Novel anthelmintic compounds

Abstract

The present invention relates to novel anthelmintic compounds, in particular novel compounds of general formula (I) wherein A is A1 or A2, and wherein T, X, Y, Ro, R1, R10 and R11 are as defined herein; to processes for preparing such compounds; intermediate compounds useful in the preparation of such compounds; pharmaceutical compositions and combinations comprising such compounds; and the use of said compounds as sole agent or in combination with other active ingredients for the treatment, control and / or prophylaxis of diseases, in particular helminth infections. # imgabs0 #

Description

This application is a divisional application of the invention patent application filed on October 23, 2019, with application number 201980085938.9 and title "Novel Insect Repellent Compound".

[0001] This invention covers novel compounds of general formula (I) as described and defined herein; methods for preparing said compounds; intermediate compounds that can be used to prepare said compounds; pharmaceutical compositions and combinations comprising said compounds; and the use of said compounds in the manufacture of pharmaceutical compositions for controlling, treating and / or preventing diseases, particularly for controlling, treating and / or preventing worm infections in animals and humans, more particularly gastrointestinal and extraintestinal nematode infections; formulations containing such compounds; and methods for controlling, treating and / or preventing worm infections in animals and humans, more particularly gastrointestinal and extraintestinal nematode infections, as the sole agent or in combination with other active ingredients. Background Technology

[0002] Resistance to all commercial anthelmintics appears to be a growing problem in veterinary medicine. The widespread use of anthelmintics in an attempt to control nematodes has led to significant selection for highly resistant worm populations. Therefore, the spread of resistance across all classes of anthelmintics threatens effective worm control in cattle, goats, sheep, and horses. Furthermore, the current reliance solely on macrolides for the successful prevention of canine heartworm disease is at risk, as several instances of loss of efficacy with macrolides have been described in areas of the United States—particularly in regions with high rates of heartworm infection. Finally, an experimental infection study using larvae of *Dirofilaria immitis* from suspected loss-of-efficacy field cases in the Lower Mississippi Delta region provided in vivo confirmation of the presence of macrolide resistance.

[0003] Although resistance to anthelmintics in human worms currently appears rare, the spread of anthelmintic resistance in the veterinary field, as described above, needs to be considered in the treatment of human helminthiasis. Persistent, inadequate-dose treatment of filariasis can lead to highly resistant genotypes and resistance to certain anthelmintics (e.g., praziquantel, benzimidazole, and niclosamide).

[0004] Therefore, there is an urgent need for insect repellents with novel molecular mechanisms of action to block drug resistance.

[0005] The object of the present invention is to provide compounds that can be used as anthelmintics in the medical, especially veterinary, fields, having satisfactory or improved anthelmintic activity against a broad spectrum of worms, particularly at relatively low doses, for the control, treatment and / or prevention of worm infections in animals and humans, preferably without any adverse toxic effects on the treated organism.

[0006] WO 2005012283 describes the preparation of certain benzothiophene formamides as IKK kinase inhibitors for the treatment of inflammation, cancer, and autoimmune diseases. US20140235612 describes novel azabenzimidazole compounds as PDE4 inhibitors. WO 2009155388 discloses imidazopyridine and imidazopyrazine compounds as kinase inhibitors. WO2016123392 describes pyrazolopyrimidines as inhibitors of glucocorticoid receptor translocation and their preparation. WO2007092403 discloses novel N-phenylbenzotriazoles as c-Kit inhibitors. Naumchuk et al. described the inhibitory activity of imidazolinone derivatives and their precursors on human protein kinase CK2 (Ukrainica Bioorganica Acta 2015, 13(1), 32-38). US20080242695 discloses the preparation of 1H-imidazo[4,5-b]pyridine-2-ol derivatives that regulate skeletal muscle. WO 2012106472 describes naphthidine derivatives as inhibitors of hypoxia-inducible factor (HIF) hydroxylases, their preparation, and their use in the treatment of HIF-mediated diseases. Furthermore, WO 2009100250 outlines chromone-3-ylamide derivatives as inhibitors of hypoxia-inducible factor hydroxylases. (Bioorganic & Medicinal Chemistry Letters (2002), 12(7), 1063-1066) discloses 2-oxo-1,2-dihydroquinoline-3-carboxamides as potent and novel small molecule inhibitors of plasminogen activator inhibitor-1. WO 2009100250 discloses chromone-3-ylamide derivatives as inhibitors of hypoxia-inducible factor hydroxylases. In addition, WO 2002070509 describes benzodioxane, quinoxaline, benzoxazine and related compounds as antagonists of MCP-1 for the treatment of inflammatory and autoimmune diseases.

[0007] WO 2017178416 describes a novel pyrazolopyrimidine derivative and its anthelmintic activity.

[0008] WO 2018087036 describes a novel quinoline-3-carboxamide derivative and its anthelmintic activity.

[0009] However, the prior art does not describe novel compounds of general formula (I) of the present invention as described and defined herein.

[0010] It has now been discovered that the compounds of the present invention possess surprising and advantageous properties, which form the basis of the present invention.

[0011] In particular, and surprisingly, it has been found that the compounds of the present invention effectively interact with the Slo-1 molecule of nematodes. This interaction is characterized by paralysis / inhibition, particularly of gastrointestinal nematodes, free-living nematodes, and filarial worms, the data of which are given in the biological experiments section. Therefore, the compounds of the present invention can be used as anthelmintics for the control, treatment, and / or prevention of gastrointestinal and extraintestinal worm infections, particularly gastrointestinal and extraintestinal nematode infections (including filarial worms). Summary of the Invention

[0012] According to a first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof: in: A is either A1 or A2. o can be 0, 1, 2, 3, or 4; R is selected from: hydrogen, halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl, -S(O)-C1-C4 haloalkyl and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; X and Y are independently selected from: CR 7 R 8 O, S and NR 9 Where at least one of X and Y is CR 7 R 8 ,or X and Y together form a ring member selected from the following: -C(O)-O-, -C(O)-NR 9 -、-S(O)-NR 9 -、-SO2-NR 9 -and-SO2-O-; T is selected from: 10-membered aryl and 8 to 10-membered heteroaryl, each of which is optionally partially saturated and optionally surrounded by 1, 2, 3, 4, 5 or 6 molecules selected from R. 2 R 3 R 4 R 5 R 6 Substitution with Q substituents, or T is selected from T1 T 2 T 3 T 4 T 5 T 6 T 7 T 8a T 8b and T 9 : L is selected from: O and NR 9 ; M is selected from: C=O and CR 7 R 8 ; U is selected from: CR 7 and N; V is selected from: CR 7 and N; R 1 Selected from: hydrogen, cyano, -CHO, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C3-C6 cycloalkyl, C3-C6 halocycloalkyl having 1 to 5 halogen atoms, C3-C4 alkenyl, C3-C4 alkoxy-C1-C4 alkyl, C3-C6 cycloalkyl-C1-C3 alkyl, cyano-C1-C4 alkyl, -NH-C1-C4 alkyl, -N(C1-C (4 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 haloalkyl-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 haloalkyl having 1 to 5 halogen atoms; A phenyl-C1-C4-alkyl group, optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the following: halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; a heterocyclic-C1-C4 alkyl group, wherein the heterocyclic-C1-C4 alkyl group is a alkyl group with ... The cyclosubstituents are selected from 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl groups, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms. R 2 Selected from: 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 -SO2 R 15 ; C1-C6 alkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, C3-C6 cycloalkenyl, C2-C4 alkynyl, or phenyl-C1-C4 alkyl, each optionally substituted by 1, 2, 3, 4, or 5 independently selected from the following substituents: 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 groups, C1-C4 haloalkyl groups having 1 to 5 halogen atoms, C1-C4 alkoxy groups, -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 haloalkyl groups having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl groups having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl groups having 1 to 5 halogen atoms; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, and wherein the heterocyclic substituent and / or the C1-C4 alkyl group is optionally substituted by 1, 2, or 3 independently selected substituents from: halogen, -OH, -NO2, cyano, -COOH, C1-C4 alkyl-C(O)-, C1-C4 alkoxy-C(O)-, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy -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 alkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 alkyl with 1 to 5 halogen atoms, and -SO2-C1-C4 alkyl with 1 to 5 halogen atoms; Phenyl, optionally substituted with one, two or three independent substituents selected from the following: halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; or monocyclic or bicyclic heterocyclic selected from: 4- to 10-membered heterocyclic alkyl, heterospirocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, 3, or 4 independently selected substituents from: halogen, cyano, nitro, -OH, oxo , thiocarbonyl, -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 alkyl-C(O)-, C1-C4 haloalkyl with 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl-, C1-C4 haloalkyl with 1 to 5 halogen atoms Alkyl groups, C3-C6 cycloalkyl groups, -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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and 4 to 10-membered heterocyclic alkyl groups; R 3 Selected from: hydrogen, halogens, or C1-C4 alkyl groups; R 4 Selected from: hydrogen, halogen, -OH, cyano, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C1-C4 alkyl-C(O)-, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -S-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl; R 5Selected from: hydrogen, halogen, -OH, cyano, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-C(O)-, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -S-C1-C4 alkyl, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl; R 6 Selected from: hydrogen, halogen, -OH, cyano, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C1-C4 alkyl-C(O)-, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -S-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl; R 7 Selected from: hydrogen, -OH, halogen, C1-C4 alkyl and C1-C4 alkoxy; R 8 Selected from: hydrogen, -OH, halogen, C1-C4 alkyl and C1-C4 alkoxy; Or R 7 and R 8 Together with the carbon atoms to which they are attached, they form 3- to 6-membered rings selected from the following: C3-C6 cycloalkyl and 3- to 6-membered heteroalkyl; R 9 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy groups having 1 to 5 halogen atoms; R 10 Selected from: hydrogen, -OH, C1-C4 alkyl and C1-C4 alkoxy; R 11 Selected from: hydrogen, C1-C4 alkyl, and C1-C4 alkoxy; Or R 10 and R 11 Together with the carbon atoms they are attached to, they form 3- to 6-membered rings selected from the following: C3-C6 cycloalkyl and 3- to 6-membered heteroalkyl rings. R 12 and R 13 Selected independently from: 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 optionally substituted with one, two or three independent substituents selected from the following: 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 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms, and (C1-C4 alkoxy)2P(=O)-; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C 4. Alkoxy, hydroxy-C1-C4 alkyl, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, benzo-C5-C6 cycloalkyl, each optionally substituted with one, two or three independent substituents selected from the following: halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five 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 haloalkyl having one to five halogen atoms, -S(O)-C1-C4 haloalkyl having one to five halogen atoms and -SO2-C1-C4 haloalkyl having one to five halogen atoms; Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms. R 14 Selected from: -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2; C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each optionally substituted with one, two or three independent substituents selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, having 1 to 5 halogen atoms C1-C4 halogenated alkoxy groups with 5 halogen atoms, C3-C6 cycloalkyl groups, -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 halogenated alkyl groups with 1 to 5 halogen atoms, -S(O)-C1-C4 halogenated alkyl groups with 1 to 5 halogen atoms, and -SO2-C1-C4 halogenated alkyl groups with 1 to 5 halogen atoms; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C 4. Alkoxy, hydroxy-C1-C4 alkyl, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; A phenyl group, optionally substituted with one, two, or three substituents independently selected from the following: halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five 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 haloalkyl having one to five halogen atoms, -S(O)-C1-C4 haloalkyl having one to five halogen atoms, and -SO2-C1-C4 haloalkyl having one to five halogen atoms; and Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms. R 15 Selected from: C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each optionally substituted with one, two or three independent substituents selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, having 1 to 5 halogen atoms C1-C4 halogenated alkoxy groups with 5 halogen atoms, C3-C6 cycloalkyl groups, -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 halogenated alkyl groups with 1 to 5 halogen atoms, -S(O)-C1-C4 halogenated alkyl groups with 1 to 5 halogen atoms, and -SO2-C1-C4 halogenated alkyl groups with 1 to 5 halogen atoms; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C 4. Alkoxy, hydroxy-C1-C4 alkyl, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; A phenyl group, optionally substituted with one, two, or three substituents independently selected from the following: halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five 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 haloalkyl having one to five halogen atoms, -S(O)-C1-C4 haloalkyl having one to five halogen atoms, and -SO2-C1-C4 haloalkyl having one to five halogen atoms; and Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms. R 16 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy groups having 1 to 5 halogen atoms; R 17 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy groups having 1 to 5 halogen atoms; Q is selected from: 6- to 10-membered aryl and 5- to 10-membered heteroaryl, each optionally substituted by 1, 2, 3, 4 or 5 substituents selected from the following: halogen; SF5; cyano; -CHO; nitro; oxo; C1-C4 alkyl; C1-C4 hydroxyalkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; -OH; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 haloalkyl having 1 to 5 halogen atoms. Alkoxy; -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 heterocyclic groups optionally substituted with one or two substituents selected from fluorine, chlorine, bromine, methyl, and cyano; -CH2-O-(C1-C4 alkyl), -CH2-NH(C1-C4 alkyl), -CH 2-N(C1-C4 alkyl)2; methyl group substituted with a 4- to 6-membered heterocyclic group, wherein the 4- to 6-membered heterocyclic group itself is optionally substituted with one or two substituents selected from 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); having 1 to -S- (C1-C4 haloalkyl) with 5 halogen atoms; -S(O)- (C1-C4 haloalkyl) with 1 to 5 halogen atoms; -SO2- (C1-C4 haloalkyl) with 1 to 5 halogen atoms; -CONH (C1-C4 alkyl); -CONH (C3-C6 cycloalkyl); -NHCO (C1-C4 alkyl); -NHCO (C3-C6 cycloalkyl); -NHCO (C1-C4 haloalkyl) with 1 to 5 halogen atoms; Where Y is O, S or NR 9 At that time, R 7 R 8 R 10 and R 11 None of them are -OH, and when X is O, S or NR 9 At that time, R 7 and R 8 None of them are -OH.

[0013] definition The term "substituted" means that one or more hydrogen atoms on a specified atom or group are replaced by a selection from the specified group, provided that the replacement does not exceed the normal valence of the specified atom. Combinations of substituents and / or variables are permitted.

[0014] The term "optionally substituted" means that the number of substituents may be equal to or different from zero. Unless otherwise indicated, the optionally substituted group may be substituted with as many optional substituents as possible, which are accommodated by replacing hydrogen atoms with non-hydrogen substituents on any available carbon or nitrogen atom. Typically, the number of optional substituents may be 1, 2, 3, 4, or 5, especially 1, 2, or 3, if present.

[0015] As used herein, the term "one or more", for example in the definition of substituents in compounds of general formula (I) of the present invention, means "1, 2, 3, 4 or 5, particularly 1, 2, 3 or 4, more particularly 1, 2 or 3, and even more particularly 1 or 2".

[0016] As used in this article, an oxygen substituent refers to an oxygen atom bonded to a carbon or sulfur atom via a double bond.

[0017] The term "cyclic substituent" refers to a substituent attached to an aromatic or non-aromatic ring, which replaces a available hydrogen atom on that ring.

[0018] If a complex substituent consists of more than one part, such as (C1-C4 alkoxy)-(C1-C4 alkyl)-, then the position of a given part can be at any suitable position of the complex substituent; that is, the C1-C4 alkoxy part can be attached to any carbon atom of the C1-C4 alkyl part of the (C1-C4 alkoxy)-(C1-C4 alkyl)- group. A hyphen at the beginning or end of such a complex substituent indicates the point of attachment between the complex substituent and the rest of the molecule. If a ring containing a carbon atom and optionally one or more heteroatoms (such as nitrogen, oxygen, or sulfur atoms) is substituted, for example, the substituent can be bonded to any suitable position of the ring, attached to a suitable carbon atom and / or a suitable heteroatom.

[0019] As used herein, the locations through which each substituent connects to the remainder of the molecule in the drawn structure can be indicated by a hash (#) or a dashed line in the substituent.

[0020] The term "comprising" as used in this specification includes "consisting of".

[0021] If any item is referred to as "as mentioned herein" in the context of this invention, it means that it may be mentioned anywhere in the context of this invention.

[0022] As used in the context of this invention, the terms have the following meanings: The term "halogen atom" refers to a fluorine, chlorine, bromine, or iodine atom, especially a fluorine, chlorine, or bromine atom, and even more so a chlorine or fluorine atom.

[0023] The term "C1-C6 alkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon group having 1, 2, 3, 4, 5, or 6 carbon atoms. The term "C1-C4 alkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon group having 1, 2, 3, or 4 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, or tert-butyl, or their isomers. Specifically, the group has 1, 2, or 3 carbon atoms ("C1-C3 alkyl"), such as methyl, ethyl, n-propyl, or isopropyl.

[0024] The term "C1-C4 hydroxyalkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon group, where the term "C1-C4 alkyl" is as defined above, and one or two hydrogen atoms are replaced by hydroxyl groups, such as hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropyl-2-yl, 2-hydroxypropyl-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropyl-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, and 1-hydroxy-2-methyl-propyl.

[0025] The terms “-NH(C1-C4 alkyl)” or “-N(C1-C4 alkyl)2” refer to a straight-chain or branched saturated monovalent group, wherein the term “C1-C4 alkyl” is as defined above, such as methylamino, ethylamino, n-propylamino, isopropylamino, N,N-dimethylamino, N-methyl-N-ethylamino, or N,N-diethylamino.

[0026] The terms “-S-C1-C4 alkyl”, “-S(O)-C1-C4 alkyl”, or “-SO2-C1-C4 alkyl” refer to straight-chain or branched saturated groups, wherein the term “C1-C4 alkyl” is as defined above, such as methyl thioalkyl, ethyl thioalkyl, n-propyl thioalkyl, isopropyl thioalkyl, n-butyl thioalkyl, sec-butyl thioalkyl, isobutyl thioalkyl or tert-butyl thioalkyl, methyl sulfinyl, ethyl sulfinyl, n-propyl sulfinyl, isopropyl sulfinyl, n-butyl sulfinyl, sec-butyl sulfinyl, isobutyl sulfinyl or tert-butyl sulfinyl, or methanesulfonyl, ethanesulfonyl, n-propanesulfonyl, isopropanesulfonyl, n-butanesulfonyl, sec-butanesulfonyl, isobutanesulfonyl or tert-butanesulfonyl.

[0027] The term "S-C1-C4 haloalkyl" refers to a straight-chain or branched group, wherein the term "C1-C4 haloalkyl" is as defined below, and wherein one or more hydrogen atoms are replaced by halogen atoms in the same or different ways. In particular, the halogen atom is a fluorine atom. More particularly, all of the halogen atoms are fluorine atoms ("C1-C4 fluoroalkyl"). The C1-C4 haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, or 1,3-difluoropropyl-2-yl, with trifluoromethyl being particularly preferred.

[0028] The term "C1-C4 haloalkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon group, wherein the term "C1-C4 alkyl" is as defined above, and one or more hydrogen atoms are replaced by halogen atoms in the same or different ways. In particular, the halogen atom is a fluorine atom. More particularly, all of the halogen atoms are fluorine atoms ("C1-C4 fluoroalkyl"). The C1-C4 haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, or 1,3-difluoropropyl-2-yl, with trifluoromethyl being particularly preferred.

[0029] The term “C1-C4 alkoxy” refers to a straight-chain or branched saturated monovalent group of the formula (C1-C4 alkyl)-O-, wherein the term “C1-C4 alkyl” is as defined above, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy or isomers thereof, with methoxy being particularly preferred.

[0030] The term "C1-C4 haloalkoxy" refers to a straight-chain or branched saturated monovalent C1-C4 alkoxy group as defined above, wherein one or more hydrogen atoms are replaced by halogen atoms, either identically or differently. Specifically, the halogen atom is a fluorine atom. The C1-C4 haloalkoxy group is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, or pentafluoroethoxy.

[0031] The term "C2-C4 alkenyl" refers to a straight-chain or branched monovalent hydrocarbon group containing a double bond and having 2, 3, or 4 carbon atoms. The C2-C4 alkenyl group is, for example, ethenyl (or "vinyl"), propen-2-en-1-yl (or "allyl"), propen-1-en-1-yl, but-3-enyl, but-2-enyl, but-1-enyl, propen-1-en-2-yl (or "isopropenyl"), 2-methylpropen-2-enyl, 1-methylpropen-2-enyl, 2-methylpropen-1-enyl, or 1-methylpropen-1-enyl. In particular, the group is allyl.

[0032] The term "C2-C4 ynyl" refers to a straight-chain monovalent hydrocarbon group containing a triple bond and 2, 3, or 4 carbon atoms. The C2-C4 ynyl group is, for example, ethynyl, prop-1-ynyl, prop-2-ynyl (or "propynyl"), but-1-ynyl, but-2-ynyl, but-3-ynyl, or 1-methylprop-2-ynyl. Specifically, the ynyl group is prop-1-ynyl or prop-2-ynyl.

[0033] The term "C3-C6 cycloalkyl" refers to a saturated monovalent monocyclic hydrocarbon ring containing 3, 4, 5, or 6 carbon atoms ("C3-C6 cycloalkyl"). The C3-C6 cycloalkyl is, for example, a monocyclic hydrocarbon ring, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0034] The term "C3-C6 halocycloalkyl" refers to a saturated monovalent monocyclic hydrocarbon ring, wherein the term "C3-C6 cycloalkyl" is as defined above, and one or more hydrogen atoms are replaced by halogen atoms, either the same or different. Specifically, the halogen atom is a fluorine or chlorine atom. The C3-C6 halocycloalkyl 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.

[0035] The term “heterocyclic-C1-C4 alkyl” refers to a straight-chain or branched saturated monovalent group, wherein the term “C1-C4 alkyl” is as defined above, and one or two hydrogen atoms are replaced by a heterocyclic group as defined below.

[0036] The terms "-NH(C3-C6 cycloalkyl)" or "-N(C1-C4 alkyl)(C3-C6 cycloalkyl)" refer to a straight-chain or branched saturated monovalent group, wherein the terms "C1-C4 alkyl" and "C3-C6 cycloalkyl" are as defined above, such as cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, N-methyl-N-cyclopropylamino, N-ethyl-N-cyclopropylamino, N-methyl-N-cyclobutylamino, N-ethyl-N-cyclobutylamino, N-methyl-N-cyclopentylamino, N-ethyl-N-cyclopentylamino, N-methyl-N-cyclohexylamino, or N-ethyl-N-cyclohexylamino.

[0037] The term "benzo-C5-C6 cycloalkyl" refers to a monovalent bicyclic hydrocarbon ring in which a saturated monovalent monocyclic hydrocarbon ring ("C5-C6 cycloalkyl") containing 5 or 6 carbon atoms is fused to a benzene ring. The benzo-C5-C6 cycloalkyl is, for example, a bicyclic hydrocarbon ring, such as an indene (i.e., 2,3-dihydro-1H-indene) or tetrahydronaphthalene (i.e., 1,2,3,4-tetrahydronaphthalene) group.

[0038] The term "spirocycloalkyl" refers to a saturated monovalent bicyclic hydrocarbon group in which two rings share a common ring carbon atom, and wherein 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 via any carbon atom other than the spirocarbon atom. The spirocycloalkyl group is, for example, 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, or spiro[5.5]undecyl.

[0039] The term “heterocyclic alkyl” refers to 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 heterocyclic alkyl” groups), particularly 4, 5 or 6 ring atoms (“4 to 6-membered heterocyclic alkyl” groups), containing one or two identical or different cyclic heteroatoms selected from N, O and S, wherein the heterocyclic alkyl group may be attached to the rest of the molecule via any one of the carbon atoms or a nitrogen atom (if present).

[0040] The heterocyclic alkyl group can be (but is not limited to) a 4-membered ring, such as, for example, azirrobutyl, oxacyclobutyl, or thiohexacyclobutyl; or a 5-membered ring, such as, for example, tetrahydrofuranyl, 1,3-dioxolanecycloyl, thiohexacyclopentyl, pyrrolidinyl, imidazolidinyl, pyrazolyl, 1,1-dioxothiohexacyclopentyl, 1,2-oxazolyl, 1,3-oxazolyl, 1,3-thiazolidinyl, or 1,2,4-triazolyl; or a 6-membered ring, such as, for example, tetrahydropyranyl, tetrahydrothiaranyl, piperidinyl, morpholinyl, dithiazolidinyl, thiomorpholinyl, piperazine, 1,3-dioxacyclohexyl, 1,4-dioxacyclohexyl, or 1,2-oxaazacyclohexyl; or a 7-membered ring, such as... Examples include azirmonyl heptyl, 1,4-diazacycloheptyl, or 1,4-oxazacycloheptyl; or bicyclic 7-membered rings, such as, for example, 6-oxa-3-azabicyclo[3.1.1]heptane; or bicyclic 8-membered rings, such as, for example, 5,6-dihydro-4H-furano[2,3-c]pyrrole or 8-oxa-3-azabicyclo[3.2.1]octane; or bicyclic 9-membered rings, such as, for example, 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; or bicyclic 10-membered rings, such as, for example, decahydroquinoline or 3,4-dihydroisoquinoline.

[0041] The term "heterospirocycloalkyl" refers to a bicyclic saturated heterocycle having a total of 6, 7, 8, 9, 10, or 11 ring atoms, wherein the two rings share a common ring carbon atom, and the "heterospirocycloalkyl" contains one or two identical or different ring heteroatoms selected from N, O, and S; the heterospirocycloalkyl may be attached to the rest of the molecule via any carbon atom other than the spirocarbon atom or a nitrogen atom (if present).

[0042] The spirocycloalkyl group is, for example, azezospiro[2.3]hexyl, azezospiro[3.3]heptyl, oxazezospiro[3.3]heptyl, thiaazezospiro[3.3]heptyl, oxazezospiro[3.3]heptyl, oxazezospiro[5.3]nonyl, oxazezospiro[4.3]octyl, oxazezospiro[2.5]octyl, azezospiro[4.5]decyl, oxazezospiro[5.5]undecyl, di... Azaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl or one of the following other homologous scaffolds: 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]-.

[0043] The term "6 to 10 aryl" refers to a monovalent monocyclic or bicyclic aromatic ring having 6 to 10 carbon ring atoms, particularly including phenyl and naphthyl groups.

[0044] The term “heteroaryl” refers to a monovalent monocyclic, bicyclic, or tricyclic aromatic ring having 5, 6, 9, or 10 ring atoms (“5- to 10-membered heteroaryl” groups), particularly 5 or 6 ring atoms (“5- to 6-membered heteroaryl” groups), containing at least one cyclic heteroatom selected from the N, O, and / or S series and optionally one, two, or three other cyclic heteroatoms bonded via a cyclic carbon atom or optionally via a cyclic nitrogen atom (if the valence allows).

[0045] The heteroaryl group may be a 5-membered heteroaryl group, such as, for example, thienyl, furanyl, pyrroleyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiazolyl, or tetrazolyl; or a 6-membered heteroaryl group, such as, for example, pyridinyl, pyrimidinyl, pyrazinyl, or triazinyl.

[0046] The term "heterocyclic" refers to a heterocycle selected from heterocyclic alkyl and heteroaryl groups. In particular, the term "4- to 6-membered heterocyclic" refers to a heterocycle selected from 4- to 6-membered heterocyclic alkyl and 5- to 6-membered heteroaryl groups.

[0047] Generally, and unless otherwise mentioned, heteroaryl or heteroarylene includes all its possible isomer forms, such as tautomers and positional isomers associated with the linking sites of the rest of the molecule. Thus, for some illustrative and non-limiting examples, the term pyridyl includes pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl; or the term thiophenyl includes thiophenin-2-yl and thiophenin-3-yl.

[0048] As used herein, for example in the context of the definitions of “C1-C4 alkyl”, “C1-C4 haloalkyl”, “C1-C4 hydroxyalkyl”, “C1-C4 alkoxy” or “C1-C4 haloalkoxy”, the term “C1-C4” means an alkyl group having a finite number of carbon atoms, i.e., 1, 2, 3 or 4 carbon atoms.

[0049] Furthermore, as used herein, such as in the context of the definition of “C3-C6 cycloalkyl” or C3-C6 halocycloalkyl, the term “C3-C6” means a cycloalkyl group having a finite number of carbon atoms, i.e., 3, 4, 5 or 6 carbon atoms.

[0050] When a range of values ​​is given, the range covers every value within that range and its subranges.

[0051] For example: "C1-C4" includes C1, C2, C3, C4, C1-C4, C1-C3, C1-C2, C2-C4, C2-C3 and C3-C4; "C2-C6" includes 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" includes C3, C4, and C3-C4; C3-C 10 "Including 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-C10 ; "C3-C8" includes 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" includes 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 "Including 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 ; C6-C 10 "Including 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 .

[0052] As used herein, the term "leaving group" refers to an atom or atomic group that, along with its bonded electrons, is replaced by a stable species in a chemical reaction. In particular, such leaving groups are selected from: halide ions, especially fluoride, chloride, bromide, or iodide ions; (methanesulfonyl)oxy, [(trifluoromethyl)sulfonyl]oxy, [(nonafluorobutyl)sulfonyl]oxy, (benzenesulfonyl)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.

[0053] In the context of this invention, an oxygen substituent means an oxygen atom that is bonded to a carbon atom via a double bond.

[0054] Compounds of general formula (I) can exist as isotopic variants. Therefore, the present invention includes one or more isotopic variants of compounds of general formula (I), particularly deuterium-containing compounds of general formula (I).

[0055] The term "isotopic variant" of a compound or reagent is defined as a compound that exhibits a non-natural proportion of one or more of the isotopes that make up such a compound.

[0056] The term “isotopic variant of a compound of general formula (I)” is defined as a compound of general formula (I) that shows one or more non-natural proportions of the isotopes that constitute such a compound.

[0057] The term "non-natural proportion" means that such isotopes are present in proportions higher than their natural abundance. In this case, the natural abundance of the isotopes to be applied is described in "Isotopic Compositions of the Elements 1997", Pure Appl. Chem., 70(1), 217-235, 1998.

[0058] Examples of such isotopes include stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine, such as... 2 H (deuterium) 3 H (tritium) 11 C 13 C 14 C 15 N、 17 O、 18 O、 32 P, 33 P, 33S, 34 S, 35 S, 36 S, 18 F, 36 Cl、 82 Br、 123 I, 124 I, 125 I, 129 I and 131 I.

[0059] Regarding the treatment and / or prevention of the conditions specified herein, isotopic variants of compounds of general formula (I) preferably contain deuterium (“compounds of general formula (I) containing deuterium”). This includes one or more radioactive isotopes (such as…) 3 H or 14 Isotopic variants of compounds of general formula (I) (C) can be used, for example, in studies of drug and / or matrix tissue distribution. These isotopes are particularly preferred due to their ease of incorporation and detectability. Positron-emitting isotopes such as 18 F or 11 C is incorporated into compounds of general formula (I). Isotopic variants of these compounds of general formula (I) are used for in vivo imaging applications. Deuterium-containing and... 13 Compounds of general formula (I) of C can be used for mass spectrometry analysis in preclinical or clinical studies.

[0060] Isotopic variants of compounds of general formula (I) can typically be prepared by methods known to those skilled in the art, such as those described in the schemes and / or examples herein, by substituting the reagent with an isotopic variant, preferably a deuterium-containing reagent. Depending on the desired deuteration site, in some cases, deuterium from D₂O can be directly incorporated into the compound or into a reagent that can be used to synthesize such a compound. Deuterium is also a useful reagent for incorporating deuterium into a molecule. Catalytic deuteration of alkene and alkyne bonds is a rapid route for deuterium incorporation. In the presence of deuterium, metal catalysts (i.e., Pd, Pt, and Rh) can be used to directly exchange hydrogen in functionalized hydrocarbons for deuterium. Various deuterating agents and synthetic structural units are commercially available from companies such as: C / D / N Isotopes, Quebec, Canada; Cambridge Isotope Laboratories Inc., Andover, MA, USA; and CombiPhos Catalysts, Inc., Princeton, NJ, USA.

[0061] 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 are replaced by one or more deuterium atoms and in which the abundance of deuterium at each deuteration position in the compound of general formula (I) is higher than the natural abundance of deuterium, which is about 0.015%. In particular, in the deuterium-containing compound of general formula (I), the abundance of deuterium at each deuteration position in 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 even more preferably greater than 98% or 99% at said position. It should be understood that the abundance of deuterium at each deuteration position is independent of the abundance of deuterium at other deuteration positions.

[0062] Selectively incorporating one or more deuterium atoms into a compound of general formula (I) can alter the physicochemical properties of the molecule (such as, for example, 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, and can cause changes in the ratio of the parent compound to metabolites or the amount of metabolites formed. Such changes can produce certain therapeutic advantages and are therefore preferred in some cases. Decreased rates of metabolism and metabolic conversion, with changes in the ratio of metabolites, have been reported (AEMutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). These changes in exposure to parent drugs and metabolites can have significant consequences for the pharmacodynamics, tolerability, and efficacy of deuterium-containing compounds of general formula (I). In some cases, deuteration reduces or eliminates the formation of unwanted or toxic metabolites and promotes the formation of desired metabolites (e.g., Nevirapine: AMSharma 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 reduce systemic clearance. As a result, the biological half-life of the compound increases. Potential clinical benefits would include the ability to maintain similar systemic exposure with reduced peak levels and increased trough levels. Depending on the specific compound's pharmacokinetic / pharmacodynamic relationship, this could lead to fewer side effects and enhanced efficacy. ML-337 (CJ Wenthhur et al., J. Med. Chem., 2013, 56, 5208) and Odanacatib (K. Kassahun et al., WO2012 / 112363) are examples of this deuteration effect. Other cases have been reported where a decrease in metabolic rate leads to increased drug exposure without altering 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 exhibiting this effect may have reduced dosing requirements (e.g., reduced frequency or dose to achieve the desired effect) and / or produce a lower metabolite load.

[0063] Compounds of general formula (I) may possess multiple potential metabolic attack sites. To optimize the effects on physicochemical properties and metabolic profiles described above, deuterium-containing compounds of general formula (I) with one or more deuterium hydrogen exchange modes can be selected. In particular, one or more deuterium atoms in deuterium-containing compounds of general formula (I) are attached to carbon atoms and / or located at metabolic enzymes (such as, for example, cytochrome P) in compounds of general formula (I). 450 The location of the attack site.

[0064] When this text uses the plural forms of terms such as compound, salt, polymorph, hydrate, solvate, etc., it also refers to a single compound, salt, polymorph, isomer, hydrate, solvate, etc.

[0065] "Stable compound" or "stable structure" means a compound that is robust enough to withstand separation from the reaction mixture to a suitable purity and formulation into an effective therapeutic agent.

[0066] Depending on the position and nature of the various desired substituents, the compounds of the present invention optionally contain one or more asymmetric centers. One or more asymmetric carbon atoms may exist in (R) or (S) configurations, which can produce racemic mixtures in the case of a single asymmetric center and diastereomeric mixtures in the case of multiple asymmetric centers. In some cases, asymmetry may also exist due to restrictive rotation around a given bond (e.g., a central bond adjacent to the two substituted aromatic rings of a specified compound).

[0067] Preferred compounds are those that produce the desired biological activity. Isolated, pure, or partially purified isomers and stereoisomers, or mixtures of racemic or diastereomers of the compounds of this invention are also included within the scope of this invention. Purification and isolation of such materials can be accomplished using standard techniques known in the art.

[0068] Preferred isomers are those that produce the desired biological activity. These isolated, pure, or partially purified isomers or racemic mixtures of the compounds of this invention are also included within the scope of this invention. Purification and isolation of such materials can be accomplished using standard techniques known in the art.

[0069] Optical isomers can be obtained by resolving racemic mixtures according to conventional methods, such as by forming diastereomeric salts or covalent diastereomers using optically active acids or bases. Examples of suitable acids are tartaric acid, diacetyltartaric acid, benzoyltartaric acid, and camphorsulfonic acid. Mixtures of diastereomers can be separated into their individual diastereomers based on their physical and / or chemical differences using methods known in the art (e.g., by chromatography or stepwise crystallization). The optically active base or acid is then released from the separated diastereomeric salt. Different methods for separating optical isomers involve the use of chiral chromatography (e.g., HPLC columns using chiral phases) with or without conventional derivatization, the optimal choice being to maximize the separation of enantiomers. Suitable HPLC columns using chiral phases are commercially available, such as those manufactured by Daicel, such as Chiracel OD and Chiracel OJ, as well as many other columns, all of which are routinely chosen. Enzymatic separation, with or without derivatization, is also useful. The optically active compounds of the present invention can also be obtained by chiral synthesis using optically active starting materials.

[0070] To distinguish between different types of isomers, refer to section E of IUPAC rule (Pure Appl Chem 45, 11-30, 1976).

[0071] This invention includes all possible stereoisomers of the compounds of this invention, as a single stereoisomer or as any mixture of said stereoisomers (e.g., (R) or (S) isomers) in any ratio. The separation of a single stereoisomer of the compounds of this invention (e.g., a single enantiomer or a single diastereomer) is achieved by any suitable prior art method such as, for example, chromatography (especially chiral chromatography).

