Isoquinoline Derivatives and Their Use for the Treatment of Parasitic Infections - Patent application

Abstract

The present invention relates to a compound represented by general formula (I) (wherein A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Q is as defined herein), processes for preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds, as sole agents or in combination with other active ingredients, to manufacture pharmaceutical compositions for the treatment, control and / or prevention of diseases, particularly helminth infections. [Formula 1] TIFF2022542682000112.tif47157

Description

[Technical Field]

[0001] The present invention relates to novel isoquinoline derivatives of general formula (I) as described and defined herein, to processes for preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, and to the use of said compounds for the manufacture of pharmaceutical compositions for the control, treatment and / or prevention of diseases, in particular infections by helminths, more particularly infections by gastrointestinal and extraintestinal nematodes in animals and humans, to formulations and methods containing such compounds as single agents or in combination with other active ingredients, for the inhibition, treatment and / or prevention of infections by helminths, more particularly infections by gastrointestinal and extraintestinal nematodes in animals and humans. [Background technology]

[0002] background The development of resistance to all commercially available anthelmintics appears to be an increasing problem in veterinary medicine. The widespread use of anthelmintics to manage nematode suppression has significantly selected for highly resistant roundworm populations. Therefore, the spread of resistance to all anthelmintic classes threatens effective roundworm control in cattle, goats, sheep, and horses. Furthermore, the current successful prevention of canine heartworm disease, which relies solely on the use of macrocyclic lactones, is at risk due to reported loss of efficacy for multiple macrocyclic lactones in some areas of the United States—particularly in areas with a high heartworm burden for infection. Finally, experimental infection studies with Dirofilaria immitis larvae from cases of suspected loss of efficacy in the Lower Mississippi River Delta confirmed the presence of macrocyclic lactone resistance in vivo.

[0003] Although resistance of human helminths to anthelmintics is currently thought to be rare, the spread of anthelmintic resistance in veterinary medicine, as mentioned above, needs to be considered in the treatment of human helminthiasis as well. Continuous low-dose treatment for filariasis may result in highly resistant genotypes, and resistance has already been reported to certain anthelmintics (e.g., praziquantel, benzimidazoles, and niclosamide).

[0004] Therefore, resistance-breaking anthelmintics with new molecular mechanisms of action are urgently needed. Summary of the Invention [Problem to be solved by the invention]

[0005] The object of the present invention is to provide compounds that can be used as anthelmintics in the medical field, in particular in the veterinary field, for the control, treatment and / or prevention of helminth infections in animals and humans, which have sufficient or improved anthelmintic activity against a wide range of helminths, in particular at relatively low doses, preferably without any adverse toxic effects on the treated organisms.

[0006] Certain isoquinoline-3-carboxamides are described in DE 19746287 / US 6093730 as prolyl-4-hydroxylase inhibitors.

[0007] Bioorganic & Medicinal Chemistry Letters 2005, 15(3), 733-736 describes 1-(phenyl)isoquinoline-3-carboxamides as a new class of subtype-selective inhibitors of the thyrotropin-releasing hormone (TRH) receptor.

[0008] WO 2004099206 claims isoquinoline-3-carboxamides as α7 nicotinic acetylcholine receptor agonists.

[0009] WO 2004108681 describes the use of isoquinoline-3-carboxamides in mediating hypoxia inducible factor and increasing endogenous erythropoietin.

[0010] WO 2005014533 claims isoquinoline-3-carboxamides as antagonists of factor IX and / or factor XI.

[0011] WO 2007090068 claims cyanoisoquinoline-3-carboxamides that stabilize hypoxia-inducible factors.

[0012] US 20060217416 claims isoquinoline-3-carboxamides suitable for use in mediating hypoxia inducible factor and treating erythropoietin-associated conditions.

[0013] US 20120101125 relates to substituted isoquinoline-3-carboxamides useful as inhibitors of β-secretase.

[0014] WO 2018087036 describes quinoline-3-carboxamides and their use as anthelmintics in medicine, especially in the veterinary field.

[0015] However, the state of the art does not describe the novel isoquinoline derivatives of general formula (I) of the present invention as described and defined herein.

[0016] It has been found that the compounds of the invention have surprising and advantageous properties, which form the basis of the present invention.

[0017] In particular, the compounds of the present invention have surprisingly been found to effectively interact with the Slo-1 calcium-dependent potassium channel of nematodes. This interaction is characterized by achieving paralysis / inhibition of gastrointestinal nematodes, free-living nematodes, and filarial nematodes, and these data are shown in the biological experiments section. Therefore, the compounds of the present invention can be used as anthelmintics for the inhibition, treatment, and / or prevention of gastrointestinal and extraintestinal helminth infections, especially gastrointestinal and extraintestinal infections caused by nematodes, including filarial nematodes. The novel compounds of the present invention also exhibit high stability, which is advantageous compared to other compounds known in the prior art. [Prior art documents] [Patent documents]

[0018] [Patent Document 1] DE 19746287 [Patent Document 2] US 6093730 [Patent Document 3] WO 2004099206 [Patent Document 4] WO 2004108681 [Patent Document 5] WO 2005014533 [Patent Document 6] WO 2007090068 [Patent Document 7] US 20060217416 [Patent Document 8] US 20120101125 [Patent Document 9] WO 2018087036 [Non-patent literature]

[0019] [Non-Patent Document 1] Bioorganic & Medicinal Chemistry Letters 2005, 15(3), 733-736 [Means for solving the problem]

[0020] Description of the Invention According to a first aspect, the present invention provides a compound of general formula (I): [ka]

[0021] [During the ceremony: A is A1 or A2, [ka]

[0022] o is 0, 1, 2, 3 or 4; R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -OH, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl, -S(O)-C-C-halogenoalkyl and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms, R p is selected from the group consisting of hydrogen, C1-C4-alkyl, X and Y are CR 7 R 8 , O, S, and NR 9 wherein at least one of X and Y is independently selected from the group consisting of CR 7 R 8 or X and Y together represent -C(O)-O- and -C(O)-NR 9 -, -S(O)-NR 9 -, -SO2-NR 9 - and -SO2-O-, R 1represents hydrogen, cyano, -CHO, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, C3-C6-halogenocycloalkyl having 1 to 5 halogen atoms, C3-C4-alkenyl, C3-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6-cycloalkyl-C1-C3-alkyl, cyano-C1-C4-alkyl, -NH-C1-C4-alkyl, - N(C1-C4-alkyl)2, NH2-C1-C4-alkyl-, C1-C4-alkyl-NH-C1-C4-alkyl-, (C1-C4-alkyl)2N-C1-C4-alkyl-, C1-C4-alkyl-C(O)-, C1-C4-halogenoalkyl-C(O)- having 1 to 5 halogen atoms, C1-C4-alkoxy-C(O)-, benzyloxy-C(O)-, C1-C4-alkoxy-C1-C4-alkyl-C(O)-, -SO2-C1-C4-alkyl, and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl-C1-C4-alkyl, which may be substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, —OH, —NO2, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl) ), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms. is selected from the group consisting of R 2 teeth, Hydrogen, halogen, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2; -NR 12 R 13 ; -OR 14 ; -SR 15 , -S(O)R 15 , -SO2R 15 ; C1-C6-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or phenyl-C1-C4-alkyl, each of which is halogen, -OH, -NO2, cyano, C1-C4-alkyl-C(O)-, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -NH2, -NH(C1-C4-alkyl) optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of -C(O)-C-C-alkyl), -N(C-C-alkyl), -NH(C(O)-C-C-alkyl), -N(C-C-alkyl)(C(O)-C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, —OH, —NO2, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl) ), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl, which may be substituted by one, two or three substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; and monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, -C(O)-NH(C-C-alkyl), -C(O)-N(C-C-alkyl)2, C-C-alkyl, C-C-alkyl-C(O)-, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, hydroxy-C-C-alkyl, C-C-alkoxy-C-C-aromatic and optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, and 4- to 10-membered heterocycloalkyl. is selected from the group consisting of R 3 is hydrogen or C1-C4-alkyl, R 4 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C-C-alkyl, C-C-cycloalkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy-C-C-alkyl, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-alkyl-C(O)—, —NH, —NH(C-C-alkyl), —N(C-C-alkyl)2, —S—C-C-alkyl, —S(O)—C-C-alkyl, —SO—C-C-alkyl, preferably hydrogen and halogen, more preferably fluorine and chlorine, R 5 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C-C-alkyl, C-C-cycloalkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy-C-C-alkyl, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-alkyl-C(O)—, —NH, —NH(C-C-alkyl), —N(C-C-alkyl)2, —S—C-C-alkyl, —S(O)—C-C-alkyl, —SO—C-C-alkyl, R 6 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C-C-alkyl, C-C-cycloalkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy-C-C-alkyl, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-alkyl-C(O)—, —NH, —NH(C-C-alkyl), —N(C-C-alkyl)2, —S—C-C-alkyl, —S(O)—C-C-alkyl, —SO—C-C-alkyl, R 7 is selected from the group consisting of hydrogen, —OH, fluorine, C1-C4-alkyl and C1-C4-alkoxy, R8 is selected from the group consisting of hydrogen, —OH, fluorine, C1-C4-alkyl and C1-C4-alkoxy, or R 7 and R 8 together form an oxo group (=O), or or R 7 and R 8 together with the carbon atoms to which they are attached form a 3- to 6-membered ring selected from the group consisting of C3-C6-cycloalkyl and 3- to 6-membered heterocycloalkyl, R 9 is selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy, R 10 is selected from the group consisting of hydrogen, —OH, C1-C4-alkyl and C1-C4-alkoxy, R 11 is selected from the group consisting of hydrogen, C1-C4-alkyl and C1-C4-alkoxy, or R 10 and R 11 together with the carbon atoms to which they are attached form a 3- to 6-membered ring selected from the group consisting of C3-C6-cycloalkyl and 3- to 6-membered heterocycloalkyl, R 12 and R 13 teeth, Hydrogen, -OH, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH(-C(O)-C1-C4-alkyl), -N(C1-C4-alkyl)(-C(O)-C1-C4-alkyl), C1-C4-alkoxy, C1-C4-alkoxy-C(O)-; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)(-C(O)-C1-C4-alkyl), C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkyl having 1 to 5 halogen atoms. optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of alkoxy, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4-alkoxy)2P(=O)-; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, ... optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; phenyl, benzo-C5-C6-cycloalkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, having 1 to 5 halogen atoms; and optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms. are independently selected from the group consisting of R 14 teeth, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cyclo optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of alkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, ... optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; phenyl, which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; and monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, -C(O)-NH(C-C-alkyl), -C(O)-N(C-C-alkyl), C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, hydroxy-C-C-alkyl, C-C-alkyl having 1 to 5 halogen atoms; and optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms. is selected from the group consisting of R 15 teeth, hydrogen; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cyclo optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of alkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, ... optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; phenyl, which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; and monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, -C(O)-NH(C-C-alkyl), -C(O)-N(C-C-alkyl), C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, hydroxy-C-C-alkyl, C-C-alkyl having 1 to 5 halogen atoms; and optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms. is selected from the group consisting of Q is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl, each of which is selected from halogen, SF5, cyano, -CHO, nitro, oxo, C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C 1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-SO2-(C1-C4-alkyl), -N(SO2-[C1-C4-alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered heterocyclyl (which may be substituted by one or two substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano), -CH2-O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkoxy). methyl substituted with a 4- to 6-membered heterocyclyl which itself may be substituted by one or two substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -S-(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-(C1-C4-halogeno) having 1 to 5 halogen atoms; optionally substituted by 1, 2, 3, 4 or 5 substituents selected from the group consisting of -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C1-C4-alkyl), -CONH(C3-C6-cycloalkyl), -NHCO(C1-C4-alkyl), -NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, where Y is O, S or NR 9 If R 7, R 8 , R 10 and R 11 is not —OH or C1-C4-alkoxy, and X is O, S, or NR 9 If R 7 and R 8 is not —OH or C1-C4-alkoxy] and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0023] definition The term "substituted" means that one or more hydrogen atoms on a specified atom or group are replaced with a selection from the specified group, provided that the replacement does not exceed the normal valence of the specified atom under the existing circumstances. Combinations of substituents and / or variables are permissible.

[0024] The term "optionally substituted" means that the number of substituents can be equal to or different from zero. Unless otherwise specified, an optionally substituted group can be substituted with as many optional substituents as can be accommodated by replacing hydrogen atoms on any available carbon or nitrogen atom with non-hydrogen substituents. Generally, if present, the number of optional substituents can be 1, 2, 3, 4, or 5, particularly 1, 2, or 3.

[0025] As used herein, the term "one or more" means "1, 2, 3, 4 or 5, particularly 1, 2, 3 or 4, more particularly 1, 2 or 3, even more particularly 1 or 2", for example in the definition of substituents of compounds of general formula (I) of the present invention.

[0026] As used herein, an oxo substituent represents an oxygen atom that is attached to a carbon or sulfur atom via a double bond.

[0027] The term "ring substituent" means a substituent attached to an aromatic or non-aromatic ring that replaces an available hydrogen atom on the ring.

[0028] When a composite substituent is composed of multiple moieties, e.g., (C-C-alkoxy)-(C-C-alkyl)-, the position of a given moiety can be at any suitable position on the composite substituent, i.e., the C-C-alkoxy moiety can be bonded to any atom of the C-C-alkyl moiety of the (C-C-alkoxy)-(C-C-alkyl) group. A hyphen at the beginning or end of such a composite substituent indicates the point of attachment of the composite substituent to the rest of the molecule. For example, when a ring containing carbon atoms and optionally one or more heteroatoms such as nitrogen, oxygen, or sulfur atoms is substituted with a substituent, the substituent can be bonded to any suitable position on the ring and can be bonded to any suitable carbon atom and / or heteroatom.

[0029] As used herein, the position at which each subcomponent is connected to the remainder of the molecule may be indicated in the drawn structure by a hash symbol (#) or a dashed line in the substituent.

[0030] As used herein, the term "comprising" includes "consisting of."

[0031] Within this specification, when any item is referred to as "as mentioned herein", it means that it may be mentioned anywhere within this specification.

[0032] Terms referred to in this text have the following meanings: The term "halogen atom" means a fluorine, chlorine, bromine or iodine atom, in particular a fluorine, chlorine or bromine atom, more preferably fluorine or chlorine.

[0033] The term "C1-C6-alkyl" refers to a linear or branched, saturated, monovalent hydrocarbon group having 1, 2, 3, 4, 5, or 6 carbon atoms. The term "C1-C4-alkyl" refers to a linear or branched, saturated, monovalent hydrocarbon group having 1, 2, 3, or 4 carbon atoms, such as a methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, or tert-butyl group, or an isomer thereof. In particular, the group has 1, 2, or 3 carbon atoms ("C1-C3-alkyl"), such as a methyl, ethyl, n-propyl, or isopropyl group. The tert-butyl group is also preferred.

[0034] The term "C1-C4-hydroxyalkyl" means a straight-chain or branched, saturated, monovalent hydrocarbon radical, wherein the term "C1-C4-alkyl" is as defined above, in which one or two hydrogen atoms have been replaced by a hydroxy group, such as, for example, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl radicals.

[0035] The term "-NH(C1-C4-alkyl)" or "-N(C1-C4-alkyl)2" means a linear or branched, saturated, monovalent radical, as defined above for example methylamino, ethylamino, n-propylamino, isopropylamino, N,N-dimethylamino, N-methyl-N-ethylamino or N,N-diethylamino, where the term "C1-C4-alkyl" is as defined above.

[0036] The term "-S-C-C-alkyl", "-S(O)-C-C-alkyl" or "-SO-C-C-alkyl" is as defined above for the term "C-C-alkyl" and denotes a straight-chain or branched, saturated group, such as a methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl, n-butylsulfanyl, sec-butylsulfanyl, isobutylsulfanyl or tert-butylsulfanyl group, or a methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, sec-butylsulfinyl, isobutylsulfinyl or tert-butylsulfinyl group, or a methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, sec-butylsulfonyl, isobutylsulfonyl or tert-butylsulfonyl group.

[0037] The term "C-C-halogenoalkyl" refers to a linear or branched, saturated, monovalent hydrocarbon group, in which the term "C-C-alkyl" is defined as above, and in which one or more hydrogen atoms are replaced with identical or different halogen atoms. In particular, the halogen atoms are fluorine atoms. More particularly, all the halogen atoms are fluorine atoms ("C-C-fluoroalkyl"). The C-C-halogenoalkyl group is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl or 1,3-difluoropropan-2-yl.

[0038] The term "-S-C1-C4-halogenoalkyl", "-S(O)-C1-C4-halogenoalkyl" or "-SO2-C1-C4-halogenoalkyl" is as defined above for the term "C1-C4-halogenoalkyl" and means a linear or branched, saturated group, such as a mono-, di- or tri-fluoromethylsulfanyl, mono-, di- or tri-chloromethylsulfanyl, mono-, di- or tri-fluoroethylsulfanyl, mono-, di- or tri-chloroethylsulfanyl, mono-, di- or tri-fluoropropylsulfanyl, mono-, di- or tri-chloropropylsulfanyl, mono-, di- or tri-fluorobutylsulfanyl, mono-, di- or tri-chlorobutylsulfanyl group or a mono-, di- or tri-fluoromethylsulfinyl, mono-, di- or tri-chloro It means methylsulfinyl, mono-, di- or tri-fluoroethylsulfinyl, mono-, di- or tri-chloroethylsulfinyl, mono-, di- or tri-fluoropropylsulfinyl, mono-, di- or tri-chloropropylsulfinyl, mono-, di- or tri-fluorobutylsulfinyl, mono-, di- or tri-chlorobutylsulfinyl group, or mono-, di- or tri-fluoromethylsulfonyl, mono-, di- or tri-chloromethylsulfonyl, mono-, di- or tri-fluoroethylsulfonyl, mono-, di- or tri-chloroethylsulfonyl, mono-, di- or tri-fluoropropylsulfonyl, mono-, di- or tri-chloropropylsulfonyl, mono-, di- or tri-fluorobutylsulfonyl, mono-, di- or tri-chlorobutylsulfonyl group.

[0039] The term "C1-C4-alkoxy", as the term "C1-C4-alkyl" is defined above, means a straight-chain or branched, saturated, monovalent radical of the formula (C1-C4-alkyl)-O-, such as a methoxy, ethoxy, n-propoxy, isopropoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy group, or variants thereof.

[0040] The term "C1-C4-halogenoalkoxy" means a linear or branched, saturated, monovalent C1-C4-alkoxy group, as defined above, in which one or more hydrogen atoms are replaced by identical or different halogen atoms. In particular, the halogen atoms are fluorine atoms. The C1-C4-halogenoalkoxy group is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy.

[0041] The term "C2-C4-alkenyl" refers to a straight-chain or branched monovalent hydrocarbon radical containing one double bond and having 2, 3, or 4 carbon atoms. The C2-C4-alkenyl radical is, for example, ethenyl (or "vinyl"), prop-2-en-1-yl (or "allyl"), prop-1-en-1-yl, but-3-enyl, but-2-enyl, but-1-enyl, prop-1-en-2-yl (or "isopropenyl"), 2-methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, or 1-methylprop-1-enyl radical. In particular, the radical is allyl.

[0042] The term "C2-C4-alkynyl" refers to a straight-chain monovalent hydrocarbon group containing one triple bond and containing 2, 3, or 4 carbon atoms. The C2-C4-alkynyl group is, for example, an ethynyl, prop-1-ynyl, prop-2-ynyl (or "propargyl"), but-1-ynyl, but-2-ynyl, but-3-ynyl, or 1-methylprop-2-ynyl group. In particular, the alkynyl group is prop-1-ynyl or prop-2-ynyl.

[0043] The term "C3-C6-cycloalkyl" means a saturated, monovalent, monocyclic hydrocarbon ring ("C3-C6-cycloalkyl") containing 3, 4, 5, or 6 carbon atoms. The C3-C6-cycloalkyl group is, for example, a monocyclic hydrocarbon ring, such as a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group.

[0044] The term "C3-C6-halogenocycloalkyl" refers to a saturated, monovalent, monocyclic hydrocarbon ring, in which the term "C3-C6-cycloalkyl" is as defined above, and in which one or more hydrogen atoms are replaced by identical or different halogen atoms. In particular, the halogen atoms are fluorine or chlorine atoms. The C3-C6-halogenocycloalkyl group is, for example, a monocyclic hydrocarbon ring substituted with one or two fluorine or chlorine atoms, such as 1-fluorocyclopropyl, 2-fluorocyclopropyl, 2,2-difluorocyclopropyl, 2,3-difluorocyclopropyl, 1-chlorocyclopropyl, 2-chlorocyclopropyl, 2,2-dichlorocyclopropyl, 2,3-dichlorocyclopropyl, 2-fluoro-2-chlorocyclopropyl and 2-fluoro-3-chlorocyclopropyl groups.

[0045] The term "benzo-C5-C6-cycloalkyl" refers to a monovalent, bicyclic hydrocarbon ring in which a saturated, monovalent, monocyclic hydrocarbon ring containing 5 or 6 carbon atoms ("C5-C6-cycloalkyl") is fused to a phenyl ring. The benzo-C5-C6-cycloalkyl group is, for example, a bicyclic hydrocarbon ring, such as an indane (i.e., 2,3-dihydro-1H-indene) or tetralin (i.e., 1,2,3,4-tetrahydronaphthalene) group.

[0046] The term "spirocycloalkyl" refers to a saturated, monovalent bicyclic hydrocarbon group in which two rings share one common ring carbon atom, and the bicyclic hydrocarbon group contains 5, 6, 7, 8, 9, 10, or 11 carbon atoms, and the spirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms except the spiro carbon atom. Examples of the spirocycloalkyl group include spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[2.4]heptyl, spiro[2.5]octyl, spiro[2.6]nonyl, spiro[3.3]heptyl, spiro[3.4]octyl, spiro[3.5]nonyl, spiro[3.6]decyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.6]undecyl, and spiro[5.5]undecyl.

[0047] The term "heterocycloalkyl" means a monocyclic or bicyclic saturated or partially saturated heterocycle having a total of 4, 5, 6, 7, 8, 9 or 10 ring atoms ("4- to 10-membered heterocycloalkyl" groups), in particular 4, 5 or 6 ring atoms ("4- to 6-membered heterocycloalkyl" groups), which contains one or two identical or different ring heteroatoms from the N, O and S series, and wherein said heterocycloalkyl group can be attached to the remainder of the molecule via any one of the carbon atoms or, if present, the nitrogen atom.

[0048] The heterocycloalkyl group may be, but is not limited to, a 4-membered ring such as azetidinyl, oxetanyl, or thietanyl; or a 5-membered ring such as tetrahydrofuranyl, oxolanyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,1-dioxidothiolanyl, 1,2-dioxazolidinyl, 1,3-oxazolidinyl, 1,3-thiazolidinyl, or 1,2,4-triazolidinyl; or a 6-membered ring such as tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, oxanyl, 1,3-dioxanyl, 1,4-dioxanyl, or 1,2-oxazolidinyl. or a 7-membered ring, such as 1,4-diazepanyl or 1,4-oxazepanyl, for example; or a bicyclic 7-membered ring, such as 6-oxa-3-azabicyclo[3.1.1]heptane, for example; a bicyclic 8-membered ring, such as 5,6-dihydro-4H-furo[2,3-c]pyrrole or 8-oxa-3-azabicyclo[3.2.1]octane, for example; or a bicyclic 9-membered ring, such as octahydro-1H-pyrrolo[3,4-b]pyridine, 1,3-dihydro-isoindole, 2,3-dihydro-indole or 3,9-dioxa-7-azabicyclo[3.3.1]nonane, for example; or a bicyclic 10-membered ring, such as decahydroquinoline or 3,4-dihydroisoquinoline.

[0049] The term "heterospirocycloalkyl" means a bicyclic, saturated heterocycle having a total of 6, 7, 8, 9, 10, or 11 ring atoms, where two rings share one common ring carbon atom, and "heterospirocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said heterospirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms, excluding the spiro carbon atom, or through the nitrogen atom, if present.

[0050] Examples of the heterospiroalkyl group include azaspiro[2.3]hexyl, azaspiro[3.3]heptyl, oxazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, oxaspiro[3.3]heptyl, oxazaspiro[5.3]nonyl, oxazaspiro[4.3]octyl, oxazaspiro[2.5]octyl, azaaspiro[4.5]decyl, and oxazaspiro[5.5]undecyl. thiazaspiro[3.3]heptyl, diazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl, or one of the further homologous skeletons, such as spiro[3.4]-, spiro[4.4]-, spiro[2.4]-, spiro[2.5]-, spiro[2.6]-, spiro[3.5]-, spiro[3.6]-, spiro[4.5]- and spiro[4.6]-.

[0051] The term "6- or 10-membered aryl" means a monovalent, monocyclic or bicyclic aromatic ring having 6 or 10 carbon ring atoms, such as a phenyl or naphthyl group.

[0052] The term "heteroaryl" means a monovalent, monocyclic, bicyclic, or tricyclic aromatic ring having 5, 6, 9, or 10 ring atoms ("5- to 10-membered heteroaryl" groups), especially 5 or 6 ring atoms ("5- to 6-membered heteroaryl" groups), which contains at least one ring heteroatom and optionally one, two, or three additional ring heteroatoms from the series: N, O, and / or S, bonded via a ring carbon atom or optionally bonded via a ring nitrogen atom (where valence allows).

[0053] The heteroaryl group can be a 5-membered heteroaryl group, such as thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, or tetrazolyl; or a 6-membered heteroaryl group, such as pyridinyl, dihydropyridinyl, pyridazinyl, pyrimidinyl, tetrahydropyrimidinyl, pyrazinyl, or triazinyl.

[0054] The term "heterocyclyl" refers to a heterocycle selected from the group consisting of heterocycloalkyl and heteroaryl. In particular, the term "4- to 6-membered heterocyclyl" refers to a heterocycle selected from the group consisting of 4- to 6-membered heterocycloalkyl and 5- to 6-membered heteroaryl.

[0055] In general, unless otherwise specified, a heteroaryl or heteroarylene group includes all possible isomeric forms thereof, such as tautomers and positional isomers with respect to the point of attachment to the remainder of the molecule. Thus, in some illustrative, non-limiting examples, the term pyridinyl includes pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl, or the term thienyl includes thien-2-yl and thien-3-yl.

[0056] The term "C1-C4" as used herein denotes an alkyl group having a finite number of carbon atoms, from 1 to 4, i.e., 1, 2, 3 or 4 carbon atoms, for example in the definition of "C1-C4-alkyl", "C1-C4-halogenoalkyl", "C1-C4-hydroxyalkyl", "C1-C4-alkoxy" or "C1-C4-halogenoalkoxy".

[0057] Furthermore, as used herein, the term "C3-C6" refers to a cycloalkyl group having a finite number of carbon atoms from 3 to 6, i.e., 3, 4, 5 or 6 carbon atoms, as used herein, for example, in the definition of "C3-C6-cycloalkyl" or "C3-C6-halogenocycloalkyl".

[0058] When a range of values ​​is given, the range includes each value and sub-range within the range.

[0059] for example: "C1-C4" encompasses C1, C2, C3, C4, C1-C4, C1-C3, C1-C2, C2-C4, C2-C3, and C3-C4; "C2-C6" encompasses C2, C3, C4, C5, C6, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6; "C3-C4" encompasses C3, C4, and C3-C4; "C3-C 10 ” is C3, C4, C5, C6, C7, C8, C9, C 10 , C3-C 10 , C3-C9, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4, C4-C 10 , C4-C9, C4-C8, C4-C7, C4-C6, C4-C5, C5-C 10 , C5-C9, C5-C8, C5-C7, C5-C6, C6-C 10 , C6-C9, C6-C8, C6-C7, C7-C 10 , C7-C9, C7-C8, C8-C 10 , C8-C9 and C9-C 10 encompasses; "C3-C8" encompasses C3, C4, C5, C6, C7, C8, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4, C4-C8, C4-C7, C4-C6, C4-C5, C5-C8, C5-C7, C5-C6, C6-C8, C6-C7 and C7-C8; "C3-C6" encompasses C3, C4, C5, C6, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6; "C4-C8" includes C4, C5, C6, C7, C8, C4-C8, C4-C7, C4-C6, C4-C5, C5-C8, C5-C7, C5-C6, C6-C8, C6-C7 and C7-C8; "C4-C7" includes C4, C5, C6, C7, C4-C7, C4-C6, C4-C5, C5-C7, C5-C6, and C6-C7; "C4-C6" includes C4, C5, C6, C4-C6, C4-C5, and C5-C6; "C5-C 10 ” is C5, C6, C7, C8, C9, C 10 , C5-C 10, C5-C9, C5-C8, C5-C7, C5-C6, C6-C 10 , C6-C9, C6-C8, C6-C7, C7-C 10 , C7-C9, C7-C8, C8-C 10 , C8-C9 and C9-C 10 encompasses; "C6-C 10 " is C6, C7, C8, C9, C 10 , C6-C 10 , C6-C9, C6-C8, C6-C7, C7-C 10 , C7-C9, C7-C8, C8-C 10 , C8-C9 and C9-C 10 Includes.

[0060] As used herein, the term "leaving group" refers to an atom or group of atoms that, together with the bonding electrons, is displaced in a chemical reaction as a stable species. In particular, such leaving groups are selected from the group comprising: halide, especially fluoride, chloride, bromide or iodide, (methylsulfonyl)oxy, [(trifluoromethyl)sulfonyl]oxy, [(nonafluorobutyl)sulfonyl]oxy, (phenylsulfonyl)oxy, [(4-methylphenyl)sulfonyl]oxy, [(4-bromophenyl)sulfonyl]oxy, [(4-nitrophenyl)sulfonyl]oxy, [(2-nitrophenyl)sulfonyl]oxy, [(4-isopropylphenyl)sulfonyl]oxy, [(2,4,6-triisopropylphenyl)sulfonyl]oxy, [(2,4,6-trimethylphenyl)sulfonyl]oxy, [(4-tert-butylphenyl)sulfonyl]oxy and [(4-methoxyphenyl)sulfonyl]oxy.

