Pharmaceutical composition for treating fibrotic diseases

Abstract

The present invention provides compounds of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer, or mixtures thereof. [Formula 1] TIFF2023533220000153.tif45114 and pharmaceutical compositions comprising the compound of formula (I), and the use of the compound of formula (I), or a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer, or a mixture thereof, in the treatment of fibrotic diseases, preferably idiopathic pulmonary fibrosis (IPF) or non-alcoholic steatohepatitis (NASH). A further aspect of the present invention includes combination therapy using the compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer, or a mixture thereof, in combination with a known anti-fibrotic or anti-inflammatory agent for fibrotic diseases.

Description

Technical Field

[0001] Field of the Invention The present invention relates to a compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer, or a mixture thereof.

[0002]

Chemical Formula

[0003] And a pharmaceutical composition comprising a compound of formula (I), and the use of a compound of formula (I), or a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer, or a mixture thereof, in the treatment of fibrotic diseases, preferably idiopathic pulmonary fibrosis (IPF) or non-alcoholic steatohepatitis (NASH). A further aspect of the present invention includes a combination therapy in which a compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer, or a mixture thereof, is used in combination with a known antifibrotic or anti-inflammatory agent for fibrotic diseases.

Background Art

[0004] Background of the Invention Pulmonary fibrosis can be caused by a variety of different conditions, such as sarcoidosis, hypersensitivity pneumonitis, collagen vascular diseases, and inhalation exposures. The diagnosis of these conditions can usually be made by a detailed medical history, physical examination, chest radiography including high-resolution computed tomography scan (HRCT), and open lung biopsy or transbronchial biopsy. However, in a significant number of patients, the underlying cause of pulmonary fibrosis has not been found. These conditions with unknown etiology are called idiopathic interstitial pneumonia. Histological examination of the tissue obtained by open lung biopsy can classify these patients into several categories, including usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), and nonspecific interstitial pneumonia (NSIP).

[0005] Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia and is characterized by a histological UIP pattern. Idiopathic pulmonary fibrosis and other interstitial lung diseases (ILDs) are serious conditions of progressive lung scarring with extracellular matrix deposition and lung matrix destruction, leading to loss of lung function. The pathology of IPF is chronic and progressive. IPF has a median survival of 3.8 years and is ultimately fatal. Anti-inflammatory and immunosuppressive therapies, including corticosteroids, have shown limited effectiveness in the treatment of IPF. Currently, the available pharmacological treatment options for pulmonary fibrosis consist of the antifibrotic effects of nintedanib and pirfenidone. Nintedanib acts as a multi-receptor tyrosine kinase (RTK) inhibitor, blocking VEGF receptor signaling, FGF receptor signaling, and PDGF receptor signaling, thereby reducing fibroblast proliferation and differentiation. Pirfenidone interferes with TGF-β signaling, thereby reducing fibroblast proliferation and differentiation into myofibroblasts.

[0006] Neither pharmacological intervention achieves, at best, an extension of the progression-free survival period or reduces the disease burden without conferring a benefit on the patient's survival. Therefore, an important unmet need is to identify new molecular targets and agents that interfere with the key molecular pathways involved in the pathogenesis of pulmonary fibrosis to prevent or reverse the progression of fibrosis in patients.

[0007] Fatty liver disease, which may also be referred to as hepatic steatosis, is a condition generally characterized by abnormal retention of lipids in the cells of the liver. Fatty liver disease can have various causes. For example, non-alcoholic fatty liver disease (NAFLD) generally refers to various hepatic lipid disorders characterized by fatty liver of unknown secondary cause. NAFLD can be subcategorized into (a) non-alcoholic fatty liver (NAFL), defined as the presence of fatty liver in the absence of histological evidence of hepatocyte injury, and (b) non-alcoholic steatohepatitis (NASH), fatty liver accompanied by hepatocyte injury and inflammation; NASH may occur with or without fibrosis, but may progress to fibrosis and cirrhosis. Currently, there are no pharmaceuticals approved for the treatment of NAFLD / NASH. SUMMARY OF THE INVENTION PROBLEM TO BE SOLVED BY THE INVENTION

[0008] Accordingly, an object of the present invention is to provide a compound capable of treating fibrosis or preventing the onset of fibrosis. Furthermore, an object of the present invention is to provide an improved treatment option for patients suffering from fibrotic diseases, preferably idiopathic pulmonary fibrosis, by using the compounds of the present invention alone or in combination therapy. MEANS FOR SOLVING THE PROBLEM

[0009] BRIEF SUMMARY OF THE INVENTION The present invention provides a method for treating a fibrotic disease, preferably idiopathic pulmonary fibrosis (IPF) or non-alcoholic steatohepatitis (NASH); a method for prolonging the survival period of an individual having a fibrotic disease; and a method for reducing the risk of death of an individual having a fibrotic disease. The method generally comprises administering to an individual having a fibrotic disease a therapeutically effective amount of a compound of formula (I) in the form of, optionally, a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof.

[0010] Accordingly, in a first aspect, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof

[0011] [Chemical formula]

[0012] (wherein, R 1 is selected from halogen and -(optionally substituted hydrocarbon group containing 1 to 20 carbon atoms and optionally 1 to 15 heteroatoms selected from O, N, and S); R 21 is hydrogen, -(optionally substituted C 1~6 alkyl) which may contain 1 to 3 oxygen atoms between carbon atoms, and -(optionally substituted C 3~6 cycloalkyl); R 3 is selected from -(optionally substituted heterocyclyl), -(optionally substituted carbocyclyl), -(optionally substituted C 1~6 alkylene)-(optionally substituted heterocyclyl), and -(optionally substituted C 1~6 alkylene)-(optionally substituted carbocyclyl); X 1 X 2 ​, and X 3 Each of them is independently selected from N, CH, and CR x and the X 1 , X 2 and X 3 At least one of them is N, and more preferably, at least one of the X 2 and X 3 is N; even more preferably, X 2 and X 3 are both N, and still more preferably, X 2 and X 3 are both N, X 1 is CH; R 31 is selected from -hydrogen, -C 1~6 -alkyl, and -(C 1~6 -alkyl substituted with one or more F); R 3 and any R 31 can be optionally linked; E is absent or is selected from -CH2-, -CHR x (-), -CR x 2(-), -NH(-), -NR x (-), -O(-), -L 1 -L 2 (-), and -L 2 -L 1 (-), where L 1 is selected from -CH2-, -CHR x (-), -CR x 2(-), -NH(-), -NR x (-), and -O(-), and L 2 is selected from -CH2-, -CHR x (-), and -CR x 2(-); R 6x is selected from -halogen, -OH, =O, C 1~6 alkyl, C 1~6 haloalkyl, C 1~6 alkyl substituted with one or more OH, monocyclic aryl optionally substituted with one or more R xb in one or more R xbA monocyclic heteroaryl optionally substituted therein, one or more Rs xb A monocyclic cycloalkyl optionally substituted therein, one or more Rs xb A monocyclic heterocycloalkyl optionally substituted therein, one or more Rs xb A monocyclic cycloalkenyl optionally substituted therein, one or more Rs xb A monocyclic heterocycloalkenyl optionally substituted therein, wherein said R xb is independently selected from - halogen, -OH, =O, C 1~4 alkyl, C 1~2 haloalkyl, C substituted with one or two OHs 1~2 alkyl; Ring A may be further substituted with one or more R x groups, and any two R x groups of ring A may optionally be linked, and / or any R x group of ring A may optionally be linked to R 21 ; and / or, ring A may, together with R 6x form a bicyclic moiety having the following substructure:

[0013]

Chemical formula

[0014] and may be further substituted with one R x group; Ring B is - (optionally substituted heterocyclic ring) or - (optionally substituted carbocyclic ring); each R x is - halogen, -OH, -O - (optionally substituted C 1~6 alkyl), -NH - (optionally substituted C 1~6 alkyl), -N(optionally substituted C 1~6 alkyl)2, =O, - (optionally substituted C 1~6 alkyl), - (optionally substituted carbocyclyl), - (optionally substituted heterocyclyl), - (optionally substituted C 1~6-(alkylene)-(optionally substituted carbocyclic), -(optionally substituted C 1~6 alkylene)-(optionally substituted heterocyclic), -O-(optionally substituted C 1~6 alkylene)-(optionally substituted carbocyclic), and -O-(optionally substituted C 1~6 alkylene)-(optionally substituted heterocyclic), independently selected from optionally substituted hydrocarbon group, optionally substituted C 3~6 cycloalkyl, optionally substituted heterocyclic, optionally substituted heterocycle, optionally substituted carbocyclic, optionally substituted carbocycle and optionally substituted C 1~6 Optional substituents of alkylene are -(optionally substituted by one or more halogens C 1~6 alkyl), -halogen, -CN, -NO2, oxo, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -N(R * )-S(O)2R * , -OR * , -O-C(O)R * , -O-C(O)-NR * R * , -SR * , -S(O)R * , -S(O)2R * , -S(O)2-NR * R * , -N(R * )-S(O)2-NR * R * , halogen or C 1~6 heterocyclic optionally substituted in alkyl, and halogen or C1~6 independently selected from carbocyclyl optionally substituted in the alkyl; each R * is H, C 1~6 alkyl optionally substituted in the halogen, halogen or C 1~6 heterocyclyl optionally substituted in the alkyl, and halogen or C 1~6 independently selected from carbocyclyl optionally substituted in the alkyl; any two Rs attached to the same nitrogen atom * can be optionally linked, optionally substituted C 1~6 alkyl and optionally substituted C 1~6 Optional substituents of alkylene are -halogen, -CN, -NO2, oxo, -C(O)R ** , -COOR ** , -C(O)NR ** R ** , -NR ** R ** , -N(R ** )-C(O)R ** , -N(R ** )-C(O)-OR ** , -N(R ** )-C(O)-NR ** R ** , -N(R ** )-S(O)2R ** , -OR ** , -O-C(O)R ** , -O-C(O)-NR ** R ** , -SR ** , -S(O)R ** , -S(O)2R ** , -S(O)2-NR ** R ** and -N(R ** )-S(O)2-NR ** R ** independently selected from; R ** is H, C 1~6 alkyl optionally substituted in the halogen, halogen or C 1~6 heterocyclyl optionally substituted in the alkyl, and halogen or C 1~6Independently selected from carbocyclic groups optionally substituted in the alkyl; any two Rs attached to the same nitrogen atom ** (which can be optionally linked).

[0015] In particular, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof

[0016]

Chemical formula

[0017] (wherein R 1 is selected from halogen and an optionally substituted hydrocarbon group containing 1 to 20 carbon atoms and 1 to 15 heteroatoms optionally selected from O, N, and S; R 21 is hydrogen, an optionally substituted C 1~6 alkyl which may contain 1 to 3 oxygen atoms between carbon atoms, and an optionally substituted C 3~6 cycloalkyl; R 3 is selected from an optionally substituted heterocyclyl, an optionally substituted carbocyclyl, an optionally substituted C 1~6 alkylene - heterocyclyl, and an optionally substituted C 1~6 alkylene - carbocyclyl); X 1 、X 2 、and X 3 each is independently selected from N, CH, and CR x , wherein at least one of said X 1 、X 2 、and X 3 is N; R 31 is hydrogen, C 1~6-Alkyl, and C substituted with one or more Fs 1~6 -Selected from -alkyl; R 3 And any R 31 Can optionally be linked; E is absent or is -CH2-, -CHR x -, -CR x 2-, -NH-, -NR x -, -O-, -L 1 -L 2 -And -L 2 -L 1 -Selected from -, L 1 L is -CH2-, -CHR x -, -CR x 2-, -NH-, -NR x -, and -O-, L 2 L is selected from -CH2-, -CHR x -And -CR x 2-Selected from; R 6x Is -halogen, -OH, =O, C 1~6 Alkyl, C 1~6 Haloalkyl, C substituted with one or more OHs 1~6 Alkyl, one or more Rs xb Optionally substituted monocyclic aryl, one or more Rs xb Optionally substituted monocyclic heteroaryl, one or more Rs xb Optionally substituted monocyclic cycloalkyl, one or more Rs xb Optionally substituted monocyclic heterocycloalkyl, one or more Rs xb Optionally substituted monocyclic cycloalkenyl, one or more Rs xb Optionally substituted monocyclic heterocycloalkenyl, said R xb Is halogen, OH, =O, C 1~4 Alkyl, C 1~2 Haloalkyl, C substituted with one or two OHs 1~2 Independently selected from alkyl; Ring A is one or more Rs xIt may be further substituted with a radical, and any two Rs of ring A x radicals can optionally be linked, and / or any R of ring A x radical can optionally be linked to R 21 ; and / or, ring A, together with R 6x forms a bicyclic moiety having the following partial structure:

[0018]

Chemical formula

[0019] and may be further substituted with one R x radical, Ring B is an optionally substituted heterocyclic ring or an optionally substituted carbocyclic ring; Each R x is independently selected from halogen, OH, optionally substituted O-C 1~6 alkyl, optionally substituted NH-C 1~6 alkyl), optionally substituted N(C 1~6 alkyl)2, =O, optionally substituted C 1~6 alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted C 1~6 alkylene-carbocyclyl), optionally substituted C 1~6 alkylene-heterocyclyl), optionally substituted O-C 1~6 alkylene-carbocyclyl, and optionally substituted O-C 1~6 alkylene-heterocyclyl, and the optional substituent of the optionally substituted hydrocarbon group, optionally substituted C cycloalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclic ring, optionally substituted carbocyclyl, optionally substituted carbocyclic ring and optionally substituted C 3~6 alkylene is optionally substituted with one or more halogens on C 1~6 alkyl, halogen, CN, NO2, oxo, -C(O)R 1~6 ​* ,-COOR * ,-C(O)NR * R * ,-NR * R * ,-N(R * )-C(O)R * ,-N(R * )-C(O)-OR * ,-N(R * )-C(O)-NR * R * ,-N(R * )-S(O)2R * ,-OR * ,-O-C(O)R * ,-O-C(O)-NR * R * ,-SR * ,-S(O)R * ,-S(O)2R * ,-S(O)2-NR * R * ,-N(R * )-S(O)2-NR * R * ,- halogen or C 1~6 heterocyclyl optionally substituted in alkyl, and halogen or C 1~6 carbocyclyl optionally substituted in alkyl, independently selected; each R * is independently selected from H, C 1~6 alkyl optionally substituted by halogen, halogen or C 1~6 heterocyclyl optionally substituted in alkyl, and halogen or C 1~6 carbocyclyl optionally substituted in alkyl; any two R * connected to the same nitrogen atom can be optionally linked, optionally substituted C 1~6 alkyl and optionally substituted C 1~6 any optional substituent of alkylene is - halogen, -CN, -NO2, oxo, -C(O)R ** ,-COOR ** ,-C(O)NR ** R **, -NR ** R ** , -N(R ** )-C(O)R ** , -N(R ** )-C(O)-OR ** , -N(R ** )-C(O)-NR ** R ** , -N(R ** )-S(O)2R ** , -OR ** , -O-C(O)R ** , -O-C(O)-NR ** R ** , -SR ** , -S(O)R ** , -S(O)2R ** , -S(O)2-NR ** R ** , and -N(R ** )-S(O)2-NR ** R ** is independently selected from; R ** is H, C optionally substituted with halogen 1~6 alkyl, halogen or C 1~6 heterocyclyl optionally substituted with alkyl, and halogen or C 1~6 carbocyclyl optionally substituted with alkyl, and any two R ** connected to the same nitrogen atom can optionally be linked).

[0020] In a preferred embodiment of the present invention, the compound of formula (I) is a compound of formula (V).

[0021]

Chemical formula

[0022] In a more preferred embodiment of the present invention, the compound of formula (I) is a compound of formula (VI).

[0023]

Chemical formula

[0024] In another preferred embodiment of the present invention, X 2 and X 3 are N, and preferably X 1 is CH.

[0025] In another preferred embodiment of the present invention, R 21 is CH3 or CH2CH3, and preferably R 21 is CH3.

[0026] In another preferred embodiment of the present invention, R 31 is selected from hydrogen and C 1~2 -alkyl, and preferably R 31 is hydrogen.

[0027] In another preferred embodiment of the present invention, E is selected from -CH2-, -O-, -CH2-O- and -CH2-CH2-, and preferably E is -CH2-.

[0028] In another preferred embodiment of the present invention, the number of R x groups in ring A is 0, 1, or 2, and preferably each R x is halogen, OH, O-C xa alkyl optionally substituted in one or more R 1~2 , NH-C xa alkyl optionally substituted in one or more R 1~2 , N(C xa alkyl)2 optionally substituted in one or more R 1~2 =O, C xa alkyl optionally substituted in one or more R 1~3 C 1~2 haloalkyl, -W-monocyclic carbocyclyl optionally substituted in one or more R xa , -W-monocyclic heterocyclyl optionally substituted in one or more R xa independently selected from, -W- is absent or -C 1~2alkylene- or -O-C 1~2 is alkylene, the monocyclic carbocyclyl is selected from phenyl and C 3~6 cycloalkyl, the monocyclic heterocyclyl is selected from thiophenyl, pyridyl, pyrazinyl and pyrimidinyl, and said R xa is independently selected from Cl, F, and OH.

[0029] In another preferred embodiment of the present invention, R 1 is selected from optionally substituted heterocyclyl and optionally substituted carbocyclyl, preferably R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl independently containing one or more ring heteroatoms each independently selected from O, S and N, and 8- to 10-membered bicyclic heteroaryl, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, C 1~6 alkyl, C 1~6 haloalkyl, -O-C 1~6 alkyl, -O-C 1~6 haloalkyl, OH, CN, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R*)-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R *and one or more substituents independently and optionally selected from monocyclic carbocyclyl of 3 to 6 members and monocyclic heterocyclyl of 3 to 6 members containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic carbocyclyl and heterocyclyl being independently and optionally substituted with one or more substituents selected from halogen, C 1~4 alkyl, C 1~4 haloalkyl, -O-C 1~4 alkyl, -O-C 1~4 haloalkyl, -OH, =O, -C(O)R * and -C(O)NR * R * and independently and optionally substituted with one or more substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-.

[0030] In another preferred embodiment of the present invention, R 3 is selected from phenyl, monocyclic heteroaryl of 6 members independently containing one or more ring heteroatoms each independently selected from O, B, S and N, and bicyclic heteroaryl of 8 to 10 members, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl being optionally oxidized, said phenyl, said monocyclic heteroaryl of 6 members, and said bicyclic heteroaryl of 8 to 10 members being halogen, C 1~6 alkyl, C 1~6 haloalkyl, -O-C 1~6 alkyl, -O-C 1~6 haloalkyl, -OH, -CN, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R** )-C(O)R * 、-N(R ** )-C(O)-OR * 、-N(R ** )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R * 、and one or more substituents independently and optionally selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, each monocyclic carbocyclyl and heterocyclyl being independently and optionally substituted with one or more substituents selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-C 1~4 alkyl, -O-C 1~4 haloalkyl, -OH, =O, -C 1~3 alkylene-OR * 、-C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, cyclopropyl, cyclobutyl, oxetanyl, -C 1~2 alkylene-OH, -C 1~2 alkylene-O(C 1~2 alkyl), phenyl, each R ** is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene such as -CH2-CH2- and -CH2-CH2-CH2-, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0031] In another preferred embodiment of the present invention, X 2 and X 3 is N, and X 1 is CH; E is -CH2-; R 21 is CH3; R 6x is CH3; Ring A does not form a bicyclic moiety.

[0032] In another preferred embodiment of the present invention, the fibrotic disease is selected from the group consisting of pulmonary fibrosis, idiopathic pulmonary fibrosis, radiation-induced pneumonia, radiation fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, interstitial lung disease, myocardial infarction, cardiac fibrosis and hypertrophy, ischemic stroke, ischemic kidney disease, renal fibrosis, rheumatoid arthritis, liver fibrosis, NASH (non-alcoholic steatohepatitis), chronic hepatitis, cirrhosis, inflammatory bowel disease, Crohn's disease, scleroderma, keloid, postoperative fibrosis, chemotherapy-induced fibrosis (e.g., chemotherapy-induced pulmonary fibrosis or ovarian cortical fibrosis), nephrogenic systemic fibrosis, retroperitoneal fibrosis, myelofibrosis, mediastinal fibrosis, cystic fibrosis, asbestosis, asthma, pulmonary hypertension, systemic fibrosis, dermal fibrosis, hypertension-induced renal fibrosis and cardiac fibrosis.

[0033] In another preferred embodiment of the present invention, the fibrotic disease is interstitial lung disease (ILD), and optionally the interstitial lung disease is idiopathic interstitial pneumonia (IIP).

[0034] In a more preferred embodiment of the present invention, the idiopathic interstitial pneumonia is selected from the group consisting of chronic fibrotic interstitial pneumonia, smoking-related interstitial pneumonia and acute / subacute interstitial pneumonia.

[0035] In another more preferred embodiment of the present invention, the chronic fibrotic interstitial pneumonia is idiopathic pulmonary fibrosis (IPF).

[0036] In another preferred embodiment of the present invention, the fibrotic disease is non-hepatic steatohepatitis (NASH).

[0037] Further aspects and embodiments of the present invention will become apparent as the description continues.

Brief Description of the Drawings

[0038]

Figure 1

Figure 2

Modes for Carrying Out the Invention

[0039] Detailed Description Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The embodiments, preferred embodiments, and highly preferred embodiments described and disclosed herein are to be applied to all aspects and other embodiments, preferred embodiments, and highly preferred embodiments, whether specifically recited again or the repetition thereof is avoided for brevity.

[0040] As used herein, the articles "a" and "an" refer to one or more than one (i.e., at least one) of the grammatical objects of the article. The term "or" as used herein is to be understood to mean "and / or" unless the context clearly dictates otherwise.

[0041] The term "preferably" is not required in the present invention, but may result in improved technical effects, and is therefore used to describe features or embodiments that are desirable but not essential.

[0042] In the expression "optionally linked" as used herein, the term "linked" refers to a linking group obtained from two substituents by theoretically removing one hydrogen radical from each substituent and thus forming a single bond between the two radicals formed on the two substituents. This can be illustrated as follows:

[0043] [Chemical formula]

[0044] Although two aryl groups are used as examples in this description, the meaning of the term "linked" is clearly not limited to such groups.

[0045] The term "hydrocarbon group containing from 1 to 20 carbon atoms and optionally from 1 to 15 heteroatoms selected from O, N and S" refers to any group having from 1 to 20 carbon atoms and optionally from 1 to 15 (preferably from 1 to 10, more preferably from 1 to 8) heteroatoms selected from O, N and S, preferably containing at least one ring. "Hydrocarbon group containing from 1 to 20 carbon atoms and optionally from 1 to 15 heteroatoms selected from O, N and S" is not limited in any way, provided that it is a group containing from 1 to 20 carbon atoms and optionally from 1 to 15 heteroatoms selected from O, N, and S. For example, when the hydrocarbon group is an aliphatic group, it may contain one or more heteroatoms in the main chain or in one or more side chains. This term also means that it includes their bicyclic, tricyclic and polycyclic versions. When multiple rings are present, they can be separated from each other or fused. Examples of bicyclic hydrocarbon groups include fused bicyclic hydrocarbon groups such as naphthalene, as well as linked hydrocarbon groups such as biphenyl, bridged bicyclic hydrocarbon groups such as 1,4-diazabicyclo[2.2.2]octane, and spiro-type hydrogen groups. The rings can be either carbocyclic or heterocyclic and can be saturated, unsaturated or aromatic. All of the carbon atoms and heteroatoms can be present in one or more rings, or some of the carbon atoms and / or heteroatoms can be outside the ring, for example in a linking group (such as -(CH2) p - etc.). Examples of these groups include -(optionally substituted heterocyclyl) and -(optionally substituted carbocyclyl).

[0046] As used herein, the term "-(optionally substituted C 1~6 alkyl) which may contain from 1 to 3 oxygen atoms between carbon atoms" preferably refers to C 1~6Refers to a group in which one or more direct C-C bonds in an alkyl group are replaced by a C-O-C moiety. Examples thereof are -CH2-CH2-O-CH3, -CH2-CH2-O-CH2-CH3, -CH2-CH2-O-CH2-CH2-O-CH3 and -CH2-CH2-O-CH2-CH2-O-CH2-CH3.