[0072] Furthermore, the compounds of the present invention can exist as tautomers. For example, any compound of the present invention containing a substitution pattern on the α-CH- moiety of azaquinoline that produces enhanced CH acidity can exist as a tautomer or even as a mixture of two tautomers in any amount.

[0073] This invention includes all possible tautomers of the compounds of this invention, either as a single tautomer or as any mixture of said tautomers in any ratio.

[0074] Furthermore, the compounds of the present invention can exist as N-oxides, defined as compounds in which at least one nitrogen atom is oxidized. The present invention includes all such possible N-oxides.

[0075] This invention also covers useful forms of the compounds of this invention, such as metabolites, hydrates, solvates, prodrugs, salts (especially pharmaceutically acceptable salts) and / or coprecipitates.

[0076] The compounds of the present invention can exist as hydrates or as solvates, wherein the compounds contain a polar solvent (especially, for example, water, methanol, or ethanol) as a structural element of the compound lattice. The amount of the polar solvent (especially water) can be present in stoichiometric or non-stoichiometric ratios. In the case of stoichiometric solvates (e.g., hydrates), hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-, etc., solvates or hydrates are each possible. The present invention includes all such hydrates or solvates.

[0077] Furthermore, the compounds of the present invention may exist in free form (e.g., as a free base or as a free acid), as a zwitterion, or as a salt. The salt may be any salt commonly used in pharmaceutical science or used, for example, for the isolation or purification of the compounds of the present invention, an organic or inorganic addition salt, especially any pharmaceutically acceptable organic or inorganic addition salt.

[0078] The term "pharmaceutical-acceptable salt" refers to an inorganic or organic acid addition salt of the compounds of the present invention. See, for example, SMBerge et al., "Pharmaceutical Salts", J. Pharm. Sci. 1977, 66, 1-19.

[0079] Suitable pharmaceutically acceptable salts of the compounds of the present invention may be, for example, acid addition salts of the compounds of the present invention having a nitrogen atom in the chain or ring, for example, being sufficiently basic, such as acid addition salts with inorganic acids or "mineral acids" such as, for example, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, aminosulfonic acid, bisulfuric acid, phosphoric acid, or nitric acid; or acid addition salts with organic acids such as, for example, 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. Acids, camphoric acid, cinnamic acid, cyclopentanepropionic acid, digluconic acid, 3-hydroxy-2-naphtholic acid, nicotinic acid, pyruvic acid, pectinic acid, 3-phenylpropionic acid, tervaline, 2-hydroxyethanesulfonic acid, itaconic acid, trifluoromethanesulfonic acid, dodecyl sulfate, ethanesulfonic acid, benzenesulfonic acid, p-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 thiocyanate.

[0080] In addition, another suitable pharmaceutically acceptable salt of the sufficiently acidic compounds of the present invention is an alkali metal salt, such as a sodium or potassium salt; an alkaline earth metal salt, such as a calcium, magnesium, or strontium salt; or an aluminum or zinc salt; or an ammonium salt derived from ammonia or an organic primary, secondary, or tertiary amine having 1 to 20 carbon atoms, such as ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol, tris(hydroxymethyl)aminomethane, procaine, dibenzylamine, N-methylmorpholine, arginine, lysine. Acids, 1,2-ethylenediamine, N-methylpiperidine, N-methylglucosamine, N,N-dimethylglucosamine, N-ethylglucosamine, 1,6-hexanediamine, glucosamine, sarcosine, serine, 2-amino-1,3-propanediol, 3-amino-1,2-propanediol, 4-amino-1,2,3-butanetriol; or salts of 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 chloride.

[0081] Those skilled in the art will further recognize that the acid addition salts of the claimed compounds can be prepared by reacting the compound with a suitable inorganic or organic acid via any of a variety of known methods. Alternatively, the alkali metal and alkaline earth metal salts of the acidic compounds of the present invention can be prepared by reacting the compounds of the present invention with a suitable base via a variety of known methods.

[0082] This invention includes all possible salts of the compounds of this invention, either as a single salt or as any mixture of said salts in any ratio.

[0083] In the context of this invention, particularly in the experimental section, the precise stoichiometric composition of the salt form obtained by the respective preparation and / or purification methods is, in most cases, unknown for the synthesis of intermediates and embodiments of this invention, when the compounds are mentioned as salts formed with the corresponding bases or acids.

[0084] Unless otherwise specified, suffixes relating to the chemical name or structural formula of a salt, such as, for example, “hydrochloride,” “trifluoroacetate,” “sodium salt,” or “x HCl,” “x CF3 COOH,” “x Na,” etc. + "This refers to the salt form, the stoichiometry of which is not specified."

[0085] This similarly applies to situations where, by the aforementioned preparation and / or purification methods, a synthetic intermediate or example compound or its salt is obtained as a solvate, such as a hydrate, of unknown stoichiometric composition (if defined).

[0086] Furthermore, the present invention includes all possible crystalline forms or polymorphs of the compounds of the present invention, which are either a single polymorph or a mixture of more than one polymorph in any ratio.

[0087] Furthermore, the present invention also includes prodrugs of compounds according to the invention. The term "prodrug" herein refers to a compound that may be biologically active or inactive on its own, but is converted (e.g., by metabolism or hydrolysis) into a compound according to the invention during its residence time in the body.

[0088] According to a second embodiment of the first aspect, the present invention covers compounds of the above general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: A is A1 or A2. o can be 0, 1, 2, 3, or 4; R is selected from: hydrogen, halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl, -S(O)-C1-C4 haloalkyl and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; X and Y are independently selected from: CR 7 R 8 O, S and NR 9 Where at least one of X and Y is CR 7 R 8 ,or X and Y together form a ring member selected from the following: -C(O)-O-, -C(O)-NR 9 -、-S(O)-NR 9 -、-SO2-NR 9 -and-SO2-O-; T is selected from T as defined above. 1 T 2 T 3 T 4 T 5 T 6 T 7 T 8a T 8b and T 9 ; R 1Selected from: hydrogen, cyano, -CHO, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C3-C6 cycloalkyl, C3-C6 halocycloalkyl having 1 to 5 halogen atoms, C3-C4 alkenyl, C3-C4 alkoxy-C1-C4 alkyl, C3-C6 cycloalkyl-C1-C3 alkyl, cyano-C1-C4 alkyl, -NH-C1-C4 alkyl, -N(C1-C (4 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 haloalkyl-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 haloalkyl having 1 to 5 halogen atoms; A phenyl-C1-C4 alkyl group, optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the following: halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; a heterocyclic-C1-C4 alkyl group, wherein the heterocyclic-C1-C4 alkyl group is a alkyl group with ... The cyclosubstituents are selected from 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl groups, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms. R 2 Selected from: 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 -SO2 R 15 ; C1-C6 alkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, C3-C6 cycloalkenyl, C2-C4 alkynyl, or phenyl-C1-C4 alkyl, each optionally substituted by 1, 2, 3, 4, or 5 independently selected from the following substituents: 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 groups, C1-C4 haloalkyl groups having 1 to 5 halogen atoms, C1-C4 alkoxy groups, -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 haloalkyl groups having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl groups having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl groups having 1 to 5 halogen atoms; Heterocyclic -C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl and 6-membered heteroaryl, each optionally substituted by 1, 2 or 3 independently selected from the following substituents: halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; A phenyl group, optionally substituted with one, two, or three substituents independently selected from the following: halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five 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 haloalkyl having one to five halogen atoms, -S(O)-C1-C4 haloalkyl having one to five halogen atoms, and -SO2-C1-C4 haloalkyl having one to five halogen atoms; and Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, heterospirocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, 3, or 4 independently selected substituents from: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 alkyl-C(O)-, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C 1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl-, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and 4 to 10-membered heterocyclic alkyl; R 3 Selected from: hydrogen, halogens, or C1-C4 alkyl groups; R 4 Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 5 Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; R 6Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 7 Selected from: hydrogen, -OH, halogen, C1-C4 alkyl and C1-C4 alkoxy; R 8 Selected from: hydrogen, -OH, halogen, C1-C4 alkyl and C1-C4 alkoxy; R 9 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy groups having 1 to 5 halogen atoms; R 10 Selected from: hydrogen, -OH, C1-C4 alkyl and C1-C4 alkoxy; R 11 Selected from: hydrogen, C1-C4 alkyl, and C1-C4 alkoxy; R 12 and R 13 Selected independently from: 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 optionally substituted with one, two or three independent substituents selected from the following: 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 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms, and (C1-C4 alkoxy)2P(=O)-; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C 4. Alkoxy, hydroxy-C1-C4 alkyl, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, benzo-C5-C6 cycloalkyl, each optionally substituted with one, two or three independent substituents selected from the following: halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five 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 haloalkyl having one to five halogen atoms, -S(O)-C1-C4 haloalkyl having one to five halogen atoms and -SO2-C1-C4 haloalkyl having one to five halogen atoms; Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms. R 14 Selected from: -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2; C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each optionally substituted with one, two or three independent substituents selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, having 1 to 5 halogen atoms C1-C4 halogenated alkoxy groups with 5 halogen atoms, C3-C6 cycloalkyl groups, -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 halogenated alkyl groups with 1 to 5 halogen atoms, -S(O)-C1-C4 halogenated alkyl groups with 1 to 5 halogen atoms, and -SO2-C1-C4 halogenated alkyl groups with 1 to 5 halogen atoms; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C 4. Alkoxy, hydroxy-C1-C4 alkyl, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; A phenyl group, optionally substituted with one, two, or three substituents independently selected from the following: halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five 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 haloalkyl having one to five halogen atoms, -S(O)-C1-C4 haloalkyl having one to five halogen atoms, and -SO2-C1-C4 haloalkyl having one to five halogen atoms; and Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms. R 15 Selected from: C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each optionally substituted with one, two or three independent substituents selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, having 1 to 5 halogen atoms C1-C4 halogenated alkoxy groups with 5 halogen atoms, C3-C6 cycloalkyl groups, -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 halogenated alkyl groups with 1 to 5 halogen atoms, -S(O)-C1-C4 halogenated alkyl groups with 1 to 5 halogen atoms, and -SO2-C1-C4 halogenated alkyl groups with 1 to 5 halogen atoms; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C 4. Alkoxy, hydroxy-C1-C4 alkyl, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; A phenyl group, optionally substituted with one, two, or three substituents independently selected from the following: halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five 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 haloalkyl having one to five halogen atoms, -S(O)-C1-C4 haloalkyl having one to five halogen atoms, and -SO2-C1-C4 haloalkyl having one to five halogen atoms; and Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 independently selected from the following substituents: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms. R 16 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy groups having 1 to 5 halogen atoms; R 17 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy groups having 1 to 5 halogen atoms; Q is selected from: 6-membered aryl and 5 to 6-membered heteroaryl, each optionally substituted by 1, 2, 3, 4 or 5 substituents selected from the following: halogen; SF5; cyano; -CHO; nitro; oxo; C1-C4 alkyl; C1-C4 hydroxyalkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; -OH; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 haloalkoxy 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 heterocyclic groups optionally substituted with one or two substituents selected from fluorine, chlorine, bromine, methyl, and cyano; -CH2-O-(C1-C4 alkyl), -CH2-NH(C1-C4 alkyl), -CH2- N(C1-C4 alkyl)2; a methyl group substituted with a 4- to 6-membered heterocyclic group, wherein the 4- to 6-membered heterocyclic group itself is optionally substituted with one or two substituents selected from 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); having 1 to 5 -S- (C1-C4 haloalkyl) with 1 to 5 halogen atoms; -S(O)- (C1-C4 haloalkyl) with 1 to 5 halogen atoms; -SO2- (C1-C4 haloalkyl) with 1 to 5 halogen atoms; -CONH (C1-C4 alkyl); -CONH (C3-C6 cycloalkyl); -NHCO (C1-C4 alkyl); -NHCO (C3-C6 cycloalkyl); -NHCO (C1-C4 haloalkyl) with 1 to 5 halogen atoms; Where Y is O, S or NR 9 At that time, R 7 R 8 R 10 and R 11 None of them are -OH, and when X is O, S or NR 9 At that time, R 7 and R 8 None of them are -OH.

[0089] According to a third embodiment of the first aspect, the present invention covers compounds of the above general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: A is either A1 or A2. o can be 0, 1, or 2; R is selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; X and Y are independently selected from: CR 7 R 8 O, S and NR 9 Where at least one of X and Y is CR 7 R 8 ; T is selected from T as defined above. 1 T 2 T 3 T 4 T 5 T 6 T 7 T 8a T 8b and T 9 ; R 1 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; R 2 Selected from: 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 -SO2 R 15 ; C1-C6 alkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, C3-C6 cycloalkenyl, C2-C4 alkynyl, or phenyl-C1-C4 alkyl, each optionally substituted by 1, 2, 3, 4, or 5 independently selected from the following substituents: 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 groups, C1-C4 haloalkyl groups having 1 to 5 halogen atoms, C1-C4 alkoxy groups, -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 haloalkyl groups having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl groups having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl groups having 1 to 5 halogen atoms; Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, heterospirocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, 3, or 4 independently selected substituents from: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 alkyl-C(O)-, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C 1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl-, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and 4 to 10-membered heterocyclic alkyl; R 3 Selected from: hydrogen, halogens, or C1-C4 alkyl groups; R 4 Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 5Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; R 6 Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 7 Selected from: hydrogen, halogens, C1-C4 alkyl groups; R 8 Selected from: hydrogen, halogens, C1-C4 alkyl groups; R 9 Selected from: hydrogen, C1-C4 alkyl; R 10 Selected from: hydrogen, -OH, C1-C4 alkyl and C1-C4 alkoxy; R 11 Selected from: hydrogen; R 12 and R 13 Selected independently from: hydrogen; C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each optionally substituted with one, two or three independent substituents selected from the following: 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 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy with 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 haloalkyl with 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl with 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl with 1 to 5 halogen atoms, and (C1-C4 alkoxy)2P(=O)-; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 independently selected from the following substituents: halogen, cyano, -OH, oxo, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; Phenyl, benzo-C5-C6 cycloalkyl, each optionally substituted by one, two or three substituents independently selected from the following: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five halogen atoms; Selected from the following monocyclic or bicyclic heterocycles: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each optionally substituted by 1, 2, or 3 substituents independently selected from the following: halogen, cyano, -OH, oxo, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C1-C4 alkyl, and C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 14 Selected from: C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each optionally substituted by one, two or three substituents independently selected from the following: halogen, -OH, cyano, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five halogen atoms, C3-C6 cycloalkyl; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 independently selected from the following substituents: halogen, cyano, -OH, oxo, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 15 Selected from: C1-C4 alkyl, phenyl-C1-C4 alkyl, each optionally substituted by one, two or three substituents independently selected from the following: halogen, -OH, cyano, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five halogen atoms; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 independently selected from the following substituents: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 16 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy groups having 1 to 5 halogen atoms; R 17 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy groups having 1 to 5 halogen atoms; Q is selected from: 6-membered aryl and 5 to 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents selected from the following: halogen, cyano, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, -OH, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, -NH (C1-C4 alkyl), -N (C1-C4 alkyl) 2, 4 to 6-membered heterocyclic groups, which are optionally substituted by 1 or 2 substituents selected from the following: fluorine, chlorine, bromine, methyl and cyano; Where Y is O, S or NR 9 At that time, R 7 R 8 R 10 and R 11 None of them are -OH, and when X is O, S or NR 9 At that time, R 7 and R 8 None of them are -OH.

[0090] According to a fourth embodiment of the first aspect, the present invention covers compounds of the above general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: A is either A1 or A2. o is 0 or 1; R is selected from: hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; X is selected from: CR 7 R 8 O, S and NR 9 , Y is CR 7 R 8 ; T is selected from T as defined above. 1 T 2 T 3 T 4 T 5 T 6 T 7 T 8a T 8b and T 9 ; R 1 Selected from: hydrogen and C1-C4 alkyl groups; R 2 Selected from: Hydrogen, halogens; -NR 12 R 13 ; -OR 14 ; -SR 15 -S(O)R 15 -SO2 R 15 ; C1-C6 alkyl or C3-C6 cycloalkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the following: halogen, cyano, C1-C4 alkyl; Monocyclic or bicyclic heterocycles selected from: 4- to 10-membered heterocyclic alkyl, heterospirocyclic alkyl, 5-membered heteroaryl and 6-membered heteroaryl, each optionally substituted by 1, 2, 3 or 4 independently selected from the following substituents: halogen, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 3 Selected from: hydrogen, halogens, or C1-C4 alkyl groups; R 4 Selected from: hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms; R 5 Selected from: hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms; R 6 Selected from: hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms; R 7 Selected from: hydrogen, halogens, C1-C4 alkyl groups; R 8 Selected from: hydrogen, halogens, C1-C4 alkyl groups; R 9 Selected from: hydrogen, C1-C4 alkyl; R 10 Selected from: hydrogen, C1-C4 alkyl; R 11 Selected from: hydrogen; R 12 and R 13 Selected independently from: hydrogen; C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each optionally substituted by one, two or three substituents independently selected from the following: halogen, -OH, cyano, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five halogen atoms, C3-C6 cycloalkyl; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from 4 to 10-membered heterocyclic alkyl groups, which may optionally be substituted by 1, 2 or 3 substituents independently selected from the following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; Phenyl, optionally substituted by one, two or three substituents independently selected from the following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five halogen atoms; Selected from the following monocyclic or bicyclic heterocycles: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl and 6-membered heteroaryl, each optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 14 Selected from: C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each optionally substituted by one, two or three substituents independently selected from the following: halogen, -C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five halogen atoms; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl and 6-membered heteroaryl, each optionally substituted by 1, 2 or 3 independently selected from the following substituents: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 15 Selected from: C1-C4 alkyl, phenyl-C1-C4 alkyl, each optionally substituted by one, two or three substituents independently selected from the following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having one to five halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having one to five halogen atoms; Heterocyclic-C1-C4 alkyl, wherein the heterocyclic substituent is selected from: 4- to 10-membered heterocyclic alkyl, 5-membered heteroaryl and 6-membered heteroaryl, each optionally substituted by 1, 2 or 3 independently selected from the following substituents: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 16 Selected from: hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl having 1 to 5 halogen atoms; R 17 Selected from: hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl having 1 to 5 halogen atoms; Q is selected from: 6-membered aryl and 5 to 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents selected from the following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms. Where Y is O, S or NR 9 At that time, R 7 R 8 R 10 and R 11 None of them are -OH, and when X is O, S or NR 9 At that time, R 7 and R 8 None of them are -OH.

[0091] According to a fifth embodiment of the first aspect, the present invention covers compounds of general formula (I) as defined in any of the first to fourth embodiments above, and their stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts, and mixtures thereof, wherein: Q is the substituted benzene ring of formula (Q1). in: Z 1 , Z 2 , Z 3 , Z 4 and Z 5Independently selected from: hydrogen; halogen; SF5; cyano; -CHO; nitro; C1-C4 alkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; hydroxyl; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 haloalkoxy 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 heterocyclic group, optionally substituted with one or two substituents selected from fluorine, chlorine, bromine, methyl and cyano; -CH2-O-(C1-C4 alkyl); -CH2-NH(C1-C4 alkyl); -CH2-N(C1-C4 alkyl)2; methyl group substituted with 4- to 6-membered heterocyclic group The 4- to 6-membered heterocyclic basic body is optionally substituted with one or two substituents selected from 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 haloalkyl; -S(O)- (C1-C4 haloalkyl) having 1 to 5 halogen atoms; -SO2- (C1-C4 haloalkyl) 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 haloalkyl) having 1 to 5 halogen atoms, or Z 1 and Z 2 Together with the carbon atoms they are attached to, they form 5- or 6-membered saturated or partially saturated heterocycles, 5-membered heteroaryl groups, or 6-membered heteroaryl groups, each of which may optionally be substituted by one or two substituents selected from the following: methyl, fluorine, and oxo, and Z. 3 , Z 4 and Z 5Independently selected from: hydrogen; halogen; SF5; cyano; CHO; nitro; C1-C4 alkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; hydroxyl; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 alkoxy-C(O)-; C1-C4 haloalkoxy 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 heterocyclic alkyl groups optionally substituted with one or two substituents selected from fluorine, methyl, or cyano; -CH2-O-(C1-C4 alkyl); -CH2-NH(C1-C4 alkyl); -CH2-N(C1-C4 alkyl)2; 4- to 6-membered heterocyclic alkyl groups. Alkyl-substituted methyl groups, wherein the 4- to 6-membered heterocyclic alkyl group is optionally substituted by one or two substituents selected from fluorine, 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 alkyl) having 1 to 5 halogen atoms 1-C4 haloalkyl; -S(O)- (C1-C4 haloalkyl) having 1 to 5 halogen atoms; -SO2- (C1-C4 haloalkyl) 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 haloalkyl) having 1 to 5 halogen atoms, or Z 2 and Z 3 Together with the carbon atoms they are attached to, they form 5- or 6-membered saturated or partially saturated heterocycles, 5-membered heteroaryl groups, or 6-membered heteroaryl groups, each of which may optionally be substituted by one or two substituents selected from the following: methyl, fluorine, and oxo, and Z. 1 , Z 4 and Z 5Independently selected from: hydrogen; halogen; SF5; cyano; CHO; nitro; C1-C4 alkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; hydroxyl; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 haloalkoxy having 1 to 5 halogen atoms; -NH(C1-C4 alkyl); -N(C1-C4 alkyl)2; -NH-SO2-(C 1-C4 alkyl); -N(SO2-[C1-C4 alkyl])(C1-C4 alkyl); (C1-C4 alkoxyimino)-C1-C4 alkyl; 4- to 6-membered heterocyclic alkyl groups optionally substituted with one or two substituents selected from fluorine, methyl or cyano; -CH2-O-(C1-C4 alkyl); -CH2-NH(C1-C4 alkyl); -CH2-N(C1-C4 alkyl)2; methyl groups substituted with 4- to 6-membered heterocyclic alkyl groups The 4- to 6-membered heterocyclic alkyl group is optionally substituted with one or two substituents selected from fluorine, 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 alkyl) having 1 to 5 halogen atoms 4-Halogenated alkyl groups; -S(O)- (C1-C4 halogenated alkyl groups) having 1 to 5 halogen atoms; -SO2- (C1-C4 halogenated alkyl groups) having 1 to 5 halogen atoms; -CONH (C1-C4 alkyl groups); -CONH (C3-C6 cycloalkyl groups); -NHCO (C1-C4 alkyl groups); -NHCO (C3-C6 cycloalkyl groups); -NHCO (C1-C4 halogenated alkyl groups) having 1 to 5 halogen atoms, or Q is the pyridine ring of formula (Q2). in: Z 6 , Z 7 , Z 8 and Z 9The group is independently selected from: hydrogen; halogen; cyano; C1-C4 alkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; C1-C4 alkoxy; C1-C4 haloalkoxy having 1 to 5 halogen atoms; C1-C4 hydroxyalkyl; NH2; -NH(C1-C4 alkyl); -N(C1-C4 alkyl)2; -NH-CO-C1-C4 alkyl; and monocyclic heterocycles selected from: 4- to 7-membered heterocyclic alkyl or 5-membered heteroaryl having at least one nitrogen atom, the heteroaryl ring being linked to a pyridine ring via said at least one nitrogen atom, each optionally substituted by 1, 2 or 3 substituents independently selected from: halogen, cyano, nitro, -OH, oxygen. Sub-, thiocarbonyl, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4 haloalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4 haloalkyl) having 1 to 5 halogen atoms, or Q is the pyrimidine ring of formula (Q3). in: Z 10 , Z 11 and Z 12 Independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or Q is the pyridine ring of formula (Q4). in: Z 13 , Z 14 , Z 15 and Z 16 Independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or Q is the pyridine ring of formula (Q5). in: Z17 , Z 18 , Z 19 and Z 20 Independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or Q is a 5-membered aromatic heterocycle of formula (Q6). in: G 1 -G 4 Independently selected from: N, O, S, CZ 21 and NZ 22 G 1 -G 4 No more than one of them is O, G 1 -G 4 No more than one of them is S, G 1 -G 4 No more than one of them is NZ 22 And among them Each Z 21 Independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, and each Z 22 Independently selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkyl-C3-C6 cycloalkyl, C1-C4 alkoxy-C1-C4 alkyl, or Q is a 5-membered aromatic heterocycle of formula (Q7). in: U 1 -U 4 Selected independently from: N and CZ 23 U 1 -U 4 There are no more than three N's, and each of them is Z' 23 It is independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, and C1-C4 haloalkoxy having 1 to 5 halogen atoms.

[0092] The 5-membered aromatic heterocycle in formula (Q6) can preferably be selected from: in: Each Z 21 Independently selected from: hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl, methoxy, and Z 22 It is hydrogen, methyl, or The 5-membered aromatic heterocycle of formula (Q7) can preferably be selected from: in: Each Z 23 Independently selected from: hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl, methoxy, or Q can be selected from:

[0093] According to a sixth embodiment of the first aspect, the present invention covers compounds of the above general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: A is selected from: T is selected from T as defined above. 1 T 2 T 3 T 4 T 5 T 6 T 7 T 8a T 8b and T 9 ; R 1 Selected from: hydrogen or methyl; R 2 Selected from: Hydrogen, chlorine, fluorine, bromine; -NR 12 R 13 ; -OR 14 ; Methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclohexyl, each of which may be optionally substituted by one or two independent substituents selected from the following: fluorine, chlorine, cyano, methyl, ethyl, propyl, and isopropyl; Monocyclic or bicyclic heterocycles selected from: aza-butane, pyrrolidine, pyrazolidine, imidazoline, 1,2,4-triazolidine, piperidine, piperazine, tetrahydropyridine, dihydro-2H-pyran, tetrahydropyran, 1,2-oxazolidine, 1,2-oxazine, morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indole, 1,3-dihydro-isoindole, 3,9-dioxa-7-azabicyclic [3.3.1]nonane Alkane, 6-oxa-3-azabicyclo[3.1.1]heptane, 8-oxa-3-azabicyclo[3.2.1]octane, imidazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole, 4-oxa-7-azaspiro[2.5]octane, each optionally substituted with 1, 2, 3 or 4 substituents independently selected from fluorine, chlorine, -OH, methyl, trifluoromethyl, methoxymethyl, trifluoromethoxymethyl; R 3 Selected from: hydrogen, chlorine, or methyl; R 4 Selected from: hydrogen, fluorine, chlorine, methyl, methoxy, trifluoromethyl, trifluoromethoxy; R 5 Selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl; R 6 Selected from: hydrogen, fluorine, chlorine, methyl, methoxy, trifluoromethyl, trifluoromethoxy; R 7 Selected from: hydrogen, fluorine, chlorine, methyl; R 8 Selected from: hydrogen, fluorine, chlorine, methyl; R 9 Selected from: hydrogen, methyl; R 10 Selected from: hydrogen, methyl; R 11 Selected from: hydrogen; R 12 and R 13 Selected independently from: Hydrogen and methyl; R 14 It is methyl; R 16 Selected from: hydrogen, methyl, ethyl, propyl, isopropyl, trifluoromethyl; R 17 Selected from: hydrogen, methyl, ethyl, propyl, isopropyl, trifluoromethyl; Q is the benzene ring of formula (Q1). in: Z 1 To Z 5 Independently selected from: hydrogen, fluorine, chlorine, methyl, and trifluoromethyl; or Q is the benzene ring of formula (Q2). in: Z 6 To Z 9 Independently selected from: hydrogen, fluorine, chlorine, methyl and trifluoromethyl.

[0094] According to a seventh embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to sixth embodiments above, wherein: Q is the benzene ring of formula (Q1). in: Z 1 , Z3 and Z 5 Independently selected from: hydrogen, fluorine, and chlorine; Z 2 and Z 4 Independently selected from: hydrogen, fluorine, chlorine, and trifluoromethyl; or Q is the benzene ring of formula (Q2). in: Z 6 To Z 9 Independently selected from: hydrogen, fluorine, and chlorine.

[0095] According to an eighth embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to seventh embodiments above, wherein: A is selected from:

[0096] According to a ninth embodiment of the first aspect, the present invention covers compounds of the above general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: A is selected from: T is selected from T as defined above. 1 T 2 T 3 T 4 T 5 T 6 T 7 T 8a T8b and T 9 ; R 1 It is hydrogen; R 2 Selected from Hydrogen, chlorine; -NR 12 R 13 ; -OR 14 ; Methyl, isopropyl; Morpholine; R 3 It can be hydrogen or methyl; R 4 It is hydrogen or fluorine; R 5 It can be hydrogen or methyl; R 6 It is hydrogen or fluorine; R 7 It can be hydrogen or methyl; R 8 It is hydrogen; R 9 It is hydrogen; R 10 It is hydrogen; R 11 It is hydrogen; R 12 and R 13 Selected independently from: Hydrogen and methyl; R 14 It is methyl; R 16 It is methyl or isopropyl; R 17 It is methyl; Q is the benzene ring of formula (Q1). in: Z 1 , Z 3 and Z 5 Independently selected from: hydrogen, fluorine, and chlorine; Z 2 and Z 4 Independently selected from: hydrogen, fluorine, chlorine, and trifluoromethyl; or Q is the benzene ring of formula (Q2). in: Z 6 To Z 9 It is independently selected from hydrogen and chlorine.

[0097] According to a tenth embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to ninth embodiments above, wherein: A is selected from: Preferably, A is

[0098] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 1 : and A, U, Q, and R 1 To R 15 It has the meaning as defined in any implementation of the first aspect above.

[0099] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 2 : and A, U, V, Q, and R 1 To R 16 It has the meaning as defined in any implementation of the first aspect above.

[0100] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 3 : and A, Q, and R 1 To R 15 It has the meaning as defined in any implementation of the first aspect above.

[0101] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 4 : and A, U, V, Q, and R 1 To R 15 It has the meaning as defined in any implementation of the first aspect above.

[0102] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 5 : and A, Q, and R 1 To R 17 It has the meaning as defined in any implementation of the first aspect above.

[0103] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 6 : and A, U, Q, and R 1 To R 15 It has the meaning as defined in any implementation of the first aspect above.

[0104] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 7 : and A, U, V, Q, and R 1 To R 15It has the meaning as defined in any implementation of the first aspect above.

[0105] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 8a : and A, L, M, Q, and R 1 To R 15 It has the meaning as defined in any implementation of the first aspect above.

[0106] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 8b : and A, Q, and R 1 To R 15 It has the meaning as defined in any implementation of the first aspect above.

[0107] According to another particular embodiment of the first aspect, the present invention covers compounds of general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, as defined in any of the first to tenth embodiments above, wherein: T is T as defined above. 9 : and A, Q, and R 1 To R 15 It has the meaning as defined in any implementation of the first aspect above.

[0108] In a particularly further embodiment of the first aspect, the invention covers a combination of two or more of the above embodiments under the title “Another Embodiment of the First Aspect of the Invention”.

[0109] This invention covers any sub-combination of any embodiment or aspect of the invention of compounds of general formula (I) above.

[0110] This invention covers compounds of general formula (I) disclosed in the Examples section below. Examples include, in particular, the compound S1-1, S1-2, S1-3, S1-4, S1-5, S1-6, S1-7, S1-8, S1-9, S1-10, S1-11, S1-12, S1-13, S1-14, S1-15, S1-16, S1-17, S1-18, S2-1, S2-2, S2-3, S2-4, S2-5, S2-6, S2-7, S3-1, and S4-1. S4-2, S4-3, S4-4, S4-5, S4-6, S4-7, S4-8, S4-9, S4-10, S5-1, S6-1, S6-2, S7-1, S7-2, S8a-1, S8a-2, S8a-3, S8a-4, S8a-5, S8a-6, S8b-1, S8b-2, S8b-3, S9-1, S9-2, S9-3, S9-4, S9-5, S9-6.

[0111] Compounds of general formula (I) according to the invention can be prepared according to schemes 1 to 10 (general synthetic schemes) as shown in the experimental section of the invention. The described schemes and procedures illustrate synthetic routes for compounds of general formula (I) of the invention and are not intended to be limiting. It will be apparent to those skilled in the art that the sequence of transformations illustrated in schemes 1 to 10 can be modified in various ways. Therefore, the sequence of transformations illustrated in these schemes is not intended to be limiting. In addition, substituents T, Q, A, R can be implemented before and / or after the illustrated transformations. 1 R 2 R 3 R 4 R 5 Or R 6 The interconversion of any of the substituents. These modifications can be, for example, the introduction of a protecting group, the cleavage of a protecting group, the reduction or oxidation of a functional group, halogenation, metallization, substitution, or other reactions known to those skilled in the art. These conversions include those that introduce functional groups that allow for further interconversion of the substituents. Suitable protecting groups and their introduction and cleavage are well known to those skilled in the art (see, for example, TW Greene and PGM Uts, Protective Groups in Organic Synthesis, 3rd Edition, Wiley 1999). Specific examples are described in the following paragraphs.

[0112] In the following text, several routes for preparing compounds of general formula (I) are described in schemes 1 to 10.

[0113] According to a second aspect, the present invention covers a method for preparing compounds of general formula (I) as defined above, said method comprising the steps of: reacting intermediate compounds of general formulas Int-I-T1, Int-I-T2, Int-I-T3, Int-I-T4, Int-I-T5, Int-I-T6, Int-I-T7, Int-I-T8a, Int-I-T8b or Int-I-T9: Among them L, M, U, V, A, R 1 R 2 R 3 R 4 R 5 and R 6 As defined for compounds of general formula (I) as defined above, where Hal is a halogen, particularly chlorine, bromine, or iodine, Reaction with compounds of general formula 1H: QB(OR)2 1H, Where Q is defined for compounds of general formula (I) as defined above, and each R may be H or Me individually, or both R may be pinacol esters. Thus, compounds of general formula (I) are obtained: Among them T, L, M, U, A, R 1 R 2 R 3 R 4 R 5 R 6 Q is as defined above.

[0114] According to an alternative embodiment of the second aspect, the present invention covers a method for preparing compounds of general formula (I) as defined above, said method comprising the steps of: reacting intermediate compounds of general formulas Int-II-T1, Int-II-T2, Int-II-T3, Int-II-T4, Int-II-T5, Int-II-T6, Int-II-T7, Int-II-T8a, Int-II-T8b or Int-II-T9: Among them, L, M, U, V, Q, R 2 R 3 R 4 R 5 and R 6 As defined for compounds of general formula (I) as defined above, Reaction with compounds of general formula 1V: Where R 1 And A is defined for compounds of general formula (I) as defined above. Thus, compounds of general formula (I) are obtained: Among them, T, A and R 1 As defined above.

[0115] According to a third aspect, the present invention covers a method for preparing a compound of general formula (I) as defined above, the method comprising the steps of preparing an intermediate compound as described above, and then converting the resulting compound into its solvate, salt and / or solvate using a suitable (i) solvent and / or (ii) base or acid.

[0116] This invention covers a method for preparing compounds of general formula (I), the method comprising the steps described in the experimental section below.

[0117] According to the fourth aspect, the present invention covers intermediate compounds for preparing compounds of the above general formula (I).

[0118] In particular, the present invention covers intermediate compounds having the following general formula and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof: Among them L, M, U, V, A, R 1 R 2 R 3 R 4 R 5 and R 6 As defined for compounds of general formula (I) above, and Hal is a halogen.

[0119] Furthermore, this invention covers intermediate compounds having the following general formula and their stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts, and mixtures thereof: Among them, L, M, U, V, Q, R 2 R 3 R 4 R 5 and R 6 As defined for compounds of general formula (I) as defined above.

[0120] This invention particularly covers the intermediate compounds disclosed in the Examples section below.

[0121] Compounds of general formula (I) of the present invention 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 compounds of general formula (I) of the present invention can be converted into the free compound by any method known to those skilled in the art.

[0122] The compounds of general formula (I) of the present invention exhibit an unexpectedly valuable pharmacological spectrum. It has been surprisingly found that the compounds of the present invention interact effectively with Slo-1, and therefore, the compounds can be used to treat or prevent diseases, preferably worm infections in humans and animals, especially gastrointestinal and extraintestinal worm infections, and even more particularly gastrointestinal and extraintestinal nematode infections.

[0123] The compounds of this invention can be used to control, treat, and / or prevent worm infections, particularly gastrointestinal and extraintestinal worm infections. The method involves administering a measured amount of the compound of this invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate, or ester thereof, to a mammal in need; which is effective in treating the aforementioned conditions.

[0124] In an alternative approach, the method comprises administering to a bird in need, i.e., a caged bird, or especially a poultry, a certain amount of the compound of the invention or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate, or ester thereof, which is effective in treating the condition.

[0125] Specifically, in the field of veterinary medicine, the compounds of this invention are suitable for the control of parasites, especially worms, occurring in animal reproduction and livestock in warm-blooded animals with favorable toxicity. They are active against all or specific developmental stages of parasites, especially worms.

[0126] Agricultural livestock include, for example, mammals such as sheep, goats, horses, donkeys, camels, buffalo, rabbits, reindeer, deer, and especially cattle and pigs; or poultry such as turkeys, ducks, geese, and especially chickens; or, for example, fish or crustaceans in aquaculture.