[0061] An oxo substituent in the context of this invention means an oxygen atom which is attached to a carbon atom via a double bond.

[0062] Compounds of general formula (I) may exist as isotopic variations. Accordingly, the present invention includes one or more isotopic variations of compounds of general formula (I), particularly deuterium-containing compounds of general formula (I).

[0063] The term "isotopic variant" of a compound or reagent is defined as a compound that exhibits an unnatural proportion of one or more isotopes that constitute such compound.

[0064] The term "isotopic variant of a compound of general formula (I)" is defined as a compound of general formula (I) that exhibits unnatural proportions of one or more isotopes that constitute such compound.

[0065] The expression "unnatural proportion" should be understood to mean that the proportion of such isotope is higher than its natural abundance. The natural abundance of an isotope applicable in this context is described in "Isotopic Compositions of Elements 1997", Pure Appl. Chem., 70(1), 217-235, 1998.

[0066] Such isotopes include stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, for example, 2 H (deuterium), 3 H (tritium), 11 C. 13 C. 14 C. 15 N, 17 O. 18 O. 32 P, 33 P, 33 S, 34 S, 35 S, 36 S, 18 F, 36 Cl, 82 Br, 123 I, 124 I, 125 I, 129 I and 131 I.

[0067] For the treatment and / or prevention of the disorders specified herein, isotopic variants of the compounds of general formula (I) preferably contain deuterium ("deuterium-containing compounds of general formula (I)"). 3H or 14 Isotopic variations of compounds of general formula (I) incorporating one or more radioactive isotopes, such as C, are useful, for example, in drug and / or substrate tissue distribution studies. These isotopes are particularly preferred for their ease of incorporation and detectability. 18 F or 11 Positron-emitting isotopes such as C may be incorporated into the compounds of general formula (I). These isotopic variants of the compounds of general formula (I) are useful for in vivo imaging applications. Deuterium-containing and 13 C-containing compounds can be used for mass spectrometry analysis in the context of preclinical or clinical trials.

[0068] Isotopic variants of compounds of general formula (I) can generally be prepared by replacing a reagent with an isotopic variant of the reagent, preferably a deuterium-containing reagent, by methods known to those skilled in the art (e.g., those described in the schemes and / or examples herein). Depending on the desired site of deuteration, deuterium from DO can optionally be incorporated directly into the compound or into a reagent effective for synthesizing such a compound. Deuterium gas is also a useful reagent for incorporating deuterium into molecules. Catalytic deuteration of olefinic bonds and catalytic deuteration of acetylenic bonds are rapid routes for deuterium incorporation. Metal catalysts (i.e., Pd, Pt, and Rh) in the presence of deuterium gas can be used to directly exchange hydrogen for deuterium in hydrocarbon-containing functional groups. A variety of deuterated reagents and synthetic building blocks are commercially available from companies such as, for example, C / D / N Isotopes, Quebec, Canada; Cambridge Isotope Laboratories Inc., Andover, MA, USA; and CombiPhos Catalysts, Inc., Princeton, NJ, USA.

[0069] The term "deuterium-containing compound of general formula (I)" is defined as a compound of general formula (I) in which one or more hydrogen atoms have been replaced with one or more deuterium atoms, and the abundance of deuterium at each deuteration position of the compound of general formula (I) is greater than the natural abundance of deuterium (about 0.015%). In particular, in a deuterium-containing compound of general formula (I), the abundance of deuterium at each deuteration position of the compound of general formula (I) is greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, or 80%, preferably greater than 90%, 95%, 96%, or 97%, and more preferably greater than 98% or 99% at that position. It is understood that the abundance of deuterium at each deuteration position is independent of the abundance of deuterium at other deuteration positions.

[0070] Selective incorporation of one or more deuterium atoms into compounds of general formula (I) can alter the physicochemical properties (e.g., acidity [CL Perrin et al., J. Am. Chem. Soc., 2007, 129, 4490], basicity [CL Perrin et al., J. Am. Chem. Soc., 2005, 127, 9641], lipophilicity [B. Testa et al., Int. J. Pharm., 1984, 19(3), 271]) and / or metabolic profile of the molecule, and can change the ratio of metabolites to parent compounds or the amount of metabolites formed. Such changes can confer certain therapeutic advantages and may therefore be desirable in some situations. A slowing of the rate of metabolism and metabolic switching (changing the ratio of metabolites) has been reported (AEMutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). These changes in exposure to the parent drug and metabolites can have important consequences regarding the pharmacodynamics, tolerability, and efficacy of deuterium-containing compounds of general formula (I). In some cases, deuterium substitution reduces or eliminates the formation of undesirable or toxic metabolites and enhances the formation of desirable metabolites (e.g., Nevirapine: AM Sharma et al., Chem. Res. Toxicol., 2013, 26, 410; Efavirenz: AEMutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). In other cases, the primary effect of deuteration is to decrease the rate of systemic clearance, thereby increasing the biological half-life of the compound. Potential clinical benefits may include the ability to maintain similar systemic exposure with reduced peak levels and increased trough levels. This may result in fewer side effects and enhanced efficacy, depending on the pharmacokinetic / pharmacodynamic relationship of the particular compound. Indiplon (AJ Morales et al., Abstract 285, The 15 thNorth American Meeting of the International Society of Xenobiotics, San Diego, CA, October 12-16, 2008), ML-337 (C.J. Wenthur et al., J.Med.Chem., 2013, 56, 5208), and odanacatib (K. Kassahun et al., WO2012 / 112363) are examples of this deuteration effect. Additional cases have been reported in which a decrease in metabolic rate results in increased drug exposure without altering the rate of systemic clearance (e.g., rofecoxib: F. Schneider et al., Arzneim.Forsch. / Drug.Res., 2006, 56, 295; telaprevir: F. Maltais et al., J.Med.Chem., 2009, 52, 7993). Deuterated drugs that exhibit this effect may have reduced dosage requirements (e.g., fewer administrations or lower doses to achieve the desired effect) and / or may produce a lower metabolite burden.

[0071] The compound of general formula (I) may have multiple potential attack sites for metabolism. To optimize the above effects on physicochemical properties and metabolic profile, a deuterium-containing compound of general formula (I) with one or more specific patterns of deuterium-hydrogen exchange can be selected. In particular, the deuterium atoms of the deuterium-containing compound of general formula (I) are bonded to carbon atoms and / or to the cytochrome P of the compound of general formula (I), for example. 450 It is located in a position that is an attack site for metabolic enzymes such as

[0072] When plural forms of words such as compounds, salts, polymorphs, hydrates, solvates, etc. are used herein, this is understood to also mean a single compound, salt, polymorph, isomer, hydrate, solvate, etc.

[0073] By "stable compound" or "stable structure" is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

[0074] The compounds of the present invention may contain one or more asymmetric centers, depending on the location and nature of the various substituents desired. The asymmetric carbon atoms may be in the (R) or (S) configuration, resulting in a racemic mixture in the case of a single asymmetric center, and a diastereomeric mixture in the case of multiple asymmetric centers. In certain instances, asymmetry may also exist due to restricted rotation around a given bond, for example, the central bond adjacent to the two substituted aromatic rings of a particular compound.

[0075] Preferred compounds are those that produce the more desirable biological activity. Also included within the scope of the present invention are separated, pure or partially purified isomers and stereoisomers or racemic or diastereomeric mixtures of the compounds of the present invention. Purification and separation of such materials can be accomplished by standard techniques known in the art.

[0076] Preferred isomers are those which result in the more desirable biological activity. These separated, pure, or partially purified isomers or racemic mixtures of the compounds of the present invention are also included within the scope of the present invention. Purification and separation of such materials can be accomplished by standard techniques known in the art.

[0077] Optical isomers can be obtained by resolving racemic mixtures according to conventional processes, for example, by the formation of diastereomeric salts or covalent diastereomers using optically active acids or bases. Examples of suitable acids are tartaric acid, diacetyltartaric acid, ditoluoyltartaric acid, and camphorsulfonic acid. Diastereomeric mixtures can be separated into their individual diastereomers based on their physical and / or chemical differences by methods known in the art, such as chromatography or fractional crystallization. The optically active base or acid is then liberated from the separated diastereomeric salts. Different methods for the separation of optical isomers include the use of chiral chromatography (e.g., chiral HPLC columns) with or without conventional derivatization, optimally selected to maximize the separation of the enantiomers. Suitable chiral HPLC columns using chiral phases are manufactured by Daicel (e.g., Chiracel OD and Chiracel OJ, among many others), and are all routinely selectable. Enzymatic separations, with or without derivatization, are also useful. The optically active compounds of this invention can likewise be obtained by chiral syntheses utilizing optically active starting materials.

[0078] For the purpose of limiting different types of isomers to one another, see IUPAC Rules Section E (Pure Appl Chem 45, 11-30, 1976).

[0079] The present invention includes all possible stereoisomers of the compounds of the present invention, either as a single stereoisomer or as any mixture of said stereoisomers, e.g., (R)- or (S)-isomers, in any ratio. Isolation of a single stereoisomer of a compound of the present invention, e.g., a single enantiomer or a single diastereomer, can be achieved by any suitable state-of-the-art method, such as, for example, chromatography, especially chiral chromatography.

[0080] The present invention includes all possible tautomers of the compounds of the present invention, either as single tautomers or as any mixture of said tautomers, in any proportion.

[0081] Additionally, the compounds of the present invention can exist as N-oxides, which are defined in that at least one nitrogen of the compounds of the present invention is oxidized, and the present invention encompasses all such possible N-oxides.

[0082] The present invention also relates to useful forms of the compounds of the present invention, such as metabolites, hydrates, solvates, prodrugs, salts, particularly pharmaceutically acceptable salts, and / or coprecipitates.

[0083] The compounds of the present invention can exist as hydrates or solvates, where the compounds of the present invention contain polar solvents, particularly water, methanol or ethanol, for example, as structural elements of the crystal lattice of the compounds. The amount of polar solvent, particularly water, can be in a stoichiometric or non-stoichiometric ratio. In the case of stoichiometric solvates, for example, hydrates, hemi-, semi-, mono-, sesqui-, di-, tri-, tetra-, penta-, etc., can be solvates or hydrates, respectively. The present invention includes all such hydrates or solvates.

[0084] Furthermore, the compounds of the present invention can exist in free form, for example as a free base, or as a free acid, or as a zwitterion, or can exist in the form of a salt, which can be any salt, organic or inorganic addition salt, in particular any pharmaceutically acceptable organic or inorganic addition salt, which is conventionally used in pharmacy, or which is used, for example, to isolate or purify the compounds of the present invention.

[0085] The term "pharmaceutically acceptable salt" refers to an inorganic or organic acid addition salt of a compound of the present invention. See, e.g., S. M. Berge et al., "Pharmaceutical Salts," J. Pharm. Sci. 1977, 66, 1-19.

[0086] Suitable pharmaceutically acceptable salts of the compounds of the present invention can be, for example, acid addition salts of compounds of the present invention having, for example, a nitrogen atom in the chain or ring, which is sufficiently basic, for example, acid addition salts with inorganic acids or "mineral acids", such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, bisulfuric acid, phosphoric acid or nitric acid, for example, acid addition salts with organic acids, such as formic acid, acetic acid, acetoacetic acid, pyruvic acid, trifluoroacetic acid, propionic acid, butyric acid, hexanoic acid, heptanoic acid, undecanoic acid, lauric acid, benzoic acid, salicylic acid, 2-(4-hydroxybenzoyl)-benzoic acid, camphoric acid, cinnamic acid, cyclopentanepropionic acid, digluconic acid, 3-hydroxy-2-naphthoic ... acid addition salts with acetic acid, nicotinic acid, pamoic acid, pectic acid, 3-phenylpropionic acid, pivalic acid, 2-hydroxyethanesulfonic acid, itaconic acid, trifluoromethanesulfonic acid, dodecyl sulfate, ethanesulfonic acid, benzenesulfonic acid, para-toluenesulfonic acid, methanesulfonic acid, 2-naphthalenesulfonic acid, naphthalenedisulfonic acid, camphorsulfonic acid, citric acid, tartaric acid, stearic acid, lactic acid, oxalic acid, malonic acid, succinic acid, malic acid, adipic acid, alginic acid, maleic acid, fumaric acid, D-gluconic acid, mandelic acid, ascorbic acid, glucoheptanoic acid, glycerophosphate, aspartic acid, sulfosalicylic acid, or thiocyanic acid, etc.

[0087] Further suitable pharmaceutically acceptable salts of the compounds of the present invention that are sufficiently acidic include alkali metal salts, such as sodium or potassium salts, alkaline earth metal salts, such as calcium, magnesium or strontium salts, or aluminum or zinc salts, or salts of ammonia or organic primary, secondary or tertiary amines having 1 to 20 carbon atoms, such as ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol, tris(hydroxymethyl)aminomethane, procaine, dibenzylethylamine, N-methyldimethyl ... Ammonium salts derived from foline, arginine, lysine, 1,2-ethylenediamine, N-methylpiperidine, N-methylglucamine, N,N-dimethylglucamine, N-ethylglucamine, 1,6-hexanediamine, glucosamine, sarcosine, serinol, 2-amino-1,3-propanediol, 3-amino-1,2-propanediol, 4-amino-1,2,3-butanetriol, or quaternary ammonium ions having 1 to 20 carbon atoms, such as tetramethylammonium, tetraethylammonium, tetra(n-propyl)ammonium, tetra(n-butyl)ammonium, N-benzyl-N,N,N-trimethylammonium, choline, or benzalkonium.

[0088] Those skilled in the art will further recognize that acid addition salts of the claimed compounds can be prepared via any of a number of known methods by reacting the compounds with a suitable inorganic or organic acid. Alternatively, alkali and alkaline earth metal salts of acidic compounds of the invention are prepared via a variety of known methods by reacting the compounds of the invention with a suitable base.

[0089] The present invention includes all possible salts of the compounds of the present invention, either as single salts or as any mixture of said salts, in any proportion.

[0090] When compounds are referred to herein, particularly in the experimental part, for the synthesis of intermediates and examples of the present invention, as salt forms with corresponding bases or acids, the exact stoichiometry of said salt forms obtained by the respective preparation and / or purification process is in most cases unknown.

[0091] Unless otherwise specified, the term "hydrochloride", "trifluoroacetate", "sodium salt", or "xHCl", "xCF3COOH", "xNa + " to a salt-related chemical name or structural formula, for example, indicates a salt form, the stoichiometry of which is not specified.

[0092] This also applies if the described preparation and / or purification process results in the synthesis intermediate or the example compound or a salt thereof being obtained as a solvate, such as a hydrate, having an unknown stoichiometry (if defined).

[0093] Furthermore, the present invention includes all possible crystalline forms or polymorphs of the compounds of the present invention, either as a single polymorph or as a mixture of two or more polymorphs, in any proportion.

[0094] Furthermore, the present invention also includes prodrugs of compounds according to the present invention. The term "prodrug" refers to compounds which may themselves be biologically active or inactive, but which are converted (e.g., metabolically or hydrolytically) into compounds according to the present invention during their residence in the body.

[0095] According to a second embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: A is A1 or A2, [ka]

[0096] o is 0, 1, 2, 3 or 4; R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -OH, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl, -S(O)-C-C-halogenoalkyl and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms, R p is selected from the group consisting of hydrogen, C1-C4-alkyl, X and Y are CR 7 R 8 , O, S, and NR 9 wherein at least one of X and Y is independently selected from the group consisting of CR 7 R 8 or X and Y together form -C(O)-O- and -C(O)-NR 9 -, -S(O)-NR 9 -, -SO2-NR 9 - and -SO2-O-, R 1is hydrogen, cyano, -CHO, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, C3-C6-halogenocycloalkyl having 1 to 5 halogen atoms, C3-C4-alkenyl, C3-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6-cycloalkyl-C1-C3-alkyl, cyano-C1-C4-alkyl, -NH-C1-C4-alkyl, -N(C1-C4-alkyl)2, NH2-C1-C4-alkyl-, C1-C4-alkyl-NH-C1-C4-alkyl-, (C1-C4-alkyl)2N-C1-C4-alkyl-, C1-C4-alkyl-C(O)-, C1-C4-halogenoalkyl-C(O)- having 1 to 5 halogen atoms, C1-C4-alkoxy-C(O)-, benzyloxy-C(O)-, C1-C4-alkoxy-C1-C4-alkyl-C(O)-, -SO2-C1-C4-alkyl and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl-C1-C4-alkyl, which may be substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, —OH, —NO2, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl) ), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms. is selected from the group consisting of R 2 but, Hydrogen, halogen, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl) 2; -NR 12 R 13 ; -OR 14 ; -SR 15 , -S(O)R 15 , -SO2R 15 ; C1-C6-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or phenyl-C1-C4-alkyl, each of which is halogen, -OH, -NO2, cyano, C1-C4-alkyl-C(O)-, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -NH2, -NH(C1-C4-alkyl) optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of -C(O)-C-C-alkyl), -N(C-C-alkyl), -NH(C(O)-C-C-alkyl), -N(C-C-alkyl)(C(O)-C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, —OH, —NO2, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl) ), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl, which may be substituted by one, two or three substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; and monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, -C(O)-NH(C-C-alkyl), -C(O)-N(C-C-alkyl)2, C-C-alkyl, C-C-alkyl-C(O)-, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, hydroxy-C-C-alkyl, C-C-alkoxy-C-C-aromatic and optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and 4- to 10-membered heterocycloalkyl. is selected from the group consisting of R 3 is hydrogen or C1-C4-alkyl, R 4 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl), —N(C1-C4-alkyl)2, preferably hydrogen and halogen, more preferably fluorine and chlorine, R 5 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl), —N(C1-C4-alkyl)2, R 6 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl), —N(C1-C4-alkyl)2, R 7 is selected from the group consisting of hydrogen, —OH, fluorine, C1-C4-alkyl and C1-C4-alkoxy, R 8 is selected from the group consisting of hydrogen, —OH, fluorine, C1-C4-alkyl and C1-C4-alkoxy, or R 7 and R 8 together form an oxo group (=O), R 9 is selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy, R 10is selected from the group consisting of hydrogen, —OH, C1-C4-alkyl and C1-C4-alkoxy, R 11 is selected from the group consisting of hydrogen, C1-C4-alkyl and C1-C4-alkoxy, R 12 and R 13 but, Hydrogen, -OH, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)-(-C(O)-C1-C4-alkyl), C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkyl having 1 to 5 halogen atoms. optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of alkoxy, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4-alkoxy)2P(=O)-; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which may be halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, 1 to 5 optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; phenyl, benzo-C5-C6-cycloalkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; and monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, having 1 to 5 halogen atoms; and optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms. are independently selected from the group consisting of R 14 but, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cyclo optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of alkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, ... optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; phenyl, which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; and monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, -C(O)-NH(C-C-alkyl), -C(O)-N(C-C-alkyl), C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, hydroxy-C-C-alkyl, C-C-alkyl having 1 to 5 halogen atoms; and optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms. is selected from the group consisting of R 15 but, hydrogen; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cyclo optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of alkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, ... optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; phenyl, which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; and monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, -C(O)-NH(C-C-alkyl), -C(O)-N(C-C-alkyl), C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, hydroxy-C-C-alkyl, C-C-alkyl having 1 to 5 halogen atoms; and optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms. is selected from the group consisting of Q is the formula (Q1) [ka]

[0097] [In formula: Z 1 , Z 2 , Z 3 , Z 4 , and Z 5represents hydrogen, halogen, SF5, cyano, -CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-SO2-(C1-C4-alkyl), -N(SO2-[C1-C4-alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered heterocyclyl, which may be substituted by one or two substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -CH2-O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, which itself is fluorine, chlorine, bromine, methyl and and cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -S-(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms. independently selected from the group consisting of -C(O)-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C-C-alkyl), -CONH(C-C-cycloalkyl), -NHCO(C-C-alkyl), -NHCO(C-C-cycloalkyl), -NHCO(C-C-halogenoalkyl) having 1 to 5 halogen atoms, or Z 1 and Z 2together with the carbon atoms to which they are attached form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which may be optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine, and oxo; and Z 3 , Z 4 , and Z 5is hydrogen, halogen, SF5, cyano, CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1-C4-alkoxy, C1-C4-alkoxy-C(O)-, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-SO 2-(C1-C4-alkyl), -N(SO2-[C1-C4-alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered heterocycloalkyl, which may be substituted by one or two substituents selected from the group consisting of fluorine, methyl or cyano, -CH2-O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, itself fluorine, Methyl substituted with a 4- to 6-membered heterocyclyl optionally substituted by 1 or 2 substituents selected from the group consisting of methyl or cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -S-(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-(C1-C4-halogeno) having 1 to 5 halogen atoms. independently selected from the group consisting of -S(O)-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -SO-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C-C-alkyl), -CONH(C-C-cycloalkyl), -NHCO(C-C-alkyl), -NHCO(C-C-cycloalkyl), -NHCO(C-C-halogenoalkyl) having 1 to 5 halogen atoms, or Z 2 and Z 3together with the carbon atoms to which they are attached form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine, and oxo; and Z 1 , Z 4 , and Z 5is hydrogen, halogen, SF5, cyano, CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-SO2-(C1-C4-alkyl) -C1-C4-alkyl), -N(SO2-[C1-C4-alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered heterocycloalkyl, which may be substituted by one or two substituents selected from the group consisting of fluorine, methyl or cyano, -CH2-O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, which itself is fluorine, methyl or cyano. methyl substituted with a 4- to 6-membered heterocyclyl optionally substituted by 1 or 2 substituents selected from the group consisting of -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -S-(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms; alkyl), -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C1-C4-alkyl), -CONH(C3-C6-cycloalkyl), -NHCO(C1-C4-alkyl), -NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms] or a substituted phenyl ring of Q is the formula (Q2) [ka]

[0098] [In formula: Z 6 , Z 7 , Z 8 and Z 9 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2] or Q is the formula (Q3) [ka]

[0099] [In formula: Z 10 , Z 11 and Z 12 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2] or Q is the formula (Q4) [ka]

[0100] [In formula: Z 13 , Z 14 , Z 15 and Z 16is a monocyclic heterocycle selected from the group consisting of hydrogen, halogen, cyano, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-hydroxyalkyl, NH, -NH(C-C-alkyl), -N(C-C-alkyl), -NH-CO-C-C-alkyl, and 5-membered heteroaryl or 4- to 7-membered heterocycloalkyl having at least one nitrogen atom whereby the heteroaryl ring is connected to a pyridine ring (each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, C-C-alkyl, C-C-hydroxyalkyl having 1 to 5 halogen atoms, C-C-hydroxyalkyl, NH, -NH(C-C-alkyl), -N(C-C-alkyl), -NH-CO-C-C-alkyl, and 5-membered heteroaryl or 4- to 7-membered heterocycloalkyl having at least one nitrogen atom whereby the heteroaryl ring is connected to a pyridine ring). 4-halogenoalkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms). or Q is the formula (Q5) [ka]

[0101] [In formula: Z 17 , Z 18 , Z 19 and Z 20are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2] or Q is the formula (Q6) [ka]

[0102] [In formula: T 1 ~T 4 are N, O, S, CZ 21 and NZ 22 wherein T 1 ~T 4 At most one of is O and T 1 ~T 4 At most one of is S, and T 1 ~T 4 One or less of NZ 22 where: Individual Z 21 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, and Individual Z 22 are independently selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl] or Q is the formula (Q7) [ka]

[0103] [In formula: U 1 ~U 4 are N and CZ 23 independently selected from the group consisting of U 1 ~U 4 N is three or fewer of Individual Z 23 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms. is a five-membered aromatic heterocycle of where Y is O, S or NR 9 If R 7 , R 8 , R 10 and R 11 None of the groups are -OH and X is O, S or NR 9 If R 7 and R 8 None of the groups are -OH. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0104] According to a third embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: A is A1 or A2, [ka]

[0105] o is 0, 1 or 2; R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, R p is selected from the group consisting of hydrogen, C1-C4-alkyl, X and Y are CR 7 R 8 , O, S, and NR 9wherein at least one of X and Y is independently selected from the group consisting of CR 7 R 8 and R 1 is selected from the group consisting of hydrogen, C1-C4-alkyl, C3-C6-cycloalkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6-cycloalkyl-C1-C3-alkyl, cyano-C1-C4-alkyl, R 2 but, Hydrogen, halogen, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2; -NR 12 R 13 ; -OR 14 ; -SR 15 , -S(O)R 15 , -SO2R 15 ; C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or phenyl-C1-C4-alkyl, each of which is halogen, -OH, cyano, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -NH2, -NH(C1-C4-alkyl), -N(C1-C4- optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of -C(O)-C-C-alkyl, -NH(C(O)-C-C-alkyl), -N(C-C-alkyl)(C(O)-C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-C-C-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C-C-halogenoalkyl having 1 to 5 halogen atoms and -SO-C-C-halogenoalkyl having 1 to 5 halogen atoms; and monocyclic or bicyclic heterocycles selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, -OH, oxo, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, -C(O)-NH(C-C-alkyl), -C(O)-N(C-C-alkyl), C-C-alkyl, C-C-alkyl-C(O)-, 1 to 5 halo and optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of C-C-halogenoalkyl having halogen atoms, C-C-alkoxy, hydroxy-C-C-alkyl, C-C-alkoxy-C-C-alkyl-, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl) and 4- to 10-membered heterocycloalkyl. is selected from the group consisting of R 3 is hydrogen or C1-C4-alkyl, R 4 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl), —N(C1-C4-alkyl)2, preferably hydrogen and halogen, more preferably fluorine and chlorine, R 5 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl), —N(C1-C4-alkyl)2, R 6 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, —NH(C1-C4-alkyl), —N(C1-C4-alkyl)2, R 7 is selected from the group consisting of hydrogen and C1-C4-alkyl, R 8 is selected from the group consisting of hydrogen and C1-C4-alkyl, or R 7 and R 8 together form an oxo group (=O), R 9 is C1-C4-alkyl, R 10 is selected from the group consisting of hydrogen, —OH, C1-C4-alkyl and C1-C4-alkoxy, R 11 is hydrogen, R 12 and R 13 but, hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)-(-C(O)-C1-C4-alkyl), C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkyl having 1 to 5 halogen atoms. optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of alkoxy, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4-alkoxy)2P(=O)-; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituents are selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, —OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; phenyl, benzo-C5-C6-cycloalkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; are independently selected from the group consisting of R 14 but, C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl; and Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituents are selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, —OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms. selected from the group consisting of: R 15 but, hydrogen; C1-C4-alkyl, phenyl-C1-C4-alkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; Heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituents are selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms. selected from the group consisting of: Q is the formula (Q1) [ka]

[0106] [In formula: Z 1 , Z 2 , Z 3 , Z 4 , and Z 5is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, 4- to 6-membered heterocyclyl (which may be substituted with one or two substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano); independently selected from the group consisting of -(C-C-alkyl), -S(O)-(C-C-alkyl), -SO-(C-C-alkyl), -S-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -SO-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, or Z 1 and Z 2 together with the carbon atom to which they are attached form a 5- or 6-membered heterocycloalkyl, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine, and oxo; and Z 3 , Z 4 , and Z 5 are independently selected from the group consisting of hydrogen, halogen, cyano, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-alkoxy-C(O)-, C-C-halogenoalkoxy having 1 to 5 halogen atoms, or Z 2 and Z 3 together with the carbon atoms to which they are attached form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine, and oxo; and Z 1 , Z 4 , and Z5 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms. is a substituted phenyl ring of the formula and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0107] According to a fourth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: A is A1 or A2, [ka]

[0108] o is 0, 1 or 2; R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, R p is selected from the group consisting of hydrogen, C1-C4-alkyl, X is CR 7 R 8 , O, S, and NR 9 is selected from the group consisting of Y is CR 7 R 8 or O, R 1 is hydrogen or C1-C4-alkyl, R 2 but, Hydrogen, halogen, -C(O)-N(C1-C4-alkyl)2; -NR 12 R 13 ; -OR 14 ; -SR 15 , -S(O)R 15 , -SO2R 15 ; C-C-alkyl, C-C-cycloalkyl, C-C-alkenyl or C-C-cycloalkenyl, each of which may be substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, —OH, cyano, C-C-alkoxy-C(O)— and —C(O)—NH, C-C-alkoxy, —NH, —N(C-C-alkyl), —N(C-C-alkyl)(C(O)—C-C-alkyl); and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, -OH, oxo, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, C-C-alkyl, C-C-alkyl-C(O)-, C-C-halogenoalkyl having 1 to 5 halogen atoms, hydroxy-C-C-alkyl-, C-C-alkoxy-C-C-alkyl-, -NH, -N(C-C-alkyl) and 4- to 10-membered heterocycloalkyl; is selected from the group consisting of R 3 is hydrogen or C1-C4-alkyl, R 4 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, —NH2, preferably hydrogen and halogen, more preferably fluorine and chlorine, R 5 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, R 6is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, R 7 is selected from the group consisting of hydrogen and C1-C4-alkyl, R 8 is selected from the group consisting of hydrogen and C1-C4-alkyl, or R 7 and R 8 together form an oxo group (=O), R 9 is C1-C4-alkyl, R 10 is selected from the group consisting of hydrogen, —OH and C1-C4-alkyl, R 11 is hydrogen, R 12 and R 13 but, hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, C1-C4-alkyl, C1-C4-alkoxy, C3-C6-cycloalkyl, -NH2, -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl and (C1-C4-alkoxy)2P(=O)-; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituents are selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, —OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy; Phenyl and benzo-C5-C6-cycloalkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, oxo, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; are independently selected from the group consisting of R 14 but, C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, —OH, C1-C4-alkyl, C1-C4-alkoxy and C3-C6-cycloalkyl; and 4-10 membered heterocycloalkyl is selected from the group consisting of R 15 but, hydrogen; C1-C4-alkyl, which may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of -OH and -COOH; and 6-membered heteroaryl is selected from the group consisting of Q is the formula (Q1) [ka]