[0047] As used herein, the term "alkyl" refers to a monovalent saturated acyclic (i.e., non-cyclic) hydrocarbon group which may be straight-chain or branched-chain. Thus, an "alkyl" group does not contain a carbon-carbon double bond or a carbon-carbon triple bond. "C 1~6 "alkyl" means an alkyl group having 1 to 6 carbon atoms. Preferred exemplary alkyl groups are methyl, ethyl, propyl (e.g., n-propyl or isopropyl), or butyl (e.g., n-butyl, isobutyl, sec-butyl, or tert-butyl). Unless otherwise defined, the term "alkyl" preferably refers to C 1~4 alkyl, more preferably methyl or ethyl, and even more preferably methyl.

[0048] As used herein, the term "alkylene" refers to an alkanediyl group, i.e., a divalent saturated acyclic hydrocarbon group which may be straight-chain or branched-chain. "C 1~6 "alkylene" denotes an alkylene group having 1 to 6 carbon atoms, and the term "C 0~3 "alkylene" indicates the presence of a covalent bond (corresponding to any "C0 alkylene") or C 1~3 "alkylene". Preferred exemplary alkylene groups are methylene (-CH2-), ethylene (e.g., -CH2-CH2- or -CH(-CH3)-), propylene (e.g., -CH2-CH2-CH2-, -CH(-CH2-CH3)-, -CH2-CH(-CH3)-, or -CH(-CH3)-CH2-), or butylene (e.g., -CH2-CH2-CH2-CH2-). Unless otherwise defined, the term "alkylene" preferably refers to C 1~4 alkylene (especially straight-chain C 1~4(including alkylene), more preferably methylene or ethylene, even more preferably methylene.

[0049] As used herein, the term "carbocyclic" refers to a hydrocarbon ring group including monocyclic rings as well as bridged, spiro and / or fused ring systems (e.g., which may be composed of two or three rings), and said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. Unless otherwise defined, "carbocyclic" preferably refers to aryl, cycloalkyl or cycloalkenyl. The number of carbon atoms of the carbocyclic group is not particularly limited, and is preferably 3 to 14, more preferably 3 to 7.

[0050] As used in the present invention, the term "heterocyclyl" refers to a ring group including monocyclic rings as well as bridged, spiro and / or fused ring systems (e.g., which may be composed of two or three rings), and said ring group contains one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, and the remaining ring atoms are carbon atoms, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further, said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. Unless otherwise defined, "heterocyclyl" preferably refers to heteroaryl, heterocycloalkyl or heterocycloalkenyl. The number of carbon atoms of the carbocyclic group is not particularly limited, and is preferably 5 to 14, more preferably 5 to 10.

[0051] As used herein, the term "aryl" refers to an aromatic hydrocarbon ring group containing a monocyclic aromatic ring, as well as a bridged ring and / or a fused ring system containing at least one aromatic ring (e.g., a ring system composed of two or three fused rings, at least one of these fused rings being aromatic; or a bridged ring system composed of two or three rings, at least one of these bridged rings being aromatic). "Aryl" can refer to, for example, phenyl, naphthyl, dihydronaphthyl (i.e., 1,2-dihydronaphthyl), tetrahydronaphthyl (i.e., 1,2,3,4-tetrahydronaphthyl), anthracenyl, or phenanthrenyl. Unless otherwise defined, "aryl" preferably has 5 to 14 ring atoms, more preferably 5 to 10 ring atoms, and most preferably refers to phenyl.

[0052] As used herein, the term "heteroaryl" refers to an aromatic ring group that includes a monocyclic aromatic ring, as well as a bridged ring and / or a fused ring system containing at least one aromatic ring (e.g., a ring system composed of two or three fused rings, at least one of these fused rings being aromatic; or a bridged ring system composed of two or three rings, at least one of these bridged rings being aromatic), the aromatic ring group containing one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, the remaining ring atoms being carbon atoms, one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further, one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group)."Heteroaryl" can refer to, for example, thienyl (i.e., thiophenyl), benzothienyl, naphtho[2,3-b]thienyl, thianthrenyl, furyl (i.e., furanyl), benzofuranyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathiinyl, pyrrolyl (e.g., 2H-pyrrolyl), imidazolyl, pyrazolyl, pyridyl (i.e., pyridinyl; e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl), pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, indolyl (e.g., 3H-indolyl), indazolyl, purinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl (e.g., [1,10]phenanthrolinyl, [1,7]phenanthrolinyl, or [4,7]phenanthrolinyl), phenazinyl, thiazolyl, isothiazolyl, phenothiazinyl, oxazolyl, isoxazolyl, furazanyl, phenoxazinyl, pyrazolo[1,5-a]pyrimidinyl (e.g., pyrazolo[1,5-a]pyrimidin-3-yl), 1,2-benzisoxazol-3-yl, benzothiazolyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, 1H-tetrazolyl, 2H-tetrazolyl, coumarinyl, or chromonyl.Unless otherwise defined, "heteroaryl" preferably refers to a 5- to 14-membered (more preferably 5- to 10-membered) monocyclic ring or fused ring system containing one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, where one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and one or more carbocyclic atoms are optionally oxidized; even more preferably, "heteroaryl" refers to a 5- or 6-membered monocyclic ring containing one or more (e.g., 1, 2, or 3) ring heteroatoms independently selected from O, S, and N, where one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and one or more carbocyclic atoms are optionally oxidized.

[0053] As used herein, the term "cycloalkyl" refers to a saturated hydrocarbon ring group including monocyclic rings as well as bridged rings, spiro rings and / or fused ring systems (e.g., which may be composed of two or three rings; by way of example, a fused ring system composed of two or three fused rings). "Cycloalkyl" can refer to, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or adamantyl. Unless otherwise defined, "cycloalkyl" preferably refers to C 3~14 refers to cycloalkyl, more preferably C 3~7 refers to cycloalkyl. Particularly preferred "cycloalkyl" is a monocyclic saturated hydrocarbon ring having 3 to 7 ring members.

[0054] As used herein, the term "heterocycloalkyl" refers to a saturated cyclic group that includes monocyclic rings as well as bridged, spiro, and / or fused ring systems (e.g., which may be composed of two or three rings; by way of example, a fused ring system composed of two or three fused rings), said cyclic group containing one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, with the remaining ring atoms being carbon atoms, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further, one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). "Heterocycloalkyl" may refer to, for example, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, morpholine (e.g., morpholin-4-yl), pyrazolidinyl, tetrahydrothienyl, octahydroquinolinyl, octahydroisoquinolinyl, oxazolidinyl, isoxazolidinyl, azepanyl, diazepanyl, oxazepanyl or 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl. Unless otherwise defined, "heterocycloalkyl" preferably refers to a saturated cyclic group of 3 to 14 members, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), said cyclic group containing one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and one or more carbon ring atoms are optionally oxidized; more preferably, "heterocycloalkyl" refers to a 5- to 7-membered saturated monocyclic ring group containing one or more (e.g., 1, 2, or 3) ring heteroatoms independently selected from O, S, and N, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and one or more carbon ring atoms are optionally oxidized.

[0055] As used herein, the term "cycloalkenyl" refers to an unsaturated alicyclic (non-aromatic) hydrocarbon ring group that includes monocyclic rings as well as bridged, spiro, and / or fused ring systems (e.g., may be composed of two or three rings; by way of example, a fused ring system composed of two or three fused rings), wherein the hydrocarbon ring group contains one or more (e.g., one or two) carbon-carbon double bonds and no carbon-carbon triple bonds. "Cycloalkenyl" can refer to, for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, or cycloheptadienyl. Unless otherwise defined, "cycloalkenyl" preferably refers to C 3~14 cycloalkenyl, more preferably to C 3~7 cycloalkenyl. Particularly preferred "cycloalkenyl" is a monocyclic unsaturated alicyclic hydrocarbon ring having 3 to 7 ring members and containing one or more (e.g., one or two; preferably one) carbon-carbon double bonds.

[0056] As used herein, the term "heterocycloalkenyl" refers to an unsaturated alicyclic (non-aromatic) ring group that includes monocyclic rings as well as bridged, spiro, and / or fused ring systems (e.g., which may be composed of two or three rings; by way of example, a fused ring system composed of two or three fused rings), said ring group containing one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, with the remaining ring atoms being carbon atoms, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further, said ring group contains at least one double bond between adjacent ring atoms and no triple bond between adjacent ring atoms. "Heterocycloalkenyl" can refer to, for example, 1,2,3,6-tetrahydropyridinyl. Unless otherwise defined, "heterocycloalkenyl" preferably refers to an unsaturated alicyclic ring group having 3 to 14 members, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), said ring group containing one or more (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and one or more carbon ring atoms are optionally oxidized; said ring group contains at least one double bond between adjacent ring atoms and no triple bond between adjacent ring atoms; more preferably, "heterocycloalkenyl" refers to a monocyclic unsaturated non-aromatic ring group having 3 to 7 members containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S, and N, and one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and one or more carbon ring atoms are optionally oxidized; said ring group contains at least one double bond between adjacent ring atoms and no triple bond between adjacent ring atoms.

[0057] As used herein, the term "halogen" refers to fluoro (-F), chloro (-Cl), bromo (-Br), or iodo (-I).

[0058] As used herein, the term "haloalkyl" refers to an alkyl group substituted with one or more (preferably 1 to 6, more preferably 1 to 3) halogen atoms independently selected from fluoro, chloro, bromo and iodo, preferably all fluoro atoms. The maximum number of halogen atoms is limited by the number of available bonding sites and thus it will be understood to depend on the number of carbon atoms in the alkyl portion of the haloalkyl group. "Haloalkyl" can refer to, for example, -CF3, -CHF2, -CH2F, -CF2-CH3, -CH2-CF3, -CH3-CHF2, -CH2-CF2-CH3, -CH2-CF2-CF3, or -CH(CF3)2. Highly preferred "haloalkyls" as substituents of the compounds of the present invention are -CF3, -CHF2, and -CH2-CF3, and even more preferably -CF3 and -CHF2.

[0059] In this specification, various groups are referred to as "optionally substituted". In general, these groups can have one or more substituents, for example, one, two, three, or four substituents. It will be understood that the maximum number of substituents is limited by the number of available bonding sites in the substituted moiety. Unless otherwise defined, an "optionally substituted" group referred to herein preferably has two or fewer substituents, and in particular may have only one substituent. Further, unless otherwise defined, it is preferred that no optional substituent is present, i.e., the corresponding group is unsubstituted.

[0060] As used herein, the terms "any", "optionally" and "may" indicate that the indicated feature may or may not be present. Whenever the terms "any", "optionally" and "may" are used, the invention specifically relates to both possibilities, namely, the corresponding feature is present or the corresponding feature is not present. For example, the expression "X is optionally substituted with Y" (or "X may be substituted with Y") means that X is either substituted with Y or unsubstituted. Similarly, when it is indicated that a component of a composition is "optional", the invention specifically relates to both possibilities, namely, the corresponding component is present (included in the composition) or the corresponding component is not present in the composition.

[0061] One of ordinary skill in the art will understand that the substituents contained in the compounds of formula (I) can each be attached to the remainder of the respective compound via a plurality of different positions of the corresponding specific substituent. Unless otherwise defined, the preferred attachment positions of the various specific substituents are as shown in the Examples.

[0062] As used herein, the term "about" preferably refers to ±10% of the indicated numerical value, more preferably ±5% of the indicated numerical value, particularly the exact numerical value indicated.

[0063] The scope of the present invention includes all pharmaceutically acceptable salt forms of the compounds of formula (I) which can be formed, for example, by protonation of an atom having a lone pair which is susceptible to protonation by an inorganic or organic acid, such as an amino group, or as a salt of an acid group (such as a carboxylic acid group) with a physiologically acceptable cation. Exemplary base addition salts include, for example, alkali metal salts such as sodium or potassium salts; alkaline earth metal salts such as calcium or magnesium salts; zinc salts; ammonium salts; aliphatic amine salts such as trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, procaine salt, meglumine salt, ethylenediamine salt, or choline salt; aralkylamine salts such as N,N-dibenzylethylenediamine salt, benzathine salt, benethamine salt; heterocyclic aromatic amine salts such as pyridine salt, picoline salt, quinoline salt or isoquinoline salt; quaternary ammonium salts such as tetramethylammonium salt, tetraethylammonium salt, benzyltrimethylammonium salt, benzyltriethylammonium salt, benzyltributylammonium salt, methyltrioctylammonium salt or tetrabutylammonium salt; and basic amino acid salts such as arginine salt, lysine salt, or histidine salt.Exemplary acid addition salts include, for example: mineral acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate (e.g., sulfate or bisulfate), nitrate, phosphate (e.g., phosphate, hydrogen phosphate, or dihydrogen phosphate), carbonate, bicarbonate, perchlorate, borate, or thiocyanate; organic acid salts such as acetate, propionate, butyrate, pentanoate, hexanoate, heptanoate, octanoate, cyclopentanepropionate, decanoate, undecanoate, oleate, stearate, lactate, maleate, oxalate, fumarate, tartrate, malate, citrate, succinate, adipate, gluconate, glycolate, nicotinate, benzoate, salicylate, ascorbate, pamoate (embonate), camphorate, heptanoate, or pivalate; sulfonate salts such as methanesulfonate (mesylate), ethanesulfonate (esylate), 2-hydroxyethanesulfonate (isethionate), benzenesulfonate (besylate), p-toluenesulfonate (tosylate), 2-naphthalenesulfonate (napsylate), 3-phenylsulfonate, or camphorsulfonate; glycerophosphate salts; and acidic amino acid salts such as aspartate or glutamate. Preferred pharmaceutically acceptable salts of the compound of formula (I) include hydrochloride, hydrobromide, mesylate, sulfate, tartrate, fumarate, acetate, citrate, and phosphate. A particularly preferred pharmaceutically acceptable salt of the compound of formula (I) is hydrochloride. Accordingly, the compound of formula (I) includes any one of the specific compounds of formula (I) described herein and is preferably in the form of hydrochloride, hydrobromide, mesylate, sulfate, tartrate, fumarate, acetate, citrate, or phosphate, and particularly preferably in the form of hydrochloride.

[0064] "Solvate" refers to an association or complex of one or more solvent molecules with a compound of formula (I). Examples of solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide (DMSO), ethyl acetate, acetic acid, acetonitrile, and ethanolamine. The term "hydrate" refers to a complex in which the solvent molecule is water. It should be understood that such solvates of the compound of formula (I) also include solvates of pharmaceutically acceptable salts of the compound of formula (I).

[0065] "Co-crystal" refers to a crystal structure containing at least two different compounds that are solids in their pure form under ambient conditions. Co-crystals are made from neutral molecular species and all species remain neutral after crystallization; furthermore, typically and preferably, they are crystalline homogeneous phase materials in which two or more building compounds are present in a defined stoichiometric ratio. See Wang Y and Chen A, 2013; and Springuel GR et al., 2012; and U.S. Patent 6,570,036.

[0066] Furthermore, the compound of formula (I) can exist in different isomeric forms, particularly stereoisomers (e.g., including geometric isomers (or cis / trans isomers), enantiomers, and diastereomers) or tautomers. All such isomers of the compound of formula (I) are considered to be part of the present invention, either in a mixture or in pure or substantially pure form. With respect to stereoisomers, the present invention encompasses isolated optical isomers of the compounds according to the invention, as well as any mixtures thereof (particularly including racemic mixtures / racemates). Racemates can be resolved, for example, by physical methods such as fractional crystallization, separation or crystallization of diastereomeric derivatives, or separation by chiral column chromatography. Individual optical isomers can also be obtained from the racemate via salt formation with an optically active acid followed by crystallization. The present invention further encompasses any tautomers of the compounds provided herein.

[0067] The scope of the present invention also encompasses compounds of formula (I) in which one or more atoms are replaced by specific isotopes of the corresponding atoms. For example, the present invention encompasses compounds of formula (I) in which one or more hydrogen atoms (or, for example, all hydrogen atoms) are replaced by deuterium atoms (i.e., 2 H; also called "D"). Thus, the present invention also encompasses deuterium-enriched compounds of formula (I). Naturally occurring hydrogen is an isotopic mixture containing approximately 99.98 mol-% hydrogen-1 ( 1 H) and approximately 0.0156 mol-% deuterium ( 2 H or D). The deuterium content at one or more hydrogen positions in the compounds of formula (I) can be increased using deuteration techniques known in the art. For example, a compound of formula (I) or a reactant or precursor used in the synthesis of a compound of formula (I) can be subjected to an H / D exchange reaction using, for example, heavy water (D2O). Further suitable deuteration techniques are described below: Atzrodt J et al., Bioorg Med Chem, 20(18), 5658 - 5667, 2012; William JS et al., Journal of Labelled Compounds and Radiopharmaceuticals, 53(11 - 12), 635 - 644, 2010; Modvig A et al., J Org Chem, 79, 5861 - 5868, 2014. The deuterium content can be determined, for example, using mass spectrometry or NMR spectroscopy. Unless otherwise specified, it is preferred that the compounds of formula (I) are not deuterium-enriched. Thus, it is preferred that hydrogen atoms that are naturally present in the compounds of formula (I) or 1 H hydrogen atoms are present.

[0068] The present invention also encompasses compounds in which one or more atoms are positron-emitting isotopes of the corresponding atoms, for example, 18 F, 11 C, 13 N, 15 O, 76 Br, 77 Br, 120 I and / or 124I. It includes compounds of formula (I) that are replaced thereby. Such compounds can be used as tracers or imaging probes for positron emission tomography (PET). Thus, the present invention relates to (i) compounds of formula (I) in which one or more fluorine atoms (or, for example, all fluorine atoms) are 18 replaced by F atoms, (ii) compounds of formula (I) in which one or more carbon atoms (or, for example, all carbon atoms) are 11 replaced by C atoms, (iii) compounds of formula (I) in which one or more nitrogen atoms (or, for example, all nitrogen atoms) are 13 replaced by N atoms, (iv) compounds of formula (I) in which one or more oxygen atoms (or, for example, all oxygen atoms) are 15 replaced by O atoms, (v) compounds of formula (I) in which one or more bromine atoms (or, for example, all bromine atoms) are 76 replaced by Br atoms, (vi) compounds of formula (I) in which one or more bromine atoms (or, for example, all bromine atoms) are 77 replaced by Br atoms, (vii) compounds of formula (I) in which one or more iodine atoms (or, for example, all iodine atoms) are 120 replaced by I atoms, and (viii) compounds of formula (I) in which one or more iodine atoms (or, for example, all iodine atoms) are 124 replaced by I atoms. Generally, it is preferred that no atom in the compounds of formula (I) is replaced by a specific isotope.

[0069] In a first aspect, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof

[0070]

Chemical formula

[0071] (wherein, R 1 is selected from halogen and -(optionally substituted hydrocarbon group containing 1 to 20 carbon atoms and optionally 1 to 15 heteroatoms selected from O, N, and S); R 21 is hydrogen, -(optionally substituted C 1~6 alkyl) which may contain 1 to 3 oxygen atoms between carbon atoms, and -(optionally substituted C 3~6 cycloalkyl); R 3 is -(optionally substituted heterocyclyl), -(optionally substituted carbocyclyl), -(optionally substituted C 1~6 alkylene)-(optionally substituted heterocyclyl), and -(optionally substituted C 1~6 alkylene)-(optionally substituted carbocyclyl); X 1 、X 2 、and X 3 each is independently selected from N, CH, and CR x ; at least one of said X 1 、X 2 、and X 3 is N; more preferably, at least one of X 2 and X 3 is N; even more preferably, X 2 and X 3 are both N; still more preferably, X 2 and X 3 are both N, and X 1 is CH; R 31 is -hydrogen, -C 1~6 -alkyl, and -(C 1~6 -alkyl substituted with one or more F); R 3 and any R 31 can be optionally linked; E is absent or -CH2-, -CHR x -, -CRx 2-, -NH-, -NR x -, -O-, -L 1 -L 2 -, and -L 2 -L 1 selected from -, L1 is -CH2-, -CHR x -, -CR x 2-, -NH-, -NR x -, and -O-; and L 2 is selected from -CH2-, -CHR x - and -CR x 2-; R 6x is -halogen, -OH, =O, C 1~6 alkyl, C 1~6 haloalkyl, C substituted with one or more OH 1~6 alkyl, monocyclic aryl optionally substituted with one or more R xb in, monocyclic heteroaryl optionally substituted with one or more R xb in, monocyclic cycloalkyl optionally substituted with one or more R xb in, monocyclic heterocycloalkyl optionally substituted with one or more R xb in, monocyclic cycloalkenyl optionally substituted with one or more R xb in, monocyclic heterocycloalkenyl optionally substituted with one or more R, and said R xb is selected independently from -halogen, -OH, =O, C xb alkyl, C 1~4 haloalkyl, C substituted with one or two OH 1~2 alkyl; 1~2 Ring A may be further substituted with one or more R groups, and any two R x groups of ring A may be optionally linked, and / or any R x group of ring A may be optionally linked to R x ; and / or, ring A, together with R 21 has the following partial structure: 6x ;

[0072]

Chem.

[0073] To form a bicyclic moiety having one group R x which may be further substituted with Ring B is -(optionally substituted heterocyclic ring) or -(optionally substituted carbocyclic ring); Each R x is selected independently from - halogen, -OH, -O-(optionally substituted C 1~6 alkyl), -NH-(optionally substituted C 1~6 alkyl), -N(optionally substituted C 1~6 alkyl)2, =O, -(optionally substituted C 1~6 alkyl), -(optionally substituted carbocyclyl), -(optionally substituted heterocyclyl), -(optionally substituted C 1~6 alkylene)-(optionally substituted carbocyclyl), -(optionally substituted C 1~6 alkylene)-(optionally substituted heterocyclyl), -O-(optionally substituted C 1~6 alkylene)-(optionally substituted carbocyclyl), and -O-(optionally substituted C 1~6 alkylene)-(optionally substituted heterocyclyl), The optional substituents of the optionally substituted hydrocarbon group, optionally substituted C 3~6 cycloalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclic ring, optionally substituted carbocyclyl, optionally substituted carbocyclic ring and optionally substituted C 1~6 alkylene are -(optionally substituted C 1~6 alkyl which is substituted with one or more halogens optionally), - halogen, -CN, -NO2, oxo, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R* , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -N(R * )-S(O)2R * , -OR * , -O-C(O)R * , -O-C(O)-NR * R * , -SR * , -S(O)R * , -S(O)2R * , -S(O)2-NR * R * , -N(R * )-S(O)2-NR * R * , halogen or a heterocyclyl optionally substituted in C 1~6 alkyl, and a carbocyclyl optionally substituted in halogen or C 1~6 alkyl, independently selected; each R * is independently selected from H, C 1~6 alkyl optionally substituted in halogen, halogen or C 1~6 alkyl optionally substituted in heterocyclyl, and halogen or C 1~6 alkyl optionally substituted in carbocyclyl; any two R * connected to the same nitrogen atom can optionally be linked, optionally substituted C 1~6 alkyl and optionally substituted C 1~6 alkylene optional substituents are -halogen, -CN, -NO2, oxo, -C(O)R ** , -COOR ** , -C(O)NR ** R ** , -NR ** R ** , -N(R ** )-C(O)R ** , -N(R **)-C(O)-OR ** 、-N(R ** )-C(O)-NR ** R ** 、-N(R ** )-S(O)2R ** 、-OR ** 、-O-C(O)R ** 、-O-C(O)-NR ** R ** 、-SR ** 、-S(O)R ** 、-S(O)2R ** 、-S(O)2-NR ** R ** 、および-N(R ** )-S(O)2-NR ** R ** is independently selected from; R ** is H, C 1~6 alkyl optionally substituted with halogen, halogen or C 1~6 heterocyclyl optionally substituted in alkyl, and halogen or C 1~6 carbocyclyl optionally substituted in alkyl; any two R ** connected to the same nitrogen atom can optionally be linked).

[0074] In a preferred embodiment, at least one of said X 1 , X 2 and X 3 is N. In a more preferred embodiment, at least one of said X 2 and X 3 is N. In a more preferred embodiment, X 2 is N. In another preferred embodiment, X 2 and X 3 are both N. Thus, in a more preferred embodiment, the compound of formula (I) is a compound of formula (Ia).

