyl, oxo, C ３ to C ６ cycloalkyl, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ , -SC １ to C ４ alkyl, -S(O)C １ to C ４ alkyl, and -SO ２ C １ to C ４ alkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, oxo, C １ to C ６ alkoxy, -NR ７ C(O)(C １ to C ４alkyl), and is independently selected from the group consisting of halogen, cyano, hydroxyl, C ３ -C ６ cycloalkyl, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), and -N(C １ -C ４ alkyl) ２ The C １ -C ４ alkyl may be substituted with 1 to 5 substituents independently selected from the group consisting of, wherein R ７ is hydrogen and C １ -C ４ alkyl, and -NR ７ C(O)(C １ -C ４ alkyl), -C(O)NR ７ (C １ -C ４ alkyl), and is independently selected from the group consisting of halogen, cyano, hydroxyl, C ３ -C ６ cycloalkyl, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), and -N(C １ -C ４ alkyl) ２ The C １ -C ４ alkyl may be substituted with 1 to 5 substituents independently selected from the group consisting of, wherein R ７ is hydrogen and C １ -C ４ alkyl, and -C(O)NR ７ (C １ -C ４ alkyl), -SC １ -C ６ alkyl, and is independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, oxo, C ３ -C ６ cycloalkyl, C １ -C ４ alkoxy, -NH ２ -, C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), and -N(C １ -C ４ alkyl) ２ optionally substituted with 1 to 5 substituents independently selected from the group consisting of -SC １ -C ６ alkyl, and -S(O)C １ -C ６ alkyl which is halogen, cyano, nitro, hydroxyl, oxo, C ３ -C ６ cycloalkyl, C １ -C ４ alkoxy, -NH ２ -, C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), and -N(C １ -C ４ alkyl) ２ optionally substituted with 1 to 5 substituents independently selected from the group consisting of -S(O)C １ -C ６ alkyl, independently selected from the group consisting of, R ６ is, each occurrence, oxo, C １ -C ４ alkyl, and C ３ -C ６ cycloalkyl, independently selected from the group consisting of, A ３ is O or S, A ４ is CH or N, A ５ is CH or N, A ６ is CH or N, A ７ is CHO, S, a bond, or N, A ８ is CHO, S, a bond, or N, A ９ is CH or N, A １０ is CH or N, A １１ is CH or N, A １２ is CH or N, A １３ is CH or N, A １４ is CH or N, A １５ is CH or N, A １６ is NR, O, or S, where R is hydrogen, C １ to C ４ alkyl, and C ３ to C ６ cycloalkyl, selected from the group consisting of, W １ is -O-, -S-, -NR ８ -, -NC(O)R ９ -, -CH ２ -, and -C(O)-, selected from the group consisting of, W ２ is -O-, -S-, -NR ８ -, -NC(O)R ９ -, -CH ２ -, and -C(O)-, selected from the group consisting of, However, W １ is -O-, -S-, -NR ８ -, or -NC(O)R ９ - when W ２ is -CH ２ -, or -C(O)-, and also W ２ is -O-, -S-, -NR ８ -, or -NC(O)R ９ - when W １ is -CH ２ -, or -C(O)-, W ３ is selected from the group consisting of nil (none), -O-, -S-, -S(O)-, -S(O) ２ -, -NR ８ -, -CH-, -N-, -CH ２ -, and -C(O)-, W ４ is selected from the group consisting of nil (none), -O-, -S-, -S(O)-, -S(O) ２ -, -NR ８ -, -CH-, -N-, -CH ２ -, and -C(O)-, W ５ is selected from the group consisting of nil (none), -O-, -S-, -S(O)-, -S(O) ２ -, -NR ８ -, -CH-, -N-, -CH ２ -, and -C(O)-, W ６ is selected from the group consisting of nil (none), -O-, -S-, -S(O)-, -S(O) ２ -, -NR ８ -, -CH-, -N-, -CH ２ -, and -C(O)-, Wherein, W １ , W ２ , W ３ , and W ４ The bond between can be a single bond or a double bond, Provided that (i) Two or less of W １ , W ２ , W ３ , and W ４ are nil (none), (ii) Two or less of W １ , W ２ , W ３ , and W ４ are -O-, -S-, -S(O)-, -S(O) ２ -, -NR ８ -, or -C(O)-, (iii) W １ , W ２ , W ３ , and W ４If two of them are -O- and / or -S-, there is at least one carbon atom between them, and (iv) W １ , W ２ , W ３ , or W ４ is -CH- and / or -NR ８ -, then a double bond is formed within the ring formed by W １ , W ２ , W ３ , and W ４ and is as follows, R ８ is, each occurrence, hydrogen, and C １ to C ６ alkyl which is halogen, cyano, nitro, hydroxyl, oxo, C ３ to C ６ cycloalkyl, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ , -SC １ to C ４ alkyl, -S(O)C １ to C ４ alkyl, and -SO ２ C １ to C ４ alkyl, and is independently selected from the group consisting of 1 to 5 substituents which may be substituted, and is C １ to C ６ alkyl independently selected from the group consisting of, R ９ is, each occurrence, oxo, C １ to C ４ alkyl, and C ３ to C ６ cycloalkyl independently selected from the group consisting of, X is 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S, and N, The carbon of the 5- to 10-membered heteroaryl may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, C １ - C ４ alkyl which is halogen, cyano, hydroxyl, oxo, C １ - C ４ alkoxy, -NH ２ , C １ - C ７ aminocarbonyl, -NH(C １ - C ４ alkyl), -N(C １ - C ４ alkyl) ２ , -SC １ - C ４ alkyl, -S(O)C １ - C ４ alkyl, -SO ２ C １ - C ４ alkyl, -C(O)NH-C ３ - C ６ cycloalkyl, -C(O)NH-C １ - C ６ alkyl, and -C(O)NH-C １ - C ６ haloalkyl and may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ - C ４ alkyl, C ３ - C ６ cycloalkyl, C １ - C ４ haloalkyl, C １ - C ４ alkoxy, -NH ２ , -NH(C １ - C ４ alkyl), -N(C １ - C ４ alkyl) ２ , -C(O)NH-C ３ - C ６ cycloalkyl, -C(O)NH-C １ - C ６ alkyl, and -C(O)NH-C １ - C ６ haloalkyl and may be substituted with 1, 2, or 3 substituents independently selected from the group consisting of wherein any N of the heteroaryl, if the valence allows, is hydrogen, C １ - C ４ - alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ - C ４ - alkoxy, - NH ２ , C １ - C ７ - aminocarbonyl, - NH(C １ - C ４ - alkyl), - N(C １ - C ４ - alkyl) ２ , - SC １ - C ４ - alkyl, - S(O)C １ - C ４ - alkyl, - SO ２ C １ - C ４ - alkyl, - C(O)NH - C ３ - C ６ - cycloalkyl, - C(O)NH - C １ - C ６ - alkyl, and - C(O)NH - C １ - C ６ - haloalkyl, and is optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ - C ４ - alkyl, and C ３ - C ６ - cycloalkyl, and is optionally substituted with a substituent selected from the group consisting of or X is selected from the group consisting of [Chemical Formula 3] wherein R １０ is hydrogen, C １ - C ４ - alkyl, C １ - C ４ - haloalkyl, C ３ - C ６ - cyclo - alkyl, C ４ - C ７ - alkylcycloalkyl, C ２ - C ７ Alkylcarbonyl, C ２ ~C ５ Alkoxycarbonyl, C ２ ~C ６ Alkenyl, and C ２ ~C ６ selected from the group consisting of alkynyl, W is, (i) hydrogen, (ii) C １ ~C ６ alkyl which may be substituted with 1 to 3 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, oxo, C １ ~C ４ alkoxy, and independently halogen and cyano, and which may be substituted with 1 to 3 substituents selected from the group consisting of halogen and cyano, C ３ ~C ６ cycloalkyl, acetylenyl, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, hydroxyl, cyano and C １ ~C ４ alkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C １ ~C ４ alkoxy, C ３ ~C ６ cycloalkyl and -NH ２ and which may be substituted with 1 to 3 substituents independently selected from the group consisting of C １ ~C ４ alkyl and which may be substituted with 1 to 3 substituents independently selected from the group consisting of -C(O)NH-C ３ ~C ６Cycloalkyl, -C(O)NH-C １ -C ６ alkyl, which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C １ -C ４ alkoxy, C ３ -C ６ cycloalkyl and -NH ２ -C(O)NH-C １ -C ６ alkyl, -C(O)NH-C １ -C ６ cyanoalkyl, which may be substituted with 1 to 3 halogens, -C(O)NH-C １ -C ６ cyanoalkyl, -C(O)NH-C １ -C ６ haloalkyl, -C(O)-4- to 7-membered heterocycloalkyl having a nitrogen atom bonded thereto and optionally having 1 or 2 other heteroatoms selected from the group consisting of O, S and N, wherein the carbon atoms of said 4- to 7-membered heterocycloalkyl are halogen, cyano, nitro, hydroxyl, oxo, -NH ２ , C １ -C ７ aminocarbonyl, C １ -C ４ alkyl, which may be substituted with halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl and -C(O)NH-C １ ~C ６ Optionally substituted with 1 to 5 substituents independently selected from the group consisting of alkyl C １ ~C ４ alkyl, and C ３ ~C ６ Optionally substituted with 1 to 4 substituents independently selected from the group consisting of cycloalkyl, and in the formula, the other N of the 4- to 7-membered heterocycloalkyl is, if the valence allows, hydrogen, -NH ２ , C １ ~C ７ aminocarbonyl, -SO ２ C １ ~C ４ alkyl, -SO ２ C １ ~C ４ haloalkyl and C １ ~C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, C １ ~C ４ alkoxy, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, -C(O)NH-C １ ~C ６ alkyl and -C(O)NH-C １ ~C ６ Optionally substituted with 1 to 5 substituents independently selected from the group consisting of haloalkyl C １ ~C ４-C(O)-4- to 7-membered heterocycloalkyl, 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S, and N, substituted with a substituent selected from the group consisting of alkyl, wherein the carbon of the 5- to 10-membered heteroaryl is halogen, cyano, nitro, hydroxyl, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, oxo, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl, -C(O)NH-C １ -C ６ alkyl and -C(O)NH-C １ -C ６ haloalkyl, and which may be independently substituted with 1 to 5 substituents selected from the group consisting of C １ -C ４ alkyl, C ３ -C ６ cycloalkyl, C １ -C ４ haloalkyl, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ and -C(O)NH-C ３ -C ６Optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cycloalkyl, wherein any N of said heteroaryl, if the valence allows, is hydrogen, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C ３ -C ６ cycloalkyl, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl and -C(O)NH-C １ -C ６ alkyl independently selected from the group consisting of 1 to 5 substituents which may be optionally substituted, C １ -C ４ alkyl, and C ３ -C ６ cycloalkyl which may be optionally substituted with a substituent selected from the group consisting of, wherein any S of said heteroaryl may be optionally substituted with 1 or 2 oxygen atoms, 5- to 10-membered heteroaryl, phenyl which may be optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C １ -C ４ alkyl, cyano and hydroxyl, C ３ -C ６ cycloalkyl which is halogen, cyano, hydroxyl, oxo, C １ -C ４ alkoxy, C １ -C ４C which may be substituted with 1 to 3 groups selected from the group consisting of halogen and cyano １ -C ４ alkyl, C １ -C ４ haloalkyl, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl, -C(O)NH-C １ -C ６ alkyl, -C(O)NH-C １ -C ６ haloalkyl, C ２ -C ６ alkenyl and C ２ -C ６ alkynyl, which may be substituted with 1 to 5 substituents independently selected from the group consisting of C ３ -C ６ cycloalkyl, and 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S, B, and N, wherein the heterocycloalkyl in the formula may be benzo-fused, and the carbon atoms of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused are halogen, cyano, nitro, hydroxyl, oxo, and C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, C ３ -C ６ cycloalkyl, -NH ２ , C １ -C ７Aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, -C(O)NH-C １ ~C ６ alkyl and -C(O)NH-C １ ~C ６ haloalkyl, optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, optionally substituted with 1 to 4 substituents independently selected from the group consisting of, wherein any B of said 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl is substituted with hydroxyl if the valence permits, and any N of said 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl is hydrogen, -NH ２ , C １ ~C ７ aminocarbonyl, -SO ２ C １ ~C ４ alkyl, -SO ２ C １ ~C ４ haloalkyl, -C(O)-NH ２ , C １ ~C ４ alkyl, which is halogen, cyano, hydroxyl, ethynyl, C １ ~C ４ alkoxy, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ Alkyl, -S(O)C １ ~C ４ Alkyl, -SO ２ C １ ~C ４ Alkyl, -C(O)NH-C ３ ~C ６ Cycloalkyl and -C(O)NH-C １ ~C ６ Optionally substituted with 1 to 5 substituents independently selected from the group consisting of haloalkyl, C １ ~C ４ Alkyl, C ３ ~C ６ Cycloalkyl, 5- to 6-membered heteroaryl, and phenyl, which may be substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C １ ~C ４ Optionally substituted with 1 to 3 substituents independently selected from the group consisting of alkyl, cyano, and hydroxyl, and is selected from the group consisting of phenyl substituted with substituents, wherein any S of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl optionally fused with benzocycloalkyl may be optionally substituted with 1 or 2 oxygen atoms, and is optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ６ Alkyl, (iii) C ３ ~C ６ Cycloalkyl, which may be substituted with 1 to 3 groups selected from the group consisting of halogen, cyano, hydroxyl, oxo, carboxyl, C １ ~C ４ Alkoxy, C １ ~C ４ Alkyl, which may be substituted with 1 to 3 groups selected from the group consisting of halogen and cyano, C １ ~C ４ Alkyl, C １ ~C ４ Haloalkyl, -NH ２ , C １ ~C ７ Aminocarbonyl, -NH(C １ ~C ４ Alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, -C(O)NH-C １ ~C ６ alkyl, -C(O)NH-C １ ~C ６ haloalkyl, C ２ ~C ６ alkenyl optionally substituted with 1 to 3 halogens, C ２ ~C ６ alkenyl, and C ２ ~C ６ alkynyl, optionally substituted with 1 to 5 substituents