[0127] Livestock includes, for example, mammals such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets, or especially dogs and cats; caged birds; reptiles; amphibians or ornamental fish.

[0128] This invention also provides a method for treating worm infections, particularly gastrointestinal and extraintestinal worm infections, and even more particularly gastrointestinal and extraintestinal nematode infections.

[0129] These conditions have been well characterized in animals and can be treated by administering the pharmaceutical compositions of the present invention.

[0130] As used in the context of this invention, the term "treating" is used conventionally, for example, to manage or care for an object to combat, alleviate, reduce, relieve, or improve symptoms of a disease or condition (such as nematode infection). In particular, and especially in the fields of animal health or veterinary medicine, the term "treating" includes preventative, remedial, metaphylactic, or therapeutic treatment.

[0131] Pathogenic worms to humans or animals include, for example, acanthocephala, nematodes, pentastoma, and platyhelmintha (e.g., monogenea, tapeworms, and flukes).

[0132] Exemplary worms include, but are not limited to: Solitary insects: such as Dactylogyrus spp., Gyrodactylus spp., Microbothrium spp., Polystoma spp., and Troglocephalus spp.; Tapeworms: from the order of the Pseudophyllidea, such as: Bothridium spp., Diphyllobothrium spp., Diplogonoporus spp., Ichthyobothrium spp., Ligulaspp., Schistocephalus spp., and Spirometra spp.; From the order of the Cyclophyllida, such as: *Andyras* pp., *Anoplocephala* spp., *Avitellina* spp., *Bertiella* spp., *Cittotaenia* spp., *Davainea* spp., *Diorchis* spp., *Diplopylidium* spp., *Dipylidium* spp., *Echinococcus* spp., *Echinocotyle* spp., *Echinolepis* spp., and *Hydatigera*. spp.), Hymenolepis spp., Joyeuxiella spp., Mesocestoides spp., Moniezia spp., Paraanoplocephala spp., Raillietina spp., Stilesia spp., Taenia spp., Thysaniezia spp., Thysanosoma spp.; Trematodes: Derived from the class of the Digenea, such as: *Austrobilharzia* spp., *Brachylaima* spp., *Calicophorons* spp., *Catatropis* spp., *Clonorchis* spp., *Collyriclum* spp., *Cotylophoron* spp., *Cyclocoelum* spp., *Dicrocoelium* spp., *Diplostomum* spp., *Echinochasmus* spp., *Echinoparyphium* 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., Metagonimus spp., Metarchis spp., Nanophyetus spp., Notocotylus spp., Opisthorchis spp.), *Ornithobilharzias* pp., *Paragonimus* spp., *Paramphistomum* spp., *Plagiorchis* spp., *Posthodiplostomum* spp., *Prosthogonimus* spp., *Schistosoma* spp., *Trichobilharzias* spp., *Troglotrema* spp.), Typhlocoelum spp.; Nematodes: from the order of the Trichinellida, such as: *Capillaria* spp., *Eucoleus* spp., *Paracapillaria* spp., *Trichinella* spp., *Trichomosoides* spp., and *Trichuris* spp.; From the order of the Tylenchida, such as the genera *Micronemaspp.*, *Parastrongyloides* spp., and *Strongyloides* spp.; From the suborder Rhabditina, such as: *Aelurostrongylus* spp., *Amidostomum* spp., *Ancylostomas* spp., *Angiostrongylus* spp., *Bronchonema* spp., *Bunostomum* spp., *Chabertia* spp., *Cooperia* spp., *Cooperioides* spp., *Crenosoma* spp., *Cyathostomum* spp., *Cyclococercus* spp., *Cyclodontostomum* spp., and *Cylicocyclus* spp.), *Cylicostephanus* spp., *Cylindropharynx* spp., *Cystocaulus* spp., *Dictyocaulus* spp., *Elaphostrongylus* spp., *Filaroides* spp., *Globocephalus* spp., *Graphidium* spp., *Gyalocephalus* spp., *Haemonchus* spp., *Heligmosomoides* spp., *Hyostrongylus* spp., *Marshallagia* spp., *Metastrongylus* The genera *Muellerius*, *Necator*, *Nematodirus*, *Neostrongylus*, *Nippostrongylus*, *Obeliscoides*, *Oesophagodontus*, *Oesophagostomum*, *Ollulanus*, and *Ornithostrongylus* are all species of nematodes.The genera *Oslerus*, *Ostertagia*, *Paracooperia*, *Paracrenosoma*, *Parafilaroides*, *Parelaphostrongylus*, *Pneumocaulus*, *Pneumostrongylus*, *Poteriostomum*, *Protostrongylus*, *Spicocaulus*, *Stephanurus*, *Strongylus*, *Syngamus*, and *Teladorsagia* are listed. The genera *Trichonema*, *Trichostrongylus*, *Triodontophorus*, *Troglostrongylus*, and *Uncinaria* are listed in the genus *spp.*. From the order Spirurida, such as: *Acanthocheilonema* spp., *Anisakis* spp., *Ascaridias* spp.; *Ascaris* spp., *Ascarops* spp., *Aspiculuris* spp., *Baylisascaris* spp., *Brugia* spp., *Cercopithifilaria* spp., *Crassicauda* spp., *Dipetalonemas* spp., *Dirofilaria* spp., *Dracunculus* spp.; *Draschia* spp. 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., 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 of the Olicacanthorhynchida, such as the genera *Macracanthorhynchus* and *Prosthenorchis*; from the order of the Moniliformida, such as the genus *Moniliformis*. From the order of the Polymorphida, for example: *Filicollis* spp.; from the order of the Echinorhynchida, for example: *Acanthocephalus* spp., *Echinorhynchus* spp., *Leptorhynchoides* spp.; Pentastoma: from the order of the Porocephalida, for example, the genus Linguatula.

[0133] The compounds of the present invention can be used, in particular, for the treatment and prevention of worm infections, especially gastrointestinal and extraintestinal worm infections, and even more so for gastrointestinal and extraintestinal nematode infections.

[0134] By using the compounds of this invention to control animal parasites, especially worms, it is intended to reduce or prevent disease, mortality, and performance degradation (in the case of meat, milk, hair, hides, eggs, honey, etc.), thereby enabling more economical and simpler animal husbandry and achieving better animal well-being.

[0135] As used herein in the context of animal health, the term "control" means that the compounds of the present invention effectively reduce the incidence of each parasite in infected animals to a harmless level. More specifically, as used herein, "control" means that the compounds of the present invention effectively kill, inhibit, or suppress the growth or proliferation of the parasites.

[0136] According to another aspect, the present invention covers compounds of general formula (I) as described above, or stereoisomers, tautomers, N-oxides, hydrates, solvates and salts thereof, especially pharmaceutically acceptable salts thereof, or mixtures thereof, for the treatment or prevention of diseases, especially worm infections, especially gastrointestinal and extraintestinal worm infections, and even more particularly gastrointestinal and extraintestinal nematode infections.

[0137] The pharmaceutical activity of the compounds according to the present invention can be explained by their interaction with the Slo-1 ion channel.

[0138] According to another aspect, the present invention covers the use of compounds of general formula (I) as described above, or stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially pharmaceutically acceptable salts thereof), or mixtures thereof, for the treatment or prevention of diseases, especially worm infections, particularly gastrointestinal and extraintestinal worm infections, and even more particularly gastrointestinal and extraintestinal nematode infections.

[0139] According to another aspect, the present invention covers the use of compounds of general formula (I) as described above, or stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially pharmaceutically acceptable salts thereof), or mixtures thereof, in methods of treating or preventing diseases, particularly worm infections, especially gastrointestinal and extraintestinal worm infections, and even more particularly gastrointestinal and extraintestinal nematode infections.

[0140] According to another aspect, the present invention covers the use of compounds of general formula (I) as described above, or stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially pharmaceutically acceptable salts thereof), or mixtures thereof, for the preparation of pharmaceutical compositions for the treatment or prevention of diseases, preferably pharmaceuticals, said diseases being particularly worm infections, particularly gastrointestinal and extraintestinal worm infections, and even more particularly gastrointestinal and extraintestinal nematode infections.

[0141] According to another aspect, the present invention covers a method for treating or preventing diseases, particularly worm infections, especially gastrointestinal and extraintestinal worm infections, and even more particularly gastrointestinal and extraintestinal nematode infections, the method using an effective amount of a compound of general formula (I) as described above, or its stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts (especially pharmaceutically acceptable salts thereof), or mixtures thereof.

[0142] According to another aspect, the present invention covers compounds of general formula (I) as described above, or their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially pharmaceutically acceptable salts thereof), or mixtures thereof, used as antiendoparasitical agents.

[0143] According to another aspect, the present invention covers compounds of general formula (I) as described above, or their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially pharmaceutically acceptable salts thereof), or mixtures thereof, used as anthelmintics, especially as nematicides, flatworm icides, acanthocephalan icides or lingula icides.

[0144] According to another aspect, the present invention covers pharmaceutical compositions, particularly veterinary preparations, comprising a compound of general formula (I) as described above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, salt (especially a pharmaceutically acceptable salt thereof), or a mixture thereof, and one or more excipients, particularly one or more pharmaceutically acceptable excipients. Such pharmaceutical compositions can be prepared into suitable dosage forms using conventional procedures.

[0145] According to another aspect, the present invention covers a method for preparing a pharmaceutical composition, particularly a veterinary preparation, comprising the steps of mixing a compound of general formula (I) as described above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, salt (especially a pharmaceutically acceptable salt), or a mixture thereof, with one or more excipients (especially one or more pharmaceutically acceptable excipients).

[0146] According to another aspect, the present invention covers a method for treating or preventing diseases, particularly worm infections, especially gastrointestinal and extraintestinal worm infections, and even more particularly gastrointestinal and extraintestinal nematode infections, said method using a pharmaceutical composition, particularly a veterinary preparation, comprising an effective amount of a compound of general formula (I) as described above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, and salt (especially a pharmaceutically acceptable salt thereof) or a mixture thereof.

[0147] Therefore, the present invention covers a method for controlling worm infection in humans and / or animals by administering an effective amount of at least one compound of the above general formula (I) to humans or animals in need.

[0148] The present invention further covers pharmaceutical compositions, particularly veterinary preparations, comprising at least one compound according to the invention, usually together with one or more pharmaceutically suitable excipients, and their use for the purposes mentioned above.

[0149] The compounds according to the invention can have systemic and / or local activity. For this purpose, they can be administered in suitable manner, such as via, for example, oral, parenteral, pulmonary, nasal, sublingual, tongue, buccal, rectal, vaginal, skin, transdermal, conjunctival, ear routes, or as implants or scaffolds. Such administration can be preventative, remedial, preventative, or therapeutic.

[0150] Regarding these routes of application, the compounds according to the invention can be administered in suitable forms.

[0151] For oral administration, compounds according to the invention can be formulated into known dosage forms in the art for rapid and / or modified delivery of the compounds, such as, for example, tablets (uncoated or coated tablets, e.g., with delayed-dissolving or insoluble enteric or controlled-release coatings), orally disintegrating tablets, films / sheets, films / lyophylisates, capsules (e.g., hard or soft gelatin capsules), sugar-coated tablets, granules, pills, chewable tablets (e.g., soft chewable tablets), powders, emulsions, suspensions, aerosols, or solutions. Compounds according to the invention can be incorporated into said dosage forms in crystalline and / or amorphous and / or soluble forms.

[0152] Parenteral administration can avoid absorption steps (e.g., intravenous, intra-arterial, intracardiac, intraspinal, or lumbar) or include absorption (e.g., intramuscular, subcutaneous, intradermal, percutaneous, or intraperitoneal). Suitable forms of administration for parenteral administration are, in particular, preparations for injection and infusion, in the form of solutions, suspensions, emulsions, lyophilized powders, or sterile powders.

[0153] Examples of other routes of administration include pharmaceutical forms for inhalation [especially powder inhalers, nebulizers], nasal drops, nasal solutions, nasal sprays; tablets / films / capsules for tongue, sublingual or buccal administration; suppositories; eye drops, eye ointments, eye washes, eye inserts, ear drops, ear sprays, ear powders, ear rinses, ear tampons; vaginal capsules, aqueous suspensions (washes, shaken mixtures), lipophilic suspensions, emulsions, ointments, creams, transdermal therapy systems (such as, for example, patches), milk, pastes, foams, spot-ons, powders, implants or stents.

[0154] The compounds according to the invention can be incorporated into the described administration form. This can be done in a manner known per se by mixing with pharmaceutically suitable excipients. Pharmaceutically suitable excipients particularly include: • Fillers and carriers (e.g., cellulose, microcrystalline cellulose, such as...) ), lactose, mannitol, starch, calcium phosphate (such as, for example) )), • Ointment base (e.g., petrolatum, paraffin, triglycerides, wax, lanolin, lanolin alcohol, hydrophilic ointments, polyethylene glycol), • Suppository base (e.g., polyethylene glycol, cocoa butter, stearate), Solvents (e.g., water, ethanol, isopropanol, glycerol, propylene glycol, medium-chain triglyceride fatty oils, liquid polyethylene glycol, paraffin), Surfactants, emulsifiers, dispersants or wetting agents (e.g., sodium lauryl sulfate), lecithin, phospholipids, fatty alcohols (such as...) ), dehydrated sorbitol fatty acid esters (such as, for example) ), polyoxyethylene dehydrated sorbitol fatty acid esters (such as, for example) ), polyoxyethylene fatty acid glycerides (such as, for example) ), polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, glycerol fatty acid esters, poloxamers (such as, for example) ), • Buffers, acids and bases (e.g., phosphates, carbonates, citric acid, acetic acid, hydrochloric acid, sodium hydroxide solution, ammonium carbonate, tromethamine, triethanolamine), • Isotonic agents (e.g., glucose, sodium chloride), • Adsorbent (e.g., highly dispersed silica), • Tackifiers, gelling agents, thickeners and / or adhesives (e.g., polyvinylpyrrolidone, methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, starch, carbomers), polyacrylic acid (such as...) (); alginate, gelatin), • Disintegrants (e.g., modified starch, sodium carboxymethyl cellulose, sodium glycolate starch (such as...) ), cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose (such as, for example) )), • Flow regulators, lubricants, flow aids, and release agents (e.g., magnesium stearate, stearic acid, talc, highly dispersed silica (such as...) )), • Coating materials (e.g., sugar, shellac) and film-forming agents for thin or diffused films that dissolve rapidly or in a modified manner (e.g., polyvinylpyrrolidone (such as...) Polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate, cellulose acetate phthalate, polyacrylate, polymethacrylate, etc. )), • Capsule materials (e.g., gelatin, hydroxypropyl methylcellulose), • Synthetic polymers (e.g., polylactic acid, polyglycolic acid, polyacrylate, polymethacrylate (such as...) ), polyvinylpyrrolidone (such as, for example) Polyvinyl alcohol, polyvinyl acetate, polyoxyethylene, polyethylene glycol and their copolymers and block copolymers), Plasticizers (e.g., polyethylene glycol, propylene glycol, glycerin, triacetyl triacetate, triacetyl citrate, dibutyl phthalate), • Penetration enhancer • Stabilizers (e.g., antioxidants, such as ascorbic acid, ascorbyl palmitate, sodium ascorbate, butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate), • Preservatives (such as parabens, sorbic acid, thimerosal, benzalkonium chloride, chlorhexidine acetate, sodium benzoate), • Colorants (e.g., inorganic pigments, such as iron oxide, titanium dioxide), Flavoring agents, sweeteners, and flavor and / or odor masking agents.

[0155] Furthermore, the present invention relates to a pharmaceutical composition comprising at least one compound according to the invention (usually together with one or more pharmaceutically suitable excipients); and its use according to the invention.

[0156] According to another aspect, the present invention covers pharmaceutical combinations, particularly pharmaceuticals, which comprise at least one compound of general formula (I) of the present invention and at least one or more additional active ingredients, especially for the treatment and / or prevention of internal and / or external parasitic infections.

[0157] In this invention, the term "endoparasite" is used as known to those skilled in the art, and in particular refers to worms. In this invention, the term "ectoparasite" is used as known to those skilled in the art, and in particular refers to arthropods, especially insects or mites.

[0158] In particular, the present invention covers pharmaceutical combinations, especially veterinary combinations, comprising: • One or more first active ingredients, especially compounds of general formula (I) as defined above, and • One or more additional active ingredients, especially one or more endoparasitic drugs and / or ectoparasitic drugs.

[0159] In this invention, the term "combination" is used as is known to those skilled in the art, and the combination may be a fixed combination, a non-fixed combination, or a kit of parts.

[0160] In this invention, "fixed combination" is used as is known to those skilled in the art and is defined as a combination in which, for example, a first active ingredient (such as one or more compounds of general formula (I) of this invention) and another active ingredient are present together in a unit dose or a single entity. An example of a "fixed combination" is a pharmaceutical composition in which the first active ingredient and another active ingredient are present in a blend for simultaneous administration, such as in a formulation. Another example of a "fixed combination" is a pharmaceutical combination in which the first active ingredient and another active ingredient are present in a single unit, rather than in a blend.

[0161] The non-fixed combination or "kit kit" in this invention is used as is known to those skilled in the art, and is defined as a combination in which a first active ingredient and other active ingredients are present in more than one unit. An example of a non-fixed combination or kit kit is a combination in which the first active ingredient and other active ingredients are present separately. The components of a non-fixed combination or kit kit may be administered separately, sequentially, simultaneously, in parallel, or in an alternating time sequence.

[0162] The compounds of this invention can be administered as a single agent or in combination with one or more other pharmaceutically active ingredients, wherein such combination does not cause unacceptable side effects. This invention also covers such drug combinations. For example, the compounds of this invention can be combined with known ectoparasite-killing and / or endoparasite-killing agents.

[0163] Other or additional active ingredients specified herein by their common names are known and 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). The classification is based on the current IRAC Mode of Action Classification Scheme at the time of filing of this patent application.

[0164] Examples of ectoparasite-killing agents and / or endoparasite-killing agents are insecticides, acaricides, and nematicides, and particularly include: (1) Acetylcholinesterase (AChE) inhibitors, such as carbamates, including alanycarb, aldicarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, and furathiazole. ocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, XMC, and xylylcarb; or organophosphates, such as acephate, azamethiphos, ethyl glutathione ( azinphos-ethyl, azinphos-methyl, cadusafos, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorpyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos / DDVP, dicrotoph os), dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, imicyafos, isofenphos, isopropyl O-(methoxyaminothiophosphoryl)salicylic acid.O-(methoxyaminothiophosphoryl)salicylate), isoxathion, malathion, mecarbam, methamidophos, methidathion, mevinphos, monocotophos, naled, omethoate, oxydemeton-methyl, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phospha The following are listed: midon, phoxim, pirimiphos-methyl, profenofos, propetamphos, prothiofos, piraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, trichlorfon, and vamidothion.

[0165] (2) GABA-gated chloride channel blockers, such as cyclopentadiene organochlorines, such as chlordane and endosulfan, or fiproles, such as ethiprole and fipronil.

[0166] (3) Sodium channel modulators, such as pyrethroids, including acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin S-cyclopentenyl isomer, bioresmethrin, cycloprothrin, cyfluthrin, β-cyfluthrin, cyhalothrin, λ-cyfluthrin, γ-cyfluthrin, cypermethrin, α-cypermethrin, β-cypermethrin, and θ-cypermethrin. ζ-Cypermethrin, Cyphenothrin [(1R)-trans-isomer], Deltamethrin, Ementhrin [(EZ)-(1R)-isomer], Esfenvalerate, Etofenprox, Fenpropathrin, Fenvalerate, Flufenvalerate Pyrethrin, flumethrin, tau-fluvalinate, halfenprox, imiprothrin, kadethrin, momfluorothrin, permethrin, phenothrin [(1R)-trans-isomer], prallethrin, pyrethrins (pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin, tetramethrin [(1R)-isomer], tralomethrin, and transfluthrin, or DDT or methoxychlor.

[0167] (4) Competitive modulators of nicotinic acetylcholine receptors (nAChR), such as neonicotinoids, such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid and thiamethoxam, or nicotine or sulfoxaflor or flupyradifurone.

[0168] (5) Nicotinic acetylcholine receptor (nAChR) allosteric modulators, such as spinosyns, for example, spinosyns and spinosad.

[0169] (6) Glutamate-gated chloride channel (GluCl) allosteric modulators, such as avermectins / milbemycins, for example abamectin, emamectinbenzoate, lepimectin and milbemectin.

[0170] (7) Juvenile hormone mimics, such as, for example, juvenile hormone analogs, such as hydroprene, kinoprene and methoprene, or fenoxycarb or pyriproxyfen.

[0171] (9) Modulators of the string organs, such as pymetrozine or flonicamid.

[0172] (10) Mite growth inhibitors, such as clofentezine, hexythiazox, diflovidazin, or etoxazole.

[0173] (12) Inhibitors of mitochondrial ATP synthase, such as ATP interfering agents, such as diafenthiuron or organotin compounds, such as azocyclotin, cyhexatin and fenbutatin oxide, or propargite or tetradifon.

[0174] (13) via oxidative phosphorylation uncoupling agents that disrupt the proton gradient, such as chlorfenapyr, DNOC and sulfluramid.

[0175] (14) Nicotinic acetylcholine receptor channel blockers, such as bensultap, cartap hydrochloride, thiocyclam and thiosultap-sodium.

[0176] (15) Type O chitin biosynthesis inhibitors, such as bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, and triflumuron.

[0177] (16) Type I chitin biosynthesis inhibitors, such as buprofezin.

[0178] (17) Molting disruptors (especially for Diptera, i.e., Diptera), such as cyromazine.

[0179] (18) Ecdysone receptor agonists, such as chromafenozide, halofenozide, methoxyfenozide and tebufenozide.

[0180] (19) Octopus amine receptor agonists, such as, for example, amitraz.

[0181] (20) Inhibitors of electron transport in mitochondrial complex III, such as, for example, hydramethylnone, acequinocyl, or fluacrypyrim.

[0182] (21) Inhibitors of electron transport of mitochondrial complex I, such as, for example, from the METI group of acaricides, such as fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, and tolfenpyrad or rotenone (rotenone).

[0183] (22) Voltage-dependent sodium channel blockers, such as, for example, indoxacarb or metaflumizone.

[0184] (23) Inhibitors of acetyl-CoA carboxylase, such as tetronic acid and tetramic acid derivatives, such as spirodiclofen, spiromesifen and spirotetramat.

[0185] (25) Inhibitors of electron transport in mitochondrial complex II, such as, for example, β-ketonitrile derivatives, such as cyenopyrafen and cyflumetofen; and formamides, such as, for example, pyflubumide.

[0186] (28) Ryanodine receptor modulators, such as diamides, for example, chlorantraniliprole, cyantraniliprole, and flubendiamide. Other active ingredients include, for example, afidopyropen, afoxolaner, azadirachtin, benclothiaz, benzoximate, bifenazate, broflanilide, bromopropylate, chinomethionat, chlorpyrifos, cryolite, cyclaniliprole, and cyclophosphamide. Cycloxaprid, Cyhalodiamide, Dicloromezotiaz, Dicofol, epsilon-Metofluthrin, epsilon-Momfluthrin, Flometoquin, Fluazaindolizine, Fluensulfone, Flufenerim, Flufenoxystrobin, Flufiprole, Fluhexafon, Flupyridamole Fluopyram, Fluralaner, Fluxametamide, Fufenozide, Guadipyr, Heptafluthrin, Imidaclothiz, Iprodione, kappa-Bifenthrin, kappa-Tefluthrin, Lotilaner, Meperfluthrin, Paichongding, Trifluralin Pyridalyl, Pyrifluquinazon, Pyriminostrobin, Spirobudiclofen, Tetramethylfluthrin, Tetraniliprole, Tetrachlorantraniliprole, Tioxazafen, Thiofluoximate, Triflumezopyrim, and Iodomethane; based on Bacillus thuringiensis.Other formulations of firmus (I-1582, BioNeem, Votivo); and also 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 in WO2006 / 043635) (CAS 885026-50-6), {1'-[(2E)-3-(4-chlorophenyl)prop-2-en-1-yl]-5-fluorospiro[indol-3,4'-piperidin]-1(2H)-yl}(2-chloropyridin-4-yl) methyl ketone (known in 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 in 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 in WO 2010052161)(CAS1225292-17-0), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-ylethyl ester (known in EP2647626)(CAS1440516-42-6), 4-(but-2-yn-1-yloxy)-6-(3,5-dimethylpiperidin-1-yl)-5-fluoropyrimidine (known in WO2004 / 099160)(CAS 792914-58-0), PF1364 (known in JP2010 / 018586) (CAS1204776-60-2), N-[(2E)-1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (known in WO2012 / 029672) (CAS1363400-41-2), (3E)-3-[1-[(6-chloro-3-pyridinyl)methyl]-2-pyridinyl]-1,1,1-trifluoro-prop-2-one (known in WO20) 13 / 144213)(CAS1461743-15-6), N-[3-(benzylcarbamoyl)-4-chlorophenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (known in WO2010 / 051926)(CAS1226889-14-0), 5-bromo-4-chloro-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloro-2-pyridyl)pyrazole-3-carboxamide (known in CN103232431)(CAS1449220-44-3), 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxo-3-thiecyclobutyl)-benzamide, 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(trans-1-oxo-3-thiecyclobutyl)-benzamide and 4-[(5S)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxo-3-thiecyclobutyl)benzamide (known from WO 2013 / 050317A1)(CAS1332628-83-7), N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propionamide, (+)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propionamide and (-)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propionamide (known in WO 2013 / 162715 A2, WO 2013 / 162716) A2, US2014 / 0213448 A1)(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-carboxylonitrile (known in CN 101337937 A)(CAS1105672-77-2), 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)thioxomethyl]phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxamide, (thiobenzamide, known in CN 103109816) A)(CAS1232543-85-9); N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methylphenyl]-1-(3-chloro-2-pyridyl)-3-(fluoromethoxy)-1H-pyrazole-5-carboxamide (ascertained in WO2012 / 034403A1)(CAS1268277-22-0), N-[2-(5-amino-1,3,4-thiadiazol-2-yl)-4-chloro-6-methylphenyl]-3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxamide (ascertained in WO 2011 / 085575)A1)(CAS1233882-22-8), 4-[3-[2,6-dichloro-4-[(3,3-dichloro-2-propen-1-yl)oxy]phenoxy]propoxy]-2-methoxy-6-(trifluoromethyl)-pyrimidine (known in CN 101337940 A)(CAS1108184-52-6); (2E)- and 2(Z)-2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]-hydrazine carbamate (known in CN 101715774 A)(CAS1232543-85-9); 3-(2,2-dichlorovinyl)-2,2-dimethyl-4-(1H-benzimidazol-2-yl)phenyl-cyclopropane carbamate (known in CN) 103524422A)(CAS1542271-46-4); (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-[(trifluoromethyl)thio]phenyl]amino]carbonyl]-indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-methyl carbamate (known in CN 102391261 A)(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 in US2014 / 0275503) A1)(CAS1181213-14-8); 8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (CAS1253850-56-4), (8-trans)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (CAS 933798-27-7), (8-cis)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (known from WO 2007040280A1, WO 2007040282 A1)(CAS 934001-66-8) and N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)thio]-propionamide (known in WO 2015 / 058021 A1, WO2015 / 058028A1)(CAS1477919-27-9) and N-[4-(aminothiocarbonyl)-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxamide (known in CN 103265527 A)(CAS1452877-50-7), 5-(1,3-dioxane-2-yl)-4-[[4-(trifluoromethyl)phenyl]methoxy]pyrimidine (known in WO 2013 / 115391 A1)(CAS1449021-97-9), 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-methoxy-1-methyl-1,8-diazaspiro[4,5]dec-3-en-2-one (known in WO 2010 / 066780A1, WO 2011 / 151146 A1)(CAS1229023-34-0), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-1,8-diazaspiro[4.5]decane-2,4-dione (known in WO 2014 / 187846 A1)(CAS1638765-58-8), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-yl-ethyl carbonate (known in WO 2010 / 066780 A1, WO 2011151146) A1)(CAS1229023-00-0), N-[1-[(6-chloro-3-pyridyl)methyl]-2(1H)-pyridylyl]-2,2,2-trifluoroacetamide (known in DE 3639877A1, WO 2012029672 A1)(CAS1363400-41-2), [N(E)]-N-[1-[(6-chloro-3-pyridyl)methyl]-2(1H)-pyridylyl]-2,2,2-trifluoroacetamide (known in WO 2016005276) A1)(CAS1689566-03-7), [N(Z)]-N-[1-[(6-chloro-3-pyridyl)methyl]-2(1H)-pyridylene]-2,2,2-trifluoroacetamide, (CAS1702305-40-5), 3-endo-3-[2-propoxy-4-(trifluoromethyl)phenoxy]-9-[[5-(trifluoromethyl)-2-pyridyl]oxy]-9-azabicyclo[3.3.1]nonane (known in WO 2011 / 105506 A1, WO 2016 / 133011A1)(CAS1332838-17-1).

[0187] Active ingredients with unknown or non-specific modes of action, such as fentrifanil, fenoxacrim, cycloprene, chlorobenzilate, chlordimeform, flubenzimine, dicyclanil, amidoflumet, quinomethionate, triarathene, clothiazoben, tetrasul, potassium oleate, petroleum, metoxadiazone, gossyplure, flutenzin, bromopropylate, and cryolite; Active ingredients from other categories, such as butacarb, dimetilan, cloethocarb, phosphocarb, pirimiphos (-ethyl), parathion (-ethyl), methacrifos, isopropyl o-salicylate, trichlorfon, sulprofos, propaphos, sebufos, pyridathion, prothoate, dichlofenthion, demeton-S-methylsulfone, isazofofos, cyanofenphos, dialifos, carbophenothion, and pyrimimethoxam. autathiofos), aromfenvinfos(-methyl), azinphos(-ethyl)), chlorpyrifos(-ethyl)), fosmethilan, iodofenphos, dioxabenzofos, formothion, fonofos, flupyrazofos, fensulfothion, etrimfos; Organochlorine compounds, such as camphechlor, lindane, and heptachlor; or phenylpyrazole compounds, such as acetoprole, pyrafluprole, pyriprole, vaniliprole, and sisapronil; or isoxazoline compounds, such as sarolaner, afoxolaner, lotilana, and fluralaner; Pyrethroids, such as (cis- and trans-), include metofluthrin, profluthrin, flufenprox, flubrocythrinate, fuffenprox, fenfluthrin, protrifenbute, pyresmethrin, RU15525, terallethrin, and cis-resmethrin. Heptafluthrin, bioethanomethrin, bioopermethrin, fenpyrithrin, cis-cypermethrin, cis-permethrin, clocythrin, (λ-)cyhalothrin (lambda-), chlovaporthrin, or halogenated hydrocarbons (HCHs); Neonicotinoids, such as nithiazine; dicloromezotiaz, triflumezopyrim; Macrocyclic lactones, such as nemadectin, ivermectin, latidectin, moxidectin, selamectin, eprinomectin, doramectin, emamectin benzoate; milbemycin oxime; Triperene, epofenonane, and diofenolan; Biological agents, hormones, or pheromones, such as natural products like thuringiensin, codlemone, or neem components; Dinitrophenols, such as dinocap, dinobuton, and binapacryl; Benzoylurea derivatives, such as fluazuron and penfluron; Amidone derivatives, such as chlormebuform, cymiazole, and demiditraz; Beehive varroa acaricides, such as organic acids like formic acid and oxalic acid.

[0188] Non-limiting examples of insecticides and acaricides of particular interest for animal health are, and particularly include, [i.e., Mehlhorn et al., Encyclpaedic Reference of Parasitology, 4th Edition (ISBN)]. [978-3-662-43978-4]: Effectors of arthropod ligand-gated chloride channels: chlordane, heptachlor, endoculfan, Dieldrin, bromocyclen, toxaphene, lindane, fipronil, pyriprole, sisapronil, afoxolaner, fluralaner, sarolaner, lotilaner, fluxametamide, broflanilide, avermectin, doramectin, eprinomectin, ivermectin, milbemycin, moxidectin, selamectin; Arthropod octopus amino receptor modulators: amitraz, BTS27271, cymiazole, and demiditraz; Effectors of voltage-gated sodium channels in arthropods: DDT, methoxychlor, metaflumizone, indoxacarb, cinerin I, cinerin II, jasmolin I, jasmolin II, pyrethrin I, pyrethrin II II), allethrin, alpha-cypermethrin, bioallethrin, beta-cypermethrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, etofenprox, fenvalerate, flucythrinate, flumethrin, halfenprox, permethrin, phenothrin, resmethrin, tau-fluvalinate, tetramethrin; Effectors of arthropod nicotinic cholinergic synapses (acetylcholinesterase, acetylcholine receptors): bromoprypylate, bendiocarb, carbaryl, methomyl, promacyl, propoxur, azamethiphos, chlorfenvinphos, chlorpyrifos, coumaphos, cythioate, diazinon, dichlorvos, dirotophos, dimethoate, ethion, and chlorpyrifos. Phosphorus, fenitrothion, fenthion, heptenophos, malathion, naled, phosmet, phoxim, phtalofos, propetamphos, temephos, tetrachlorvinphos, trichlorfon, imidacloprid, nitenpyram, dinotefuran, spinosad, spintoram; Effectors in arthropod development: cyromazine, dicyclanil, diflubenzuron, fluazuron, lufenuron, triflumuron, fenoxycarb, hydroprene, methoprene, pyriproxyfen, fenoxycarb, hydroprene, S-methoprene, and pyriproxyfen.

[0189] Exemplary active ingredients from the group of endoparasitic agents that are other or other active ingredients in this invention include, but are not limited to, anti-worm active compounds and anti-protozoan active compounds.

[0190] Anti-worm active compounds include, but are not limited to, the following nematode-killing, fluke-killing, and / or tapeworm-killing active compounds: Derived from macrolides, such as: eprinomectin, abamectin, nemadectin, moxidectin, doramectin, selamectin, lepimectin, latidectin, milbemectin, ivermectin, emamectin, and milbemycin; Derived from benzimidazoles and benzimidazole precursors, such as: oxibendazole, mebendazole, trichlorobenzyl ... Derived from peptides, preferably cyclic peptides, especially 24-membered cyclic peptides, such as emodepside and PF1022A; Derived from tetrahydropyrimidines, such as: morantel, pyrantel, oxantel; Derived from imidazothiazides, such as: butamisole, levamisole, tetramisole; Derived from aminophenylamidines, such as: amidantel, deacylated amidantel (dAMD), tribendimidine; Derived from aminoacetonitrs, such as monepantel; Derived from paraherquamides, such as paraherquamide and derquantel; Derived from salicylanilides, such as: tribromsalan, bromoxanide, brotianide, clioxanide, closantel, niclosamide, oxyclozanide, and rafoxanide; Derived from substituted phenols, such as: nitroxynil, bithionol, disophenol, hexachlorophene, niclofolan, and meniclopholan; Derived from organophosphates, such as trichlorfon, naphthalofos, dichlorvos / DDVP, crufomate, coumaphos, and haloxon; derived from piperazine / quinoline derivatives, such as praziquantel and epsiprantel; Derived from piperazines, such as piperazine and hydroxyzine; Derived from tetracyclines, such as tetracycline, chlorotetracycline, doxycycline, oxytetracycline, and rolitetracycline; From different other categories, such as bunamidine, niridazole, resorantel, omphalotin, oltipraz, nitroscanate, nitroxynile, oxamniquine, mirasan, miracil, lucanhon, hycanthone, hetolin, emetine, diethylcarbamazine, dichlorophen, diamfenetide, clonazepam, bephenium, amoscanate, and clorsulon.

[0191] The antigenic animal active ingredients of the present invention include, but are not limited to, the following active ingredients: Derived from triazines, such as: diclazuril, ponazuril, letrazuril, toltrazuril; Derived from polyether ion carriers, such as: monensin, salinomycin, maduramicin, and narasin; Derived from macrolides, such as milbemycin and erythromycin; Derived from quinolones, such as enrofloxacin and pradofloxacin; Derived from quinine derivatives, such as chloroquine; Derived from pyrimidines, such as pyrimethamine; Derived from sulfonamides, such as sulfaquinoxaline, trimethoprim, and sulfaclozin; Derived from thiamines, such as amprolium; Derived from lincosamides, such as clindamycin; Derived from diphenylurea, such as imidocarb; Derived from nifurtimox; Derived from quinazolinone alkaloids, such as halofuginon; From different other categories, such as oxamniquin and paromomycin; Vaccines or antigens derived from microorganisms, such as: 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, and Dictyocaulus viviparus.

[0192] All other named active ingredients in this invention may optionally form salts with a suitable base or acid, provided that their functional groups permit.

[0193] Based on standard laboratory techniques known for evaluating compounds that can be used to treat worm infections, the effective dose of the compounds of the present invention for treating each desired indication can be readily determined by standard toxicity tests and standard pharmacological assays for determining treatment of the specified conditions in animals, and by comparing these results with those of known active ingredients or drugs for treating these conditions. The amount of active ingredient to be administered in treating one of these conditions can be varied widely depending on considerations such as the specific compound and dosage unit used, the administration method, the duration of treatment, the age and sex of the treated subject, and the nature and severity of the treated condition.