[0075]

Chemical formula

[0076] In a further preferred embodiment, X1 is nitrogen or CH, and X 2 and X 3 are both N. In a further highly preferred embodiment, X 1 is CH, and X 2 and X 3 are both N. Accordingly, in a further preferred embodiment, the compound of formula (I) is a compound of formula (Ib).

[0077]

Chemical formula

[0078] R 31 is selected from -hydrogen, -C 1~6 -alkyl, and -(C 1~6 -alkyl substituted with one or more F); R 3 and any R 31 can be optionally linked. When R 3 and R 31 are linked, a cyclic group such as a 3- to 8-membered ring containing 1 to 8 carbon atoms and optionally 1 to 4 heteroatoms selected from N, O, and S can be formed. These cyclic groups usually contain carbon or nitrogen to which R 31 is attached as one ring member. Examples of such cyclic groups are cyclopentane ring, cyclohexane ring, pyrrolidine ring, piperidine ring, and morpholine ring. In a further preferred embodiment, said R 31 is selected from -hydrogen, -C 1~4 -alkyl, and -C 1~2 -fluoroalkyl. In a further preferred embodiment, said R 31 is selected from -hydrogen, -C 1~2 -alkyl, and -C1-fluoroalkyl. In a further preferred embodiment, said R 31 is selected from -hydrogen and methyl. In a further highly preferred embodiment, said R 31 is hydrogen. Accordingly, in a further preferred embodiment, the compound of formula (I) is a compound of formula (II).

[0079]

Chem.

[0080] In a further preferred embodiment, the compound of formula (I) is a compound of formula (IIa).

[0081]

Chem.

[0082] In an even more preferred embodiment, the compound of formula (I) is a compound of formula (IIb).

[0083]

Chem.

[0084] In a further preferred embodiment, E is selected from -CH2-, -NH-, -O-, -CH2-O-, -O-CH2-, -CH2-NH-, -NH-CH2- and -CH2-CH2-. More preferably, E is selected from CH2-, -O-, -CH2-O-, -O-CH2-, and -CH2-CH2-. Even more preferably, E is selected from CH2-, -O-, -CH2-O-, and -CH2-CH2-. Even more preferably, E is CH2. Accordingly, in a further preferred embodiment, the compound of formula (I) is a compound of formula (III).

[0085]

Chem.

[0086] In a further preferred embodiment, the compound of formula (I) is a compound of formula (IIIa).

[0087]

Chem.

[0088] In an even more preferred embodiment, the compound of formula (I) is a compound of formula (IIIb).

[0089]

Chem.

[0090] In an even more highly preferred embodiment, the compound of formula (I) is a compound of formula (IV).

[0091]

Chem.

[0092] In a further preferred embodiment, the compound of formula (I) is a compound of formula (IVa).

[0093]

Chem.

[0094] In an even more preferred embodiment, the compound of formula (I) is a compound of formula (IVb).

[0095]

Chem.

[0096] In further aspects and embodiments, the present invention provides a compound of formula (I), preferably a compound of formula (Ia), more preferably a compound of formula (Ib), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof, for use in a method of treating a fibrotic disease.

[0097]

Chem.

[0098] The inventors have further surprisingly found that the enantiomers of the compounds of the present invention represented by formula (V) are significantly more active than the other enantiomers or diastereomers of said compounds. Thus, in further aspects and embodiments, the present invention provides a compound of formula (I), said compound of formula (I) being a compound of formula (V), preferably formula (Va), more preferably formula (Vb) for use in a method of treating a fibrotic disease, optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof

[0099]

Chemical formula

[0100] (wherein R 1 is selected from halogen and -(optionally substituted hydrocarbon group containing 1 to 20 carbon atoms and optionally 1 to 15 heteroatoms selected from O, N, and S); R 21 is hydrogen, -(optionally substituted C 1~6 alkyl) which may contain 1 to 3 oxygen atoms between carbon atoms, and -(optionally substituted C 3~6 cycloalkyl); R 3 is -(optionally substituted heterocyclyl), -(optionally substituted carbocyclyl), -(optionally substituted C 1~6 alkylene)-(optionally substituted heterocyclyl), and -(optionally substituted C 1~6 alkylene)-(optionally substituted carbocyclyl); X 1 、X 2 、and X 3 each is independently selected from N, CH, and CR x ; said X 1 、X 2 、and X3 At least one of which is N, and more preferably, X 2 and X 3 At least one of which is N; even more preferably, X 2 and X 3 Both are N, and even more preferably, X 2 and X 3 Both are N, X 1 is CH; R 31 is selected from -hydrogen, -C 1~6 -alkyl, and -(C-alkyl substituted with one or more F 1~6 -alkyl); R 3 and any R 31 can be optionally linked; E is absent or is selected from -CH2-, -CHR x -, -CR x 2-, -NH-, -NR x -, and -O-, -L 1 -L 2 -, and -L 2 -L 1 -; L 1 is selected from -CH2-, -CHR x -, -CR x 2-, -NH-, -NR x -, and -O-; L 2 is selected from -CH2-, -CHR x - and -CR x 2-; R 6x is selected from -halogen, -OH, =O, C 1~6 alkyl, C 1~6 haloalkyl, C-alkyl substituted with one or more OH 1~6 alkyl, monocyclic aryl optionally substituted with one or more R xb in, monocyclic heteroaryl optionally substituted with one or more R xb in, monocyclic cycloalkyl optionally substituted with one or more R xb in, one or more R xbOptionally substituted monocyclic heterocycloalkyl, one or more Rs xb Optionally substituted monocyclic cycloalkenyl, one or more Rs xb Optionally substituted monocyclic heterocycloalkenyl, said Rs xb are independently selected from: - halogen, -OH, =O, C 1~4 alkyl, C 1~2 haloalkyl, C substituted with one or two OHs 1~2 alkyl; Ring A may be further substituted with one or more Rs x groups, and any two Rs on ring A x groups may optionally be linked, and / or any R on ring A x group may optionally be linked to R 2 ; and / or, ring A may, together with R 6x form a bicyclic moiety having the following partial structure:

[0101]

Chemical formula

[0102] be further substituted with one R x group; Ring B is -(optionally substituted heterocycle) or -(optionally substituted carbocycle); Each R x is independently selected from: - halogen, -OH, -O-(optionally substituted C 1~6 alkyl), -NH-(optionally substituted C 1~6 alkyl), -N(optionally substituted C 1~6 alkyl)2, =O, -(optionally substituted C 1~6 alkyl), -(optionally substituted carbocyclyl), -(optionally substituted heterocyclyl), -(optionally substituted C 1~6 alkylene)-(optionally substituted carbocyclyl), -(optionally substituted C 1~6(alkylene)-(optionally substituted heterocyclyl), -O-(optionally substituted C 1~6 (alkylene)-(optionally substituted carbocyclyl), and -O-(optionally substituted C 1~6 (alkylene)-(optionally substituted heterocyclyl) independently selected from; optionally substituted hydrocarbon group, optionally substituted C 3~6 cycloalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclic ring, optionally substituted carbocyclyl, optionally substituted carbocyclic ring and optionally substituted C 1~6 Optional substituents of alkylene are -(optionally substituted with one or more halogens C 1~6 alkyl), -halogen, -CN, -NO2, oxo, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -N(R * )-S(O)2R * , -OR * , -O-C(O)R * , -O-C(O)-NR * R * , -SR * , -S(O)R * , -S(O)2R * , -S(O)2-NR * R * , -N(R * )-S(O)2-NR * R * , halogen or C 1~6 heterocyclyl optionally substituted in alkyl, and halogen or C 1~6 carbocyclyl optionally substituted in alkyl, independently selected; each R* is independently selected from C optionally substituted in H, halogen 1~6 alkyl, halogen or C 1~6 heterocyclyl optionally substituted in alkyl, and halogen or C 1~6 carbocyclyl optionally substituted in alkyl; any two Rs connected to the same nitrogen atom * can be optionally linked, optionally substituted C 1~6 alkyl and optionally substituted C 1~6 Optional substituents of alkylene are -halogen, -CN, -NO2, oxo, -C(O)R ** , -COOR ** , -C(O)NR ** R ** , -NR ** R ** , -N(R ** )-C(O)R ** , -N(R ** )-C(O)-OR ** , -N(R ** )-C(O)-NR ** R ** , -N(R ** )-S(O)2R ** , -OR ** , -O-C(O)R ** , -O-C(O)-NR ** R ** , -SR ** , -S(O)R ** , -S(O)2R ** , -S(O)2-NR ** R ** , and -N(R ** )-S(O)2-NR ** R ** and are independently selected from; R ** is H, C optionally substituted in halogen 1~6 alkyl, halogen or C 1~6 heterocyclyl optionally substituted in alkyl, and halogen or C 1~6Independently selected from carbocyclic groups optionally substituted in the alkyl; any two Rs attached to the same nitrogen atom ** (which can optionally be linked). In a further preferred embodiment, X 2 and X 3 are both nitrogen. In a further preferred embodiment, X 1 is CH.

[0103] In a further preferred embodiment, said R 31 is selected from -hydrogen, -C 1~4 -alkyl, and -C 1~2 -fluoroalkyl. In a further preferred embodiment, said R 31 is selected from -hydrogen, -C 1~2 -alkyl, and -C1-fluoroalkyl. In a further preferred embodiment, said R 31 is selected from -hydrogen and methyl. In a further preferred embodiment, said R 31 is -hydrogen.

[0104] In a preferred embodiment, said R 21 is selected from hydrogen, C 1~6 alkyl, C 1~6 haloalkyl, C 1~6 alkyl optionally substituted in one or more OH, C 1~6 alkyl containing 1 to 3 oxygen atoms between carbon atoms, and C 22 cycloalkyl optionally substituted in one or more R 3~6 , where R 22 is selected from halogen, preferably -Cl, -F, and -OH. In a further preferred embodiment, said R 21 is selected from hydrogen, C 1~2 alkyl, C 1~2 haloalkyl, C 1~2 alkyl optionally substituted in one or two OH, and C 22 cycloalkyl optionally substituted in one or more R 3~4 , where R 22is selected from -Cl, -F, and -OH. In a further preferred embodiment, said R 21 is C 1~2 alkyl, C 1~2 haloalkyl and C 3~4 cycloalkyl. In a further preferred embodiment, said R 21 is C 1~2 alkyl and cyclopropyl. In a further preferred embodiment, said R 21 is methyl. In a further preferred embodiment, said R 21 is ethyl. In a further preferred embodiment, said R 21 is cyclopropyl.

[0105] Ring A may be further substituted with one or more R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 ; the number of R x groups on ring A is understood to be 0, 1, 2, 3, or 4, preferably 0, 1, 2, or 3, more preferably 0, 1, or 2, or alternatively preferably 0 or 1. Ring A may be substituted with one or more R x groups, and if one of said R x groups on ring A is optionally linked to R 21 , said one of the R 21 groups on ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0106] Thus, in a preferred embodiment, said ring A is further substituted with 1, 2, 3, or 4 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 . One of said R x groups on ring A is R21 When optionally linked to R 21 Said R of ring A optionally linked to x One of said groups is a substituent at the 2-position of ring A.

[0107] In a preferred embodiment, said ring A is further substituted with 1, 2 or 3 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to 21 R is a substituent at the 2-position of ring A. 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to

[0108] In a preferred embodiment, said ring A is further substituted with 1 or 2 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to 21 R is a substituent at the 2-position of ring A. 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to

[0109] In a preferred embodiment, said ring A is further substituted with 1 R x group, and said R x group of ring A is optionally linked to R 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to 21 R is a substituent at the 2-position of ring A. 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to

[0110] In a preferred embodiment, the ring A is further substituted with one R x group, and the R x group of the ring A is not linked to R 21 .

[0111] In a preferred embodiment, the ring A is further substituted with one R x group, and the R x group of the ring A is not linked to R 21 . In a further preferred embodiment, the R x group is -F, and preferably, the R x group that is -F is at the 3-position of the ring A, and the position connects the ring A to the X 1 , X 2 , X 3 ring system.

[0112] In a preferred embodiment, the ring A is not further substituted. Thus, in a preferred embodiment, the ring A is not further substituted with an R x group.

[0113] In a further preferred embodiment, the E is selected from -CH2-, -CHCH3-, -C(CH3)2-, -NH-, -N(CH3)-, -O-, -L 1 -L 2 - and -L 2 -L 1 , where L 1 is selected from -CH2-, -CHCH3-, -C(CH3)2-, -NH-, -N(CH3)-, and -O-, and L 2 is selected from -CH2-, -CHCH3-, -C(CH3)2-. In a further preferred embodiment, the E is selected from -CH2-, -CHCH3-, -NH-, -N(CH3)-, -O-, -L 1 -L 2 - and -L 2 -L 1 , where L 1 is selected from -CH2-, -CHCH3-, -NH-, -N(CH3)-, and -O-, and L 2is selected from -CH2- and -CHCH3-. In a further preferred embodiment, E is selected from -CH2-, -NH-, -O-, -CH2-O-, -O-CH2-, -CH2-NH-, -NH-CH2- and -CH2-CH2-. Preferably, E is selected from CH2-, -O-, -CH2-O-, -O-CH2- and -CH2-CH2-. More preferably, E is selected from CH2-, -O-, -CH2-O-, and -CH2-CH2-. Even more preferably, E is CH2; In a preferred embodiment, each R x is -halogen, -OH, -O-C xa alkyl optionally substituted in one or more R 1~3 -NH-C xa alkyl optionally substituted in one or more R 1~3 -N(C xa alkyl optionally substituted in one or more R 1~3 )2, =O, -C xa alkyl optionally substituted in one or more R 1~4 -C 1~4 haloalkyl, -(C xa alkylene optionally substituted in one or more R 1~2 )(optionally substituted carbocyclic), -(C xa alkylene optionally substituted in one or more R 1~2 )(optionally substituted heterocyclic), -O-(C xa alkylene optionally substituted in one or more R 1~2 )(optionally substituted carbocyclic), -O-(C xa alkylene optionally substituted in one or more R 1~2 )(optionally substituted heterocyclic), -(optionally substituted carbocyclic), and -(optionally substituted heterocyclic), independently selected, wherein said R xa is halogen, preferably independently selected from -Cl, -F, and -OH.

[0114] In a preferred embodiment, each R x is selected independently from -halogen, -OH, -O-C xa alkyl optionally substituted in one or more R 1~3 s, -NH-C xa alkyl optionally substituted in one or more R 1~3 s, -N(C xa alkyl optionally substituted in one or more R 1~3 s)2, =O, -C xa alkyl optionally substituted in one or more R 1~4 s, C 1~4 haloalkyl, -(C xa alkylene optionally substituted in one or more R 1~2 s)-(optionally substituted carbocyclic), -(C xa alkylene optionally substituted in one or more R 1~2 s)-(optionally substituted heterocyclic), -O-(C xa alkylene optionally substituted in one or more R 1~2 s)-(optionally substituted carbocyclic), -O-(C xa alkylene optionally substituted in one or more R 1~2 s)-(optionally substituted heterocyclic), -(optionally substituted carbocyclic), and -(optionally substituted heterocyclic), and said R xa is selected independently from halogen, preferably -Cl, -F, and -OH.

[0115] In a preferred embodiment, each R x is selected independently from -halogen, -OH, -O-C xa alkyl optionally substituted in one or more R 1~3 s, -NH-C xa alkyl optionally substituted in one or more R 1~3 s, -N(C xa alkyl optionally substituted in one or more R 1~3 s)2, =O, -Cxa C optionally substituted in 1~4 alkyl, C 1~4 haloalkyl, -(one or more Rs xa C optionally substituted in 1~2 alkylene)-(one or more Rs xa monocyclic carbocyclyl optionally substituted in -(one or more Rs xa C optionally substituted in 1~2 alkylene)-(one or more Rs xa monocyclic heterocyclyl optionally substituted in -(one or more Rs, -O-(one or more Rs xa C optionally substituted in 1~2 alkylene)-(one or more Rs xa monocyclic carbocyclyl optionally substituted in -(one or more Rs, -O-(optionally one or more Rs xa C substituted with 1~2 alkylene)-(one or more Rs xa heterocyclyl optionally substituted in -(optionally substituted carbocyclyl), and -(optionally substituted monocyclic heterocyclyl), and is independently selected from, said Rs xa is independently selected from halogen, preferably -Cl, -F, and -OH.

[0116] In a preferred embodiment, each R x is -halogen, -OH, one or more Rs xa -O-C optionally substituted in 1~3 alkyl, one or more Rs xa -NH-C optionally substituted in 1~3 alkyl, -N(one or more Rs xa C optionally substituted in 1~3 alkyl)2, =O, one or more Rs xa C optionally substituted in 1~4 alkyl, C 1~4 haloalkyl, -(one or more Rs xa C optionally substituted in 1~2(Alkylene)-(one or more Rs xa monocyclic carbocyclyl optionally substituted in xa C optionally substituted in 1~2 (Alkylene)-(one or more Rs xa monocyclic heterocyclyl optionally substituted in xa C optionally substituted in 1~2 (Alkylene)-(one or more Rs xa monocyclic carbocyclyl optionally substituted in xa C substituted with 1~2 (Alkylene)-(one or more Rs xa monocyclic heterocyclyl optionally substituted in xa monocyclic carbocyclyl optionally substituted in xa monocyclic heterocyclyl optionally substituted in, and is independently selected from xa wherein the Rs are independently selected from halogen, preferably -Cl, -F, and -OH.

[0117] In a more preferred embodiment, each R x is -halogen, -OH, -O-C xa alkyl optionally substituted in 1~2 , -NH-C xa alkyl optionally substituted in 1~2 , -N(one or more Rs xa alkyl optionally substituted in 1~2 )2, =O, -C xa alkyl optionally substituted in 1~3 , C 1~2 haloalkyl, -(one or more Rs xa alkyl optionally substituted in 1~2 (alkylene)-(one or more Rs xa monocyclic carbocyclyl optionally substituted in xaC optionally substituted therein 1~2 (alkylene)-(one or more R xa (optionally substituted monocyclic heterocyclyl), -O-(one or more R xa C optionally substituted therein 1~2 (alkylene)-(one or more R xa (optionally substituted monocyclic carbocyclyl), -O-(one or more R xa C optionally substituted therein 1~2 (alkylene)-(one or more R xa (optionally substituted monocyclic heterocyclyl), one or more R xa (optionally substituted monocyclic carbocyclyl, one or more R xa independently selected from optionally substituted monocyclic heterocyclyls, said R xa is independently selected from halogen, preferably -Cl, -F, and -OH.

[0118] In a more preferred embodiment, each R x is -halogen, -OH, -O-C xa optionally substituted alkyl, -NH-C 1~2 optionally substituted alkyl, -N(one or more R xa optionally substituted C 1~2 alkyl)2, =O, -O-C xa optionally substituted C 1~2 alkyl, C xa optionally substituted C 1~3 alkyl, C 1~2 haloalkyl, -W-(one or more R xa (optionally substituted monocyclic carbocyclyl), -W-(one or more R xa (optionally substituted monocyclic heterocyclyl), -W- is absent or is -(C 1~2 alkylene)- or -O-(C 1~2 alkylene)-, said R xais independently selected from -Cl, -F, and -OH.

[0119] In a further preferred embodiment, each R x is -halogen, -OH, -O-C xa alkyl optionally substituted in one or more R 1~2 s, -NH-C xa alkyl optionally substituted in one or more R 1~2 s, -N(alkyl substituted optionally in one or more R xa s)2, =O, -C 1~2 alkyl optionally substituted in one or more R xa s, -C 1~3 alkyl, C 1~2 haloalkyl, -W-(monocyclic carbocyclyl optionally substituted in one or more R xa s), -W-(monocyclic heterocyclyl optionally substituted in one or more R xa s), and is independently selected from, -W- is absent or is -(C 1~2 alkylene)- or -O-(C 1~2 alkylene)-, monocyclic carbocyclyl is selected from phenyl and C 3~6 cycloalkyl, monocyclic heterocyclyl is selected from thiophenyl, pyridyl, pyrazinyl, and pyrimidinyl, and said R xa is independently selected from -Cl, -F, and -OH.

[0120] In a further preferred embodiment, each R x is -halogen, -OH, -O-C 1~2 alkyl, -NH-C 1~2 alkyl, -N(C 1~2 alkyl)2, =O, C 1~3 alkyl, C 1~2 haloalkyl, -W-(monocyclic carbocyclyl optionally substituted in one or more R xa s), -W-(monocyclic heterocyclyl optionally substituted in one or more R xa s), and is independently selected from, -W- is absent or is -(C1~2 -(alkylene)- or -O-(C 1~2 -alkylene)-, the monocyclic carbocyclyl is selected from phenyl and C 3~6 -cycloalkyl, the monocyclic heterocyclyl is selected from thiophenyl, pyridyl, pyrazinyl and pyrimidinyl, and said R xa is independently selected from -F and -OH.

[0121] Said ring A, together with R 6x has the following partial structure:

[0122]

Chemical formula

[0123] It should be understood that it may be further substituted with one R x group to form a bicyclic moiety having (wherein, in a preferred embodiment, said ring B is optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, or optionally substituted heterocycloalkenyl, and said optional substituents of said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl are -C 1~4 -alkyl, -C 1~2 -haloalkyl, -halogen, -oxo, -NR * R * -, -OR * are independently selected; each R * is independently selected from H and C 1~4 -alkyl). In a more preferred embodiment, said ring B is optionally substituted cycloalkyl or optionally substituted heterocycloalkyl, and said optional substituents of said cycloalkyl or said heterocycloalkyl are -C 1~4 -alkyl, -C 1~2 -haloalkyl, -halogen, -oxo, -NR * R * -, -OR * are independently selected; each R* is independently selected from H and C 1~4 alkyl. In a further preferred embodiment, said ring B is an optionally substituted monocyclic cycloalkyl or an optionally substituted monocyclic heterocycloalkyl, and said optional substituent of said monocyclic cycloalkyl or said monocyclic heterocycloalkyl is -C 1~4 alkyl, -C 1~2 haloalkyl, -halogen, -oxo, -NR * R * , -OR * and is independently selected from; each R * is independently selected from H and C 1~4 alkyl.

[0124] In a further preferred embodiment, R 6x is selected from -halogen, -OH, =O, C 1~4 alkyl, C 1~2 haloalkyl and C substituted with one or more OH 1~3 alkyl. In a further preferred embodiment, R 6x is selected from -halogen, -OH, =O, C 1~3 alkyl, C 1~2 haloalkyl and C substituted with one or two OH 1~3 alkyl. In a further preferred embodiment, R 6x is selected from C 1~3 alkyl, C 1~2 haloalkyl and C substituted with one or two OH 1~3 alkyl. In a further preferred embodiment, R 6x is selected from C 1~2 alkyl, C 1~2 haloalkyl and C substituted with one or two OH 1~3 alkyl. In a further preferred embodiment, R 6x is selected from C 1~3 alkyl and C 1~2 haloalkyl. In a further preferred embodiment, R 6x is selected from C 1~2 alkyl and C1 haloalkyl. In a further preferred embodiment, R 6x is CHF2. In a further preferred embodiment, R 6x is CF3. In a further preferred embodiment, R 6x is ethyl. In a further highly preferred embodiment, R 6x is methyl.

[0125] In a further preferred embodiment, R 1 is selected from -(optionally substituted heterocyclyl) and -(optionally substituted carbocyclyl).

[0126] In a further preferred embodiment, R 1 is selected from -(optionally substituted heteroaryl) and -(optionally substituted aryl), and the optional substituents of said, preferably one or two, of said heteroaryl or said phenyl are -(C 1~6 alkyl optionally substituted in one or more halogens), -halogen, -CN, -NO2, oxo, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -N(R * )-S(O)2R * , -OR * , -O-C(O)R * , -O-C(O)-NR * R * , -SR * , -S(O)R * , -S(O)2R * , -S(O)2-NR * R * , -N(R * )-S(O)2-NR * R* and independently selected from heterocyclyl optionally substituted in halogen or C 1~6 alkyl, and carbocyclyl optionally substituted in halogen or C 1~6 alkyl; each R * is independently selected from H, C 1~6 alkyl optionally substituted in halogen, halogen or C 1~6 alkyl, and heterocyclyl optionally substituted in halogen or C 1~6 alkyl, and carbocyclyl optionally substituted in halogen or C * alkyl; any two Rs attached to the same nitrogen atom may optionally be linked.