[0109] [In formula: Z 1 and Z 5 are independently selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, Z 2 and Z 4 are independently selected from the group consisting of hydrogen, halogen, cyano, -OH, C-C-alkyl, C-C-alkoxy, -NH(C-C-alkyl), -N(C-C-alkyl), C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-halogenoalkoxy having 1 to 5 halogen atoms, -S-(C-C-alkyl), S-(C-C-halogenoalkyl) having 1 to 5 halogen atoms and 4- to 6-membered heterocycloalkyl; Z 3 is selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, and -N(C1-C4-alkyl)2, or Z 1 and Z 2 together with the carbon atoms to which they are attached form a 5-membered heterocycloalkyl or a 5-membered heteroaryl, each of which is optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine and oxo; Z 3 and Z 5 is hydrogen, and Z 4is selected from the group consisting of hydrogen and C1-C4-alkoxy-C(O)-. is a substituted phenyl ring of the formula and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0110] According to a fifth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: A, [ka] TIFF0007669343000016.tif122166

[0111] is selected from the group consisting of R 1 is hydrogen or methyl, R 2 but, Hydrogen, chlorine, iodine, -C(O)-N(CH3)2, -NR 12 R 13 ; -OR 14 ; -SR 15 , -S(O)R 15 , -SO2R 15 ; methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethenyl, propenyl, cyclopentenyl, cyclohexenyl, each of which is optionally substituted with one or two substituents independently selected from the group consisting of -OH, cyano, ethoxy-C(O)-, -C(O)-NH, methoxy, NH, N(CH), N(CH)(C(O)CH); and Azetidine, oxetane, pyrrolidine, tetrahydrofuran, pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine, piperazine, tetrahydropyran, tetrahydropyridine, dihydro-2H-pyran, 1,2-oxazolidine, 1,2-oxazine, morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indole, 1,3-dihydro-isoindole (isoindole), 3,9-dioxa-7-azabicyclo[3.3.1]nonane, 6-oxa-3-azabicyclo[3.1.1]heptane, 8-oxa-3-azabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole, 1,2,4-triazolidine, methylpropanol ... a monocyclic or bicyclic heterocycle selected from the group consisting of azole, 1,2,3-triazole, 1,2,3,4-tetrazole, pyridine, dihydropyridine, pyrimidine, tetrahydropyrimidine, and 4-oxa-7-azaspiro[2.5]octane, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of fluorine, chlorine, cyano, —OH, oxo, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH2, methyl, methyl-C(O)—, difluoromethyl, trifluoromethyl, hydroxymethyl-, methoxymethyl-, —NH2, —NMe2, and pyrrolidine; is selected from the group consisting of R 3 is hydrogen or methyl, R 4 is selected from the group consisting of hydrogen, fluorine, chlorine, —OH, cyano, methyl, methoxy, trifluoromethyl, trifluoromethoxy and NH2, preferably hydrogen, fluorine and chlorine; R 5 is selected from the group consisting of hydrogen, fluorine, chlorine, —OH, cyano, methyl, methoxy, and trifluoromethyl; R 6 is selected from the group consisting of hydrogen, fluorine, chlorine, —OH, cyano, methyl, and methoxy; R 12 and R 13 but, hydrogen, -NH(-C(O)-methyl), methoxy; methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, benzyl, 1-phenylethyl, each of which is optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of fluorine, —OH, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH2, —C(O)-NMe2, —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH2, NMe2, S-methyl, S(O)-methyl, SO2-methyl, and (EtO)2P(═O)—; heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocyclyl substituents are selected from the group consisting of oxetane, tetrahydrofuran, tetrahydropyran, pyrrolidine, morpholine, pyrazole, imidazole, 1,2,4-oxadiazole, pyridine, each of which is optionally substituted with one substituent independently selected from the group consisting of fluorine, chlorine, —OH, oxo, and methyl; phenyl; 2,3-dihydro-1H-indene, and a monocyclic or bicyclic heterocycle selected from the group consisting of oxetane, thietane, pyrrolidine, morpholine, tetrahydropyran, pyridine, and pyrazole, each of which may be substituted with one or two substituents independently selected from the group consisting of fluorine, chlorine, —OH, oxo, and methyl; independently selected from the group consisting of: R 14 but, methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is optionally substituted with one or two substituents independently selected from the group consisting of fluorine, —OH, methyl, methoxy, and cyclopentyl; and a monocyclic or bicyclic heterocycle selected from the group consisting of pyrrolidine and tetrahydropyran; is selected from the group consisting of R 15 but, methyl and ethyl, each of which is optionally substituted with one substituent independently selected from the group consisting of —OH and —COOH; and Pyridine is selected from the group consisting of Q is the formula (Q1) [ka]

[0112] [In formula: Z 1 and Z 5 are independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, trifluoromethyl, and methoxy; Z 2 and Z 4 are independently selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2, trifluoromethyl, methoxy, trifluoromethoxy, -SMe, 2,2,2-trifluoroethyl)sulfanyl, and morpholinyl; and Z 3 are independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy, and -NMe2. is a substituted phenyl ring of the formula and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0113] According to a sixth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: A, [ka]

[0114] is selected from the group consisting of R 1 is hydrogen or methyl, R 2 but, Chlorine, iodine, -C(O)-N(CH3)2, -NR 12 R 13 ; -OR 14 ; -SR 15 , -S(O)R 15 , -SO2R 15 ; methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, ethenyl, propenyl, each of which is optionally substituted with one or two substituents independently selected from the group consisting of -OH, cyano, ethoxy-C(O)-, -C(O)-NH, methoxy, NH, N(CH), N(CH)(C(O)CH); and Azetidine, oxetane, pyrrolidine, tetrahydrofuran, pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine, piperazine, tetrahydropyran, dihydro-2H-pyran, 1,2-oxazolidine, morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indole, 1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo[3.3.1]nonane, 6-oxa-3-azabicyclo[3.1.1]heptane, 8-oxa-3-azabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole a monocyclic or bicyclic heterocycle selected from the group consisting of 1,2,3-triazole, 1,2,3,4-tetrazole, pyridine, dihydropyridine, pyrimidine, and tetrahydropyrimidine, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of fluorine, —OH, oxo, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH2, methyl, methyl-C(O)—, difluoromethyl, trifluoromethyl, hydroxymethyl, methoxymethyl, —NH2, —NMe2, and pyrrolidine; is selected from the group consisting of R 3 is hydrogen or methyl, R 4is selected from the group consisting of hydrogen, chlorine, fluorine, methyl, methoxy and trifluoromethyl, preferably hydrogen, fluorine and chlorine; R 5 is selected from the group consisting of hydrogen, chlorine, fluorine, —OH, cyano, methyl, trifluoromethoxy, and NH; R 6 is selected from the group consisting of hydrogen, fluorine, chlorine, —OH, cyano, methyl, and methoxy; R 12 and R 13 but, hydrogen, -NH(-C(O)-methyl), methoxy; methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, benzyl, 1-phenylethyl, each of which may be substituted by 1, 2, or 3 substituents independently selected from the group consisting of fluorine, —OH, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH2, —C(O)-NMe2, —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH2, —NMe2, SO2-methyl, and (EtO)2P(═O)—; heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocyclyl substituents are selected from the group consisting of oxetane, tetrahydrofuran, tetrahydropyran, pyrrolidine, pyrazole, imidazole, 1,2,4-oxadiazole, morpholine, pyridine, each of which is optionally substituted with one substituent independently selected from the group consisting of oxo and methyl; phenyl; 2,3-Dihydro-1H-indene, and Monocyclic or bicyclic heterocycles selected from the group consisting of oxetane, morpholine, tetrahydropyran, pyridine and pyrazole. independently selected from the group consisting of: R 14 but, methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is optionally substituted with one or two substituents independently selected from the group consisting of fluorine, —OH, methyl, methoxy, and cyclopentyl; and a monocyclic or bicyclic heterocycle selected from the group consisting of pyrrolidine and tetrahydropyran; is selected from the group consisting of R 15 but, methyl and ethyl, each of which is optionally substituted with one substituent independently selected from the group consisting of —OH and —COOH; and Pyridine is selected from the group consisting of Q is the formula (Q1) [ka]

[0115] [In formula: Z 1 and Z 5 are independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, methoxy, and trifluoromethyl; Z 2 and Z 4 are independently selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2, trifluoromethyl, methoxy, trifluoromethoxy, -SMe, 2,2,2-trifluoroethyl)sulfanyl, and morpholinyl; and Z 3 are independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy, and -NMe2. is a substituted phenyl ring of the formula and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0116] According to a seventh embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: A, [ka]

[0117] is selected from the group consisting of R 1 is hydrogen or methyl, R 2is hydrogen, (2-amino-2-oxoethyl)amino, (2-aminoethyl)amino, (2-hydroxyethyl)amino, hydroxymethyl, methoxymethyl, 2-hydroxyethyl, (2-hydroxyethyl)oxy, (2-methoxy-2-oxoethyl)amino, (3-methoxy-3-oxopropyl)-methylamino, (2-methoxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)oxy, (2R,6S)-2,6-dimethylmorpholin-4-yl, 2-(trifluoromethyl)amino, (2S)-2-methylmorpholin-4-yl, 2,2-difluoroethyl(methyl)amino, (3,3,3-trifluoropropyl)amino, (3-methoxybenzyl)oxy, (3rac,4rac)-3-amino-4-fluoropyrrolidin-1-yl, (3S)-3-(hydroxymethyl)pyrrolidin-1-yl, (carboxyethyl)amino, (cyclopentylmethyl)oxy, (pyridin-2-ylmethyl)amino, (rac)-3-hydroxypyrrolidin-1-yl, [2-(di Methylamino)ethyl]amino, 1,1-dioxidethiomorpholin-4-yl, 1,2-oxazolidin-2-yl, 1H-1,2,3-triazol-1-yl, 1H-imidazol-1-yl, 1H-pyrazol-1-yl, 1H-pyrazol-4-yl, 2,2-dimethylmorpholin-4-yl, 2,2-dimethylpyrrolidin-1-yl, 2,4-dimethyl-3,5-dioxo-1,2,4-triazolidin-1-yl, 2-amino-2-oxoethyl, 2H-1,2,3-triazol-2-yl, 1H-tetrazolium pyrazol-5-yl, 3-(pyrrolidin-1-yl)azetidin-1-yl, 3,3-difluoroazetidin-1-yl, 3,3-difluoropyrrolidin-1-yl, 3-fluoroazetidin-1-yl, 3-hydroxyazetidin-1-yl, 3-methylazetidin-1-yl, 3-oxopyrazolidin-1-yl, 1-(difluoromethyl)-1H-pyrazol-4-yl, 4-(trifluoromethyl)-1H-pyrazol-1-yl, 1-methyl-piperidin-4-yl, 4-fluoropiperidin-1-yl, 4,4-difluoropiperidin-1-yl, 4-oxoimidazolidin-1-yl, amino, anilino, azetidin-1-yl, benzyl(methyl)amino, chlorine, iodine, cyanomethyl, cyclobutyl(methyl)amino, cyclopentyloxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclopropyl(ethyl)amino, cyclopropyl(methyl)amino, cyclopropylamino, diethylamino, dimethylamino, dimethylaminocarbonyl, aminomethyl, 2-aminoethyl, (dimethylamino)methyl, 2-(dimethylamino)ethyl, ethenyl, ethyl, ethylamino, ethyloxy, ethylsulfanyl, ethylsulfinyl, ethylsulfonyl, isopropyl, isopropyloxy, methoxyamino, methyl, methyl(2,2,2-trifluoroethyl)amino, oxetan-3-ylmethylamino, methyl(oxetan-3-yl)amino, methylamino, methyloxy, methylsulfanyl, morpholin-4-yl, morpholin-4-ylamino, nitrilomethyl, prop-1-en-2-yl, propyl, propylamino, pyridin-4-yloxetan-3-yl, tetrahydrofuran-3-yl, 3,6-dihydro-2H-pyran-4-yl, tetrahydropyran-4-yl, tetrahydro-2H-pyran-4-yloxy, 3-thienyl, and thiomorpholin-4-yl; R 3 is hydrogen or methyl, R 4 is selected from the group consisting of hydrogen, chlorine, fluorine, —OH, cyano, methyl, methoxy, trifluoromethyl, trifluoromethoxy and NH2, preferably hydrogen, fluorine and chlorine; R 5 is selected from the group consisting of hydrogen, chlorine, fluorine, —OH, cyano, methyl, methoxy, and trifluoromethyl; R 6 is selected from the group consisting of hydrogen, fluorine, chlorine, —OH, cyano, methyl, and methoxy; Q is phenyl, 2,5-bis(trifluoromethyl)phenyl, 2,3,4-trifluorophenyl, 2,3,5-trichlorophenyl, 2,3,5-trifluorophenyl, 2,3,6-trifluorophenyl, 2,3-dichlorophenyl, 2,3-dichloro-5-cyanophenyl, 2,3-dichloro-5-hydroxyphenyl, 2,3-difluorophenyl, 2,4,5-trifluorophenyl, 2,4,6-trifluoro-3-methoxyphenyl, 2,4-difluoro-3-hydroxyphenyl, 2,4-difluoro-3-methoxyphenyl, 2,5-dichlorophenyl, 2-chloro-5-cyanophenyl, 2-chloro-5-methylphenyl, 2,5-difluoro-4-methoxyphenyl, 2,6-difluorophenyl, 2-chloro-3-fluorophenyl, 2-chloro-4-(dimethylamino)phenyl, 2-chloro-4-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro -6-fluorophenyl, 2-chlorophenyl, 3,5-difluoropyridin-4-yl, 2-chloro-3-fluoropyridin-4-yl, 2-fluoro-5-methylphenyl, 3-fluoro-5-methylphenyl, 2-fluoro-3-(trifluoromethoxy)phenyl, 2-fluoro-3-(trifluoromethyl)phenyl, 5-fluoro-2-(trifluoromethyl)phenyl, 3-cyano-5-methylphenyl, 3-(trifluoromethyl)phenyl, 3-(trifluoromethoxy)phenyl, 3,4,5-trifluorophenyl, 3,4-dichlorophenyl, 3,4-difluoro-2-methoxyphenyl, 3,4-difluorophenyl, 3,5-dichloro-4-(dimethylamino)phenyl, 3,5-dichloro-4-fluorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 4-(difluoromethoxy)-3,5-difluorophenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 3-tert-butyl-5-methylphenyl, 5-tert-butyl-2-chloro-3-methylphenyl, 3-chloro-2-fluoro-5-methylphenyl, 3-chloro-2-fluorophenyl, 3-chloro-2-methylphenyl, 3-chloro-4-fluorophenyl, 3-chloro-4-methylphenyl, 2-chloro-3-(trifluoromethyl)phenyl, 2-methyl-5-(trifluoromethyl)phenyl, 3-chloro-5-(trifluoromethyl)phenyl, 3-chloro-5-ethylphenyl, 3-chloro-5-fluorophenyl, 3-chloro-5-methoxyphenyl, 3-chloro-5-methylphenyl, 3-chlorophenyl, 3-fluoro-2-methylphenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-5-methylphenyl, 4-fluoro-3-methoxyphenyl, 5-chloro 2,4-difluorophenyl, 5-chloro-2-fluoro-3-methylphenyl, 5-chloro-2-fluoro-4-methylphenyl, 5-chloro-2-fluorophenyl, 5-chloro-2-methoxyphenyl, 5-fluoro-2-methylphenyl, 5-fluoro-2-methoxyphenyl, 3,5-diethylphenyl, 2-chloro-3,5-diethylphenyl, 3-chloro-2-thienyl, 4-chloro-2-thienyl, 5-chloro-2-thienyl, 2,5-dichloro-3-thienyl, 5-fluoro-2-thienyl, 5-cyano-2-thienyl, 5-cyano-4-methyl-2-thienyl, 5-methyl-2-thienyl, 2,5-dimethyl-3-thienyl, 5-(trifluoromethyl)-2-thienyl, 3-tert-butyl-5-fluorophenyl, and 3-tert-butyl-5-chlorophenyl, and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0118] According to an eighth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: A is A3 or A4, [ka]

[0119] o is 0 or 1, R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, R p is selected from the group consisting of hydrogen, C1-C4-alkyl, X is CR 7 R 8 , O, S, and NR 9 is selected from the group consisting of Y is CR 7 R 8 or O, R 1 is hydrogen or C1-C4-alkyl, R 2 but, Hydrogen, halogen, -C(O)-N(C1-C4-alkyl)2; -NR 12 R 13 ; -OR 14 ; -SR 15 , -S(O)R 15 , -SO2R 15 ; C-C-alkyl, C-C-cycloalkyl, C-C-alkenyl or C-C-cycloalkenyl, each of which may be substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, cyano, C-C-alkoxy-C(O)- and -C(O)-NH, C-C-alkoxy, -NH, -N(C-C-alkyl), -N(C-C-alkyl)(C(O)-C-C-alkyl), and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, -OH, oxo, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, C-C-alkyl, C-C-alkyl-C(O)-, C-C-halogenoalkyl having 1 to 5 halogen atoms, hydroxy-C-C-alkyl-, C-C-alkoxy-C-C-alkyl-, -NH, -N(C-C-alkyl) and 4- to 10-membered heterocycloalkyl; selected from the group consisting of: R 3 is hydrogen or C1-C4-alkyl, R 4 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, NH2, preferably hydrogen and halogen, more preferably fluorine and chlorine, R 5 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, R 6 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, R 7 is selected from the group consisting of hydrogen and C1-C4-alkyl, R 8 is selected from the group consisting of hydrogen and C1-C4-alkyl, or R 7 and R8 together form an oxo group (=O), R 9 is C1-C4-alkyl, R 10 is selected from the group consisting of hydrogen, —OH and C1-C4-alkyl, R 11 is hydrogen, R 12 and R 13 but, hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy; C-C-alkyl, C-C-cycloalkyl, phenyl-C-C-alkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, -COOH, C-C-alkoxy-C(O)-, -C(O)-NH, -C(O)-N(C-C-alkyl), -NH-C(O)-C-C-alkyl, C-C-alkyl, C-C-alkoxy, C-C-cycloalkyl, -NH, -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl and (C-C-alkoxy)P(=O)-; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituents are selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, —OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy; Phenyl and benzo-C5-C6-cycloalkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, oxo, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; are independently selected from the group consisting of R 14 but, C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which may be substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, —OH, C1-C4-alkyl, C1-C4-alkoxy and C3-C6-cycloalkyl; and 4-10 membered heterocycloalkyl is selected from the group consisting of R 15 but, hydrogen; C1-C4-alkyl, which may be substituted with 1, 2 or 3 substituents independently selected from the group consisting of -OH and -COOH; and 6-membered heteroaryl is selected from the group consisting of Q is the formula (Q1) [ka]

[0120] [In formula: Z 1 and Z 5 are independently selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-halogenoalkyl having 1 to 5 halogen atoms, Z 2 and Z 4are independently selected from the group consisting of hydrogen, halogen, cyano, -OH, C-C-alkyl, C-C-alkoxy, -NH(C-C-alkyl), -N(C-C-alkyl), C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-halogenoalkoxy having 1 to 5 halogen atoms, -S-(C-C-alkyl), S-(C-C-halogenoalkyl) having 1 to 5 halogen atoms and 4- to 6-membered heterocycloalkyl, and Z 3 is selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms and -N(C1-C4-alkyl)2, or Z 1 and Z 2 together with the carbon atoms to which they are attached form a 5-membered heterocycloalkyl or a 5-membered heteroaryl, each of which is optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine and oxo; Z 3 and Z 5 is hydrogen, and Z 4 is selected from the group consisting of hydrogen and C1-C4-alkoxy-C(O)-. or a substituted phenyl ring of Q is the formula (Q4) [ka]

[0121] [In formula: Z 13 , Z 14 , Z 15 and Z 16is a monocyclic heterocycle selected from the group consisting of hydrogen, halogen, cyano, C-C-alkyl, C-C-alkoxy, C-C-hydroxyalkyl, NH, -NH(C-C-alkyl), -N(C-C-alkyl)2, -NH-CO-C-C-alkyl, and 5-membered heteroaryl or 4- to 7-membered heterocycloalkyl having at least one nitrogen atom whereby the heteroaryl ring is connected to a pyridine ring (each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, 1 to 5 halogen atoms). C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms). or Q is the formula (Q5) [ka]

[0122] [In formula: Z 17 , Z 18 , and Z 19 is hydrogen, and Z 20 is a halogen] or Q is the formula (Q6) [ka]

[0123] [In formula: T 1 ~T 4 are N, O, S, CZ 21 and NZ 22 wherein T 1 ~T 4 At most one of is O and T 1 ~T 4 At most one of is S, and T 1 ~T 4 One or less of NZ 22 where Individual Z 21 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, and Individual Z 22 are independently selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl] or Q is the formula (Q7) [ka]

[0124] [In formula: U 1 ~U 4 are N and CZ 23 independently selected from the group consisting of U 1 ~U 4 N is three or fewer of Individual Z 23 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy] is a five-membered aromatic heterocycle and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0125] Further embodiments of the first aspect of the present invention: In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: A is A1 or A2, [ka]

[0126] o is 0, 1 or 2; R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, R p is selected from the group consisting of hydrogen, C1-C4-alkyl, X and Y are CR 7 R 8 , O, S, and NR 9 wherein at least one of X and Y is independently selected from the group consisting of CR 7 R 8 and R 7 is selected from the group consisting of hydrogen and C1-C4-alkyl, R 8 is selected from the group consisting of hydrogen and C1-C4-alkyl, or R 7 and R 8 together form an oxo group (=O), R 9 is C1-C4-alkyl, R 10 is selected from the group consisting of hydrogen, —OH, C1-C4-alkyl and C1-C4-alkoxy, and R 11 is hydrogen, where Y is O, S or NR 9 If R 10 is not -OH or C1-C4-alkoxy] and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0127] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: A is A1 or A2, [ka]

[0128] o is 0, 1 or 2; R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, R p is hydrogen, X and Y are independent, CR 7 R 8 , O, and S; where at least one of X and Y is CR 7 R 8 and R 7 is selected from the group consisting of hydrogen and C1-C4-alkyl, R 8 is selected from the group consisting of hydrogen and C1-C4-alkyl , or R 7 and R 8 together form an oxo group (=O), R 10 is selected from the group consisting of hydrogen, —OH, C1-C4-alkyl and C1-C4-alkoxy, and R 11 is hydrogen, where Y is O, S or NR 9 If R 10 is not -OH) and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0129] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: A is A1 or A2, [ka]

[0130] o is 0 or 1, R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, R p is selected from the group consisting of hydrogen, C1-C4-alkyl, X is CR 7 R 8 , O, S, and NR 9 is selected from the group consisting of Y is CR 7 R 8 or O, R 7 is selected from the group consisting of hydrogen and C1-C4-alkyl, R 8 is selected from the group consisting of hydrogen and C1-C4-alkyl, or R 7 and R 8 together form an oxo group (=O), R 9 is C1-C4-alkyl, R 10 is selected from the group consisting of hydrogen, —OH and C1-C4-alkyl, R 11 is hydrogen] and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0131] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: A is A1 or A2, [ka]

[0132] o is 0 or 1, R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, R p is hydrogen, X is CR 7 R 8 , O and S; Y is CR 7 R 8 or O, R 7 is selected from the group consisting of hydrogen and C1-C4-alkyl, R 8 is selected from the group consisting of hydrogen and C1-C4-alkyl, or R 7 and R 8 together form an oxo group (=O), R 10 is selected from the group consisting of hydrogen, —OH and C1-C4-alkyl, and R 11 is hydrogen] and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0133] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: A, [ka]

[0134] selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0135] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: A, [ka]

[0136] The compounds include compounds selected from the group consisting of:

[0137] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R p is hydrogen or C1-C4-alkyl, preferably methyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0138] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2is hydrogen, (2-amino-2-oxoethyl)amino, (2-aminoethyl)amino, (2-hydroxyethyl)amino, hydroxymethyl, methoxymethyl, 2-hydroxyethyl, (2-hydroxyethyl)oxy, (2-methoxy-2-oxoethyl)amino, (3-methoxy-3-oxopropyl)-methylamino, (2-methoxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)oxy, (2R,6S)-2,6-dimethylmorpholin-4-yl, 2-(trifluoromethyl)amino, (2S)-2-methylmorpholin-4-yl, 2,2-difluoroethyl(methyl)amino, (3,3,3-trifluoropropyl)amino, (3-methoxybenzyl)oxy, (3rac,4rac)-3-amino-4-fluoropyrrolidin-1-yl, (3S)-3-(hydroxymethyl)pyrrolidin-1-yl, (carboxyethyl)amino, (cyclopentylmethyl)oxy, (pyridin-2-ylmethyl)amino, (rac)-3-hydroxypyrrolidin-1-yl, [2-(di Methylamino)ethyl]amino, 1,1-dioxidethiomorpholin-4-yl, 1,2-oxazolidin-2-yl, 1H-1,2,3-triazol-1-yl, 1H-imidazol-1-yl, 1H-pyrazol-1-yl, 1H-pyrazol-4-yl, 2,2-dimethylmorpholin-4-yl, 2,2-dimethylpyrrolidin-1-yl, 2,4-dimethyl-3,5-dioxo-1,2,4-triazolidin-1-yl, 2-amino-2-oxoethyl, 2H-1,2,3-triazol-2-yl, 1H-tetrazolium pyrazol-5-yl, 3-(pyrrolidin-1-yl)azetidin-1-yl, 3,3-difluoroazetidin-1-yl, 3,3-difluoropyrrolidin-1-yl, 3-fluoroazetidin-1-yl, 3-hydroxyazetidin-1-yl, 3-methylazetidin-1-yl, 3-oxopyrazolidin-1-yl, 1-(difluoromethyl)-1H-pyrazol-4-yl, 4-(trifluoromethyl)-1H-pyrazol-1-yl, 1-methyl-piperidin-4-yl, 4-fluoropiperidin-1-yl, 4,4-difluoropiperidin-1-yl, 4-oxoimidazolidin-1-yl, amino, anilino, azetidin-1-yl, benzyl(methyl)amino, chlorine, iodine, cyanomethyl, cyclobutyl(methyl)amino, cyclopentyloxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclopropyl(ethyl)amino, cyclopropyl(methyl)amino, cyclopropylamino, diethylamino, dimethylamino, dimethylaminocarbonyl, aminomethyl, 2-aminoethyl, (dimethylamino)methyl, 2-(dimethylamino)ethyl, ethenyl, ethyl, ethylamino, ethyloxy, ethylsulfanyl, ethylsulfinyl, ethylsulfonyl, isopropyl, isopropyloxy, methoxyamino, methyl, methyl(2,2,2-trifluoroethyl)amino, oxetan-3-ylmethylamino, methyl(oxetan-3-yl)amino, methylamino, methyloxy, methylsulfanyl, morpholin-4-yl, morpholin-4-ylamino, nitrilomethyl, prop-1-en-2-yl, propyl, propylamino, pyridin-4-yloxetan-3-yl, tetrahydrofuran-3-yl, 3,6-dihydro-2H-pyran-4-yl, tetrahydropyran-4-yl, tetrahydro-2H-pyran-4-yloxy, 3-thienyl, and thiomorpholin-4-yl; and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0139] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is selected from the group consisting of hydrogen, 3-(pyrrolidin-1-yl)azetidin-1-yl, 3,3-difluoroazetidin-1-yl, 3-fluoroazetidin-1-yl, 3-hydroxyazetidin-1-yl, 3-methylazetidin-1-yl, azetidin-1-yl, dimethylamino, isopropyl, methyl, and morpholin-4-yl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0140] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 3 is hydrogen or C1-C4-alkyl, preferably methyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0141] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is selected from the group consisting of hydrogen, halogen, preferably chlorine and fluorine, —OH, cyano, C1-C4-alkyl, preferably methyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, preferably trifluoromethyl, C1-C4-alkoxy, preferably methoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, preferably trifluoromethoxy, and NH2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0142] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 5 is selected from the group consisting of hydrogen, halogen, preferably chlorine and fluorine, —OH, cyano, C1-C4-alkyl, preferably methyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, preferably trifluoromethyl, C1-C4-alkoxy, preferably methoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0143] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 6 is selected from the group consisting of hydrogen, halogen, preferably chlorine and fluorine, —OH, cyano, C1-C4-alkyl, preferably methyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, preferably methoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0144] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Q is the formula (Q1) [ka]

