Alkenyl pyrimidine compounds, preparation methods and applications thereof

Abstract

The present invention relates to alkenyl pyrimidine compounds, their preparation methods, and uses. Specifically, it relates to compounds with EGFR inhibitory activity and pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof, their preparation methods, pharmaceutical compositions containing the compounds, and the use of these compounds in the preparation of drugs for the prevention and / or treatment of EGFR kinase-mediated cancers and other diseases. #imgabs0#

Description

Technical Field

[0001] The present invention relates to the field of medicinal chemistry, and in particular to alkenyl pyrimidine compounds, preparation methods and applications thereof. Background Art

[0002] The epidermal growth factor receptor (EGFR) is a tyrosine kinase widely distributed on human cell membranes. Upon stimulation by endogenous ligands, EGFR dimerizes and autophosphorylates, activating downstream signaling pathways and promoting cell growth, proliferation, migration, and other activities. Mutations in EGFR, such as the most common exon 19 deletion (19Del) or exon 20 point mutation (L858R), increase its kinase activity, increasing activation of downstream signaling pathways and ultimately leading to tumorigenesis. Studies have shown that at least 10% of patients with non-small cell lung cancer harbor EGFR mutations (Nature Reviews Cancer, 2007, 7, 169-181). Therefore, targeting EGFR has become an effective treatment for non-small cell lung cancer.

[0003] Gefitinib and erlotinib are the first approved ATP-competitive EGFR inhibitors, which have a good inhibitory effect on 19Del and L858R mutations. However, after a period of treatment, patients are prone to drug resistance, the main way of which is that EGFR further acquires the T790M mutation. Subsequently, researchers developed second- and third-generation inhibitors, such as afatinib and osimertinib, which form a covalent bond with the cysteine ​​residue at position 797 of EGFR, irreversibly blocking the binding of ATP to EGFR, thereby overcoming the T790M mutation. In addition, due to the weak inhibitory activity against wild-type EGFR, the third-generation inhibitors reduce the toxic side effects of the second-generation inhibitors.

[0004] However, third-generation inhibitors also face the problem of drug resistance (Nature Medicine, 2015, 21, 560-562). The main mechanism is that the cysteine ​​residue at position 797 of EGFR mutates to a serine residue (C797S), resulting in the disappearance of the covalent bond between Cys and the inhibitor, leading to a decrease in the inhibitory effect.

[0005] Therefore, the development of fourth-generation EGFR inhibitors that can overcome the C797S mutation is of great significance and clinical value. Summary of the Invention

[0006] After extensive and in-depth research, the inventors of the present application designed and synthesized a series of small molecule compounds with novel structures, which have a good inhibitory effect on multiple common mutants of EGFR kinase in clinical practice, including mutants containing C797S.

[0007] The present invention provides the following compounds:

[0008]

[0009] or a stereoisomer of the above-mentioned compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

[0010] The definitions of the substituents and symbols are detailed below.

[0011] One object of the present invention is to provide a class of compounds having the ability to inhibit EGFR kinase activity, and stereoisomers, prodrugs, pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof.

[0012] Another object of the present invention is to provide a method for preparing the above compound.

[0013] Another object of the present invention is to provide a pharmaceutical composition comprising the above compound.

[0014] Another object of the present invention is to provide the use of the above-mentioned compound and a pharmaceutical composition comprising the above-mentioned compound in the preparation of a drug for the prevention and / or treatment of EGFR kinase-mediated cancer or other diseases.

[0015] Another object of the present invention is to provide a method for treating cancer, which comprises administering an effective amount of the compound or composition of the present invention to a subject. Detailed Description of the Invention

[0017] Various specific embodiments, modes and examples are described herein, including exemplary embodiments and definitions for the purpose of understanding the claimed invention. Although the following detailed description sets forth specific preferred embodiments, it will be understood by those skilled in the art that these embodiments are exemplary only and that the invention may be practiced in other ways. For the purpose of determining infringement, the scope of the invention will be directed to any one or more of the appended claims, including their equivalents, and to those elements or limitations that are equivalent thereto.