[0127] In a more preferred embodiment, R 1 is selected from -(optionally substituted heteroaryl) and -(optionally substituted phenyl), wherein the heteroaryl is a 5- or 6-membered monocyclic ring, or a 10- to 12-membered fused ring system, contains one or more ring heteroatoms independently selected from O, S and N, one or two carbocyclic atoms are optionally oxidized, and the one or two optional substituents of the heteroaryl or the phenyl are -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -halogen, -CN, =O, -C(O)R * -COOR * -C(O)NR * R * -NR * R * -N(R * )-C(O)R * -N(R * )-C(O)-OR * -N(R * )-C(O)-NR * R * -O-C(O)R * -O-C(O)-NR * R * -OR *; and each independently optionally substituted with one or preferably two halogens or C 1~4 selected independently from carbocyclic and heterocyclic rings each independently optionally substituted with 1~4 ; each R * is H, C 1~4 alkyl, C 1~4 selected independently from haloalkyl.

[0128] In a further preferred embodiment, R 1 is phenyl, azaindryl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, azaindryl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl is halogen, -OH, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -C(O)-C 1~6 alkyl, -C(O)-C 1~6 haloalkyl, -NH-C(O)-C 1~6 alkyl, -NH-C(O)-C 1~6 haloalkyl and -C(O)-NH-C 1~6 alkyl, -C(O)-NH-C 1~6 haloalkyl, optionally substituted with one or more, preferably one or two substituents selected from.

[0129] In a further preferred embodiment, R 1 is phenyl, azaindryl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, azaindryl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl is halogen, -OH, -C 1~3 alkyl, C 1~2 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~2 haloalkyl), -C(O)-C 1~3 alkyl, -C(O)-C 1~2 haloalkyl, -NH-C(O)-C 1~3 alkyl, -NH-C(O)-C 1~2Haloalkyl and -C(O)-NH-C 1~3 alkyl, -C(O)-NH-C 1~2 is optionally substituted in one or more, preferably one or two substituents selected from haloalkyl,

[0130] In a further preferred embodiment, R 1 is 3-pyridyl or at the meta-position (5-position), halogen, -OH, -C 1~3 alkyl, C 1~2 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~2 haloalkyl), -C(O)-C 1~3 alkyl, -C(O)-C 1~2 haloalkyl, -NH-C(O)-C 1~3 alkyl, -NH-C(O)-C 1~2 haloalkyl and -C(O)-NH-C 1~3 alkyl, -C(O)-NH-C 1~2 haloalkyl, and is 3-pyridyl substituted with one substituent selected therefrom. In a further preferred embodiment, R 1 is 3-pyridyl.

[0131] In a further preferred embodiment, said R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -OH, -(C 1~2 alkylene)-O-(C 1~4 alkylene)-OR * ,-(C 1~4(alkylene)-OR * 、-O-(C 1~4 (alkylene)-OR * 、-(C 1~2 (alkylene)-O-(C 1~4 (alkylene)-N(R°°)2、-O-(C 1~4 (alkylene)-N(R°°)2、-O-(C 1~4 (alkylene)-C(O)N(R°°)2、-CN、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R * 、as well as one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic carbocyclyl and heterocyclyl being independently and optionally substituted with one or more, preferably one or two substituents selected independently from halogen, -C 1~4 (alkyl), C 1~4 (haloalkyl), -O-(C 1~4 (alkyl)), -O-(C 1~4 (haloalkyl)), -OH, =O, -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 (alkyl), C 1~4 (haloalkyl), and each R°° is independently selected from H, C 1~4Selected independently of alkyl or, together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F 1~3 alkylene and is independently optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-.

[0132] In a further preferred embodiment, said R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms each independently selected from O, S, and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, -(C 1~2 alkylene)-O-(C 1~4 alkylene)-OR * 、-O-(C 1~4 alkylene)-OR * 、-(C 1~2 alkylene)-O-(C 1~4 alkylene)-N(R°°)2、-O-(C 1~4 alkylene)-N(R°°)2、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR* R * , -OC(O)R * , -OC(O)-NR * R * and 3-6 membered monocyclic heterocyclyl containing 1-4 heteroatoms selected from O, S and N, wherein each monocyclic heterocyclyl is independently optionally substituted with one or more, preferably one or two, substituents selected from halogen, -C 1~3 Alkyl, C 1~3 Haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * and each R * is H, C 1~3 Alkyl, C 1~3 haloalkyl, and each R°° is independently selected from H, C 1~4 alkyl, or together with the nitrogen atom to which they are attached form a 6-membered monocyclic heterocyclyl, preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is selected from C 1~3 Alkylene, C substituted with 1-4 F 1~3 is optionally substituted independently with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0133] In a further preferred embodiment, the R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl and an 8- to 10-membered bicyclic heteroaryl, each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, wherein one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are optionally oxidized to -F, -Cl, -C1~2 Alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° )2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * selected from one or more, preferably one or two substituents independently and optionally substituted; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R °° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, form a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is C 1~3Alkylene, C substituted with 1 to 4 Fs 1~3 is independently and optionally substituted with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0134] In a further preferred embodiment, said R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and an 8- to 10-membered bicyclic heteroaryl containing one or more, preferably 1 to 4, ring nitrogen heteroatoms, one or two, preferably one, carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -F, -Cl, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° ), =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and is independently and optionally substituted with one or more, preferably one or two, substituents independently selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2Haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * is independently and optionally substituted with one or more, preferably one or two substituents selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R °° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0135] In a more preferred embodiment, said R 1 is selected from 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4 ring nitrogen heteroatoms, one or two, preferably one carbon ring atom of said monocyclic heteroaryl or said bicyclic heteroaryl is optionally oxidized, and said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° )2, =O, -C(O)R * , -COOR * , -C(O)NR * R* 、 -NR * R * 、 -N(R * )-C(O)R * 、 -N(R * )-C(O)-OR * 、 -N(R * )-C(O)-NR * R * 、 -O-C(O)R * 、 -O-C(O)-NR * R * 、 and independently selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, independently optionally substituted with one or two substituents, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * selected from one or two, preferably one, independently optionally substituted substituents; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, and each R °° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, form a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, independently optionally substituted with one divalent substituent selected from.

[0136] In a more preferred embodiment, said R 1is selected from a 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and an 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4 ring nitrogen heteroatoms, and one or two, preferably one, of the carbon ring atoms of the monocyclic heteroaryl or the bicyclic heteroaryl is optionally oxidized, and the 5- or 6-membered monocyclic heteroaryl and the 8- to 10-membered bicyclic heteroaryl are -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° )2, =O, and is independently optionally substituted with one or two, preferably one, substituents independently selected from a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, and is independently optionally substituted with one or two, preferably one, substituents; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R °° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 Fs, -CH2-O-CH2- and -CH2-NH-CH2-.

[0137] In a more preferred embodiment, said R 1 is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl is -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° )2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and is optionally substituted in one or two, preferably one substituent independently selected from 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * is optionally substituted in one or two, preferably one substituent independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, and each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected from the group consisting of

[0138] In a more preferred embodiment, said R 1 is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl is -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * -O-(C 1~2 alkylene)-N(R °° )2, =O, and is independently optionally substituted in one or two, preferably one, substituents selected from a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, and is independently optionally substituted in one or two, preferably one, substituents selected from the group consisting of; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, and each R °° is independently selected from H, C 1~2Independently selected from alkyl or, together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is C 1~3 alkylene, C substituted with 1 to 4 F 1~3 alkylene, and is independently optionally substituted in one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-.

[0139] In a more preferred embodiment, said R 1 is selected from 5-membered monocyclic heteroaryl containing one or two heteroatoms selected from S and N, said 5-membered monocyclic heteroaryl is optionally substituted in one or two, preferably one substituent selected from -C 1~2 alkyl or R 1 is selected from formulas (A) and (B)

[0140] [Chemical formula]

[0141] (wherein Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * 、-O-(C 1-2 alkylene)-N(R °° )2、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R* )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R * 、and selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, each monocyclic heterocyclyl being optionally substituted in one or two, preferably one, substituents independently selected from -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R °° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-).

[0142] In a more preferred embodiment, said R 1 is selected from thiophenyl, pyrrolyl and pyrazolyl, preferably thiophenyl and pyrrolyl, said thiophenyl, pyrrolyl and pyrazolyl being independently optionally substituted with methyl or ethyl, or R 1 is selected from formulas (A) and (B)

[0143]

Chem.

[0144] (wherein, Y 1 is NH, N(C 1~2 alkyl), or CH2, and Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1-2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° )2, =O, and is selected from a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and the monocyclic heterocyclyl is optionally substituted in one or two, preferably one, substituents selected from -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R °° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is optionally independently substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I)).

[0145] In a further preferred embodiment, said R 1 is selected from formulas (A) and (B)

[0146] [Chemical formula]

[0147] (wherein Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° )2, =O, and is selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, and said monocyclic heterocyclyl is optionally substituted in one or two, preferably one, substituents selected from -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R °° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is C 1~3 alkylene, C substituted with 1 to 4 F 1~3Optionally and independently substituted by one divalent substituent selected from alkylene, -CH2-O-CH2- and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0148] In a further preferred embodiment, said R 1 is of formula (B),

[0149]

Chemical formula

[0150] wherein, Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, and the arrow indicates the bond of the compound of formula (I).

[0151] In a further preferred embodiment, said R 1 is of formula (A),

[0152]

Chemical formula

[0153] wherein, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, =O, and is selected from 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, said monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°° ) 2, and optionally substituted in one or two substituents selected from =O, preferably one; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, independently selected; each R °° is H, C 1~2 alkyl, independently selected, or together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F 1~3 alkylene, independently optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0154] In a more preferred embodiment, said R 1 is of formula (A),

[0155] [Chemical formula]

[0156] wherein, B 1 is CH, and A 1 is hydrogen, -C 1-2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, =O, and a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, said monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, -O-(C 1~2 alkylene)-OR * ,-O-(C 1~2 alkylene)-N(R °°)2. Optionally substituted with one or two, preferably one substituent selected from =O; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, independently selected; each R °° is H, C 1~2 alkyl, independently selected, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0157] In a further very preferred embodiment, said R 1 is of formula (A),

[0158]

Chemical formula

[0159] wherein, B 1 is CH, A 1 is hydrogen, and the arrow indicates the bond of the compound of formula (I). Thus, in a further very preferred embodiment, said R 1 is 3-pyridyl.

[0160] In a further preferred embodiment, said R 1 is of formula (A),

[0161]

Chemical formula

[0162] wherein, B 1 is N, A 1is selected from hydrogen and C 1~2 alkyl; the arrow indicates the bond of the compound of formula (I).

[0163] In a further preferred embodiment, said R 1 is of formula (A),

[0164]

Chemical formula

[0165] wherein B 1 is N, A 1 is hydrogen, and the arrow indicates the bond of the compound of formula (I). Thus, in a further very preferred embodiment, said R 1 is 2-pyrazinyl.

[0166] In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-C 1~6 alkyl, and -O-C 1~6 haloalkyl. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from halogen, -C 1~3 alkyl, C 1~2 haloalkyl, -O-C 1~2 alkyl, and -O-C 1~3 haloalkyl. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from -F, -Cl, -C 1~2 alkyl, C1 haloalkyl, -OCH3. In a further preferred embodiment, R 3is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is phenyl or 3-pyridyl or 4-pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is phenyl, 3-pyridyl or 4-pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3 and -OCH3 at the meta-position of said phenyl, 3-pyridyl or 4-pyridyl. In a further preferred embodiment, R 3 is phenyl or phenyl substituted at the meta-position with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is 3-pyridyl or 3-pyridyl substituted at the meta-position (5-position) with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is 4-pyridyl or 4-pyridyl substituted at the meta-position (5-position) with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is phenyl. In a further preferred embodiment, R 3 is 3-pyridyl. In a further preferred embodiment, R 3 is 4-pyridyl.

[0167] R 3 is -(optionally substituted heterocyclyl), -(optionally substituted carbocyclyl), -(optionally substituted C 1~6-(alkylene)-(optionally substituted heterocyclyl), and -(optionally substituted carbocyclyl). 1~6 It is selected from -(alkylene)-(optionally substituted carbocyclyl). Preferably, R 3 is -(optionally substituted carbocyclyl). More preferably, R 3 is phenyl optionally substituted with one or more groups selected from halogen, -(C 1~6 alkyl optionally substituted in one or more Fs) and -O-(C 1~6 alkyl optionally substituted in one or more Fs). Even more preferably, R 3 is a compound that is pyridinyl which may have the same substituents as the optionally substituted heterocyclyl. In other preferred compounds, R 3 is quinazoline or cinnoline, each of which may have the same substituents as the optionally substituted heterocyclyl.

[0168] In a further preferred embodiment, said R 3 is selected from phenyl, 6-membered monocyclic heteroaryl and 8-10 membered bicyclic heteroaryl each independently containing one or more, typically 1 to 5, preferably 1 to 4 ring heteroatoms independently selected from O, B, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, typically and preferably to provide a C=O functional group, and said phenyl, said 6-membered monocyclic heteroaryl, and said 8-10 membered bicyclic heteroaryl are halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -OH, -CN, =O, -C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R ** )-C(O)R* ,-N(R ** )-C(O)-OR * ,-N(R ** )-C(O)-NR * R * ,-O-C(O)R * ,-O-C(O)-NR * R * , and one or more, typically and preferably 1-5, more preferably 1-4, even more preferably 1-3 substituents independently and optionally selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S and N, each monocyclic carbocyclyl and heterocyclyl being independently and optionally substituted with one or more substituents preferably 1 or 2 substituents selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, cyclopropyl, cyclobutyl, oxetanyl, -C 1~2 alkylene-OH, -C 1~2 alkylene-O(C 1~2 alkyl), phenyl, each R ** is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene such as -CH2-CH2- and -CH2-CH2-CH2-, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-.

[0169] In a more preferred embodiment, said R 3 is selected from formula (C), formula (D), formula (E), formula (F) and formula (G)

[0170] [Chemical formula]

[0171] (wherein, B 31 is N, CH or C(A 31 ), A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl) and is selected from, A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl); B 32 is N, CH or C(A 32 ), A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclic group and 1 to 4 heteroatoms selected from O, B, S and N and is selected from 3- to 6-membered monocyclic heterocyclic groups containing, each monocyclic carbocyclic group and heterocyclic group is halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3Alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1-4 F, -CH2-O-CH2- and -CH2-NH-CH2-; In a further preferred embodiment, B 32 is N, CH or C(A 32 ), where A 32 is selected from -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and 3-6 membered monocyclic heterocyclyl containing 1-4 heteroatoms selected from O, S and N, where each monocyclic heterocyclyl is independently optionally substituted with one or more, preferably one or two substituents independently selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 alkyl, C 1~4Independently selected from haloalkyl and phenyl; In a further preferred embodiment, B 32 is N, CH or C(A 32 ), where A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl and phenyl; B 33 is N, CH or C(A 33 ), where A 33 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl) selected from; A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2(alkyl), -C(O)NH(C 1-2 (alkyl), -C(O)N(C 1-2 (alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, each monocyclic carbocyclyl and heterocyclyl being selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C substituted with 1 to 4 F 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2-; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4(alkyl), -O-(C 1~4 (haloalkyl), -OH, =O, -C 1~3 (alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 (alkyl), C 1~4 (haloalkyl), and phenyl; In a further preferred embodiment, A 2 is -C 1~2 (alkyl), C 1~2 (haloalkyl), -F, -Cl, -O(C 1~2 (alkyl)), =O, -OH, -NHC(O)(C 1~2 (alkyl)), -C(O)NH(C 1~2 (alkyl)), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 (alkyl), C 1~3 (haloalkyl), -O-(C 1~3 (alkyl)), -O-(C 1~3 (haloalkyl)), -OH, =O, -C 1~3 (alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~3 (alkyl), C 1~3 (haloalkyl), and phenyl; Y 41 is N, CH or C(A 41 ), where A 41 is selected from methyl and ethyl; Y 42 is N, CH or C(A42 ) and A 42 is selected from methyl and ethyl; Y 43 is N, CH or C(A 43 ) and A 43 is selected from methyl and ethyl; A 3D is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; Y 44 is N, NH, N(A 44 ), C(O), CH, or C(A 44 ) and A 44 is independently selected from methyl and ethyl; Y 45 is N, NH, N(A 45 ), C(O), CH, or C(A 45 ) and A 45 is independently selected from methyl and ethyl; Y 46 is N, NH, N(A 46 ), C(O), CH, or C(A 46 ) and A 46 is independently selected from methyl and ethyl, and said Y 44 , Y 45 and Y 46 at least one of which is NH, N(CH3) or N(C2H5); A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2(alkyl), -C(O)NH(C 1~2 (alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl); In a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; Y 47 is N, NH, N(A 47 ), C(O), CH, or C(A 47 ), where A 47 is independently selected from methyl and ethyl; Y 48 is N, NH, N(A 48 ), C(O), CH, or C(A 48 ), where A 48 is independently selected from methyl and ethyl; Y 49 is N, NH, N(A 49 ), C(O), CH, or C(A 49 ), where A 49 is independently selected from methyl and ethyl, and said Y 47 , Y 48 and Y 49 at least one of which is NH, N(CH3) or N(C2H5); A 3F is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); In a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; G 1 , G 2 , G 3, G 4 is independently selected from N, CH, C(O), NH, or N(C 1~2 alkyl); The arrow indicates the bond of the compound of formula (I).

[0172] In a further preferred embodiment, said R 3 is selected from the following formulas

[0173] [Chemical formula]

[0174] (wherein, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, independently selected for each formula, each monocyclic carbocyclyl and heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is C 1~3Alkylene, C substituted with 1 to 4 Fs 1~3 Alkylene, independently and optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and independently selected for each formula from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * and independently optionally substituted with one or more, preferably one or two substituents independently selected from ; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2(alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, independently selected for each formula, and each monocyclic heterocyclyl is halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl), independently selected for each formula; A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, independently selected for each formula, and each monocyclic carbocyclyl and heterocyclyl is halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4(haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1-4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; In a further preferred embodiment, A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3-6 membered monocyclic heterocyclyl containing 1-4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents independently selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a further preferred embodiment, A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and independently selected for each formula from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl and phenyl; A 35 is independently selected for each formula from -C 1~2 alkyl; The arrow indicates the bond of the compound of formula (I). In an even more preferred embodiment, said R 3 is selected from the following formulas,

[0175]

Chemical formula

[0176] wherein, A 2 and A 32 are hydrogen, -C 1~2 alkyl, C 1~2Haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and independently selected for each formula from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being optionally independently substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; In a further highly preferred embodiment, said R 3 is selected from the following formulas,

[0177] [Chemical formula]

[0178] wherein, A 2 is independently selected for each formula from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl); A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 and 4-6 membered monocyclic heterocyclyl containing 1-4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being independently selected for each formula from halogen, cyclopropyl, -C 1~3 Alkyl, C 1~3 Haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 Alkylene-OR * , -C(O)R * and -C(O)NR * R * and each R * is H, C 1~3 Alkyl, C 1~3 Independently selected from haloalkyl and phenyl. In a further highly preferred embodiment, said R 3 is selected from the following formula:

[0179] [ka]

[0180] During the ceremony, A 2 is hydrogen, -C 1~2 Alkyl, C 1~2 independently selected for each formula from haloalkyl, -F; A 32 -C 1~2 Alkyl, C 1~2 Haloalkyl, -F, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2((Alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 3 heteroatoms selected from O and N, independently selected for each formula, and each monocyclic heterocyclyl is halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or two substituents independently selected from; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl and phenyl, independently selected from.

[0181] In a very preferred embodiment, the compound of formula (V) is a compound selected from the compounds of formula (VI), (VIa) and (IVb). In a very preferred embodiment, the compound of formula (V) is a compound of formula (VI). In a very preferred embodiment, the compound of formula (V) is a compound of formula (VIa). In a very preferred embodiment, the compound of formula (V) is a compound of formula (VIb).

[0182] Accordingly, in a further aspect and embodiment, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (VI), preferably formula (VIa), and more preferably formula (VIb), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof.

[0183]

Chemical formula

[0184] In yet further aspects and embodiments, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (VII), preferably formula (VIIa), and more preferably formula (VIIb), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof;

[0185]

Chemical formula

[0186] In yet further aspects and embodiments, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (VIII), preferably formula (VIIIa), and more preferably formula (VIIIb), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof;

[0187]

Chemical formula

[0188] In yet further aspects and embodiments, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (IX), preferably formula (IXa), and more preferably formula (IXb), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof;

[0189]

Chemical formula

[0190] In the formula, R 1 is selected from -(optionally substituted heterocyclyl) and -(optionally substituted carbocyclyl).

[0191] In a more preferred embodiment, said R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl and an 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -OH, -(C 1~2 alkylene)-O-(C 1~4 alkylene)-OR * 、-O-(C 1~4 alkylene)-OR * 、-(C 1~2 alkylene)-O-(C 1~4 alkylene)-N(R°°)2, -O-(C 1~4 alkylene)-N(R°°)2, -CN, =O, -C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R *, and one or more, preferably one or two substituents selected from monocyclic carbocyclyl of 3 to 6 members and monocyclic heterocyclyl of 3 to 6 members containing 1 to 4 heteroatoms selected from O, S and N, are independently optionally substituted, and each monocyclic carbocyclyl and heterocyclyl is halogen, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * are independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, each R°° is independently selected from H, C 1~4 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected from.

[0192] In a further preferred embodiment, said R 1 is phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5 ring heteroatoms independently selected from O, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4(alkyl), -O-(C 1~4 (haloalkyl), -OH, -(C 1~2 (alkylene)-O-(C 1~4 (alkylene)-OR * , -O-(C 1~4 (alkylene)-OR * , -(C 1~2 (alkylene)-O-(C 1~4 (alkylene)-N(R°°)2, -O-(C 1~4 (alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being halogen, -C 1~3 (alkyl), C 1~3 (haloalkyl), -O-(C 1~3 (alkyl), -O-(C 1~3 (haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * selected from one or more, preferably one or two substituents independently and optionally substituted; each R * is independently selected from H, C 1~3 (alkyl), C 1~3 (haloalkyl), and each R°° is H, C 1~4Selected independently of alkyl or, together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C substituted with 1 to 4 F 1~3 alkylene and is independently optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-.

[0193] In a further preferred embodiment, said R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S, and N, one or two carbocyclic atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -F, -Cl, -C 1~2 alkyl, -CHF3, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R *, and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, form a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2- and is independently and optionally substituted with one divalent substituent selected from.

[0194] In a further preferred embodiment, said R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and 8- to 10-membered bicyclic heteroaryl containing one or more, preferably 1 to 4 ring nitrogen heteroatoms, one or two, preferably one carbon ring atom of said monocyclic heteroaryl or said bicyclic heteroaryl is optionally oxidized, said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -F, -Cl, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2(alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C substituted with 1 to 4 F 1~3It is independently and optionally substituted with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0195] In a more preferred embodiment, said R 1 is selected from a 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and an 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4, ring nitrogen heteroatoms, and one or two, preferably one, of the carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl is optionally oxidized, and said 5- or 6-membered monocyclic heteroaryl and said 8- to 10-membered bicyclic heteroaryl are -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and is independently and optionally substituted with one or two, preferably one, substituents independently selected from a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2(haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or two, preferably one, substituents independently selected from; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, and each R°° is H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F, 1~3 is independently optionally substituted with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0196] In a more preferred embodiment, said R 1 is selected from 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4, ring nitrogen heteroatoms, and one or two, preferably one, of the carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl is optionally oxidized, and said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, and 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and is independently optionally substituted with one or two, preferably one, substituents, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2Haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, and is independently optionally substituted with one or two, preferably one, substituents independently selected therefrom; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, independently selected, and each R°° is H, C 1~2 alkyl, independently selected, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected therefrom.