[0194] The total amount of active ingredient to be administered is typically from about 0.001 mg / kg to about 200 mg / kg body weight daily, and preferably from about 0.01 mg / kg to about 20 mg / kg body weight daily. Clinically useful dosing schedules range from once to three times daily to once every four weeks. Furthermore, a "withdrawal period" is possible, in which the drug is not administered to the subject for a specific period of time, thereby benefiting the overall balance between pharmacological effects and tolerability. Additionally, long-acting treatment is possible, in which the subject is treated once every four weeks or more. Unit doses may contain from about 0.5 mg to about 1500 mg of active ingredient and may be administered once or more daily or less than once daily. The average daily dose administered by injection (including intravenous, intramuscular, subcutaneous, and parenteral injection) and using infusion techniques is preferably from 0.01 to 200 mg / kg body weight. The average daily rectal administration regimen is preferably from 0.01 to 200 mg / kg body weight. The average daily vaginal administration regimen is preferably from 0.01 to 200 mg / kg body weight. The preferred average daily topical administration regimen is 0.1 to 200 mg administered once to four times daily. The preferred transdermal concentration is the concentration required to maintain a daily dose of 0.01 to 200 mg / kg. The preferred average daily inhalation administration regimen is 0.01 to 100 mg / kg of total body weight.

[0195] Of course, for each individual, the specific initial and continuous dosing regimen will vary depending on the nature and severity of the condition as determined by the attending physician, the activity of the specific compound used, the age and general condition of the individual, the timing of administration, the route of administration, the drug excretion rate, the drug combination, etc. The desired therapeutic modality and dosage of the compounds of the present invention, or their pharmaceutically acceptable salts or esters or compositions, can be determined by those skilled in the art using conventional therapeutic testing.

[0196] Experimental Section The various aspects of the invention described in this application are illustrated by the following embodiments, which are not intended to limit the invention in any way.

[0197] The embodiments and test experiments described herein are for illustrative purposes only, and the invention is not limited to the given embodiments.

[0198] Abbreviations and Acronyms abbreviation: atm (standard atmosphere) DAD Diode Array Detector DMSO (dimethyl sulfoxide) DME 1,2-dimethoxyethane ELSD Evaporative Light Scattering Detector ESI Electrospray Ionization h hours LC-MS (Liquid Chromatography-Coupled Mass Spectrometry) min minutes NMR (Nuclear Magnetic Resonance) spectroscopy R t Retention time TLC (Thin Layer Chromatography)

[0199] Experimental Section - Overview All reagents not described in the experimental section are either commercially available, or are known compounds, or can be formed by those skilled in the art from known compounds by known methods.

[0200] The compounds and intermediates produced by the method according to the invention may require purification. Purification of organic compounds is well known to those skilled in the art, and various methods for purifying the same compound may exist. In some cases, purification may not be necessary. In some cases, the compound may be purified by crystallization. In some cases, impurities may be stirred out using a suitable solvent. In some cases, the compound may be purified by chromatography, particularly rapid column chromatography, using, for example, pre-packed silica gel columns (e.g., Biotage SNAP columns). or Combined with the Biotage automated purification system ( or Isolera Purification can be achieved using eluents (such as a gradient of hexane / ethyl acetate or dichloromethane / 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, combined with a suitable pre-packed reversed-phase column and eluents (such as a gradient of water and acetonitrile, which may contain additives such as trifluoroacetic acid, formic acid, or ammonia).

[0201] In some cases, the purification methods described above can provide those compounds of the present invention having sufficiently basic or acidic functionality in the form of salts, such as trifluoroacetate or formate salts in the case of sufficiently basic compounds of the present invention, or ammonium salts in the case of sufficiently acidic compounds of the present invention. Salts of this type can be converted to their free base or free acid forms respectively by various methods known to those skilled in the art, or used in salt form in subsequent bioassays. It is to be understood that the specific form (e.g., salt, free base, etc.) of the compounds of the present invention isolated and described herein is not necessarily the only form in which said compounds can be used in bioassays to quantify specific biological activities.

[0202] Analytical methods Analytical liquid chromatography Analytical (UP) LC-MS is performed using the different equipment described below. Unless a negative mode (ESI-) is specified, the mass (m / z) is reported by positive mode electrospray ionization.

[0203] LC-MS method Method 1: MS instrument type: Agilent Technologies 6130 Quadrupole LC-MS; HPLC instrument type: Agilent Technologies 1260 Infinity; Column: Waters XSelect (C18, 30×2.1mm, 3.5μ); Flow rate: 1mL / min; Column temperature: 35℃; Eluent A: 0.1% formic acid in acetonitrile; Eluent B: 0.1% formic acid in water; Linear gradient: t=0min 5% A, t=1.6min 98% A, t=3min 98% A; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative (ESIpos / neg)), mass range: 100-800; Detection: ELSD (PL-ELS2100): gas flow rate 1.2mL / min, gas temperature: 70℃, neb: 50℃.

[0204] Method 2: MS instrument type: Agilent Technologies 6130 Quadrupole LC-MS; HPLC instrument type: Agilent Technologies 1260 Infinity; Column: Waters XSelect (C18, 50×2.1mm, 3.5μ); Flow rate: 0.8mL / min; Column temperature: 35℃; Eluent A: 0.1% formic acid in acetonitrile; Eluent B: 0.1% formic acid in water; Linear gradient: t=0min 5% A, t=3.5min 98% A, t=6min 98% A; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative), mass range: 100-800; Detection: ELSD (PL-ELS2100): gas flow rate 1.2mL / min, gas temperature: 70℃, nebulization: 50℃.

[0205] Method 3: MS instrument type: Agilent Technologies LC / MSD SL; HPLC instrument type: Agilent Technologies 1100 series; Column: Waters XSelect (C18, 30×2.1mm, 3.5μ); Flow rate: 1mL / min; Column temperature: 25℃; Eluent A: 95% acetonitrile + 5% 10mM ammonium bicarbonate in water; Eluent B: 10mM ammonium bicarbonate in water, pH=9.0; Linear gradient: t=0min 5% A, t=1.6min 98% A, t=3min 98% A; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative) mass range: 100-800.

[0206] Method 4: MS instrument type: Agilent Technologies LC / MSD SL; HPLC instrument type: Agilent Technologies 1100 series; Column: Waters XSelect (C18, 50×2.1mm, 3.5μm); Flow rate: 0.8mL / min; Column temperature: 25℃; Eluent A: 95% acetonitrile + 5% 10mM ammonium bicarbonate in water; Eluent B: 10mM ammonium bicarbonate in water, pH=9.0; Linear gradient: t=0min 5% A, t=3.5min 98% A, t=6min 98% A; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative) mass range: 100-800.

[0207] Method 5: Instrument type: Reveleris TM Flash Chromatography System; Column: Reveleris TM C18 Flash Cartridge; 4g, flow rate 18mL / min; 12g, flow rate 30mL / min; 40g, flow rate 40mL / min; 80g, flow rate 60mL / min; 120g, flow rate 80mL / min; Eluent A: 0.1% formic acid in acetonitrile; Eluent B: 0.1% formic acid in water; Gradient: t=0min 5% A, t=1min 5% A, t=13min 100% A, t=16min 100% A; Detection: UV (200-360nm), ELSD.

[0208] Method 6: Instrument type: Reveleris TMFlash Chromatography System; Column: GraceResolv TM Silica Cartridges; 4g, flow rate 15mL / min; 12g, flow rate 28mL / min; 24g, flow rate 30mL / min; 40g, flow rate 40mL / min; 80g, flow rate 55mL / min; 120g, flow rate 80mL / min and Davisil TM Chromatographic silica medium (LC60A 20-45 microns); 300 g, flow rate 70 mL / min; 500 g, flow rate 70 mL / min; eluent: see experiment; detection: UV (200-360 nm), ELSD.

[0209] Method 7: Instrument type: Büchi pump manager C-615, Büchi pump module C-601; Column: GraceResolv TM Silica Cartridges; 4g, flow rate 15mL / min; 12g, flow rate 28mL / min; 24g, flow rate 30mL / min; 40g, flow rate 40mL / min; 80g, flow rate 55mL / min; 120g, flow rate 80mL / min and Davisil TM Chromatographic silica medium (LC60A20-45 microns); 300 g, flow rate 70 mL / min; 500 g, flow rate 70 mL / min; eluent: see experiment; detection: TLC plate; TLC silica gel 60F254 (Merck).

[0210] Method 8: MS instrument type: Agilent Technologies 6130 Quadrupole LC-MS; HPLC instrument type: Agilent Technologies 1260 Infinity; Column: Waters XSelect (C18, 50×2.1mm, 3.5μ); Flow rate: 0.8mL / min; Column temperature: 35℃; Eluent A: 0.1% formic acid in acetonitrile; Eluent B: 0.1% formic acid in water; Linear gradient: t=0min 5% A, t=3.5min 98% A, t=8min 98% A; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative), mass range: 100-800; Detection: ELSD (PL-ELS2100): gas flow rate 1.2mL / min, gas temperature: 70℃, nebulization: 50℃.

[0211] Method 9: MS instrument type: Agilent Technologies G1956B Quadrupole LC-MS; HPLC instrument type: Agilent Technologies 1200 preparative LC; Column: Waters Sunfire (C18, 150×19mm, 5μm); Flow rate: 25mL / min; Column temperature: RT; Eluent A: 0.1% formic acid in acetonitrile; Eluent B: 0.1% formic acid in water; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative), mass range: 100-800; Collect fractions based on MS and DAD, or MS instrument type: ACQ-SQD2; HPLC instrument type: Waters Modular preparative HPLC system; Column: Waters XSelect (C18, 150×19mm, 10μm); Flow rate: 24mL / min preparative pump, 1mL / min loading pump; Column temperature: RT; Eluent A: 0.1% formic acid in acetonitrile; Eluent B: 0.1% formic acid in water; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative), mass range: 100-800; Collection fractions based on MS and DAD.

[0212] Method 10: MS instrument type: Agilent Technologies G1956B Quadrupole LC-MS; HPLC instrument type: Agilent Technologies 1200 preparative LC; Column: Waters XSelect (C18, 150×19mm, 5μm); Flow rate: 25mL / min; Column temperature: RT; Eluent A: 99% acetonitrile + 1% 10mM ammonium bicarbonate in water, pH=9.0; Eluent B: 10mM ammonium bicarbonate in water, pH=9.0; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative), mass range: 100-800; Collect fractions based on MS and DAD, or MS instrument type: ACQ-SQD2; HPLC instrument type: Waters Modular preparative HPLC system; Column: Waters XSelect (C18, 150×19mm, 10μm); Flow rate: 24mL / min preparative pump, 1mL / min loading pump; Column temperature: RT; Eluent A: 99% acetonitrile + 1% 10mM ammonium bicarbonate in water, pH=9.5; Eluent B: 10mM ammonium bicarbonate in water, pH=9.5; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative), mass range: 100-800; Collection fractions based on MS and DAD.

[0213] Method 11: Instrument type: Reveleris preparative; Detection: UV (220-360nm), ELSD; Column: XSelect TM CSH C18, 145×25mm, 10μ or GEMINI TM C18, 185×25mm, 10μ flow rate: 40mL / min; Eluent A: 10mM ammonium bicarbonate in water (pH=9.0), Eluent B: 99% acetonitrile + 1% 10mM ammonium bicarbonate in acetonitrile or Eluent A: 250mM ammonia, Eluent B: 250mM ammonia in acetonitrile.

[0214] Method 12: MS instrument type: Agilent Technologies LC / MSD SL; HPLC instrument type: Agilent Technologies 1100 series; Column: Phenomenex Gemini NX (C18, 50×2.0mm, 3.0μm); Flow rate: 0.8mL / min; Column temperature: 25℃; Eluent A: 95% acetonitrile + 5% 10mM ammonium bicarbonate in water, pH=9.0; Eluent B: 10mM ammonium bicarbonate in water, pH=9.0; Linear gradient: t=0min 5% A, t=3.5min 98% A, t=6min 98% A; Detection: DAD (220-320nm); Detection: MSD (ESI positive / negative) mass range: 100-800.

[0215] Method 13: [M+H] was analyzed by LC-MS under acidic chromatographic conditions. + Or M - The determination was performed using 1 ml formic acid / L acetonitrile and 0.9 ml formic acid / L Millipore water as eluents. A Zorbax Eclipse Plus C18 column (50 mm × 2.1 mm) was used. The column oven temperature was 55 °C.

[0216] Instruments: Agilent 1290LC, Agilent MSD, HTS PAL autosampler. Linear gradient from 10% acetonitrile to 95% acetonitrile in 0.0 to 1.80 min, constant 95% acetonitrile in 1.80 to 2.50 min, flow rate 1.0 ml / min.

[0217] In all cases, retention time exponents were calculated based on straight-chain alkyl-2-ones with 3 to 16 carbons from the same series, with the exponent for the first alkylone set to 300 and the exponent for the last alkylone set to 1600, and the exponents between them were calculated accordingly using linear interpolation between successive alkylones.

[0218] Method 14: [M+H] was analyzed by LC-MS under acidic chromatographic conditions. + Or M - The determination was performed using 1 ml formic acid / L acetonitrile and 0.9 ml formic acid / L Millipore water as eluents. A Zorbax Eclipse Plus C18 column (50 mm × 2.1 mm) was used. The column oven temperature was 55 °C.

[0219] [M+H] was analyzed by LC-MS under neutral chromatographic conditions. + The determination was performed using acetonitrile and Millipore water containing 79 mg / L ammonium carbonate as eluents.

[0220] instrument: LC-MS3: Waters UPLC with SQD2 mass spectrometer and Sample Manager autosampler. Linear gradient: 0.0 to 1.70 min from 10% acetonitrile to 95% acetonitrile, 1.70 to 2.40 min constant 95% acetonitrile, flow rate 0.85 ml / min.

[0221] LC-MS5: An Agilent 1100LC system with an MSD mass spectrometer and an HTS PAL autosampler (column: Zorbax XDBC18 1.8μm 50mm × 4.6mm, oven temperature 55℃). Linear gradient: 0.0 to 4.25 min from 10% acetonitrile to 95% acetonitrile, 4.25 to 5.80 min constant 95% acetonitrile, flow rate 2.0 ml / min.

[0222] In all cases, retention time exponents were calculated based on straight-chain alkyl-2-ones with 3 to 16 carbons from the same series, with the exponent for the first alkylone set to 300 and the exponent for the last alkylone set to 1600, and the exponents between them were calculated accordingly using linear interpolation between successive alkylones.

[0223] Method 15: MCW-SQ-HSST3 Instruments: Waters ACQUITY SQD UPLC system; Column: Waters Acquity UPLC HSS T3 1.8μm 50×1mm; Eluent A: 1L water + 0.25ml 99% formic acid, Eluent B: 1L acetonitrile + 0.25ml 99% formic acid; Gradient: 0.0min 90% A → 1.2min 5% A → 2.0min 5% A; Oven: 50℃; Flow rate: 0.40ml / min; UV detection: 210nm.

[0224] GC-MS Method and Instrumentation: GC: Agilent 6890N, FID: detection temperature: 300℃; MS: 5973MSD, EI-positive, detection temperature: 280℃; mass range: 50-550; column: RXI-5MS20m, ID 180μm, df 0.18μm; average velocity: 50cm / s; injection volume: 1μl; syringe temperature: 250℃; split ratio: 20 / 1; carrier gas: He.

[0225] Method S: Initial temperature: 60℃; initial time: 1.0 min; solvent delay: 1.3 min; rate: 50℃ / min; final temperature: 250℃; final time: 3.5 min.

[0226] Method A: Initial temperature: 100℃; initial time: 1.5 min; solvent delay: 1.3 min; rate: 75℃ / min; final temperature: 250℃; final time: 2.5 min.

[0227] Method C: Initial temperature: 100℃; initial time: 1.0 min; solvent delay: 1.3 min; rate: 75℃ / min; final temperature: 280℃; final time: 2.6 min.

[0228] Method U: Initial temperature: 100℃; initial time: 1.0 min; solvent delay: 1.3 min; rate: 120℃ / min; final temperature: 280℃; final time: 6.5 min.

[0229] Ion exchange chromatography Anion exchange chromatography: ISOLUTE TM SAX; Chemical description: Quaternary ammonium (uncapped) functionalized silica manufactured using trifunctional silanes; Adsorbent type: Strong anion exchange; Average particle size: 50 μm; Pore size: Exchange capacity: 0.6 meq / g.

[0230] microwave Biotage TM Initiator, microwave synthesizer; temperature range: 40℃-250℃; pressure range: 0-20 bar; power range: 0-400W.

[0231] Nuclear magnetic resonance spectroscopy 1 H- and 13 C-NMR instrument type: Bruker DMX300 1 HNMR: 300MHz; 13 C NMR: 75MHz), BrukerAvance III 400( 1 HNMR: 400MHz; 13 C NMR: 100MHz) or Bruker 400 Ultrashield ( 1 HNMR: 400MHz; 13 C NMR: 100 MHz; internal standard: tetramethylsilane; chemical shift (δ) is shown in parts per million (ppm); use the following abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br. = broad peak; coupling constant is shown in Hertz (Hz).

[0232] or, 1 Determination of H-NMR data was performed using a Bruker Avance III 400MHz spectrometer equipped with a 1.7mm TCI probe, with tetramethylsilane as a reference (0.00ppm), and measurements were typically recorded in solutions in solvents such as CD3CN, CDCl3, or d6-DMSO. Alternatively, measurements were performed using a Bruker Avance III 600MHz instrument equipped with a 5mm CPNMP probe or a Bruker Avance NEO 600MHz instrument equipped with a 5mm TCI probe. Measurements were typically performed at a probe temperature of 298K. Other measurement temperatures should be carefully noted.

[0233] Experimental Section - General Procedure Compounds of formula (I) can be synthesized according to or similar schemes (schemes 1-10).

[0234] In this document and throughout the context of this invention, cross-bonds represent cis / trans mixtures.

[0235] General Reaction Scheme-1 (S1): Compounds S1-1 to S1-4 from Examples General Reaction Scheme – 2 (S1): Compounds S1-5 to S1-8 from Examples General Reaction Scheme – 3 (S1): Examples of compounds S1-9 to S1-11 General Synthetic Scheme – 4 (S1): Examples of Compounds S1-12 Where Rq represents one or more substituents of Q as defined above for compounds of general formula (I).

[0236] General Synthetic Scheme – 5 (S1): Examples of Compounds S1-13 General Synthetic Scheme – 6 (S1): Examples of compounds S1-14 to S1-6 Where Rq represents one or more substituents of Q as defined above for compounds of general formula (I).

[0237] General Synthetic Scheme – 7 (S4): Compound S4-1 from Examples Where Rq represents one or more substituents of Q as defined above for compounds of general formula (I).

[0238] General Synthesis Scheme – 8 (S4) Where R 7 It has the meaning as defined above for compounds of general formula (I).

[0239] General Synthesis Scheme – 9 (S8a): Example Compound S8a-1 General Synthesis Scheme – 10 (S8b): Example Compound S8b-1 Experimental Section - Examples Intermediate (S1) Example S1-1A 1-(3-bromo-2-fluorophenyl)-2-methylprop-1-one Diisopropylamine (740 mg, 7.31 mmol, 1.04 mL) was dissolved in tetrahydrofuran (2 mL). The solution was cooled in an ice bath. Butyllithium (2.5 M in hexane; 7.31 mmol, 2.93 mL) was slowly added. After 30 min, the mixture was cooled in a dry ice / acetone bath. A solution of 1-bromo-2-fluorobenzene (800 mg, 4.57 mmol) in tetrahydrofuran (8 mL) was slowly added. After 3 h, N-methoxy-N-methylisobutyramide (600 mg, 4.57 mmol) was slowly added. After 40 min, the dry ice / acetone bath was removed. A saturated aqueous solution of ammonium chloride, water, and diethyl ether were added. The organic layer was separated, and the aqueous layer was extracted with diethyl ether. The combined organic layers were dried over sodium sulfate. The solvent was removed under vacuum to obtain 852 mg (3.48 mmol, 76% of the theoretical value) of the title compound.

[0240] GC-MS (Method S): R t =4.46 min; m / z = 244 / 246 M + Example S1-1B ethyl 7-bromo-3-isopropyl-1-benzothiophene-2-carboxylate Ethyl 2-mercaptoethyl (478 mg, 3.98 mmol, 0.44 mL) was added to a mixture of 1-(3-bromo-2-fluorophenyl)-2-methylprop-1-one (848 mg, 3.46 mmol) and potassium carbonate (1435 mg, 10.38 mmol) in N,N-dimethylformamide (8 mL). The mixture was heated to 100 °C for 10 h and then cooled to room temperature. Ethyl acetate and water were added. Hydrochloric acid (1 N) was added until an acidic pH was obtained. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with water and brine. After drying with sodium sulfate, the solvent was removed under vacuum to obtain 861 mg (2.63 mmol, 76% of the theoretical value) of the title compound.

[0241] LC-MS (Method 1): R t =2.27min; m / z=297 / 299(M-C2H5) - Example S1-1C 7-Bromo-3-isopropyl-1-benzothiophene-2-carboxylic acid Ethyl 7-bromo-3-isopropyl-1-benzothiophene-2-carboxylate (861 mg, 2.63 mmol) was dissolved in tetrahydrofuran (8 mL). An aqueous solution of lithium hydroxide monohydrate (1 N; 7.89 mmol, 7.89 mL) was added. After 20 h, hydrochloric acid (1 N) was added until an acidic pH was obtained. Ethyl acetate was added. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate. The solvent was removed under vacuum to give 718 mg (2.40 mmol, 91% of theoretical value) of the title compound.

[0242] LC-MS (Method 1): R t =2.28min; m / z=297 / 299(MH) - Example S1-1D 7-Bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide Triethylamine (729 mg, 7.20 mmol, 1.00 mL) was added to a mixture of 7-bromo-3-isopropylbenzo[b]thiophene-2-carboxylic acid (718 mg, 2.40 mmol) and (S)-chromium-4-amine hydrochloride (535 mg, 2.88 mmol) in dichloromethane (20 mL). Diethyl cyanophosphonate (783 mg, 4.80 mmol) was added. After 75 min, the volatiles were removed under vacuum. Purification by rapid column chromatography (Method 7; 80 g; heptane, 2%–20% ethyl acetate) yielded 442 mg (1.03 mmol, 42% of theoretical value) of the title compound.

[0243] LC-MS (Method 1): R t =2.32min; m / z=430 / 432(M+H) + Examples S1-2A Ethyl 3-amino-7-bromo-1-benzothiophene-2-carboxylate Ethyl 2-mercaptoacetate (0.721 g, 6.00 mmol, 0.66 mL) was added to a mixture of 3-bromo-2-fluorobenzonitrile (1.000 g, 5.00 mmol) and potassium carbonate (2.073 g, 15.00 mmol) in dried N,N-dimethylformamide (4 mL). The reaction mixture was stirred at 100 °C for 16 h, cooled to room temperature, and concentrated under vacuum. Water (50 mL) was added until a precipitate formed. The solid was filtered off and dried in air. 1.470 g (4.90 mmol, 98% of theoretical value) of the title compound was obtained.

[0244] LC-MS (Method 1): R t =2.24min; m / z=300 / 302(M+H) + 1H NMR (400MHz, DMSO-d6) δ = 8.21 (d, J = 8.1Hz, 1H), 7.78 (d, J = 7.6Hz, 1H), 7.39 (t, J = 7.9Hz, 1H), 7.24 (s, 2H), 4.28 (q, J = 7.1Hz, 2H), 1.30 (t, J = 7.1Hz, 3H).

[0245] Examples S1-2B ethyl 7-bromo-3-(dimethylamino)-1-benzothiophene-2-carboxylate Decorborane (0.36 g, 2.94 mmol) was added to a solution of ethyl 3-amino-7-bromo-1-benzothiophene-2-carboxylate (1.47 g, 4.90 mmol) and paraformaldehyde (0.59 g, 19.59 mmol) in methanol (20 mL). The reaction mixture was stirred for 4 h. Decorborane (0.15 g, 1.23 mmol) was then added. After 16 h, the reaction mixture was concentrated under vacuum. Purification by rapid column chromatography (Method 6; 80 g; heptane, 0%–50% ethyl acetate) gave 1.05 g (3.20 mmol, 65% of theoretical value) of the title compound.

[0246] LC-MS (Method 1): R t =2.42min; m / z=328 / 330(M+H) + 1H NMR (400MHz, DMSO-d6) δ = 8.05 (d, J = 8.2Hz, 1H), 7.78 (d, J = 7.6Hz, 1H), 7.40 (t, J = 7.9Hz, 1H), 4.29 (q, J = 7.1Hz, 2H), 3.08 (s, 6H), 1.32 (t, J = 7.1Hz, 3H).

[0247] Example S1-2C7-bromo-3-(dimethylamino)-1-benzothiophene-2-carboxylic acid Lithium hydroxide monohydrate (0.81 g, 19.19 mmol) was added to a suspension of ethyl 7-bromo-3-(dimethylamino)-1-benzothiophene-2-carboxylate (1.05 g, 3.20 mmol) in a mixture of water (20 mL) and tetrahydrofuran (20 mL). The mixture was stirred at room temperature for 16 h. Lithium hydroxide monohydrate (0.81 g, 19.19 mmol) was added, and the reaction mixture was stirred at room temperature for 1 h and then at 70 °C for 16 h. The reaction mixture was cooled to room temperature and acidified with hydrochloric acid (2 M) until a precipitate formed. The solid was filtered off, washed with water, and dried in air. 0.93 g (3.10 mmol, 97% of theoretical value) of the title compound was given.

[0248] LC-MS (Method 1): R t =1.78min; m / z=300 / 302(M+H) + 1H NMR (400MHz, DMSO-d6) δ = 13.83 (s, 1H), 8.09 (d, J = 8.1Hz, 1H), 7.79 (d, J = 7.6Hz, 1H), 7.42 (t, J = 7.9Hz, 1H), 3.06 (s, 6H).

[0249] Examples S1-2D 7-Bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide Diethyl cyanophosphonate (657 mg, 4.03 mmol, 0.6 mL) was added to a solution of 7-bromo-3-(dimethylamino)-1-benzothiophene-2-carboxylic acid (930 mg, 3.10 mmol), (S)-chromium-4-amine hydrochloride (690 mg, 3.72 mmol), and triethylamine (941 mg, 9.29 mmol, 1.3 mL) in dichloromethane (20 mL). The mixture was stirred at room temperature for 16 h. Purification by rapid column chromatography (Method 6; 80 g; heptane, 0%–50% ethyl acetate) yielded 1080 mg (2.50 mmol, 81% of theoretical value) of the title compound.

[0250] LC-MS (Method 1): R t =2.36min; m / z=431 / 433(M+H) + 1H NMR (400MHz, DMSO-d6) δ = 9.91 (d, J = 8.0Hz, 1H), 8.13 (d, J = 8.1Hz, 1H), 7.75 (d, J = 7.6Hz, 1H), 7 .41(t,J=7.9Hz,1H),7.31(d,J=7.4Hz,1H),7.24-7.14(m,1H),6.97-6.88(m,1H),6.83(d,J=8 .2Hz,1H),5.24(q,J=6.7Hz,1H),4.32(ddd,J=10.7,7.5,2.9Hz,1H),4.21(ddd,J=11.0,7.5,3 .0Hz,1H),2.88(s,6H),2.24(ddt,J=13.1,8.1,3.9Hz,1H),2.11(dtd,J=14.0,7.3,3.0Hz,1H).

[0251] Examples S1-3A Methyl 3-amino-7-bromo-1-benzothiophene-2-carboxylate Methyl 2-mercaptoacetate (2.37 g, 22.33 mmol, 2.0 mL) was added to a mixture of 3-bromo-2-fluorobenzonitrile (3.72 g, 18.61 mmol) and potassium carbonate (7.71 g, 55.80 mmol) in N,N-dimethylformamide (20 mL). The reaction mixture was stirred at 100 °C for 16 h and then cooled to room temperature. The mixture was poured into water. The resulting precipitate was filtered and dried in air to give 5.16 g (18.02 mmol, 97% of the theoretical value) of the title compound.

[0252] LC-MS (Method 1): R t =2.12min; m / z=286 / 288(M+H) + .

[0253] Examples S1-3B methyl 7-bromo-3-chloro-1-benzothiophene-2-carboxylate Copper(II) chloride (1.489 g, 11.07 mmol) was suspended in acetonitrile (100 mL). Isoamyl nitrite (1.621 g, 13.84 mmol, 1.86 mL) was added and the mixture was cooled in an ice bath. Methyl 3-amino-7-bromo-1-benzothiophene-2-carboxylate (2.640 g, 9.23 mmol) was added fractionally. The mixture was heated to room temperature. After 16 h, the volatiles were removed under vacuum. Water and diethyl ether were added to the residue. The mixture was filtered through a layer of diatomaceous earth. The organic layer of the filtrate was separated and the aqueous layer was extracted with diethyl ether. The combined organic layers were dried over sodium sulfate and the solvent was removed under vacuum. The residue was suspended in dimethyl sulfoxide. The solids were removed by filtration. The filtrate was purified by rapid column chromatography (Method 5; 120 g). 0.569 g (1.86 mmol, 20% of theoretical value) of the title compound was obtained.

[0254] LC-MS (Method 1): R t =2.30min; m / z=305 / 307(M+H) + .

[0255] Examples S1-3C methyl 7-bromo-3-methoxy-1-benzothiophene-2-carboxylate Sodium hydride (60% in mineral oil; 223 mg, 5.59 mmol) was suspended in anhydrous tetrahydrofuran (4 mL). Methanol (179 mg, 5.59 mmol, 0.23 mL) was added. The reaction mixture was stirred for 30 min. A solution of methyl 7-bromo-3-chloro-1-benzothiophene-2-carboxylate (569 mg, 1.86 mmol) in anhydrous tetrahydrofuran (5 mL) was added. After 20 h, the mixture was added to hydrochloric acid (1 N). This mixture was extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate and the solvent was removed under vacuum. The residue was coated onto a hydromatrix. Purification by rapid column chromatography (Method 7; 24 g; heptane, 5% to 40% ethyl acetate containing 1% acetic acid) gave 158 mg (0.53 mmol, 28% of the theoretical value) of the title compound.

[0256] LC-MS (Method 1): R t =2.23min; m / z=301 / 303(M+H) + .

[0257] Example S1-3D 7-Bromo-3-methoxy-1-benzothiophene-2-carboxylic acid An aqueous solution of lithium hydroxide monohydrate (1N; 1.574 mmol, 1.574 mL) was added to a solution of methyl 7-bromo-3-methoxy-1-benzothiophene-2-carboxylate (158 mg, 0.525 mmol) in tetrahydrofuran (2 mL). The reaction mixture was stirred for 4 h and hydrochloric acid (1N) was added until an acidic pH was obtained. Ethyl acetate and water were added. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and the solvent was removed under vacuum. 147 mg (0.512 mmol, 98% of the theoretical value) of the title compound was obtained.

[0258] LC-MS (Method 1): R t =2.07min; m / z=287 / 289(M+H) + .

[0259] Examples S1-3E 7-Bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxy-1-benzothiophene-2-carboxamide 7-Bromo-3-methoxy-1-benzothiophene-2-carboxylic acid (295 mg, 1.03 mmol) was dissolved in anhydrous N,N-dimethylformamide (3 mL). Triethylamine (260 mg, 2.57 mmol, 0.36 mL) and (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxafluorophosphate) (391 mg, 1.03 mmol) were added. The reaction mixture was stirred for 30 min and (S)-chromium-4-amine hydrochloride (191 mg, 1.03 mmol) was added. Stirring was continued for 16 h. Ethyl acetate and water were added. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with water and dried over sodium sulfate. The solvent was removed under vacuum to give 398 mg (0.951 mmol, 93% of the theoretical value) of the title compound.

[0260] LC-MS (Method 1): R t =2.270min; m / z=418 / 420(M+H) + .

[0261] Examples S1-4A ethyl 7-bromo-3-chlorobenzothiophene-2-carboxylate Copper(II) chloride (1.114 g, 8.28 mmol) was suspended in acetonitrile (80 mL). Amyl nitrite (1.213 g, 10.35 mmol, 1.39 mL) was added, and the mixture was cooled in an ice bath. Ethyl 3-amino-7-bromobenzothiophene-2-carboxylate (2.072 g, 6.90 mmol) was added fractionally. The mixture was heated to room temperature. After 16 h, diethyl ether and water were added. The organic layer was separated, and the aqueous layer was extracted with diethyl ether. The combined organic layers were washed with brine and dried over sodium sulfate. The solvent was removed under vacuum. The residue was purified by rapid column chromatography (Method 5; 120 g). 0.860 g (2.69 mmol, 39% of theoretical value) of the title compound was obtained.

[0262] LC-MS (Method 1): R t =2.41min; m / z=319 / 321(M+H) + .

[0263] Examples S1-4B 7-Bromo-3-chloro-1-benzothiophene-2-carboxylic acid An aqueous solution of lithium hydroxide monohydrate (1N; 1.891 mmol, 1.891 mL) was added to a solution of ethyl 7-bromo-3-chlorobenzothiophene-2-carboxylate (403 mg, 1.261 mmol) in tetrahydrofuran (12 mL) at 0 °C. The reaction mixture was heated to room temperature after 0.5 h. Stirring was continued for 64 h, and hydrochloric acid (1N) was added until an acidic pH was obtained. The precipitate formed was filtered and dried in air to give 351 mg (1.204 mmol, 95% of the theoretical value) of the title compound.

[0264] LC-MS (Method 1): R t =2.23min; m / z=245 / 247(M-COO-H) - .

[0265] Examples S1-4C 7-Bromo-3-chloro-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1-benzothiophene-2-carboxamide Triethylamine (451 mg, 4.46 mmol, 0.62 mL) was added to a mixture of 7-bromo-3-chloro-1-benzothiophene-2-carboxylic acid (433 mg, 1.49 mmol) and (S)-chromium-4-amine hydrochloride (331 mg, 1.78 mmol) in dichloromethane (10 mL). Diethyl cyanophosphonate (242 mg, 1.49 mmol, 0.23 mL) was added to the resulting solution. The reaction mixture was stirred for 16 h. Diethyl cyanophosphonate (242 mg, 1.49 mmol, 0.23 mL) was added. After 20 h, the volatiles were removed under vacuum. The residue was purified by rapid column chromatography (Method 7; 40 g; heptane, 2%–20% ethyl acetate). 254 mg (0.60 mmol, 40% of the theoretical value) of the title compound was given.

[0266] LC-MS (Method 1): R t =2.33min; m / z=422 / 424(M+H) + .

[0267] Example S1-1F 3-Chloroisocyanate ethyl ester 3-Chloroisonicotinic acid (5.00 g, 32 mmol) was suspended in ethanol (200 mL). Sulfuric acid (9.34 g, 95 mmol, 5.07 mL) was added, and the mixture was stirred at reflux for 64 h. Most of the solvent was removed under vacuum. The residue was partitioned between a saturated aqueous solution of sodium bicarbonate (200 mL) and ethyl acetate (100 mL). The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (2 × 50 mL). The combined organic layers were dried over sodium sulfate and concentrated under vacuum to give 5.15 g (28 mmol, 87% of theoretical value) of the title compound.

[0268] LC-MS (Method 1): R t =1.79min; m / z = 186(M+1) + .

[0269] Examples S1-2F ethyl 3-hydroxythiopheno[2,3-c]pyridine-2-carboxylate Ethyl 3-chloroisonicotinic acid (4.95 g, 27 mmol) was dissolved in N,N-dimethylformamide (50 mL). Ethyl 2-mercaptoethyl (6.40 g, 53 mmol, 5.84 mL) was added, and the mixture was cooled in an ice bath. Sodium hydride (2.66 g, 67 mmol; 60% in mineral oil) was added fractionally, and the mixture was stirred for 45 min in an ice bath. Stirring was continued at room temperature for 2.5 h. Water (500 mL) was added, and the mixture was acidified to pH 3 with acetic acid. The mixture was extracted with ethyl acetate (3 × 100 mL). The combined organic layers were washed with a saturated aqueous solution of sodium bicarbonate (100 mL), water (3 × 100 mL), and brine. The organic layers were dried over sodium sulfate, and the solvent was removed under vacuum. Purification was achieved by grinding in diisopropyl ether (100 mL) to give 4.17 g (19 mmol, 70% of the theoretical value) of the title compound.

[0270] LC-MS (Method 1): R t =1.65min; m / z = 224(M+1) + ¹H NMR (400MHz, chloroform-d) δ 10.07 (s, ¹H), 9.09 (s, ¹H), 8.58 (d, J = 5.4 Hz, ¹H), 7.80 (dd, J = 5.5, 0.9 Hz, ¹H), 4.46 (q, J = 7.1 Hz, 2H), 1.44 (t, J = 7.1 Hz, 3H).