[0018] The present invention is achieved through the following technical solutions.

[0019] In the first aspect of the present invention, the present invention provides the following compounds:

[0020]

[0021] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0022] in:

[0023] R1 Selected from:

[0024] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0025] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0026] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1,5-diethyl-3- Pyrazolyl, 1,5-diisopropyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 1-methyl-5-isopropyl-3-pyrazolyl, 1-ethyl-5-methyl-3-pyrazolyl, 1-ethyl-5-isopropyl-3-pyrazolyl, 1-isopropyl-5-methyl-3-pyrazolyl, 1-isopropyl-5-ethyl-3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-Ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-4-pyrazolyl, 1,3-diethyl-4-pyrazolyl, 1,3-diisopropyl-4-pyrazolyl, 1-methyl-3-ethyl-4-pyrazolyl, 1-methyl-3-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl oxazolyl, 1-ethyl-3-isopropyl-4-pyrazolyl, 1-isopropyl-3-methyl-4-pyrazolyl, 1-isopropyl-3-ethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0027] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0028] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0029] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0030] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0031] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, N-tert-butyloxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0032] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0033] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0034] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0035] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(piperazine-1-)piperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4 -(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0036] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0037] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0038] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0039] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0040] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0041] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0042] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0043] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0044] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0045] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0046] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0047] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0048] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0049] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0050] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0051] (16)

[0052] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those for Y1,

[0053] (18) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0054] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0055] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0056] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0057] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0058] R 2 Selected from:

[0059] 1) Wherein, Z1 and Z2 are each independently selected from C1-C6 alkyl, C3-C8 cycloalkyl;

[0060] 2) wherein Z3 and Z4 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, and Z4 is not hydrogen;

[0061] 3) Wherein, Z5 is selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0062] 4) wherein Z6 and Z7 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, or Z6 and Z7 together with N form a substituted or unsubstituted 4-8 membered ring containing 1 to 2 heteroatoms, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl; preferably, Z6 and Z7 are each independently selected from hydrogen, C1-C6 alkyl; more preferably, Z6 and Z7 are each independently selected from hydrogen, methyl, isopropyl, and most preferably, any one of Z6 and Z7 is hydrogen and the other is selected from methyl, isopropyl;

[0063] R 3 、R 4 、R 5 Each independently selected from:

[0064] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0065] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0066] 3) R 3 、R 4Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl;

[0067] Furthermore, the compound represented by formula (A) is not selected from

[0068] In some embodiments, R 1 Selected from:

[0069] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0070] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0071] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1,5-diethyl-3-pyrazolyl, 1,5-diisopropyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 1-methyl-5-isopropyl-3-pyrazolyl, 1-ethyl-5-methyl-3-pyrazolyl, 1-ethyl-5-isopropyl-3-pyrazolyl, 1-isopropyl-5-methyl-3-pyrazolyl, 1-isopropyl-5-ethyl- 3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-4-pyrazolyl, 1,3-diethyl-4-pyrazolyl, 1,3-diisopropyl-4-pyrazolyl, 1-methyl-3-ethyl-4-pyrazolyl, 1-methyl-3-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl, 1-ethyl-3-isopropyl-4-pyrazolyl, 1-isopropyl-3-methyl-4-pyrazolyl, 1-isopropyl-3-ethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0072] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0073] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0074] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0075] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl,

[0076] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0077] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0078] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0079] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(piperazine-1-)piperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0080] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0081] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N- Isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0082] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0083] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0084] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0085] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0086] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0087] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0088] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0089] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0090] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0091] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0092] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0093] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido,

[0094] (14)

[0095] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0096] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0097] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0098] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0099] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0100] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0101] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0102] In some embodiments, R 1 Selected from:

[0103] 1) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0104] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0105] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C2-C6 alkenyl, C3-C6 cycloalkyl,