[0197] In a more preferred embodiment, said R 1 is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl is -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R* , -OC(O)R * , -OC(O)-NR * R * and a 4- to 6-membered monocyclic heterocyclyl containing 1 or 2 heteroatoms selected from O and N, wherein each monocyclic heterocyclyl is independently optionally substituted with 1 or 2, preferably 1, substituents selected from -C 1~2 Alkyl, C 1~2 Haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * and each R is independently optionally substituted with one or two substituents independently selected from * is H, C 1~2 Alkyl, C 1~2 haloalkyl, and each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached form a 6-membered monocyclic heterocyclyl, preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is selected from C 1~3 Alkylene, C substituted with 1-4 F 1~3 is optionally substituted independently with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0198] In a further preferred embodiment, the R 1 is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindolyl, pyrazinyl, pyridyl or pyrimidinyl is -C 1~2 Alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C1~2 and each of the monocyclic heterocyclyls is independently optionally substituted with one or two, preferably one, substituent selected from -C(alkylene)-N(R°°), =O, and 4-6 membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, 1~2 Alkyl, C 1~2 Haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O; each R * , H, C 1~2 Alkyl, C 1~2 haloalkyl, and each R° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, form a 6-membered monocyclic heterocyclyl, preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is selected from C 1~3 Alkylene, C substituted with 1-4 F 1~3 Optionally substituted independently with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0199] In a further preferred embodiment, the R 1 is selected from a 5-membered monocyclic heteroaryl containing 1 or 2 heteroatoms selected from S and N, said 5-membered monocyclic heteroaryl being selected from -C 1~2 Optionally substituted with one or two, preferably one, substituents selected from alkyl, or R 1 is selected from formula (A) and (B):

[0200] [ka]

[0201] During the ceremony, Y 1 NH, N(C1~2 is alkyl or CH2, and Y 2 is N or CH, and B 1 is N or CH, and A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * -COOR * -C(O)NR * R * -NR * R * -N(R * )-C(O)R * -N(R * )-C(O)-OR * -N(R * )-C(O)-NR * R * -O-C(O)R * -O-C(O)-NR * R * and is selected from 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, each monocyclic heterocyclyl being optionally substituted in one or two, preferably one, substituents independently selected from -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, and each R°° is independently selected from H, C 1~2Independently selected from alkyl or, together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C substituted with 1 to 4 F 1~3 alkylene, and is independently optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-.

[0202] In a more preferred embodiment, said R 1 is selected from thiophenyl, pyrrolyl and pyrazolyl, preferably thiophenyl and pyrrolyl, and said thiophenyl, pyrrolyl and pyrazolyl are independently optionally substituted with methyl or ethyl, or R 1 is selected from formulas (A) and (B),

[0203]

Chemical formula

[0204] wherein, Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * -O-(C 1~2 alkylene)-N(R°°)2, =O, and is selected from a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and said monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2is optionally substituted in one or two, preferably one, substituent selected from haloalkyl), -OH, and =O; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, independently selected, each R°° is H, C 1~2 alkyl, independently selected, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F 1~3 alkylene, and is independently optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0205] In a more preferred embodiment, said R 1 is selected from formulas (A) and (B),

[0206]

Chemical formula

[0207] wherein Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * -O-(C 1~2 alkylene)-N(R°°)2, =O, and a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, said monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2Haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, and is optionally substituted in one or two, preferably one, of the substituents selected therefrom; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0208] In a further preferred embodiment, said R 1 is of formula (B),

[0209]

Chemical formula

[0210] wherein Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, and the arrow indicates the bond of the compound of formula (I).

[0211] In a further preferred embodiment, said R 1 is of formula (A),

[0212]

Chemical formula

[0213] wherein, B 1is N or CH, and A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, =O, and is selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, wherein said monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -O-(C 1~2 alkylene)-OR * , -OH, -O-(C 1~2 alkylene)-N(R°°)2, and =O, and is optionally substituted in one or two, preferably one, of the substituents selected therefrom; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 Fs, -CH2-O-CH2- and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected therefrom; the arrow indicates the bond of the compound of formula (I).

[0214] In a more preferred embodiment, said R 1 is of formula (A),

[0215]

Chemical formula

[0216] wherein, B 1 is CH, and A 1 is hydrogen, -C1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, =O, and a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, wherein the monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -O-(C 1~2 alkylene)-OR * , -OH, -O-(C 1~2 alkylene)-N(R°°)2, and =O, and is optionally substituted in one or two, preferably one, of the substituents selected therefrom; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F, 1~3 -CH2-O-CH2- and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected therefrom; the arrow indicates the bond of the compound of formula (I).

[0217] In a further highly preferred embodiment, said R 1 is of formula (A),

[0218]

Chemical formula

[0219] wherein, B 1 is CH, A 1is hydrogen, and the arrow indicates the bond of the compound of formula (I). Therefore, in an even more preferred embodiment, said R 1 is 3-pyridyl.

[0220] In a more preferred embodiment, said R 1 is of formula (A),

[0221]

Chemical formula

[0222] wherein, B 1 is N, A 1 is hydrogen, and C 1~2 alkyl is selected from; the arrow indicates the bond of the compound of formula (I).

[0223] In a more preferred embodiment, said R 1 is of formula (A),

[0224]

Chemical formula

[0225] wherein, B 1 is N, A 1 is hydrogen, and the arrow indicates the bond of the compound of formula (I). Therefore, in an even more preferred embodiment, said R 1 is 2-pyrazinyl.

[0226] R 21 is selected from hydrogen, C 1~6 alkyl, C 1~6 haloalkyl, C 1~6 alkyl optionally substituted at one or more OH, C 1~6 alkyl containing 1 to 3 oxygen atoms between carbon atoms, and C 22 cycloalkyl optionally substituted at one or more R 3~6 ; R 22is selected from halogen, preferably -Cl, -F, and -OH. In a more preferred embodiment, said R 21 is hydrogen, C 1~2 alkyl, C 1~2 haloalkyl, C 1~2 alkyl optionally substituted at one or two OHs, and C 22 cycloalkyl optionally substituted at one or more R 3~4 and is selected from cycloalkyl, R 22 is selected from -Cl, -F, and -OH. In a more preferred embodiment, said R 21 is C 1~2 alkyl, C 1~2 haloalkyl and C 3~4 cycloalkyl. In a more preferred embodiment, said R 21 is C 1~2 alkyl and cyclopropyl. In a more preferred embodiment, said R 21 is cyclopropyl. In a very more preferred embodiment, said R 21 is ethyl. In a very more preferred embodiment, said R 21 is methyl.

[0227] R 3 is -(optionally substituted heterocyclyl), -(optionally substituted carbocyclyl), -(optionally substituted C 1~6 alkylene)-(optionally substituted heterocyclyl), and -(optionally substituted C 1~6 alkylene)-(optionally substituted carbocyclyl). Preferably, R 3 is -(optionally substituted carbocyclyl). More preferably, R 3 is phenyl optionally substituted with one or more groups selected from halogen, -(C 1~6 alkyl optionally substituted at one or more Fs), and -O-(C 1~6 alkyl optionally substituted at one or more Fs). Even more preferably, R 3is a compound that is pyridinyl and can have the same substituents as an optionally substituted heterocyclyl. In other preferred compounds, R 3 is quinazoline or cinnoline, each of which can have the same substituents as an optionally substituted heterocyclyl.

[0228] In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-C 1~6 alkyl, and -O-C 1~6 haloalkyl. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from halogen, -C 1~3 alkyl, C 1~2 haloalkyl, -O-C 1~2 alkyl, and -O-C 1~3 haloalkyl. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from -F, -Cl, -C 1~2 alkyl, C1 haloalkyl, -OCH3. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3is phenyl, 3-pyridyl or 4-pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is phenyl, 3-pyridyl or 4-pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3, and -OCH3 at the meta-position of said phenyl, 3-pyridyl or 4-pyridyl. In a further preferred embodiment, R 3 is phenyl, or phenyl substituted at the meta-position with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is 3-pyridyl or 3-pyridyl substituted at the meta-position (5-position) with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is 4-pyridyl or 4-pyridyl substituted at the meta-position (5-position) with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is phenyl. In a further preferred embodiment, R 3 is 3-pyridyl. In a further preferred embodiment, R 3 is 4-pyridyl.

[0229] In a further preferred embodiment, said R 3 is selected from phenyl, 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, typically 1 to 5, preferably 1 to 4 ring heteroatoms independently selected from O, B, S and N, wherein one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, typically and preferably to provide a C=O functional group, and said phenyl, said 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6(alkyl), -O-(C 1~6 (haloalkyl), -OH, -CN, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R ** )-C(O)R * , -N(R ** )-C(O)-OR * , -N(R ** )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or more, typically and preferably 1 to 5, more preferably 1 to 4, and even more preferably 1 to 3 substituents selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, are independently optionally substituted, and each monocyclic carbocyclyl and heterocyclyl is halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, cyclopropyl, cyclobutyl, oxetanyl, -C 1~2 alkylene-OH, -C 1~2 alkylene-O(C 1~2 alkyl), phenyl, and each R ** is H, C 1~4 alkyl, C 1~4Independently selected from haloalkyl and / or each monocyclic heterocyclyl is C such as -CH2-CH2- and -CH2-CH2-CH2- 1~3 alkylene, C substituted with 1 to 4 F 1~3 alkylene, and is independently and optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-.

[0230] In a more preferred embodiment, said R 3 is selected from formula (C), formula (D), formula (E), formula (F) and formula (G)

[0231]

Chemical formula

[0232] (wherein B 31 is N, CH or C(A 31 ), A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl), and A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl); B 32 is N, CH or C(A 32 ), A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2(alkyl)2, -NHC(O)(phenyl), and selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, each monocyclic carbocyclyl and heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; In a more preferred embodiment, B 32 is N, CH or C(A 32 ), where A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and selected from 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C1~4 (haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is selected independently from H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a further preferred embodiment, B 32 is N, CH or C(A 32 ), and A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is selected independently from H, C 1~3 alkyl, C 1~3 haloalkyl and phenyl; B 33 is N, CH or C(A 33 ), and A 33 is -C 1~2Alkyl, C 1~2 Haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl) and is selected from; A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1-2 alkyl), -C(O)N(C 1-2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S and N, each monocyclic carbocyclyl and heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * -C(O)R * and -C(O)NR * R * and is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C1~2 (alkyl), -C(O)NH(C 1~2 (alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a more preferred embodiment, A 2 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and selected from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R *Independently and optionally substituted with one or more, preferably one or two substituents selected independently therefrom; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; Y 41 is N, CH or C(A 41 ), where A 41 is selected from methyl and ethyl; Y 42 is N, CH or C(A 42 ), where A 42 is selected from methyl and ethyl; Y 43 is N, CH or C(A 43 ), where A 43 is selected from methyl and ethyl; A 3D is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; Y 44 is N, NH, N(A 44 ), C(O), CH, or C(A 44 ), where A 44 is independently selected from methyl and ethyl; Y 45 is N, NH, N(A 45 ), C(O), CH, or C(A 45 ), where A 45 is independently selected from methyl and ethyl; Y 46 is N, NH, N(A 46 ), C(O), CH, or C(A 46 ), where A46 is independently selected from methyl and ethyl, said Y 44 , Y 45 and Y 46 at least one of which is NH, N(CH3) or N(C2H5); A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; Y 47 is N, NH, N(A 47 ), C(O), CH, or C(A 47 ), where A 47 is independently selected from methyl and ethyl; Y 48 is N, NH, N(A 48 ), C(O), CH, or C(A 48 ), where A 48 is independently selected from methyl and ethyl; Y 49 is N, NH, N(A 49 ), C(O), CH, or C(A 49 ), where A 49 is independently selected from methyl and ethyl, said Y 47 , Y 48 and Y 49 at least one of which is NH, N(CH3) or N(C2H5); A 3F is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2(alkyl), -C(O)NH(C 1~2 (alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl); in a further preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; G 1 , G 2 , G 3 , G 4 is independently selected from N, CH, C(O), NH, or N(C 1~2 (alkyl); the arrow indicates the bond of the compound of formula (I)).

[0233] In a further preferred embodiment, said R 3 is selected from the following formulae

[0234] [Chemical formula]

[0235] (wherein, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclic ring and a 3- to 6-membered monocyclic heterocyclic ring containing 1 to 4 heteroatoms selected from O, B, S, and N, each monocyclic carbocyclic ring and heterocyclic ring being independently selected for each formula from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3Alkylene-OR * 、-C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents independently selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * 、-C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a further preferred embodiment, A2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(cyclopropyl), -NHC(O)(phenyl), and is independently selected for each formula from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * and is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl) and is independently selected for each formula; A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2(alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N are independently selected for each formula, and each monocyclic carbocyclyl and heterocyclyl is halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C substituted with 1 to 4 F 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2- is independently optionally substituted with one divalent substituent selected from; In a more preferred embodiment, A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N are independently selected for each formula, and each monocyclic heterocyclyl is halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C1~3 alkylene-OR * 、-C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a further preferred embodiment, A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * 、-C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; A 35 is independently selected from -C 1~2 alkyl for each formula; (the arrow indicates the bond of the compound of formula (I)).

[0236] Furthermore, in a highly preferred embodiment, said R 3 is selected from the following formulas,

[0237]

Chemical formula

[0238] wherein, A 2 and A 32 are each independently selected from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, independently for each formula, and each monocyclic heterocyclyl is independently optionally substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; Furthermore, in a highly preferred embodiment, said R 3 is selected from the following formulas,

[0239]

Chemical formula

[0240] In the formula, A 2 is independently selected from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl) for each formula; A 32 is independently selected from -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N for each formula, and each monocyclic heterocyclyl is independently optionally substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; and each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl.

[0241] In a further highly preferred embodiment, said R 3 is selected from the following formulas,

[0242]

Chemical formula

[0243] In the formula, A 2is selected independently for each formula from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F; A 32 is selected independently for each formula from -C 1~2 alkyl, C 1~2 haloalkyl, -F, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and 4- to 6-membered monocyclic heterocyclyl containing 1 to 3 heteroatoms selected from O and N, each monocyclic heterocyclyl being independently optionally substituted with one or two substituents independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl.

[0244] X 1 , X 2 , and X 3 are each independently selected from N, CH, and CR x , with at least one of said X 1 , X 2 , and X 3 being N; more preferably, at least one of X 2 and X 3 is N; even more preferably, X 2 , and X 3 are both N; still more preferably, X 2 , and X 3 are both N, and X 1is CH.

[0245] E is selected from -CH2-, -CHR x -, -CR x 2-, -NH-, -NRx-, and -O-, -L 1 -L 2 -, and -L 2 -L 1 - and is selected from L 1 is -CH2-, -CHR x -, -CR x 2-, -NH-, -NR x -, and -O- and is selected from L 2 is -CH2-, -CHR x - and -CR x 2- and is selected. In a further preferred embodiment, said E is selected from -CH2-, -NH-, -O-, -CH2-O-, -O-CH2-, -CH2-NH-, -NH-CH2- and -CH2-CH2-. Preferably, E is selected from CH2-, -O-, -CH2-O-, -O-CH2- and -CH2-CH2-. More preferably, E is selected from CH2-, -O-, -CH2-O-, and -CH2-CH2-. In a further preferred embodiment, E is CH2.

[0246] R 6x is -halogen, -OH, =O, C 1~6 alkyl, C 1~6 haloalkyl, C substituted with one or more OH 1~6 alkyl, one or more R xb in which optionally substituted monocyclic aryl, one or more R xb in which optionally substituted monocyclic heteroaryl, one or more R xb in which optionally substituted monocyclic cycloalkyl, one or more R xb in which optionally substituted monocyclic heterocycloalkyl, one or more R xb in which optionally substituted monocyclic cycloalkenyl, one or more R xbis an optionally substituted monocyclic heteroalkenyl, and said R xb is independently selected from -halogen, -OH, =O, C 1~4 alkyl, C 1~2 haloalkyl, C 1~2 alkyl; In a more preferred embodiment, R 6x is selected from -halogen, -OH, =O, C 1~4 alkyl, C 1~2 haloalkyl and C 1~3 alkyl substituted with one or more OH. In a more preferred embodiment, R 6x is selected from -halogen, -OH, =O, C 1~3 alkyl, C 1~2 haloalkyl and C 1~3 alkyl substituted with one or two OH. In a more preferred embodiment, R 6x is selected from C 1~3 alkyl, C 1~2 haloalkyl and C 1~3 alkyl substituted with one or two OH. In a more preferred embodiment, R 6x is selected from C 1~2 alkyl, C 1~2 haloalkyl and C 1~3 alkyl substituted with one or two OH. In a more preferred embodiment, R 6x is selected from C 1~3 alkyl and C 1~2 haloalkyl. In a more preferred embodiment, R 6x is selected from C 1~2 alkyl and C1 haloalkyl.

[0247] In a more preferred embodiment, R 6x is CHF2. In a more preferred embodiment, R 6x is CF3. In a more preferred embodiment, R 6x is ethyl. In a very highly preferred embodiment, R 6x is methyl.

[0248] Ring A is further optionally substituted with one or more R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 ; the number of R x groups of ring A is 0, 1, 2, 3, or 4, preferably 0, 1, 2, or 3, more preferably 0, 1, or 2, or alternatively preferably 0 or 1. It should be understood that ring A may be substituted with one or more R x groups, and when one of the said R x groups of ring A is optionally linked to R 21 , the said one of the R 21 groups of ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0249] Thus, in a preferred embodiment, the said ring A is further substituted with 1, 2, 3, or 4 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 . When one of the said R x groups of ring A is optionally linked to R 21 , the said one of the R 21 groups of ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0250] In a preferred embodiment, the said ring A is further substituted with 1, 2, or 3 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 . When one of the said R x groups of ring A is21 When optionally linked to R 21 Said R of ring A optionally linked to x One of said groups is a substituent at the 2-position of ring A.

[0251] In a preferred embodiment, said ring A is further substituted with one or two R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to R 21 is a substituent at the 2-position of ring A. 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to R

[0252] In a preferred embodiment, said ring A is further substituted with one R x group, and said R x group of ring A is optionally linked to R 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to R 21 is a substituent at the 2-position of ring A. 21 When one of said R groups of ring A is optionally linked to R x One of said R groups of ring A optionally linked to R

[0253] In a preferred embodiment, said ring A is further substituted with one R x group, and said R x group of ring A is not linked to R 21 In a further preferred embodiment, said R

[0254] In a preferred embodiment, said ring A is further substituted with one R x group, and said R x group of ring A is not linked to R 21 In a further preferred embodiment, said R x group is -F, and preferably said R xThe base is at the 3-position of ring A, and said position connects said ring A to the X 1 , X 2 , X 3 ring system.

[0255] In a preferred embodiment, said ring A is further unsubstituted. Thus, in a preferred embodiment, said ring A is not further substituted with an R x group.

[0256] In a preferred embodiment, said R 21 is selected from hydrogen, C 1~6 alkyl, C 1~6 haloalkyl, C 1~6 alkyl optionally substituted with one or more OH, C 1~6 alkyl containing 1 to 3 oxygen atoms between carbon atoms, and C 22 cycloalkyl optionally substituted with one or more R 3~6 , where R 22 is selected from halogen, preferably -Cl, -F, and -OH. In a more preferred embodiment, said R 21 is selected from hydrogen, C 1~2 alkyl, C 1~2 haloalkyl, C 1~2 alkyl optionally substituted with one or two OH, and C 22 cycloalkyl optionally substituted with one or more R 3~4 , where R 22 is selected from -Cl, -F, and -OH. In a more preferred embodiment, said R 21 is selected from C 1~2 alkyl, C 1~2 haloalkyl and C 3~4 cycloalkyl. In a more preferred embodiment, said R 21 is selected from C 1~2 alkyl and cyclopropyl. In a more preferred embodiment, said R 21 is ethyl. In a more preferred embodiment, said R 21 is cyclopropyl. In a very highly preferred embodiment, said R21 is methyl.

[0257] In a preferred embodiment, each R x is -halogen, -OH, -O-C xa optionally substituted in one or more R 1~3 alkyl, -NH-C xa optionally substituted in one or more R 1~3 alkyl, -N(one or more R xa optionally substituted in C 1~3 alkyl)2, =O, -C xa optionally substituted in one or more R 1~4 alkyl, C 1~4 haloalkyl, -(one or more R xa optionally substituted in C 1~2 alkylene)-(optionally substituted carbocyclic), -(one or more R xa optionally substituted in C 1~2 alkylene)-(optionally substituted heterocyclic), -O-(one or more R xa optionally substituted in C 1~2 alkylene)-(optionally substituted carbocyclic), -O-(one or more R xa optionally substituted in C 1~2 alkylene)-(optionally substituted heterocyclic), -(optionally substituted carbocyclic), and -(optionally substituted heterocyclic), and is independently selected from the group consisting of, said R xa is independently selected from halogen, preferably -Cl, -F, and -OH.

[0258] In an even more preferred embodiment, each R x is -halogen, -OH, -O-C xa optionally substituted in one or more R 1~2 alkyl, -NH-C xa optionally substituted in one or more R 1~2 alkyl, -N(one or more R xaC optionally substituted therein 1~2 (alkyl)2, =O, one or more R xa C optionally substituted therein 1~3 alkyl, C 1~2 haloalkyl, -(one or more R xa C optionally substituted therein 1~2 alkylene)-(one or more R xa monocyclic carbocyclyl optionally substituted therein), -(one or more R xa C optionally substituted therein 1~2 alkylene)-(one or more R xa monocyclic heterocyclyl optionally substituted therein), -O-(one or more R xa C optionally substituted therein 1~2 alkylene)-(one or more R xa monocyclic carbocyclyl optionally substituted therein), -O-(one or more R xa C optionally substituted therein 1~2 alkylene)-(one or more R xa monocyclic heterocyclyl optionally substituted therein), one or more R xa monocyclic carbocyclyl optionally substituted therein, one or more R xa independently selected from monocyclic heterocyclyl optionally substituted therein, said R xa is independently selected from halogen, preferably -Cl, -F, and -OH.

[0259] In a more preferred embodiment, each R x is -halogen, -OH, one or more R xa -O-C optionally substituted therein 1~2 alkyl, one or more R xa -NH-C optionally substituted therein 1~2 alkyl, -N(one or more R xa C optionally substituted therein 1~2 alkyl)2, =O, one or more R xaC optionally substituted therein 1~3 alkyl, C 1~2 haloalkyl, -W-(monocyclic carbocyclyl optionally substituted in one or more R xa ), -W-(monocyclic heterocyclyl optionally substituted in one or more R xa ), independently selected from, -W- is absent, or -(C 1~2 alkylene)- or -O-(C 1~2 alkylene)-, said R xa is independently selected from -Cl, -F, and -OH.

[0260] In a further preferred embodiment, each R x is -halogen, -OH, -O-C xa alkyl optionally substituted in one or more R 1~2 , -NH-C xa alkyl optionally substituted in one or more R 1~2 , -N(C xa alkyl optionally substituted in one or more R 1~2 )2, =O, -C xa alkyl optionally substituted in one or more R 1~3 , C 1~2 haloalkyl, -W-(monocyclic carbocyclyl optionally substituted in one or more R xa ), -W-(monocyclic heterocyclyl optionally substituted in one or more R xa ), independently selected from, -W- is absent, or -(C 1~2 alkylene)- or -O-(C 1~2 alkylene)-, monocyclic carbocyclyl is selected from phenyl and C 3~6 cycloalkyl, monocyclic heterocyclyl is selected from thiophenyl, pyridyl, pyrazinyl and pyrimidinyl, said R xa is independently selected from -Cl, -F, and -OH.

[0261] In a further preferred embodiment, each R xis selected independently from -halogen, -OH, -O-C 1~2 alkyl, -NH-C 1~2 alkyl, -N(C 1~2 alkyl)2, =O, C 1~3 alkyl, C 1~2 haloalkyl, -W-(a monocyclic carbocyclyl optionally substituted in one or more R xa ), -W-(a monocyclic heterocyclyl optionally substituted in one or more R xa ), -W- is absent or is -(C 1~2 alkylene)- or -O-(C 1~2 alkylene)-, the monocyclic carbocyclyl is selected from phenyl and C 3~6 cycloalkyl, the monocyclic heterocyclyl is selected from thiophenyl, pyridyl, pyrazinyl and pyrimidinyl, said R xa is selected independently from -F and -OH.