[0145] [In formula: Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, 4- to 6-membered heterocyclyl, which may be substituted with one or two substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano; -C-C-alkyl), -S(O)-(C-C-alkyl), -SO-(C-C-alkyl), -S-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -SO-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, or Z1 and Z 2 together with the carbon atom to which they are attached form a 5- or 6-membered heterocycloalkyl, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine, and oxo; and Z 3 , Z 4 , and Z 5 are independently selected from the group consisting of hydrogen, halogen, cyano, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-alkoxy-C(O)-, C-C-halogenoalkoxy having 1 to 5 halogen atoms, or Z 2 and Z 3 together with the carbon atoms to which they are attached form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine, and oxo; and Z 1 , Z 4 , and Z 5 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms. is a substituted phenyl ring; Or in formula (Q1), Z 1 and Z 5 are independently selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-halogenoalkyl having 1 to 5 halogen atoms, Z 2 and Z 4are independently selected from the group consisting of hydrogen, halogen, cyano, -OH, C-C-alkyl, C-C-alkoxy, -NH(C-C-alkyl), -N(C-C-alkyl), C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-halogenoalkoxy having 1 to 5 halogen atoms, -S-(C-C-alkyl), S-(C-C-halogenoalkyl) having 1 to 5 halogen atoms and 4- to 6-membered heterocycloalkyl, and Z 3 is selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms and -N(C1-C4-alkyl)2, or Z 1 and Z 2 together with the carbon atom to which they are attached form a 5-membered heterocycloalkyl or a 5-membered heteroaryl, each of which is optionally substituted with 1 or 2 substituents selected from the group consisting of methyl, fluorine and oxo; Z 3 and Z 5 is hydrogen, and Z 4 is selected from the group consisting of hydrogen and C1-C4-alkoxy-C(O)-; or Z 1 and Z 5 are independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, methoxy, and trifluoromethyl; Z 2 and Z 4 are independently selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2, trifluoromethyl, methoxy, trifluoromethoxy, -SMe, 2,2,2-trifluoroethyl)sulfanyl, and morpholinyl; and Z 3 are independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy, and -NMe2. This includes compounds of the formula:

[0146] In a further aspect in formula (I), as defined in any of the above embodiments, Q may have one of the following meanings: Q is the formula (Q2) [ka]

[0147] [During the ceremony: Z 6 , Z 7 , Z 8 and Z 9 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2. or Q is the formula (Q3) [ka]

[0148] [During the ceremony: Z 10 , Z 11 and Z 12 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2. or Q is the formula (Q4) [ka]

[0149] [During the ceremony: Z 13 , Z 14 , Z 15 and Z 16 is a monocyclic heterocycle selected from the group consisting of hydrogen, halogen, cyano, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-hydroxyalkyl, NH, -NH(C-C-alkyl), -N(C-C-alkyl), -NH-CO-C-C-alkyl, and 5-membered heteroaryl or 4- to 7-membered heterocycloalkyl having at least one nitrogen atom whereby the heteroaryl ring is connected to a pyridine ring (each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, C-C-alkyl, C-C-hydroxyalkyl having 1 to 5 halogen atoms, C-C-hydroxyalkyl, NH, -NH(C-C-alkyl), -N(C-C-alkyl), -NH-CO-C-C-alkyl, and 5-membered heteroaryl or 4- to 7-membered heterocycloalkyl having at least one nitrogen atom whereby the heteroaryl ring is connected to a pyridine ring). 4-halogenoalkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms). Is the pyridine ring; Or in formula (Q4), Z 13 , Z 14 , Z 15 and Z 16is selected from the group consisting of hydrogen, halogen, cyano, C-C-alkyl, C-C-alkoxy, C-C-hydroxyalkyl, NH, -NH(C-C-alkyl), -N(C-C-alkyl), -NH-CO-C-C-alkyl, and 5-membered heteroaryl or 4- to 7-membered heterocycloalkyl having at least one nitrogen atom whereby the heteroaryl ring is connected to a pyridine ring (each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, C-C-alkyl, C-C-halogenoalkyl having 1 to 5 halogen atoms, C-C-alkoxy, C-C-hydroxyalkyl having 1 to 5 halogen atoms, independently selected from the group consisting of C-C-halogenoalkoxy having 1 to 5 halogen atoms, C-C-cycloalkyl, -NH, -NH(C-C-alkyl), -N(C-C-alkyl), -S-C-C-alkyl, -S(O)-C-C-alkyl, -SO-C-C-alkyl, -S-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C-C-halogenoalkyl) having 1 to 5 halogen atoms, -SO-(C-C-halogenoalkyl) having 1 to 5 halogen atoms; or Z 13 , Z 14 , Z 15 and Z 16 are independently selected from the group consisting of hydrogen, fluorine, chlorine, cyano, methyl, methoxy, ethoxy, isopropoxy, hydroxymethyl, NH, -NHMe, -NMe, -NH-C(O)-Me, morpholinyl; or Q is the formula (Q5) [ka]

[0150] [During the ceremony: Z 17 , Z 18 , Z 19 and Z 20are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2. Is the pyridine ring; Or in formula (Q5), Z 17 , Z 18 , and Z 19 is hydrogen, and Z 20 is a halogen; or Z 17 , Z 18 , and Z 19 is hydrogen, and Z 20 is fluorine, chlorine; or Q is the formula (Q6) [ka]

[0151] [During the ceremony: T 1 ~T 4 are N, O, S, CZ 21 and NZ 22 wherein T 1 ~T 4 At most one of is O and T 1 ~T 4 At most one of is S, and T 1 ~T 4 One or less of NZ 22 where Individual Z 21 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, and Individual Z 22are independently selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl. Is it a five-membered aromatic heterocycle? Or in equation (Q6), T 1 ~T 4 But N, O, S, CZ 21 and NZ 22 wherein T 1 ~T 4 At most one of is O and T 1 ~T 4 At most one of is S, and T 1 ~T 4 One or less of NZ 22 where Individual Z 21 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, and Individual Z 22 are independently selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or Q is, [ka] TIFF0007669343000040.tif39147

[0152] [During the ceremony: Individual Z 21 are independently selected from the group consisting of hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl, methoxy, and Z 22 is hydrogen, methyl] or selected from the group consisting of: Q is the formula (Q7) [ka]

[0153] [During the ceremony: U 1 ~U 4 are N and CZ 23 are independently selected from the group consisting of: 1 ~U 4 where N is at most three of Individual Z 23 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy. is a five-membered aromatic heterocycle; Or in equation (Q7), U 1 ~U 4 However, N and CZ 23 independently selected from the group consisting of U 1 ~U 4 where N is at most three of Individual Z 23 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy; or Q is, [ka]

[0154] [During the ceremony: Individual Z 23 are independently selected from the group consisting of hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl, and methoxy. is selected from the group consisting of:

[0155] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Q is phenyl, 2,5-bis(trifluoromethyl)phenyl, 2,3,4-trifluorophenyl, 2,3,5-trichlorophenyl, 2,3,5-trifluorophenyl, 2,3,6-trifluorophenyl, 2,3-dichlorophenyl, 2,3-dichloro-5-cyanophenyl, 2,3-dichloro-5-hydroxyphenyl, 2,3-difluorophenyl, 2,4,5-trifluorophenyl, 2,4,6-trifluoro-3-methoxyphenyl, 2,4-difluoro-3-hydroxyphenyl, 2,4-difluoro-3-methoxyphenyl, 2,5-dichlorophenyl, 2-chloro-5-cyanophenyl, 2-chloro-5-methylphenyl, 2,5-difluoro-4-methoxyphenyl, 2,6-difluorophenyl, 2-chloro-3-fluorophenyl, 2-chloro-4-(dimethylamino)phenyl, 2-chloro-4-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro -6-fluorophenyl, 2-chlorophenyl, 3,5-difluoropyridin-4-yl, 2-chloro-3-fluoropyridin-4-yl, 2-fluoro-5-methylphenyl, 3-fluoro-5-methylphenyl, 2-fluoro-3-(trifluoromethoxy)phenyl, 2-fluoro-3-(trifluoromethyl)phenyl, 5-fluoro-2-(trifluoromethyl)phenyl, 3-cyano-5-methylphenyl, 3-(trifluoromethyl)phenyl, 3-(trifluoromethoxy)phenyl, 3,4,5-trifluorophenyl, 3,4-dichlorophenyl, 3,4-difluoro-2-methoxyphenyl, 3,4-difluorophenyl, 3,5-dichloro-4-(dimethylamino)phenyl, 3,5-dichloro-4-fluorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 4-(difluoromethoxy)-3,5-difluorophenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 3-tert-butyl-5-methylphenyl, 5-tert-butyl-2-chloro-3-methylphenyl, 3-chloro-2-fluoro-5-methylphenyl, 3-chloro-2-fluorophenyl, 3-chloro-2-methylphenyl, 3-chloro-4-fluorophenyl, 3-chloro-4-methylphenyl, 2-chloro-3-(trifluoromethyl)phenyl, 2-methyl-5-(trifluoromethyl)phenyl, 3-chloro-5-(trifluoromethyl)phenyl, 3-chloro-5-ethylphenyl, 3-chloro-5-fluorophenyl, 3-chloro-5-methoxyphenyl, 3-chloro-5-methylphenyl, 3-chlorophenyl, 3-fluoro-2-methylphenyl, 3-fluoro-4-methoxyphenyl, 3-fluoro-5-methylphenyl, 4-fluoro-3-methoxyphenyl, 5-chloro 2,4-difluorophenyl, 5-chloro-2-fluoro-3-methylphenyl, 5-chloro-2-fluoro-4-methylphenyl, 5-chloro-2-fluorophenyl, 5-chloro-2-methoxyphenyl, 5-fluoro-2-methylphenyl, 5-fluoro-2-methoxyphenyl, 3,5-diethylphenyl, 2-chloro-3,5-diethylphenyl, 3-chloro-2-thienyl, 4-chloro-2-thienyl, 5-chloro-2-thienyl, 2,5-dichloro-3-thienyl, 5-fluoro-2-thienyl, 5-cyano-2-thienyl, 5-cyano-4-methyl-2-thienyl, 5-methyl-2-thienyl, 2,5-dimethyl-3-thienyl, 5-(trifluoromethyl)-2-thienyl, 3-tert-butyl-5-fluorophenyl, and 3-tert-butyl-5-chlorophenyl, This includes compounds of the formula:

[0156] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Q is selected from the group consisting of 2,3,5-trifluorophenyl, 3,5-dichlorophenyl, 3-tert-butyl-5-fluorophenyl, and 3-tert-butyl-5-chlorophenyl.

[0157] According to the present invention, there is provided a compound of the above formula (I), Q is a substituted phenyl ring of formula (Q1) as defined anywhere herein.

[0158] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: A is A3 or A4 [ka]

[0159] [where: R p is selected from hydrogen, C1-C4-alkyl; preferably hydrogen], as well as the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0160] In certain further embodiments of the first aspect, under the heading "Further embodiments of the first aspect of the invention", the invention encompasses combinations of two or more of the above-described embodiments.

[0161] The present invention includes any sub-combination of compounds of general formula (I) above within any embodiment or aspect of the invention.

[0162] The present invention includes compounds of general formula (I) disclosed in the Examples section of the text below.

[0163] The compounds of the present invention of general formula (I) can be prepared according to Schemes 1-2, as shown in the experimental section (General Procedures) of the present invention. The described schemes and procedures are illustrative of the synthetic routes to the compounds of general formula (I) of the present invention, and are not intended to be limiting. It will be apparent to those skilled in the art that the order of the transformations as illustrated in Schemes 1-2 can be modified in various ways. Therefore, the order of the transformations illustrated in these schemes is not intended to be limiting. Furthermore, the substituents Q, A, R 1 , R2 , R 3 , R 4 , R 5 or R 6 Interconversion of any of the following can be achieved before and / or after the exemplified transformations. These modifications can be the introduction of protecting groups, cleavage of protecting groups, reduction or oxidation of functional groups, halogenation, metallation, substitution, or other reactions known to those skilled in the art. These transformations include transformations that introduce functionality that allows further interconversion of substituents. Suitable protecting groups and their introduction and cleavage are well known to those skilled in the art (see, for example, T.W. Greene and P.G.M. Buts in Protective Groups in Organic Synthesis, 3rd ed., Wiley 1999). Specific examples are described in the following paragraphs.

[0164] According to a second aspect, the present invention encompasses a method for preparing a compound of general formula (I) as defined above, said method comprising the step of reacting a compound of general formula 1C: [ka]

[0165] [In the formula, A, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is as defined for the compounds of general formula (I) defined above, and Hal is halogen, in particular chlorine and bromine. by reacting an intermediate compound of general formula 1D: [ka]

[0166] wherein each R may independently be H or Me, or both R are pinacolato. reacting with a compound of This provides a compound of general formula (I): [ka]

[0167] [In the formula, A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Q is as defined above. and then optionally converting said compound into a solvate, salt and / or solvate of such a salt using a corresponding (i) solvent and / or (ii) base or acid.

[0168] According to a third aspect, the present invention encompasses intermediate compounds useful in the preparation of compounds of general formula (I) above.

[0169] In particular, the present invention provides compounds of general formula 1A: [ka]

[0170] [During the ceremony, R 2 is as defined above for compounds of general formula (I), R 3 , R 4 , R 5 , and R 6 is as defined above for compounds of general formula (I), and Hal is bromine or chlorine. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0171] Furthermore, the present invention provides compounds of general formula 1C: [ka]

[0172] [During the ceremony, A, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is as defined above for compounds of general formula (I), and Hal is bromine or chlorine. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0173] In particular, the present invention encompasses intermediate compounds of the following general formula 1C, preferably intermediate compounds of formulas 1C-1 to 1C-9 according to Table 2 below.

[0174] According to a fourth aspect, the present invention encompasses the use of said intermediate compounds for the preparation of compounds of general formula (I) as defined above.

[0175] The present invention includes the intermediate compounds disclosed in the Examples section of the text below.

[0176] The compound of the present invention represented by general formula (I) can be converted into any salt, preferably a pharmaceutically acceptable salt, by any method known to those skilled in the art, as described herein.Similarly, any salt of the compound of the present invention represented by general formula (I) can be converted into a free compound by any method known to those skilled in the art.

[0177] The compounds of general formula (I) of the present invention exhibit an unexpected and valuable pharmacological spectrum of action. The compounds of the present invention have surprisingly been found to interact effectively with Slo-1, and therefore, said compounds can be used for the treatment or prevention of diseases, preferably helminth infections, in particular gastrointestinal and extraintestinal helminth infections, more particularly gastrointestinal and extraintestinal infections by nematodes in humans and animals. The compounds of the present invention can be used to control, treat and / or prevent helminth infections, particularly gastrointestinal and extraintestinal helminth infections. The method comprises administering to a mammal in need thereof an amount of a compound of the present invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate or ester thereof, which is effective to treat the disorder.

[0178] In another aspect, the method comprises administering to a bird, i.e., a caged bird, particularly poultry, in need thereof, an amount of a compound of the invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate, or ester thereof, which is effective to treat the disorder.

[0179] In particular, in the field of veterinary medicine, the compounds of the present invention have favorable toxicity in warm-blooded animals and are suitable for controlling parasites, especially helminths, occurring in animal breeding and animal husbandry in livestock, breeding, zoo, laboratory, experimental and domestic animals, and are active against all or specific developmental stages of parasites, especially helminths.

[0180] Agricultural livestock may include, for example: mammals, such as sheep, goats, horses, donkeys, camels, water buffalo, rabbits, reindeer, fallow deer, and in particular cattle and pigs; or poultry, such as turkeys, ducks, geese, and in particular chickens; or fish or crustaceans, for example in aquaculture.

[0181] Domestic animals may include, for example: mammals, such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets, and, in particular, dogs, cats; caged birds; reptiles, amphibians, or aquarium fish.

[0182] The present invention also provides methods for treating helminth infections, particularly gastrointestinal and extraintestinal helminth infections, and more particularly gastrointestinal and extraintestinal infections caused by nematodes.

[0183] These disorders have been well characterized in animals and can be treated by administering the pharmaceutical compositions of the present invention.

[0184] As used herein, the term "treat" or "treatment" is conventionally used for the management or care of a subject for the purpose of combating, alleviating, reducing, relieving, or ameliorating the condition of a disease or disorder, such as, for example, a nematode infection. In particular, and particularly in the field of animal health or veterinary medicine, the term "treat" or "treatment" includes prophylactic, metaphylactic, or therapeutic treatment.

[0185] Helminths that are pathogenic to humans or animals include, for example, acanthocephala, nematodes, pentastoma, and platyhelminths (e.g., monogenea, cestodes, and trematodes).

[0186] Exemplary helminths include, but are not limited to: Monogenea: for example: Dactylogyrus spp., Gyrodactylus spp., Microbothrium spp., Polystoma spp., Troglocephalus spp.; Cestodes: from the order Pseudophyllidea, for example: Bothridium spp., Diphyllobothrium spp., Diplogonoporus spp., Ichthyobothrium spp., Ligula spp., Schistocephalus spp., Spirometra spp.; From the order of the Cyclophyllida, for example: Andyra spp., Anoplocephala spp., Avitellina spp., Bertiella spp., Cittotaenia spp., Davainea spp., Diorchis spp., Diplopylidium spp., Dipylidium spp., Echinococcus spp., Echinocotyle spp., Echinolepis spp. spp.), Hydatigera spp., Hymenolepis spp., Joyeuxiella spp., Mesocestoides spp., Moniezia spp., Paranoplocephala spp., Raillietina spp., Stilesia spp., Taenia spp., Thysaniezia spp., Thysanosoma spp.; Trematodes: from the subclass Digenea, for example: Austrobilharzia spp., Brachylaima spp., Calicophoron spp., Catatropis spp., Clonorchis spp., Collyriclum spp., Cotylophoron spp., Cyclocoelum spp., Dicrocoelium spp., Diplostomum spp., Echinochasmus spp., Echinoparyphium spp. spp.), Echinostoma spp., Eurytrema spp., Fasciola spp., Fasciolides spp., Fasciolopsis spp., Fischoederius spp., Gastrothylacus spp., Gigantobilharzia spp., Gigantocotyle spp., Heterophyes spp., Hypoderaeum spp., Leucochloridium spp. spp.), Metagonimus spp., Metorchis spp., Nanophyetus spp., Notocotylus spp., Opisthorchis spp., Ornithobilharzia spp., Paragonimus spp., Paramphistomum spp., Plagiorchis spp.), Posthodiplostomum spp., Prosthogonimus spp., Schistosoma spp., Trichobilharzia spp., Troglotrema spp., Typhlocoelum spp.;. Nematodes: from the order Trichinellida, for example: Capillaria spp., Eucoleus spp., Paracapillaria spp., Trichinella spp., Trichomosoides spp., Trichuris spp.; From the order Tylenchida, for example: Micronema spp., Parastrangyloides spp., Strongyloides spp.; From the order of the Rhabditina, for example: Aelurostrongylus spp., Amidostomum spp., Ancylostoma spp., Angiostrongylus spp., Bronchonema spp., Bunostomum spp., Chabertia spp., Cooperia spp., Cooperioides spp., Crenosoma spp., Cyathostomum spp., Cyclococercus spp. spp.), Cyclodontostomum spp., Cyclocercus spp., Cylicocyclus spp., Cylicostephanus spp., Cylindropharynx spp., Cystocaulus spp., Dictyocaulus spp., Elaphostrongylus spp., Filaroides spp., Globocephalus spp., Graphidium spp., Gyalocephalus spp., Haemonchus spp. spp.), Heligmosomoides spp., Hyostrongylus spp., Marshallagia spp., Metastrongylus spp., Muellerius spp., Necator spp., Nematodirus spp., Neostrongylus spp.), Nippostrongylus spp., Obeliscoides spp., Oesophagodontus spp., Oesophagostomum spp., Ollulanus spp.; Ornithostrongylus spp., Oslerus spp., Ostertagia spp., Paracooperia spp., Paraclenosoma spp., Parafilaroides spp., Parelaphostrongylus spp. spp.), Pneumocaulus spp., Pneumostrongylus spp., Poteriostomum spp., Protostrongylus spp., Spicocaulus spp., Stephanurus spp., Strongylus spp., Syngamus spp., Teladorsagia spp., Trichonema spp., Trichostrongylus spp., Triodontophorus spp. spp.), Troglostrongylus spp., Uncinaria spp.;. From the order of the Spirurida, for example: Acanthocheilonema spp., Anisakis spp., Ascaridia spp.; Ascaris spp., Ascarops spp., Aspiculuris spp., Baylisascaris spp., Brugia spp., Cercopithifilaria spp., Crassicauda spp., Dipetalonema spp., Dirofilaria spp., Dracunculus spp. spp.); Draschia spp., Enterobius spp., Filaria spp., Gnathostoma spp., Gongylonema spp., Habronema spp., Heterakis spp.; Litomosoides spp., Loa spp., Onchocerca spp., Oxyuris spp., Parabronema spp., Parafilaria spp., Parascaris spp. spp.), Passalurus spp., Physaloptera spp., Probstmayria spp., Pseudofilaria spp., Setaria spp., Skjrabinema spp., Spirocerca spp., Stephanofilaria spp., Strongyluris spp.), Syphacia spp., Thelazia spp., Toxascaris spp., Toxocara spp., Wuchereria spp.;. Acantocephala: from the order Oligacanthorhynchida, for example: Macracanthorhynchus spp., Prosthenorchis spp.; from the order Moniliformida, for example: Moniliformis spp.; From the order of the Polymorphida, for example: Filicollis spp.; From the order of the Echinorhynchida, for example: Acanthocephalus spp., Echinorhynchus spp., Leptorhynchoides spp.; Phylum Pentastoma: Order Porocephalida, for example, Linguatula spp.

[0187] The compounds of the present invention may be particularly useful for the treatment and prevention, i.e. prophylaxis, of helminth infections, particularly gastrointestinal and extraintestinal helminth infections, more particularly gastrointestinal and extraintestinal infections caused by nematodes.

[0188] The use of the compounds of the invention to control animal parasites, particularly helminths, is intended to reduce or prevent disease, mortality and performance loss (in the case of meat, milk, wool, hides, eggs, honey, etc.), resulting in more economical and simpler animal rearing and better animal welfare.

[0189] The terms "control" or "controlling" as used herein in relation to the animal health field mean that the compounds of the invention are effective in reducing the incidence of the respective parasite in an animal infected with such parasite to a harmless level. More specifically, "control", as used herein, means that the compounds of the invention are effective in killing, inhibiting the growth of, or inhibiting the proliferation of the respective parasite.

[0190] According to a further aspect, the present invention encompasses compounds of general formula (I) as defined above, or stereoisomers, tautomers, N-oxides, hydrates, solvates and salts thereof, in particular pharmaceutically acceptable salts thereof, or mixtures thereof, for use in the treatment or prevention of diseases, in particular helminth infections, in particular gastrointestinal and extraintestinal helminth infections, more particularly gastrointestinal and extraintestinal infections by nematodes.

[0191] The pharmaceutical activity of the compounds according to the invention can be explained by their interaction with the Slo-1 ion channel.

[0192] According to a further aspect, the present invention encompasses the use of a compound of general formula (I) as defined above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, and salt thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof, for the treatment or prevention of a disease, in particular a helminth infection, in particular a gastrointestinal and extraintestinal helminth infection, more particularly a gastrointestinal and extraintestinal infection by a nematode.

[0193] According to a further aspect, the present invention encompasses the use of a compound of general formula (I) as defined above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, and salt thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof, in a method for the treatment or prevention of disease, in particular helminth infections, in particular gastrointestinal and extraintestinal helminth infections, more particularly gastrointestinal and extraintestinal infections by nematodes.

[0194] According to a further aspect, the present invention encompasses the use of a compound of general formula (I) as defined above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, and salts thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof, for preparing a pharmaceutical composition, preferably a medicament, for the prevention or treatment of diseases, in particular helminth infections, in particular gastrointestinal and extraintestinal helminth infections, more particularly gastrointestinal and extraintestinal infections by nematodes.

[0195] According to a further aspect, the present invention encompasses a method for the treatment or prevention of diseases, in particular helminth infections, in particular gastrointestinal and extraintestinal helminth infections, more particularly gastrointestinal and extraintestinal infections by nematodes, using an effective amount of a compound of general formula (I) as above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, and salts thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof.

[0196] According to a further aspect, the present invention encompasses a compound of general formula (I) above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, and salts thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof, for use as an anti-endoparasitic agent.

[0197] According to a further aspect, the present invention covers compounds of general formula (I) as defined above, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, in particular pharmaceutically acceptable salts thereof, or mixtures thereof, for use as an antiparasitic agent, in particular for use as a nematicide, flatwormicide, thornyheadicide, or rheumicide.

[0198] According to a further aspect, the present invention encompasses pharmaceutical compositions, particularly veterinary formulations, comprising a compound of general formula (I) above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, salt thereof, particularly a pharmaceutically acceptable salt, or a mixture thereof, and one or more excipients, particularly one or more pharmaceutically acceptable excipients. Conventional procedures for preparing such pharmaceutical compositions in suitable dosage forms can be utilized.

[0199] According to a further aspect, the present invention encompasses a process for preparing a pharmaceutical composition, in particular a veterinary formulation, comprising the step of mixing a compound of general formula (I) as defined above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, salt thereof, in particular a pharmaceutically acceptable salt, or a mixture thereof, with one or more excipients, in particular one or more pharmaceutically acceptable excipients.

[0200] According to a further aspect, the present invention encompasses a method for the treatment or prevention of diseases, in particular helminth infections, in particular gastrointestinal and extraintestinal helminth infections, more particularly gastrointestinal and extraintestinal infections by nematodes, using a pharmaceutical composition, in particular a veterinary formulation, comprising an effective amount of a compound of general formula (I) as defined above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, and salt thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof.

[0201] According to a further aspect, the present invention encompasses a method for controlling helminth infections in humans and / or animals by administering to said human or animal in need thereof an anthelmintic effective amount of at least one compound of general formula (I) as defined anywhere herein.

[0202] The present invention further encompasses pharmaceutical compositions, in particular veterinary formulations, comprising at least one compound according to the invention, usually together with one or more pharmaceutically suitable excipients, and their use for the above purposes.

[0203] The compounds of the present invention can have systemic and / or local activity.To this end, they can be administered in a suitable manner, for example, orally, parenterally, pulmonary, nasal, sublingual, lingual, buccal, rectal, vaginal, cutaneous, transdermal, conjunctival, auricular, or as an implant or stent.Such administration can be prophylactically, metaphylactically, or therapeutically.

[0204] For these administration routes, the compounds of the present invention can be administered in suitable dosage forms.

[0205] For oral administration, the compounds of the present invention can be formulated into dosage forms known in the art that deliver the compounds of the present invention rapidly and / or in a modified manner, such as tablets (uncoated or coated tablets, e.g., tablets with enteric or controlled-release coatings that dissolve slowly or are insoluble), orally disintegrating tablets, films / wafers, films / lyophilisates, capsules (e.g., hard or soft gelatin capsules), dragees, granules, pellets, chewables (e.g., soft chewables), powders, emulsions, suspensions, aerosols, or solutions. The compounds of the present invention can be incorporated into such dosage forms in crystalline and / or amorphous and / or dissolved form.

[0206] Parenteral administration can be carried out by bypassing the absorption step (for example, intravenously, intraarterially, intracardially, intraspinally or intralumbarly) or by including absorption (for example, intramuscularly, subcutaneously, intradermally, transdermally or intraperitoneally). Suitable dosage forms for parenteral administration are, inter alia, preparations for injection and infusion in the form of solutions, suspensions, emulsions, lyophilisates or sterile powders.

[0207] Examples of suitable forms for other administration routes are pharmaceutical forms for inhalation (especially powder inhalers, nebulizers), nasal drops, nasal solutions, nasal sprays; tablets / films / wafers / capsules for lingual, sublingual or buccal administration; suppositories; eye drops, eye ointments, eye baths, eye inserts, ear drops, ear sprays, ear powders, ear rinses, ear tampons; vaginal capsules, aqueous suspensions (lotions, mixturae agitandae), lipophilic suspensions, emulsions, ointments, creams, transdermal therapeutic systems (e.g. patches), milks, pastes, foams, spot-ons, dusting powders, implants or stents.

[0208] The compounds according to the invention can be incorporated into the dosage forms described. This can be achieved in a manner known per se by mixing with pharmaceutically suitable excipients. Pharmaceutically suitable excipients include, inter alia: Fillers and carriers (e.g., cellulose, microcrystalline cellulose (e.g., Avicel®), lactose, mannitol, starch, calcium phosphate (e.g., Di-Cafos®)), Ointment bases (e.g., petroleum jelly, paraffin, triglycerides, waxes, wool wax, wool wax alcohol, lanolin, hydrophilic ointments, polyethylene glycol), suppository bases (e.g., polyethylene glycol, cocoa butter, hard fats), solvents (e.g., water, ethanol, isopropanol, glycerol, propylene glycol, medium-chain triglyceride fatty oils, liquid polyethylene glycol, paraffin); surfactants, emulsifiers, dispersing agents or wetting agents (e.g. sodium dodecyl sulfate), lecithins, phospholipids, fatty alcohols (e.g. Lanette®), sorbitan fatty acid esters (e.g. Span®), polyoxyethylene sorbitan fatty acid esters (e.g. Tween®), polyoxyethylene fatty acid glycerides (e.g. Cremophor®), polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, glycerol fatty acid esters, poloxamers (e.g. Pluronic®), buffers, acids and bases (e.g., phosphates, carbonates, citric acid, acetic acid, hydrochloric acid, sodium hydroxide solution, ammonium carbonate, trometamol, triethanolamine); Isotonic agents (glucose, sodium chloride, etc.), Adsorbents (e.g., highly dispersed silica), thickening agents, gel-forming agents, thickeners and / or binders (e.g., polyvinylpyrrolidone, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, starch, carbomer, polyacrylic acid (e.g., Carbopol®); alginates, gelatin), disintegrants (e.g., modified starch, sodium carboxymethylcellulose, sodium starch glycolate (e.g., Explotab®), cross-linked polyvinylpyrrolidone, croscarmellose sodium (e.g., AcDiSol®)); flow regulators, lubricants, glidants and release agents (e.g. magnesium stearate, stearic acid, talc, highly dispersed silica (e.g. Aerosil®)); coating materials (e.g. sugar, shellac) and film-forming agents for rapidly or modified dissolving films or diffusion membranes (e.g. polyvinylpyrrolidone (e.g. Kollidon®), polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate, cellulose acetate phthalate, polyacrylates, polymethacrylates, e.g. Eudragit®), capsule materials (e.g., gelatin, hydroxypropyl methylcellulose), synthetic polymers (e.g. polylactides, polyglycolides, polyacrylates, polymethacrylates (e.g. Eudragit®), polyvinylpyrrolidones (e.g. Kollidon®), polyvinyl alcohols, polyvinyl acetates, polyethylene oxides, polyethylene glycols and their copolymers and block copolymers); Plasticizers (e.g., polyethylene glycol, propylene glycol, glycerol, triacetin, triacetyl citrate, dibutyl phthalate), penetration enhancers, stabilizers (e.g., antioxidants, e.g., ascorbic acid, ascorbyl palmitate, sodium ascorbate, butylhydroxyanisole, butylhydroxytoluene, propyl gallate), Preservatives (e.g., parabens, sorbic acid, thiomersal, benzalkonium chloride, chlorhexidine acetate, sodium benzoate), colorants (e.g. inorganic pigments, e.g. iron oxide, titanium dioxide), Flavorings, sweeteners, flavorings and / or odor masking agents.