[0106] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl,

[0107] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0108] (5) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0109] (6) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(piperazine-1-)piperidinyl, 4-hydroxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl,

[0110] (7) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl,

[0111] (8) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, 2-(N,N-dimethylamino)acetamido, cyclopropylsulfonamido, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0112] (9) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0113] (10) 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl, N-methylpiperazine-1-formyl, N-ethylpiperazine-1-formyl, N-isopropylpiperazine-1-formyl,

[0114] (11) cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0115] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl,

[0116] (12) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0117] (13)

[0118] 2) wherein Y1, Y3, Y4, and Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, and 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0119] 3) Wherein, Y1 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, fluorine, chlorine, bromine, C1-C6 fluorine-containing alkoxy, Y2 and Y5 are each independently selected from hydrogen, C1-C6 alkyl (preferably hydrogen), R y Selected from C1-C6 alkyl;

[0120] 4) Wherein, Y1, Y2, Y5 are each independently selected from hydrogen, C1-C6 alkyl (preferably hydrogen), R z is selected from C1-C6 alkyl, R is selected from hydrogen, C1-C6 alkyl (preferably selected from hydrogen, methyl);

[0121] 5) 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1,5-diethyl-3-pyrazolyl, 1,5-diisopropyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 1-methyl-5-isopropyl-3-pyrazolyl, 1-ethyl-5-methyl-3-pyrazolyl, 1-ethyl-5-isopropyl-3-pyrazolyl, 1-isopropyl-5-methyl-3-pyrazolyl, 1-isopropyl-5-ethyl-3-pyrazolyl , 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1,3-dimethyl-4-pyrazolyl, 1,3-diethyl-4-pyrazolyl, 1,3-diisopropyl-4-pyrazolyl, 1-methyl-3-ethyl-4-pyrazolyl, 1-methyl-3-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl, 1-ethyl-3-isopropyl-4-pyrazolyl, 1-isopropyl-3-methyl-4-pyrazolyl, 1-isopropyl-3-ethyl-4-pyrazolyl.

[0122] In some embodiments, R 1 Selected from:

[0123] 1) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time:

[0124] Hydrogen, fluorine, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, trifluoromethyl, trifluoromethoxy, vinyl, N-methylpiperazinyl, morpholinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-hydroxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, N-methyl-4-piperidinyl, 2-(N,N-dimethylamino)acetamido, cyclopropylsulfonamido, 2-hydroxyethylamino 1-methylpiperazine, 1-methyl-2-nitropropane, 1-methyl-3-nitropropane, 1-methyl-4-nitropropane, 1-methyl-2-nitropropane, 1-methyl-3-nitropropane, 1-methyl-4-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-3-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane, 1-methyl-2-nitropropane,

[0125] 2) wherein Y1, Y3, Y4, and Y5 are each independently selected from hydrogen, methyl, ethyl, methoxy, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methylpiperazinyl, and 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0126] 3) Wherein, Y1 is selected from hydrogen, methyl, methoxy, fluorine, chlorine, trifluoromethoxy, Y2 and Y5 are hydrogen, R y is methyl;

[0127] 4) Among them, Y1, Y2, Y5 are hydrogen, R z is methyl, R is selected from hydrogen, methyl;

[0128] 5) 3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl.

[0129] In some embodiments, Z1 and Z2 are each independently selected from C1-C6 alkyl.

[0130] In some embodiments, Z1 and Z2 are methyl.

[0131] In some embodiments, Z5 is selected from C1-C6 alkyl.

[0132] In some embodiments, Z5 is selected from methyl, isopropyl.

[0133] In some embodiments, Z3 and Z4 are each independently selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, and C3-C6 cycloalkyl.

[0134] In some embodiments, Z3 and Z4 are each independently selected from methyl, ethyl, isopropyl, cyclopropyl, and trifluoromethyl.

[0135] In some embodiments, Z6 and Z7 are each independently selected from hydrogen and C1-C6 alkyl.