independently selected from the group consisting of C ３ ~C ６ cycloalkyl, (iv) a 6-membered aryl or a 5- to 10-membered heteroaryl having 1, 2 or 3 heteroatoms selected from the group consisting of O, S and N, wherein the carbon atoms of said 6-membered aryl and 5- to 10-membered heteroaryl are halogen, cyano, nitro, hydroxyl, C １ ~C ４ alkyl which is halogen, cyano, hydroxyl, oxo, C １ ~C ４ alkoxy, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ Cycloalkyl and -C(O)NH-C １ -C ６ Optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ -C ４ Alkyl, C ３ -C ６ Cycloalkyl, C １ -C ４ Haloalkyl, C １ -C ４ Alkoxy, -NH ２ , -NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ , and -C(O)NH-C ３ -C ６ Optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cycloalkyl and -C(O)NH-C １ -C ４ Alkyl, where any N of the heteroaryl is, if valence permits, hydrogen, and C １ -C ４ Alkoxy, -NH ２ , C １ -C ７ Aminocarbonyl, -NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ , -SC １ -C ４ Alkyl, -S(O)C １ -C ４ Alkyl, -SO ２ C １ -C ４ Alkyl, -C(O)NH-C ３ -C ６ Cycloalkyl and -C(O)NH-C １ -C ６ Optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ -C ４A 6-membered aryl or 5- to 10-membered heteroaryl, which may be substituted with a substituent selected from the group consisting of alkyl, (v) A 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S, and N, wherein the heterocycloalkyl in the formula may be benzo-fused, and the carbon of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl that may be benzo-fused is halogen, cyano, nitro, hydroxyl, oxo, C １ - C ４ alkoxy, C １ - C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ - C ４ alkoxy, C ３ - C ６ cycloalkyl, -NH ２ , C １ - C ７ aminocarbonyl, -NH(C １ - C ４ alkyl), -N(C １ - C ４ alkyl) ２ , -SC １ - C ４ alkyl, -S(O)C １ - C ４ alkyl, -SO ２ C １ - C ４ alkyl, -C(O)NH-C ３ - C ６ cycloalkyl, -C(O)NH-C １ - C ６ alkyl and -C(O)NH-C １ - C ６ haloalkyl, and may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ - C ４ alkyl, may be substituted with 1 to 4 substituents independently selected from the group consisting of alkyl, and any N of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl that may be benzo-fused, if the valence allows, is hydrogen, -NH ２ , C １ - C ７ Aminocarbonyl, -SO ２ C １ -C ４ Alkyl, -SO ２ C １ -C ４ Haloalkyl, -SO ２ NH(C １ -C ４ Alkyl), -SO ２ N(C １ -C ４ Alkyl) ２ , -C(O)-NH ２ C １ -C ４ Alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ Alkoxy, C ３ -C ６ Cycloalkyl, -NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ , -SC １ -C ４ Alkyl, -S(O)C １ -C ４ Alkyl, -SO ２ C １ -C ４ Alkyl, -C(O)NH-C ３ -C ６ Cycloalkyl and -C(O)NH-C １ -C ６ Haloalkyl may be independently selected from the group consisting of 1 to 5 substituents which may be substituted C １ -C ４ Alkyl, C ３ -C ６ Cycloalkyl, 5- to 6-membered heteroaryl, and phenyl which is halogen, C １ -C ４It is substituted with a substituent selected from the group consisting of phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of alkyl, cyano, and hydroxyl, and any S of the 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl optionally benzo-fused is optionally substituted with 1 or 2 oxygen atoms, 4- to 7-membered heterocycloalkyl, and (vi) -NR １１ R １２ selected from the group consisting of wherein R １１ is hydrogen, C １ to C ６ alkyl, C ２ to C ６ alkenyl, C ２ to C ６ alkynyl, C ３ to C ６ cycloalkyl, C ４ to C ７ alkylcycloalkyl, C １ to C ７ alkylcarbonyl, C １ to C ７ aminocarbonyl, and C ２ to C ５ alkoxycarbonyl, and is selected from the group consisting of R １２ is hydrogen, C １ to C ６ alkyl which is halogen, cyano, nitro, hydroxyl, oxo, C ３ to C ６ cycloalkyl, C １ to C ４ alkoxy, -NH ２ 、C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ 、-SC １ to C ４ alkyl, -S(O)C １ to C ４ alkyl and -SO ２ C １ -C ４ optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ -C ６ alkyl, C ３ -C ６ cycloalkyl, -C(O)-C １ -C ６ alkyl, which is halogen, cyano, nitro, hydroxyl, oxo, C ３ -C ６ cycloalkyl, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl and -SO ２ C １ -C ４ optionally substituted with 1 to 5 substituents independently selected from the group consisting of -C(O)-C １ -C ６ alkyl, 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group of O, S and N, said heterocycloalkyl may be benzo-fused, wherein the carbon of said 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl is halogen, cyano, nitro, hydroxyl, oxo, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, -C(O)NH-C １ ~C ６ alkyl and -C(O)NH-C １ ~C ６ haloalkyl, optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl and C ３ ~C ６ cycloalkyl, optionally substituted with 1 to 4 substituents independently selected from the group consisting of. Any N of the 4- to 7-membered heterocycloalkyl or benzo-fused 4- to 7-membered heterocycloalkyl, if the valence allows, is hydrogen, C １ ~C ４ alkyl, which is halogen, cyano, hydroxyl, acetylenyl, C １ ~C ４ alkoxy, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, and -C(O)NH-C １ ~C ６ alkyl, optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, C ３ ~C ６ cycloalkyl, 5- to 6-membered heteroaryl, and phenyl, which may be substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C １ ~C ４ alkyl, cyano, and hydroxyl, and is substituted with a substituent selected from the group consisting of phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C １ ~C ４ alkyl, and wherein any S of said 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl optionally benzo-fused may be substituted with 1 or 2 oxygen atoms, and 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S, and N, and wherein the carbon of said 5- to 10-membered heteroaryl is halogen, cyano, nitro, hydroxyl, C １ ~C ４ alkyl, which is halogen, cyano, hydroxyl, oxo, C １ ~C ４ alkoxy, -NH ２ 、C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ 、-SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, and -C(O)NH-C １ ~C ６ alkyl, and is optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, C ３ ~C ６ cycloalkyl, C １ ~C ４ haloalkyl, C １ ~C ４alkoxy, -NH ２ , -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -C(O)NH-C ３ ~C ６ cycloalkyl, and -C(O)NH-C １ ~C ６ alkyl, and may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of, wherein any N of said heteroaryl, if the valence allows, is hydrogen, C １ ~C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ ~C ４ alkoxy, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl and -C(O)NH-C １ ~C ６ alkyl, and may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, and C ３ ~C ６ cycloalkyl, and is selected from the group consisting of 5- to 10-membered heteroaryl which may be substituted with a substituent selected from the group consisting of, or R １０And W, together with the nitrogen to which they are attached, may form a 4- to 7-membered ring optionally containing 1 to 2 heteroatoms selected from the group consisting of N, S, and O, wherein the carbon of said ring is cyano, hydroxyl, oxo, halogen, C １ -C ２ alkoxy, N,N-di-C １ -C ４ -alkylaminocarboxyl, N-C １ -C ４ -alkylaminocarboxyl, C １ -C ７ aminocarboxyl, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, C ３ -C ６ cycloalkyl, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ and -C(O)NH-C ３ -C ６ cycloalkyl, and is independently selected from the group consisting of 1 to 5 substituents and may be substituted C １ -C ４ alkyl, C ３ -C ６ cycloalkyl which is halogen, cyano, hydroxyl and C １ -C ４ alkoxy and may be substituted with 1 to 3 substituents selected from the group consisting of C ３ -C ６ cycloalkyl, -C(O)NH-C ３ -C ６ cycloalkyl, -C(O)NH-C １ -C ６ alkyl, -C(O)NH-C １ -C ６ haloalkyl, 5- to 6-membered heteroaryl, and phenyl which is halogen, C １ -C ４ Alkyl, cyano, hydroxyl, C １ ~C ２ Alkoxy, N,N-di-C １ ~C ４ -Alkylaminocarboxyl, N-C １ ~C ４ -Alkylaminocarboxyl and C １ ~C ７ A phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of aminocarboxyl, and which may be substituted with 1 to 4 substituents independently selected, wherein any N of the 4- to 7-membered ring is hydrogen, C １ ~C ４ An alkyl which is halogen, cyano, hydroxyl, C ３ ~C ６ Cycloalkyl, C １ ~C ４ Alkoxy, -NH ２ , C １ ~C ７ Aminocarbonyl, -NH(C １ ~C ４ Alkyl), -N(C １ ~C ４ Alkyl) ２ And -C(O)NH-C ３ ~C ６ Cycloalkyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ Alkyl, C ３ ~C ６ A cycloalkyl which is halogen, cyano, hydroxyl, C １ ~C ４ Alkoxy, -C(O)NH-C ３ ~C ６ Cycloalkyl and -C(O)NH-C １ ~C ６ Alkyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of C ３ ~C ６ Cycloalkyl, 5- to 6-membered heteroaryl, and a phenyl which is halogen, C １ ~C ４It is substituted with a substituent selected from the group consisting of phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of alkyl, cyano, and hydroxyl, and any S in the 4- to 7-membered ring may be substituted with 1 or 2 oxygen atoms, and also Y is C １ -C ６ alkyl, which is halogen, cyano, hydroxyl, oxo, C ３ -C ６ cycloalkyl, C １ -C ４ alkoxy, ethynyl, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -SO ２ NH(C １ -C ４ alkyl), -SO ２ N(C １ -C ４ alkyl) ２ , -SO ２ NH(C １ -C ４ haloalkyl), -C(O)NH-C ３ -C ６ cycloalkyl which is halogen, hydroxyl, cyano, and C １ -C ４ alkyl which is halogen, cyano, hydroxyl, C １ -C ４ alkoxy and -NH ２ and may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ -C ４-C(O)NH-C, which may be substituted with 1 to 3 substituents independently selected from the group consisting of alkyl ３ -C ６ -C(O)NH-C, cycloalkyl １ -C ６ -C(O)NH-C, alkyl, which may be substituted with 1 to 3 halogens １ -C ６ -C(O)NH-C, cyanoalkyl １ -C ６ -C(O)NH-C, haloalkyl, phenyl, which may be substituted with halogen, cyano, nitro, hydroxyl, C １ -C ４ -C, alkyl, which may be substituted with halogen, cyano, hydroxyl, C ３ -C ６ -C, cycloalkyl, C １ -C ４ -C, haloalkyl, C １ -C ４ -C, alkoxy, -NH ２ -NH(C １ -C ４ -N(C １ -C ４ -alkyl), and -C(O)NH-C ２ -C ３ -C ６ -C, cycloalkyl, which may be substituted with 1 to 3 substituents independently selected from the group consisting of alkyl １ -C ４ -C, alkyl, and C ３ -C ６ -C, cycloalkyl, which may be substituted with halogen, cyano, hydroxyl, oxo, C １ -C ４ -C, alkoxy, -NH ２ -C, C １ -C ７ -C, aminocarbonyl, -NH(C １ -C ４ -N(C １ -C ４ -alkyl), and -SC ２ -C １ -C ４ -C, alkyl, -S(O)C １ -C ４ -C, -SO ２ -C １ -C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, -C(O)NH-C １ ~C ６ alkyl, C ２ ~C ６ alkenyl and C ２ ~C ６ C optionally substituted with 1 to 5 substituents independently selected from the group consisting of alkynyl ３ ~C ６ cycloalkyl, phenyl optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, wherein the carbon of said 5- to 10-membered heteroaryl is halogen, cyano, nitro, hydroxyl, C １ ~C ４ alkyl which is halogen, cyano, hydroxyl, oxo, C １ ~C ４ alkoxy, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl and -C(O)NH-C １ ~C ６ C optionally substituted with 1 to 5 substituents independently selected from the group consisting of alkyl １ ~C ４ alkyl, C ３ ~C ６ cycloalkyl, C １ ~C ４ haloalkyl, C １ ~C ４alkoxy, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -C(O)NH-C ３ ~C ６ cycloalkyl and -C(O)NH-C １ ~C ６ alkyl, and may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of, wherein any N of said heteroaryl, if the valence allows, is hydrogen, C １ ~C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ ~C ４ alkoxy, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl and -C(O)NH-C １ ~C ６ alkyl, and may be substituted with 1 - 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, and C ３ ~C ６A 5- to 10-membered heteroaryl substituted with a substituent selected from the group consisting of cycloalkyl, and a 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S, and N, wherein said heterocycloalkyl may be benzo-fused, and the carbon of said 4- to 7-membered heterocycloalkyl or benzo-fused 4- to 7-membered heterocycloalkyl is halogen, cyano, nitro, hydroxyl, oxo, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl and -C(O)NH-C １ -C ６ alkyl independently selected from the group consisting of 1 to 5 substituents which may be substituted, and C １ -C ４ alkyl and C ３ -C ６ cycloalkyl independently selected from the group consisting of 1 to 4 substituents which may be substituted, wherein any N of said 4- to 7-membered heterocycloalkyl or benzo-fused 4- to 7-membered heterocycloalkyl, if the valence permits, is hydrogen, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, and -C(O)NH-C １ ~C ６ alkyl, which may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, C ３ ~C ６ cycloalkyl and 5- to 6-membered heteroaryl, and the 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl which may be benzo-fused, wherein any S of the 4- to 7-membered heterocycloalkyl may be substituted with 1 or 2 oxygen atoms, which may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ６ alkyl, a compound of formula (I), or a salt thereof.