[0262] In a further highly preferred aspect and embodiment, the invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (IXb), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer or diastereomer or a mixture thereof,

[0263]

Chemical formula

[0264] wherein, In a more preferred embodiment, said R 1is selected from phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms each independently selected from O, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl being optionally oxidized, said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl being halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -OH, -(C 1~2 alkylene)-O-(C 1~4 alkylene)-OR * 、-O-(C 1~4 alkylene)-OR * 、-(C 1~2 alkylene)-O-(C 1~4 alkylene)-N(R°°)2、-O-(C 1~4 alkylene)-N(R°°)2、-CN、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R * 、and one or more, preferably one or two, substituents independently selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic carbocyclyl and heterocyclyl being optionally independently substituted with halogen, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C1~4 (alkyl), -O-(C 1~4 (haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 (alkyl), C 1~4 (haloalkyl) and is independently selected, each R°° is H, C 1~4 (alkyl) or together with the nitrogen atom to which they are attached preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 (alkylene), C(alkylene) substituted with 1 to 4 F, 1~3 (alkylene), -CH2-O-CH2- and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected from.

[0265] In a more preferred embodiment, said R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~4 (alkyl), C 1~4 (haloalkyl), -O-(C 1~4 (alkyl)), -O-(C 1~4 (haloalkyl)), -OH, -(C 1~2 (alkylene))-O-(C 1~4 (alkylene))-OR * , -O-(C 1~4 (alkylene))-OR * , -(C 1~2 (alkylene))-O-(C 1~4(alkylene)-N(R°°)2, -O-(C 1~4 (alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being independently and optionally substituted with one or more, preferably one or two substituents selected from halogen, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, each R°° is independently selected from H, C 1~4 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0266] In a more preferred embodiment, said R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl independently containing one or more, preferably 1 to 5, ring heteroatoms each independently selected from O, S, and N, and an 8- to 10-membered bicyclic heteroaryl, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -F, -Cl, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and are independently optionally substituted with one or more, preferably one or two substituents selected from a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R *Independently selected from one or more, preferably one or two substituents independently and optionally substituted; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, and is independently and optionally substituted with one divalent substituent selected therefrom.

[0267] In a more preferred embodiment, said R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and an 8- to 10-membered bicyclic heteroaryl containing one or more, preferably 1 to 4 ring nitrogen heteroatoms, one or two, preferably one carbon ring atom of said monocyclic heteroaryl or said bicyclic heteroaryl is optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -F, -Cl, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -(C 1~2 alkylene)-OR * 、-O-(C 1~2 alkylene)-N(R°°)2、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R* )-C(O)-NR * R * 、 -O-C(O)R * 、 -O-C(O)-NR * R * 、 and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * selected independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2- independently and optionally substituted with one divalent substituent selected from.

[0268] In a more preferred embodiment, said R 1is selected from a 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and an 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4, ring nitrogen heteroatoms, and one or two, preferably one, of the carbon ring atoms of the monocyclic heteroaryl or the bicyclic heteroaryl is optionally oxidized, and the 5- or 6-membered monocyclic heteroaryl and the 8- to 10-membered bicyclic heteroaryl are -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and is independently optionally substituted with one or two, preferably one, substituents independently selected from a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * and is independently optionally substituted with one or two, preferably one, substituents independently selected from; each R * is H, C 1~2Alkyl, C 1~2 Independently selected from haloalkyl, each R°° is H, C 1~2 Independently selected from alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 Alkylene, C substituted with 1 to 4 F 1~3 Alkylene, independently and optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-.

[0269] In a more preferred embodiment, said R 1 Is selected from 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4, ring nitrogen heteroatoms, one or two, preferably one, of the carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl is optionally oxidized, and said 5- or 6-membered monocyclic heteroaryl and said 8- to 10-membered bicyclic heteroaryl are -C 1~2 Alkyl, -CHF2, -CF3, -O-(C 1~2 Alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 Alkylene)-OR * , -O-(C 1~2 Alkylene)-N(R°°)2, =O, and one or two, preferably one, substituents selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, independently and optionally substituted, each monocyclic heterocyclyl being -C 1~2 Alkyl, C 1~2 Haloalkyl, -O-(C 1~2 Alkyl), -O-(C 1~2 Haloalkyl), -OH, and =O, independently and optionally substituted with one or two, preferably one, substituents; each R * Is H, C 1~2 Alkyl, C1~2 Independently selected from haloalkyl, each R°° is H, C 1~2 Independently selected from alkyl, or together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 Alkylene, C substituted with 1 to 4 F 1~3 Alkylene, and is independently optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-.

[0270] In a more preferred embodiment, said R 1 Is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl are -C 1~2 Alkyl, -CHF2, -CF3, -O-(C 1~2 Alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 Alkylene)-OR * 、-O-(C 1~2 Alkylene)-N(R°°)2, =O, -C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R *and one or two substituents independently and optionally selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, each monocyclic heterocyclyl being independently and optionally substituted with one or two, preferably one, substituent, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * independently and optionally substituted with one or two substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, form a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-.

[0271] In a further preferred embodiment, said R 1 is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl being -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2Selected from (alkylene)-N(R°°)2, =O, and a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, independently optionally substituted with one or two, preferably one, substituents, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, independently optionally substituted with one or two substituents independently selected therefrom; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 Fs, -CH2-O-CH2- and -CH2-NH-CH2-, independently optionally substituted with one divalent substituent selected therefrom.

[0272] In a further preferred embodiment, said R 1 is selected from 5-membered monocyclic heteroaryl containing one or two heteroatoms selected from S and N, said 5-membered monocyclic heteroaryl being optionally substituted in one or two, preferably one, substituents selected from -C 1~2 alkyl, or R 1 is selected from formulas (A) and (B),

[0273]

Chemical formula

[0274] wherein, Y 1 is NH, N(C 1~2is alkyl) or CH2, and Y 2 is N or CH, and B 1 is N or CH, and A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * ), -C(O)R * , -N(R * ), -C(O)-OR * , -N(R * ), -C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and is selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, each monocyclic heterocyclyl being, -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * is optionally substituted in one or two, preferably one, substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is, C1~3 alkylene, C substituted with 1 to 4 Fs 1~3 is independently and optionally substituted with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0275] In a further preferred embodiment, said R 1 is selected from thiophenyl, pyrrolyl, and pyrazolyl, preferably thiophenyl and pyrrolyl, and said thiophenyl, pyrrolyl, and pyrazolyl are independently and optionally substituted with methyl or ethyl, or R 1 is selected from formulae (A) and (B),

[0276]

Chemical formula

[0277] wherein, Y 1 is NH, N(C 1~2 alkyl), or CH2, Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * 、-O-(C 1~2 alkylene)-N(R°°)2, =O, and is selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, and said monocyclic heterocyclyl is optionally substituted in one or two, preferably one, substituents selected from -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O; each R * is H, C 1~2 alkyl, C 1~2Independently selected from haloalkyl, each R°° is H, C 1~2 Independently selected from alkyl, or together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 Alkylene, C substituted with 1 to 4 F 1~3 Alkylene, and is independently optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0278] In a more preferred embodiment, said R 1 Is selected from formulas (A) and (B),

[0279]

Chemical formula

[0280] Wherein, Y 1 Is NH, N(C 1~2 Alkyl) or CH2, Y 2 Is N or CH, B 1 Is N or CH, A 1 Is hydrogen, -C 1~2 Alkyl, -CHF2, -CF3, -O-(C 1~2 Alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 Alkylene)-OR * 、-O-(C 1~2 Alkylene)-N(R°°)2, =O, and is selected from a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, said monocyclic heterocyclyl being -C 1~2 Alkyl, C 1~2 Haloalkyl, -O-(C 1~2 Alkyl), -O-(C 1~2 Haloalkyl), -OH, and =O, and is optionally substituted in one or two, preferably one, substituents selected therefrom; each R* is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, and each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C alkylene substituted with 1 to 4 F, 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0281] In a more preferred embodiment, said R 1 is of formula (B),

[0282]

Chemical formula

[0283] wherein Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, and the arrow indicates the bond of the compound of formula (I).

[0284] In a more preferred embodiment, said R 1 is of formula (A),

[0285]

Chemical formula

[0286] wherein B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2Selected from (alkyl), -OCHF2, -OCHF3, -OH, =O, and 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, said monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° )2, and =O, and is optionally substituted in one or two, preferably one, substituents selected therefrom; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R °° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0287] In a more preferred embodiment, said R 1 is of formula (A),

[0288]

Chemical formula

[0289] wherein, B 1 is CH, A 1 is hydrogen, -C 1-2 alkyl, -CHF2, -CF3, -O-(C 1~2Selected from alkyl), -OCHF2, -OCHF3, -OH, =O, and 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, said monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R °° )2, and =O, and is optionally substituted in one or two, preferably one, of the substituents selected therefrom; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, and each R °° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine; and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0290] In a further very preferred embodiment, said R 1 is of formula (A),

[0291]

Chemical formula

[0292] wherein B 1 is CH, A 1 is hydrogen, and the arrow indicates the bond of the compound of formula (I). Thus, in a further very preferred embodiment, said R 1 is 3-pyridyl. In a further preferred embodiment, said R 1 is of formula (A),

[0293]

Chemical formula

[0294] wherein, B 1 is N, A 1 is hydrogen, and C 1~2 alkyl; the arrow indicates the bond of the compound of formula (I). In a further preferred embodiment, said R 1 is of formula (A),

[0295]

Chemical formula

[0296] wherein, B 1 is N, A 1 is hydrogen, and the arrow indicates the bond of the compound of formula (I). Thus, in a further very preferred embodiment, said R 1 is 2-pyrazinyl. R 21 is selected from hydrogen, C 1~6 alkyl, C 1~6 haloalkyl, C 1~6 alkyl optionally substituted with one or more OH, C 1~6 alkyl containing 1 to 3 oxygen atoms between carbon atoms, and C 22 cycloalkyl optionally substituted with one or more R 3~6 ; R 22 is selected from halogen, preferably -Cl, -F, and -OH. In a further preferred embodiment, said R 21 is selected from hydrogen, C 1~2 alkyl, C 1~2 haloalkyl, C 1~2Alkyl, and one or more R 22 optionally substituted C 3~4 selected from cycloalkyl, R 22 is selected from -Cl, -F, and -OH. In a further preferred embodiment, said R 21 is C 1~2 alkyl, C 1~2 haloalkyl and C 3~4 selected from cycloalkyl. In a further preferred embodiment, said R 21 is C 1~2 selected from alkyl and cyclopropyl. In a further preferred embodiment, said R 21 is cyclopropyl. In a further very preferred embodiment, said R 21 is ethyl. In a further very preferred embodiment, said R 21 is methyl.

[0297] In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-C 1~6 alkyl, and -O-C 1~6 haloalkyl. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from halogen, -C 1~3 alkyl, C 1~2 haloalkyl, -O-C 1~2 alkyl, and -O-C 1~3 haloalkyl. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from -F, -Cl, -C 1~2 alkyl, C1 haloalkyl, -OCH3. In a further preferred embodiment, R3 is phenyl or pyridyl, each of which is optionally substituted with one or more, preferably one or two substituents selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is phenyl or pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is phenyl or 3-pyridyl or 4-pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is phenyl, 3-pyridyl or 4-pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3, and -OCH3 at the meta-position of said phenyl, 3-pyridyl or 4-pyridyl. In a further preferred embodiment, R 3 is phenyl or phenyl substituted at the meta-position with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is 3-pyridyl or 3-pyridyl substituted at the meta-position (5-position) with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is 4-pyridyl or 4-pyridyl substituted at the meta-position (5-position) with one substituent selected from -F, -Cl, -CH3, and -OCH3. In a further preferred embodiment, R 3 is phenyl. In a further preferred embodiment, R 3 is 3-pyridyl. In a further preferred embodiment, R 3 is 4-pyridyl.

[0298] In a further preferred embodiment, said R 3is selected from phenyl, 6-membered monocyclic heteroaryl and 8-10 membered bicyclic heteroaryl each independently containing one or more, typically 1 to 5, preferably 1 to 4 ring heteroatoms each independently selected from O, B, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl being optionally oxidized, typically and preferably to provide a C=O functional group, said phenyl, said 6-membered monocyclic heteroaryl, and said 8-10 membered bicyclic heteroaryl being halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -OH, -CN, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R ** )-C(O)R * , -N(R ** )-C(O)-OR * , -N(R ** )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or more, typically and preferably 1 to 5, more preferably 1 to 4, still more preferably 1 to 3 substituents independently selected from 3-6 membered monocyclic carbocyclyl and 3-6 membered monocyclic heterocyclyl containing 1-4 heteroatoms selected from O, B, S and N, each monocyclic carbocyclyl and heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R* is independently optionally substituted with one or more, preferably one or two substituents selected independently therefrom; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, cyclopropyl, cyclobutyl, oxetanyl, -C 1~2 alkylene-OH, -C 1~2 alkylene-O(C 1~2 alkyl), phenyl, and each R ** is H, C 1~4 alkyl, C 1~4 haloalkyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene such as -CH2-CH2- and -CH2-CH2-CH2-, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0299] In a more preferred embodiment, said R 3 is selected from formula (C), formula (D), formula (E), formula (F) and formula (G)

[0300]

Chemical formula

[0301] (wherein, B 31 is N, CH or C(A 31 ), and A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl), and A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2selected from (alkyl); B 32 is N, CH or C(A 32 ), and A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S and N, each monocyclic carbocyclyl and heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-; In a more preferred embodiment, B 32 is N, CH or C(A 32 ), and A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2(alkyl), -C(O)NH(C 1~2 (alkyl), -C(O)N(C 1~2 )(alkyl)2, -NHC(O)(phenyl), and selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a more preferred embodiment, B 32 is N, CH or C(A 32 ), and A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and selected from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R* is independently and optionally substituted with one or more, preferably one or two substituents selected independently therefrom; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl, selected independently; B 33 is N, CH or C(A 33 ), where A 33 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl), selected; A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S and N, each monocyclic carbocyclyl and heterocyclyl being independently and optionally substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently and optionally substituted with one or more, preferably one or two substituents selected from H, C * alkyl, C 1~4 haloalkyl, phenyl, selected independently, and / or each monocyclic heterocyclyl is C 1~4 haloalkyl, phenyl, selected independently, and / or each monocyclic heterocyclyl is C 1~3Alkylene, C substituted with 1 to 4 Fs 1~3 Alkylene, independently and optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * independently selected from one or more, preferably one or two substituents, and independently and optionally substituted; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl, independently selected; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2Selected from (alkyl)2, -NHC(O)(phenyl), and 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; Y 41 is N, CH or C(A 41 ), where A 41 is selected from methyl and ethyl; Y 42 is N, CH or C(A 42 ), where A 42 is selected from methyl and ethyl; Y 43 is N, CH or C(A 43 ), where A 43 is selected from methyl and ethyl; A 3D is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a further preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; Y44 is N, NH, N(A 44 ), C(O), CH, or C(A 44 ), where A 44 is independently selected from methyl and ethyl; Y 45 is N, NH, N(A 45 ), C(O), CH, or C(A 45 ), where A 45 is independently selected from methyl and ethyl; Y 46 is N, NH, N(A 46 ), C(O), CH, or C(A 46 ), where A 46 is independently selected from methyl and ethyl, and at least one of said Y 44 , Y 45 and Y 46 is NH, N(CH3) or N(C2H5); A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; Y 47 is N, NH, N(A 47 ), C(O), CH, or C(A 47 ), where A 47 is independently selected from methyl and ethyl; Y 48 is N, NH, N(A 48 ), C(O), CH, or C(A 48 ), where A 48 is independently selected from methyl and ethyl; Y 49 is N, NH, N(A 49), C(O), CH, or C(A 49 ) and A 49 is independently selected from methyl and ethyl, and said Y 47 , Y 48 and Y 49 at least one of is NH, N(CH3), or N(C2H5); A 3F is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; G 1 , G 2 , G 3 , G 4 is independently selected from N, CH, C(O), NH, or N(C 1~2 alkyl); (The arrow indicates the bond of the compound of formula (I)).

[0302] In a more preferred embodiment, said R 3 is selected from the following formulas

[0303]

Chemical formula

[0304] (wherein A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2(alkyl), -C(O)NH(C 1~2 (alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, each independently selected for each formula, and each monocyclic carbocyclyl and heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; In a more preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each independently selected for each formula, and each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C1~4 (alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and independently selected for each formula from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2(alkyl), -OH, -NHC(O)(C 1~2 selected independently for each formula from (alkyl); A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, each monocyclic carbocyclyl and heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents selected independently from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * selected independently from, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C * alkylene, C alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-; 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-; 1~3 In a further preferred embodiment, A is -C 32 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2(alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and independently selected for each formula from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a more preferred embodiment, A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and independently selected for each formula from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R *independently optionally substituted with one or more, preferably one or two substituents selected independently therefrom; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; A 35 is independently selected from -C 1~2 alkyl for each formula; (the arrow indicates the bond of the compound of formula (I)).

[0305] In a further highly preferred embodiment, said R 3 is selected from the following formulas,

[0306]

Chemical formula

[0307] wherein, A 2 and A 32 are each independently selected from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being optionally substituted with halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R *is independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; In an even more preferred embodiment, said R 3 is selected from the following formulas,

[0308]

Chemical formula

[0309] wherein, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl) independently selected for each formula; A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being independently and optionally substituted with one or more, preferably one or two substituents independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R *is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl, independently selected.

[0310] In a further highly preferred embodiment, said R 3 is selected from the following formulae:

[0311]

Chemical formula

[0312] wherein A 2 is independently selected for each formula from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F; A 32 is independently selected for each formula from -C 1~2 alkyl, C 1~2 haloalkyl, -F, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 3 heteroatoms selected from O and N, each monocyclic heterocyclyl being independently optionally substituted with one or two substituents independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * -C(O)R * and -C(O)NR * R * ; and each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl. R 6x is -halogen, -OH, =O, C 1~4Alkyl, C 1~2 haloalkyl and C substituted with one or more OH 1~3 is selected from. In a further preferred embodiment, R 6x is - halogen, - OH, = O, C 1~3 alkyl, C 1~2 haloalkyl and C substituted with one or two OH 1~3 is selected from alkyl. In a further preferred embodiment, R 6x is C 1~3 alkyl, C 1~2 haloalkyl and C substituted with one or two OH 1~3 is selected from alkyl. In a further preferred embodiment, R 6x is C 1~2 alkyl, C 1~2 haloalkyl and C substituted with one or two OH 1~3 is selected from alkyl. In a further preferred embodiment, R 6x is C 1~3 alkyl and C 1~2 is selected from haloalkyl. In a further preferred embodiment, R 6x is C 1~2 is selected from alkyl and C1 haloalkyl. In a further preferred embodiment, R 6x is CHF2. In a further preferred embodiment, R 6x is CF3. In a further preferred embodiment, R 6x is ethyl. In a further very preferred embodiment, R 6x is methyl.

[0313] Ring A may be further substituted with one or more R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 ; R of ring A xIt should be understood that the number of the groups is 0, 1, 2, 3 or 4, preferably 0, 1, 2 or 3, more preferably 0, 1 or 2, or alternatively preferably 0 or 1. When ring A is substituted with one or more R x groups, and when one of the R x groups of ring A is optionally linked to R 21 and, the one of the R 21 groups of ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0314] Thus, in a preferred embodiment, the ring A is further substituted with 1, 2, 3 or 4 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 . When one of the R x groups of ring A is optionally linked to R 21 and, the one of the R 21 groups of ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0315] In a preferred embodiment, the ring A is further substituted with 1, 2 or 3 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 . When one of the R x groups of ring A is optionally linked to R 21 and, the one of the R 21 groups of ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0316] In a preferred embodiment, the ring A is further substituted with 1 or 2 R x groups, and any two Rx groups, preferably adjacent R x groups are optionally linked and / or any R of ring A x group is R 21 is optionally linked to. Said R of ring A x one of the groups is R 21 is optionally linked to, R 21 the said R of ring A that is optionally linked to R x one of the groups is a substituent at the 2-position of ring A.

[0317] In a preferred embodiment, said ring A is further substituted with one R x group, and said R of ring A x group is R 21 is optionally linked to. Said R of ring A x one of the groups is R 21 is optionally linked to, R 21 the said R of ring A that is optionally linked to R x one of the groups is a substituent at the 2-position of ring A.

[0318] In a preferred embodiment, said ring A is further substituted with one R x group, and said R of ring A x group is not linked to R 21 .

[0319] In a preferred embodiment, said ring A is further substituted with one R x group, and said R of ring A x group is not linked to R 21 . In a further preferred embodiment, said R x group is -F, preferably, said R x group that is -F is at the 3-position of ring A, and said position connects said ring A to the X 1 , X 2 , X 3 ring system.

[0320] In a preferred embodiment, said ring A is not further substituted. Thus, in a preferred embodiment, said ring A is not further substituted with an R x group.

[0321] In a preferred embodiment, said R 21 is selected from hydrogen, C 1~6 alkyl, C 1~6 haloalkyl, C 1~6 alkyl optionally substituted at one or more OH, C 1~6 alkyl containing 1 to 3 oxygen atoms between carbon atoms, and C 22 cycloalkyl optionally substituted at one or more R 3~6 , and R 22 is selected from halogen, preferably -Cl, -F, and -OH. In a more preferred embodiment, said R 21 is selected from hydrogen, C 1~2 alkyl, C 1~2 haloalkyl, C 1~2 alkyl optionally substituted at one or two OH, and C 22 cycloalkyl optionally substituted at one or more R 3~4 , and R 22 is selected from -Cl, -F, and -OH. In a further preferred embodiment, said R 21 is selected from C 1~2 alkyl, C 1~2 haloalkyl and C 3~4 cycloalkyl. In a further preferred embodiment, said R 21 is selected from C 1~2 alkyl and cyclopropyl. In a further preferred embodiment, said R 21 is ethyl. In a further preferred embodiment, said R 21 is cyclopropyl. In a further very preferred embodiment, said R 21 is methyl.

[0322] In a preferred embodiment, each R x is -halogen, -OH, -O-C xa alkyl optionally substituted at one or more R 1~3 , -NH-C xa alkyl optionally substituted at one or more R 1~3Alkyl, -N(one or more R xa optionally substituted C 1~3 alkyl)2, =O, one or more R xa optionally substituted C 1~4 alkyl, C 1~4 haloalkyl, -(one or more R xa optionally substituted C 1~2 alkylene)-(optionally substituted carbocyclic), -(one or more R xa optionally substituted C 1~2 alkylene)-(optionally substituted heterocyclic), -O-(one or more R xa optionally substituted C 1~2 alkylene)-(optionally substituted carbocyclic), -O-(one or more R xa optionally substituted C 1~2 alkylene)-(optionally substituted heterocyclic), -(optionally substituted carbocyclic), and -(optionally substituted heterocyclic), independently selected from, said R xa is independently selected from halogen, preferably -Cl, -F, and -OH.

[0323] In a more preferred embodiment, each R x is -halogen, -OH, one or more R xa optionally substituted -O-C 1~2 alkyl, one or more R xa optionally substituted -NH-C 1~2 alkyl, -N(one or more R xa optionally substituted C 1~2 alkyl)2, =O, one or more R xa optionally substituted C 1~3 alkyl, C 1~2 haloalkyl, -(one or more R xa optionally substituted C 1~2 alkylene)-(one or more R xa(optionally substituted monocyclic carbocyclyl), -(one or more Rs xa (optionally substituted C 1~2 alkylene)-(one or more Rs xa (optionally substituted monocyclic heterocyclyl), -O-(one or more Rs xa (optionally substituted C 1~2 alkylene)-(one or more Rs xa (optionally substituted monocyclic carbocyclyl), -O-(one or more Rs xa (optionally substituted C 1~2 alkylene)-(one or more Rs xa (optionally substituted monocyclic heterocyclyl), one or more Rs xa (optionally substituted monocyclic carbocyclyl, one or more Rs xa (optionally substituted monocyclic heterocyclyl), and is independently selected from, said Rs xa are independently selected from halogen, preferably -Cl, -F, and -OH.