[0136] In some embodiments, Z6 and Z7 are each independently selected from hydrogen, methyl, and isopropyl.

[0137] In some embodiments, either Z6 or Z7 is hydrogen, and the other is selected from methyl and isopropyl.

[0138] In some embodiments, R 3 、R 4 、R 5 Each independently selected from:

[0139] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl;

[0140] 2) substituted or unsubstituted aryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0141] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 Selected from hydrogen, C1-C6 alkyl.

[0142] In some embodiments, R 3 、R 4 、R 5 Each independently selected from:

[0143] 1) Hydrogen, methyl, ethoxy, cyclopropyl;

[0144] 2) phenyl;

[0145] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5For hydrogen.

[0146] In a second aspect of the present invention, the present invention provides a compound which is the following:

[0147]

[0148] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0149] in:

[0150] R 1 Selected from:

[0151] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0152] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0153] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0154] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0155] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0156] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0157] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0158] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N , N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0159] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0160] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0161] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0162] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2- cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0163] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0164] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-5-amino 4-aminopiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0165] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0166] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0167] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0168] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0169] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0170] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0171] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0172] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0173] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0174] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0175] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0176] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0177] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0178] (16) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0179] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0180] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0181] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0182] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0183] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0184] Z1 and Z2 are each independently selected from C1-C6 alkyl, C3-C8 cycloalkyl;

[0185] R 3 、R 4 、R 5 Each independently selected from:

[0186] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0187] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0188] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl;

[0189] Furthermore, the compound represented by formula (I) is not selected from

[0190] In some embodiments, R 1 Selected from:

[0191] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0192] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0193] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0194] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0195] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0196] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0197] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl,

[0198] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0199] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0200] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0201] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0202] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0203] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0204] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0205] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0206] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0207] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0208] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0209] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0210] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0211] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0212] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0213] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0214] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0215] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido;

[0216] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0217] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0218] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0219] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0220] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0221] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0222] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0223] In some embodiments, R 1 Selected from:

[0224] 1) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0225] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0226] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl,

[0227] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,

[0228] (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0229] (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl,

[0230] (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0231] (7) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl;

[0232] 2) wherein Y1, Y3, Y4, and Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, and 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0233] 3) Wherein, Y1 is selected from fluorine, chlorine, and bromine, Y2 and Y5 are each independently selected from hydrogen, C1-C6 alkyl (preferably hydrogen), R y Selected from C1-C6 alkyl;

[0234] 4) Wherein, Y1, Y2, Y5 are each independently selected from hydrogen, C1-C6 alkyl (preferably hydrogen), R z is selected from C1-C6 alkyl, and R is selected from hydrogen, C1-C6 alkyl (preferably hydrogen).

[0235] In some embodiments, R 1 Selected from:

[0236] 1) in:

[0237] Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0238] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, N-methyl-4-piperidinyl;

[0239] Preferably, Y1, Y2, Y4, Y5 are each independently selected from hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methyl-4-piperidinyl; Y3 is selected from hydrogen, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl;

[0240] 2) in:

[0241] Y1, Y3, Y4, Y5 are each independently selected from hydrogen, methyl, ethyl, methoxy, 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time,

[0242] Preferably, Y1, Y4, and Y5 are each independently selected from hydrogen, methyl, ethyl, and methoxy, and Y3 is 4-(N-methylpiperazine-1-)piperidinyl;

[0243] 3) Among them, Y1 is fluorine, Y2 and Y5 are hydrogen, R y is methyl;

[0244] 4) Among them, Y1, Y2, Y5 are hydrogen, R z is methyl, and R is hydrogen.

[0245] In some embodiments, Z1 and Z2 are each independently selected from C1-C6 alkyl.

[0246] In some embodiments, Z1 and Z2 are methyl.

[0247] In some embodiments, R 3 、R 4 、R 5 Each independently selected from:

[0248] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl;

[0249] 2) substituted or unsubstituted aryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0250] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 Selected from hydrogen, C1-C6 alkyl.