[0271] Examples S1-3F 3-(((trifluoromethyl)sulfonyl)oxy)thienro[2,3-c]pyridine-2-carboxylic acid ethyl ester Under a nitrogen atmosphere at room temperature, triethylamine (1.13 g, 11.2 mmol, 1.56 mL) was added to a stirred solution of ethyl 3-hydroxythieno[2,3-c]pyridine-2-carboxylate (1.00 g, 4.5 mmol) and N-phenyltrifluoromethanesulfonylimide (1.68 g, 4.7 mmol) in dichloromethane (20 mL). The mixture was stirred at room temperature for 16 h. N-phenyltrifluoromethanesulfonylimide (0.40 g, 1.1 mmol) and triethylamine (0.23 mg, 2.2 mmol, 0.31 mL) were added and stirring was continued for 2 h. The reaction mixture was concentrated under vacuum. Purification by rapid column chromatography (Method 6, 40 g; heptane, 5%–100% ethyl acetate) gave 1.51 g (4.3 mmol, 95% of theoretical value) of the title compound.

[0272] LC-MS (Method 1): R t=2.13min; m / z = 356(M+1) + ¹H NMR (400MHz, chloroform-d) δ 9.21 (d, J = 0.9Hz, 1H), 8.69 (d, J = 5.7Hz, 1H), 7.70 (d, J = 5.7Hz, 1H), 4.51 (q, J = 7.1Hz, 2H), 1.46 (t, J = 7.1Hz, 3H).

[0273] Examples S1-4F ethyl 3-(dimethylamino)thiopheno[2,3-c]pyridine-2-carboxylate A mixture of ethyl 3-(((trifluoromethyl)sulfonyl)oxy)thieno[2,3-c]pyridine-2-carboxylate (0.50 g, 1.4 mmol), potassium carbonate (1.17 g, 8.4 mmol), and dimethylamine hydrochloride (0.34 g, 4.2 mmol) in N,N-dimethylformamide (5 mL) was stirred at 90 °C for 1 h. The reaction mixture was cooled to room temperature and filtered. The filter cake was washed with ethyl acetate (2 × 10 mL). The filtrate was concentrated under vacuum. Purification by rapid column chromatography (Method 6, 40 g; heptane, 5%–100% ethyl acetate) gave 0.20 g (0.8 mmol, 56% of theoretical value) of the title compound.

[0274] LC-MS (Method 1): R t =1.73min; m / z = 251(M+1) + ¹H NMR (400MHz, chloroform-d) δ 9.03 (d, J = 1.0Hz, 1H), 8.49 (d, J = 5.7Hz, 1H), 7.78 (dd, J = 5.7, 1.1Hz, 1H), 4.37 (q, J = 7.1Hz, 2H), 3.14 (s, 6H), 1.41 (t, J = 7.1Hz, 3H).

[0275] Examples S1-5F 3-(dimethylamino)-7-iodothieno[2,3-c]pyridine-2-carboxylic acid ethyl ester At -78 °C, a 2,2,6,6-tetramethyl-piperidinyl magnesium chloride-lithium chloride complex (1 M; 0.80 mmol, 0.80 mL) was added dropwise to a stirred solution of ethyl 3-(dimethylamino)thieno[2,3-c]pyridine-2-carboxylate (50 mg, 0.200 mmol) in tetrahydrofuran (1.00 mL). The resulting solution was stirred for 15 min while being heated to room temperature. The solution was cooled back to -78 °C and a solution of iodine (253 mg, 1.00 mmol) in tetrahydrofuran (1.00 mL) was added. The resulting mixture was stirred at -78 °C for 15 min. The reaction mixture was quenched in an aqueous solution of sodium thiosulfate (1 M, 10 mL) and extracted with ethyl acetate (2 × 5 mL). The combined organic extracts were dried over sodium sulfate and concentrated under vacuum. Purification by rapid column chromatography (Method 6, 40 g; heptane, 5%–50% ethyl acetate) yielded 23 mg (0.06 mmol, 30% of theoretical value) of the title compound.

[0276] LC-MS (Method 1): R t =2.25min; m / z = 377(M+1) + ¹H NMR (400MHz, chloroform-d) δ 8.24 (d, J = 5.5Hz, 1H), 7.78 (d, J = 5.5Hz, 1H), 4.38 (q, J = 7.1Hz, 2H), 3.12 (s, 6H), 1.42 (t, J = 7.1Hz, 3H).

[0277] Examples S1-6F ethyl 7-(2,3-dichlorophenyl)-3-(dimethylamino)thiopheno[2,3-c]pyridine-2-carboxylate The mixture of ethyl 3-(dimethylamino)-7-iodothiophene[2,3-c]pyridine-2-carboxylate (40 mg, 0.11 mmol), sodium carbonate (23 mg, 0.21 mmol), and 1,4-dioxane (1.00 mL) and water (0.15 mL) was purged with nitrogen. 1,1'-bis-(diphenylphosphino)-ferrocene)palladium dichloride (5 mg, 0.01 mmol) was added, and the mixture was stirred in a sealed vial at 60 °C under nitrogen for 8 h. After cooling to room temperature, (2,3-dichlorophenyl)boronic acid (21 mg, 0.11 mmol) and sodium carbonate (11 mg, 0.11 mmol) were added. The mixture was purged with nitrogen. 1,1'-bis-(diphenylphosphino)-ferrocene)palladium dichloride (5 mg, 0.01 mmol) was added, and the reaction mixture was stirred in a sealed vial at 60 °C under nitrogen for 4 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (1 mL), and filtered. The filter cake was washed with ethyl acetate (1 mL). The filtrate was concentrated under vacuum. Purification by rapid column chromatography (Method 6, 4 g; heptane, 5%–100% ethyl acetate) yielded 38 mg (0.10 mmol, 90% of theoretical value) of the title compound.

[0278] LC-MS (Method 1): R t =2.34min; m / z=395 / 397(M+1) + 1H NMR (400MHz, DMSO-d6) δ8.64(d,J=5.7Hz,1H),8.05(d,J=5.7Hz,1H),7.86(dd,J=6.3,3 .3Hz,1H),7.63-7.49(m,2H),4.25(q,J=7.1Hz,2H),3.13(s,6H),1.26(t,J=7.1Hz,3H).

[0279] Examples S1-7F Lithium 7-(2,3-dichlorophenyl)-3-(dimethylamino)thiopheno[2,3-c]pyridine-2-carboxylate An aqueous solution of lithium hydroxide monohydrate (1 M; 0.13 mmol, 0.13 mL) was added to a stirred solution of ethyl 7-(2,3-dichlorophenyl)-3-(dimethylamino)thieno[2,3-c]pyridine-2-carboxylate (34 mg, 0.09 mmol) in tetrahydrofuran (0.20 mL). The resulting mixture was stirred at 60 °C for 16 h. The reaction mixture was cooled to room temperature, diluted with brine (5 mL), and extracted with tetrahydrofuran (3 × 2 mL). The combined organic extracts were concentrated under vacuum to give 23 mg (0.06 mmol, 71% of theoretical value) of the title compound.

[0280] LC-MS (Method 1): R t =1.81min; m / z=365 / 367(MH) - [Free acid] Examples S1-8F ethyl 3-methoxythiopheno[2,3-c]pyridine-2-carboxylate Ethyl 3-hydroxythiopheno[2,3-c]pyridine-2-carboxylate (2.00 g, 9.0 mmol) was dissolved in tetrahydrofuran (40 mL). Triphenylphosphine (2.82 g, 10.8 mmol) and methanol (0.32 mg, 9.9 mmol, 0.40 mL) were added to the resulting solution. A solution of di-tert-butyl azodicarbonate (2.48 g, 10.8 mmol) in tetrahydrofuran (10 mL) was slowly added while cooling in an ice bath. The mixture was stirred for 10 min while cooling in an ice bath. The reaction was continued for 1.5 h while the temperature was increased to room temperature. The reaction mixture was concentrated under vacuum. Ethyl acetate (100 mL) and an aqueous solution of sodium hydroxide (1 M; 100 mL) were added with stirring. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (2 × 50 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under vacuum. Purification by rapid column chromatography (Method 6, 120 g; heptane, 7%–60% ethyl acetate) yielded 1.94 g (8.2 mmol, 91% of theoretical value) of the title compound.

[0281] LC-MS (Method 1): R t =1.66min; m / z = 238(M+1) + .

[0282] Examples S1-9F 2-(ethoxycarbonyl)-3-methoxythiopheno[2,3-c]pyridine 6-oxide m-chloroperbenzoic acid (249 mg, 1.01 mmol; 70%) was added to a stirred solution of ethyl 3-methoxythieno[2,3-c]pyridine-2-carboxylate (200 mg, 0.84 mmol) in dichloromethane (5 mL). The resulting mixture was stirred for 16 h while being heated to room temperature. The reaction mixture was diluted with dichloromethane (20 mL), washed with saturated aqueous sodium bicarbonate solution (2 × 10 mL), dried over sodium sulfate, and concentrated under vacuum to give 180 mg (0.71 mmol, 84% of theoretical value) of the title compound.

[0283] LC-MS (Method 1): R t =1.62min; m / z = 254(M+1) + .

[0284] Examples S1-10F 7-Bromo-3-methoxythiopheno[2,3-c]pyridine-2-carboxylic acid ethyl ester Phosphorus oxybromide (473 mg, 1.65 mmol) was added in a single addition to a stirred solution of 2-(ethoxycarbonyl)-3-methoxythio[2,3-c]pyridine 6-oxide (209 mg, 0.83 mmol) in dichloromethane (5 mL). The resulting mixture was stirred and heated to room temperature for 16 h. The reaction mixture was slowly poured into a saturated aqueous solution of sodium bicarbonate (20 mL). After stirring for 15 min, the layers were separated and the aqueous layer was extracted with dichloromethane (20 mL). The combined organic layers were dried over sodium sulfate and concentrated under vacuum. Purification by rapid column chromatography (Method 6, 12 g; heptane, 5%–50% ethyl acetate) gave 122 mg (0.39 mmol, 47% of theoretical value) of the title compound.

[0285] LC-MS (Method 1): R t =2.16min; m / z=316 / 318(M+1) + ¹H NMR (400MHz, chloroform-d) δ 8.32 (d, J = 5.4Hz, ¹H), 7.72 (d, J = 5.4Hz, ¹H), 4.43 (q, J = 7.1Hz, 2H), 4.18 (s, 3H), 1.44 (t, J = 7.1Hz, 3H).

[0286] Examples S1-11F 7-Bromo-3-methoxythiopheno[2,3-c]pyridine-2-carboxylic acid An aqueous solution of lithium hydroxide monohydrate (1 M; 0.59 mmol, 0.59 mL) was added to a stirred solution of ethyl 7-bromo-3-methoxythiopheno[2,3-c]pyridine-2-carboxylate (123 mg, 0.28 mmol) in tetrahydrofuran (3 mL). The resulting mixture was stirred for 16 h. The reaction mixture was acidified with hydrochloric acid (1 M; 5 mL). The resulting precipitate was filtered and dried in air to give 104 mg (0.36 mmol, 93% of the theoretical value) of the title compound.

[0287] LC-MS (Method 1): R t =1.90min; m / z=288 / 290(M+1) + 1H NMR (400MHz, DMSO-d6) δ13.98 (s, 1H), 8.39 (d, J = 5.4Hz, 1H), 7.93 (d, J = 5.4Hz, 1H), 4.12 (s, 3H).

[0288] Examples S1-12F 7-Bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxythiopheno[2,3-c]pyridine-2-carboxamide Triethylamine (105 mg, 1.04 mmol, 0.15 mL) was added to a stirred suspension of 7-bromo-3-methoxythieno[2,3-c]pyridine-2-carboxylic acid (100 mg, 0.35 mmol) in N,N-dimethylformamide (2 mL). O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethylureonium hexafluorophosphate (139 mg, 0.36 mmol) and (S)-chromium-4-amine hydrochloride (71 mg, 0.38 mmol) were added to the resulting clear solution. The mixture was stirred in a sealed vial for 72 h at room temperature. The reaction mixture was concentrated under vacuum. The residue was partitioned between dichloromethane (2 mL) and water (3 mL). The layers were separated, and the aqueous layer was extracted with dichloromethane (1 mL). The combined organic layers were purified by rapid column chromatography (Method 6, 12 g; heptane, 5%-100% ethyl acetate) to give 83 mg (0.20 mmol, 57% of the theoretical value) of the title compound.

[0289] LC-MS (Method 1): R t =2.16min; m / z=419 / 421(M+1) + 1H NMR (400MHz, DMSO-d6) δ8.55(d,J=8.2Hz,1H),8.38(d,J=5.5Hz,1H),8.02(d,J=5.5Hz,1H),7.27(d,J=7.5Hz,1H),7.23-7.15(m,1H) ,6.95-6.88(m,1H),6.82(dd,J=8.2,1.1Hz,1H),5.29(q,J=6.5Hz,1H),4.27(dd,J=6.3,4.3Hz,2H),4.12(s,3H),2.22-2.14(m,2H).

[0290] Intermediate (S4) Example S4-1G Sodium 1-cyanoprop-1-en-2-ol 5-Methylisoxazole (25.5 g, 291 mmol, 25 mL) was added dropwise to a solution of sodium methoxide (5.4 M in methanol; 320 mmol, 59 mL) in anhydrous methanol (250 mL) at 0 °C. The resulting mixture was stirred at room temperature for 2 h. The solvent was removed under vacuum. The solid residue was ground in diethyl ether for 30 min. The solid was filtered off and dried in air. 24.2 g (230 mmol, 79% of the theoretical value) of the title compound was obtained as a mixture of E / Z isomers.

[0291] 1H NMR (400MHz, DMSO-d6) δ3.12 (s, 0.5H), 2.92 (s, 0.5H), 1.70 (s, 1.5H), 1.48 (s, 1.5H).

[0292] Example S4-2G 1-(3,5-Dichlorophenyl)-3-methyl-1H-pyrazole-5-amine A mixture of sodium 1-cyanoprop-1-en-2-ol (0.98 g, 9.4 mmol) and 3,5-dichlorophenylhydrazine hydrochloride (2.00 g, 9.4 mmol) in ethanol (50 mL) was stirred under reflux for 16 h. The reaction mixture was cooled to room temperature and concentrated under vacuum. The residue was poured into water (200 mL). The precipitate was filtered off and dried in air. 1.56 g (6.44 mmol, 68% of theoretical value) of the title compound was given.

[0293] LC-MS (Method 1): R t =1.91min; m / z=242 / 244(M+H) + 1H NMR (400MHz, DMSO-d6) δ7.67 (d, J = 1.8 Hz, 2H), 7.47 (t, J = 1.8 Hz, 1H), 5.54 (s, 2H), 5.37 (s, 1H), 2.06 (s, 3H).

[0294] Example S4-3G 1-(2,6-Difluorophenyl)-3-methyl-1H-pyrazole-5-amine A mixture of sodium 1-cyanoprop-1-en-2-ol (1.4 g, 13.3 mmol) and 2,6-difluorophenylhydrazine hydrochloride (2.0 g, 11.1 mmol) in trifluoroacetic acid (20 mL) was stirred at 100 °C for 1 h. Volatile substances were removed under vacuum, and the residue was dissolved in ethyl acetate (50 mL). This solution was washed with a saturated aqueous sodium carbonate solution and brine. The organic layer was dried over sodium sulfate, and the solvent was removed under vacuum. The crude product was coated onto a hydromatrix column and purified by rapid column chromatography (Method 6; 120 g; heptane, 0%–50% ethyl acetate). 1.97 g (9.4 mmol, 85% of theoretical value) of the title compound was obtained.

[0295] LC-MS (Method 1): R t =1.96min; m / z = 210(M+H) + Example S4-4G 1-(3,5-Dichlorophenyl)-1H-pyrazole-5-amine 3-Methoxyacrylonitrile (0.93 g, 11.2 mmol, 0.94 mL) was added to a suspension of 3,5-dichlorophenylhydrazine hydrochloride (2.00 g, 9.4 mmol) in trifluoroacetic acid (50 mL). The reaction mixture was stirred at 100 °C for 1 h. The solvent was removed under vacuum, and the residue was dissolved in ethyl acetate (50 mL). The solution was washed with a saturated aqueous sodium carbonate solution. The layers were separated, and the organic layer was washed with brine, dried over sodium sulfate, and concentrated under vacuum. The crude product was coated onto a hydromatrix column and purified by rapid column chromatography (Method 6; 80 g; heptane, 0%–40% ethyl acetate). 1.60 g (4.98 mmol, 53% of theoretical value; 71% purity) of the title compound was obtained.

[0296] LC-MS (Method 1): R t =1.93min; m / z=228 / 230(M+H) + .

[0297] Example S4-5G 1-(2,6-Difluorophenyl)-1H-pyrazole-5-amine 3-Methoxyacrylonitrile (1.1 g, 13.3 mmol, 1.12 mL) was added to a suspension of 2,6-difluorophenylhydrazine hydrochloride (2.0 g, 11.1 mmol) in trifluoroacetic acid (50 mL). The reaction mixture was stirred at 100 °C for 1 h. The solvent was removed under vacuum, and the residue was dissolved in ethyl acetate (50 mL). The solution was washed with a saturated aqueous sodium carbonate solution. The layers were separated, and the organic layer was washed with brine, dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by rapid column chromatography (Method 6; 80 g; heptane, 0%–50% ethyl acetate) and (Method 6; 120 g; heptane, 0%–30% ethyl acetate). 1.1 g (5.4 mmol, 48% of the theoretical value) of the title compound was obtained.

[0298] LC-MS (Method 3): R t =1.60min; m / z = 196(M+H) + 1H NMR (400MHz, DMSO-d6) δ7.59 (tt, J = 8.5, 6.4 Hz, 1H), 7.35-7.23 (m, 3H), 5.38 (d, J = 1.8 Hz, 1H), 5.35 (s, 2H).

[0299] Example S4-6G 2-(((1-(3,5-dichlorophenyl)-3-methyl-1H-pyrazole-5-yl)amino)methylene)diethyl malonate Diethyl ethoxymethylene malonate (2.29 g, 10.6 mmol, 2.1 mL) was added to a solution of 1-(3,5-dichlorophenyl)-3-methyl-1H-pyrazole-5-amine (1.28 g, 5.3 mmol) in ethanol (50 mL). The mixture was stirred under reflux for 16 h and cooled to room temperature. The precipitate formed was collected by filtration, washed with ethanol, and dried in air. 1.32 g (3.2 mmol, 60% of the theoretical value) of the title compound was obtained.

[0300] LC-MS (Method 1): R t =2.31min; m / z=412 / 414(M+H) + Example S4-7G 2-(((1-(2,6-difluorophenyl)-3-methyl-1H-pyrazole-5-yl)amino)methylene)diethyl malonate Diethyl ethoxymethylene malonate (1.2 g, 5.7 mmol, 1.2 mL) was added to a solution of 1-(2,6-difluorophenyl)-3-methyl-1H-pyrazole-5-amine (1.0 g, 4.8 mmol) in ethanol (20 mL). The mixture was stirred under reflux for 16 h and cooled to room temperature. Volatiles were removed under vacuum. The crude product was purified by rapid column chromatography (Method 6; 80 g; heptane, 0%–50% ethyl acetate). 1.6 g (4.2 mmol, 88% of theoretical value) of the title compound was obtained.

[0301] LC-MS (Method 1): R t =2.17min; m / z = 380(M+H) + 1H NMR (400MHz, DMSO-d6) δ10.47(d,J=13.0Hz,1H),8.04(d,J=13.0Hz,1H),7.68(ddd,J=14.8,8.3,6.6Hz,1 H), 7.42 (t, J = 8.5Hz, 2H), 6.42 (s, 1H), 4.08 (p, J = 6.9Hz, 4H), 2.21 (s, 3H), 1.17 (dt, J = 29.7, 7.1Hz, 6H).

[0302] Example S4-8G 2-(((1-(3,5-dichlorophenyl)-1H-pyrazole-5-yl)amino)methylene)diethyl malonate Diethyl ethoxymethylene malonate (1.3 g, 6 mmol, 1.2 mL) was added to a solution of 1-(3,5-dichlorophenyl)-1H-pyrazole-5-amine (1.6 g, 5 mmol; 71% purity) in ethanol (20 mL). The mixture was stirred under reflux for three days and cooled to room temperature. The precipitate formed was filtered off, washed with cold ethanol, and dried in air. 1.2 g (3 mmol, 60% of theoretical value) of the title compound was given.

[0303] LC-MS (Method 1): R t =2.25min; m / z=398 / 400(M+H) + 1H NMR (400MHz, DMSO-d6) δ10.61(d,J=11.6Hz,1H),8.04(d,J=12.7Hz,1H),7.72(s,4H),6.60(s,1H),4.12(dt,J=13.9,7.1Hz,4H),1.21(t,J=7.1Hz,6H).

[0304] Example S4-9G 2-(((1-(2,6-difluorophenyl)-1H-pyrazole-5-yl)amino)methylene)diethyl malonate Diethyl ethoxymethylene malonate (1.4 g, 6.4 mmol, 1.3 mL) was added to a solution of 1-(2,6-difluorophenyl)-1H-pyrazole-5-amine (1.1 g, 5.4 mmol) in ethanol (20 mL). The mixture was stirred under reflux for 16 h and cooled to room temperature. Volatiles were removed under vacuum. The crude product was purified by rapid column chromatography (Method 6; 80 g; heptane, 0%–50% ethyl acetate). 1.7 g (4.7 mmol, 88% of theoretical value) of the title compound was obtained.

[0305] LC-MS (Method 1): R t =2.04min; m / z = 366(M+H) + 1H NMR (400MHz, DMSO-d6) δ10.51(d,J=12.9Hz,1H),8.07(d,J=13.0Hz,1H),7.78(d,J=1.8Hz,1H),7.71(ddd,J=14. 9,8.5,6.4Hz,1H),7.45(t,J=8.4Hz,2H),6.68-6.53(m,1H),4.09(p,J=7.0Hz,4H),1.18(dt,J=28.7,7.1Hz,6H).

[0306] Example S4-10G 4-Chloro-1-(3,5-dichlorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester A solution of diethyl 2-(((1-(3,5-dichlorophenyl)-3-methyl-1H-pyrazol-5-yl)amino)methylene)malonate (1.1 g, 2.7 mmol) in phosphorus oxychloride (32.9 g, 215 mmol, 20 mL) was stirred under reflux for 16 h. Volatile substances were removed under vacuum. The residue was poured onto ice. The mixture was heated to room temperature and extracted with ethyl acetate (2 × 50 mL). The combined organic layers were washed with brine and dried over sodium sulfate. The solvent was removed under vacuum. 0.9 g (2.3 mmol, 88% of theoretical value) of the title compound was obtained.

[0307] LC-MS (Method 1): R t = 2.82 min; No mass detected 1H NMR (400MHz, DMSO-d6) δ9.08 (s, 1H), 8.34 (d, J = 1.9Hz, 2H), 7.65 (t, J = 1.8Hz, 1H), 4.40 (q, J = 7.1Hz, 2H), 2.79 (s, 3H), 1.37 (t, J = 7.1Hz, 3H).

[0308] Example S4-11G 4-Chloro-1-(2,6-difluorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester A solution of diethyl 2-(((1-(2,6-difluorophenyl)-3-methyl-1H-pyrazol-5-yl)amino)methylene)malonate (1.6 g, 4.1 mmol) in phosphorus oxychloride (82.0 g, 536 mmol, 50 mL) was stirred under reflux for 16 h. Volatile substances were removed under vacuum. The residue was dissolved in ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was washed with brine and dried over sodium sulfate. The solvent was removed under vacuum. 1.2 g (3.4 mmol, 82% of theoretical value) of the title compound was obtained.

[0309] LC-MS (Method 1): R t =2.23min; m / z = 352(M+H) + 1H NMR (400MHz, DMSO-d6) δ 8.93 (s, 1H), 7.76 (tt, J = 8.5, 6.4Hz, 1H), 7.47 (t, J = 8.4Hz, 2H), 4.39 (q, J = 7.1Hz, 2H), 2.78 (s, 3H), 1.36 (t, J = 7.1Hz, 3H).

[0310] Example S4-12G 4-Chloro-1-(3,5-dichlorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester A solution of diethyl 2-(((1-(3,5-dichlorophenyl)-1H-pyrazol-5-yl)amino)methylene)malonate (1.2 g, 3.01 mmol) in phosphorus oxychloride (82.0 g, 536 mmol, 50 mL) was stirred under reflux for 16 h. Volatile substances were removed under vacuum. The residue was dissolved in ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was washed with brine and dried over sodium sulfate. The solvent was removed under vacuum. 1.1 g (2.97 mmol, 98% of theoretical value) of the title compound was obtained.

[0311] LC-MS (Method 1): R t = 2.65 min; No mass detected 1H NMR (400MHz, DMSO-d6) δ9.16 (s, 1H), 8.83 (s, 1H), 8.36 (s, 2H), 7.70 (s, 1H), 4.42 (q, J = 7.1Hz, 2H), 1.38 (t, J = 7.1Hz, 3H).

[0312] Example S4-13G 4-Chloro-1-(2,6-difluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester A solution of diethyl 2-(((1-(2,6-difluorophenyl)-1H-pyrazol-5-yl)amino)methylene)malonate (1.7 g, 4.7 mmol) in phosphorus oxychloride (82.0 g, 536 mmol, 50 mL) was stirred under reflux for 16 h. Volatile substances were removed under vacuum. The residue was dissolved in ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was washed with brine and dried over sodium sulfate. The solvent was removed under vacuum. 1.4 g (4.0 mmol, 85% of theoretical value) of the title compound was obtained.

[0313] LC-MS (Method 1): R t =2.18min; m / z = 338(M+H) + 1H NMR (400MHz, DMSO-d6) δ9.02 (s, 1H), 8.85 (s, 1H), 7.79 (ddd, J = 15.0, 8.6, 6. 4Hz, 1H), 7.50 (t, J = 8.4Hz, 2H), 4.41 (d, J = 7.1Hz, 2H), 1.37 (t, J = 7.1Hz, 3H).

[0314] Example S4-14G 4-Chloro-1-(3,5-dichlorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid Lithium hydroxide monohydrate (458 mg, 10.92 mmol) was added to a suspension of ethyl 4-chloro-1-(3,5-dichlorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (700 mg, 1.82 mmol) in a mixture of tetrahydrofuran (20 mL) and water (20 mL). The mixture was stirred at room temperature for 16 h. Hydrochloric acid (2 M) was added until a white precipitate formed. The solid was filtered off, washed with water, and dried in air. 636 mg (1.78 mmol, 98% of the theoretical value) of the title compound was given.

[0315] LC-MS (Method 1): R t =2.77min; m / z=354 / 356(MH) - 1H NMR (400MHz, DMSO-d6) δ 13.83 (s, 1H), 9.05 (s, 1H), 8.31 (d, J = 1.8Hz, 2H), 7.61 (t, J = 1.8Hz, 1H), 2.77 (s, 3H).

[0316] Example S4-15G 4-Chloro-1-(2,6-difluorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid Lithium hydroxide monohydrate (0.86 g, 20.5 mmol) was added to a suspension of ethyl 4-chloro-1-(2,6-difluorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (1.20 g, 3.4 mmol) in a mixture of tetrahydrofuran (20 mL) and water (20 mL). The mixture was stirred at room temperature for 16 h and concentrated under vacuum. The aqueous solution of the residue was acidified by adding hydrochloric acid (1 M) until a white precipitate formed. The solid was filtered off, washed with water, and dried in air. 1.06 g (3.2 mmol, 96% of theoretical value) of the title compound was given.

[0317] LC-MS (Method 1): R t =2.04min; m / z = 324(M+H) + 1H NMR (400MHz, DMSO-d6) δ 13.77 (s, 1H), 8.94 (s, 1H), 7.81-7.70 (m, 1H), 7.47 (t, J = 8.3Hz, 2H), 2.78 (s, 3H).

[0318] Example S4-16G 4-Chloro-1-(3,5-dichlorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid Lithium hydroxide monohydrate (0.75 g, 17.8 mmol) was added to a suspension of ethyl 4-chloro-1-(3,5-dichlorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (1.10 g, 3.0 mmol) in a mixture of tetrahydrofuran (20 mL) and water (20 mL). The mixture was stirred at room temperature for 16 h and concentrated under vacuum. The aqueous solution of the residue was acidified by adding hydrochloric acid (1 M) until a white precipitate formed. The solid was filtered off, washed with water, and dried in air. 0.87 g (2.5 mmol, 86% of the theoretical value) of the title compound was given.

[0319] LC-MS (Method 1): R t =2.58min; m / z=340 / 342(MH) - 1H NMR (400MHz, DMSO-d6) δ 13.89 (s, 1H), 9.15 (s, 1H), 8.79 (s, 1H), 8.36 (d, J = 1.8Hz, 2H), 7.69 (s, 1H).

[0320] Example S4-17G 4-Chloro-1-(2,6-difluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid Lithium hydroxide monohydrate (1.00 g, 24.0 mmol) was added to a solution of ethyl 4-chloro-1-(2,6-difluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (1.35 g, 4.0 mmol) in a mixture of tetrahydrofuran (20 mL) and water (20 mL). The mixture was stirred at room temperature for 16 h. Hydrochloric acid (1 M) was added until a white precipitate formed. The solid was filtered off, washed with water, and dried in air. 0.97 g (3.1 mmol, 78% of the theoretical value) of the title compound was given.

[0321] LC-MS (Method 1): R t =2.02min; m / z = 310(M+H)+ 1H NMR (400MHz, DMSO-d6) δ 13.86 (s, 1H), 9.03 (s, 1H), 8.83 (s, 1H), 7.78 (ddd, J = 14.9, 8.5, 6.4Hz, 1H), 7.50 (t, J = 8.4Hz, 2H).

[0322] Example S4-18G 1-(3,5-Dichlorophenyl)-4-(dimethylamino)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid A suspension of 4-chloro-1-(3,5-dichlorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (0.20 g, 0.56 mmol) in a solution of dimethylamine in tetrahydrofuran (2.0 M; 1.78 g, 4.00 mmol, 2.0 mL) was stirred at 80 °C for 16 h. The reaction mixture was cooled to room temperature and hydrochloric acid (1 M) was added until a white precipitate formed. The solid was filtered off, washed with water, and dried in air. 0.20 g (0.54 mmol, 98% of theoretical value) of the title compound was given.

[0323] LC-MS (Method 1): R t =2.51min; m / z=365 / 367(M+H) + ¹H NMR (400MHz, DMSO-d6) δ 8.36 (d, J = 21.0Hz, 3H), 7.46 (s, 1H), 3.01 (s, 6H), 2.64 (s, 3H) [Acid protons not detected].

[0324] Example S4-19G 1-(2,6-Difluorophenyl)-4-(dimethylamino)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid A solution of 4-chloro-1-(2,6-difluorophenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (0.20 g, 0.62 mmol) in a solution of dimethylamine in tetrahydrofuran (2.0 M; 1.78 g, 4.00 mmol, 2.0 mL) was stirred at 80 °C for 1 h. The reaction mixture was cooled to room temperature and hydrochloric acid (1 M) was added until a white precipitate formed. The solid was filtered off, washed with water, and dried in air. 0.14 g (0.43 mmol, 70% of the theoretical value) of the title compound was given.

[0325] LC-MS (Method 1): R t =1.93min; m / z = 333(M+H) + .

[0326] Example S4-20G 1-(3,5-Dichlorophenyl)-4-(dimethylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid A suspension of 4-chloro-1-(3,5-dichlorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (0.20 g, 0.58 mmol) in a solution of dimethylamine in tetrahydrofuran (2.0 M; 1.78 g, 4.00 mmol, 2.0 mL) was stirred at 80 °C for 1 h. The reaction mixture was cooled to room temperature and hydrochloric acid (1 M) was added until a white precipitate formed. The solid was filtered off, washed with water, and dried in air. 0.17 g (0.48 mmol, 83% of theoretical value) of the title compound was given.

[0327] LC-MS (Method 1): R t =2.23min; m / z=351 / 353(M+H) + 1H NMR (400MHz, DMSO-d6) δ 12.83 (s, 1H), 8.66 (s, 1H), 8.58 (s, 1H), 8.42 (d, J = 1.8Hz, 2H), 7.58 (s, 1H), 3.25 (s, 6H).

[0328] Example S4-21G 1-(2,6-Difluorophenyl)-4-(dimethylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid A solution of 4-chloro-1-(2,6-difluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (0.20 g, 0.65 mmol) in dimethylamine in tetrahydrofuran (2.0 M; 1.78 g, 4.00 mmol, 2.0 mL) was stirred at 80 °C for 1 h. The reaction mixture was cooled to room temperature and hydrochloric acid (1 M) was added until a white precipitate formed. The solid was filtered off, washed with water, and dried in air. 0.12 g (0.37 mmol, 57% of theoretical value) of the title compound was given.

[0329] LC-MS (Method 1): R t =1.71 min; m / z = 319(M+H) + .

[0330] Intermediate (S8) Example S8a-1A 2-Acetoxy-3-bromobenzoic acid A mixture of 3-bromo-2-hydroxybenzoic acid (10 g, 46 mmol) and phosphoric acid (0.2 mL, 4 mmol) in acetic anhydride (50.0 mL, 530 mmol) was stirred at 50 °C for 18 h. The reaction mixture was cooled to room temperature, and water (120 mL) was added. The resulting mixture was stirred at 50 °C for 1 h and cooled in an ice-water bath. The solid was filtered off. The filtrate was stirred again at 50 °C for 1 h. A clear solution was obtained. After cooling in an ice-water bath, a precipitate formed. The precipitate was filtered off, washed with water, and dried in air. 8 g (31 mmol; 68% of theoretical value) of the title compound was given.

[0331] LC-MS (Method 1): R t =1.80min; m / z=257 / 259(MH) - 1H NMR (400MHz, chloroform-d) δ 10.65 (s, 1H), 8.06 (m, 1H), 7.86 (m, 1H), 7.29–7.19 (m, 1H), 2.40 (s, 3H).

[0332] Example S8a-2A Methyl 8-bromo-4-hydroxy-2-oxo-2H-chromene-3-carboxylate N,N'-dicyclohexylcarbodiimide (6.5 g, 31.7 mmol) was added to a solution of 2-acetoxy-3-bromobenzoic acid (8.1 g, 31.3 mmol) and 1-hydroxy-benzotriazole hydrate (4.8 g, 31.3 mmol) in tetrahydrofuran (120 mL) at 0 °C. A suspension was obtained after stirring for 5 min. The reaction mixture was stored at 5 °C for 20 h. The solids were filtered off, and the filtrate was used for subsequent steps (see below).

[0333] Sodium hydride (60% in mineral oil; 2.6 g, 65.7 mmol) was added to a stirred solution of dimethyl malonate (3.6 mL, 31.3 mmol) in tetrahydrofuran (240 mL). The filtrate obtained from the preceding step was added (see above). After 2 h, the reaction mixture was concentrated under vacuum. A mixture of hydrochloric acid (10% (v / v); 120 mL, 390 mmol) and methanol (120 mL) was added to the residue. The mixture was stirred for four days. The precipitate was filtered off, washed with methanol (120 mL), and dried in air. 3.6 g (12.3 mmol; 39% of theoretical value) of the title compound was obtained.

[0334] LC-MS (Method 1): R t =1.92min; m / z=299 / 301(M+H) + ¹H NMR (400 MHz, chloroform-d) δ 14.66 (s, ¹H), 7.99 (m, ¹H), 7.91 (m, ¹H), 7.23 (t, J = 7.9 Hz, ¹H), 4.05 (s, ³H).

[0335] Example S8a-3A (S)-8-bromo-N-(chroman-4-yl)-4-hydroxy-2-oxo-2H-chromene-3-carboxamide A mixture of (S)-chromium-4-amine hydrochloride (0.248 g, 1.337 mmol) and sodium methoxide (0.072 g, 1.337 mmol) was stirred in methanol (3 mL) for 1 h. Volatile substances were removed under vacuum. A mixture of methyl 8-bromo-4-hydroxy-2-oxo-2H-chromene-3-carboxylate (0.100 g, 0.334 mmol) in tetrahydrofuran (3 mL) was added, and the suspension was stirred at 60 °C for 72 h. The reaction mixture was cooled to room temperature. Volatile substances were removed under vacuum. The residue was ground in methanol. The solid was filtered off, washed with methanol, and dried in air. 0.068 g of the title compound was given. The filtrate was concentrated under vacuum. The residue was ground in diisopropyl ether. The solid was filtered off, washed with diisopropyl ether and water, and dried in air. 0.077 g of the title compound was given. A total of 0.145 g (0.317 mmol; 94% of the theoretical value) of the title compound was obtained, with a purity of >90% according to LC-MS.