[0324] In a more preferred embodiment, each R x is -halogen, -OH, one or more Rs xa (optionally substituted -O-C 1~2 alkyl, one or more Rs xa (optionally substituted -NH-C 1~2 alkyl, -N(two C alkyls optionally substituted in one or more Rxa), =O, one or more Rs 1~2 (optionally substituted C xa (optionally substituted C 1~3 alkyl, C 1~2 haloalkyl, -W-(one or more Rs xa (optionally substituted monocyclic carbocyclyl), -W-(one or more Rs xa (optionally substituted monocyclic heterocyclyl), and is independently selected from, -W- is absent or -(C 1~2 alkylene)- or -O-(C1~2 is (alkylene)-, and the above R xa is independently selected from -Cl, -F, and -OH.

[0325] In a more preferred embodiment, each R x is -halogen, -OH, -O-C xa alkyl optionally substituted in 1~2 one or more R xa -NH-C 1~2 alkyl optionally substituted in xa one or more R 1~2 -N(alkyl optionally substituted in xa one or more R 1~3 alkyl)2, =O, -C 1~2 alkyl optionally substituted in xa one or more R xa -W-(monocyclic carbocyclyl optionally substituted in 1~2 one or more R 1~2 -W-(monocyclic heterocyclyl optionally substituted in 3~6 one or more R xa is independently selected from -Cl, -F, and -OH.

[0326] In a more preferred embodiment, each R x is -halogen, -OH, -O-C 1~2 alkyl, -NH-C 1~2 alkyl, -N(C 1~2 alkyl)2, =O, -C 1~3 alkyl, -C 1~2 haloalkyl, -W-(monocyclic carbocyclyl optionally substituted in xa one or more R xaindependently selected from (monocyclic heterocyclyl) optionally substituted therein, -W- is absent or -(C 1~2 alkylene)- or -O-(C 1~2 alkylene)-, the monocyclic carbocyclyl is selected from phenyl and C 3~6 cycloalkyl, the monocyclic heterocyclyl is selected from thiophenyl, pyridyl, pyrazinyl and pyrimidinyl, and said R xa is independently selected from -F and -OH.

[0327] In further aspects and embodiments, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (X), preferably formula (Xa), and more preferably formula (Xb), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof;

[0328]

Chemical formula

[0329] In further aspects and embodiments, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (XI), preferably formula (XIa), and more preferably formula (XIb), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof,

[0330]

Chemical formula

[0331] In yet further aspects and embodiments, the present invention provides a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (XII), preferably formula (XIIa), and more preferably formula (XIIb) for use in a method of treating a fibrotic disease, optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof,

[0332]

Chemical formula

[0333] wherein, R 1 is selected from -(optionally substituted heterocyclyl) and -(optionally substituted carbocyclyl).

[0334] In a more preferred embodiment, said R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl and an 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, one or two carbocyclic atoms of said monocyclic heteroaryl or said bicyclic heteroaryl being optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl being halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -OH, -(C 1~2 alkylene)-O-(C 1~4 alkylene)-OR * 、-O-(C 1~4 alkylene)-OR * 、-(C 1~2 alkylene)-O-(C 1~4 alkylene)-N(R°°)2、-O-(C 1~4(alkylene)-N(R°°)2, -CN, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic carbocyclyl and heterocyclyl being independently and optionally substituted with one or more, preferably one or two substituents selected from halogen, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, each R°° is independently selected from H, C 1~4 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-.

[0335] In a more preferred embodiment, said R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S, and N, and an 8- to 10-membered bicyclic heteroaryl, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, -(C 1~2 alkylene)-O-(C 1~4 alkylene)-OR * 、-O-(C 1~4 alkylene)-OR * 、-(C 1~2 alkylene)-O-(C 1~4 alkylene)-N(R°°)2、-O-(C 1~4 alkylene)-N(R°°)2、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R * 、and one or more, preferably one or two, substituents independently and optionally selected from a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, -C 1~3 alkyl, C 1~3Haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents selected from; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, each R°° is independently selected from H, C 1~4 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-.

[0336] In a more preferred embodiment, said R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -F, -Cl, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR* R * 、 -N(R * )-C(O)R * 、 -N(R * )-C(O)-OR * 、 -N(R * )-C(O)-NR * R * 、 -O-C(O)R * 、 -O-C(O)-NR * R * 、 and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S and N, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or together with the nitrogen atom to which they are attached forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2- independently and optionally substituted with one divalent substituent selected from.

[0337] In a more preferred embodiment, said R 1is selected from 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from phenyl, S and N, and 8- to 10-membered bicyclic heteroaryl containing one or more, preferably 1 to 4, ring nitrogen heteroatoms, and one or two, preferably one, of the carbon ring atoms of the monocyclic heteroaryl or the bicyclic heteroaryl is optionally oxidized, and the phenyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are -F, -Cl, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and is independently optionally substituted with one or more, preferably one or two, substituents selected from 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * and is independently optionally substituted with one or more, preferably one or two, substituents selected from; each R* is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, and each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl, preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C alkylene substituted with 1 to 4 F, 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2-.

[0338] In a more preferred embodiment, said R 1 is selected from 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4, ring nitrogen heteroatoms, and one or two, preferably one, carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said 5- or 6-membered monocyclic heteroaryl and said 8- to 10-membered bicyclic heteroaryl are -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * 、-O-(C 1~2 alkylene)-N(R°°)2、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R *, -O-C(O)-NR * R * , and independently selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, and independently optionally substituted with one or two, preferably one, substituents, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * and independently optionally substituted with one or two, preferably one, substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected from.

[0339] In a further preferred embodiment, said R 1 is selected from 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4, ring nitrogen heteroatoms, one or two, preferably one, carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl being optionally oxidized, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl being -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2(alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, and one or two substituents independently and optionally selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, independently and optionally substituted with one or two, preferably one, substituents independently selected therefrom; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F, 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2-, independently and optionally substituted with one divalent substituent selected therefrom.

[0340] In a further preferred embodiment, said R 1 is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl being -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2(alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or two substituents independently and optionally substituted from a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * and independently and optionally substituted with one or two substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, and independently and optionally substituted with one divalent substituent selected from

[0341] In a more preferred embodiment, said R 1is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl is -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, and one or two substituents selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, independently and optionally substituted with one or two, preferably one, substituents, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, independently and optionally substituted with one or two substituents independently selected therefrom; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, independently selected, each R°° is H, C 1~2 alkyl, independently selected, or together with the nitrogen atom to which they are attached, preferably form a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F, 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2-, independently and optionally substituted with one divalent substituent selected therefrom.

[0342] In a further preferred embodiment, said R 1 is selected from 5-membered monocyclic heteroaryls containing one or two heteroatoms selected from S and N, said 5-membered monocyclic heteroaryl being -C 1~2Optionally substituted with one or two, preferably one substituent selected from alkyl, or R 1 is selected from formulas (A) and (B),

[0343]

Chemical Formula

[0344] wherein, Y 1 is NH, N(C 1~2 alkyl) or CH2, and Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and is selected from 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR *R * is optionally substituted in one or two, preferably one, substituents independently selected from; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, independently selected, and each R°° is H, C 1~2 alkyl, independently selected, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, independently optionally substituted with one divalent substituent selected from.

[0345] In a more preferred embodiment, said R 1 is selected from thiophenyl, pyrrolyl and pyrazolyl, preferably thiophenyl and pyrrolyl, and said thiophenyl, pyrrolyl and pyrazolyl are independently optionally substituted with methyl or ethyl, or R 1 is selected from formulas (A) and (B),

[0346]

Chemical formula

[0347] wherein, Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * -O-(C 1~2Selected from (alkylene)-N(R°°)2, =O, and 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, wherein the monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, and is optionally substituted in one or two, preferably one, substituents selected therefrom; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected therefrom; the arrow indicates the bond of the compound of formula (I).

[0348] In a more preferred embodiment, said R 1 is selected from formula (A) and (B),

[0349]

Chemical formula

[0350] wherein, Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, B 1 is N or CH, A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C1~2 (alkylene)-OR * 、-O-(C 1~2 (alkylene)-N(R°°)2, =O, and a 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, wherein said monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, and is optionally substituted in one or two, preferably one, substituents selected therefrom; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F, 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected therefrom; the arrow indicates the bond of the compound of formula (I).

[0351] In a further preferred embodiment, said R 1 is of formula (B),

[0352]

Chemical formula

[0353] wherein Y 1 is NH, N(C 1~2 alkyl) or CH2, Y 2 is N or CH, and the arrow indicates the bond of the compound of formula (I).

[0354] In a further preferred embodiment, said R 1is of formula (A),

[0355]

Chemical formula

[0356] wherein, B 1 is N or CH, and A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, =O, and is selected from 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, wherein the monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -O-(C 1~2 alkylene)-OR * , -OH, -O-(C 1~2 alkylene)-N(R°°)2, and =O, and is optionally substituted in one or two, preferably one, substituents selected therefrom; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected therefrom; the arrow indicates the bond of the compound of formula (I).

[0357] In a further preferred embodiment, said R 1 is of formula (A),

[0358] [Chem.]

[0359] wherein, B 1 is CH, and A 1 is hydrogen, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, =O, and is selected from 4- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms selected from O and N, and said monocyclic heterocyclyl is optionally substituted in one or two, preferably one, substituent selected from -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -O-(C 1~2 alkylene)-OR * , -OH, -O-(C 1~2 alkylene)-N(R°°)2, and =O; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; the arrow indicates the bond of the compound of formula (I).

[0360] In a further very preferred embodiment, said R 1 is of formula (A),

[0361] [Chem.]

[0362] In the formula, B 1 is CH, A 1 is hydrogen, and the arrow indicates the bond of the compound of formula (I). Thus, in an even more preferred embodiment, said R 1 is 3-pyridyl.

[0363] In a more preferred embodiment, said R 1 is of formula (A),

[0364]

Chemical formula

[0365] In the formula, B 1 is N, A 1 is selected from hydrogen and -C 1~2 alkyl; the arrow indicates the bond of the compound of formula (I).

[0366] In a more preferred embodiment, said R 1 is of formula (A),

[0367]

Chemical formula

[0368] In the formula, B 1 is N, A 1 is hydrogen, and the arrow indicates the bond of the compound of formula (I). Thus, in an even more preferred embodiment, said R 1 is 2-pyrazinyl.

[0369] R 21 is hydrogen, C 1~6 alkyl, C 1~6 haloalkyl, C 1~6Alkyl, C containing 1 to 3 oxygen atoms between carbon atoms 1~6 Alkyl, and one or more R 22 Optionally substituted C in 3~6 Selected from cycloalkyl, R 22 Is selected from halogen, preferably -Cl, -F, and -OH. In a more preferred embodiment, the said R 21 Is hydrogen, C 1~2 Alkyl, C 1~2 Haloalkyl, C optionally substituted in one or two OH 1~2 Alkyl, and one or more R 22 Optionally substituted C in 3~4 Selected from cycloalkyl, R 22 Is selected from -Cl, -F, and -OH. In a more preferred embodiment, the said R 21 Is C 1~2 Alkyl, C 1~2 Haloalkyl and C 3~4 Selected from cycloalkyl. In a more preferred embodiment, the said R 21 Is C 1~2 Selected from alkyl and cyclopropyl. In a more preferred embodiment, the said R 21 Is cyclopropyl. In an even more preferred embodiment, the said R 21 Is ethyl. In an even more preferred embodiment, the said R 21 Is methyl.

[0370] R 3 Is -(optionally substituted heterocyclyl), -(optionally substituted carbocyclyl), -(optionally substituted C 1~6 Alkylene)-(optionally substituted heterocyclyl), and -(optionally substituted C 1~6 Alkylene)-(optionally substituted carbocyclyl). Preferably, R 3 Is -(optionally substituted carbocyclyl). More preferably, R 3 Is halogen, -(C optionally substituted in one or more F1~6 alkyl) and -O-(C optionally substituted in one or more F 1~6 phenyl optionally substituted in one or more groups selected from). More preferably, R 3 is a compound in which pyridinyl can have the same substituents as an optionally substituted heterocyclyl. In other preferred compounds, R 3 is quinazoline or cinnoline, each of which can have the same substituents as an optionally substituted heterocyclyl.

[0371] In a more preferred embodiment, R 3 is phenyl or pyridinyl, each of which is halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-C 1~6 alkyl, and -O-C 1~6 haloalkyl, and is optionally substituted in one or more, preferably one or two substituents selected from. In a more preferred embodiment, R 3 is phenyl or pyridinyl, each of which is halogen, -C 1~3 alkyl, C 1~2 haloalkyl, -O-C 1~2 alkyl, and -O-C 1~3 haloalkyl, and is optionally substituted in one or more, preferably one or two substituents selected from. In a more preferred embodiment, R 3 is phenyl or pyridinyl, each of which is -F, -Cl, -C 1~2 alkyl, C1 haloalkyl, -OCH3, and is optionally substituted in one or more, preferably one or two substituents selected from. In a more preferred embodiment, R 3 is phenyl or pyridinyl, each of which is -F, -Cl, -CH3 and -OCH3, and is optionally substituted in one or more, preferably one or two substituents selected from. In a more preferred embodiment, R 3is phenyl or pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is phenyl or 3-pyridyl or 4-pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is phenyl, 3-pyridyl or 4-pyridyl, each of which is optionally substituted with one substituent selected from -F, -Cl, -CH3 and -OCH3 at the meta-position of said phenyl, 3-pyridyl or 4-pyridyl. In a further preferred embodiment, R 3 is phenyl or phenyl substituted at the meta-position with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is 3-pyridyl or 3-pyridyl substituted at the meta-position (5-position) with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is 4-pyridyl or 4-pyridyl substituted at the meta-position (5-position) with one substituent selected from -F, -Cl, -CH3 and -OCH3. In a further preferred embodiment, R 3 is phenyl. In a further preferred embodiment, R 3 is 3-pyridyl. In a further preferred embodiment, R 3 is 4-pyridyl.

[0372] In a further preferred embodiment, said R 3is selected from phenyl, 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, typically 1 to 5, preferably 1 to 4 ring heteroatoms each independently selected from O, B, S, and N, wherein one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, typically and preferably to provide a C=O functional group, and said phenyl, said 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -OH, -CN, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R ** )-C(O)R * , -N(R ** )-C(O)-OR * , -N(R ** )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and one or more, typically and preferably 1 to 5, more preferably 1 to 4, even more preferably 1 to 3 substituents independently selected from 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, each monocyclic carbocyclyl and heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R* independently and optionally substituted with one or more, preferably one or two substituents selected independently therefrom; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, cyclopropyl, cyclobutyl, oxetanyl, -C 1~2 alkylene-OH, -C 1~2 alkylene-O(C 1~2 alkyl), phenyl, and each R ** is H, C 1~4 alkyl, C 1~4 haloalkyl, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene such as -CH2-CH2- and -CH2-CH2-CH2-, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-.

[0373] In a more preferred embodiment, said R 3 is selected from formula (C), formula (D), formula (E), formula (F) and formula (G)

[0374]

Chemical formula

[0375] (wherein B 31 is N, CH or C(A 31 ), and A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl), and A 31 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2selected from (alkyl); B 32 is N, CH or C(A 32 ), and A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S and N, each monocyclic carbocyclyl and heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4F, -CH2-O-CH2- and -CH2-NH-CH2-; In a more preferred embodiment, B 32 is N, CH or C(A 32 ), and A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2(alkyl), -C(O)NH(C 1~2 (alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a further preferred embodiment, B 32 is N, CH or C(A 32 ), and A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and selected from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R* is independently and optionally substituted with one or more, preferably one or two substituents selected independently from; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; B 33 is N, CH or C(A 33 ), where A 33 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl); A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S and N, where each monocyclic carbocyclyl and heterocyclyl is independently and optionally substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is C 1~3alkylene, C substituted with 1 to 4 Fs 1~3 alkylene, independently and optionally substituted with one divalent substituent selected from -CH2-O-CH2- and -CH2-NH-CH2-; In a further preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * independently selected from one or more, preferably one or two substituents independently and optionally substituted; each R * is H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl independently selected; In a further preferred embodiment, A 2 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2Selected from (alkyl)2, -NHC(O)(phenyl), and 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; Y 41 is N, CH or C(A 41 ), where A 41 is selected from methyl and ethyl; Y 42 is N, CH or C(A 42 ), where A 42 is selected from methyl and ethyl; Y 43 is N, CH or C(A 43 ), where A 43 is selected from methyl and ethyl; A 3D is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a further preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; Y44 is N, NH, N(A 44 ), C(O), CH, or C(A 44 ), where A 44 is independently selected from methyl and ethyl; Y 45 is N, NH, N(A 45 ), C(O), CH, or C(A 45 ), where A 45 is independently selected from methyl and ethyl; Y 46 is N, NH, N(A 46 ), C(O), CH, or C(A 46 ), where A 46 is independently selected from methyl and ethyl, and said Y 44 , Y 45 and Y 46 at least one of which is NH, N(CH3) or N(C2H5); A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; Y 47 is N, NH, N(A 47 ), C(O), CH, or C(A 47 ), where A 47 is independently selected from methyl and ethyl; Y 48 is N, NH, N(A 48 ), C(O), CH, or C(A 48 ), where A 48 is independently selected from methyl and ethyl; Y 49 is N, NH, N(A 49)、C(O), CH, or C(A 49 ) where A 49 is independently selected from methyl and ethyl, and said Y 47 , Y 48 and Y 49 at least one of which is NH, N(CH3) or N(C2H5); A 3F is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl); in a more preferred embodiment, A 3E is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH; G 1 , G 2 , G 3 , G 4 is independently selected from N, CH, C(O), NH, or N(C 1~2 alkyl); (The arrow indicates the bond of the compound of formula (I)).

[0376] In a more preferred embodiment, said R 3 is selected from the following formulas

[0377]

Chemical formula

[0378] (wherein A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2(alkyl), -C(O)NH(C 1~2 (alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N, each independently selected for each formula, and each monocyclic carbocyclyl and heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * independently selected from one or more, preferably one or two substituents, and each is independently optionally substituted; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C substituted with 1 to 4 F 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2-; In a more preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each independently selected for each formula, and each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4Haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a more preferred embodiment, A 2 is hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and is independently selected for each formula from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being independently and optionally substituted with one or more, preferably one or two substituents independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * is independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; A 31 is -C 1~2 alkyl, C 1~2Haloalkyl, -F, -Cl, -O(C 1~2 alkyl), -OH, -NHC(O)(C 1~2 alkyl) is independently selected for each formula; A 32 is, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S, and N are independently selected for each formula, and each monocyclic carbocyclyl and heterocyclyl is independently optionally substituted with one or more, preferably one or two substituents selected from halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-; In a further preferred embodiment, A 32 is, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2(alkyl), -C(O)NH(C 1~2 (alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and independently selected for each formula from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * and independently optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, and phenyl; In a further preferred embodiment, A 32 is -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 (alkyl)2, -NHC(O)(phenyl), and independently selected for each formula from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R *independently and optionally substituted with one or more, preferably one or two substituents selected independently therefrom; each R * is selected independently from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; A 35 is selected independently from -C 1~2 alkyl for each formula; (the arrow indicates the bond of the compound of formula (I)).

[0379] In a further very preferred embodiment, said R 3 is selected from the following formulas,

[0380]

Chemical formula

[0381] wherein, A 2 and A 32 are each independently selected from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R *Independently selected from one or more, preferably one or two substituents, and independently and optionally substituted; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; In an even more preferred embodiment, said R 3 is selected from the following formulas,

[0382]

Chemical formula

[0383] wherein, A 2 and A 32 are hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and are independently selected for each formula from 4- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, and each monocyclic heterocyclyl is halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * Independently selected from one or more, preferably one or two substituents, and independently and optionally substituted; each R * is H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl; In an even more preferred embodiment, said R3 is selected from the following formulas,

[0384] [Chemical formula]

[0385] wherein, A 2 is independently selected for each formula from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl); A 32 is independently selected for each formula from -C 1~2 alkyl, C 1~2 haloalkyl, -F, -Cl, -O(C 1~2 alkyl), =O, -OH, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, with each monocyclic heterocyclyl being independently optionally substituted with one or more, preferably one or two substituents independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl.

[0386] In a further highly preferred embodiment, said R 3 is selected from the following formulas,

[0387] [Chem.]

[0388] In the formula, A 2 is independently selected from hydrogen, -C 1~2 alkyl, C 1~2 haloalkyl, and -F for each formula; A 32 is independently selected from -C 1~2 alkyl, C 1~2 haloalkyl, -F, -NHC(O)(C 1~2 alkyl), -C(O)NH(C 1~2 alkyl), -C(O)N(C 1~2 alkyl)2, -NHC(O)(phenyl), and a 4- to 6-membered monocyclic heterocyclyl containing 1 to 3 heteroatoms selected from O and N for each formula, each monocyclic heterocyclyl being independently optionally substituted with one or two substituents independently selected from halogen, cyclopropyl, -C 1~3 alkyl, C 1~3 haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C 1~3 alkylene-OR * , -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~3 alkyl, C 1~3 haloalkyl, and phenyl.

[0389] Each of X 1 , X 2 , and X 3 is independently selected from N, CH, and CR x , at least one of said X 1 , X 2 , and X 3 is N, and more preferably, X 2 and X3 At least one of them is N; and even more preferably, X 2 , and X 3 are both N, and even more preferably, X 2 , and X 3 are both N, X 1 is CH.

[0390] E is selected from -CH2-, -CHR x -, -CR x 2-, -NH-, -NRx-, and -O-, -L 1 -L 2 -, and -L 2 -L 1 -L 1 is selected from -CH2-, -CHR x -, -CR x 2-, -NH-, -NR x -, and -O-, L 2 is selected from -CH2-, -CHR x - and -CR x 2-. In a more preferred embodiment, said E is selected from -CH2-, -NH-, -O-, -CH2-O-, -O-CH2-, -CH2-NH-, -NH-CH2- and -CH2-CH2-. Preferably, E is selected from CH2-, -O-, -CH2-O-, -O-CH2- and -CH2-CH2-. More preferably, E is selected from CH2-, -O-, -CH2-O-, and -CH2-CH2-. In a further preferred embodiment, E is CH2.

[0391] Ring A may be further substituted with one or more R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 ; the R xIt should be understood that the number of the groups is 0, 1, 2, 3 or 4, preferably 0, 1, 2 or 3, more preferably 0, 1 or 2, or alternatively preferably 0 or 1. When ring A is substituted with one or more R x groups, and one of the said R x groups of ring A is optionally linked to R 21 and, when one of the said R 21 groups of ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0392] Thus, in a preferred embodiment, the said ring A is further substituted with 1, 2, 3 or 4 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 . When one of the said R x groups of ring A is optionally linked to R 21 and, when one of the said R 21 groups of ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0393] In a preferred embodiment, the said ring A is further substituted with 1, 2 or 3 R x groups, and any two R x groups of ring A, preferably adjacent R x groups, are optionally linked, and / or any R x group of ring A is optionally linked to R 21 . When one of the said R x groups of ring A is optionally linked to R 21 and, when one of the said R 21 groups of ring A that is optionally linked to R x is a substituent at the 2-position of ring A.

[0394] In a preferred embodiment, the said ring A is further substituted with 1 or 2 R x groups, and any two Rx groups, preferably adjacent R x groups are optionally linked and / or any R of ring A x group is R 21 is optionally linked to R. Said R of ring A x group of one is R 21 is optionally linked to R, when one of the said R 21 groups of ring A that is optionally linked to R x group of one is a substituent at the 2-position of ring A.

[0395] In a preferred embodiment, said ring A is further substituted with one R x group, and said R of ring A x group is R 21 is optionally linked to R. Said R of ring A x group of one is R 21 is optionally linked to R, when one of the said R 21 groups of ring A that is optionally linked to R x group of one is a substituent at the 2-position of ring A.