[0251] In some embodiments, R 3 、R 4 、R 5 Each independently selected from:

[0252] 1) Hydrogen, methyl, ethoxy, cyclopropyl;

[0253] 2) phenyl;

[0254] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 For hydrogen.

[0255] In some embodiments, R 3 is selected from hydrogen, methyl, R 4 is selected from hydrogen, methyl, ethoxy, cyclopropyl, phenyl, R 5 is selected from hydrogen, methyl; or, R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 For hydrogen.

[0256] In a third aspect of the present invention, the present invention provides a compound which is the following:

[0257]

[0258] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0259] in:

[0260] R 1 Selected from:

[0261] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0262] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0263] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1,5-diethyl-3- Pyrazolyl, 1,5-diisopropyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 1-methyl-5-isopropyl-3-pyrazolyl, 1-ethyl-5-methyl-3-pyrazolyl, 1-ethyl-5-isopropyl-3-pyrazolyl, 1-isopropyl-5-methyl-3-pyrazolyl, 1-isopropyl-5-ethyl-3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-Ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-4-pyrazolyl, 1,3-diethyl-4-pyrazolyl, 1,3-diisopropyl-4-pyrazolyl, 1-methyl-3-ethyl-4-pyrazolyl, 1-methyl-3-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl oxazolyl, 1-ethyl-3-isopropyl-4-pyrazolyl, 1-isopropyl-3-methyl-4-pyrazolyl, 1-isopropyl-3-ethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0264] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0265] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0266] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0267] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0268] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl, N-tert-butyloxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0269] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0270] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0271] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0272] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(piperazine-1-)piperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4 -(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0273] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0274] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0275] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0276] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0277] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0278] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0279] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0280] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0281] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0282] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0283] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0284] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0285] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0286] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0287] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0288] (16)

[0289] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those for Y1,

[0290] (18) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0291] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0292] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0293] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0294] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0295] Z3 and Z4 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, and Z4 is not hydrogen;

[0296] R 3 、R 4 、R 5 Each independently selected from:

[0297] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0298] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0299] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl.

[0300] In some embodiments, R 1 Selected from:

[0301] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0302] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0303] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1,5-diethyl-3-pyrazolyl, 1,5-diisopropyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 1-methyl-5-isopropyl-3-pyrazolyl, 1-ethyl-5-methyl-3-pyrazolyl, 1-ethyl-5-isopropyl-3-pyrazolyl, 1-isopropyl-5-methyl-3-pyrazolyl, 1-isopropyl-5-ethyl- 3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-4-pyrazolyl, 1,3-diethyl-4-pyrazolyl, 1,3-diisopropyl-4-pyrazolyl, 1-methyl-3-ethyl-4-pyrazolyl, 1-methyl-3-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl, 1-ethyl-3-isopropyl-4-pyrazolyl, 1-isopropyl-3-methyl-4-pyrazolyl, 1-isopropyl-3-ethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0304] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0305] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0306] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0307] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl,

[0308] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0309] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0310] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0311] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(piperazine-1-)piperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0312] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0313] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N- Isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0314] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0315] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0316] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0317] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0318] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0319] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0320] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0321] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0322] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0323] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0324] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0325] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido,

[0326] (14)

[0327] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0328] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0329] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0330] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0331] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0332] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0333] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0334] In some embodiments, R 1 Selected from:

[0335] 1) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0336] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0337] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl,

[0338] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl,

[0339] (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0340] (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(piperazine-1-)piperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl,

[0341] (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene, benzyl,

[0342] (7) 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0343] (8) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0344] (9)

[0345] 2) wherein Y1, Y3, Y4, and Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, and 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0346] 3) Wherein, Y1 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, fluorine, chlorine, bromine, C1-C6 fluorine-containing alkoxy, Y2 and Y5 are hydrogen, R y Selected from C1-C6 alkyl;

[0347] 4) Among them, Y1, Y2, Y5 are hydrogen, R z , R are each independently selected from C1-C6 alkyl;