[0209] The present invention further relates to pharmaceutical compositions comprising at least one compound according to the invention, usually together with one or more pharmaceutically suitable excipients, and to their uses according to the invention.

[0210] According to another aspect, the present invention encompasses pharmaceutical combinations, in particular medicaments, comprising at least one compound of general formula (I) according to the present invention and at least one or more further active ingredients, in particular for the treatment and / or prevention of endo- and / or ectoparasitic infections.

[0211] The term "endoparasite" in the present invention is used as known to those skilled in the art and refers in particular to helminths. The term "ectoparasite" in the present invention is used as known to those skilled in the art and refers in particular to arthropods, in particular insects or mites.

[0212] In particular, the present invention provides: one or more first active ingredients, in particular compounds of general formula (I) as defined above, and one or more further active ingredients, in particular one or more endo- and / or ecto-parasiticides The present invention also encompasses pharmaceutical combinations, particularly veterinary combinations, comprising:

[0213] The term "combination" in the present invention is used as known to those skilled in the art, and said combination can be a fixed combination, a non-fixed combination, or a kit-of-parts combination.

[0214] "Fixed combination" in the present invention is used as known to those skilled in the art, and is defined as, for example, a combination in which a first active ingredient, for example, one or more compounds of general formula (I) of the present invention, and an additional active ingredient are present together in one unit dosage or one single entity.One example of a "fixed combination" is a pharmaceutical composition in which the first active ingredient and the additional active ingredient are present in a mixture for simultaneous administration, such as in a pharmaceutical preparation.Another example of a "fixed combination" is a pharmaceutical combination in which the first active ingredient and the additional active ingredient are present in one unit, not in a mixture.

[0215] In the present invention, the term "unfixed combination" or "kit of parts" is used as known to those skilled in the art and is defined as a combination in which a first active ingredient and an additional active ingredient are present in two or more units. An example of a non-fixed combination or kit of parts is a combination in which a first active ingredient and an additional active ingredient are present separately. The components of a non-fixed combination or kit of parts can be administered separately, sequentially, simultaneously, concurrently, or chronologically staggered.

[0216] The compound of the present invention can be administered as a sole pharmaceutical or in combination with one or more other medicament active ingredients, and this combination does not cause unacceptable adverse effects.The present invention also encompasses such pharmaceutical combinations.For example, the compound of the present invention can be combined with known ectoparasiticides and / or endoparasiticides.

[0217] Other or further active ingredients identified herein by common name are known and are described, for example, in the Pesticide Manual ("The Pesticide Manual" 16th Edition, British Crop Protection Council 2012) or can be found on the internet (e.g., http: / / www.alanwood.net / pesticides). Classification is based on the IRAC Mode of Action Classification Scheme current at the time of filing this patent application.

[0218] Examples of ecto- and / or endoparasiticides are insecticides, acaricides and nematicides, including in particular: (1) Acetylcholinesterase (AChE) inhibitors, such as carbamates, e.g., alanycarb, aldicarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, XMC, and xylylcarb; or organophosphates, e.g., acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, cadusafos, chlorethoxyphos, chlorfenvinphos, chlormephos, chlorpyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos / DDVP, Dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famfur, fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, imidiyaphos, isofenphos, O-(methoxyaminothiophosphoryl) isopropyl salicylate, isoxathion, malathion, mecarbam, methamidophos, methidathion, mevinphos, monocrotophos, naled, Omethoate, oxydemeton-methyl, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimiphos-methyl, profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, trichlorfon and vamidothion.

[0219] (2) GABA-regulated chloride channel blockers, such as cyclodiene-organochlorines, such as chlordane and endosulfan; or phenylpyrazoles (fiproles), such as ethiprole and fipronil.

[0220] (3) Sodium channel modulators, for example, pyrethroids, for example, acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin s-cyclopentenyl isomer, bioresmethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin [(1R)-trans-isomer], deltamethrin, empenthrin [(EZ)-(1R)-isomer], esfenvalerate, etofenprox, fenpropanol thrin, fenvalerate, flucythrinate, flumethrin, tau-fluvalinate, halfenprox, imiprothrin, kadethrin, momfluorotrin, permethrin, fenothrin [(1R)-trans-isomer], prallethrin, pyrethrins (pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin, tetramethrin [(1R)-isomer], tralomethrin and transfluthrin or DDT or methoxychlor.

[0221] (4) Nicotinic acetylcholine receptor (nAChR) competitive modulators, neonicotinoids, such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam, or nicotine, or sulfoxaflor, or flupyradifurone.

[0222] (5) Nicotinic acetylcholine receptor (nAChR) allosteric modulators, for example, spinosyns, such as spinetoram and spinosad.

[0223] (6) Glutamate-gated chloride channel (GluCl) allosteric modulators, for example, avermectins / milbemycins, such as abamectin, emamectin benzoate, lepimectin, and milbemectin.

[0224] (7) Juvenile hormone mimetics, for example, juvenile hormone analogs, such as hydroprene, kinoprene, and methoprene or fenoxycarb or pyriproxyfen.

[0225] (9) Chordotonal organ modulators, such as pymetrozine or flonicamide.

[0226] (10) Mite growth inhibitors, such as clofentezine, hexythiazox, and diflobidazine or etoxazole.

[0227] (12) Inhibitors of mitochondrial ATP synthase, for example, ATP disruptors such as diafenthiuron or organotin compounds such as azocyclotin, cyhexatin and fenbutatin oxide or propargite or tetradifon.

[0228] (13) Uncouplers of oxidative phosphorylation by disrupting the proton gradient, such as chlorfenapyr, DNOC, and sulfluramide.

[0229] (14) Nicotinic acetylcholine receptor channel blockers, such as bensultap, cartap hydrochloride, thiocylam, and thiosultap-sodium.

[0230] (15) Inhibitors of chitin biosynthesis (type 0), such as bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, and triflumuron.

[0231] (16) Chitin biosynthesis inhibitors, type 1, e.g., buprofezin.

[0232] (17) Molting disruptors (especially in Diptera, i.e., flies), e.g., Cyromazine.

[0233] (18) Ecdysone receptor agonists, such as chromafenozide, halofenozide, methoxyfenozide, and tebufenozide.

[0234] (19) Octopamine receptor agonists, such as amitraz.

[0235] (20) Mitochondrial complex III electron transport inhibitors, such as hydramethylnon or acequinocyl or fluacrypyrim.

[0236] (21) Mitochondrial complex I electron transport inhibitors, such as fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad and tolfenpyrad or rotenone (Derris), from the group of METI acaricides.

[0237] (22) Voltage-gated sodium channel blockers, such as indoxacarb or metaflumizone.

[0238] (23) Inhibitors of acetyl-CoA carboxylase, such as tetronic acid derivatives and tetramic acid derivatives, such as spirodiclofen, spiromesifen, and spirotetramat.

[0239] (25) Mitochondrial complex II electron transport inhibitors, for example, β-ketonitrile derivatives, such as cyenopyrafen and cyflumetofen, and carboxanilides, such as piflubumid.

[0240] (28) Ryanodine receptor modulators, for example, diamides, such as chlorantraniliprole, cyantraniliprole, and flubendiamide.

[0241] The following further active compounds are also known: Afidopiropen, Afoxolaner, Azadirachtin, Benclotiaz, Benzoximate, Bifenazate, Brofuranilide, Bromopropylate, Chinomethionate, Chlorprallethrin, Cryolite, Cyclaniliprole, Cycloxaprid, Cyhalodiamide, Dichloromezothiaz, Dicofol, ε-Metofluthrin, ε-Momfluorothrin Momfluthrin, flometoquin, fluazaindolizine, fluensulfone, flufenerim, flufenoxystrobin, flufiprole, fluhexafon, fluopyram, fluralaner, fluxamethamide, fufenozide, guadipyr, heptafluthrin, imidaclothiz, iprodione, kappa-bifenthrin, kappa-tefluthrin, lotilaner, meperfluthrin, paichongding, pyridalyl, pyrifluquinazone, pyriminostrobin, spirobudiclofen, tetramethylfluthrin, tetraniliprole, tetrachlorantraniliprole, thioxazaphen, thiofluoximate, triflumezopyrim, and iodomethane; and Bacillus firmus (Bacillus firmus) (I-1582, BioNeem, Votivo), and the following compounds: 1-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)sulfinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazol-5-amine (known from WO 2006 / 043635) (CAS 885026-50-6), {1'-[(2E)-3-(4-chlorophenyl)prop-2-en-1-yl]-5-fluorospiro[indole-3,4'-piperidin]-1(2H)-yl}(2-chloropyridin-4-yl)methanone (known from WO2003 / 106457) (CAS 637360-23-7), 2-chloro-N-[2-{1-[(2E)-3-(4-chlorophenyl)prop-2-en-1-yl]piperidin-4-yl}-4-(trifluoromethyl)phenyl]isonicotinamide (known from WO2006 / 003494) (CAS 872999-66-1), 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one (known from WO2010052161) (CAS 1225292-17-0), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-yl ethyl carbonate (known from EP2647626) (CAS 1440516-42-6), 4-(but-2-yn-1-yloxy)-6-(3,5-dimethylpiperidin-1-yl)-5-fluoropyrimidine (known from WO2004 / 099160) (CAS 792914-58-0), PF1364 (known from JP2010 / 018586) (CAS 1204776-60-2), N-[(2E)-1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-ylindene]-2,2,2-trifluoroacetamide (known from WO2012 / 029672) (CAS 1363400-41-2), (3E)-3-[1-[(6-chloro-3-pyridyl)methyl]-2-pyridylidene]-1,1,1-trifluoro-propan-2-one (known from WO2013 / 144213) (CAS 1461743-15-6), N-[3-(benzylcarbamoyl)-4-chlorophenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (known from WO2010 / 051926) (CAS 1226889-14-0), 5-bromo-4-chloro-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloro-2-pyridyl)pyrazole-3-carboxamide (known from CN103232431) (CAS 1449220-44-3), 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxido-3-thietanyl)benzamide, 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(trans-1-oxido-3-thietanyl)benzamide and 4-[(5S)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxido-3-thietanyl)benzamide (known from WO2013 / 050317A1) (CAS 1332628-83-7), N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]propanamide, (+)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]propanamide and (-)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]propanamide (known from WO2013 / 162715A2, WO2013 / 162716A2, US2014 / 0213448A1) (CAS 1477923-37-7), 5-[[(2E)-3-chloro-2-propen-1-yl]amino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile (known from CN101337937A) (CAS 1105672-77-2), 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)thioxomethyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, (Liudaibenjiaxuanan, known from CN103109816A) (CAS 1232543-85-9); N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-(fluoromethoxy)-1H-pyrazole-5-carboxamide (known from WO2012 / 034403A1) (CAS 1268277-22-0), N-[2-(5-amino-1,3,4-thiadiazol-2-yl)-4-chloro-6-methylphenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide (known from WO2011 / 085575A1) (CAS 1233882-22-8), 4-[3-[2,6-dichloro-4-[(3,3-dichloro-2-propen-1-yl)oxy]phenoxy]propoxy]-2-methoxy-6-(trifluoromethyl)pyrimidine (CN101337940A) (CAS 1108184-52-6); (2E)- and 2(Z)-2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]hydrazinecarboxamide (known from CN101715774A) (CAS 1232543-85-9; cyclopropanecarboxylic acid 3-(2,2-dichloroethenyl)-2,2-dimethyl-4-(1H-benzimidazol-2-yl)phenyl ester (known from CN103524422A) (CAS 1542271-46-4); (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-[(trifluoromethyl)thio]phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylic acid methyl ester (known from CN102391261A) (CAS 1370358-69-2;6-deoxy-3-O-ethyl-2,4-di-O-methyl-1-[N-[4-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1H-1,2,4-triazol-3-yl]phenyl]carbamate]-α-L-mannopyranose (known from US2014 / 0275503A1) (CAS 1181213-14-8); 8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3-azabicyclo[3.2.1]octane (CAS 1253850-56-4), (8-anti)-8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3-azabicyclo[3.2.1]octane (CAS 933798-27-7), (8-syn)-8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3-azabicyclo[3.2.1]octane (known from WO2007040280A1 and WO2007040282A1) (CAS 934001-66-8), N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)thio]propanamide (known from WO2015 / 058021A1 and WO2015 / 058028A1) (CAS 1477919-27-9), N-[4-(aminothioxomethyl)-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide (known from CN103265527A) (CAS 1452877-50-7), 5-(1,3-dioxan-2-yl)-4-[[4-(trifluoromethyl)phenyl]methoxy]pyrimidine (known from WO2013 / 115391A1) (CAS 1449021-97-9), 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-methoxy-1-methyl-1,8-diazaspiro[4.5]dec-3-en-2-one (known from WO2010 / 066780A1 and WO2011 / 151146A1) (CAS 1229023-34-0), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-1,8-diazaspiro[4.5]decane-2,4-dione (known from WO2014 / 187846A1) (CAS 1638765-58-8), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-yl-carboxylic acid ethyl ester (known from WO2010 / 066780A1, WO2011151146A1) (CAS 1229023-00-0), N-[1-[(6-chloro-3-pyridinyl)methyl]-2(1H)-pyridinylindene]-2,2,2-trifluoro-acetamide (known from DE3639877A1, WO2012029672A1) (CAS 1363400-41-2), [N(E)]-N-[1-[(6-chloro-3-pyridinyl)methyl]-2(1H)-pyridinylindene]-2,2,2-trifluoro-acetamide, (known from WO2016005276A1) (CAS 1689566-03-7), [N(Z)]-N-[1-[(6-chloro-3-pyridinyl)methyl]-2(1H)-pyridinylindene]-2,2,2-trifluoro-acetamide, (CAS 1702305-40-5), 3-endo-3-[2-propoxy-4-(trifluoromethyl)phenoxy]-9-[[5-(trifluoromethyl)-2-pyridinyl]oxy]-9-azabicyclo[3.3.1]nonane (WO20, 11 / 105506A1, known from WO2016 / 133011A1) (CAS 1332838-17-1).

[0242] Active ingredients with unknown or unspecified mechanism of action, such as fentrifanil, fenoxacrim, cycloprene, chlorobenzilate, chlordimeform, flubenzimine, dicyclanil, amidoflumet, chinomethionate, triatene, clothiazobene, tetrasul, potassium oleate, petroleum, methoxadiazone, gossypurle, flutenzin, bromopropylate, cryolite.

[0243] Ingredients from another class, such as butacarb, dimethylan, cloetocarb, phosphocarb, pirimiphos(-ethyl), parathion(-ethyl), methacrifos, isopropyl o-salicylate, trichlorfon, sulprofos, propafos, cebufos, pyridathion, protoate, diclofenthion, demeton-S-methylsulfone, isazofos, cyanofenphos, dialifos, carbophenothion, autathiofos, allomfenvinphos(-methyl), azinphos(-ethyl), chlorpyrifos(-ethyl), fosmetilan, iodofenphos, dioxabenzophos, formothion, fonofos, flupyrazophos, fensulfothion, etrimphos; Organochlorines, such as camphechlor, lindane, heptachlor; or phenylpyrazoles, such as acetoprole, pyrafluprole, pyriprole, vaniliprole, cisapronil; or isoxazolines, such as sarolaner, afoxolaner, lotilaner, fluralaner; Pyrethroids, such as (cis-, trans-)metofluthrin, profluthrin, flufenprox, flubrocythrinate, fubufenprox, fenfluthrin, protrifenbut, pyresmethrin, RU15525, terallethrin, cis-resmethrin, heptafluthrin, bioethanomethrin, biopermethrin, fenpyrithrin, cis-cypermethrin, cis-permethrin, clocithrin, cyhalothrin (lambda-), clovaporthrin, or halogenated hydrocarbons (HCHs); Neonicotinoids, for example, nithiazine; Dichloromezotiaz, triflumezopyrim; Macrocyclic lactones, such as nemadectin, ivermectin, latidectin, moxidectin, selamectin, eprinomectin, doramectin, emamectin benzoate; milbemycin oxime; Triplene, epofenonane, diofenolan; Biological agents, hormones, or pheromones, such as natural products, e.g., thuringiensin, codlemone, or neem components; Dinitrophenols, such as dinocap, dinobuton, binapacryl; Benzoylureas, for example, fluazuron, penfluron; Amidine derivatives, such as chlormebuform, cymiazole, demiditraz; Bee hive varroa acaricides, for example, organic acids, for example, formic acid, oxalic acid.

[0244] Non-limiting examples of insecticides and acaricides of particular interest for use in animal health are in particular [i.e., Mehlhorn et al. Encyclpaedic Reference of Parasitology 4th Edition (ISBN 978-3-662-43978-4)] and include: Effectors at arthropod ligand-gated chloride channels: chlordane, heptachlor, endoculfan, dieldrin, bromocyclen, toxaphen, lindane, fipronil, pyriprole, cisapronil, afoxolaner, fluraner, sarolaner, lotilaner, fluxametamide, broflanilide, avermectin, doramectin, eprinomectin, ivermectin, milbemycin, moxidectin, selamectin; Modulators of arthropod octopaminergic receptors: amitraz, BTS27271, cymiazole, demiditraz; Effectors at arthropod voltage-gated sodium channels: DDT, methoxychlor, metaflumizone, indoxacarb, cinerin I, cinerin II, jasmolin I, jasmolin II, pyrethrin I, pyrethrin II, allethrin, alpha-cypermethrin, bioallethrin, beta-cyfluthrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, etofenprox, fenvalerate, flucythrinate, flumethrin, halfenprox, permethrin, fenothrin, resmethrin, tau-fluvalinate, tetramethrin; Effectors at arthropod nicotinic cholinergic synapses (acetylcholinesterase, acetylcholine receptors): bromoprypylate, bendiocarb, carbaryl, methomyl, promacil, propoxur, azamethiphos, chlorfenvinphos, chlorpyrifos, coumaphos, cythioate, diazinon, dichlorvos, dicrotophos, dimethoate, ethion, fanfon, fenitrothion, fenthion, heptenophos, malathion, naled, phosmet, phoxim, phthalofos, propetamphos, temephos, tetrachlorvinphos, trichlorfon, imidacloprid, nitenpyram, dinotefuran, spinosad, spinetoram; Effectors during arthropod development: cyromazine, dicyclanil, diflubenzuron, fluazuron, lufenuron, triflumuron, fenoxycarb, hydroprene, methoprene, pyriproxyfen, fenoxycarb, hydroprene, S-methoprene, pyriproxyfen.

[0245] Exemplary active ingredients from the group of endoparasiticides as additional or other active ingredients in the present invention include, but are not limited to, anthelmintic active compounds and antiprotozoal active compounds.

[0246] Anthelmintic active compounds may include, but are not limited to, the following nematicidally, trematicidally and / or cestocidally active compounds: From the class of macrocyclic lactones, for example: eprinomectin, abamectin, nemadectin, moxidectin, doramectin, selamectin, lepimectin, latidectin, milbemectin, ivermectin, emamectin, milbemycin; From the class of the benzimidazoles and probenzimidazoles, for example: oxibendazole, mebendazole, triclabendazole, thiophanate, parbendazole, oxfendazole, netobimin, fenbendazole, febantel, thiabendazole, cyclobendazole, cambendazole, albendazole sulfoxide, albendazole, flubendazole; From the class of the depsipeptides, preferably from the class of the cyclic depsipeptides, in particular from the class of the 24-membered cyclic depsipeptides, for example: emodepside, PF1022A; From the class of the tetrahydropyrimidines, for example: morantel, pyrantel, oxantel; From the class of imidazothiazoles, for example: butamisole, levamisole, tetramisole; From the class of aminophenylamidines, for example: amidantel, deacylated amidantel (dAMD), tribendimidine; From the class of the aminoacetonitriles, for example: monepantel; From the class of the paraherquamides, for example: paraherquamide, delquantel; From the class of the salicylanilides, for example: tribromsalan, bromoxanide, brothianide, clioxanide, closantel, niclosamide, oxyclozanide, lafoxanide; From the class of substituted phenols, for example: nitroxynil, bithionol, disophenol, hexachlorophene, niclofolan, meniclopholan; From the class of organophosphates, for example: trichlorfon, naphthalofos, dichlorvos / DDVP, crufomate, coumaphos, haloxon; From the class of the piperazinones / quinolines, for example: praziquantel, epsiprantel; From the class of piperazines, for example: piperazine, hydroxyzine; From the class of tetracyclines, for example: tetracycline, chlortetracycline, doxycycline, oxytetracycline, rolitetracycline; From various other classes, for example: bunamidine, niridazole, resorantel, omfalotin, oltipraz, nitroscanate, nitroxynil, oxamniquine, mirasan, miracil, lucanthone, hycanthone, hetolin, emetine, diethylcarbamazine, dichlorophene, diamfenetide, clonazepam, bephenium, amoscanate, clorsulon.

[0247] Antiprotozoan active ingredients can include, but are not limited to, the following active ingredients: From the class of triazines, for example: diclazuril, ponazuril, letrazuril, toltrazuril; From the class of polyether ionophores, for example: monensin, salinomycin, maduramycin, narasin; From the class of macrocyclic lactones, for example: milbemycin, erythromycin; From the class of quinolones, for example: enrofloxacin, pradofloxacin; From the quinine class, for example: chloroquine; From the class of pyrimidines, for example: pyrimethamine; From the class of sulfonamides, for example: sulfaquinoxaline, trimethoprim, sulfaclozine; From the class of thiamines, for example: amprolium; From the class of lincosamides, for example: clindamycin; From the class of carbanilides, for example: imidocarb; From the class of nitrofurans, for example: nifurtimox; From the class of quinazolinone alkaloids, for example: halofuginone; Of various different classes, for example: oxamniquine, paromomycin; From the class of vaccines or microbial antigens, for example: Babesia canis rossi, Eimeria tenella, Eimeria praecox, Eimeria necatrix, Eimeria mitis, Eimeria maxima, Eimeria brunetti, Eimeria acervulina, Babesia canis vogeli, Leishmania infantum, Babesia canis canis, Dictyocaulus viviparus.

[0248] All named other or further active ingredients in the present invention can optionally form salts with suitable bases or acids, if their functional groups allow this.

[0249] Based on known standard laboratory techniques for evaluating compounds useful in the treatment of helminth infections, by standard toxicity tests and by standard pharmacological assays for determining the treatment of the above conditions in animals, and by comparing these results with those of known active ingredients or drugs used to treat these conditions, the effective dose of the compounds of the present invention can be easily determined for the treatment of each desired indication. The amount of active ingredient administered in the treatment of one of these conditions can vary widely depending on such considerations as the particular compound and dosage unit used, the mode of administration, the duration of treatment, the age and sex of the subject being treated, and the nature and severity of the condition being treated.

[0250] The total amount of active ingredient administered will generally range from about 0.001 mg / kg to about 200 mg / kg body weight per day, preferably from about 0.01 mg / kg to about 20 mg / kg body weight per day. Clinically useful dosing schedules range from one to three times daily to once every four weeks. A "drug holiday" during which the subject is not administered a period of time may be beneficial in balancing the overall pharmacological activity and tolerability. Furthermore, it is possible for subjects to receive long-acting treatments in which the treatment is administered once every four weeks. A unit dose may contain from about 0.5 mg to about 1500 mg of active ingredient and may be administered more than once per day or less than once per day. The average daily dose for administration by injection, including intravenous, intramuscular, subcutaneous, and parenteral injections, as well as the use of infusion techniques, is preferably 0.01 to 200 mg / kg total body weight. The average daily rectal dosing regimen is preferably 0.01 to 200 mg / kg total body weight. The average daily vaginal dosage regimen is preferably 0.01 to 200 mg / kg total body weight. The average daily topical dosage regimen is preferably 0.1 to 200 mg administered between 1 and 4 times daily. The transdermal concentration is preferably that required to maintain a daily dose of 0.01 to 200 mg / kg. The average daily inhalation dosage regimen is preferably 0.01 to 100 mg / kg total body weight.

[0251] Of course, the particular initial and continued dosing regimens for each subject will vary according to the nature and severity of the condition as determined by the attending diagnostician, the activity of the particular compound used, the age and general condition of the subject, the time of administration, the route of administration, the rate of excretion of the drug, the combination of drugs, etc. The desired mode of treatment and frequency of administration of the compounds of the invention or pharmaceutically acceptable salts or esters thereof or compositions thereof can be ascertained by one skilled in the art using conventional therapeutic trials.

[0252] Experimental Section Abbreviations and acronyms aq. water atm standard atmosphere BOP Benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphonate Brine: saturated aqueous sodium chloride solution CDCl3 deuterated chloroform DAD Diode Array Detector DCM dichloromethane DMF N,N-dimethylformamide DMSO dimethyl sulfoxide DMSO-d6 Deuterated Dimethyl Sulfoxide ELSD Evaporative Light Scattering Detector ESI electrospray ionization EtOAc ethyl acetate g grams h time HBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) LC-MS Liquid Chromatography Combined Mass Spectrometry MeOH Methanol min mg milligram MTBE Methyl tert-butyl ether NMR nuclear magnetic resonance spectroscopy p. page R tretention time THF tetrahydrofuran Tf Trifluoromethanesulfonyl TLC thin layer chromatography Various aspects of the invention described in this application are illustrated by the following examples, which are not meant to limit the invention in any way.

[0253] The test experiments described herein serve to illustrate the invention, and the invention is not limited to the experiments given.

[0254] Experimental section - General section All reagents whose synthesis is not described in the experimental section are either commercially available, are known compounds, or can be formed from known compounds by known methods by those skilled in the art.

[0255] The compounds and intermediates produced according to the methods of the present invention may require purification. Purification of organic compounds is well known to those skilled in the art, and there may be several ways to purify the same compound. In some cases, purification may not be necessary. In some cases, compounds can be purified by crystallization. In some cases, impurities can be removed by trituration with an appropriate solvent. In some cases, compounds can be purified by chromatography, particularly flash column chromatography, using, for example, a Biotage SNAP cartridge KP-Sil® or KP-NH® in combination with a pre-packed silica gel cartridge, such as a Biotage automated purification system (SP4® or Isolera Four®) and an eluent (e.g., a gradient of hexane / ethyl acetate or DCM / methanol). In some cases, compounds can be purified by preparative HPLC using, for example, a Waters automated purifier equipped with a diode array detector and / or an online electrospray ionization mass spectrometer in combination with a suitable pre-packed reverse-phase column and an eluent such as a gradient of water and acetonitrile (which may contain additives such as trifluoroacetic acid, formic acid, aqueous ammonia, etc.).

[0256] In some cases, the purification methods described above can provide compounds of the present invention having sufficiently basic or acidic functionalities in the form of a salt, such as a trifluoroacetate or formate salt in the case of a sufficiently basic compound of the present invention, or an ammonium salt in the case of a sufficiently acidic compound of the present invention. This type of salt can be converted to its free base or free acid form, respectively, by various methods known to those skilled in the art, or can be used as a salt in subsequent biological assays. It should be understood that the specific form (e.g., salt, free base, etc.) of a compound of the present invention isolated and described herein is not necessarily the only form in which the compound can be applied to biological assays to determine specific biological activity.

[0257] Analytical and chromatographic methods Analytical and Preparative Liquid Chromatography Analytical (UP) LC-MS was performed using different instruments as described below. Masses (m / z) are reported from positive mode electrospray ionization (ESI-) unless negative mode is indicated.

[0258] M+1 (or M+H) refers to the molecular ion peak ±1 a.mu (atomic mass unit), respectively, as observed in mass spectrometry by electrospray ionization (ESI+ or -).

[0259] [M+H] by LC-MS under acidic chromatographic conditions + or M - Measurements were performed using 1 ml formic acid per liter of acetonitrile and 0.9 ml formic acid per liter of Millipore water as eluents. A linear gradient from 10% acetonitrile to 95% acetonitrile was applied from 0 to 1.8 min and held constant at 95:5 from 1.80 to 2.50 min; oven temperature 55°C. LC-MS (Method L3): Waters UPLC with SQD2 mass spectrometer and SampleManager autosampler. Linear gradient from 10% acetonitrile to 95% acetonitrile from 0.0 to 1.70 min, constant 95% acetonitrile from 1.70 to 2.40 min, flow rate 0.85 ml / min.

[0260] LC-MS (Method L6) and LC-MS (Method L7): Agilent 1290 LC, Agilent MSD, HTS PAL autosampler. Linear gradient from 10% acetonitrile to 95% acetonitrile from 0.0 to 1.80 min, constant 95% acetonitrile from 1.80 to 2.50 min, flow rate 1.0 ml / min.

[0261] [M+H] by LC-MS under neutral chromatographic conditions +The determination was carried out using acetonitrile and Millipore water containing 79 mg / L ammonium carbonate as eluent. Linear gradient from 10% acetonitrile to 95% acetonitrile. Apparatus: LC-MS (Method L4): Waters IClass Acquity with QDA mass spectrometer and FTN autosampler (Waters Acquity 1.7 μm 50 mm × 2.1 mm column, oven temperature 45 °C, flow rate 0.7 ml / min, gradient 0 (10% ACN) - 2.10 min (95% ACN), 2.10-3.00 min constant 95% ACN). Calibration was performed using linear alkan-2-ones (with 3 to 16 carbon atoms) with known logP values ​​(measurement of logP values ​​using retention times by linear interpolation between successive alkanones). Lambda maxima were determined using the peak values ​​of the UV spectrum and chromatographic signal from 200 nm to 400 nm.