2. The compound according to claim 1, wherein W is (i) hydrogen, (ii) C １ ~C ６ alkyl which may be substituted with 1 to 3 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, oxo, C １ ~C ４ alkoxy, C ３ ~C ６ cycloalkyl, ethynyl, -NH ２ , C １ ~C ７Aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, hydroxyl, cyano and C １ ~C ４ alkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C １ ~C ４ alkoxy, C ３ ~C ６ cycloalkyl and -NH ２ and which may be substituted with 1 to 3 substituents independently selected from the group consisting of -C(O)NH-C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, -C(O)NH-C １ ~C ６ alkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C １ ~C ４ alkoxy, C ３ ~C ６ cycloalkyl and -NH ２ and which may be substituted with 1 to 3 substituents independently selected from the group consisting of -C(O)NH-C １ ~C ６ alkyl, -C(O)NH-C １ ~C ６ cyanoalkyl which may be substituted with 1 to 3 halogens and which may be substituted with 1 to 3 substituents independently selected from the group consisting of -C(O)NH-C １ ~C ６ cyanoalkyl, -C(O)NH-C １ ~C ６Haloalkyl, -C(O)-4- to 7-membered heterocycloalkyl having a nitrogen atom bonded thereto and optionally having one or two other heteroatoms selected from the group consisting of O, S and N, wherein the carbon atoms of said 4- to 7-membered heterocycloalkyl are halogen, cyano, nitro, hydroxyl, oxo, -NH ２ , C １ -C ７ -aminocarbonyl, C １ -C ４ -alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ -alkoxy, -NH ２ , C １ -C ７ -aminocarbonyl, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -SC １ -C ４ -alkyl, -S(O)C １ -C ４ -alkyl, -SO ２ C １ -C ４ -alkyl, -C(O)NH-C ３ -C ６ -cycloalkyl and -C(O)NH-C １ -C ６ -alkyl which may be independently substituted with 1 to 5 substituents selected from the group consisting of C １ -C ４ -alkyl, and C ３ -C ６ -cycloalkyl which may be independently substituted with 1 to 4 substituents, wherein the other N of said 4- to 7-membered heterocycloalkyl, if valence permits, is hydrogen, -NH ２ , C １ -C ７ -aminocarbonyl, -SO ２ C １ -C ４ -alkyl, -SO ２ C １ -C ４ -haloalkyl and C １ -C ４ alkyl which is substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, ethynyl, C １ to C ４ alkoxy, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ , -SC １ to C ４ alkyl, -S(O)C １ to C ４ alkyl, -SO ２ C １ to C ４ alkyl, -C(O)NH-C ３ to C ６ cycloalkyl, -C(O)NH-C １ to C ６ alkyl and -C(O)NH-C １ to C ６ haloalkyl and which may be substituted with a substituent selected from the group consisting of C １ to C ４ alkyl is -C(O)-4- to 7-membered heterocycloalkyl, 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, wherein the carbon of said 5- to 10-membered heteroaryl is halogen, cyano, nitro, hydroxyl, C １ to C ４ alkyl which is halogen, cyano, hydroxyl, oxo, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ , -SC １ to C ４ alkyl, -S(O)C １ to C ４ alkyl, -SO ２ C １ to C ４ alkyl, -C(O)NH-C ３ to C ６ cycloalkyl, -C(O)NH-C １ to C ６ alkyl and -C(O)NH-C １ to C ６ optionally substituted with 1 to 5 substituents independently selected from the group consisting of haloalkyl, C １ to C ４ alkyl, C ３ to C ６ cycloalkyl, C １ to C ４ haloalkyl, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ and -C(O)NH-C ３ to C ６ optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cycloalkyl, and wherein any N of said heteroaryl, if valency permits, is hydrogen, C １ to C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C ３ to C ６ cycloalkyl, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ , -SC １ to C ４ alkyl, -S(O)C １ to C ４ alkyl, -SO ２ C １ to C ４ alkyl, -C(O)NH-C ３ to C ６Cycloalkyl and -C(O)NH-C １ -C ６ Optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ -C ４ alkyl, and C ３ -C ６ Optionally substituted with a substituent selected from the group consisting of cycloalkyl, and 5- to 10-membered heteroaryl, phenyl, where any S of the heteroaryl may be substituted with 1 or 2 oxygen atoms, phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C １ -C ４ alkyl, cyano and hydroxyl, C ３ -C ６ cycloalkyl optionally substituted with halogen, cyano, hydroxyl, oxo, C １ -C ４ alkoxy, C １ -C ４ alkyl optionally substituted with 1 to 3 groups selected from the group consisting of halogen and cyano, C １ -C ４ alkyl, C １ -C ４ haloalkyl, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl, -C(O)NH-C １ -C ６ alkyl, -C(O)NH-C １ -C ６ haloalkyl, C ２ -C ６ Alkenyl and C ２ -C ６ optionally substituted with 1 to 5 substituents independently selected from the group consisting of alkynyl C ３ -C ６ cycloalkyl, and 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group of O, S, B and N, wherein said heterocycloalkyl may be benzo-fused, and the carbon of said 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl is halogen, cyano, nitro, hydroxyl, oxo, and C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, C ３ -C ６ cycloalkyl, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl, -C(O)NH-C １ -C ６ alkyl and -C(O)NH-C １ -C ６ optionally substituted with 1 to 5 substituents independently selected from the group consisting of haloalkyl C １ -C ４It may be substituted with 1 to 4 substituents independently selected from the group consisting of alkyl. In the formula, any B of the 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl is substituted with hydroxyl if the valence allows. In the formula, any N of the 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl is hydrogen, -NH ２ , C １ ~C ７ -aminocarbonyl, -SO ２ C １ ~C ４ -alkyl, -SO ２ C １ ~C ４ -haloalkyl, -C(O)-NH ２ , C １ ~C ４ -alkyl which is halogen, cyano, hydroxyl, acetylenyl, C １ ~C ４ -alkoxy, -NH(C １ ~C ４ -alkyl), -N(C １ ~C ４ -alkyl) ２ , -SC １ ~C ４ -alkyl, -S(O)C １ ~C ４ -alkyl, -SO ２ C １ ~C ４ -alkyl, -C(O)NH-C ３ ~C ６ -cycloalkyl and -C(O)NH-C １ ~C ６ -haloalkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ -alkyl, C ３ ~C ６ -cycloalkyl, 5- to 6-membered heteroaryl, and phenyl which are halogen, C １ ~C ４ It is substituted with a substituent selected from the group consisting of phenyl, which may be substituted with 1 to 3 substituents independently selected from the group consisting of alkyl, cyano, and hydroxyl. In the formula, any S of the 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl optionally fused with benzo is 4- to 7-membered heterocycloalkyl, which may be substituted with 1 to 5 substituents independently selected from the group consisting of those optionally substituted with 1 or 2 oxygen atoms, C １ ~C ６ alkyl, (iii) C ３ ~C ６ cycloalkyl, which is halogen, cyano, hydroxyl, oxo, carboxyl, C １ ~C ４ alkoxy, C １ ~C ４ alkyl, which may be substituted with 1 to 3 groups selected from the group consisting of halogen and cyano, C １ ~C ４ alkyl, C １ ~C ４ haloalkyl, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ , -C(O)NH-C ３ ~C ６ cycloalkyl, -C(O)NH-C １ ~C ６ , -C(O)NH-C １ ~C ６ , -C(O)NH-C ２ ~C ６ alkenyl, which may be substituted with 1 to 3 halogens, C ２ ~C ６ Alkenyl, and C ２ to C ６ Cycloalkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of alkynyl, and C ３ to C ６ Cycloalkyl, (iv) 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, wherein the carbon of the 5- to 10-membered heteroaryl is halogen, cyano, nitro, hydroxyl, C １ to C ４ Alkyl which is halogen, cyano, hydroxyl, oxo, C １ to C ４ Alkoxy, -NH ２ , C １ to C ７ Aminocarbonyl, -NH(C １ to C ４ Alkyl), -N(C １ to C ４ Alkyl) ２ , -SC １ to C ４ Alkyl, -S(O)C １ to C ４ Alkyl, -SO ２ C １ to C ４ Alkyl, -C(O)NH-C ３ to C ６ Cycloalkyl and -C(O)NH-C １ to C ６ Alkyl which may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ to C ４ Alkyl, C ３ to C ６ Cycloalkyl, C １ to C ４ Haloalkyl, C １ to C ４ Alkoxy, -NH ２ , -NH(C １ to C ４ Alkyl), -N(C １ to C ４ Alkyl) ２ , and -C(O)NH-C ３ to C ６Optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cycloalkyl, wherein N of the heteroaryl in the formula, if the valence allows, is hydrogen, and C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl and -C(O)NH-C １ -C ６ alkyl independently selected from the group consisting of 1 to 5 substituents, and optionally substituted with a substituent selected from the group consisting of C １ -C ４ alkyl, a 5- to 10-membered heteroaryl (v) A 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, wherein the heterocycloalkyl may be benzo-fused, and the carbon of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused is halogen, cyano, nitro, hydroxyl, oxo, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, C ３ -C ６ cycloalkyl, -NH ２ , C １ -C ７Aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, -C(O)NH-C １ ~C ６ alkyl and -C(O)NH-C １ ~C ６ haloalkyl, optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, optionally substituted with 1 to 4 substituents independently selected from the group consisting of, and wherein any N of said 4- to 7-membered heterocycloalkyl or optionally benzo-fused 4- to 7-membered heterocycloalkyl, if the valence allows, is hydrogen, -NH ２ , C １ ~C ７ aminocarbonyl, -SO ２ C １ ~C ４ alkyl, -SO ２ C １ ~C ４ haloalkyl, -C(O)-NH ２ , C １ ~C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, C １ ~C ４ alkoxy, C ３ ~C ６ cycloalkyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl and -C(O)NH-C １ -C ６ optionally substituted with 1 to 5 substituents independently selected from the group consisting of haloalkyl, C １ -C ４ alkyl, C ３ -C ６ cycloalkyl, 5- to 6-membered heteroaryl, and phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C １ -C ４ alkyl, cyano and hydroxyl, and is selected from the group consisting of substituents, wherein any S of said 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl which may be benzo-fused may be substituted with 1 or 2 oxygen atoms, 4- to 7-membered heterocycloalkyl, and (vi) -NR １１ R １２ selected from the group consisting of, wherein R １１ is hydrogen, C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C ３ -C ６ cycloalkyl, C ４ -C ７ alkylcycloalkyl, C １ -C ７ alkylcarbonyl, C １ -C ７ aminocarbonyl, and C ２ -C ５ alkoxycarbonyl, and is selected from the group consisting of R １２ is hydrogen, C １ -C ６ alkyl which is halogen, cyano, nitro, hydroxyl, oxo, C ３ -C ６ Cycloalkyl, C １ ~C ４ Alkoxy, -NH ２ , C １ ~C ７ Aminocarbonyl, -NH(C １ ~C ４ Alkyl), -N(C １ ~C ４ Alkyl) ２ , -SC １ ~C ４ Alkyl, -S(O)C １ ~C ４ Alkyl and -SO ２ C １ ~C ４ Alkyl which may be independently substituted with 1 to 5 substituents selected from the group consisting of C １ ~C ６ Alkyl, C ３ ~C ６ Cycloalkyl, -C(O)-C １ ~C ６ Alkyl, wherein the alkyl is halogen, cyano, nitro, hydroxyl, oxo, C ３ ~C ６ Cycloalkyl, C １ ~C ４ Alkoxy, -NH ２ , C １ ~C ７ Aminocarbonyl, -NH(C １ ~C ４ Alkyl), -N(C １ ~C ４ Alkyl) ２ , -SC １ ~C ４ Alkyl, -S(O)C １ ~C ４ Alkyl and -SO ２ C １ ~C ４ Alkyl which may be independently substituted with 1 to 5 substituents selected from the group consisting of -C(O)-C １ ~C ６Alkyl, 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group of O, S and N, said heterocycloalkyl may be benzo-fused, and in the formula, the carbon of said 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl which may be benzo-fused is halogen, cyano, nitro, hydroxyl, oxo, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl, -C(O)NH-C １ -C ６ alkyl and -C(O)NH-C １ -C ６ haloalkyl, and may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ -C ４ alkyl and C ３ -C ６ cycloalkyl, and may be substituted with 1 to 4 substituents independently selected from the group consisting of, and any N of said 4- to 7-membered heterocycloalkyl or 4- to 7-membered heterocycloalkyl which may be benzo-fused, if the valence permits, is hydrogen, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, and -C(O)NH-C １ ~C ６ alkyl independently selected from the group consisting of 1 to 5 substituents which may be substituted, C １ ~C ４ alkyl, C ３ ~C ６ cycloalkyl, 5- to 6-membered heteroaryl, and phenyl which may be substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C １ ~C ４ alkyl, cyano and hydroxyl, a 4- to 7-membered heterocycloalkyl or a 4- to 7-membered heterocycloalkyl which may be benzofused, wherein any S of the 4- to 7-membered heterocycloalkyl may be substituted with 1 or 2 oxygen atoms, and a 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, wherein the carbon of the 5- to 10-membered heteroaryl is halogen, cyano, nitro, hydroxyl, C １ ~C ４ alkyl which is halogen, cyano, hydroxyl, oxo, C １ ~C ４ alkoxy, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, and -C(O)NH-C １ ~C ６ optionally substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, C ３ ~C ６ cycloalkyl, C １ ~C ４ haloalkyl, C １ ~C ４ alkoxy, -NH ２ , -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -C(O)NH-C ３ ~C ６ cycloalkyl, and -C(O)NH-C １ ~C ６ optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of C １ ~C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ ~C ４ alkoxy, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ -C ４ Alkyl, -C(O)NH-C ３ -C ６ Cycloalkyl and -C(O)NH-C １ -C ６ Optionally substituted with 1 to 5 substituents independently selected from the group consisting of alkyl, C １ -C ４ Alkyl, and C ３ -C ６ Optionally substituted with a substituent selected from the group consisting of 5- to 10-membered heteroaryl optionally substituted with 1 to 5 substituents independently selected from the group consisting of cycloalkyl and -C(O)NH-C Or R １０ And W, together with the nitrogen to which they are attached, form a 4- to 7-membered ring optionally containing 1 to 2 heteroatoms selected from the group consisting of N, S, and O, wherein the carbon of the ring is cyano, hydroxyl, oxo, halogen, C １ -C ２ Alkoxy, N,N-di-C １ -C ４ -Alkylaminocarboxyl, N-C １ -C ４ -Alkylaminocarboxyl, C １ -C ７ Aminocarboxyl, C １ -C ４ Alkyl which is halogen, cyano, hydroxyl, C ３ -C ６ Cycloalkyl, C １ -C ４ Alkoxy, -NH ２ , C １ -C ７ Aminocarbonyl, -NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ And -C(O)NH-C ３ -C ６ Optionally substituted with 1 to 5 substituents independently selected from the group consisting of cycloalkyl and -C(O)NH-C １ -C ４ Alkyl, C ３ -C ６A cycloalkyl which is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, cyano, hydroxyl and C １ to C ４ alkoxy may be a C ３ to C ６ cycloalkyl, -C(O)NH-C ３ to C ６ cycloalkyl, -C(O)NH-C １ to C ６ alkyl, -C(O)NH-C １ to C ６ haloalkyl, 5- to 6-membered heteroaryl, and phenyl which is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C １ to C ４ alkyl, cyano, hydroxyl, C １ to C ２ alkoxy, N,N-di-C １ to C ４ -alkylaminocarboxyl, N-C １ to C ４ -alkylaminocarboxyl and C １ to C ７ aminocarboxyl may be a phenyl substituted with 1 to 4 substituents independently selected from the group consisting of halogen, C １ to C ４ alkyl which is substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C ３ to C ６ cycloalkyl, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ and -C(O)NH-C ３ to C ６ cycloalkyl may be a C １ to C ４ alkyl, C ３ to C ６ A cycloalkyl group which may be substituted with 1 to 3 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, C １ ~C ４ alkoxy, -C(O)NH-C ３ ~C ６ cycloalkyl and -C(O)NH-C １ ~C ６ alkyl, and is selected from the group consisting of a C ３ ~C ６ cycloalkyl group, a 5- to 6-membered heteroaryl group, and a phenyl group which may be substituted with 1 to 3 substituents independently selected from the group consisting of halogen, C １ ~C ４ alkyl, cyano, and hydroxyl; any S in the 4- to 7-membered ring may be substituted with 1 or 2 oxygen atoms; and Y is C １ ~C ６ alkyl which may be substituted with halogen, cyano, hydroxyl, oxo, C ３ ~C ６ cycloalkyl, C １ ~C ４ alkoxy, ethynyl, -NH ２ , C １ ~C ７ aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl which may be substituted with halogen, hydroxyl, cyano, and C １ ~C ４ alkyl which may be substituted with halogen, cyano, hydroxyl, C １ ~C ４ alkoxy and -NH ２ C optionally substituted with 1 to 5 substituents independently selected from the group consisting of １ -C ４ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of alkyl ３ -C ６ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of cycloalkyl １ -C ６ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen １ -C ６ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of cyanoalkyl １ -C ６ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of haloalkyl, phenyl which is halogen, cyano, nitro, hydroxyl, C １ -C ４ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of alkyl which is halogen, cyano, hydroxyl, C ３ -C ６ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of cycloalkyl １ -C ４ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of haloalkyl １ -C ４ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of alkoxy, -NH ２ -NH(C １ -C ４ -N(C １ -C ４ -alkyl) ２ and -C(O)NH-C ３ -C ６ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of cycloalkyl １ -C ４ -alkyl, and C ３ -C ６ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of cycloalkyl which is halogen, cyano, hydroxyl, oxo, C １ -C ４ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of alkoxy, -NH ２ -C(O)NH-C optionally substituted with 1 to 3 substituents independently selected from the group consisting of aminocarbonyl, -NH(C １ -C ７ -alkyl), -N(C １ -C ４ -alkyl) １ -C ４ -alkyl), -SC ２ -SC １ -C ４ -alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl, -C(O)NH-C １ -C ６ alkyl, C ２ -C ６ alkenyl and C ２ -C ６ alkynyl, which may be substituted with 1 to 5 substituents independently selected from the group consisting of C ３ -C ６ cycloalkyl, phenyl which may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of 5- to 10-membered heteroaryl having 1 or 2 heteroatoms selected from the group consisting of O, S and N, wherein the carbon of said 5- to 10-membered heteroaryl is halogen, cyano, nitro, hydroxyl, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, oxo, C １ -C ４ alkoxy, -NH ２ , C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ , -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl and -C(O)NH-C １ -C ６ alkyl, which may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ -C ４ alkyl, C ３ -C ６ cycloalkyl, C １ to C ４ haloalkyl, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ , -C(O)NH-C ３ to C ６ cycloalkyl and -C(O)NH-C １ to C ６ alkyl, and may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of, wherein any N of said heteroaryl, if the valence allows, is hydrogen, C １ to C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ to C ４ alkoxy, -NH ２ , C １ to C ７ aminocarbonyl, -NH(C １ to C ４ alkyl), -N(C １ to C ４ alkyl) ２ , -SC １ to C ４ alkyl, -S(O)C １ to C ４ alkyl, -SO ２ C １ to C ４ alkyl, -C(O)NH-C ３ to C ６ cycloalkyl and -C(O)NH-C １ to C ６ alkyl, and may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ to C ４ alkyl, and C ３ to C ６A 5- to 10-membered heteroaryl substituted with a substituent selected from the group consisting of cycloalkyl, and a 4- to 7-membered heterocycloalkyl having 1 or 2 heteroatoms selected from the group consisting of O, S, and N, wherein the heterocycloalkyl may be benzo-fused, and wherein the carbon of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused is halogen, cyano, nitro, hydroxyl, oxo, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, oxo, C １ -C ４ alkoxy, -NH ２ -, C １ -C ７ aminocarbonyl, -NH(C １ -C ４ alkyl), -N(C １ -C ４ alkyl) ２ -, -SC １ -C ４ alkyl, -S(O)C １ -C ４ alkyl, -SO ２ C １ -C ４ alkyl, -C(O)NH-C ３ -C ６ cycloalkyl and -C(O)NH-C １ -C ６ alkyl, independently selected from the group consisting of 1 to 5 substituents which may be substituted, and C １ -C ４ alkyl and C ３ -C ６ cycloalkyl, independently selected from the group consisting of 1 to 4 substituents which may be substituted, and any N of the 4- to 7-membered heterocycloalkyl or the 4- to 7-membered heterocycloalkyl which may be benzo-fused, if the valence permits, is hydrogen, C １ -C ４ alkyl which is halogen, cyano, hydroxyl, ethynyl, C １ -C ４ alkoxy, -NH ２ -, C １ -C ７ Aminocarbonyl, -NH(C １ ~C ４ alkyl), -N(C １ ~C ４ alkyl) ２ , -SC １ ~C ４ alkyl, -S(O)C １ ~C ４ alkyl, -SO ２ C １ ~C ４ alkyl, -C(O)NH-C ３ ~C ６ cycloalkyl, and -C(O)NH-C １ ~C ６ alkyl, which may be substituted with 1 to 5 substituents independently selected from the group consisting of C １ ~C ４ alkyl, C ３ ~C ６ cycloalkyl and 5- to 6-membered heteroaryl, and is substituted with a substituent selected from the group consisting of 4- to 7-membered heterocycloalkyl which may be optionally benzo-fused, and in which any S of the 4- to 7-membered heterocycloalkyl may be substituted with 1 or 2 oxygen atoms, C １ ~C ６ alkyl, The compound according to claim 1, or a salt thereof.