[0348] 5) 3-pyrazolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1,5-diethyl-3-pyrazolyl, 1,5-diisopropyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 1-methyl-5-isopropyl-3-pyrazolyl, 1-ethyl-5-methyl-3-pyrazolyl, 1-ethyl-5-isopropyl-3-pyrazolyl, 1-isopropyl-5-methyl-3-pyrazolyl, 1-isopropyl-5-ethyl-3-pyrazolyl , 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1,3-dimethyl-4-pyrazolyl, 1,3-diethyl-4-pyrazolyl, 1,3-diisopropyl-4-pyrazolyl, 1-methyl-3-ethyl-4-pyrazolyl, 1-methyl-3-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl, 1-ethyl-3-isopropyl-4-pyrazolyl, 1-isopropyl-3-methyl-4-pyrazolyl, 1-isopropyl-3-ethyl-4-pyrazolyl.

[0349] In some embodiments, R 1 Selected from:

[0350] 1) in:

[0351] Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0352] hydrogen, fluorine, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, benzyl, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, 4-(piperazine-1-)piperidinyl, N-(N-methyl-4-piperidinyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl,

[0353] Preferably, Y1, Y2, Y4, Y5 are each independently selected from hydrogen, fluorine, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, benzyl; Y3 is selected from fluorine, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 2-hydroxyethylamino, 2-N,N-dimethylaminoethylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, 4-(piperazine-1-)piperidinyl, N-(N-methyl-4-piperidinyl)piperazinyl, 4-(N-methyl-azetidin-3-yl)piperazinyl,

[0354] 2) in:

[0355] Y1, Y3, Y4, Y5 are each independently selected from hydrogen, ethyl, methoxy, 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time,

[0356] Preferably, Y1, Y4, and Y5 are each independently selected from hydrogen, ethyl, and methoxy, and Y3 is 4-(N-methylpiperazine-1-)piperidinyl;

[0357] 3) Wherein, Y1 is selected from hydrogen, methyl, methoxy, fluorine, chlorine, trifluoromethoxy, Y2 and Y5 are hydrogen, R y is methyl;

[0358] 4) Among them, Y1, Y2, Y5 are hydrogen, R z , R is a methyl group;

[0359] 5) 3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1,5-dimethyl-3-pyrazolyl, 1-methyl-5-ethyl-3-pyrazolyl, 4-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-ethyl-3-methyl-4-pyrazolyl.

[0360] In some embodiments, Z3 and Z4 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, and C3-C6 cycloalkyl.

[0361] In some embodiments, Z3 and Z4 are each independently selected from hydrogen, methyl, ethyl, isopropyl, cyclopropyl, and trifluoromethyl.

[0362] In some embodiments, Z3 is selected from hydrogen, methyl, ethyl, isopropyl, cyclopropyl, and Z4 is selected from methyl, ethyl, isopropyl, cyclopropyl, and trifluoromethyl.

[0363] In some embodiments, R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, phenyl; or, R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 Selected from hydrogen, C1-C6 alkyl.

[0364] In some embodiments, R 3 、R 4 、R 5 are each independently selected from hydrogen, methyl, cyclopropyl, phenyl; or, R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 For hydrogen.

[0365] In some embodiments, R 3 is selected from hydrogen, methyl, R 4 is selected from hydrogen, methyl, cyclopropyl, phenyl, R 5 is selected from hydrogen, methyl; or, R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 For hydrogen.

[0366] In a fourth aspect of the present invention, the present invention provides a compound which is the following:

[0367]

[0368] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0369] in:

[0370] R 1 Selected from:

[0371] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0372] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0373] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0374] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0375] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0376] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0377] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0378] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N , N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0379] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0380] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0381] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0382] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2- cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0383] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0384] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-5-amino 4-aminopiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0385] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0386] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0387] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0388] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0389] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0390] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0391] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0392] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0393] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0394] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0395] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0396] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0397] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0398] (16) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0399] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0400] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0401] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0402] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0403] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0404] Z5 is selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0405] R 3 、R 4 、R 5 Each independently selected from:

[0406] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0407] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0408] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl.