[0262] 1 H-NMR data 1 H-NMR data were obtained using a Bruker Avance 400 equipped with a 60 μL flow cell, or a Bruker AVIII 400 (400.13 MHz) equipped with a 1.7 mm cryo CPTCI probehead, or a Bruker AVIII 400 (400.13 MHz) equipped with a 5 mm probehead, or a Bruker AVII 600 (600.13 MHz) equipped with a 5 mm cryo TCI probehead, or a Bruker AVIII 600 (601.6 MHz) equipped with a 5 mm cryo CPMNP probehead, or a Bruker AVIII 500 (500.13 MHz) equipped with a 5 mm broadband head or a 5 mm Prodigy™ probehead, or a Bruker Avance NEO 600 MHz (5 mm TCI cryo The concentration was determined using a probe head (probe head) with tetramethylsilane as the standard (0.00 ppm) and solvents of CD3CN, CDCl3, or DMSO-d6. 1 H- and13 C-NMR instrument type: Bruker DMX300( 1 H-NMR: 300 MHz; 13 C NMR:75MHz), Bruker Avance III 400( 1 H-NMR: 400 MHz; 13 C NMR: 100 MHz) or Bruker 400 Ultrashield ( 1 H-NMR: 400 MHz; 13 C NMR: 100 MHz).

[0263] Chemical shifts (δ) are expressed in parts per million [ppm]; the following abbreviations are used: s = singlet, d = doublet, dd = doublet of doublets, t = triplet, q = quartet, sept = septet, m = multiplet, br = broad line; coupling constants are expressed in hertz [Hz].

[0264] Experimental Section - General Procedures The synthesis of compounds of formula (I) can be carried out according to or analogous to the following schemes (Scheme 1, Scheme 2-1 and Scheme 2-2).

[0265] Scheme 1: [ka]

[0266] Coupling of carboxylic acid 1A with commercially available amine 1E can proceed via conventional peptide coupling procedures. This coupling reaction is typically carried out using well-known coupling reagents such as N-(3-dimethylaminoisopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), dicyclohexylcarbodiimide, 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide, BOP reagent, N,N'-carbonyldiimidazole, or HBTU to give amide 1C. Similar syntheses are described in Chem. Commun., 1999, pp. 1847-1848; J. Org. Chem., 1962, 27, 6, 2094-2099; US20120101125; or WO2007090068. Suitable solvents are dichloromethane, chloroform, butyl acetate, ethyl acetate, toluene, tetrahydrofuran, dimethoxyethane, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, nitromethane, pyridine, and the like.

[0267] Alternatively, the free carboxylic acid 1A can be converted to the acid chloride 1B, which can be coupled with commercially available amine 1E to give the intermediate carboxamide 1C.

[0268] Acid halides 1B can be prepared by contacting the free carboxylic acid 1A with an inorganic acid halide, such as phosphorus oxychloride, phosphorus oxybromide, thionyl chloride, phosphorus pentachloride, or oxalyl chloride, under conventional conditions. Generally, the reaction is carried out using about 1 to 5 molar equivalents of the inorganic acid halide or oxalyl chloride, either neat or in an inert solvent such as dichloromethane, tetrahydrofuran, or toluene, at temperatures ranging from about 0°C to about 80°C for about 1 to about 48 hours. A catalyst, such as dimethylformamide, can also be used in this reaction.

[0269] The acid chloride 1B is then contacted with at least 1 equivalent, preferably about 1.1 to about 1.5 equivalents, of a commercially available amine 1E under basic conditions. Suitable bases include, for example, trimethylamine, as described in Chemical Biology & Drug Design (2015), 85(5), 549-564 or WO2007090068, or tertiary amines such as N,N-diisopropylethylamine, N-methylmorpholine, etc. Suzuki cross-coupling reaction of intermediate carboxamide 1C with commercially available boronic acids or boronic esters 1D QB(OR)2 (R=H; R=Me or R,R=pinacolato) in the presence of a palladium catalyst, as described in Chem. Soc. Rev., 2014, 43, 412-443, Tetrahedron, 58(2002), 9633-9695 or WO2008148867, gives the final products of formula (I).

[0270] The synthesis of compounds of formula 1A can be carried out according to or analogous to the following schemes (Scheme 2-1, Scheme 2-2).

[0271] Scheme 2-1: [ka]

[0272] The synthesis of substituted isoquinoline-3-carboxylic acids is generally known in the art and is described in US609373, US2006217416, WO2004099206, WO2004108681, WO2005014533, WO2013030358, WO2016129983 or US2007090068.

[0273] In J. Chem. Soc., Perkin Trans. 1, 2002, 529-532, methyl-1-bromoisoquinoline-3-carboxylate is used as a precursor for a combinatorial approach to the core structures of novel potential peripheral benzodiazepine receptor ligands.

[0274] A novel synthesis of isoquinoline-3-carboxylates based on palladium(0)-catalyzed Heck-type arylation of 2-amidoacrylates with suitable 2-substituted iodobenzenes is reported in Tetrahedron Lett, 2002, 43(29), 5079-5081.

[0275] Tetrahedron Lett., 2002, 43(29), 5079-5081 describes a new and general synthesis of methyl isoquinoline-3-carboxylates starting from aromatic 1,2-dialdehydes by reaction with protected phosphonoglycine derivatives, which is particularly useful for the synthesis of new isoquinolines bearing electron-withdrawing groups.

[0276] By using the key trifluoromethanesulfonate precursor 5, various substituted isoquinoline-3-carboxylic acids are accessible. Isoquinoline triflates are preferred building blocks for the preparation of substituted isoquinolines. Further examples can be found, for example, in J. Med. Chem. 1997, 40, 18, 2910-2921.

[0277] Starting from commercially available methyl 2-(bromomethyl)-3-nitrobenzoate 2, it is reacted with commercially available methyl N-[(4-methylphenyl)sulfonyl]glycinate 2a to give intermediate 3. The synthesis of similar protected glycine ester compounds is described in WO2007090068 or US2006217416.

[0278] Compound 3 can be cyclized to isoquinoline ester 4 by treatment with a suitable base such as sodium methoxide or potassium tert-butoxide in methanol, as described, for example, in WO2007090068.

[0279] Compound 4 reacts with triflic anhydride in pyridine to give the key intermediate 5, similar to Ann. Chim. 1962, 52, 112-120.

[0280] Isoquinoline triflate 5 reacts with commercially available amine 1f to give intermediate 6. After reduction of the nitro group of intermediate 6, the amino group is converted to the corresponding bromoester 8 by a Sandmeyer reaction. A similar reaction is carried out in the synthesis of 4,5-dibromoisoquinoline as described in J. Het. Chem., 1967, 410-412. The ester intermediate 8 can be readily hydrolyzed to the corresponding carboxylic acid 1A-1 using, for example, aqueous sodium hydroxide or aqueous lithium hydroxide in a suitable solvent such as an alcohol or cyclic ether, as described, for example, in WO2005014533.

[0281] Scheme 2-2: [ka]

[0282] Isoquinoline triflate 5 and commercially available boronic acid or boronic acid ester 1g R were prepared as described in Letters in Organic Chemistry, 2007, 4(2), 86-91, Chem. Soc. Rev. 2014, 43, 412-443, Tetrahedron 2002, 58(48), 9633-9695 or WO2008148867. 2 Suzuki cross-coupling reaction with -B(OR)2 (R=H; R=Me or R,R=pinacolato) leads to the nitro intermediate 12.

[0283] Organic Lett. 2011, 13(16), 4374-4377 describes the palladium(0) catalyzed reaction of tosylates with boronic acids.

[0284] Nitroester 12 is converted to the ester intermediate 14 after hydrogenation and subsequent Sandmeyer reaction of aminoester 13, analogous to J. Het. Chem., 1967, 410-412.

[0285] Ester 14 is finally hydrolyzed to carboxylic acid 1A-2 using, for example, aqueous sodium hydroxide or lithium hydroxide in a suitable solvent such as an alcohol or a cyclic ether, as described, for example, in WO2005014533.

[0286] Experimental Section - Examples Synthesis of N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)-8-(2,3,5-trifluorophenyl)isoquinoline-3-carboxamide (Example I-1) [ka]

[0287] Step 1 Methyl 2-({(2-methoxy-2-oxoethyl)[(4-methylphenyl)sulfonyl]amino}methyl)-3-nitrobenzoate 3 [ka]

[0288] To a mixture of methyl N-[(4-methylphenyl)sulfonyl]glycinate (170.0 g, 698.8 mmol, 1 equiv.) of compound 2a in DMF (425 mL) was added NaH (33.7 g, 841.2 mmol, 60% purity, 1.2 equiv.) portionwise under nitrogen at 25° C. The mixture was stirred at 25° C. for 2 h, and then a solution of commercially available methyl 2-(bromomethyl)-3-nitrobenzoate (212.8 g, 768.7 mmol, 1.1 equiv.) of compound 2 in DMF (425 mL) was added. The mixture was stirred at 25° C. for 2 h. The reaction mixture was quenched by the addition of 1 M HCl (1 L) at 0° C., then diluted with water (1 L) and extracted three times with EtOAc (2 L). The combined organic layers were washed with brine (2 L), dried over NaSO, filtered, and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO, petroleum ether: EtOAc = 50:1 to 2:1) to give compound 3 (289.0 g, purity 91.5%, 86.7% of theory) as a pale yellow solid.

[0289] LCMS: R t = 0.839 min; m / z = 437 (M+H) + Step 2 Methyl 4-hydroxy-8-nitroisoquinoline-3-carboxylate 4 [ka]

[0290] To a mixture of sodium (20.4 g, 886.9 mmol, 3 equiv.) in MeOH (645 mL) was added compound 3, methyl 2-({(2-methoxy-2-oxoethyl)[(4-methylphenyl)sulfonyl]amino}methyl)-3-nitrobenzoate (Step 1) (129.0 g, 295.6 mmol, 1 equiv.) under nitrogen. The mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated under reduced pressure to remove MeOH. The residue was adjusted to pH = 6-7 by adding 1 N HCl (300 mL), filtered, and the filter cake was concentrated under reduced pressure to give compound 4, methyl 4-hydroxy-8-methylisoquinoline-3-carboxylate (58.35 g, 91.4% purity, 72.7% of theory) as a yellow solid.

[0291] LCMS: R t = 0.717 min; m / z = 249 (M+H) + 1 H-NMR (400 MHz, DMSO-d6) δ = 11.66 (s, 1H), 9.28 (s, 1H), 8.71 (d, J=8.2 Hz, 1H), 8.62 (dd, 1H), 8.06 (t, J=8.2 Hz, 1H), 4.01 (s, 3H). Step 3 Methyl 8-nitro-4-{[(trifluoromethyl)sulfonyl]oxy}isoquinoline-3-carboxylate 5 [ka]

[0292] To a mixture of compound 4 (Step 2) (52.0 g, 209.5 mmol, 1 equiv.) and pyridine (66.6 g, 842.5 mmol, 68 mL, 4.02 equiv.) in DCM (260 mL) was added TfO (118.0 g, 418.2 mmol, 69 mL, 2 equiv.) dropwise at 0 °C under nitrogen. The mixture was stirred at 25 °C for 1 h. The reaction mixture was diluted with water (800 mL) and extracted three times with DCM (1 L). The combined organic layers were washed with brine (1 L), dried over NaSO, filtered, and concentrated under reduced pressure to give a residue, which was purified by column chromatography (SiO, petroleum ether: EtOAc = 20:1 to 10:1) to give compound 5 (67.0 g, 99.8% purity, 83.9% of theory) as a pale yellow solid.

[0293] LCMS: R t = 0.821 min; m / z = 381 (M+H) + 1 H-NMR (400 MHz, CDCl3) δ = 10.11 (d, J=1.0 Hz, 1H), 8.63 - 8.52 (m, 2H), 8.09 (dd, J=7.8, 8.6 Hz, 1H), 4.12 (s, 3H). Step 4 Methyl 4-(morpholin-4-yl)-8-nitroisoquinoline-3-carboxylate 6 [ka]

[0294] To a mixture of compound 5 (Step 3) (30.0 g, 78.7 mmol, 1 equiv.) and morpholine (8.23 g, 94.5 mmol, 1.2 equiv.) in DMF (150 mL) was added TEA (15.9 g, 157.5 mmol, 2 equiv.) under nitrogen. The mixture was stirred at 80 °C for 2 h. The reaction mixture was diluted with water (500 mL) and extracted with EtOAc (800 mL). The combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give a residue which was washed with petroleum ether and EtOAc (10:1, 300 mL), then filtered, and the filter cake was concentrated under reduced pressure to give compound 6 (24.0 g, 100.0% purity, 96.1% of theory) as a brown solid.

[0295] LCMS: R t = 0.126 min; m / z = 318 (M+H) + 1 H-NMR (400 MHz, CDCl3) δ = 9.74 (s, 1H), 8.73 (d, J=8.6 Hz, 1H), 8.39 (d, J=7.6 Hz, 1H), 7.88 (t, J=8.2 Hz, 1H), 4.09 (s, 3H), 3.95 (t, J=4.6 Hz, 4H), 3.25 (s, 4H). Step 5 Methyl 8-amino-4-(morpholin-4-yl)isoquinoline-3-carboxylate 7 [ka]

[0296] To a solution of compound 6 (Step 4) (12.0 g, 37.8 mmol, 1 equiv.) in THF (60 mL) was added wet Pd / C (10%, 1.20 g) under nitrogen. The suspension was degassed under reduced pressure and purged with H2 several times. Stirred under H2 (15 psi) at 25 °C for 1 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give compound 7 (10.0 g, 99.2% purity, 91.3% of theory) as a brown solid.

[0297] LCMS: Rt = 0.595 min; m / z = 288 (M+H) + 1 H-NMR (400 MHz, CDCl3) δ = 9.08 (d, J=0.8 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.55 (dd, 1H), 7.27 (s, 1H), 6.88 (dd, 1H), 4.05 (s, 3H), 3.91 (t, J=4.6 Hz, 4H), 3.23 (s, 4H). Step 6 Methyl 8-bromo-4-(morpholin-4-yl)isoquinoline-3-carboxylate, HBr salt 8 [ka]

[0298] To a mixture of compound 7 (Step 5) (15.0 g, 51.8 mmol, 1 equiv.) in HBr (75 mL), water (30 mL), and MeCN (75 mL) was added a solution of NaNO (4.64 g, 67.3 mmol, 1.3 equiv.) in water (30 mL) at 0 °C. The mixture was stirred at 0 °C for 0.5 h, and then added to a solution of CuBr (6.95 g, 31.1 mmol, 0.6 equiv.) in HBr (120 mL) at 0 °C. The mixture was stirred at 25 °C for 1 h. The reaction mixture was slowly poured into water (2 L), filtered, and the filter cake was concentrated under reduced pressure to give compound 8 (13.3 g as the HBr salt, 81.1% purity, 48.2% of theory) as a brown solid.

[0299] LCMS: R t = 0.917 min; m / z = 352 (M+H) + 1 H-NMR (400 MHz, DMSO-d6) δ = 9.67 - 8.91 (m, 1H), 8.35 (d, J=8.4 Hz, 1H), 8.09 (d, J=7.4 Hz, 1H), 7.78 (t, J=8.0 Hz, 1H), 3.96 (s, 3H), 3.83 - 3.77 (m, 4H), 3.13 - 3.05 (m, 4H). Step 7 8-Bromo-4-(morpholin-4-yl)isoquinoline-3-carboxylic acid 1A-3 [ka]

[0300] To a mixture of compound 8 (Step 6) (15.0 g, 34.7 mmol, 1 equiv., HBr salt) in water (15 mL), THF (30 mL), and MeOH (30 mL) was added lithium hydroxide monohydrate (7.28 g, 173.6 mmol, 5 equiv.). The mixture was stirred at 40 °C for 1 h. The reaction mixture was changed to pH 3-4 by the addition of 1 M HCl (150 mL) and then extracted with DCM (200 mL × 3). The combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 1A-3 (5.50 g, 96.5% purity, 45.4% of theory) as a yellow solid.

[0301] LCMS: R t = 0.680 min; m / z = 339 (M+H) + 1 H-NMR (400 MHz, DMSO- d6) δ = 13.59 (s, 1H), 9.23 (s, 1H), 8.35 (s, 1H), 8.06 (s, 1H), 7.76 (s, 1H), 3.82 (s, 4H), 3.15 (s, 4H). Step 8 8-Bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)quinoline-3-carboxamide 1C-1 [ka]

[0302] To a suspension of 8-bromo-4-(morpholin-4-yl)isoquinoline-3-carboxylic acid (1.0 g, 2.97 mmol) from 1A-3 (Step 7) in dry toluene (25 mL) was added two drops of DMF. Then, thionyl chloride (530 mg, 4.46 mmol) was added dropwise within 2 min. After stirring at 70 °C for 3 h, the mixture was concentrated in vacuo, and THF (25 mL), (S)-chroman-4-amine hydrochloride (550 mg, 2.96 mmol), and N,N-diisopropylethylamine (1.3 g, 10 mmol) were added. Stirring was continued overnight at room temperature.

[0303] The solvent was removed under reduced pressure, and the residue was partitioned between water (50 mL) and DCM (50 mL). The combined organic layers were dried through a sodium sulfate / silica gel cartridge and concentrated in vacuo. Purification by flash chromatography using EtOAc / cyclohexanediene gave 410 mg (97.6% pure, 28.8% of theory) of the title compound.

[0304] LC-MS (Method L3): Index = 923; m / z = 469 (M+H) + 1 H-NMR (400 MHz, DMSO- d6) δ = 9.25 (s, 1H), 9.03 - 9.01 (m, 1H), 8.39 - 8.37 (m, 1H), 8.06 - 8.04 (m, 1H), 7.78 - 7.74 (m, 1H), 7.36 - 7.34 (m, 1H), 7.20 - 7.15 (m, 1H), 6.95 - 6.91 (m, 1H), 6.81 - 6.79 (m, 1H), 5.31 (m, 1H), 4.30 - 4.27 (m, 2H), 3.87 - 3.78 (m, 4H), 3.20 - 3.17 (m, 4H), 2.23 - 2.18 (m, 1H), 2.12 - 2.06 (m, 1H). Step 9 N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)-8-(2,3,5-trifluorophenyl)isoquinoline-3-carboxamide (Example I-1) [ka]

[0305] A mixture of 8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)quinoline-3-carboxamide (Step 8) (100 mg, 0.214 mmol) and bis(triphenylphosphine)dichloropalladium(II) (14 mg, 0.02 mmol) in 1,4-dioxane (10 mL) was stirred at room temperature for 2 hours. After the addition of (2,3,5-trifluorophenyl)boronic acid (80 mg, 0.455 mmol), sodium carbonate (230 mg, 2.17 mmol), and water (0.85 mL), stirring was continued at 90 °C for 18 hours. The mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with DCM (3 × 20 mL). The solvent was dried and removed under reduced pressure. Purification by flash chromatography with EtOAc / cyclohexanediene gave 27 mg of the title compound (94.5% pure, 23% of theory).

[0306] LC-MS (Method L6): Index = 1019; m / z = 520 (M+H) + 1 H-NMR (400 MHz, DMSO- d6) δ = 8.99 - 8.97 (m, 1H), 8.76 - 8.75 (m, 1H), 8.50 - 8.48 (m, 1H), 7.98 - 7.96 (m, 1H), 7.75 - 7.72 (m, 2H), 7.34 - 7.32 (m, 2H), 7.18 - 7.14 (m, 1H), 6.93 - 6.89 (m, 1H), 6.80 - 6.78 (m, 1H), 5.31 (m, 1H), 4.29 - 4.26 (m, 2H), 3.90 - 3.81 (m, 4H), 3.21 (m, 4H), 2.19 - 2.07 (m, 2H). Intermediate 1A-4 was prepared in a similar manner as described in Step 7 as a yellow solid.

[0307] 8-Bromo-4-(dimethylamino)isoquinoline-3-carboxylic acid 1A-4 [ka]

[0308] LCMS: R t = 0.722 min; m / z = 295 (M) + 1 H-NMR (400 MHz, DMSO- d6) δ = 9.19 (s, 1H), 8.28 (d, J=8.6 Hz, 1H), 8.05 (d, J=7.0 Hz, 1H), 7.74 (t, J= 8.4 Hz, 1H), 2.94 (s, 6H). Synthesis of N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-methyl-8-(2,3,5-trifluorophenyl)isoquinoline-3-carboxamide (Example I-2) [ka]

[0309] Step 1 Methyl 4-methyl-8-nitroisoquinoline-3-carboxylate 12 [ka]

[0310] A mixture of methyl 8-nitro-4-{[(trifluoromethyl)sulfonyl]oxy}isoquinoline-3-carboxylate 5 (30.0 g, 78.9 mmol, 1.00 equiv.), methylboronic acid (14.2 g, 237 mmol, 3.00 equiv.), KPO (67.0 g, 316 mmol, 4.00 equiv.), and Pd(dppf)Cl (5.77 g, 7.89 mmol, 0.10 equiv.) was degassed under reduced pressure and purged with nitrogen three times. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure. The residue was triturated with petroleum ether / EtOAc / DCM (100 mL / 100 mL / 30 mL) to give compound 12 (17.0 g, 97.3% purity, 85.2% of theory) as a brown solid.

[0311] LCMS: R t = 0.889 min; m / z = 247 (M+H) + 1 H-NMR (400 MHz, DMSO- d6) δ = 9.60 (s, 1H), 8.66 (d, J = 8.8 Hz, 1H), 8.53 (d, J = 7.6 Hz, 1H), 8.08 (t, J = 8.0 Hz, 1H), 3.95 (s, 3H), 2.79 (s, 3H). Step 2 Methyl 8-amino-4-methylisoquinoline-3-carboxylate 13 [ka]

[0312] To a solution of compound 12 (Step 1) (17.0 g, 69.0 mmol, 1.00 equiv) in THF (63.0 mL) / MeOH (21.0 mL) was added Pd / C (10.0 g, 10.0% purity). The reaction mixture was degassed under vacuum and purged with hydrogen three times. The mixture was stirred under H2 (15 Psi) at 20 °C for 5 h. The reaction mixture was filtered through a pad of Celite. The filter cake was washed with MeOH (100 mL), and the filtrate was concentrated under vacuum to give compound 13 (15.2 g, 93.6% purity, 95.3% of theory) as a yellow solid.

[0313] LCMS: R t = 0.857 min; m / z = 217 (M+H) + 1 H-NMR (400 MHz, DMSO- d6) δ = 9.35 (s, 1H), 7.56-7.52 (m, 1H), 7.25 (t, J = 8.4 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 6.39 (s, 2H), 3.92 (s, 3H), 2.60 (s, 3H). Step 3 Methyl 8-bromo-4-methylisoquinoline-3-carboxylate 14 [ka]

[0314] A mixture of compound 13 (Step 2) (11.4 g, 52.7 mmol, 1.00 equiv.) in HBr (50.0 mL, 40% purity) / water (20.0 mL) / CHCN (50.0 mL) was cooled to 0 °C, and a mixture of NaNO (4.73 g, 68.6 mmol, 1.30 equiv.) in water (20.0 mL) was added. The mixture was stirred at 0 °C for 30 min. Then, the mixture was added to CuBr (7.64 g, 34.2 mmol, 1.60 mL, 0.65 equiv.) in HBr (75 mL, 40% purity) at 25 °C and stirred at 25 °C for 1 h. The reaction mixture was poured into water (200 mL), adjusted to pH = 10 with 10% aqueous NaOH, extracted with DCM (500 mL), and separated. The organic phase was dried over NaSO, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: EtOAc: DCM = 6:1:0.2 to 3:1:0.2) to give compound 14 (3.20 g, purity 98.5%, 21.2% of theory) as a yellow solid.

[0315] LCMS: R t = 0.868 min; m / z = 281 (M+H) + Step 4 8-Bromo-4-methylisoquinoline-3-carboxylic acid 1A-5 [ka]

[0316] To a solution of compound 14 (Step 3) (3.20 g, 11.4 mmol, 1.00 equiv.) in water (30.0 mL) / THF (30.0 mL) was added lithium hydroxide monohydrate (1.92 g, 45.7 mmol, 4.00 equiv.). The reaction mixture was stirred at 25-30 °C for 3 h. The reaction mixture was concentrated under reduced pressure. The residue was diluted with water (200 mL) and adjusted to pH 3-4 with 4 N HCl, resulting in the appearance of a yellow precipitate. The mixture was filtered, and the filter cake was dried in vacuo to give 1A-5 (2.50 g, 99.6% purity, 82.2% of theory) as a yellow solid.

[0317] LCMS: R t= 0.668 min; m / z = 266 (M) + 1 H-NMR (400 MHz, DMSO- d6) δ = 13.4 (brs, 1H), 9.37 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.13-8.07 (m, 1H), 7.81 (t, J = 8.0 Hz, 1H), 2.78 (s, 3H). Step 5 8-Bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-methylisoquinoline-3-carboxamide 1C-2 [ka]

[0318] A suspension of 8-bromo-4-methylisoquinoline-3-carboxylic acid (Step 4) (400 mg, 1.50 mmol) and di-1H-imidazol-1-ylmethanone (265 mg, 1.63 mmol) in dry THF (15 mL) was stirred overnight at 60° C. After addition of (S)-chroman-4-amine hydrochloride (283 mg, 1.52 mmol) and N,N-diisopropylethylamine (900 mg, 6.96 mmol), stirring was continued overnight at 60° C.

[0319] The solvent was removed under reduced pressure and the residue was partitioned between water (50 mL) and DCM (50 mL). The combined organic layers were dried through a sodium sulfate / silica gel cartridge and concentrated in vacuo to give 375 mg (95% pure by H-NMR, 62.8% of theory) of the title compound.

[0320] LC-MS (Method L3): Index = 1027; m / z = 398 (M+H) + 1H-NMR (400 MHz, DMSO- d6) δ = 9.36 (s, 1H), 9.05 - 9.03 (m, 1H), 8.30 - 8.28 (m, 1H), 8.10 - 8.08 (m, 1H), 7.82 - 7.78 (m, 1H), 7.30 - 7.28 (m, 1H), 7.19 - 7.15 (m, 1H), 6.93 - 6.89 (m, 1H), 6.81 - 6.79 (m, 1H), 5.35 - 5.30 (m, 1H), 4.29 - 4.26 (m, 2H), 2.86 (s, 3H), 2.21 - 2.10 (m, 2H). Step 6 N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-methyl-8-(2,3,5-trifluorophenyl)isoquinoline-3-carboxamide (Example I-2) [ka]

[0321] A mixture of 8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-methylisoquinoline-3-carboxamide (Step 5) (150 mg, 0.378 mmol) and bis(triphenylphosphine)dichloropalladium(II) (36 mg, 0.051 mmol) in 1,4-dioxane (20 mL) was stirred at room temperature for 2 hours. After the addition of (2,3,5-trifluorophenyl)boronic acid (275 mg, 1.56 mmol), sodium carbonate (730 mg, 6.89 mmol), and water (1.05 mL), stirring was continued at 90 °C for 18 hours. The mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with DCM (3 × 20 mL). The solvent was dried and removed under reduced pressure. Purification by flash chromatography using an EtOAc / cyclohexane gradient gave 111 mg of the title compound (100% pure, 65.6% of theory).

[0322] LC-MS (Method L3): Index = 1109; m / z = 449 (M+H) + 1H-NMR (400 MHz, DMSO- d6) δ = 9.00 - 8.97 (m, 1H), 8.85 (m, 1H), 8.40 - 8.38 (m, 1H), 8.02 - 7.99 (m, 1H), 7.78 - 7.71 (m, 2H), 7.36 (br, 1H), 7.28 - 7.26 (m, 1H), 7.18 - 7.14 (m, 1H), 6.91 - 6.87 (m, 1H), 6.80 - 6.78 (m, 1H), 5.33 - 5.28 (m, 1H), 4.28 - 4.25 (m, 2H), 2.92 (s, 3H), 2.20 - 2.08 (m, 2H). Synthesis of N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-isopropyl-8-(2,3,5-trifluorophenyl)isoquinoline-3-carboxamide (Example I-3) [ka]

[0323] Step 1 Methyl 8-nitro-4-(prop-1-en-2-yl)isoquinoline-3-carboxylate 15 [ka]

[0324] A mixture of methyl 8-nitro-4-{[(trifluoromethyl)sulfonyl]oxy}isoquinoline-3-carboxylate 5 (30.0 g, 78.9 mmol, 1 equiv.), potassium trifluoro(prop-1-en-2-yl)borate (23.4 g, 158 mmol, 2 equiv.), Pd(dppf)Cl (5.50 g, 7.52 mmol, 0.095 equiv.), and NaCO (25.1 g, 237 mmol, 3.01 equiv.) in dioxane (150 mL) was degassed and purged with nitrogen and stirred at 70 °C under a nitrogen atmosphere for 2 h. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to leave a residue, which was stirred in petroleum ether / EtOAc (1:1, 150 mL) for 0.5 h. The precipitate was filtered and dried to give compound 15 (18.5 g, 99.0% purity, 85.3% of theory) as a brown solid.