[0336] LC-MS (Method 1): R t =2.32min; m / z=414 / 416(MH) - ¹H NMR (400MHz, DMSO-d6) δ 9.46 (s, ¹H), 8.10 (d, J = 7.5Hz, ¹H), 8.00 (d, J = 7.6Hz, ¹H), 7.39 (t, J = 7.8Hz, ¹H), 7.24 (dd, J = 20.5, 7.5Hz, 2H), 6.92 (t, J = 7.3Hz, 1H), 6.84 (d, J = 8.1Hz, 1H), 5.30 (d, J = 6.3Hz, 1H), 4.29 (d, J = 7.3Hz, 1H), 4.20 (d, J = 7.5Hz, 1H), 2.29–2.11 (m, 2H). [No OH signal detected].

[0337] Example S8a-4A Methyl 8-bromo-4-chloro-2-oxo-2H-chromene-3-carboxylate A mixture of methyl 8-bromo-4-hydroxy-2-oxo-2H-chromene-3-carboxylate (3.64 g, 12.17 mmol), N,N-diisopropylethylamine (2.1 mL, 12.17 mmol), and phosphorus oxychloride (12.48 mL, 134 mmol) was stirred at 110 °C for 1.5 h. The reaction mixture was concentrated under vacuum, purged with argon, and used as is in the next step.

[0338] Example S8a-5A methyl 8-bromo-4-(dimethylamino)-2-oxo-2H-chromene-3-carboxylate Under an argon atmosphere, triethylamine (5.1 mL, 36.5 mmol) and dimethylamine (2 M in tetrahydrofuran; 30.4 mL, 60.9 mmol) were added to a solution of crude methyl 8-bromo-4-chloro-2-oxo-2H-chromene-3-carboxylate (3.86 g, 12.2 mmol) in anhydrous tetrahydrofuran (25 mL). The resulting suspension was stirred at room temperature for 1 h. The solid was filtered off. The filtrate was concentrated under vacuum. The residue was dissolved in ethyl acetate (120 mL). The solution was washed with water (2 × 100 mL) and brine (50 mL), dried over sodium sulfate, and concentrated under vacuum. 3.85 g (11.6 mmol; 96% of the theoretical value after two steps) of the title compound was given.

[0339] LC-MS (Method 1): R t =1.84min; m / z=326 / 328(M+H) + ¹H NMR (400MHz, chloroform-d) δ 7.76 (dd, J = 7.8, 1.2Hz, ¹H), 7.70 (dd, J = 8.2, 1.2Hz, ¹H), 7.14 (t, J = 8.0Hz, ¹H), 3.95 (s, ³H), 3.08 (s, ⁶H).

[0340] Examples S8a-6A methyl 8-bromo-4-isopropyl-2-oxo-2H-chromene-3-carboxylate Under a nitrogen atmosphere at 0 °C, magnesium isopropyl bromide (1 M in tetrahydrofuran; 3.2 mL, 3.24 mmol) was added dropwise to a solution of methyl 8-bromo-4-(dimethylamino)-2-oxo-2H-chromene-3-carboxylate (0.96 g, 2.94 mmol) in anhydrous tetrahydrofuran (50 mL). The reaction mixture was stirred at 0 °C for 30 min. A saturated aqueous solution of ammonium chloride (30 mL) and brine (30 mL) were added. The mixture was heated to room temperature. The layers were separated. The aqueous layer was extracted with ethyl acetate (30 mL). The combined organic layers were dried over sodium sulfate. The solvent was removed under vacuum. Purification by rapid column chromatography (Method 6; 40 g; heptane, 3%–25% ethyl acetate) gave 0.38 g (1.12 mmol; 38% of the theoretical value) of the title compound.

[0341] LC-MS (Method 1): R t =2.06min; m / z=325 / 327(M+H) + ¹H NMR (400MHz, chloroform-d) δ 7.81 (t, J = 8.7Hz, 2H), 7.20 (t, J = 8.0Hz, 1H), 3.95 (s, 3H), 3.43–3.23 (m, 1H), 1.44 (d, J = 7.1Hz, 6H).

[0342] Examples S8a-7A methyl 8-(3,5-dichlorophenyl)-4-isopropyl-2-oxo-2H-chromene-3-carboxylate A mixture of methyl 8-bromo-4-isopropyl-2-oxo-2H-chromene-3-carboxylate (330 mg, 1.02 mmol), (3,5-dichlorophenyl)boronic acid (194 mg, 1.02 mmol), and sodium carbonate (323 mg, 3.04 mmol) in a mixture of 1,4-dioxane (9.0 mL) and water (1.5 mL) was purged with argon. 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (74 mg, 0.10 mmol) was added. The reaction mixture was stirred at 100 °C for 1.5 h and then cooled to room temperature. The reaction mixture was combined with the crude material obtained from the same reaction starting with 50 mg (0.15 mmol) of methyl 8-bromo-4-isopropyl-2-oxo-2H-chromene-3-carboxylate. The resulting mixture was diluted with dichloromethane (20 mL). The layers were separated by a phase separator. The organic layer was concentrated under vacuum. Purification by rapid column chromatography (Method 6; 24 g; heptane; 2%–20% ethyl acetate) yielded 31 mg (0.79 mmol; 68% based on the theoretical value of 1.17 mmol) of the title compound.

[0343] LC-MS (Method 1): R t =2.33min; m / z=391 / 393(M+H) + 1H NMR (400MHz, chloroform-d) δ7.91 (dd, J=8.3, 1.6Hz, 1H), 7.53 (dd, J=7.6, 1.5Hz, 1H), 7 .40(d,J=6.4Hz,4H),3.95(s,3H),3.38(p,J=7.2Hz,1H),1.48(d,J=7.1Hz,6H).

[0344] Examples S8a-8A Lithium 8-(3,5-dichlorophenyl)-4-isopropyl-2-oxo-2H-chromene-3-carboxylate Lithium hydroxide monohydrate (100 mg, 2.377 mmol) was added to a solution of methyl 8-(3,5-dichlorophenyl)-4-isopropyl-2-oxo-2H-chromene-3-carboxylate (310 mg, 0.792 mmol) in a mixture of tetrahydrofuran (5 mL) and water (5 mL). The reaction mixture was stirred at room temperature for 25 min and concentrated under vacuum. The crude product was used as is.

[0345] LC-MS (Method 1): R t =2.19min; m / z=377 / 379(M+H) + [Free acid].

[0346] (Target) Example Compound (S1) Compound S1-1 of the Examples 7-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide Bis(triphenylphosphine)palladium(II) chloride (7 mg, 0.010 mmol) was added to a mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide (88 mg, 0.204 mmol), (3,5-dichlorophenyl)boronic acid (43 mg, 0.225 mmol), and sodium carbonate (65 mg, 0.613 mmol) in a degassed mixture of 1,2-dimethoxyethane (4 mL) and water (1 mL). The mixture was stirred at 100 °C for 16 h. Water and dichloromethane were added. The mixture was passed through a phase separator and the organic layer was passed through a layer of sodium sulfate. The solvent was removed under vacuum. The residue was purified by rapid column chromatography (Method 7; 4 g; heptane, 2%–20% ethyl acetate) to give 58 mg (0.111 mmol, 54% of the theoretical value) of the title compound.

[0347] LC-MS (Method 2): R t =4.65min; m / z=496 / 498(M+H) + 1H NMR (400MHz, chloroform-d) δ = 8.06 (dd, J = 8.3, 1.0Hz, 1H), 7.54-7.45 (m, 3H), 7.42 (t, J = 1.9Hz, 1H) ,7.36(dd,J=7.3,1.0Hz,1H),7.31-7.26(m,1H),7.24-7.16(m,1H),6.98-6.90(m,1H),6.86 (dd,J=8.2,1.2Hz,1H),6.20(d,J=7.2Hz,1H),5.33(q,J=5.6Hz,1H),4.37-4.27(m,1H),4.2 6-4.16(m,1H),4.16-4.03(m,1H),2.42-2.27(m,1H),2.26-2.13(m,1H),1.66-1.48(m,6H).

[0348] Examples of compounds S1-2 7-(3-Chlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide Bis(triphenylphosphine)palladium(II) chloride (7 mg, 0.010 mmol) was added to a mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide (88 mg, 0.204 mmol), (3-chlorophenyl)boronic acid (35 mg, 0.225 mmol), and sodium carbonate (65 mg, 0.613 mmol) in a degassed mixture of 1,2-dimethoxyethane (4 mL) and water (1 mL). The mixture was stirred at 100 °C for 16 h. Water and dichloromethane were added. The mixture was passed through a phase separator and the organic layer was passed through a layer of sodium sulfate. The solvent was removed under vacuum. The residue was purified by rapid column chromatography (Method 7; 4 g; heptane, 2%–20% ethyl acetate) to give 74 mg (0.155 mmol, 76% of theoretical value) of the title compound.

[0349] LC-MS (Method 2): R t =4.45min; m / z=462 / 463(M+H) + 1H NMR (400MHz, chloroform-d)δ=8.10-7.95(m,1H),7.63-7.57(m,1H),7.57-7.45(m,2H), 7.45-7.34(m,3H),7.27(d,J=6.9Hz,1H),7.23-7.15(m,1H),6.96-6.89(m,1H) ,6.89-6.82(m,1H),6.19(d,J=7.6Hz,1H),5.41-5.20(m,1H),4.37-4.25(m,1H ),4.25-4.03(m,2H),2.40-2.26(m,1H),2.26-2.13(m,1H),1.62-1.47(m,6H).

[0350] Examples of compounds S1-3 7-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide Bis(triphenylphosphine)palladium(II) chloride (7 mg, 0.010 mmol) was added to a mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide (88 mg, 0.204 mmol), (2,3-dichlorophenyl)boronic acid (43 mg, 0.225 mmol), and sodium carbonate (65 mg, 0.613 mmol) in a degassed mixture of 1,2-dimethoxyethane (4 mL) and water (1 mL). The mixture was stirred at 100 °C for 16 h. Water and dichloromethane were added. The mixture was passed through a phase separator and the organic layer was passed through a layer of sodium sulfate. The solvent was removed under vacuum. The residue was purified by rapid column chromatography (Method 7; 4 g; heptane, 2%–20% ethyl acetate) to give 32 mg (0.061 mmol, 30% of the theoretical value) of the title compound.

[0351] LC-MS (Method 2): R t =4.45min; m / z=496 / 498(M+H) + 1H NMR (400MHz, chloroform-d)δ=8.13-8.04(m,1H),7.58-7.52(m,1H),7.52-7.45(m,1H) ),7.36-7.28(m,2H),7.26(s,2H),7.22-7.14(m,1H),6.91(t,J=7.5Hz,1H),6 .87-6.80(m,1H),6.14(d,J=7.4Hz,1H),5.35-5.21(m,1H),4.35-4.24(m,1H) ,4.23-4.06(m,2H),2.37-2.24(m,1H),2.24-2.08(m,1H),1.65-1.47(m,6H).

[0352] Examples of compounds S1-4 7-(3,4-Difluorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide Bis(triphenylphosphine)palladium(II) chloride (7 mg, 0.010 mmol) was added to a mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-isopropyl-1-benzothiophene-2-carboxamide (88 mg, 0.204 mmol), (3,4-difluorophenyl)boronic acid (36 mg, 0.225 mmol), and sodium carbonate (65 mg, 0.613 mmol) in a degassed mixture of 1,2-dimethoxyethane (4 mL) and water (1 mL). The mixture was stirred at 100 °C for 16 h. Water and dichloromethane were added. The mixture was passed through a phase separator and the organic layer was passed through a layer of sodium sulfate. The solvent was removed under vacuum. The residue was purified by rapid column chromatography (Method 7; 4 g; heptane, 2%–20% ethyl acetate) to give 68 mg (0.144 mmol, 70% of the theoretical value) of the title compound.

[0353] LC-MS (Method 2): R t =4.33min; m / z = 464(M+H) + 1H NMR (400MHz, chloroform-d)δ=8.08-7.99(m,1H),7.53-7.47(m,1H),7.47-7.40(m,1H) ,7.39-7.33(m,2H),7.32-7.25(m,2H),7.25-7.17(m,1H),6.98-6.90(m,1H), 6.90-6.82(m,1H),6.18(d,J=7.0Hz,1H),5.37-5.25(m,1H),4.37-4.27(m,1H ),4.26-4.03(m,2H),2.40-2.27(m,1H),2.26-2.13(m,1H),1.63-1.46(m,6H).

[0354] Examples of compounds S1-5 7-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide A mixture of 3,5-dichlorophenylboronic acid (44 mg, 0.232 mmol), 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide (100 mg, 0.232 mmol), and saturated sodium carbonate aqueous solution (0.34 mL) in 1,2-dimethoxyethane (4 mL) was purged with argon for 5 min. Tetra(triphenylphosphine)palladium(0) (13 mg, 0.012 mmol) was added, and the mixture was stirred at 100 °C for 1 h. Dichloromethane (2 mL) was added, and the layers were separated using a phase separator. The organic layer was dried over sodium sulfate, and the solvent was removed under vacuum. The crude product was purified by rapid column chromatography (Method 6; 24 g; heptane, 0%–50% ethyl acetate) and by reversed-phase rapid column chromatography (Method 10; 24 g). 72 mg (0.14 mmol, 62% of the theoretical value) of the title compound was obtained.

[0355] LC-MS (Method 2): R t =4.66min; m / z=497 / 499(M+H) + 1H NMR (400MHz, DMSO-d6) δ = 9.96 (d, J = 8.0Hz, 1H), 8.14 (dd, J = 6.6, 2.6Hz, 1H), 7.76 (dd, J = 9.7, 1.8 Hz,3H),7.64-7.49(m,2H),7.29(d,J=7.5Hz,1H),7.25-7.12(m,1H),6.92(t,J=7.4Hz,1H),6.83( d,J=8.2Hz,1H),5.23(q,J=6.8Hz,1H),4.31(ddd,J=10.6,7.5,2.8Hz,1H),4.21(ddd,J=11.0,7.5 ,3.0Hz,1H),2.90(s,6H),2.24(ddd,J=12.9,9.0,4.1Hz,1H),2.09(dtd,J=13.9,7.2,2.9Hz,1H).

[0356] Examples of compounds S1-6 7-(3-Chlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide A mixture of 3-chlorophenylboronic acid (36 mg, 0.232 mmol), 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide (100 mg, 0.232 mmol), and saturated sodium carbonate aqueous solution (0.34 mL) in 1,2-dimethoxyethane (4 mL) was purged with argon for 5 min. Tetra(triphenylphosphine)palladium (0) (13 mg, 0.012 mmol) was added, and the mixture was stirred at 100 °C for 1 h. Dichloromethane (2 mL) was added, and the layers were separated using a phase separator. The organic layer was dried over sodium sulfate, and the solvent was removed under vacuum. The crude product was purified by rapid column chromatography (Method 6; 24 g; heptane, 0%–50% ethyl acetate). 98 mg (0.21 mmol, 91% of theoretical value) of the title compound was obtained.

[0357] LC-MS (Method 2): R t =4.43min; m / z = 463(M+H) + 1H NMR (400MHz, DMSO-d6) δ = 9.97 (d, J = 8.0Hz, 1H), 8.11 (dd, J = 7.1, 2.0Hz, 1H), 7.75-7 .52(m,6H),7.29(d,J=7.4Hz,1H),7.22-7.15(m,1H),6.95-6.88(m,1H),6.83(d,J= 8.2Hz, 1H), 5.22 (q, J=6.7Hz, 1H), 4.31 (ddd, J=10.6, 7.5, 2.9Hz, 1H), 4.21 (ddd, J= 11.0, 7.5, 3.0Hz, 1H), 2.91 (s, 6H), 2.20 (s, 1H), 2.09 (dtd, J = 13.8, 7.2, 2.9Hz, 1H).

[0358] Examples of compounds S1-7 7-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide A mixture of 2,3-dichlorophenylboronic acid (44 mg, 0.232 mmol), 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide (100 mg, 0.232 mmol), and saturated sodium carbonate aqueous solution (0.34 mL) in 1,2-dimethoxyethane (4 mL) was purged with argon for 5 min. Tetra(triphenylphosphine)palladium (0) (13 mg, 0.012 mmol) was added, and the mixture was stirred at 100 °C for 1 h. Dichloromethane (2 mL) was added, and the layers were separated using a phase separator. The organic layer was dried over sodium sulfate, and the solvent was removed under vacuum. The crude product was purified by rapid column chromatography (Method 6; 24 g; heptane, 0%–50% ethyl acetate) and by reversed-phase rapid column chromatography (Method 10; 24 g). The title compound was obtained in a dose of 61 mg (0.12 mmol, 52% of the theoretical value).

[0359] LC-MS (Method 2): R t =4.42min; m / z=497 / 499(M+H) + 1H NMR (400MHz, DMSO-d6) δ=9.92(d,J=7.8Hz,1H),8.14(d,J=8.1Hz,1H),7.81(dd,J=7.8,1.7 Hz,1H),7.61-7.41(m,4H),7.27(d,J=7.5Hz,1H),7.22-7.14(m,1H),6.94-6.87(m,1H),6. 82(d,J=8.2Hz,1H),5.20(q,J=6.5Hz,1H),4.30(ddd,J=10.6,7.4,2.9Hz,1H),4.20(ddd,J =10.9,7.4,2.9Hz,1H),2.92(s,6H),2.21(ddd,J=13.3,8.1,3.1Hz,1H),2.12-2.02(m,1H).

[0360] Examples of compounds S1-8 7-(3,4-Difluorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide A mixture of 3,4-difluorophenylboronic acid (37 mg, 0.232 mmol), 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)-1-benzothiophene-2-carboxamide (100 mg, 0.232 mmol), and saturated sodium carbonate aqueous solution (0.34 mL) in 1,2-dimethoxyethane (4 mL) was purged with argon for 5 min. Tetra(triphenylphosphine)palladium(0) (13 mg, 0.012 mmol) was added, and the mixture was stirred at 100 °C for 1 h. Dichloromethane (2 mL) was added, and the layers were separated using a phase separator. The organic layer was dried over sodium sulfate, and the solvent was removed under vacuum. The crude product was purified by rapid column chromatography (Method 6; 24 g; heptane, 0%–50% ethyl acetate). 104 mg (0.22 mmol, 97% of theoretical value) of the title compound was obtained.

[0361] LC-MS (Method 2): R t =4.30min; m / z = 465(M+H) + 1H NMR (400MHz, DMSO-d6) δ = 9.97 (d, J = 8.0 Hz, 1H), 8.14-8.07 (m, 1H), 7.78 (ddd, J = 11. 3,7.7,2.0Hz,1H),7.70-7.48(m,4H),7.29(d,J=7.5Hz,1H),7.23-7.14(m,1H),6.95 -6.87(m,1H),6.83(d,J=8.1Hz,1H),5.22(q,J=6.6Hz,1H),4.31(td,J=7.9,3.7Hz,1 H), 4.25-4.16 (m, 1H), 2.90 (s, 6H), 2.23 (dt, J = 10.1, 5.4Hz, 1H), 2.11-2.03 (m, 1H).

[0362] Examples of compounds S1-9 7-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxy-1-benzothiophene-2-carboxamide Bis(triphenylphosphine)palladium(II) chloride (8 mg, 0.012 mmol) was added to a mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxy-1-benzothiophene-2-carboxamide (100 mg, 0.239 mmol), (3,5-dichlorophenyl)boronic acid (50 mg, 0.263 mmol), and sodium carbonate (76 mg, 0.717 mmol) in a degassed mixture of 1,2-dimethoxyethane (4 mL) and water (1 mL). The mixture was stirred at 100 °C for 16 h. Water and dichloromethane were added. The layers were separated using a phase separator. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate and the solvent was removed under vacuum. The crude product was purified by rapid column chromatography (Method 7; 4 g; heptane, 2%–20% ethyl acetate). 72 mg (0.146 mmol, 60% of the theoretical value) of the title compound was obtained.

[0363] LC-MS (Method 2): R t =4.57min; m / z=484 / 486(M+H) + 1H NMR (400MHz, chloroform-d) δ = 7.80 (dd, J = 8.0, 1.1Hz, 1H), 7.72 (d, J = 7.7Hz, 1H), 7.57 ( dd,J=1.9,0.7Hz,2H),7.54-7.47(m,1H),7.47-7.39(m,2H),7.35-7.29(m,1H) ,7.22(td,J=8.2,1.6Hz,1H),6.98-6.83(m,2H),5.44-5.35(m,1H),4.38-4.29 (m,1H),4.29-4.19(m,1H),4.03(s,3H),2.44-2.31(m,1H),2.26-2.14(m,1H).

[0364] Examples of compounds S1-10 7-(3-Chlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxy-1-benzothiophene-2-carboxamide Bis(triphenylphosphine)palladium(II) chloride (8 mg, 0.012 mmol) was added to a mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxy-1-benzothiophene-2-carboxamide (100 mg, 0.239 mmol), (3-chlorophenyl)boronic acid (41 mg, 0.263 mmol), and sodium carbonate (76 mg, 0.717 mmol) in a degassed mixture of 1,2-dimethoxyethane (4 mL) and water (1 mL). The mixture was stirred at 100 °C for 16 h. Water and dichloromethane were added. The layers were separated using a phase separator. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate and the solvent was removed under vacuum. The crude product was purified by rapid column chromatography (Method 7; 4 g; heptane, 2%–20% ethyl acetate). 57 mg (0.123 mmol, 51% of the theoretical value) of the title compound was obtained.

[0365] LC-MS (Method 2): R t =4.36 min; m / z = 450(M+H) + ¹H NMR (400MHz, chloroform-d) δ=7.78(dd,J=7.9,1.2Hz,1H),7.73(d,J=7.8Hz,1H),7.65(dt,J=1.7,1.1Hz,1H),7.61(dt,J=6.9,1.9Hz,1H),7.53-7.47(m,1H),7.47-7.40(m,3H),7.35-7.29(m,1H),7.2 1(dd,J=8.1,1.0Hz,1H),6.93(td,J=7.5,1.2Hz,1H),6.89(dd,J=8.3,1.2Hz,1H),5.45-5.33(m ,1H),4.39-4.29(m,1H),4.29-4.19(m,1H),4.03(s,3H),2.43-2.30(m,1H),2.26-2.13(m,1H).

[0366] Compound S1-11 of Examples 7-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxy-1-benzothiophene-2-carboxamide Bis(triphenylphosphine)palladium(II) chloride (8 mg, 0.012 mmol) was added to a mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxy-1-benzothiophene-2-carboxamide (100 mg, 0.239 mmol), (2,3-dichlorophenyl)boronic acid (68 mg, 0.359 mmol), and sodium carbonate (76 mg, 0.717 mmol) in a degassed mixture of 1,2-dimethoxyethane (4 mL) and water (1 mL). The mixture was stirred at 100 °C for 16 h. Ethyl acetate and water were added. The layers were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate. The solvent was removed under vacuum. The crude product was purified by rapid column chromatography (Method 7; 4 g; heptane, 2%–20% ethyl acetate). 73 mg (0.143 mmol, 60% of the theoretical value) of the title compound was obtained.

[0367] LC-MS (Method 2): R t =4.37min; m / z=484 / 486(M+H) + ¹H NMR (400MHz, chloroform-d) δ=7.83(dd,J=8.1,1.1Hz,1H),7.72(d,J=7.7Hz,1H),7.58(dd,J=7.5,2.1Hz,1H),7.51(dd,J=8.1,7.3Hz,1H),7.39(dd,J=7.3,1.1Hz,1H),7.37-7.28(m,3H) ,7.24-7.18(m,1H),6.97-6.90(m,1H),6.88(dd,J=8.3,1.0Hz,1H),5.43-5.31(m,1H),4 .38-4.28(m,1H),4.28-4.17(m,1H),4.06(s,3H),2.41-2.29(m,1H),2.25-2.11(m,1H).

[0368] Examples of compounds S1-12 3-Chloro-7-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1-benzothiophene-2-carboxamide Bis(triphenylphosphine)palladium(II) chloride (6 mg, 0.008 mmol) was added to a mixture of 7-bromo-3-chloro-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1-benzothiophene-2-carboxamide (70 mg, 0.166 mmol), (2,3-dichlorophenyl)boronic acid (47 mg, 0.248 mmol), and sodium carbonate (53 mg, 0.497 mmol) in a degassed mixture of 1,2-dimethoxyethane (2 mL) and water (1 mL). The mixture was stirred at 100 °C for 16 h. Water and dichloromethane were added. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate and the solvent was removed under vacuum. The crude product was purified by rapid column chromatography (Method 7; 4 g; heptane, 2%–20% ethyl acetate). 43 mg (0.084 mmol, 51% of the theoretical value) of the title compound was obtained.

[0369] LC-MS (Method 2): R t =4.52min; m / z=488 / 490(M+H) + 1H NMR (400MHz, chloroform-d) δ = 7.92 (dd, J = 8.2, 0.9Hz, 1H), 7.68-7.55 (m, 2H), 7.45 (dd, J = 7.3, 0.9Hz, 1H), 7.42-7.29 (m, 4H), 7.26-7.18(m,1H),7.00-6.82(m,2H),5.38(q,J=5.7Hz,1H),4.40-4.19(m,2H),2.45-2.31(m,1H),2.29-2.15(m,1H).

[0370] Examples of compounds S1-13 7-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(dimethylamino)thiopheno[2,3-c]pyridine-2-carboxamide Triethylamine (19 mg, 0.19 mmol, 0.03 mL) was added to a stirred suspension of lithium 7-(2,3-dichlorophenyl)-3-(dimethylamino)thieno[2,3-c]pyridine-2-carboxylate (23 mg, 0.06 mmol) in N,N-dimethylformamide (1.00 mL). O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethylureonium hexafluorophosphate (35 mg, 0.09 mmol) and (S)-chromium-4-amine hydrochloride (17 mg, 0.09 mmol) were added to the resulting clear solution. The mixture was stirred in a sealed container at room temperature under nitrogen atmosphere for 16 hours. The reaction mixture was partitioned between ethyl acetate (5 mL) and water (10 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (2 × 5 mL). The combined organic extracts were washed with brine (3 × 5 mL), dried over sodium sulfate, and concentrated under vacuum. Purification by rapid column chromatography (Method 6, 4 g; heptane, 5%–100% ethyl acetate) yielded 18 mg (0.04 mmol, 58% of theoretical value) of the title compound.

[0371] LC-MS (Method 4): R t =4.16min; m / z=498 / 500(M+1) + 1H NMR(400MHz,DMSO-d6)δ9.81(d,J=8.1Hz,1H),8.64(d,J=5.6Hz,1H),8.09(d, J=5.6Hz,1H),7.90-7.83(m,1H),7.61-7.54(m,2H),7.26(d,J=7.6Hz,1H),7.2 3-7.15(m,1H),6.94-6.86(m,1H),6.81(dd,J=8.2,1.1Hz,1H),5.21(q,J=6.5 Hz,1H),4.33-4.16(m,2H),2.93(s,6H),2.27-2.15(m,1H),2.14-2.02(m,1H).

[0372] Examples of compounds S1-14 7-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxythiopheno[2,3-c]pyridine-2-carboxamide A mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxythieno[2,3-c]pyridine-2-carboxamide (40 mg, 0.10 mmol), (3,5-dichlorophenyl)boronic acid (20 mg, 0.11 mmol), and sodium carbonate (20 mg, 0.19 mmol) in 1,4-dioxane (1.00 mL) and water (0.15 mL) was purged with nitrogen. 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride (4 mg, 0.01 mmol) was added, and the resulting mixture was stirred at 60 °C in a sealed container under nitrogen atmosphere for 4 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (1 mL), and filtered. The filter cake was washed with ethyl acetate (1 mL), and the filtrate was concentrated under vacuum. Purification by rapid column chromatography (Method 6, 12 g; heptane, 5%-100% ethyl acetate) yielded 37 mg (0.08 mmol, 80% of theoretical value) of the title compound.

[0373] LC-MS (Method 2): R t =4.43min; m / z=485 / 487(M+1) + 1H NMR (400MHz, DMSO-d6) δ8.72(d,J=5.5Hz,1H),8.60(d,J=8.2Hz,1H),8.03-7.95(m,3H),7.86(t,J=1.9Hz,1H),7.27(d,J=7.6Hz,1H),7.23-7.1 5(m,1H),6.96-6.87(m,1H),6.82(dd,J=8.2,1.0Hz,1H),5.30(q,J=6.5Hz,1H),4.27(dd,J=6.3,4.4Hz,2H),4.12(s,3H),2.18(q,J=6.4Hz,2H).

[0374] Examples of compounds S1-15 7-(3-Chlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxythiopheno[2,3-c]pyridine-2-carboxamide A mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxythieno[2,3-c]pyridine-2-carboxamide (40 mg, 0.10 mmol), (3-chlorophenyl)boronic acid (16 mg, 0.11 mmol), and sodium carbonate (20 mg, 0.19 mmol) in 1,4-dioxane (1.00 mL) and water (0.15 mL) was purged with nitrogen. 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride (4 mg, 0.01 mmol) was added, and the resulting mixture was stirred at 60 °C in a sealed container under nitrogen atmosphere for 4 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (1 mL), and filtered. The filter cake was washed with ethyl acetate (1 mL), and the filtrate was concentrated under vacuum. Purification was performed by rapid column chromatography (Method 6, 12 g; heptane, 5%–100% ethyl acetate), preparative HPLC (Method 11), and grinding in diisopropyl ether to give 23 mg (0.05 mmol, 53% of theoretical value) of the title compound.

[0375] LC-MS (Method 2): R t =4.20min; m / z=451 / 453(M+1) + 1H NMR(400MHz,DMSO-d6)δ8.71(d,J=5.4Hz,1H),8.57(d,J=8.2Hz,1H),8.04-7 .98(m,2H),7.94(d,J=5.5Hz,1H),7.70-7.63(m,2H),7.27(d,J=7.6Hz,1H), 7.23-7.15(m,1H),6.95-6.88(m,1H),6.82(dd,J=8.2,1.0Hz,1H),5.29(q,J =6.4Hz, 1H), 4.27 (dd, J = 6.4, 4.4Hz, 2H), 4.12 (s, 3H), 2.18 (q, J = 6.2Hz, 2H).

[0376] Examples of compounds S1-16 7-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxythiopheno[2,3-c]pyridine-2-carboxamide The stirred mixture of 7-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methoxythieno[2,3-c]pyridine-2-carboxamide (80 mg, 0.19 mmol), (2,3-dichlorophenyl)boronic acid (40 mg, 0.21 mmol), and sodium carbonate (40 mg, 0.38 mmol) in 1,4-dioxane (2.0 mL) and water (0.3 mL) was purged with nitrogen. 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride (9 mg, 0.01 mmol) was added, and the resulting mixture was stirred at 70 °C in a sealed container under nitrogen atmosphere for 4 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (1 mL), and filtered. The filter cake was washed with ethyl acetate (1 mL), and the filtrate was concentrated under vacuum. Purification by rapid column chromatography (Method 6, 12 g; toluene, 5%-100% diisopropyl ether) yielded 68 mg (0.14 mmol, 73% of theoretical value) of the title compound.

[0377] LC-MS (Method 4): R t =4.08min; m / z=485 / 487(M+1) + 1H NMR (400MHz, DMSO-d6) δ8.69(d,J=5.6Hz,1H),8.54(d,J=8.3Hz,1H),8.01(d,J=5.6Hz,1H),7.91-7.83(m,1H),7.61-7.55(m,2H),7.24(d,J=7.5Hz, 1H),7.21-7.14(m,1H),6.93-6.86(m,1H),6.84-6.76(m,1H),5.26(q,J=6 .6Hz, 1H), 4.25 (dd, J = 6.1, 4.5Hz, 2H), 4.15 (s, 3H), 2.15 (q, J = 6.2Hz, 2H).

[0378] Examples of compounds S1-17 7-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-fluoro-3-(morpholin-4-yl)-1-benzothiophene-2-carboxamide LC-MS (Method 15): Rt = 1.41 min; MS (ESI positive (ESIpos)): m / z = 557 [M+H] + ¹H NMR (peak list): (400MHz, DMSO-d6)δ [ppm]: -0.149 (1.79), -0.008 (16.00), 0.008 (14.78), 0.146 (1.88), 1.235 (0.66), 2.162 (7.53), 2.323 (1.88), 2.327 (2.64), 2.332 (1.88), 2.366 (2.35), 2.524 (8.85), 2.66 5(2.35),2.670(3.01),2.674(2.26),2.710(2.64),3.032(3.48),4.158(3.01),4.173(2.45),4.302(4.61),4.312(2.82),4.330(3.48),5.099(4.71),5.115(4.61),5.754(11.76),6.879(7.91),6.899(8. 94), 6.915(4.71), 6.933(9.51), 6.952(5.55), 7.234(4.14), 7.238(4.71), 7.255(7.25), 7.273(3.58), 7.276(3.67), 7.324(2.82), 7.341(5.08), 7.360(2.64), 7.441(5.08), 7.462(9.32), 7.469(5.27), 7.478(4.89),7.490(12.24),7.506(8.00),7.518(8.28),7.527(10.92),7.538(4.42),7.547(10.54),7.566(4.52),7.816(9.60),7.820(9.79),7.836(8.38),7.840(8.19),10.427(4.14),10.440(4.14).

[0379] Compound S1-18 of the Examples 7-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-fluoro-3-(morpholin-4-yl)-1-benzothiophene-2-carboxamide LC-MS (Method 15): R t =1.50 min; MS (ESI positive): m / z = 557 [M+H] + 1H NMR (peak list): (600MHz, DMSO-d6)δ [ppm]: -0.023 (1.36), 0.005 (2.27), 1.232 (2.59), 2.157 (0.49), 2.164 (0.68), 2.173 (1.33), 2.181 (3.20), 2.187 (3.62), 2.195 (2.36), 2.203 (1.61), 2.210 (1.16), 2.219 (0.42), 2.227 (0.41), 2.387 ( 0.51), 2.518(1.40), 2.521(1.43), 2.524(1.13), 2.615(0.66), 3.016(0.53), 4.139(1.01), 4.145(1.07), 4.158(1.76), 4.174(1.43), 4.180(1.11), 4.317(1.11), 4.324(1.98), 4.331(1.28), 4.336(1.10), 4.343(1.70), 4.350(0.8 7), 5.120(1.02), 5.127(2.16), 5.138(2.09), 5.146(0.92), 5.761(7.62), 6.892(3.87), 6.905(4.13), 6.931(2.03), 6.943(3.96), 6.956(2.20), 7.249(1.87), 7.252(1.92), 7.264(3.16), 7.275(1.61), 7.278(1.66), 7.344(3.26), 7.357(3.11),7.461(2.42),7.474(3.01),7.480(2.46),7.493(2.72),7.630(2.85),7.638(2.92),7.644(2.69),7.651(2.44),7.722(15.12),7.725(16.00),7.785(4.30),7.788(7.12),7.791(3.39),10.462(3.29),10.473(3.14).

[0380] (Target) Example Compound (S2) Compound S2-1 of Example 7-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methyl-3H-imidazo[4,5-b]pyridine-2-carboxamide Step 1: Ethyl 7-(2,3-dichlorophenyl)-3-methyl-3H-imidazo[4,5-b]pyridine-2-carboxylate Ethyl 7-bromo-3-methyl-3H-imidazo[4,5-b]pyridine-2-carboxylate [CAS2090992-55-3] (1 g, 3.52 mmol), 2,3-dichlorophenylboronic acid (1 g, 5.28 mmol), and potassium fluoride (0.61 g, 10.5 mmol) were mixed with 50 mL of tetrahydrofuran and 4 mL of water. The mixture was degassed with argon for 5 min. Tris(dibenzylacetone)dipalladium(0) (0.32 g, 0.35 mmol) and tri-tert-butylphosphine tetrafluoroborate (0.2 g, 0.7 mmol) were added. The mixture was heated to 60 °C for 4 h. After cooling to room temperature, the mixture was diluted with water (10 mL) and extracted twice with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and evaporated under vacuum. The remaining residue was purified by silica gel chromatography using an ethyl acetate / cyclohexane gradient to give 0.96 g (72.8%) of ethyl 7-(2,3-dichlorophenyl)-3-methyl-3H-imidazo[4,5-b]pyridine-2-carboxylate as a yellow oil.

[0381] LC-MS (Method 13): Retention index 932; m / z = 350.1; 352.0 (M+H) + 1 H-NMR (400MHz, DMSO-d 6) δ8.68-8.67(d,1H),7.84-7.82(d,1H),7.58-7.50(m,2H),7.47-7.45(d,1H),4.44-4.39(q,2H),1.37-1.31(t,3H).

[0382] Step 2: 7-(2,3-dichlorophenyl)-3-methyl-3H-imidazo[4,5-b]pyridine-2-carboxylic acid Ethyl 7-(2,3-dichlorophenyl)-3-methyl-3H-imidazo[4,5-b]pyridine-2-carboxylate (0.45 g, 1.28 mmol) from step 1 was dissolved in 21 mL of dichloromethane. Boron tribromide (6.42 mL, 1 M in dichloromethane) was added dropwise at -10 °C and maintained at -10 °C for 1 hour. The reaction mixture was heated to room temperature overnight and slowly quenched with 20 mL of water. The organic layer was separated and the solvent was evaporated under reduced pressure. The crude product contained some decarboxylation impurities and was used as is in the next step.