3. Z is CR ２ , R １ is hydrogen, R ２ is trifluoromethyl, R ３ is hydrogen, and also R ４ is trifluoromethyl, The compound according to claim 1, or a salt thereof.

4. Z is CR ２ , R １ is hydrogen, R ２ is trifluoromethyl, R ３ is hydrogen, and also R ４The compound according to claim 1, or a salt thereof, which is bromo.

5. Z is CR ２ and R １ is hydrogen, R ２ is trifluoromethyl, R ３ is hydrogen, and also R ４ is difluoromethyl, the compound according to claim 1, or a salt thereof.

6. Z is CR ２ and R １ is hydrogen, R ２ is trifluoromethyl, R ３ is hydrogen, R ４ is methoxy, the compound according to claim 1, or a salt thereof.

7. Z is CR ２ and R １ is hydrogen, R ２ is trifluoromethyl, R ３ is hydrogen, R ４ is fluoro, the compound according to claim 1, or a salt thereof.

8. Z is CR ２ and R １ is hydrogen, R ２ is chloro, R ３ is hydrogen, and also R ４ is trifluoromethyl, the compound according to claim 1, or a salt thereof.

9. Z is CR ２ and R １ is hydrogen, R ２ is chloro, R ３ is hydrogen, and also R ４ is difluoromethyl, the compound according to claim 1, or a salt thereof.

10. Z is CR ２ and R １ is hydrogen, R ２ is trifluoromethoxy, R ３ is hydrogen, R ４ The compound according to claim 1, or a salt thereof, wherein A is difluoromethyl. **Claim 11** A １ is CF ３ The compound according to any one of claims 1 to 10, or a salt thereof, wherein A is CF. **Claim 12** A １ is CHF ２ The compound according to any one of claims 1 to 10, or a salt thereof, wherein A is CHF. **Claim 13** The compound according to claim 1 or 2, wherein Z is N. **Claim 14** The compound according to claim 1, which is rel-(S)-4-(5-(6-(difluoromethyl)-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(6-bromo-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(4,6-bis(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(4,6-bis(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(6-Methoxy-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(6-(Difluoromethyl)-4-(trifluoromethoxy)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(R)-4-(5-(6-Bromo-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(6-Bromo-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(R)-4-(5-(4,6-Bis(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(4,6-Bis(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(R)-4-(5-(6-Methoxy-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(6-Methoxy-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(R)-4-(5-(4-Chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(4-Chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(R)-4-(5-(4-Chloro-6-(difluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(4-Chloro-6-(difluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(R)-4-(5-(6-Fluoro-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, rel-(S)-4-(5-(6-Fluoro-4-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide, 4-((R*)-5-(4-Chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((trans)-3-(trifluoromethyl)cyclobutyl)benzamide, 4-((S*)-5-(4-Chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((trans)-3-(trifluoromethyl)cyclobutyl)benzamide, 4-((R*)-5-(4-Chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((cis)-3-(trifluoromethyl)cyclobutyl)benzamide, 4-((S*)-5-(4-Chloro-6-(trifluoromethyl)pyridin-2-yl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-((cis)-3-(trifluoromethyl)cyclobutyl)benzamide, rel-(S)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzamide, and rel-(R)-2-methyl-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(5-(trifluoromethyl)-5-(6-(trifluoromethyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzamide, The compound according to claim 1, or a salt thereof, selected from the group consisting of.

15. When Z is CR ２ then R １ is hydrogen only when R ２ is trifluoromethyl, difluoromethyl, fluoro, chloro, or bromo, R ３ is hydrogen only when one of R ２ or R ４ is any of trifluoromethyl, difluoromethyl, fluoro, chloro, or bromo, and R １ R ２ R ３ and R ４ Among them, at most three are hydrogen, the compound according to claim 1.

16. When Z is CR ２ then R １ is hydrogen only when R ２ is trifluoromethyl, difluoromethyl, or bromo, R ３ is hydrogen only when one of R ２ or R ４ is any of trifluoromethyl, difluoromethyl, or bromo, and R １ R ２ R ３ and R ４ Among them, at most three are hydrogen, the compound according to claim 1.

17. A composition comprising the compound according to claim 1, or a salt thereof, and at least one acceptable carrier.

18. Use of the compound according to claim 1, or a salt thereof, as a medicament for non-human animals.

19. Use of the compound according to claim 1, or a salt thereof, in the manufacture of a medicament for treating pests. Claim 20 Use of the compound according to claim 1 or a salt thereof in the manufacture of a medicament for treating and / or controlling ectoparasites. Claim 21 Use according to any one of claims 18 to 20, wherein the pest is a mite, a flea or a combination thereof. Claim 22 A method for treating and / or controlling a pest, optionally an ectoparasite, comprising administering a therapeutically effective amount of the compound according to claim 1 to a non-human subject in need thereof. Claim 23 The method according to claim 22, wherein the administration is once a month, quarterly, semi-annually or annually. Claim 24 The method according to claim 22 or 23, wherein the administration is oral or parenteral. Claim 25 The method according to claim 22 or 23, wherein the pest is a mite, a flea or a combination thereof.

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