[0396] In a preferred embodiment, said ring A is further substituted with one R x group, and said R of ring A x group is not linked to R. 21

[0397] In a preferred embodiment, said ring A is further substituted with one R x group, and said R of ring A x group is not linked to R. In a more preferred embodiment, said R 21 group is -F, preferably, said R x group that is -F is at the 3-position of ring A, and said position connects said ring A to the X x -, X 1 -, X 2 - ring system. 3

[0398] In a preferred embodiment, said ring A is not further substituted. Thus, in a preferred embodiment, said ring A is not further substituted with R x groups. ​​

[0399] In a preferred embodiment, the R 21 is hydrogen, C 1~6 alkyl, C 1~6 haloalkyl, C optionally substituted with one or more OH 1~6 alkyl, C containing 1 to 3 oxygen atoms between carbon atoms 1~6 alkyl, and C optionally substituted with one or more R 22 selected from cycloalkyl, and R 3~6 is selected from halogen, preferably -Cl, -F, and -OH. In a further preferred embodiment, the R 22 is hydrogen, C 21 alkyl, C 1~2 haloalkyl, C optionally substituted with one or two OH 1~2 alkyl, and C optionally substituted with one or more R 1~2 selected from cycloalkyl, and R 22 is selected from -Cl, -F, and -OH. In a further preferred embodiment, the R 3~4 is selected from C 22 alkyl, C 21 haloalkyl and C 1~2 cycloalkyl. In a further preferred embodiment, the R 1~2 is selected from C 3~4 alkyl and cyclopropyl. In a further preferred embodiment, the R 21 is selected from C 1~2 alkyl and cyclopropyl. In a further preferred embodiment, the R 21 is ethyl. In a further preferred embodiment, the R 21 is cyclopropyl. In a further very preferred embodiment, the R 21 is methyl.

[0400] In a preferred embodiment, each R x is -halogen, -OH, -O-C optionally substituted with one or more R xa alkyl, -NH-C optionally substituted with one or more R 1~3 alkyl, -NH-C optionally substituted with one or more R xa alkyl 1~3Alkyl, -N(one or more R xa optionally substituted C 1~3 alkyl)2, =O, one or more R xa optionally substituted C 1~4 alkyl, C 1~4 haloalkyl, -(one or more R xa optionally substituted C 1~2 alkylene)-(optionally substituted carbocyclic), -(one or more R xa optionally substituted C 1~2 alkylene)-(optionally substituted heterocyclic), -O-(one or more R xa optionally substituted C 1~2 alkylene)-(optionally substituted carbocyclic), -O-(one or more R xa optionally substituted C 1~2 alkylene)-(optionally substituted heterocyclic), -(optionally substituted carbocyclic), and -(optionally substituted heterocyclic), independently selected from, said R xa is independently selected from halogen, preferably -Cl, -F, and -OH.

[0401] In a further preferred embodiment, each R x is -halogen, -OH, one or more R xa optionally substituted -O-C 1~2 alkyl, one or more R xa optionally substituted -NH-C 1~2 alkyl, -N(one or more R xa optionally substituted C 1~2 alkyl)2, =O, one or more R xa optionally substituted C 1~3 alkyl, C 1~2 haloalkyl, -(one or more R xa optionally substituted C 1~2 alkylene)-(one or more R xa(optionally substituted monocyclic carbocyclyl), -(one or more R xa (optionally substituted C 1~2 alkylene)-(one or more R xa (optionally substituted monocyclic heterocyclyl), -O-(one or more R xa (optionally substituted C 1~2 alkylene)-(one or more R xa (optionally substituted monocyclic carbocyclyl), -O-(one or more R xa (optionally substituted C 1~2 alkylene)-(one or more R xa (optionally substituted monocyclic heterocyclyl), one or more R xa (optionally substituted monocyclic carbocyclyl, one or more R xa (optionally substituted monocyclic heterocyclyl) independently selected from, said R xa is independently selected from halogen, preferably -Cl, -F, and -OH.

[0402] In a more preferred embodiment, each R x is -halogen, -OH, -O-C xa (optionally substituted C 1~2 alkyl, -NH-C xa (optionally substituted C 1~2 alkyl, -N(two C 1~2 alkyls optionally substituted in one or more Rxa), =O, -C xa (optionally substituted C 1~3 alkyl, C 1~2 haloalkyl, -W-(one or more R xa (optionally substituted monocyclic carbocyclyl), -W-(one or more R xa (optionally substituted monocyclic heterocyclyl) independently selected from, -W- is absent or -(C 1~2 alkylene)- or -O-(C1~2 is (alkylene), and said R xa is independently selected from -Cl, -F, and -OH.

[0403] In a further preferred embodiment, each R x is -halogen, -OH, -O-C xa alkyl optionally substituted in 1~2 one or more R xa -NH-C 1~2 alkyl optionally substituted in xa one or more R 1~2 -N(alkyl optionally substituted in one or more R xa C 1~3 alkyl)2, =O, C 1~2 alkyl optionally substituted in one or more R xa -W-(monocyclic carbocyclyl optionally substituted in one or more R xa ), -W-(monocyclic heterocyclyl optionally substituted in one or more R 1~2 ), and is independently selected from the group consisting of, -W- is absent or is -(C 1~2 alkylene)- or -O-(C 3~6 alkylene)-, monocyclic carbocyclyl is selected from phenyl and C xa cycloalkyl, monocyclic heterocyclyl is selected from thiophenyl, pyridyl, pyrazinyl and pyrimidinyl, and said R

[0404] In a further preferred embodiment, each R x is -halogen, -OH, -O-C 1~2 alkyl, -NH-C 1~2 alkyl, -N(C 1~2 alkyl)2, =O, C 1~3 alkyl, C 1~2 haloalkyl, -W-(monocyclic carbocyclyl optionally substituted in one or more R xa ), -W-(monocyclic heterocyclyl optionally substituted in one or more R xaindependently selected from (monocyclic heterocyclyl) optionally substituted therein, -W- is absent or -(C 1~2 alkylene)- or -O-(C 1~2 alkylene)-, the monocyclic carbocyclyl is selected from phenyl and C 3~6 cycloalkyl, the monocyclic heterocyclyl is selected from thiophenyl, pyridyl, pyrazinyl and pyrimidinyl, and said R xa is independently selected from -F and -OH.

[0405] Even more preferred embodiments and aspects provide a compound of formula (I) for use in a method of treating a fibrotic disease, said compound of formula (I) being a compound of formula (XIIb), optionally in the form of a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof,

[0406]

Chemical formula

[0407] wherein, In a more preferred embodiment, said R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~6 alkyl, C 1~6 haloalkyl, -O-(C 1~6 alkyl), -O-(C 1~6 haloalkyl), -OH, -(C 1~2 alkylene)-O-(C 1~4 alkylene)-OR * -O-(C 1~4-(alkylene)-OR * 、-(C 1~2 alkylene)-O-(C 1~4 alkylene)-N(R°°)2、-O-(C 1~4 alkylene)-N(R°°)2、-CN、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R * 、and one or more, preferably one or two substituents independently selected from a 3- to 6-membered monocyclic carbocyclyl and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S and N, optionally independently substituted, each monocyclic carbocyclyl and heterocyclyl being selected from halogen, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * optionally independently substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~4 alkyl, C 1~4 haloalkyl, each R°° is independently selected from H, C 1~4 alkyl or together with the nitrogen atom to which they are attached forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C substituted with 1 to 4 F1~3 It is independently and optionally substituted with one divalent substituent selected from alkylene, -CH2-O-CH2- and -CH2-NH-CH2-.

[0408] In a more preferred embodiment, said R 1 is selected from phenyl, 5- or 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, one or two carbocyclic atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are halogen, -C 1~4 alkyl, C 1~4 haloalkyl, -O-(C 1~4 alkyl), -O-(C 1~4 haloalkyl), -OH, -(C 1~2 alkylene)-O-(C 1~4 alkylene)-OR * , -O-(C 1~4 alkylene)-OR * , -(C 1~2 alkylene)-O-(C 1~4 alkylene)-N(R°°)2, -O-(C 1~4 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R *and 3-6 membered monocyclic heterocyclyl containing 1-4 heteroatoms selected from O, S and N, wherein each monocyclic heterocyclyl is independently optionally substituted with one or more, preferably one or two, substituents selected from halogen, -C 1~3 Alkyl, C 1~3 Haloalkyl, -O-(C 1~3 alkyl), -O-(C 1~3 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * and each R * is H, C 1~3 Alkyl, C 1~3 haloalkyl, and each R°° is independently selected from H, C 1~4 alkyl, or together with the nitrogen atom to which they are attached form a 6-membered monocyclic heterocyclyl, preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is selected from C 1~3 Alkylene, C substituted with 1-4 F 1~3 is optionally substituted independently with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0409] In a further preferred embodiment, the R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl and an 8- to 10-membered bicyclic heteroaryl, each independently containing one or more, preferably 1 to 5, ring heteroatoms independently selected from O, S and N, wherein one or two carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are optionally oxidized to -F, -Cl, -C 1~2 Alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C1~2 (alkylene)-OR * 、-O-(C 1~2 (alkylene)-N(R°°)2, =O, -C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R * 、and one or more, preferably one or two substituents independently and optionally selected from 3- to 6-membered monocyclic heterocyclyls containing 1 to 4 heteroatoms selected from O, S, and N, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * independently and optionally substituted with one or more, preferably one or two substituents independently selected from; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0410] In a more preferred embodiment, said R 1 is selected from phenyl, a 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms independently selected from S and N, and an 8- to 10-membered bicyclic heteroaryl containing one or more, preferably 1 to 4, ring nitrogen heteroatoms, and one or two, preferably one, carbon ring atoms of said monocyclic heteroaryl or said bicyclic heteroaryl are optionally oxidized, and said phenyl, said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -F, -Cl, -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, -C(O)R * , -COOR * , -C(O)NR * R * , -NR * R * , -N(R * )-C(O)R * , -N(R * )-C(O)-OR * , -N(R * )-C(O)-NR * R * , -O-C(O)R * , -O-C(O)-NR * R * , and is independently optionally substituted with one or more, preferably one or two, substituents selected from 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R* is independently optionally substituted with one or more, preferably one or two substituents selected independently therefrom; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2-, and -CH2-NH-CH2-, and is independently optionally substituted with one divalent substituent selected therefrom.

[0411] In a more preferred embodiment, said R 1 is selected from 5- or 6-membered monocyclic heteroaryl containing one or two heteroatoms selected independently from S and N, and 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4 ring nitrogen heteroatoms, one or two, preferably one carbon ring atom of said monocyclic heteroaryl or said bicyclic heteroaryl is optionally oxidized, and said 5- or 6-membered monocyclic heteroaryl, and said 8- to 10-membered bicyclic heteroaryl are -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * 、-O-(C 1~2 alkylene)-N(R°°)2、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R *)-C(O)-NR * R * , -OC(O)R * , -OC(O)-NR * R * and a 4- to 6-membered monocyclic heterocyclyl containing 1 or 2 heteroatoms selected from O and N, wherein each monocyclic heterocyclyl is independently optionally substituted with 1 or 2, preferably 1, substituents selected from -C 1~2 Alkyl, C 1~2 Haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * and each R * , H, C 1~2 Alkyl, C 1~2 haloalkyl, and each R° is independently selected from H, C 1~2 alkyl, or together with the nitrogen atom to which they are attached form a 6-membered monocyclic heterocyclyl, preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is selected from C 1~3 Alkylene, C substituted with 1-4 F 1~3 Optionally substituted independently with one divalent substituent selected from alkylene, -CH2-O-CH2-, and -CH2-NH-CH2-.

[0412] In a further preferred embodiment, the R 1 is selected from 5- or 6-membered monocyclic heteroaryl containing 1 or 2 heteroatoms independently selected from S and N, and 8- to 10-membered bicyclic heteroaryl containing 1 to 5, preferably 1 to 4 ring nitrogen heteroatoms, wherein one or two, preferably one, carbon ring atom of said monocyclic heteroaryl or said bicyclic heteroaryl is optionally oxidized, and said 5- or 6-membered monocyclic heteroaryl and said 8- to 10-membered bicyclic heteroaryl are optionally oxidized1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, and one or two substituents selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, independently and optionally substituted with one or two, preferably one, substituents, each monocyclic heterocyclyl being -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, independently and optionally substituted with one or two, preferably one, substituents selected therefrom; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, independently selected, each R°° is H, C 1~2 alkyl, independently selected, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is C 1~3 alkylene, C alkylene substituted with 1 to 4 F, 1~3 alkylene, -CH2-O-CH2- and -CH2-NH-CH2-, independently and optionally substituted with one divalent substituent selected therefrom.

[0413] In a further preferred embodiment, said R 1 is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl being -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2(alkylene)-OR * 、-O-(C 1~2 (alkylene)-N(R°°)2、=O、-C(O)R * 、-COOR * 、-C(O)NR * R * 、-NR * R * 、-N(R * )-C(O)R * 、-N(R * )-C(O)-OR * 、-N(R * )-C(O)-NR * R * 、-O-C(O)R * 、-O-C(O)-NR * R * 、and one or two substituents independently and optionally selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, each monocyclic heterocyclyl being independently and optionally substituted with one or two substituents selected independently from -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, =O, -C(O)R * and -C(O)NR * R * ; each R * is independently selected from H, C 1~2 alkyl, C 1~2 haloalkyl, each R°° is independently selected from H, C 1~2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl preferably selected from morpholine, piperidine, and piperazine, and / or each monocyclic heterocyclyl is independently and optionally substituted with one divalent substituent selected from C 1~3 alkylene, C 1~3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-.

[0414] In a more preferred embodiment, said R 1 is phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl, and phenyl, thiophenyl, pyrrolyl, pyrazolyl, azaindolyl, azaindazolyl, pyrazinyl, pyridyl or pyrimidinyl is -C 1~2 alkyl, -CHF2, -CF3, -O-(C 1~2 alkyl), -OCHF2, -OCHF3, -OH, -O-(C 1~2 alkylene)-OR * , -O-(C 1~2 alkylene)-N(R°°)2, =O, and one or two substituents selected from 4- to 6-membered monocyclic heterocyclyls containing one or two heteroatoms selected from O and N, independently and optionally substituted with one or two, preferably one, substituents, and each monocyclic heterocyclyl is -C 1~2 alkyl, C 1~2 haloalkyl, -O-(C 1~2 alkyl), -O-(C 1~2 haloalkyl), -OH, and =O, independently and optionally substituted with one or two substituents independently selected therefrom; each R * is H, C 1~2 alkyl, C 1~2 haloalkyl, independently selected, each R°° is H, C 1~2 alkyl, independently selected, or together with the nitrogen atom to which they are attached, preferably forms a 6-membered monocyclic heterocyclyl selected from morph...

Claims

1. A pharmaceutical composition for treating fibrotic diseases, comprising a compound of formula (I), wherein the compound comprises a pharmaceutically acceptable salt, solvate, co-crystal, tautomer, racemate, enantiomer, or diastereomer or a mixture thereof. 【Chemical 1】 (In the formula, R １ is a 5- or 6-membered monocyclic heteroaryl independently containing one or two ring heteroatoms independently selected from phenyl, S, and N, and an 8- to 10-membered bicyclic heteroaryl containing 1 to 4 nitrogen ring heteroatoms, one or two carbon ring atoms of the monocyclic heteroaryl or the bicyclic heteroaryl are optionally oxidized, and the phenyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are selected from -F, -Cl, -C1-2 alkyl, -CHF2, -CF3, -O-(C1-2 alkyl), -OCHF2, -OCF3, -OH, -O-(C1-2 alkylene)-OR*, -O-(C1-2 alkylene)-NR°, =O, -C(O)R*, -COOR*, -C(O)NR*R*, -NR*R*, -N(R*)-C(O)R*, -N(R*)-C(O)-OR*, -N(R*)-C(O)-NR*R*, -O-C(O)R*, -O-C(O)-NR*R*, and a 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, S, and N, and are independently optionally substituted with one or two substituents, each monocyclic heterocyclyl is independently optionally substituted with one or two substituents selected from -C1-2 alkyl, C1-2 haloalkyl, -O-(C1-2 alkyl), -O-(C1-2 haloalkyl), -OH, =O, -C(O)R* and -C(O)NR*R*; each R* is independently selected from H, C1-2 alkyl, C1-2 haloalkyl, each R° is independently selected from H, C1-2 alkyl or, together with the nitrogen atom to which they are attached, forms a 6-membered monocyclic heterocyclyl selected from morpholine, piperidine and piperazine, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C1-3 alkylene, C1-3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-, R ２１ is -CH₃ or -CH₂CH₃, R ３ is selected from formula (C), formula (D), formula (E), formula (F), and formula (G), and the arrow in each formula indicates a bond in the compound of formula (I), 【Chemical 2】 B31 is N, CH or C(A31), and A31 is selected from -C1-2 alkyl, C1-2 haloalkyl, -F, -Cl, -O(C1-2 alkyl), -OH, -NHC(O)(C1-2 alkyl), B32 is N, CH or C(A32), and A32 is selected from -C1-2 alkyl, C1-2 haloalkyl, -F, -Cl, -O(C1-2 alkyl), =O, -OH, -NHC(O)(C1-2 alkyl), -NHC(O)-C1-2 alkylene-OH, -NHC(O)-C1-2 alkylene-O(C1-2 alkyl), -C(O)NH(C1-2 alkyl), -C(O)N(C1-2 alkyl)2, -NHC(O)(cyclopropyl), -NHC(O)(phenyl), and 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S and N, and each monocyclic carbocyclyl and heterocyclyl is independently optionally substituted with one or two substituents independently selected from halogen, tetrahydropyranyl, cyclopropyl, -C1-4 alkyl, C1-4 haloalkyl, -O-(C1-4 alkyl), -O-(C1-4 haloalkyl), -OH, =O, -C1-3 alkylene-OR*, -C(O)R* and -C(O)NR*R*; each R* is independently selected from H, C1-4 alkyl, C1-4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl is independently optionally substituted with one divalent substituent selected from C1-3 alkylene, C1-3 alkylene substituted with 1 to 4 F, -CH2-O-CH2- and -CH2-NH-CH2-. B 33 is N, CH or C(A 33), and A 33 is selected from -C 1-2 alkyl, C 1-2 haloalkyl, -F, -Cl, -O(C 1-2 alkyl), -OH, -NHC(O)(C 1-2 alkyl); A 2 is selected from hydrogen, -C 1-2 alkyl, C 1-2 haloalkyl, -F, -Cl, -O(C 1-2 alkyl), =O, -OH, -NHC(O)(C 1-2 alkyl), -NHC(O)-C 1-2 alkylene-OH, -NHC(O)-C 1-2 alkylene-O(C 1-2 alkyl), -C(O)NH(C 1-2 alkyl), -C(O)N(C 1-2 alkyl) 2, -NHC(O)(cyclopropyl), -NHC(O)(phenyl), and 3- to 6-membered monocyclic carbocyclyl and 3- to 6-membered monocyclic heterocyclyl containing 1 to 4 heteroatoms selected from O, B, S and N, each monocyclic carbocyclyl and heterocyclyl being independently optionally substituted with one or two substituents independently selected from halogen, tetrahydropyranyl, cyclopropyl, -C 1-4 alkyl, C 1-4 haloalkyl, -O-(C 1-4 alkyl), -O-(C 1-4 haloalkyl), -OH, =O, -C 1-3 alkylene-OR *, -C(O)R * and -C(O)NR * R *, each R * being independently selected from H, C 1-4 alkyl, C 1-4 haloalkyl, phenyl, and / or each monocyclic heterocyclyl being independently optionally substituted with one divalent substituent selected from C 1-3 alkylene, C 1-3 alkylene substituted with 1 to 4 F, -CH 2 -O-CH 2 - and -CH 2 -NH-CH 2 -, Y 31 is N, CH or C(A 31), and A 31 is selected from methyl and ethyl, Y 32 is N, CH or C(A 32), and A 32 is selected from methyl and ethyl, Y 33 is N, CH or C(A 33), and A 33 is selected from methyl and ethyl, B 34 is N, A3D is selected from hydrogen, -C1-2 alkyl, C1-2 haloalkyl, -F, -Cl, -O(C1-2 alkyl), =O, -OH, -NHC(O)(C1-2 alkyl), -C(O)NH(C1-2 alkyl), -C(O)N(C1-2 alkyl)2, -NHC(O)(phenyl), Y44 is N, NH, N(A44), C(O), CH, or C(A44), A44 is independently selected from methyl and ethyl, Y45 is N, NH, N(A45), C(O), CH, or C(A45), A45 is independently selected from methyl and ethyl, Y46 is N, NH, N(A46), C(O), CH, or C(A46), A46 is independently selected from methyl and ethyl, and at least one of said Y44, Y45 and Y46 is NH, N(CH3) or N(C2H5), A3E is selected from hydrogen, -C1-2 alkyl, C1-2 haloalkyl, -F, -Cl, -O(C1-2 alkyl), =O, -OH, -NHC(O)(C1-2 alkyl), -C(O)NH(C1-2 alkyl), -C(O)N(C1-2 alkyl)2, -NHC(O)(phenyl), Y47 is N, NH, N(A47), C(O), CH, or C(A47), A47 is independently selected from methyl and ethyl, Y48 is N, NH, N(A48), C(O), CH, or C(A48), A48 is independently selected from methyl and ethyl, Y49 is N, NH, N(A49), O, C(O), CH, or C(A49), A49 is independently selected from methyl and ethyl, and at least one of said Y47, Y48 and Y49 is NH, N(CH3) or N(C2H5); A3F is selected from hydrogen, -C1-2 alkyl, C1-2 haloalkyl, -F, -Cl, -O(C1-2 alkyl), =O, -OH, -NHC(O)(C1-2 alkyl), -C(O)NH(C1-2 alkyl), -C(O)N(C1-2 alkyl)2, -NHC(O)(phenyl), G1, G2, G3, G4 are independently selected from N, CH, C(O), NH, or N(C1-2 alkyl), X1 is CH, X2 and X3 are N, R31 is selected from hydrogen and C1-2-alkyl, E is -CH2-, R6x is selected from C1-3 alkyl and C1-2 haloalkyl.)

2. The pharmaceutical composition for treating fibrotic diseases according to claim 1, wherein the compound of formula (I) is a compound of formula (V). 【Chemical Formula 3】

3. The pharmaceutical composition for treating fibrotic diseases according to claim 1 or claim 2, wherein the compound of formula (I) is a compound of formula (VI). 【Chemical Formula 4】

4. R21 is -CH ３ The pharmaceutical composition for treating fibrotic diseases according to any one of claims 1 to 3, wherein R21 is -CH.

5. The pharmaceutical composition for treating fibrotic diseases according to any one of claims 1 to 4, wherein R31 is -hydrogen.

6. The fibrotic disease is selected from the group consisting of pulmonary fibrosis, idiopathic pulmonary fibrosis, radiation-induced pneumonia, radiation fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, interstitial lung disease, myocardial infarction, cardiac fibrosis and hypertrophy, ischemic stroke, ischemic kidney disease, renal fibrosis, rheumatoid arthritis, liver fibrosis, NASH (non-alcoholic steatohepatitis), chronic hepatitis, cirrhosis, inflammatory bowel disease, Crohn's disease, scleroderma, keloid, postoperative fibrosis, chemotherapy-induced fibrosis (e.g., chemotherapy-induced pulmonary fibrosis or ovarian cortical fibrosis), nephrogenic systemic fibrosis, retroperitoneal fibrosis, myelofibrosis, mediastinal fibrosis, cystic fibrosis, asbestosis, asthma, pulmonary hypertension, systemic fibrosis, dermal fibrosis, hypertension-induced renal fibrosis and cardiac fibrosis. The pharmaceutical composition for treating fibrotic diseases according to any one of claims 1 to 5.

7. The pharmaceutical composition for treating fibrotic diseases according to claim 6, wherein the fibrotic disease is interstitial lung disease (ILD).

8. The pharmaceutical composition for treating fibrotic diseases according to claim 7, wherein the interstitial lung disease is idiopathic interstitial pneumonia (IIP).

9. The pharmaceutical composition for treating fibrotic diseases according to claim 8, wherein the idiopathic interstitial pneumonia is selected from the group consisting of chronic fibrotic interstitial pneumonia, smoking-related interstitial pneumonia, and acute / subacute interstitial pneumonia.

10. The pharmaceutical composition for treating fibrotic diseases according to claim 9, wherein the chronic fibrotic interstitial pneumonia is idiopathic pulmonary fibrosis (IPF).

11. The pharmaceutical composition for treating fibrotic diseases according to claim 6, wherein the fibrotic disease is non-alcoholic steatohepatitis (NASH).

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