[0383] LC-MS (Method 13): Retention index 923; m / z = 322.0; 324.0 (M+H) + Step 3: 7-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-methyl-3H-imidazo-[4,5-b]pyridine-2-carboxamide N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (67 mg, 0.34 mmol), 1-hydroxy-1H-benzotriazole (24 mg, 0.17 mmol), and 4-N,N-dimethylaminopyridine (21 mg, 0.17 mmol) were added to a stirred mixture of 7-(2,3-dichlorophenyl)-3-methyl-3H-imidazo[4,5-b]pyridine-2-carboxylic acid (crude material 122 mg, 0.34 mmol), (S)-chromium-4-amine hydrochloride (71 mg, 0.38 mmol), and N,N-diisopropylethylamine (135 mg, 1.04 mmol) in dichloromethane (7.5 mL) at room temperature. The resulting mixture was stirred overnight. The reaction mixture was mixed with water (10 mL) and the dichloromethane phase was separated. The aqueous phase was extracted again with dichloromethane. The combined organic layers were dried over a sodium sulfate / silica gel column and concentrated under vacuum. The title compound was purified by rapid chromatography using an ethyl acetate / cyclohexane gradient to yield 46 mg (27.1%).

[0384] LC-MS (Method 13): Retention index: 1089; m / z = 453.1; 455.1 (M+H) + 1 H-NMR(400MHz,DMSO-d 6)δ9.24(d,1H,NH),8.61(d,1H),7.75(d,1H),7.53-7.46(m,2H),7.41(d,1H),7.17-7.12(m,2H),6.86-6.83(t,1H) ,6.77(d,1H),5.33-5.28(q,1H),4.32-4.28(m,1H),4.20-4.16(m+s,1H+3H),2.23-2.18(m,1H),2.09-2.06(m,1H).

[0385] Compound S2-2 (Example) 7-(2,3-Dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-3-methyl-3H-imidazo[4,5-b]pyridine-2-carboxamide This embodiment is prepared similarly to embodiment S2-1.

[0386] LC-MS (Method 13): Retention index: 1163; m / z = 437.1; 439.1 (M+H) + 1 H-NMR(400MHz,DMSO-d 6)δ9.13(d,1H,NH),8.61(d,1H),7.76(d,1H),7.54-7.47(m,2H),7.41(d,1H),7.26-7.15(m,4H),5.59 -5.52(q,1H),4.19(s,3H),3.02-2.95(m,1H),2.86-2.78(m,1H),2.42-2.36(m,1H),2.15-2.10(m,1H).

[0387] Compound S2-3 of the Examples 4-(2,6-Dichloropyridin-4-yl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1-(propyl-2-yl)-1H-indole-2-carboxamide This embodiment is prepared similarly to embodiment S2-1.

[0388] Compound S2-4 of the Examples N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1-(propyl-2-yl)-4-(2,3,5-trichlorophenyl)-1H-indole-2-carboxamide This embodiment is prepared similarly to embodiment S2-1.

[0389] Compounds S2-5 in Examples 4-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1-(propyl-2-yl)-1H-indole-2-carboxamide This embodiment is prepared similarly to embodiment S2-1.

[0390] Examples of compounds S2-6 N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1-(propyl-2-yl)-4-(2,3,5-trifluorophenyl)-1H-indole-2-carboxamide This embodiment is prepared similarly to embodiment S2-1.

[0391] Compounds S2-7 in Examples 4-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1-(propyl-2-yl)-1H-indole-2-carboxamide This embodiment is prepared similarly to embodiment S2-1.

[0392] (Target) Example Compound (S3) Compound S3-1 of Example 8-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-3-(prop-2-yl)imidazo[1,2-a]pyridine-2-carboxamide

[0393] (Target) Example Compound (S4) Compound S4-1 of Example 4-Chloro-1-(2,6-difluorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide Diethyl cyanophosphonate (69 mg, 0.42 mmol, 0.06 mL) was added to a solution of (S)-chromium-4-amine hydrochloride (72 mg, 0.39 mmol), 4-chloro-1-(2,6-difluorophenyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (100 mg, 0.32 mmol), and triethylamine (98 mg, 0.97 mmol, 0.14 mL) in dichloromethane (4.0 mL). The mixture was stirred at room temperature for 16 h. Volatiles were removed under vacuum. Purification by rapid column chromatography (Method 6; 24 g; heptane, 0% to 50% ethyl acetate) yielded 110 mg (0.25 mmol, 77% of theoretical value) of the title compound.

[0394] LC-MS (Method 4): R t =3.92 min; m / z = 441(M+H) + 1H NMR (400MHz, DMSO-d6) δ9.21 (d, J = 8.1Hz, 1H), 8.78 (s, 1H), 8.69 (s, 1H), 7.77 (dd d,J=14.9,8.5,6.4Hz,1H),7.49(t,J=8.4Hz,2H),7.36(d,J=7.2Hz,1H),7.21-7. 13(m,1H),6.97-6.88(m,1H),6.80(d,J=8.1Hz,1H),5.32-5.17(m,1H),4.36-4.1 6(m,2H),2.21(ddt,J=13.5,8.4,4.3Hz,1H),2.06(dtd,J=13.5,6.5,3.0Hz,1H).

[0395] Example Compound S4-2 1-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide Diethyl cyanophosphonate (58 mg, 0.36 mmol, 0.05 mL) was added to a solution of 1-(3,5-dichlorophenyl)-4-(dimethylamino)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (100 mg, 0.27 mmol), triethylamine (83 mg, 0.82 mmol, 0.11 mL), and (S)-chromium-4-amine hydrochloride (61 mg, 0.33 mmol) in dichloromethane (4.0 mL). The mixture was stirred at room temperature for 16 h. A precipitate formed. The solid was filtered off and dried. 45 mg (0.09 mmol, 33% of theoretical value) of the title compound was given.

[0396] LC-MS (Method 4): R t =4.58min; m / z=496 / 498(M+H) + 1H NMR(400MHz,DMSO-d6)δ9.06(d,J=8.2Hz,1H),8.42(d,J=1.8Hz,2H),8.37(s,1 H),7.53(t,J=1.8Hz,1H),7.36(d,J=7.4Hz,1H),7.23-7.12(m,1H),6.93(t,J=7 .0Hz,1H),6.80(d,J=8.2Hz,1H),5.21(q,J=6.1Hz,1H),4.33-4.18(m,2H),3.05 (s, 6H), 2.68 (s, 3H), 2.18 (dd, J = 8.9, 4.5Hz, 1H), 2.03 (dd, J = 14.0, 3.3Hz, 1H).

[0397] Example Compound S4-3 1-(2,6-Difluorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide Diethyl cyanophosphonate (82 mg, 0.50 mmol, 0.08 mL) was added to a solution of (S)-chromium-4-amine hydrochloride (86 mg, 0.46 mmol), 1-(2,6-difluorophenyl)-4-(dimethylamino)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (144 mg, 0.39 mmol; 89% purity) and triethylamine (117 mg, 1.16 mmol, 0.16 mL) in dichloromethane (4.0 mL). The mixture was stirred at room temperature for 16 h and concentrated under vacuum. Purification by rapid column chromatography (Method 6; 24 g; heptane, 0%–50% ethyl acetate) gave 78 mg (0.16 mmol, 43% of theoretical value) of the title compound.

[0398] LC-MS (Method 4): R t =3.75min; m / z = 464(M+H) + 1H NMR(400MHz,DMSO-d6)δ8.99(d,J=8.2Hz,1H),8.16(s,1H),7.67(ddd,J=14.8,8.5, 6.4Hz,1H),7.39(t,J=8.6Hz,2H),7.32(d,J=7.4Hz,1H),7.19-7.13(m,1H),6.91(t ,J=7.1Hz,1H),6.79(d,J=8.1Hz,1H),5.25-5.14(m,1H),4.24(qd,J=12.4,11.1,5. 3Hz, 2H), 3.07 (s, 6H), 2.66 (s, 3H), 2.17 (dq, J = 9.6, 4.6Hz, 1H), 2.09-1.93 (m, 1H).

[0399] Example Compound S4-4 1-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide Diethyl cyanophosphonate (103 mg, 0.63 mmol, 0.10 mL) was added to a solution of (S)-chromium-4-amine hydrochloride (108 mg, 0.58 mmol), 1-(3,5-dichlorophenyl)-4-(dimethylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (170 mg, 0.48 mmol), and triethylamine (147 mg, 1.45 mmol, 0.20 mL) in dichloromethane (4.0 mL). The mixture was stirred at room temperature for 16 h and concentrated under vacuum. The residue was milled in dichloromethane. The solid was filtered off and dried. 145 mg (0.30 mmol, 62% of theoretical value) of the title compound was given.

[0400] LC-MS (Method 4): R t =4.54min; m / z=482 / 484(M+H) + 1H NMR(400MHz,DMSO-d6)δ8.98(d,J=8.2Hz,1H),8.62(s,1H),8.46(d,J=1.9Hz,2 H),8.28(s,1H),7.54(t,J=1.9Hz,1H),7.33(d,J=7.3Hz,1H),7.22-7.11(m,1H ),6.96-6.87(m,1H),6.80(d,J=8.2Hz,1H),5.25-5.14(m,1H),4.25(q,J=7.9, 6.2Hz, 2H), 3.27 (s, 6H), 2.24-2.10 (m, 1H), 2.02 (dq, J = 13.8, 5.3, 4.8Hz, 1H).

[0401] Examples of compounds S4-5 1-(2,6-Difluorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(dimethylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide Diethyl cyanophosphonate (79 mg, 0.48 mmol, 0.07 mL) was added to a solution of (S)-chromium-4-amine hydrochloride (83 mg, 0.45 mmol), 1-(2,6-difluorophenyl)-4-(dimethylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (118 mg, 0.37 mmol), and triethylamine (113 mg, 1.11 mmol, 0.16 mL) in dichloromethane (4.0 mL). The mixture was stirred at room temperature for 16 h and concentrated under vacuum. Purification by rapid column chromatography (Method 6; 24 g; heptane, 0%–50% ethyl acetate) and preparative HPLC (Method 10) yielded 45 mg (0.10 mmol, 27% of theoretical value) of the title compound.

[0402] LC-MS (Method 4): R t =3.60min; m / z = 450(M+H) + .

[0403] Examples of compounds S4-6 1-(4-Chlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-4-(propyl-2-yl)-1H-benzotriazole-5-carboxamide Examples of compounds S4-7 N-[(1S)-2,3-dihydro-1H-inden-1-yl]-1-phenyl-4-(propyl-2-yl)-1H-benzotriazole-5-carboxamide Examples of compounds S4-8 1-(3-Chlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-4-(propyl-2-yl)-1H-benzotriazole-5-carboxamide Examples of compounds S4-9 N-[(1S)-2,3-dihydro-1H-inden-1-yl]-4-(propyl-2-yl)-1-[3-(trifluoromethyl)phenyl]-1H-benzotriazole-5-carboxamide Compound S4-10 of the Examples 1-(2-Chlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-4-(propyl-2-yl)-1H-benzotriazole-5-carboxamide (Target) Example Compound (S5) Compound S5-1 of the Example 3-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-7-(dimethylamino)-1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-carboxamide LC-MS (Method 15): Rt = 1.04 min; MS (ESI positive): m / z = 512 [M+H]+ ¹H NMR (peak list): (400MHz, DMSO-d6)δ[ppm]: -0.008 (3.14), 0.008 (1.66), 2.523 (1.06), 2.807 (16.00), 3.586 (7.10), 4.099 (0.52), 4.107 (0.42), 4.124 (0.62), 4.149 (0.43), 4.767 (0.48), 4.786 (0.47), 5.754 (0.50), 6 .743(0.83),6.761(0.90),6.872(0.89),6.890(0.55),7.053(0.80),7.072(0.64),7.120(0.46),7.140(0.72),7.407(1.44),7.703(0.75),7.707(1.30),7.712(0.68),8.055(2.97),8.873(0.76),8.893(0.73).

[0404] (Target) Example Compound (S6) Compound S6-1 of Example 5-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]naphthalene-2-carboxamide Compound S6-2 of the Example 1-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]isoquinoline-6-carboxamide

[0405] (Target) Example Compound (S7) Compound S7-1 of the Example 8-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-7-oxo-7,8-dihydro-1,8-naphthidine-3-carboxamide LC-MS (Method 15): Rt = 1.03 min; MS (ESI positive): m / z = 466 [M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=9.05(d,1H),8.86(d,1H),8.71(d,1H),8.14(d,1H),7.75(t,1H), 7.56(d,2H),7.22-7.14(m,2H),6.90-6.79(m,3H),5.29(q,1H),4.33-4.22(m,2H),2.19-2.00(m,2H) Compound S7-2 of the Example 1-(4-chlorobenzyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-5-(dimethylamino)-2-oxo-1,2-dihydro-1,7-naphthidine-6-carboxamide (Target) Example Compound (S8) Example compound S8a-1 8-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-4-(propyl-2-yl)-2H-chromene-3-carboxamide Example compound S8a-2 8-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2-oxo-4-(propyl-2-yl)-2H-chromene-3-carboxamide Triethylamine (0.6 mL, 4.75 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxofluorophosphate (663 mg, 1.74 mmol) were added to a mixture of crude 8-(3,5-dichlorophenyl)-4-isopropyl-2-oxo-2H-chromene-3-carboxylate (303 mg, 0.79 mmol) in anhydrous N,N-dimethylformamide (10 mL). After stirring for 30 min, (S)-chromene-4-amine hydrochloride (323 mg, 1.74 mmol) was added. The reaction mixture was stirred for 1.5 h and water was added. The resulting precipitate was filtered off, washed with water, and dried in air. Purification by rapid column chromatography (Method 6; 24 g; heptane, 2%-100% ethyl acetate) yielded 125 mg (0.25 mmol; 31% of theoretical value) of the title compound.

[0406] LC-MS (Method 4): R t =4.18min; m / z=506 / 508(MH) - 1H NMR (400MHz, DMSO-d) 6) δ8.93(d,J=8.2Hz,1H),8.13(d,J=8.0Hz,1H),7.72(m,2H),7.63(d,J=1.9H z,2H),7.48(t,J=7.8Hz,1H),7.33(d,J=7.5Hz,1H),7.19-7.11(m,1H),6.90( t,J=7.4Hz,1H),6.78(d,J=8.2Hz,1H),5.18(q,J=6.3Hz,1H),4.23(m,2H),3. 53-3.38(m,1H),2.21-2.09(m,1H),2.02-1.92(m,1H),1.45(t,J=7.6Hz,6H).

[0407] Example compound S8a-3 8-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2-oxo-2H-chromene-3-carboxamide Step 1: Ethyl 8-bromo-2-oxo-2H-chromene-3-carboxylate Diethyl malonate (1.20 g, 7.5 mmol) and piperidine (85 mg, 1.0 mmol) were added to a solution of 3-bromo-2-hydroxybenzaldehyde (1.00 g, 5.0 mmol) in ethanol (15 mL). The resulting mixture was stirred at 80 °C for 6 hours. After cooling to room temperature, the solvent was removed under vacuum and ethyl acetate was added. The resulting mixture was washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to give 700 mg (34%) of the product as a white solid.

[0408] LC-MS (Analysis Method A, 0.01-2.00 min, 5-95% B): R t =1.06min; MS (ESI positive): m / z = 297(M+H) + Step 2: 8-Bromo-2-oxo-2H-chromene-3-carboxylic acid Sodium hydroxide (170 mg, 4.4 mmol in 7 mL of water) was added to a solution of ethyl 8-bromo-2-oxo-2H-chromene-3-carboxylate (650 mg, 2.2 mmol) in tetrahydrofuran (13 mL). The resulting mixture was stirred overnight at room temperature. After the reaction was complete, the solvent was removed under vacuum. Water was added and then dilute hydrochloric acid (1 N) was added to adjust the pH to 1. The precipitated solid was collected by filtration and dried to give 540 mg (92%) of the product as a grayish-white solid.

[0409] LC-MS (Analysis Method A, 0.01-2.00 min, 5-95% B): R t =0.76min; MS (ESI positive): m / z = 269(M+H) + Step 3: 8-Bromo-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2-oxo-2H-chromene-3-carboxamide HATU (530 mg, 1.4 mmol), N,N-diisopropylethylamine (360 mg, 2.8 mmol), and (S)-chromium-4-amine (166 mg, 1.1 mmol) were added to a solution of 8-bromo-2-oxo-2H-chromene-3-carboxylic acid (250 mg, 0.93 mmol) in N,N-dimethylformamide (5 mL). The resulting mixture was stirred at room temperature for 1 hour. After the reaction was complete, water was added, and the precipitated solid was collected by filtration, washed with water, and dried under vacuum to give 200 mg (50%) of the product as a yellow solid.

[0410] LC-MS (Analytical Method E, 0.01-2.00 min 5-95% B): R t =1.20min; MS (ESI positive): m / z = 400(M+H) + Step 4: 8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2-oxo-2H-chromene-3-carboxamide To a solution of (S)-8-bromo-N-(chroman-4-yl)-2-oxo-2H-chromene-3-carboxamide (100 mg, 0.3 mmol) in a mixed solvent of tetrahydrofuran / water (v:v4:1, 2.5 mL), 2,3-dichlorophenylboronic acid (48 mg, 0.3 mmol), tris(dibenzylacetone)dipalladium chloroform complex (13 mg, 0.01 mmol), tri-tert-butylphosphine tetrafluoroborate (7 mg, 0.02 mmol), and potassium fluoride (44 mg, 0.8 mmol) were added. The resulting mixture was stirred overnight at 60 °C under a nitrogen atmosphere. After cooling to room temperature, water was added, and the resulting mixture was extracted with ethyl acetate. The combined organic phases were washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) and preparative HPLC [column: Xbridge Prep C18, 5 μm, 19*150 mm; mobile phase A: water (0.1% FA), mobile phase B: acetonitrile; gradient: 65% B to 95% B over 8 min] to give 50.9 mg (43%) of the product as a white solid.

[0411] 1 ¹H-NMR (400MHz, DMSO-d6): δ [ppm] = 2.07-2.08 (m, 1H), 2.17-2.19 (m, 1H), 4.18-4.20 (m, 1H), 4.25-4.28 (m, 1H), 5.22 (q, 1H), 6.79 (d, 1H), 6.89 (t, 1H), 7.18 (t, 1H), 7.24-7.27 (m, 1H), 7.45-7.58 (m, 3H), 7.71 (d, 1H), 7.79 (d, 1H), 8.10 (d, 1H), 8.87 (d, 1H), 8.93 (s, 1H); LC-MS (Analytical Method C, 0.01-3.00 min 5-95% B): R t =2.05min; MS (ESI positive): m / z=466 (M+H) + .

[0412] Example compound S8a-4 8-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2H-chromene-3-carboxamide Add 3,5-dichlorophenylboronic acid (50 mg, 0.3 mmol), tris(dibenzylacetone)dipalladium chloroform complex (13 mg, 0.01 mmol), tri-tert-butylphosphine tetrafluoroborate (8 mg, 0.01 mmol), and potassium fluoride (45 mg, 0.8 mmol) to a solution of (S)-8-bromo-N-(chroman-4-yl)-2H-chromenyl-3-carboxamide (100 mg, 0.3 mmol) [as described in steps 1-4 of Examples S8a-5] in a mixed solvent of tetrahydrofuran / water (v:v = 4:1, 2.5 mL). Stir the resulting mixture overnight at 60 °C under a nitrogen atmosphere. After cooling to room temperature, evaporate the solvent and redissolve the residue in ethyl acetate. Wash the mixture with water, dry it over anhydrous sodium sulfate, and evaporate to dryness. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) and preparative HPLC [column: Kinetex 5µm EVO C18 OBD, 21.2*150mm, 5µm; mobile phase A: water (0.1% FA), mobile phase B: acetonitrile; gradient: 10% B to 50% B over 10 min] to give 53.8 mg (46%) of a white solid. MS (ESI positive): m / z = 452 (M+H) + .

[0413] 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.96-2.02(m,2H),4.18-4.31(m,2H),5.00(s,2H),5.17(q,1H),6.80(d,1H) ,6.89(t,1H),7.07(t,1H),7.15-7.17(m,2H),7.27(d,1H),7.35-7.41(m,2H),7.58-7.61(m,3H),8.64(d,1H); LC-MS (Analysis Method C, 0.01-3.00 min, 5-95% B): R t =1.95min; MS (ESI positive): m / z = 452(M+H) + .

[0414] Example compound S8a-5 8-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2H-chromene-3-carboxamide Step 1: 2-((3-bromo-2-hydroxyphenyl)(hydroxy)methyl)tert-butyl acrylate A mixture of 3-bromo-2-hydroxybenzaldehyde (5.00 g, 24.9 mmol), tert-butyl acrylate (15.94 g, 124.4 mmol), and 1,4-diazabicyclo(2.2.2)octane (0.56 g, 5.0 mmol) was stirred at 65 °C for 2 days. After the reaction was complete, tert-butyl acrylate was removed under vacuum. Water was added, and the resulting mixture was extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 2:1) to give 3.00 g (37%) of a yellow oily product.

[0415] LC-MS (Analysis Method A, 0.01-1.80 min, 5-95% B): R t =0.94min; MS (ESI positive): m / z = 329(M+H) + .

[0416] Step 2: tert-butyl 8-bromo-2H-chromene-3-carboxylate Potassium hydroxide (392 mg, 7.0 mmol) was added to a solution of tert-butyl 2-((3-bromo-2-hydroxyphenyl)(hydroxy)methyl)acrylate (2.30 g, 7.00 mmol) in a mixed solvent of tetrahydrofuran / water (v:v = 1:2, 30 mL), and the resulting mixture was stirred under reflux for 5 hours. After cooling to room temperature, the solvent was removed under vacuum. Water was added, and the resulting mixture was extracted with ethyl acetate, and the combined organic phases were dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1). The collected fraction was concentrated to give 400 mg (18%) of the product as a colorless oil.

[0417] 1 H-NMR (400MHz, DMSO-d6): δ [ppm] = 1.50 (d, 9H), 5.01 (s, 2H), 6.91 (t, 1H), 7.36 (d, 1H), 7.40 (s, 1H), 7.53 (d, 1H).

[0418] Step 3: 8-Bromo-2H-chromene-3-carboxylic acid Trifluoroacetic acid (5 mL) was added to a solution of tert-butyl 8-bromo-2H-chromene-3-carboxylate (850 mg, 2.7 mmol) in dichloromethane (20 mL), and the resulting mixture was stirred at room temperature for 3 hours. After the reaction was complete, the solvent was removed under vacuum. Water was added, and a saturated sodium bicarbonate solution was added to adjust the pH to 7. The resulting mixture was extracted with dichloromethane; the combined organic phases were dried over anhydrous sodium sulfate and concentrated under vacuum to give 600 mg (85%) of the product as a yellow solid.

[0419] LC-MS (Analysis Method A, 0.01-2.00 min, 5-95% B): R t =0.90min; MS (ESI positive): m / z=255(M+H) + .

[0420] Step 4: 8-Bromo-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2H-chromene-3-carboxamide HATU (1.34 g, 3.53 mmol), N,N-diisopropylethylamine (912 mg, 7.1 mmol), and (S)-chromium-4-amine (421 mg, 2.8 mmol) were added to a solution of 8-bromo-2H-chromene-3-carboxylic acid (600 mg, 2.4 mmol) in N,N-dimethylformamide (10 mL). The resulting mixture was stirred at room temperature for 1 hour. After the reaction was complete, an aqueous brine solution was added to quench the reaction. The precipitated solid was collected by filtration, washed with water, and dried under vacuum to give 500 mg (55%) of the product as a yellow solid.

[0421] LC-MS (Analytical Method E, 0.01-2.00 min 5-95% B): R t =1.21min; MS (ESI positive): m / z = 386(M+H) + .

[0422] Step 5: 8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2H-chromene-3-carboxamide To a solution of (S)-8-bromo-N-(chroman-4-yl)-2H-chromene-3-carboxamide (100 mg, 0.3 mmol) in a mixed solvent of tetrahydrofuran / water (v:v 4:1, 2.5 mL), 2,3-dichlorophenylboronic acid (50 mg, 0.3 mmol), tris(dibenzylacetone)dipalladium chloroform complex (13 mg, 0.01 mmol), tri-tert-butylphosphine tetrafluoroborate (8 mg, 0.01 mmol), and potassium fluoride (45 mg, 0.8 mmol) were added. The resulting mixture was stirred overnight at 60 °C under a nitrogen atmosphere. After cooling to room temperature, the solvent was evaporated and the residue was redissolved in ethyl acetate. The mixture was washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) and preparative HPLC [column: Kinetex 5um EVOC18 OBD, 21.2*150mm, 5um; mobile phase A: water (0.1% FA), mobile phase B: acetonitrile; gradient: 10% B to 60% B over 12 min] to obtain 54.6 mg (46%) of a white solid product.

[0423] 1 H-NMR (400MHz, DMSO-d6): δ [ppm] = 1.96-2.08 (m, 2H), 4.22-4.29 (m, 2H), 4.93 (s, 2H), 5.15 (q, 1H), 6.80 (d, 1H), 6.86 -6.90(m,1H),7.05(t,1H),7.14-7.18(m,3H),7.28(d,1H),7.33(d,1H),7.40-7.44(m,2H),7.67(d,1H),8.64(d,1H); LC-MS (Analysis Method C, 0.01-3.00 min, 5-95% B): R t =1.95min; MS (ESI positive): m / z = 452(M+H) + .

[0424] Example compound S8a-6 8-(3,5-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-4-(morpholin-4-yl)-2-oxo-1,2-dihydroquinoline-3-carboxamide Example compound S8b-1 8-(3,5-Dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dimethyl-4H-chromene-3-carboxamide Step 1: 2-Bromo-6-(1-hydroxyethyl)phenol At 0 °C under a nitrogen atmosphere, a solution of methyl magnesium bromide (3M in ether, 150 mL, 450 mmol, 3.0 eq) was added dropwise to a cold solution of 3-bromo-2-hydroxybenzaldehyde (30.0 g, 150.0 mmol, 1.0 eq) in anhydrous diethyl ether (300 mL). The resulting reaction mixture was allowed to reach ambient temperature for 2 h. The reaction progress was monitored by TLC. The reaction mixture was cooled to 0 °C and quenched with 1M HCl. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give a crude product, which was purified by rapid column chromatography (100-200 silica gel, 50% EtOAc-hexane) to give pure 2-bromo-6-(1-hydroxyethyl)phenol (24.0 g, 74% of theoretical value) as a grayish-white solid.

[0425] TLC system: 30% EtOAc in petroleum ether 1H-NMR (400MHz, CDCl3) δ 7.61 (broad peak, 1H), 7.40-7.37 (m, 1H), 7.05-7.03 (m, 1H), 6.76-6.72 (m, 1H), 5.08-5.05 (m, 1H), 3.00 (broad peak, 1H), 1.54-1.52 (d, 3H); R f Value: 0.9.

[0426] Step 2: Ethyl 8-bromo-2-hydroxy-2,4-dimethylchroman-3-carboxylate At room temperature, under a nitrogen atmosphere, 2-bromo-6-(1-hydroxyethyl)phenol (1.0 g, 4.61 mmol, 1.0 eq) was added to a stirred solution of 2-bromo-6-(1-hydroxyethyl)phenol (1.0 g, 4.61 mmol, 1.0 eq) in dichloroethane (15 mL). Molecular sieve (4.60 g), anhydrous FeCl3 (0.037 g, 0.23 mmol), followed by the addition of ethyl acetoacetate (1.20 g, 9.25 mmol), and the resulting solution was irradiated by microwave at 60 °C for 1.30 h. The reaction progress was monitored by TLC. After completion, the reaction mixture was filtered through a diatomaceous earth mat and thoroughly washed with dichloromethane. The filtrate was washed with saturated NaHCO3 solution and brine, dried over Na2SO4, and concentrated to obtain a crude compound. The crude compound was purified by rapid chromatography (20% EtOAc-hexane) to give pure ethyl 8-bromo-2-hydroxy-2,4-dimethylchroman-3-carboxylate (1.40 g, 92.3% of theoretical value) as a thick yellow liquid.

[0427] TLC system: 50% EtOAcR in petroleum ether f Value: 0.3.

[0428] Step 3: Ethyl 8-bromo-2,4-dimethyl-4H-chromene-3-carboxylate p-Toluenesulfonic acid (7.2 g, 41.9 mmol, 1.0 eq) was added to a stirred solution of ethyl 8-bromo-2-hydroxy-2,4-dimethylchromene-3-carboxylate (13.8 g, 41.9 mmol, 1.0 eq) in toluene (140 mL), and the resulting reaction mixture was refluxed for 1 h. The reaction progress was monitored by TLC. The reaction mixture was diluted with ethyl acetate and washed successively with saturated NaHCO3 and brine solution. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give a crude compound, which was further purified by rapid column chromatography (silica gel, 50% EtOAc / hexane) to give pure ethyl 8-bromo-2,4-dimethyl-4H-chromene-3-carboxylate (9.0 g, 68% of theoretical value) as a grayish-white solid.

[0429] TLC system: 50% EtOAc in petroleum ether ¹H-NMR (400MHz, CDCl₃) δ 7.61 (broad peak, ¹H), 7.40–7.38 (m, ¹H), 7.10–7.08 (m, ¹H), 6.96–6.92 (m, ¹H), 4.25 (m, 2H), 3.89 (q, ¹H), 2.45 (s, 3H), 1.36–1.34 (t, 3H), 1.28–1.26 (d, 3H); R f Value: 0.8.

[0430] Step 4: 8-Bromo-2,4-dimethyl-4H-chromene-3-carboxylic acid To a stirred solution of ethyl 8-bromo-2,4-dimethyl-4H-chromene-3-carboxylic acid (9.0 g, 29.0 mmol) in EtOH (90 mL), LiOH·H₂O (2.3 g, 58 mmol) in water (40 mL) was added, and the resulting reaction mixture was refluxed for 4 h. The reaction progress was monitored by TLC. Volatiles were removed under reduced pressure, and the obtained crude product was poured into cold water and washed with dichloromethane. The aqueous layer was acidified with 2N HCl aqueous solution (pH = 2) and extracted with 10% MeOH-CH₂Cl₂ (3 × 50 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give a crude compound, which was further purified by grinding with 10% EtOAc / diethyl ether to give 8-bromo-2,4-dimethyl-4H-chromene-3-carboxylic acid (5.25 g, 64.1% of theoretical value) as a grayish-white solid. Purity: 99.6% LC-MS (Method 14): R t =2.20min; TLC system: 10% MeOH-CH2Cl2 1 H-NMR (400MHz, DMSO-d 6) δ7.51-7.49(m,1H),7.31-7.29(m,1H),7.09-7.05(m,1H),3.83(q,1H),2.37(s,3H),1.22-1.20(d,3H); R f Value: 0.1 LC-MS method Mobile phase-A: 10 mm ammonium formate in water Mobile phase-B: ACN Column-Xbridge BEH C18 2.5μm, 2.1×50mm Flow rate: 0.7 mL / min, temperature: 40℃ Time (min) and %B: 0-5; 3.0-100; 3.5-100; 3.8-5; 4.3-5; Gas flow rate 1.6 SLM Evaporator temperature 40℃.

[0431] Step 5: 8-Bromo-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dimethyl-4H-chromene-3-carboxamide Two drops of DMF were added to a suspension of 8-bromo-2,4-dimethyl-4H-chromene-3-carboxylic acid (949 mg, 3.35 mmol) in anhydrous toluene (15 mL). Then, thionyl chloride (450 mg, 3.78 mmol) was added dropwise over 2 minutes. After stirring at 70 °C for 4 h, the mixture was cooled to room temperature, and stirring was continued at 40 °C for 18 h after the addition of (1S)-indan-1-amine hydrochloride (460 mg, 3.45 mmol) and N,N-diisopropylethylamine (950 mg, 7.35 mmol).

[0432] The solvent was removed under reduced pressure, and the residue was partitioned between water (50 mL) and dichloromethane (50 mL). The combined organic layers were dried under reduced pressure and removed, leaving 924 mg (59% of the theoretical value) of the title compound.

[0433] LC-MS3-exponent = 1033; m / z = 397.1; 399.1(M+H) + 1 H-NMR (400MHz, DMSO-d 6) δ8.44-8.40(m,1H),7.48-7.45(m,1H),7.29-7.20(m,5H),7.03-6.99(m,1H),5.46-5.42(m,1H),3.86-1.23(m,11H).

[0434] Step 6: 8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dimethyl-4H-chromene-3-carboxamide The mixture of 8-bromo-N-[1S)-2,3-dihydro-1H-inden-1-yl]-2,4-dimethyl-4H-chromene-3-carboxamide (120 mg, 0.301 mmol) and bis(triphenylphosphine)palladium(II) dichloride (21 mg, 0.03 mmol) in 1,4-dioxane (10 mL) was stirred at room temperature for 2 h. After the addition of (3,5-dichlorophenyl)boric acid (100 mg, 0.366 mmol), sodium carbonate (370 mg, 3.49 mmol), and water (1.30 mL), stirring was continued at 90 °C for 18 h. The mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with dichloromethane (3 × 20 mL). The solvent was dried under reduced pressure and removed. Purification by rapid chromatography (cyclohexane, 80%–20% ethyl acetate) yielded 3.4 mg (theoretical 2.4%) of the title compound as a brown solid.

[0435] LC-MS3-exponent = 1350; m / z = 463.1; 465.1(M+H) + 1 H-NMR(400MHz,DMSO-d 6) δ8.37-8.33(m,1H),7.61-7.56(m,3H),7.34-7.15(m,7H),5.48-5.42(m,1H),3.91-3.86(m,1H),2.99 -2.93(m,1H),2.86-2.78(m,1H),2.46-2.39(m,1H),2.02(s,3H),1.94-1.84(m,1H),1.31-1.29(m,3H).

[0436] Example compound S8b-2 2,4-Dimethyl-N-[(1S)-1,2,3,4-tetrahydronaphth-1-yl]-8-(2,3,5-trifluorophenyl)-4H-chromene-3-carboxamide Compound S8b-2 of Example was prepared in a similar manner to compound S8b-1 of Example.

[0437] 8-Bromo-2,4-dimethyl-N-[(1S)-1,2,3,4-tetrahydronaphth-1-yl]-4H-chromene-3-carboxamide In order to prepare compound S8b-2 of example, the intermediate compound 8-bromo-2,4-dimethyl-N-[(1S)-1,2,3,4-tetrahydronaphthyl-1-yl]-4H-chromene-3-carboxamide was prepared in a similar manner to that of the intermediate compound 8-bromo-N-[(1S)-2,3-dihydro-1H-indene-1-yl]-4H-chromene-3-carboxamide (step 1 in the preparation of compound S8b-1 of example).

[0438] LC-MS3-exponent = 1083; m / z = 411.1; 413.1(M+H) + 1 H-NMR(400MHz,DMSO-d 6) δ8.39-8.37(m,1H),7.46-6.98(m,7H),5.14-5.10(m,1H),3.88-3.83(m,1H),2.76-2.72( m,2H),2.08-2.07(d,3H),1.94-1.91(m,2H),1.76-1.74(m,2H),1.28-1.27(d,J=6.8Hz,3H).

[0439] Example compound S8b-3 N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-2,4-dimethyl-8-(2,3,5-trifluorophenyl)-4H-chromen-3-carboxamide Step 1: 8-Bromo-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2,4-dimethyl-4H-chromene-3-carboxamide 1,1'-carbonyldiimidazole (95 mg, 0.586 mmol) was added to a suspension of 8-bromo-2,4-dimethyl-4H-chromene-3-carboxylic acid (150 mg, 0.53 mmol) in anhydrous tetrahydrofuran (5 mL). After stirring at 60 °C for 18 h, the mixture was cooled to room temperature, and stirring was continued at 60 °C for 18 h after the addition of (4S)-3,4-dihydro-2H-chromene-4-amine hydrochloride (95 mg, 0.512 mmol) and N,N-diisopropylethylamine (500 mg, 3.869 mmol).

[0440] The solvent was removed under reduced pressure, and the residue was partitioned between water (50 mL) and dichloromethane (50 mL). The combined organic layers were dried under reduced pressure and removed, leaving 180 mg (82% of the theoretical value) of the crude compound. Purification by rapid chromatography (cyclohexane, 80%–20% ethyl acetate) gave 25 mg (11.4% of the theoretical value) of the title compound.

[0441] LC-MS3-index = 985 1 H-NMR(400MHz,DMSO-d 6)δ8.58-8.56(m,1H),7.47-6.77(m,7H),5.18(m,1H),4.25-4.21(m,2H),3 .88-3.86(m,1H),2.10-2.08(m,1H),2.08(d,3H),1.98(m,1H),1.26(d,3H).