[0325] LCMS: Rt = 0.87 min; m / z = 273 (M+H) + 1 H-NMR (400 MHz, CDCl3) δ = 9.98 (s, 1H), 8.42 (d, J = 7.6 Hz, 2H), 7.88 (t, J = 8.0 Hz, 1H), 5.58 - 5.53 (m, 1H), 5.00 (m, 1H), 4.02 (s, 3H), 2.28 (s, 3H). Step 2 Methyl 8-amino-4-(prop-1-en-2-yl)isoquinoline-3-carboxylate 16 [ka]

[0326] To a solution of methyl 8-nitro-4-(prop-1-en-2-yl)isoquinoline-3-carboxylate 15 (Step 1) (18.0 g, 65.4 mmol, 1 equiv.) in THF (90.0 mL) and MeOH (90.0 mL) under nitrogen, Pd / C (5.00 g, 10% purity, 1.00 equiv.) was added. The suspension was degassed under reduced pressure and purged with H2 several times. The mixture was stirred under H2 (15 psi) at 20 °C for 5 h. The mixture was filtered through a pad of Celite, and the filtrate was concentrated to give compound 16 (16.5 g, 92.9% purity, 95.7% of theory) as an orange solid.

[0327] LCMS: R t = 0.61 min; m / z = 243 (M+H) + Step 3 Methyl 8-amino-4-isopropylisoquinoline-3-carboxylate 17 [ka]

[0328] To a solution of compound 16 (step 2) (16.5 g, 68.1 mmol, 1 equiv.) in MeOH (100 mL) and THF (50.0 mL) was added PtO (1.65 g, 7.27 mmol, 0.107 equiv.) under nitrogen. The suspension was degassed under reduced pressure and purged with H several times. The mixture was stirred under H (15 psi) at 35 °C for 5 h. The reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated under reduced pressure to give compound 17 (16.4 g, 93.0% purity, 91.7% of theory) as a yellow solid.

[0329] LCMS: R t = 0.671 min; m / z = 245 (M+H) + Step 4 Methyl 8-bromo-4-isopropylisoquinoline-3-carboxylate 18 [ka]

[0330] To a solution of compound 17 (step 3) (15.8 g, 64.7 mmol, 1.00 equiv) in HBr (50.0 mL) and CHCN (50.0 mL) was added a solution of NaNO (5.37 g, 77.9 mmol, 1.20 equiv) in water (20.0 mL) at -5 to 0 °C. The mixture was stirred at 0 °C for 0.5 h. Next, a solution of CuBr (7.24 g, 32.4 mmol, 1.52 mL, 0.501 equiv) in HBr (20.0 mL) was added at 20 °C. The resulting mixture was stirred at 20 to 25 °C for 0.5 h. The mixture was poured into water (200 mL) and diluted with DCM (150 mL). The pH of this mixture was adjusted to 8–9 with 10% NaOH. The organic phase was separated, washed with brine (100 ml), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give a residue which was purified by column chromatography (SiO2, petroleum ether / EtOAc = 10 / 1 to 4 / 1, R f =0.6 collected) to give compound 18 (7.40 g, 94.2% purity, 35% of theory) as a light brown oil.

[0331] LCMS: R t= 0.918 min; m / z = 308 (M) + 1 H-NMR (400 MHz, CDCl3) δ = 9.53 (s, 1H), 8.30 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.59 (dd, J = 7.6, 8.8 Hz, 1H), 4.03 (s, 3H), 3.83 (m, 1H), 1.56 (d, J = 7.2 Hz, 6H). Step 5 8-Bromo-4-isopropylisoquinoline-3-carboxylic acid 1A-6 [ka]

[0332] To a solution of compound 18 (Step 4) (6.3 g, 19.26 mmol, 1.00 equiv.) in THF (20.0 mL), MeOH (10.0 mL), and water (30.0 mL) was added lithium hydroxide monohydrate (2.42 g, 57.8 mmol, 3.00 equiv.). The mixture was stirred at 20-25 °C for 2 h. The reaction mixture was concentrated under reduced pressure to approximately 40.0 mL. Water (50.0 mL) and DCM (100 mL) were added. The resulting mixture was adjusted to pH 3-4 with 4 N HCl. The organic phase was separated, washed twice with brine (50.0 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 1A-6 (5.80 g, 95.9% purity, 98.2% of theory) as a brown solid.

[0333] LCMS: R t = 0.699 min; m / z = 295 (M+H) + 1H-NMR (400 MHz, CDCl3) δ = 9.72 (br s, 1H), 9.46 (s, 1H), 8.52 (d, J = 8.8 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.66 (dd, J = 7.6, 8.8 Hz, 1H), 5.34 - 5.23 (m, 1H), 1.61 (d, J = 7.2 Hz, 6H). Step 6 8-Bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-isopropylisoquinoline-3-carboxamide 1C-3 [ka]

[0334] To a suspension of 8-bromo-4-isopropylisoquinoline-3-carboxylic acid (Step 5) (500 mg, 1.70 mmol) in dry toluene (20 mL) was added two drops of DMF. Then, thionyl chloride (430 mg, 3.61 mmol) was added dropwise within 2 min. After stirring at 70 °C for 3 h, the mixture was concentrated in vacuo, and THF (20 mL), (S)-chroman-4-amine hydrochloride (320 mg, 1.72 mmol), and N,N-diisopropylethylamine (1.0 g, 7.74 mmol) were added. Stirring was continued overnight at room temperature.

[0335] The solvent was removed under reduced pressure, and the residue was partitioned between water (50 mL) and DCM (50 mL). The combined organic layers were dried through a sodium sulfate / silica gel cartridge and concentrated in vacuo. Purification by flash chromatography using EtOAc / cyclohexanediene gave 193 mg (100% pure, 26.7% of theory) of the title compound.

[0336] LC-MS (Method 3): Index = 1000; m / z = 426 (M+H) + 1H-NMR (400 MHz, DMSO- d6) δ = 9.37 (s, 1H), 8.98 - 8.96 (m, 1H), 8.44 - 8.42 (m, 1H), 8.06 - 8.04 (m, 1H), 7.76 - 7.72 (m, 1H), 7.33 - 7.31 (m, 1H), 7.19 - 7.15 (m, 1H), 6.95 - 6.91 (m, 1H), 6.80 - 6.78 (m, 1H), 5.32 - 5.30 (m, 1H), 4.28 - 4.25 (m, 2H), 3.82 (sept, 1H), 2.20 - 2.16 (m, 1H), 2.08 - 2.04 (m, 1H), 1.53 (dd, 6H). Step 7 N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-isopropyl-8-(2,3,5-trifluorophenyl)isoquinoline-3-carboxamide (Example I-3) [ka]

[0337] A mixture of 8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-isopropylisoquinoline-3-carboxamide (Step 6) (90 mg, 0.212 mmol) and bis(triphenylphosphine)dichloropalladium(II) (12 mg, 0.017 mmol) in 1,4-dioxane (10 mL) was stirred at room temperature for 2 hours. After the addition of (2,3,5-trifluorophenyl)boronic acid (50 mg, 0.284 mmol), sodium carbonate (220 mg, 2.08 mmol), and water (0.65 mL), stirring was continued at 90 °C for 18 hours. The mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with DCM (3 × 20 mL). The solvent was dried and removed under reduced pressure. Purification by flash chromatography with EtOAc / cyclohexanediene gave 17 mg (95% pure, 16% of theory) of the title compound.

[0338] LC-MS (Method 3): Index = 1091; m / z = 477 (M+H) + 1H-NMR (400 MHz, DMSO- d6) δ = 8.95 - 8.93 (m, 1H), 8.83 (m, 1H), 8.53 - 8.51 (m, 1H), 7.95 - 7.91 (m, 1H), 7.77 - 7.69 (m, 2H), 7.33 - 7.29 (m, 2H), 7.17 - 7.13 (m, 1H), 6.93 - 6.89 (m, 1H), 6.79 - 6.77 (m, 1H), 5.33 - 5.29 (m, 1H), 4.27 - 4.25 (m, 2H), 3.90 - 3.84 (sept, 1H), 2.20 - 2.14 (m, 1H), 2.06 - 2.01 (m, 1H), 1.57 (dd, 6H). Table 1: Example

change

Table 1

[0339] Table 1a: 1 H-NMR detector

Table 2

[0340] TIFF0007669343000081.tif76137

[0341] Table 2: Intermediates

change

Table 3

[0342] Table 2a: 1H-NMR data of intermediates

Table 4

[0343] TIFF0007669343000085.tif136139

[0344] Experimental Section - Biological Assays The examples were tested one or more times in the selected biological assay. When tested more than once, the data are reported as either the mean or median, where: The mean value, also known as the arithmetic mean, is the sum of the values ​​obtained divided by the number of tests · The median represents the middle value of a group of values ​​when ranked in ascending or descending order. If the number of values ​​in a data set is odd, the median is the middle value. If the number of values ​​in a data set is even, the median is the arithmetic mean of the two middle values.

[0345] The examples were synthesized one or more times. When synthesized more than once, the data from the biological assays represent the mean or median calculated using data sets obtained from testing one or more synthesis batches.

[0346] The in vitro activity of the compounds of the present invention can be demonstrated in the following assays: In vitro assay 1: C. elegans Slo-1a-mediated activity in recombinant C. elegans cell lines Generation of stable Caenorhabditis elegans CHO cell lines The CHO cell line was obtained from the American Type Culture Collection (ATCC), code ATCC CRL-9096. For transfection with plasmid DNA expressing C. elegans Slo-1a (accession number AAL28102), CHO cells were passaged to 40% confluence, after which the transfection solution was added to the cell culture. The transfection solution contained 300 μL of OptiMEM (Life Technologies, Nr.: 31985), 2 μL (= 6 μg) of plasmid DNA containing the C. elegans Slo-1a gene, and 9 μL of FugeneHD (Promega, Nr.: E2311), and was added to the cells before incubating them at 37°C and 5% CO2 for 48 hours. The transfection medium was replaced with selection medium containing additional G418 (2 mg / ml, Invitrogen, Nr.: 10131), and the cells were seeded into 384-well plates (300 cells / well). After several weeks, the remaining surviving cells were tested for K+ channel expression using a voltage-sensitive dye (Membrane Potential Assay Kit, Molecular Devices Nr.: R8034). Positive cell clones were purified by limiting dilution. To this end, clones with the highest and most robust signal in the voltage-sensitive dye assay were further subcloned (incubated) in 384-well plates (0.7 cells / well) to obtain clonal purity. This resulted in the generation of the final stable CHO cell line expressing C. elegans Slo-1a.

[0347] Cell culture conditions Cells were cultured at 37°C and 5% CO in MEMalpha containing Gutamax I (Invitrogen, Nr.: 32571) supplemented with 10% (v / v) heat-inactivated fetal bovine serum (Invitrogen, Nr.: 10500), G418 (1 mg / ml, Invitrogen, Nr.: 10131), and detached using Accutase (Sigma, Nr.: A6964).

[0348] Membrane potential measurement Compound testing in the laboratory was performed in 384-well microtiter plates (MTPs, Greiner, Nr.: 781092). 8000 cells / well were plated onto 384-well MTPs and cultured at 37°C and 5% CO2 for 20-24 hours. After removing the cell culture medium, the cells were washed once with Tyrode's (150 mM NaCl, 0.3 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 0.8 mM NaH2PO4, 5 mM glucose, 28 mM Hepes, pH 7.4) and then loaded with the voltage-sensitive dye from the membrane potential assay kit diluted in Tyrode's for 1 hour at room temperature.

[0349] Fluorescence measurements were initiated using a FLIPR Tetra (Molecular Devices, Exc. 510-545 nm, Emm. 565-625 nm) followed by the addition of test compound, followed by KCl Tyrode (final assay concentrations: 70 mM KCl, 2 mM CaCl, 1 mM MgCl, 0.8 mM NaHPO, 5 mM glucose, 28 mM Hepes, pH 7.4, containing voltage-sensitive dye). Measurements were completed after 7 minutes.

[0350] statistics Data were curve-fitted using ActivityBase XLfit software (IDBS) to derive the median effective concentration (EC 50 ) and is evaluated by calculating the negative common logarithm (pE 50 ) was reported.

[0351] For the following examples, pE 50 >6.5-7.5 was found: I-13.

[0352] For the following examples, pE 50 >7.5-8.5 was found: I-8.

[0353] In vitro assay 2: Effect of D. immitis Slo-1 on recombinant D. immitis cell lines Generation of a stable Dirofilaria immitis Slo-1 CHO cell line The CHO cell line was obtained from the American Type Culture Collection (ATCC), code ATCC CRL-9096. For transfection with plasmid DNA expressing Dirofilaria immitis Slo-1 (based on protein sequence JQ730003, codon-optimized for hamsters), CHO cells were passaged to 40% confluence, after which a transfection solution was added to the cell culture. The transfection solution contained 300 μL of OptiMEM (Life Technologies, Nr.: 31985), 2 μL (= 6 μg) of plasmid DNA containing the Dirofilaria Slo-1 gene, and 9 μL of FugeneHD (Promega, Nr.: E2311), and was added to the cells before incubating them at 37°C and 5% CO for 48 hours. The transfection medium was replaced with selection medium containing additional G418 (2 mg / ml, Invitrogen, Nr.: 10131), and the cells were seeded into 384-well plates (300 cells / well). After several weeks, the remaining surviving cells were tested for K+ channel expression using a voltage-sensitive dye (Membrane Potential Assay Kit, Molecular Devices Nr.: R8034). Positive cell clones were purified by limiting dilution. To this end, clones with the highest and most robust signals in the voltage-sensitive dye assay were further subcloned (incubated) in 384-well plates (0.7 cells / well) to achieve clonal purity. This resulted in the generation of the final stable CHO cell line expressing Dirofilaria immitis Slo-1.

[0354] Cell culture conditions Cells were cultured at 37°C and 5% CO in MEMalpha containing Gutamax I (Invitrogen, Nr.: 32571) supplemented with 10% (v / v) heat-inactivated fetal bovine serum (Invitrogen, Nr.: 10500), G418 (1 mg / ml, Invitrogen, Nr.: 10131), and detached using Accutase (Sigma, Nr.: A6964).

[0355] Membrane potential measurement Compound testing in the laboratory was performed in 384-well microtiter plates (MTPs, Greiner, Nr.: 781092). 8000 cells / well were plated onto 384-well MTPs and cultured at 37°C and 5% CO2 for 20-24 hours. After removing the cell culture medium, the cells were washed once with Tyrode's (150 mM NaCl, 0.3 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 0.8 mM NaH2PO4, 5 mM glucose, 28 mM Hepes, pH 7.4) and then loaded with the voltage-sensitive dye from the membrane potential assay kit diluted in Tyrode's for 1 hour at room temperature.

[0356] Fluorescence measurements were initiated using a FLIPR Tetra (Molecular Devices, Exc. 510-545 nm, Emm. 565-625 nm) followed by the addition of test compound, followed by KCl Tyrode's (final assay concentrations: 70 mM KCl, 2 mM CaCl, 1 mM MgCl, 0.8 mM NaHPO, 5 mM glucose, 28 mM Hepes, pH 7.4, containing voltage-sensitive dye). Measurements were completed after 7 min.

[0357] statistics Data were curve-fitted using ActivityBase XLfit software (IDBS) to derive the median effective concentration (EC 50 ) and is evaluated by calculating the negative common logarithm (pE 50 ) was reported.

[0358] For the following examples, pE 50 >5.3-6.5 were found: I-2, I-7, I-8, I-11, I-12, I-15.

[0359] For the following example, pE 50 >6.5-7.5 were found: I-3, I-4, I-9.

[0360] For the following examples, pE 50 >7.5-8.5 was found: I-1.

[0361] In vitro assay 3: Brazilian hookworm (Nippostrongylus brasiliensis) (NIPOBR) Adult hookworms were washed with saline buffer containing 100 U / ml penicillin, 0.1 mg / ml streptomycin, and 2.5 μg / ml amphotericin B. Test compounds were dissolved in DMSO, and nematodes were incubated in medium at a final concentration of 10 μg / ml (10 ppm). Aliquots of the medium were used to determine acetylcholinesterase activity compared with a negative control. The principles of measuring acetylcholinesterase as a readout for anthelmintic activity have been described by Rapson et al. (1986) and Rapson et al. (1987).

[0362] For the following examples, activity (reduction of AChE compared to negative control) was greater than 80% at 10 μg / ml: I-1, I-2, I-3, I-4, I-7, I-8, I-9, I-11, I-12, I-13.

[0363] In vitro assay 4: Dirofilaria immitis microfilariae (DIROIM L1) ≥250 Dirofilariae (freshly purified from blood) were added to wells of a microtiter plate containing test compound in nutrient medium and DMSO. Compounds were tested in duplicate in a concentration-response assay. Larvae exposed to DMSO and no test compound served as negative controls. Larvae were evaluated after 72 hours of incubation with compounds. Efficacy was determined as a reduction in motility compared to the negative control. A wide range of concentrations was measured, and concentration-response curves and EC 50 values ​​were calculated.

[0364] For the following examples, EC 50 were <10 ppm: I-6, I-14, 1C-1, 1C-2, 1C-3, 1C-4, 1C-5, 1C-7, 1C-9.

[0365] For the following examples, EC 50 were <1 ppm: I-5, I-10, I-15.

[0366] For the following examples, EC 50 were <0.1 ppm: I-1, I-2, I-3, I-4, I-7, I-8, I-9, I-11, I-12, I-13.

[0367] In vitro assay 5: Dirofilaria immitis (DIROIM L4) Ten third-stage larvae of Dirofilaria immitis, freshly isolated from their vector (intermediate host), were added to wells of a microtiter plate containing test compound in nutrient medium and DMSO. Compounds were tested in duplicate in a concentration-response assay. Larvae exposed to DMSO and no test compound served as negative controls. Larvae were evaluated after 72 hours of incubation with the compounds. Within these 72 hours of incubation, the majority of negative control larvae molted to fourth-stage larvae. Efficacy was determined as a reduction in motility compared to the negative control. Concentration-response curves and EC50 values ​​were calculated based on evaluation of a wide concentration range.

[0368] For the following examples, EC 50 were <1 ppm: I-5, I-7, I-10, I-13.

[0369] For the following examples, EC 50 were <0.1 ppm: I-1, I-2, I-3, I-4, I-8, I-9, I-11, I-12, I-15.

[0370] Formulation Examples F-1 to F-15 An exemplary formulation consists of an active agent in 10% Transcutol, 10% Cremophor EL, and 80% isotonic saline. First, the active agent is dissolved in Transcutol. After dissolution in Transcutol, Cremophor and isotonic saline are added.

[0371] Examples of formulations according to the present invention are the following Formulation Examples F-1 to F-15. In these, the active substances according to Examples I-1 to I-15 are dissolved in Transcutol to form stock solutions A-1 to A-15. Next, 0.100 mL of these stock solutions A-1 to A-15 are taken, and 0.100 mL of Cremophor EL and 0.800 mL of isotonic saline are added. The resulting liquid formulations (Formulation Examples F-1 to F-15) have a volume of 1 mL.

[0372] Stock solutions A-1 to A-15: 4.0 mg Compounds of Examples I-1 to I-15 0.100Ml Transcutol.

[0373] Formulation Examples I-1 to I-15: 0.100 mL Stock solutions A-1 to A-15, 0.100mL Cremophor EL, and 0.800mL isotonic saline.

Claims

1. General formula (I): 【Chemistry 1】 [In the ceremony: A is A1 or A2, 【Chemistry 2】 o is 0, 1, 2, 3 or 4; R is hydrogen, halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -Alkyl, -S-C １ -C ４ -halogenoalkyl, -S(O)-C １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ - halogenoalkyl, R ｐ is hydrogen, C １ -C ４ - alkyl, X and Y are CR ７ R ８ , O, S, and N-R ９ wherein at least one of X and Y is independently selected from the group consisting of ７ R ８ or X and Y together represent -C(O)-O- or -C(O)-NR ９ -, -S(O)-NR ９ -, -SO ２ -NR ９ - and -SO ２ forming a ring member selected from the group consisting of -O-, R １ is hydrogen, cyano, -CHO, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, C with 1 to 5 halogen atoms ３ -C ６ - halogenocycloalkyl, C ３ -C ４ -Alkenyl, C ３ -C ４ -Alkynyl, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl, C ３ -C ６ -Cycloalkyl-C １ -C ３ -Alkyl, cyano-C １ -C ４ -Alkyl, -NH-C １ -C ４ -Alkyl, -N(C １ -C ４ -alkyl) ２ , N.H. ２ -C １ -C ４ -Alkyl-, C １ -C ４ -Alkyl-NH-C １ -C ４ -alkyl-, (C １ -C ４ -alkyl) ２ N-C １ -C ４ -Alkyl-, C １ -C ４ -alkyl-C(O)-, C(O)- with 1 to 5 halogen atoms １ -C ４ -halogenoalkyl-C(O)-, C １ -C ４ -alkoxy-C(O)-, benzyloxy-C(O)-, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl-C(O)-, -SO ２ -C １ -C ４ -alkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ - halogenoalkyl; Phenyl-C １ -C ４ -Alkyl, which is halogen, -OH, -NO ２ , cyano, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halogenoalkyl; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, -OH, -NO ２ , cyano, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl is selected from the group consisting of R ２ teeth, Hydrogen, halogen, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ ; -NR １２ R １３ ; -OR １４ ; -SR １５ 、-S(O)R １５ 、-SO ２ R １５ ; C １ -C ６ -Alkyl, C ３ -C ６ -Cycloalkyl, C ２ -C ４ -Alkenyl, C ３ -C ６ -cycloalkenyl, C ２ -C ４ -alkynyl or phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, -NO ２ , Cyano, C. １ -C ４ -alkyl-C(O)-, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH(C(O)-C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl)(C(O)-C １ -C ４ -alkyl), -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halogenoalkyl; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, -OH, -NO ２ , cyano, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Phenyl (this is halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -halogenoalkyl); and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -Alkyl, C １ -C ４ -alkyl-C(O)-, C(O)- with 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -Alkyl, C １ -C ４ -Alkoxy-C １ -C ４ -alkyl-, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogenoalkyl, and 4- to 10-membered heterocycloalkyl; is selected from the group consisting of R ３ is hydrogen or C １ -C ４ - alkyl, R ４ is hydrogen, halogen, -OH, cyano, C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, C with 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C １ -C ４ -Alkyl-C(O)-, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ - alkyl, preferably selected from the group consisting of hydrogen and halogen, more preferably fluorine and chlorine; R ５ is hydrogen, halogen, -OH, cyano, C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, C with 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C １ -C ４ -Alkyl-C(O)-, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ - alkyl, R ６ is hydrogen, halogen, -OH, cyano, C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, C with 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C １ -C ４ -Alkyl-C(O)-, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ - alkyl, R ７ is hydrogen, -OH, fluorine, C １ -C ４ -Alkyl and C １ -C ４ - alkoxy, R ８ is hydrogen, -OH, fluorine, C １ -C ４ -Alkyl and C １ -C ４ -alkoxy; Or R ７ and R ８ taken together form an oxo group (=O), Or R ７ and R ８ together with the carbon atom to which they are attached, ３ -C ６ - forms a 3- to 6-membered ring selected from the group consisting of cycloalkyl and 3- to 6-membered heterocycloalkyl, R ９ is hydrogen, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and C １ -C ４ - alkoxy, R １０ is hydrogen, -OH, C １ -C ４ -Alkyl and C １ -C ４ - alkoxy, R １１ is hydrogen, C １ -C ４ -Alkyl and C １ -C ４ -alkoxy; Or R １０ and R １１ together with the carbon atom to which they are attached, ３ -C ６ - forms a 3- to 6-membered ring selected from the group consisting of cycloalkyl and 3- to 6-membered heterocycloalkyl, R １２ and R １３ teeth, Hydrogen, -OH, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH(-C(O)-C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl)(-C(O)-C １ -C ４ -alkyl), C １ -C ４ -Alkoxy, C １ -C ４ -alkoxy-C(O)-; C ３ -C ６ -cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , -NH-C(O)-C １ -C ４ -Alkyl, -N(C １ -C ４ -alkyl)(-C(O)-C １ -C ４ -alkyl), C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -halogenoalkyl and (C １ -C ４ -alkoxy) ２ P(═O)—, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Phenyl, Benzo-C ５ -C ６ -cycloalkyl, each of which is selected from halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; a monocyclic or bicyclic heterocycle selected from the group of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl are independently selected from the group consisting of: R １４ teeth, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ ; C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Phenyl, which is halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl is selected from the group consisting of R １５ teeth, hydrogen; C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Phenyl, which is halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl is selected from the group consisting of Q is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl, each of which is selected from halogen, SF ５ , cyano, -CHO, nitro, oxo, C １ -C ４ -Alkyl, C １ -C ４ -hydroxyalkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, hydroxy, C １ -C ４ -Alkoxy, C ３ -C ６ -Cycloalkyl-C １ -C ４ -Alkoxy, cyano-C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH-SO ２ - (C １ -C ４ -alkyl), -N(SO ２ - [C １ -C ４ -alkyl]) (C １ -C ４ -alkyl), (C １ -C ４ -alkoxyimino)-C １ -C ４ -alkyl, 4- to 6-membered heterocyclyl, which may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -CH ２ -O-(C １ -C ４ -alkyl), -CH ２ -NH(C １ -C ４ -alkyl), -CH ２ -N(C １ -C ４ -alkyl) ２ methyl substituted with a 4- to 6-membered heterocyclyl which itself may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano; ２ -S-(C １ -C ４ -alkyl), -CH ２ -S(O)-(C １ -C ４ -alkyl), -CH ２ -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -alkyl), -S(O)-(C １ -C ４ -alkyl), -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -halogenoalkyl), -S(O)-(C １ -C ４ -halogenoalkyl), -SO having 1 to 5 halogen atoms ２ - (C １ -C ４ -halogenoalkyl), -CONH(C １ -C ４ -alkyl), -CONH(C ３ -C ６ -cycloalkyl), -NHCO(C １ -C ４ -alkyl), -NHCO(C ３ -C ６ -cycloalkyl), -NHCO(C １ -C ４ -halogenoalkyl) is selected from the group consisting of where Y is O, S or N-R ９ If R ７ , R ８ , R １０ and R １１ Each of the above is —OH or C １ -C ４ - is not alkoxy, X is O, S or N-R ９ If R ７ and R ８ Each of the above is —OH or C １ -C ４ - not alkoxy] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

2. A is A1 or A2, 【Chemistry 3】 o is 0, 1, 2, 3 or 4; R is hydrogen, halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -Alkyl, -S-C １ -C ４ -halogenoalkyl, -S(O)-C １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ - halogenoalkyl, R ｐ is hydrogen, C １ -C ４ - alkyl, X and Y are CR ７ R ８ , O, S, and N-R ９ wherein at least one of X and Y is independently selected from the group consisting of ７ R ８ or X and Y taken together represent -C(O)-O- or -C(O)-NR ９ -, -S(O)-NR ９ -, -SO ２ -NR ９ - and -SO ２ forming a ring member selected from the group consisting of -O-, R １ is hydrogen, cyano, -CHO, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, C with 1 to 5 halogen atoms ３ -C ６ - halogenocycloalkyl, C ３ -C ４ -Alkenyl, C ３ -C ４ -Alkynyl, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl, C ３ -C ６ -Cycloalkyl-C １ -C ３ -Alkyl, cyano-C １ -C ４ -Alkyl, -NH-C １ -C ４ -Alkyl, -N(C １ -C ４ -alkyl) ２ , N.H. ２ -C １ -C ４ -Alkyl-, C １ -C ４ -Alkyl-NH-C １ -C ４ -alkyl-, (C １ -C ４ -alkyl) ２ N-C １ -C ４ -Alkyl-, C １ -C ４ -alkyl-C(O)-, C(O)- with 1 to 5 halogen atoms １ -C ４ -halogenoalkyl-C(O)-, C １ -C ４ -alkoxy-C(O)-, benzyloxy-C(O)-, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl-C(O)-, -SO ２ -C １ -C ４ -alkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ - halogenoalkyl; Phenyl-C １ -C ４ -Alkyl, which is halogen, -OH, -NO ２ , cyano, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, having 1 to 5 halogen atoms -S(O)-C １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halogenoalkyl; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, -OH, -NO ２ , cyano, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl is selected from the group consisting of R ２ but, Hydrogen, halogen, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２； -NR １２ R １３ ; -OR １４ ; -SR １５ 、-S(O)R １５ 、-SO ２ R １５ ; C １ -C ６ -Alkyl, C ３ -C ６ -Cycloalkyl, C ２ -C ４ -Alkenyl, C ３ -C ６ -cycloalkenyl, C ２ -C ４ -alkynyl or phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, -NO ２ , Cyano, C. １ -C ４ -alkyl-C(O)-, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH(C(O)-C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl)(C(O)-C １ -C ４ -alkyl), -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halogenoalkyl; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, -OH, -NO ２ , cyano, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Phenyl (this is halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -halogenoalkyl); and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -Alkyl, C １ -C ４ -alkyl-C(O)-, C(O)- with 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -Alkyl, C １ -C ４ -Alkoxy-C １ -C ４ -alkyl-, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogenoalkyl and 4- to 10-membered heterocycloalkyl is selected from the group consisting of R ３ is hydrogen, or C １ -C ４ - alkyl, R ４ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , preferably selected from the group consisting of hydrogen and halogen, more preferably fluorine and chlorine; R ５ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ is selected from the group consisting of R ６ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ is selected from the group consisting of R ７ is hydrogen, -OH, fluorine, C １ -C ４ -Alkyl and C １ -C ４ - alkoxy, R ８ is hydrogen, -OH, fluorine, C １ -C ４ -Alkyl and C １ -C ４ -alkoxy; Or R ７ and R ８ together form an oxo group (=O), R ９ is hydrogen, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and C １ -C ４ - alkoxy, R １０ is hydrogen, -OH, C １ -C ４ -Alkyl and C １ -C ４ - alkoxy, R １１ is hydrogen, C １ -C ４ -Alkyl and C １ -C ４ - alkoxy, R １２ and R １３ but, Hydrogen, -OH, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH(-C(O)-C １ -C ４ -alkyl), C １ -C ４ -alkoxy; C3-C6-cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , -NH-C(O)-C １ -C ４ -Alkyl, -N(C １ -C ４ -alkyl)-(-C(O)-C １ -C ４ -alkyl), C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -halogenoalkyl and (C １ -C ４ -alkoxy) ２ P(═O)—, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Phenyl, Benzo-C ５ -C ６ -cycloalkyl, each of which is selected from halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; and a monocyclic or bicyclic heterocycle selected from the group of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl are independently selected from the group consisting of: R １４ but, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ ; C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Phenyl, which is halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl is selected from the group consisting of R １５ but, hydrogen; C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; Phenyl, which is halogen, cyano, nitro, -OH, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl; and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkyl is selected from the group consisting of Q is a group represented by the formula (Q1) 【Chemistry 4】 [In the formula: Z １ , Z ２ , Z ３ , Z ４ , and Z ５ is hydrogen, halogen, SF ５ , cyano, -CHO, nitro, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, hydroxy, C １ -C ４ -Alkoxy, C ３ -C ６ -Cycloalkyl-C １ -C ４ -Alkoxy, cyano-C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH-SO ２ - (C １ -C ４ -alkyl), -N(SO ２ - [C １ -C ４ -alkyl]) (C １ -C ４ -alkyl), (C １ -C ４ -alkoxyimino)-C １ -C ４ -alkyl, 4- to 6-membered heterocyclyl, which may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -CH ２ -O-(C １ -C ４ -alkyl), -CH ２ -NH(C １ -C ４ -alkyl), -CH ２ -N(C １ -C ４ -alkyl) ２ methyl substituted with a 4- to 6-membered heterocyclyl which itself may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano; ２ -S-(C １ -C ４ -alkyl), -CH ２ -S(O)-(C １ -C ４ -alkyl), -CH ２ -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -alkyl), -S(O)-(C １ -C ４ -alkyl), -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -halogenoalkyl), -S(O)-(C １ -C ４ -halogenoalkyl), -SO having 1 to 5 halogen atoms ２ - (C １ -C ４ -halogenoalkyl), -CONH(C １ -C ４ -alkyl), -CONH(C ３ -C ６ -cycloalkyl), -NHCO(C １ -C ４ -alkyl), -NHCO(C ３ -C ６ -cycloalkyl), -NHCO(C １ -C ４ -halogenoalkyl); or Z １ and Z ２ together with the carbon atom to which they are attached form a 5- to 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with 1 or 2 substituents selected from the group consisting of methyl, fluorine and oxo; and Z ３ , Z ４ , and Z ５ is hydrogen, halogen, SF ５ , Cyano, CHO, Nitro, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, hydroxy, C １ -C ４ -Alkoxy, C ３ -C ６ -Cycloalkyl-C １ -C ４ -Alkoxy, cyano-C １ -C ４ -Alkoxy, C １ -C ４ -alkoxy-C(O)-, C(O)- having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH-SO ２ - (C １ -C ４ -alkyl), -N(SO ２ - [C １ -C ４ -alkyl]) (C １ -C ４ -alkyl), (C １ -C ４ -alkoxyimino)-C １ -C ４ -alkyl, 4- to 6-membered heterocycloalkyl, which may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, methyl or cyano, -CH ２ -O-(C １ -C ４ -alkyl), -CH ２ -NH(C １ -C ４ -alkyl), -CH ２ -N(C １ -C ４ -alkyl) ２ methyl substituted with a 4- to 6-membered heterocycloalkyl which itself may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, methyl and cyano; ２ -S-(C １ -C ４ -alkyl), -CH ２ -S(O)-(C １ -C ４ -alkyl), -CH ２ -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -alkyl), -S(O)-(C １ -C ４ -alkyl), -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -halogenoalkyl), -S(O)-(C １ -C ４ -halogenoalkyl), -SO having 1 to 5 halogen atoms ２ - (C １ -C ４ -halogenoalkyl), -CONH(C １ -C ４ -alkyl), -CONH(C ３ -C ６ -cycloalkyl), -NHCO(C １ -C ４ -alkyl), -NHCO(C ３ -C ６ -cycloalkyl), -NHCO(C １ -C ４ -halogenoalkyl); or Z ２ and Z ３ together with the carbon atom to which they are attached form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with 1 or 2 substituents selected from the group consisting of methyl, fluorine and oxo; and Z １ , Z ４ , and Z ５ is hydrogen, halogen, SF ５ , Cyano, CHO, Nitro, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, hydroxy, C １ -C ４ -Alkoxy, C ３ -C ６ -Cycloalkyl-C １ -C ４ -Alkoxy, cyano-C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH-SO ２ - (C １ -C ４ -alkyl), -N(SO ２ - [C １ -C ４ -alkyl]) (C １ -C ４ -alkyl), (C １ -C ４ -alkoxyimino)-C １ -C ４ -alkyl, 4- to 6-membered heterocycloalkyl, which may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, methyl or cyano, -CH ２ -O-(C １ -C ４ -alkyl), -CH ２ -NH(C １ -C ４ -alkyl), -CH ２ -N(C １ -C ４ -alkyl) ２ methyl substituted with a 4- to 6-membered heterocycloalkyl which itself may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, methyl, or cyano; ２ -S-(C １ -C ４ -alkyl), -CH ２ -S(O)-(C １ -C ４ -alkyl), -CH ２ -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -alkyl), -S(O)-(C １ -C ４ -alkyl), -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -halogenoalkyl), -S(O)-(C １ -C ４ -halogenoalkyl), -SO having 1 to 5 halogen atoms ２ - (C １ -C ４ -halogenoalkyl), -CONH(C １ -C ４ -alkyl), -CONH(C ３ -C ６ -cycloalkyl), -NHCO(C １ -C ４ -alkyl), -NHCO(C ３ -C ６ -cycloalkyl), -NHCO(C １ -C ４ -halogenoalkyl). or Q is a group represented by the formula (Q2) 【Chemistry 5】 [In the formula: Z ６ , Z ７ , Z ８ and Z ９ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ Independently selected from the group consisting of or Q is a group represented by the formula (Q3): 【Chemistry 6】 [In the formula: Z １０ , Z １１ and Z １２ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ Independently selected from the group consisting of or Q is a group represented by the formula (Q4) 【Chemistry 7】 [In the formula: Z １３ , Z １４ , Z １５ and Z １６ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C １ -C ４ -Hydroxyalkyl, NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , —NH—CO—C １ -C ４ -alkyl, a 5-membered heteroaryl having at least one nitrogen atom attached to the heteroaryl ring, or a 4- to 7-membered heterocycloalkyl, each of which is selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-(C １ -C ４ -halogenoalkyl), -S(O)-(C １ -C ４ -halogenoalkyl), -SO having 1 to 5 halogen atoms ２ - (C １ -C ４ -halogenoalkyl); or Q is a group represented by the formula (Q5): 【Chemistry 8】 [In the formula: Z １７ , Z １８ , Z １９ and Z ２０ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ Independently selected from the group consisting of or Q is a group represented by the formula (Q6): 【Chemistry 9】 [In the formula: T １ ~T ４ is N, O, S, C-Z ２１ and N.-Z. ２２ wherein T is independently selected from the group consisting of １ ~T ４ At most one of １ ~T ４ At most one of these is S, and T １ ~T ４ One or less of N-Z ２２ and where Individual Z ２１ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, and Individual Z ２２ is hydrogen, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkyl-C ３ -C ６ -Cycloalkyl, C １ -C ４ -Alkoxy-C １ -C ４ -alkyl, or Q is a group represented by the formula (Q7): 【Chemistry 10】 [In the formula: U １ ~U ４ is N and C-Z ２３ wherein U is independently selected from the group consisting of １ ~U ４ is N, and Individual Z ２３ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy] is a 5-membered aromatic heterocycle of where Y is O, S or N-R ９ If R ７ , R ８ , R １０ and R １１ is not -OH or C 1 -C 4 -alkoxy, and X is O, S or N-R ９ If R ７ and R ８ none of are -OH or C 1 -C 4 -alkoxy; 2. The compound of claim 1, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

3. A is A1 or A2, 【Chemistry 11】 o is 0, 1 or 2; R is halogen, C １ -C ４ -Alkyl and C １ -C ４ -alkoxy, cyano, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkyl, R ｐ is hydrogen, C １ -C ４ - alkyl, X and Y are CR ７ R ８ , O, S, and N-R ９ wherein at least one of X and Y is independently selected from the group consisting of ７ R ８ and R １ is hydrogen, C １ -C ４ -Alkyl, C ３ -C ６ -Cycloalkyl, C ３ -C ４ -Alkenyl, C ３ -C ４ -Alkynyl, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl, C ３ -C ６ -Cycloalkyl-C １ -C ３ -Alkyl, cyano-C １ -C ４ - alkyl, R ２ but, Hydrogen, halogen, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ ; -NR １２ R １３ ; -OR １４ ; -SR １５ 、-S(O)R １５ 、-SO ２ R １５ ; C １ -C ４ -Alkyl, C ３ -C ６ -Cycloalkyl, C ２ -C ４ -Alkenyl, C ３ -C ６ -cycloalkenyl, C ２ -C ４ -alkynyl or phenyl-C １ -C ４ -alkyl, each of which is selected from halogen, -OH, cyano, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -NH(C(O)-C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl)(C(O)-C １ -C ４ -alkyl), -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halogenoalkyl; and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, —OH, oxo, —COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , C １ -C ４ -Alkyl, C １ -C ４ -alkyl-C(O)-, C(O)- with 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, hydroxy-C １ -C ４ -Alkyl, C １ -C ４ -Alkoxy-C １ -C ４ -alkyl-, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ and 4- to 10-membered heterocycloalkyl, is selected from the group consisting of R ３ is hydrogen or C １ -C ４ - alkyl, R ４ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , preferably selected from the group consisting of hydrogen and halogen, more preferably fluorine and chlorine; R ５ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ is selected from the group consisting of R ６ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ is selected from the group consisting of R ７ is hydrogen and C １ -C ４ - alkyl, R ８ is hydrogen and C １ -C ４ - alkyl; Or R ７ and R ８ together form an oxo group (=O), R ９ But, C １ -C ４ - alkyl, R １０ is hydrogen, -OH, C １ -C ４ -Alkyl and C １ -C ４ - alkoxy, R １１ is hydrogen, R １２ and R １３ but, Hydrogen, -NH(-C(O)-C １ -C ４ -alkyl), C １ -C ４ -alkoxy; C3-C6-cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, cyano, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-NH(C １ -C ４ -alkyl), -C(O)-N(C １ -C ４ -alkyl) ２ , -NH-C(O)-C １ -C ４ -Alkyl, -N(C １ -C ４ -alkyl)-(-C(O)-C １ -C ４ -alkyl), C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, -S-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -S(O)-C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, -SO having 1 to 5 halogen atoms ２ -C １ -C ４ -halogenoalkyl and (C １ -C ４ -alkoxy) ２ P(═O)—, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, —OH, oxo, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkoxy; Phenyl, Benzo-C ５ -C ６ -cycloalkyl, each of which is selected from halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkoxy; and a monocyclic or bicyclic heterocycle selected from the group of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, cyano, —OH, oxo, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkoxy are independently selected from the group consisting of: R １４ but, C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is selected from halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, C ３ -C ６ - optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cycloalkyl; and Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, —OH, oxo, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkoxy; is selected from the group consisting of R １５ but, hydrogen; C １ -C ４ -alkyl, phenyl-C １ -C ４ -alkyl, each of which is selected from halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkoxy; Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkoxy; is selected from the group consisting of Q is a group represented by the formula (Q1) 【Chemistry 12】 [In the formula: Z １ , Z ２ , Z ３ , Z ４ , and Z ５ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, hydroxy, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , 4- to 6-membered heterocyclyl, which may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -S-(C １ -C ４ -alkyl), -S(O)-(C １ -C ４ -alkyl), -SO ２ - (C １ -C ４ -alkyl), S-(C １ -C ４ -halogenoalkyl), -S(O)-(C １ -C ４ -halogenoalkyl), -SO having 1 to 5 halogen atoms ２ - (C １ -C ４ -halogenoalkyl), or Z １ and Z ２ together with the carbon atom to which they are attached form a 5- or 6-membered heterocycloalkyl, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with 1 or 2 substituents selected from the group consisting of methyl, fluorine, and oxo; and Z ３ , Z ４ , and Z ５ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, C １ -C ４ -alkoxy-C(O)-, C(O)- having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, or Z ２ and Z ３ together with the carbon atom to which they are attached form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with 1 or 2 substituents selected from the group consisting of methyl, fluorine and oxo; and Z １ , Z ４ , and Z ５ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy] is a substituted phenyl ring of 3. A compound according to claim 1 or 2, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

4. A is A1 or A2, 【Chemistry 13】 o is 0, 1 or 2; R is halogen, C １ -C ４ -Alkyl and C １ -C ４ - alkoxy, R ｐ is hydrogen, C １ -C ４ - alkyl, X is CR ７ R ８ , O, S, and N-R ９ is selected from the group consisting of Y is CR ７ R ８ or O, R １ is hydrogen or C １ -C ４ - alkyl, R ２ but, Hydrogen, halogen, -C(O)-N(C １ -C ４ -alkyl) ２ ; -NR １２ R １３ ; -OR １４ ; -SR １５ 、-S(O)R １５ 、-SO ２ R １５ ; C １ -C ４ -Alkyl, C ３ -C ６ -Cycloalkyl, C ２ -C ４ -Alkenyl or C ３ -C ６ -cycloalkenyl, each of which is selected from halogen, —OH, cyano, C １ -C ４ -Alkoxy-C(O)- and -C(O)-NH ２ , C １ -C ４ -Alkoxy, -NH ２ , -N(C １ -C ４ -alkyl) ２ , -N(C １ -C ４ -alkyl)(C(O)-C １ -C ４ -alkyl); and a monocyclic or bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, —OH, oxo, —COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , C １ -C ４ -Alkyl, C １ -C ４ -alkyl-C(O)-, C(O)- with 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, hydroxy-C １ -C ４ -Alkyl-, C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl-, -NH ２ , -N(C １ -C ４ -alkyl) ２ and 4- to 10-membered heterocycloalkyl, is selected from the group consisting of R ３ is hydrogen or C １ -C ４ - alkyl, R ４ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH ２ , preferably selected from the group consisting of hydrogen and halogen, more preferably fluorine and chlorine; R ５ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ - alkoxy, R ６ is hydrogen, halogen, -OH, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ - alkoxy, R ７ is hydrogen and C １ -C ４ - alkyl, R ８ is hydrogen and C １ -C ４ - alkyl; Or R ７ and R ８ together form an oxo group (=O), R ９ But, C １ -C ４ - alkyl, R １０ is hydrogen, —OH and C １ -C ４ - alkyl, R １１ is hydrogen, R １２ and R １３ but, Hydrogen, -NH(-C(O)-C １ -C ４ -alkyl), C １ -C ４ -alkoxy; C3-C6-cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is halogen, -OH, -COOH, C １ -C ４ -Alkoxy-C(O)-, -C(O)-NH ２ , -C(O)-N(C １ -C ４ -alkyl) ２ , -NH-C(O)-C １ -C ４ -Alkyl, C １ -C ４ -Alkyl, C １ -C ４ -Alkoxy, C ３ -C ６ -cycloalkyl, -NH ２ , -N(C １ -C ４ -alkyl) ２ , -S-C １ -C ４ -Alkyl, -S(O)-C １ -C ４ -Alkyl, -SO ２ -C １ -C ４ -alkyl, and (C １ -C ４ -alkoxy) ２ P(═O)—, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: Heterocyclyl-C １ -C ４ -alkyl, where the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from halogen, cyano, —OH, oxo, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl and C １ -C ４ - optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of alkoxy; Phenyl and Benzo-C ５ -C ６ -cycloalkyl, each of which is selected from halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkoxy; and a monocyclic or bicyclic heterocycle selected from the group of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is selected from the group consisting of halogen, —OH, oxo, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogenoalkoxy are independently selected from the group consisting of: R １４ but, C １ -C ４ -Alkyl, C ３ -C ６ -cycloalkyl, phenyl-C １ -C ４ -alkyl, each of which is selected from halogen, -OH, C １ -C ４ -Alkyl, C １ -C ４ -Alkoxy and C ３ -C ６ - optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of cycloalkyl; and 4-10 membered heterocycloalkyl is selected from the group consisting of R １５ but, hydrogen; C １ -C ４ -alkyl, which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of -OH and -COOH; and 6-membered heteroaryl is selected from the group consisting of Q is a group represented by the formula (Q1) 【Chemistry 14】 [In the formula: Z １ and Z ５ is hydrogen, halogen, C １ -C ４ -Alkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ - halogenoalkyl; Z ２ and Z ４ is hydrogen, halogen, cyano, -OH, C １ -C ４ -Alkyl, C １ -C ４ -alkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , C having 1 to 5 halogen atoms １ -C ４ -halogenoalkyl, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -S-(C １ -C ４ -alkyl), S-(C １ -C ４ -halogenoalkyl), and 4- to 6-membered heterocycloalkyl; and Z ３ is hydrogen, halogen, C １ -C ４ -Alkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, and -N(C １ -C ４ -alkyl) ２ or Z １ and Z ２ together with the carbon atom to which they are attached form a 5-membered heterocycloalkyl or a 5-membered heteroaryl, each of which is optionally substituted with 1 or 2 substituents selected from the group consisting of methyl, fluorine and oxo; Z ３ and Z ５ is hydrogen, and Z ４ is hydrogen and C １ -C ４ -alkoxy-C(O)-] is a substituted phenyl ring of 4. A compound according to claim 1, 2 or 3, or a stereoisomer, tautomer, N-oxide, hydrate, solvate or salt thereof, or a mixture thereof.

5. A 【Chemistry 15】 【change】 is selected from the group consisting of R １ is hydrogen or methyl; R ２ but, Hydrogen, chlorine, iodine, -C(O)-N(CH ３ ) ２ , -NR １２ R １３ ; -OR １４ ; -SR １５ 、-S(O)R １５ 、-SO ２ R １５ ; Methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethenyl, propenyl, cyclopentenyl, cyclohexenyl, each of which is -OH, cyano, ethoxy-C(O)-, -C(O)-NH ２ , methoxy, NH ２ , N(CH ３ ) ２ , N(CH ３ )(C(O)CH ３ and Azetidine, oxetane, pyrrolidine, tetrahydrofuran, pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine, piperazine, tetrahydropyran, tetrahydropyridine, dihydro-2H-pyran, 1,2-oxazolidine, 1,2-oxazine, morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indole, 1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo[3.3.1]nonane, 6-oxa-3-azabicyclo[3.1.1]heptane, 8-oxa a monocyclic or bicyclic heterocycle selected from the group consisting of sa-3-azabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,3,4-tetrazole, pyridine, dihydropyridine, pyrimidine, tetrahydropyrimidine, 4-oxa-7-azaspiro[2.5]octane, each of which is selected from the group consisting of fluorine, chlorine, cyano, -OH, oxo, -COOH, methoxy-C(O)-, ethoxy-C(O)-, tert-butoxy-C(O)-, -C(O)-NH ２ , methyl, methyl-C(O)-, difluoromethyl, trifluoromethyl, hydroxymethyl-, methoxymethyl-, -NH ２ , -NMe ２ and pyrrolidine, is selected from the group consisting of R ３ is hydrogen or methyl; R ４ is hydrogen, fluorine, chlorine, -OH, cyano, methyl, methoxy, trifluoromethyl, trifluoromethoxy and NH ２ , preferably selected from the group consisting of hydrogen, fluorine and chlorine; R ５ is selected from the group consisting of hydrogen, fluorine, chlorine, —OH, cyano, methyl, methoxy and trifluoromethyl; R ６ is selected from the group consisting of hydrogen, fluorine, chlorine, —OH, cyano, methyl and methoxy; R １２ and R １３ but, Hydrogen, —NH(—C(O)-methyl), methoxy; Cyclopropyl, cyclobutyl, benzyl, 1-phenylethyl, each of which is a fluorine atom, —OH, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH ２ , -C(O)-NMe ２ , —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH ２ , NMe ２ , S-methyl, S(O)-methyl, SO ２ -methyl, and (EtO) ２ P(═O)—, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocyclyl substituents are selected from the group consisting of oxetane, tetrahydrofuran, tetrahydropyran, pyrrolidine, morpholine, pyrazole, imidazole, 1,2,4-oxadiazole, pyridine, each of which is optionally substituted with one substituent independently selected from the group consisting of fluorine, chlorine, -OH, oxo and methyl; Phenyl; 2,3-dihydro-1H-indene, and a monocyclic or bicyclic heterocycle selected from the group consisting of oxetane, thietane, pyrrolidine, morpholine, tetrahydropyran, pyridine and pyrazole, each of which is optionally substituted with one or two substituents independently selected from the group consisting of fluorine, chlorine, -OH, oxo, methyl; are independently selected from the group consisting of: R １４ but, methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is optionally substituted with 1 or 2 substituents independently selected from the group consisting of fluorine, -OH, methyl, methoxy and cyclopentyl; and A monocyclic or bicyclic heterocycle selected from the group consisting of pyrrolidine and tetrahydropyran. is selected from the group consisting of R １５ but, methyl and ethyl, each of which is optionally substituted with one substituent independently selected from the group consisting of -OH and -COOH; and Pyridine, is selected from the group consisting of Q is a group represented by the formula (Q1) 【Chemistry 16】 [In the formula: Z １ and Z ５ is independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, trifluoromethyl and methoxy; Z ２ and Z ４ is hydrogen, fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe ２ , trifluoromethyl, methoxy, trifluoromethoxy, -SMe, 2,2,2-trifluoroethyl)sulfanyl, and morpholinyl; and Z ３ is hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy and -NMe ２ Independently selected from the group consisting of is a substituted phenyl ring of 5. A compound according to claim 1, 2, 3 or 4, or a stereoisomer, tautomer, N-oxide, hydrate, solvate or salt thereof, or a mixture thereof.

6. A, 【Chemistry 17】 6. The compound according to claim 1, 2, 3, 4 or 5, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, selected from:

7. R ２ but, Hydrogen, chlorine, iodine, -C(O)-N(CH ３ ) ２ , -NR １２ R １３ ; -OR １４ ; -SR １５ 、-S(O)R １５ 、-SO ２ R １５ ; Methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethenyl, propenyl, cyclopentenyl, cyclohexenyl, each of which is -OH, cyano, ethoxy-C(O)-, -C(O)-NH ２ , methoxy, NH ２ , N(CH ３ ) ２ , N(CH ３ )(C(O)CH ３ and Azetidine, oxetane, pyrrolidine, tetrahydrofuran, pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine, piperazine, tetrahydropyridine, dihydro-2H-pyran, 1,2-oxazolidine, 1,2-oxazine, morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indole, 1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclo[3.3.1]nonane, 6-oxa-3-azabicyclo[3.1.1]heptane, 8-oxa-3-azabicyclo[3.1.1]heptane, 9-oxa-3-azabicyclo[3.1.1]heptane, 10-oxa-3-azabicyclo[3.1.1]heptane, 11-oxa-3-azabicyclo[3.1.1]heptane, 12-oxa-3-azabicyclo[3.1.1]heptane, 13-oxa-3-azabicyclo[3.1.1]heptane, 14-oxa-3-azabicyclo[3.1.1]heptane, 15-oxa-3-azabicyclo[3.1.1]heptane, 16-oxa-3-azabicyclo[3.1.1]heptane, 17-oxa-3-azabicyclo[3.1.1]heptane, 18-oxa-3-azabicyclo[3.1.1]heptane, 19-oxa-3-azabicyclo[3.1.1]heptane, 20-oxa-3-azabicyclo[3.1.1]heptane, 21-oxa-3-azabicyclo[3.1.1]heptane, 22-oxa-3-azabicyclo a monocyclic or bicyclic heterocycle selected from the group consisting of: xabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,3,4-tetrazole, pyridine, dihydropyridine, pyrimidine, tetrahydropyrimidine, 4-oxa-7-azaspiro[2.5]octane, each of which may be selected from the group consisting of fluorine, chlorine, cyano, -OH, oxo, -COOH, methoxy-C(O)-, ethoxy-C(O)-, tert-butoxy-C(O)-, -C(O)-NH ２ , methyl, methyl-C(O)-, difluoromethyl, trifluoromethyl, hydroxymethyl-, methoxymethyl-, -NH ２ , -NMe ２ and pyrrolidine, is selected from the group consisting of R １２ and R １３ but, Hydrogen, —NH(—C(O)-methyl), methoxy; Cyclopropyl, cyclobutyl, benzyl, 1-phenylethyl, each of which is a fluorine atom, —OH, —COOH, methoxy-C(O)—, ethoxy-C(O)—, tert-butoxy-C(O)—, —C(O)—NH ２ , -C(O)-NMe ２ , —NH—C(O)-methyl, methyl, methoxy, cyclopropyl, —NH ２ , NMe ２ , S-methyl, S(O)-methyl, SO ２ -methyl, and (EtO) ２ P(═O)—, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocyclyl substituents are selected from the group consisting of oxetane, tetrahydrofuran, tetrahydropyran, pyrrolidine, morpholine, pyrazole, imidazole, 1,2,4-oxadiazole, pyridine, each of which is optionally substituted with one substituent independently selected from the group consisting of fluorine, chlorine, -OH, oxo and methyl; Phenyl; 2,3-dihydro-1H-indene, and a monocyclic or bicyclic heterocycle selected from the group consisting of oxetane, thietane, pyrrolidine, morpholine, tetrahydropyran, pyridine and pyrazole, each of which is optionally substituted with one or two substituents independently selected from the group consisting of fluorine, chlorine, -OH, oxo, methyl; are independently selected from the group consisting of: R １４ but, methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is optionally substituted with 1 or 2 substituents independently selected from the group consisting of fluorine, -OH, methyl, methoxy and cyclopentyl; and A monocyclic or bicyclic heterocycle selected from the group consisting of pyrrolidine and tetrahydropyran. is selected from the group consisting of R １５ but, methyl and ethyl, each of which is optionally substituted with one substituent independently selected from the group consisting of -OH and -COOH; and Pyridine, Selected from the group consisting of 7. A compound according to any one of claims 1 to 6, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

8. Q is a group represented by the formula (Q1) 【Chemistry 18】 [In the ceremony: Z １ , Z ２ , Z ３ , Z ４ , and Z ５ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, hydroxy, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy, -NH(C １ -C ４ -alkyl), -N(C １ -C ４ -alkyl) ２ , 4- to 6-membered heterocyclyl, which may be substituted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -S-(C １ -C ４ -alkyl), -S(O)-(C １ -C ４ -alkyl), -SO ２ - (C １ -C ４ -alkyl), -S-(C １ -C ４ -halogenoalkyl), -S(O)-(C １ -C ４ -halogenoalkyl), -SO having 1 to 5 halogen atoms ２ - (C １ -C ４ -halogenoalkyl); or Z １ and Z ２ together with the carbon atom to which they are attached form a 5- or 6-membered heterocycloalkyl, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with 1 or 2 substituents selected from the group consisting of methyl, fluorine, and oxo; and Z ３ , Z ４ , and Z ５ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -Alkoxy, C １ -C ４ -alkoxy-C(O)-, C(O)- having 1 to 5 halogen atoms １ -C ４ - halogenoalkoxy, or Z ２ and Z ３ together with the carbon atom to which they are attached form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which is optionally substituted with 1 or 2 substituents selected from the group consisting of methyl, fluorine and oxo; and Z １ , Z ４ , and Z ５ is hydrogen, halogen, cyano, C １ -C ４ -alkyl, C having 1 to 5 halogen atoms １ -C ４ -Halogenoalkyl, C １ -C ４ -alkoxy, C having 1 to 5 halogen atoms １ -C ４ -halogenoalkoxy; is a substituted phenyl ring of 8. A compound according to any one of claims 1 to 7, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

9. Q is a group represented by the formula (Q1) 【Chemistry 19】 [In the ceremony: Z １ and Z ５ is independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, methoxy, and trifluoromethyl; Z ２ and Z ４ is hydrogen, fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe ２ , trifluoromethyl, methoxy, trifluoromethoxy, -SMe, 2,2,2-trifluoroethyl)sulfanyl, and morpholinyl; and Z ３ is hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy and -NMe ２ Independently selected from the group consisting of is a substituted phenyl ring of 9. A compound according to any one of claims 1 to 8, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

10. A is A3 or A4 【Chemistry 20】 [During the ceremony, R ｐ is hydrogen, C １ -C ４ -alkyl; preferably selected from the group consisting of hydrogen.

10. The compound according to any one of claims 1 to 9, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

11. A process for the preparation of a compound of general formula (I) according to any one of claims 1 to 10, comprising reacting a compound of general formula 1C: 【Chemistry 21】 [In the formula, A, R １ , R ２ , R ３ , R ４ , R ５ and R ６ is as defined for the compounds of general formula (I) according to any one of claims 1 to 10, and Hal is halogen, 【Chemical 22】 wherein each R may independently be H or Me, or both R are pinacolato, to thereby produce a compound of general formula (I): 【Chemistry 23】 [In the formula, A, R １ , R ２ , R ３ , R ４ , R ５ , R ６ and Q is as defined for the compounds of general formula (I) according to any one of claims 1 to 10.

12. General formula 1C: 【Chemistry 24】 [In the ceremony: R ２ is as defined for the compounds of general formula (I) according to any one of claims 1 to 6, A, R １ , R ３ , R ４ , R ５ , and R ６ is as defined for the compounds of general formula (I) according to any one of claims 1 to 7 and claim 10, and Hal is a halogen. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

13. A pharmaceutical composition comprising a compound of general formula (I) according to any one of claims 1 to 10 and one or more pharma- ceutically acceptable excipients.

14. A compound of general formula (I) according to any one of claims 1 to 10 or a pharmaceutical composition according to claim 13 for use in the control, treatment and / or prevention of a disease.

15. 15. The compound or pharmaceutical composition of claim 14, wherein the disease is a helminth infection.

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