[0442] Step 2: N-[(4S)-3,4-dihydro-2H-chromene-4-yl]-2,4-dimethyl-8-(2,3,5-trifluorophenyl)-4H-chromene-3-carboxamide S8b-3 The mixture of 8-bromo-N-[(4S)-3,4-dihydro-2H-chromen-4-yl]-2,4-dimethyl-4H-chromen-3-carboxamide (94 mg, 0.227 mmol) and bis(triphenylphosphine)palladium(II) dichloride (44 mg, 0.062 mmol) in 1,4-dioxane (10 mL) was stirred at room temperature for 2 h. After the addition of (2,3,5-trifluorophenyl)boronic acid (300 mg, 1.706 mmol), sodium carbonate (870 mg, 8.21 mmol), and water (3.30 mL), stirring was continued at 90 °C for 18 h. The mixture was cooled to room temperature, water was added, and the aqueous layer was extracted with dichloromethane (3 × 20 mL). The solvent was dried under reduced pressure and removed. Purification by rapid chromatography (cyclohexane, 80%–20% ethyl acetate) yielded 12 mg (10.5% of the theoretical value) of the title compound.

[0443] LC-MS7-exponent = 1091; m / z = 466.1(M+H)+ 1H-NMR(400MHz,DMSO-d6)δ8.51-8.49(m,1H),7.62-6.77(m,9H),5.16-5.11(m,1H),4.23-4.20(m,2H ),3.91-3.86(m,1H),2.12-2.08(m,1H),2.00-1.94(m,1H),1.94(s,3H),1.30-1.28(d,J=6.8Hz,3H).

[0444] (Target) Example Compound (S9) Example S9-1 2-[2-chloro-3-(trifluoromethyl)phenyl]-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]quinoxaline-6-carboxamide Compound S9-2 from Examples 2-(2-Chlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]quinoxaline-6-carboxamide Compound S9-3 of the Examples 2-(2-Chlorophenyl)-N-[(1S)-2,3-dihydro-1H-inden-1-yl]quinoxaline-6-carboxamide Example Compound S9-4 2-(2,3-Dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromene-4-yl]quinoxaline-6-carboxamide Example S9-5 2-(2,3-Dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-indene-1-yl]quinoxaline-6-carboxamide Example S9-6 2-[2-chloro-3-(trifluoromethyl)phenyl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]quinoxaline-6-carboxamide NMR Peak List Selected embodiments 1 H-NMR data with 1 The H-NMR peaks are listed in the form of a list. For each signal peak, list the δ value in ppm and the signal intensity in parentheses. The δ value-signal intensity pairs are separated by a semicolon.

[0445] The peak list of the embodiments therefore has the following form: δ1 (Intensity 1); δ2 (Intensity 2); ...; δ i (strength i );……;δ n (strength n ).

[0446] The intensity of a sharp signal is highly correlated with the signal in cm in the printed NMR spectrum example, showing the actual relationship of signal intensity. With a broad signal, multiple peaks or midpoints of the signal and their relative intensity compared to the strongest signal in the spectrum can be shown.

[0447] In order to target 1 To correct chemical shifts in NMR spectroscopy, we use the chemical shifts of tetramethylsilane and / or the solvent used, especially when measuring spectra in DMSO. Therefore, a tetramethylsilane peak may (but is not always) appear in the NMR peak list.

[0448] 1 The H-NMR peak list is similar to that of the classic 1 H-NMR printouts, and therefore typically contain all the peaks listed in classical NMR interpretations.

[0449] In addition, like the classic 1 Like H-NMR prints, they can show signals of solvent, stereoisomers of the target compound (which is also the subject of this invention), and / or impurity peaks.

[0450] To illustrate the compound signal in the δ range in solvents and / or water, in our1 The H-NMR peak list shows common peaks for solvents, such as the peaks of DMSO in DMSO-D6 and the peaks of water, and generally has high average intensity.

[0451] The peaks of the stereoisomers of the target compound and / or the peaks of impurities typically have an average intensity lower than that of the target compound (e.g., purity > 90%).

[0452] Such stereoisomers and / or impurities can be typical for a particular preparation method. Therefore, their peaks can help confirm the reproducibility of our preparation method via a "byproduct fingerprint".

[0453] Experts who calculate the peaks of the target compound using known methods (MestreC, ACD simulation, but also expected values ​​based on empirical evaluation) can optionally use additional intensity filters to separate the peaks of the target compound as needed. This separation is similar to classical... 1 Selection of relevant peaks in H-NMR interpretation.

[0454] Further details describing NMR data with peak lists can be found in the publication, Research Disclosure Database No. 564025#, “Citation of NMR Peaklist Data within Patent Applications”. .

[0456] Experimental Section - Bioassay Examples of this study involve testing once or multiple times in selected bioassays. When testing is performed more than once, data are reported as the mean or median, where... The mean, also known as the arithmetic mean, is the sum of the obtained values ​​divided by the number of tests. The median represents the middle value of a group of values ​​when ordered in ascending or descending order. If the number of values ​​in the dataset is odd, the median is the middle value. If the number of values ​​in the dataset is even, the median is the arithmetic mean of the two middle values.

[0457] Examples of synthesis may be performed once or multiple times. When synthesis is performed more than once, data from bioassays represent the average or median calculated using datasets obtained from tests of one or more synthetic batches.

[0458] The in vitro activity of the compounds of the present invention can be demonstrated in the following assays: In vitro assay 1: Caenorhabditis elegans Slo-1a cells were used in the recombinant Caenorhabditis elegans cell line. use Generate stable Caenorhabditis elegans CHO cell lines The CHO cell line was obtained from ATCC, accession number ATCC CRL-9096. For transfection with plasmid DNA to express *C. elegans* Slo-1a (accession number AAL28102), CHO cells were passaged to 40% confluence before adding transfection solution to the cell culture. The transfection solution consisted of 300 μL OptiMEM (Life Technologies, Nr.: 31985), 2 μL (=6 μg) plasmid DNA containing the *C. elegans* Slo-1a gene, and 9 μL FugeneHD (Promega, Nr.: E2311), which was added to the cells, and the cells were incubated at 37°C and 5% CO2 for 48 hours. The transfection medium was then replaced with selection medium containing additional G418 (2 mg / ml, Invitrogen, Nr.: 10131), and the cells were seeded in 384-well plates (300 cells / well). Several weeks later, K+ channel expression in the remaining surviving cells was tested using a voltage-sensitive dye (Membrane Potential Assay Kit, MolecularDevices Nr.: R8034). Positive cell clones were purified using limiting dilution techniques. For this purpose, clones exhibiting the highest and strongest signal 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 a finally stable CHO cell line expressing *C. elegans* Slo-1a.

[0459] Cell culture conditions Cells were cultured at 37°C and 5% CO2 in MEMα containing Gutamax I (Invitrogen, Nr.: 32571) supplemented with 10% (v / v) heat-inactivated fetal bovine serum (Invitrogen, Nr.: 10500) and G418 (1 mg / ml, Invitrogen, Nr.: 10131). Cells were isolated using Accutase (Sigma, Nr.: A6964).

[0460] Membrane potential measurement Laboratory compound assays were performed on 384-well microtiter plates (MTP, Greiner, Nr.: 781092). Cells were seeded at 8000 cells / well on 384-well MTP plates and cultured at 37°C and 5% CO2 for 20–24 hours. After removing the cell culture medium, cells were washed once with Tyrode's solution (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 a voltage-sensitive dye from a membrane potential assay kit diluted in Tyrode's solution for 1 hour at room temperature.

[0461] After starting fluorescence measurement using FLIPR Tetra (Molecular Devices, Exc. 510-545nm, Emm. 565-625nm), the test compound was added, followed by the addition of KCl Tyrode solution (final concentration: 70mM KCl, 2mM CaCl2, 1mM MgCl2, 0.8mM NaH2PO4, 5mM glucose, 28mM Hepes, pH 7.4, including voltage-sensitive dye). Measurement was completed after 7 minutes.

[0462] statistics To perform curve fitting and calculate the half-maximum effective concentration (EC50) 50 The data was evaluated using ActivityBase XLfit software (IDBS) and reported as a negative common logarithm (pE). 50 ).

[0463] For the following example compounds, pE 50 Listed in Table 1.

[0464] Table 1: *nd = Undetermined.

[0465] In vitro assay 2: Dirofilaria immitis microfilariae (DIROIM L1) ≥250 freshly purified canine heartworm microfilariae were added to the wells of a microtiter plate containing nutrient medium and the test compound in DMSO. The compound was tested in duplicate in a concentration-response assay. Larvae exposed to DMSO without the test compound served as a negative control. Larvae were evaluated after 72 h of incubation with the compound. Efficacy was determined by a decrease in motility compared to the negative control. Concentration-response curves and EC50 were calculated based on the evaluation over a wide concentration range. 50 -value.

[0466] For the compounds in the following examples, EC 50 Listed in Table 2.

[0467] Table 2:

[0468] In vitro assay 3: Canine heartworm (DIROIM L4) Ten freshly isolated third-stage canine heartworm larvae from their vector (intermediate host) were added to the wells of a microtiter plate containing nutrient medium and the test compound in DMSO. The compound was tested in duplicate in a concentration-response assay. Larvae exposed to DMSO without the test compound served as a negative control. Larvae were evaluated after 72 hours of incubation with the compound. During these 72 hours of incubation, most of the larvae in the negative control molted to the fourth-stage larvae. Efficacy was determined by a decrease in motility compared to the negative control. Concentration-response curves and EC50 were calculated based on evaluations over a wide concentration range. 50 -value.

[0469] For the compounds in the following examples, EC 50 Listed in Table 3.

[0470] Table 3: *nd = Undetermined.

Claims

1. Compounds of the general formula (I) and their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, in: A is A1 or A2, o is 0, 1, 2, 3, or 4; R is selected from the group consisting of: hydrogen, halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl, -S(O)-C1-C4 haloalkyl and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; X, Y are independently selected from: CR 7 R 8 , O, S and NR 9 , where at least one of X and Y is CR 7 R 8 , or X and Y together form a ring member selected from the following: -C(O)-O-, -C(O)-NR 9 -、-S(O)-NR 9 -、-SO2-NR 9 -and-SO2-O-; T is selected from: 10-membered aryl and 8- to 10-membered heteroaryl, each of which is optionally partially saturated and optionally substituted by 1, 2, 3, 4, 5 or 6 members selected from R 2 , R 3 , R 4 , R 5 , R 6 and Q is substituted with a substituent, or T is selected from T 1 、T 2 、T 3 、T 4 、T 5 、T 6 、T 7 、T 8a 、T 8b and T 9 : L is selected from: O and NR 9 ; M is selected from: C=O and CR 7 R 8 ; U selected from: CR 7 and N; V is selected from: CR 7 and N; R 1 is selected from the group consisting of: hydrogen, cyano, -CHO, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C3-C6 cycloalkyl, C3-C6 halocycloalkyl 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-C -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 haloalkyl-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 haloalkyl having 1 to 5 halogen atoms; Phenyl-C1-C4 alkyl, which is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl-C1-C4 alkyl is selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; The cycloalkyl 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 by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, R 2 Selected from: 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 optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, -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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocyclyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the following: halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl, a heterospirocycloalkyl, a 5-membered heteroaryl, and a 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, or 4 substituents independently selected from: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 alkyl-C(O)-, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C1-C4 alkyl-C(O)-, 1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl-, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and 4- to 10-membered heterocycloalkyl; R 3 Selected from: hydrogen, halogen or C1-C4 alkyl; R 4 Selected from: hydrogen, halogen, -OH, cyano, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C1-C4 alkyl-C(O)-, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -S-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl; R 5 Selected from: hydrogen, halogen, -OH, cyano, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-C(O)-, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -S-C1-C4 alkyl, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl; R 6 Selected from: hydrogen, halogen, -OH, cyano, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C1-C4 alkyl-C(O)-, -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, -S-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl; R 7 Selected from: hydrogen, -OH, halogen, C1-C4 alkyl and C1-C4 alkoxy; R 8 Selected from: hydrogen, -OH, halogen, C1-C4 alkyl and C1-C4 alkoxy; or R 7 and R 8 Together with the carbon atoms to which they are attached, they 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 haloalkyl having 1 to 5 halogen atoms, and C1-C4 alkoxy; R 10 Selected from: hydrogen, -OH, C1-C4 alkyl and C1-C4 alkoxy; R 11 Selected from: hydrogen, C1-C4 alkyl and C1-C4 alkoxy; or R 10 and R 11 Together with the carbon atoms to which they are attached, they 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 Independently selected from: 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 optionally substituted by 1, 2 or 3 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and (C1-C4 alkoxy)2P(=O)-; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C C-C4 alkyl, -S-C1-C4 alkyl, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, benzo-C5-C6 cycloalkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl group, a 5-membered heteroaryl group, and a 6-membered heteroaryl group, each of which is optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, -C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, R 14 Selected from: -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2; C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 haloalkoxy having 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C C-C4 alkyl, -S-C1-C4 alkyl, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl group, a 5-membered heteroaryl group, and a 6-membered heteroaryl group, each of which is optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, -C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, R 15 Selected from: C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 haloalkoxy having 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C C-C4 alkyl, -S-C1-C4 alkyl, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl group, a 5-membered heteroaryl group, and a 6-membered heteroaryl group, each of which is optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, -C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, R 16 is selected from the group consisting of: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, and C1-C4 alkoxy; R 17 is selected from the group consisting of: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, and C1-C4 alkoxy; Q is selected from: 6 to 10 membered aryl and 5 to 10 membered heteroaryl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents selected from the following: halogen; SF5; cyano; -CHO; nitro; oxo; C1-C4 alkyl; C1-C4 hydroxyalkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; -OH; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 haloalkyl having 1 to 5 halogen atoms; Alkoxy; -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 heterocyclic group optionally substituted by 1 or 2 substituents selected from fluorine, chlorine, bromine, methyl and cyano; -CH2-O-(C1-C4 alkyl), -CH2-NH(C1-C4 alkyl), -CH 2-N(C1-C4 alkyl)2; methyl substituted by a 4- to 6-membered heterocyclic group, which itself is optionally substituted by 1 or 2 substituents selected from 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); having 1 to -S-(C1-C4 haloalkyl) with 5 halogen atoms; -S(O)-(C1-C4 haloalkyl) with 1 to 5 halogen atoms; -SO2-(C1-C4 haloalkyl) with 1 to 5 halogen atoms; -CONH(C1-C4 alkyl); -CONH(C3-C6 cycloalkyl); -NHCO(C1-C4 alkyl); -NHCO(C3-C6 cycloalkyl); -NHCO(C1-C4 haloalkyl) with 1 to 5 halogen atoms; When Y is O, S or NR 9 When R 7 , R 8 , R 10 and R 11 are not -OH, and when X is O, S or NR 9 When R 7 and R 8 None of them is -OH.

2. The compound according to claim 1 and its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, in: A is A1 or A2, o is 0, 1, 2, 3, or 4; R is selected from the group consisting of: hydrogen, halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl, -S(O)-C1-C4 haloalkyl and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; X, Y are independently selected from: CR 7 R 8 , O, S and NR 9 , where at least one of X and Y is CR 7 R 8 , or X and Y together form a ring member selected from the following: -C(O)-O-, -C(O)-NR 9 -、-S(O)-NR 9 -、-SO2-NR 9 - and -SO2-O-; T is selected from T 1 , T 2 , T 3 , T 4 , T 5 , T 6 , T 7 , T 8a , T 8b and T 9 : L is selected from: O and NR 9 ; M is selected from: C=O and CR 7 R 8 ; U selected from: CR 7 and N; V is selected from: CR 7 and N; R 1 is selected from the group consisting of: hydrogen, cyano, -CHO, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C3-C6 cycloalkyl, C3-C6 halocycloalkyl 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-C -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 haloalkyl-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 haloalkyl having 1 to 5 halogen atoms; Phenyl-C1-C4 alkyl, which is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocyclyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, R 2 Selected from: 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 optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, -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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocyclyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the following: halogen, -OH, -NO2, cyano, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl, a heterospirocycloalkyl, a 5-membered heteroaryl, and a 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, or 4 substituents independently selected from: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 alkyl-C(O)-, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C1-C4 alkyl-C(O)-, 1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl-, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and 4- to 10-membered heterocycloalkyl; R 3 Selected from: hydrogen, halogen or C1-C4 alkyl; R 4 Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 5 is selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; R 6 Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 7 Selected from: hydrogen, -OH, halogen, C1-C4 alkyl and C1-C4 alkoxy; R 8 Selected from: hydrogen, -OH, halogen, C1-C4 alkyl and C1-C4 alkoxy; R 9 is selected from the group consisting of: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, and C1-C4 alkoxy; R 10 Selected from: hydrogen, -OH, C1-C4 alkyl and C1-C4 alkoxy; R 11 Selected from: hydrogen, C1-C4 alkyl and C1-C4 alkoxy; R 12 and R 13 Independently selected from: 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 optionally substituted by 1, 2 or 3 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and (C1-C4 alkoxy)2P(=O)-; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C C-C4 alkyl, -S-C1-C4 alkyl, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, benzo-C5-C6 cycloalkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl group, a 5-membered heteroaryl group, and a 6-membered heteroaryl group, each of which is optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, -C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, R 14 Selected from: -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2; C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 haloalkoxy having 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C C-C4 alkyl, -S-C1-C4 alkyl, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl group, a 5-membered heteroaryl group, and a 6-membered heteroaryl group, each of which is optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, -C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, R 15 Selected from: C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 haloalkoxy having 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C C-C4 alkyl, -S-C1-C4 alkyl, -S(O)-C1-C4 alkyl, -SO2-C1-C4 alkyl, -S-C1-C4 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; Phenyl, which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; and a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl group, a 5-membered heteroaryl group, and a 6-membered heteroaryl group, each of which is optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy -C1-C4 alkyl, -C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, R 16 is selected from the group consisting of: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, and C1-C4 alkoxy; R 17 is selected from the group consisting of: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, and C1-C4 alkoxy; Q is selected from: 6-membered aryl and 5- to 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents selected from the following: halogen; SF5; cyano; -CHO; nitro; oxo; C1-C4 alkyl; C1-C4 hydroxyalkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; -OH; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 haloalkoxy 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; a 4- to 6-membered heterocyclic group optionally substituted by 1 or 2 substituents selected from fluorine, chlorine, bromine, methyl and cyano; -CH2-O-(C1-C4 alkyl), -CH2-NH(C1-C4 alkyl), -CH2- N(C1-C4 alkyl)2; methyl substituted by a 4- to 6-membered heterocyclic group, which itself is optionally substituted by 1 or 2 substituents selected from 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); having 1 to 5 -S-(C1-C4 haloalkyl) having 1 to 5 halogen atoms; -S(O)-(C1-C4 haloalkyl) having 1 to 5 halogen atoms; -SO2-(C1-C4 haloalkyl) 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 haloalkyl) having 1 to 5 halogen atoms; When Y is O, S or NR 9 When R 7 , R 8 , R 10 and R 11 are not -OH, and when X is O, S or NR 9 When R 7 and R 8 None of them is -OH.

3. A compound according to claim 1 or 2 and its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: A is A1 or A2, o is 0, 1, or 2; R is selected from the group consisting of: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; X, Y are independently selected from: CR 7 R 8 , O, S and NR 9 , where at least one of X and Y is CR 7 R 8 ; T is selected from T 1 , T 2 , T 3 , T 4 , T 5 , T 6 , T 7 , T 8a , T 8b and T 9 : L is selected from: O and NR 9 ; M is selected from: C=O and CR 7 R 8 ; U selected from: CR 7 and N; V is selected from: CR 7 and N; R 1 is selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; R 2 Selected from: 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 optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, -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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, and -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms; a monocyclic or bicyclic heterocyclic ring selected from: a 4- to 10-membered heterocycloalkyl, a heterospirocycloalkyl, a 5-membered heteroaryl, and a 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, or 4 substituents independently selected from: halogen, cyano, nitro, -OH, oxo, thiocarbonyl, -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 alkyl-C(O)-, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C1-C4 alkyl-C(O)-, 1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl-, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and 4- to 10-membered heterocycloalkyl; R 3 Selected from: hydrogen, halogen or C1-C4 alkyl; R 4 Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 5 is selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; R 6 Selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 7 Selected from: hydrogen, halogen, C1-C4 alkyl; R 8 Selected from: hydrogen, halogen, C1-C4 alkyl; R 9 Selected from: hydrogen, C1-C4 alkyl; R 10 Selected from: hydrogen, -OH, C1-C4 alkyl and C1-C4 alkoxy; R 11 Selected from: hydrogen; R 12 and R 13 Independently selected from: hydrogen; C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: 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 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4 haloalkyl having 1 to 5 halogen atoms, -SO2-C1-C4 haloalkyl having 1 to 5 halogen atoms, and (C1-C4 alkoxy)2P(=O)-; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 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 following: halogen, cyano, -OH, oxo, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; Phenyl, benzo-C5-C6 cycloalkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; a monocyclic or bicyclic heterocycle selected from: 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: halogen, cyano, -OH, oxo, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C1-C4 alkyl, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 14 Selected from: C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C3-C6 cycloalkyl; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 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 following: halogen, cyano, -OH, oxo, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 15 Selected from: C1-C4 alkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, -OH, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 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 following: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 16 is selected from the group consisting of: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, and C1-C4 alkoxy; R 17 is selected from the group consisting of: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, and C1-C4 alkoxy; Q is selected from: 6-membered aryl and 5- to 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents selected from the following: halogen, cyano, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, -OH, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, 4- to 6-membered heterocyclyl optionally substituted by 1 or 2 substituents selected from fluorine, chlorine, bromine, methyl and cyano; When Y is O, S or NR 9 When R 7 , R 8 , R 10 and R 11 are not -OH, and when X is O, S or NR 9 When R 7 and R 8 None of them is -OH.

4. The compound according to claim 1, 2 or 3 and its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: A is A1 or A2, o is 0 or 1; R is selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy; X is selected from the group consisting of CR 7 R 8 , O, S and NR 9 , Y is CR 7 R 8 ; T is selected from T 1 , T 2 , T 3 , T 4 , T 5 , T 6 , T 7 , T 8a , T 8b and T 9 : L is selected from: O and NR 9 ; M is selected from: C=O and CR 7 R 8 ; U selected from: CR 7 and N; V is selected from: CR 7 and N; R 1 Selected from: hydrogen and C1-C4 alkyl; R 2 Selected from: Hydrogen, halogens; -NR 12 R 13 ; -OR 14 ; -SR 15 、-S(O)R 15 、-SO2R 15 ; C1-C6 alkyl or C3-C6 cycloalkyl, each of which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen, cyano, C1-C4 alkyl; a monocyclic or bicyclic heterocycle selected from: 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from: halogen, -OH, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, hydroxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 3 Selected from: hydrogen, halogen or C1-C4 alkyl; R 4 is selected from the group consisting of: hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms; R 5 Selected from: hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms; R 6 Selected from: hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms; R 7 Selected from: hydrogen, halogen, C1-C4 alkyl; R 8 Selected from: hydrogen, halogen, C1-C4 alkyl; R 9 Selected from: hydrogen, C1-C4 alkyl; R 10 Selected from: hydrogen, C1-C4 alkyl; R 11 Selected from: hydrogen; R 12 and R 13 Independently selected from: hydrogen; C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, C3-C6 cycloalkyl; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from 4 to 10 membered heterocycloalkyl, the 4 to 10 membered heterocycloalkyl optionally substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; Phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; monocyclic or bicyclic heterocyclic ring, which is selected from: 4 to 10 membered heterocycloalkyl, 5 membered heteroaryl and 6 membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 14 Selected from: C1-C4 alkyl, C3-C6 cycloalkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, -C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 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 following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 15 Selected from: C1-C4 alkyl, phenyl-C1-C4 alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; Heterocyclyl-C1-C4 alkyl, wherein the heterocyclyl substituent is selected from: 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 following: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; R 16 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms; R 17 Selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms; Q is selected from: 6-membered aryl and 5- to 6-membered heteroaryl, each of which is optionally substituted with 1, 2, 3, 4 or 5 substituents selected from: halogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms; When Y is O, S or NR 9 When R 7 , R 8 , R 10 and R 11 are not -OH, and when X is O, S or NR 9 When R 7 and R 8 None of them is -OH.

5. A compound according to claim 1, 2, 3 or 4 and its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: Q is a substituted benzene ring of formula (Q1) in: Z 1 , Z 2 , Z 3 , Z 4 and Z 5 independently selected from: hydrogen; halogen; SF5; cyano; -CHO; nitro; C1-C4 alkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; hydroxyl; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 haloalkoxy having 1 to 5 halogen atoms; -NH(C1-C4 alkyl); -N(C1-C4 alkyl)2; -NH-SO2-(C C1-C4 alkyl); -N(SO2-[C1-C4 alkyl])(C1-C4 alkyl); (C1-C4 alkoxyimino)-C1-C4 alkyl; 4- to 6-membered heterocyclic group optionally substituted by 1 or 2 substituents selected from fluorine, chlorine, bromine, methyl and cyano; -CH2-O-(C1-C4 alkyl); -CH2-NH(C1-C4 alkyl); -CH2-N(C1-C4 alkyl)2; methyl substituted by 4- to 6-membered heterocyclic group , the 4- to 6-membered heterocyclic group itself is optionally substituted by 1 or 2 substituents selected from 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 alkyl) having 1 to 5 halogen atoms C4 haloalkyl); -S(O)-(C1-C4 haloalkyl) having 1 to 5 halogen atoms; -SO2-(C1-C4 haloalkyl) 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 haloalkyl) having 1 to 5 halogen atoms, or Z 1 and Z 2 Together with the carbon atoms to which they are attached, they form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl group or a 6-membered heteroaryl group, each of which may be optionally substituted by one or two substituents selected from the group consisting of methyl, fluoro and oxo, and Z 3 , Z 4 and Z 5 Independently selected from: hydrogen; halogen; SF5; cyano; CHO; nitro; C1-C4 alkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; hydroxyl; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 alkoxy-C(O)-; C1-C4 haloalkoxy 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 heterocyclic alkyl optionally substituted by 1 or 2 substituents selected from fluorine, methyl or cyano; -CH2-O-(C1-C4 alkyl); -CH2-NH(C1-C4 alkyl); -CH2-N(C1-C4 alkyl)2; 4- to 6-membered heterocyclic alkyl-substituted methyl, the 4- to 6-membered heterocycloalkyl itself being optionally substituted by 1 or 2 substituents selected from fluorine, 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 alkyl) having 1 to 5 halogen atoms -S(O)-(C1-C4 haloalkyl) having 1 to 5 halogen atoms; -SO2-(C1-C4 haloalkyl) 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 haloalkyl) having 1 to 5 halogen atoms, or Z 2 and Z 3 Together with the carbon atoms to which they are attached, they form a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl group or a 6-membered heteroaryl group, each of which may be optionally substituted by one or two substituents selected from the group consisting of methyl, fluoro and oxo, and Z 1 , Z 4 and Z 5 independently selected from: hydrogen; halogen; SF5; cyano; CHO; nitro; C1-C4 alkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; hydroxyl; C1-C4 alkoxy; C3-C6 cycloalkyl-C1-C4 alkoxy; cyano-C1-C4 alkoxy; C1-C4 haloalkoxy having 1 to 5 halogen atoms; -NH(C1-C4 alkyl); -N(C1-C4 alkyl)2; -NH-SO2-(C C1-C4 alkyl); -N(SO2-[C1-C4 alkyl])(C1-C4 alkyl); (C1-C4 alkoxyimino)-C1-C4 alkyl; 4- to 6-membered heterocycloalkyl optionally substituted by 1 or 2 substituents selected from fluorine, methyl or cyano; -CH2-O-(C1-C4 alkyl); -CH2-NH(C1-C4 alkyl); -CH2-N(C1-C4 alkyl)2; methyl substituted by 4- to 6-membered heterocycloalkyl , the 4- to 6-membered heterocycloalkyl group itself is optionally substituted by 1 or 2 substituents selected from fluorine, 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 alkyl) having 1 to 5 halogen atoms -4-halogenated alkyl); -S(O)-(C1-C4-halogenated alkyl) having 1 to 5 halogen atoms; -SO2-(C1-C4-halogenated alkyl) 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-halogenated alkyl) having 1 to 5 halogen atoms, or Q is a pyridine ring of formula (Q2) in: Z 6 , Z 7 , Z 8 and Z 9 independently selected from: hydrogen; halogen; cyano; C1-C4 alkyl; C1-C4 haloalkyl having 1 to 5 halogen atoms; C1-C4 alkoxy; C1-C4 haloalkoxy having 1 to 5 halogen atoms; C1-C4 hydroxyalkyl; NH2; -NH(C1-C4 alkyl); -N(C1-C4 alkyl)2; -NH-CO-C1-C4 alkyl; and a monocyclic heterocycle selected from: a 4- to 7-membered heterocycloalkyl or a 5-membered heteroaryl having at least one nitrogen atom, the heteroaryl ring being attached to the pyridine ring via the at least one nitrogen atom, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from: halogen, cyano, nitro, -OH, oxygen halogenated, thiocarbonyl, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy 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 haloalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4 haloalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4 haloalkyl) having 1 to 5 halogen atoms, or Q is a pyrimidine ring of formula (Q3) in: Z 10 , Z 11 and Z 12 independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or Q is a pyridine ring of formula (Q4) in: Z 13 , Z 14 , Z 15 and Z 16 independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or Q is a pyridine ring of formula (Q5) in: Z 17 , Z 18 , Z 19 and Z 20 independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or Q is a 5-membered aromatic heterocyclic ring of formula (Q6) in: G 1 -G 4 Independently selected from: N, O, S, CZ 21 and NZ 22 , where G 1 -G 4 No more than one of them is O, G 1 -G 4 No more than one of them is S, G 1 -G 4 No more than one of them is NZ 22 , and among them Each Z 21 independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms, and Each Z 22 independently selected from: hydrogen, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkyl-C3-C6 cycloalkyl, C1-C4 alkoxy-C1-C4 alkyl, or Q is a 5-membered aromatic heterocyclic ring of formula (Q7) in: U 1 -U 4 Independently selected from: N and CZ 23 , where U 1 -U 4 No more than three of them are N, and among them Each Z 23 Independently selected from: hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl having 1 to 5 halogen atoms, C1-C4 alkoxy, C1-C4 haloalkoxy having 1 to 5 halogen atoms.

6. A compound according to claim 1, 2, 3, 4 or 5 and its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, and mixtures thereof, wherein: A is selected from: T is selected from T 1 、T 2 、T 3 、T 4 、T 5 、T 6 、T 7 、T 8a 、T 8b and T 9 : L is selected from: O and NR 9 ; M is selected from: C=O and CR 7 R 8 ; U selected from: CR 7 and N; V is selected from: CR 7 and N; R 1 Selected from: hydrogen or methyl; R 2 Selected from: Hydrogen, chlorine, fluorine, bromine; -NR 12 R 13 ; -OR 14 ; methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclohexyl, each of which is optionally substituted with 1 or 2 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, propyl and isopropyl; a monocyclic or bicyclic heterocycle selected from the group consisting of azetidine, pyrrolidine, pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine, piperazine, tetrahydropyridine, dihydro-2H-pyran, tetrahydropyran, 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 alkane, 6-oxa-3-azabicyclo[3.1.1]heptane, 8-oxa-3-azabicyclo[3.2.1]octane, imidazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole, 4-oxa-7-azaspiro[2.5]octane, each of which is optionally substituted with 1, 2, 3 or 4 substituents independently selected from fluoro, chloro, -OH, methyl, trifluoromethyl, methoxymethyl, trifluoromethoxymethyl; R 3 Selected from: hydrogen, chlorine or methyl; R 4 Selected from: hydrogen, fluorine, chlorine, methyl, methoxy, trifluoromethyl, trifluoromethoxy; R 5 Selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl; R 6 Selected from: hydrogen, fluorine, chlorine, methyl, methoxy, trifluoromethyl, trifluoromethoxy; R 7 Selected from: hydrogen, fluorine, chlorine, methyl; R 8 Selected from: hydrogen, fluorine, chlorine, methyl; R 9 Selected from: hydrogen, methyl; R 10 Selected from: hydrogen, methyl; R 11 Selected from: hydrogen; R 12 and R 13 Independently selected from: Hydrogen and methyl; R 14 is methyl; R 16 Selected from: hydrogen, methyl, ethyl, propyl, isopropyl, trifluoromethyl; R 17 Selected from: hydrogen, methyl, ethyl, propyl, isopropyl, trifluoromethyl; Q is a benzene ring of formula (Q1) in: Z 1 To Z 5 independently selected from: hydrogen, fluorine, chlorine, methyl and trifluoromethyl; or Q is a benzene ring of formula (Q2) in: Z 6 To Z 9 Independently selected from the group consisting of: hydrogen, fluorine, chlorine, methyl and trifluoromethyl.

7. A compound according to claim 1, 2, 3, 4, 5 or 6 and stereoisomers, tautomers, N-oxides, hydrates, solvates and salts thereof, and mixtures thereof, wherein: Q is a benzene ring of formula (Q1) in: Z 1 , Z 3 and Z 5 independently selected from: hydrogen, fluorine and chlorine; Z 2 and Z 4 independently selected from: hydrogen, fluorine, chlorine and trifluoromethyl; or Q is a benzene ring of formula (Q2) in: Z 6 To Z 9 Independently selected from: hydrogen, fluorine and chlorine.

8. A compound according to claim 1, 2, 3, 4, 5, 6 or 7 and stereoisomers, tautomers, N-oxides, hydrates, solvates and salts thereof, and mixtures thereof, wherein: A is selected from:

9. A compound according to claim 1, 2, 3, 4, 5, 6, 7 or 8 and stereoisomers, tautomers, N-oxides, hydrates, solvates and salts thereof, and mixtures thereof, wherein: A is selected from: T is selected from T 1 、T 2 、T 3 、T 4 、T 5 、T 6 、T 7 、T 8a 、T 8b and T 9 : L is selected from: O and NR 9 ; M is selected from: C=O and CR 7 R 8 ; U selected from: CR 7 and N; V is selected from: CR 7 and N; R 1 is hydrogen; R 2 Selected from Hydrogen, chlorine; -NR 12 R 13 ; -OR 14 ; Methyl, isopropyl; Morpholine; R 3 is hydrogen or methyl; R 4 is hydrogen or fluorine; R 5 is hydrogen or methyl; R 6 is hydrogen or fluorine; R 7 is hydrogen or methyl; R 8 is hydrogen; R 9 is hydrogen; R 10 is hydrogen; R 11 is hydrogen; R 12 and R 13 Independently selected from: Hydrogen and methyl; R 14 is methyl; R 16 is methyl or isopropyl; R 17 is methyl; Q is a benzene ring of formula (Q1) in: Z 1 , Z 3 and Z 5 independently selected from: hydrogen, fluorine and chlorine; Z 2 and Z 4 independently selected from: hydrogen, fluorine, chlorine and trifluoromethyl; or Q is a benzene ring of formula (Q2) in: Z 6 To Z 9 are independently selected from hydrogen and chlorine.

10. A compound according to claim 1, 2, 3, 4, 5, 6, 7, 8 or 9 and stereoisomers, tautomers, N-oxides, hydrates, solvates and salts thereof, and mixtures thereof, wherein: A is selected from:

11. A method for preparing a compound of general formula (I) according to any one of claims 1 to 10, comprising the following steps: The intermediate compound of the general formula Int-I-T1, Int-I-T2, Int-I-T3, Int-I-T4, Int-I-T5, Int-I-T6, Int-I-T7, Int-I-T8a, Int-I-T8b or Int-I-T9 is: Among them L, M, U, V, A, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 As defined in any of the preceding claims, the compounds of formula (I) wherein Hal is halogen, in particular chlorine, bromine or iodine, Reaction with a compound of formula 1H: QB(OR)2 1H， wherein Q is defined as a compound of formula (I) according to any one of the preceding claims, and each R may be independently H or Me, or both R are pinacol esters, Thus, a compound of general formula (I) is obtained: Among them T, L, M, U, V, A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Q as defined in any one of the preceding claims; or The intermediate compound of the general formula Int-II-T1, Int-II-T2, Int-II-T3, Int-II-T4, Int-II-T5, Int-II-T6, Int-II-T7, Int-II-T8a, Int-II-T8b or Int-II-T9 is: Among them, L, M, U, V, Q, R 2 , R 3 , R 4 , R 5 and R 6 As defined in any one of the preceding claims, a compound of formula (I) Reaction with a compound of formula 1V: Where R 1 and A is defined as a compound of formula (I) according to any one of the preceding claims, Thus, a compound of general formula (I) is obtained: Among them, T, A and R 1 As defined in any one of the preceding claims.

12. Compounds of general formula (I) according to any one of claims 1 to 10 for use in the control, treatment and / or prevention of diseases.

13. A compound of formula (I) according to any one of claims 1 to 10 for use in controlling, treating and / or preventing helminth infections.

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

15. A method for controlling helminth infections in humans and / or animals by administering to a human or animal in need thereof an anthelmintic effective amount of at least one compound of formula (I) according to any one of claims 1 to 10 or a pharmaceutical composition according to claim 14.

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