[0409] In some embodiments, R 1 Selected from:

[0410] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0411] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0412] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0413] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0414] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0415] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0416] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl,

[0417] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0418] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0419] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0420] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0421] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0422] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0423] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0424] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0425] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0426] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0427] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0428] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0429] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0430] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0431] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0432] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0433] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0434] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido;

[0435] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0436] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0437] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0438] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0439] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0440] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0441] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0442] In some embodiments, R 1 Selected from:

[0443] 1) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time:

[0444] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0445] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl,

[0446] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,

[0447] (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0448] (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl,

[0449] (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0450] (7) 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0451] 2) in:

[0452] Y1, Y3, Y4, Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time.

[0453] In some embodiments, R 1 Selected from:

[0454] 1) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time:

[0455] hydrogen, fluorine, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazin-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl;

[0456] Preferably, Y1, Y2, Y4, Y5 are each independently selected from hydrogen, fluorine, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene; Y3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl;

[0457] 2) in:

[0458] Y1, Y3, Y4, Y5 are each independently selected from hydrogen, ethyl, methoxy, 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time,

[0459] Preferably, Y1, Y4, and Y5 are each independently selected from hydrogen, ethyl, and methoxy, and Y3 is 4-(N-methylpiperazine-1-)piperidinyl.

[0460] In some embodiments, Z5 is selected from C1-C6 alkyl.

[0461] In some embodiments, Z5 is selected from methyl, isopropyl.

[0462] In some embodiments, R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl.

[0463] In some embodiments, R 3 、R 4 、R 5 For hydrogen.

[0464] In the fifth aspect of the present invention, the present invention provides the following compounds of the general formula:

[0465]

[0466] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0467] in:

[0468] R 1 Selected from:

[0469] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0470] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0471] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0472] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0473] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0474] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0475] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0476] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N , N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0477] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0478] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0479] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0480] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2- cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0481] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0482] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-5-amino 4-aminopiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0483] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0484] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0485] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0486] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0487] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0488] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0489] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0490] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0491] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0492] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0493] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0494] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0495] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0496] (16) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0497] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0498] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0499] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0500] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0501] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0502] Z6 is selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl;

[0503] R 3 、R 4 、R 5 Each independently selected from:

[0504] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0505] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0506] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl.

[0507] In some embodiments, R 1 Selected from:

[0508] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0509] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0510] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0511] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0512] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0513] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0514] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl,

[0515] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0516] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0517] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0518] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0519] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0520] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0521] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0522] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0523] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0524] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0525] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0526] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0527] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0528] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0529] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0530] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0531] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0532] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido;

[0533] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0534] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0535] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0536] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0537] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0538] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0539] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0540] In some embodiments, R 1 Selected from:

[0541] 1) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time:

[0542] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0543] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl,

[0544] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,

[0545] (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0546] (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl,

[0547] (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0548] (7) 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0549] 2) in:

[0550] Y1, Y3, Y4, Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time.

[0551] In some embodiments, R 1 Selected from:

[0552] 1) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time:

[0553] hydrogen, fluorine, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazin-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl;

[0554] Preferably, Y1, Y2, Y4, Y5 are each independently selected from hydrogen, fluorine, methyl, ethyl, isopropyl, cyclopropyl, methoxy, trifluoromethoxy, cyclopropylmethylene; Y3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl;

[0555] 2) in:

[0556] Y1, Y3, Y4, Y5 are each independently selected from hydrogen, ethyl, methoxy, 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time,

[0557] Preferably, Y1, Y4, and Y5 are each independently selected from hydrogen, ethyl, and methoxy, and Y3 is 4-(N-methylpiperazine-1-)piperidinyl.

[0558] In some embodiments, Z6 is selected from C1-C6 alkyl.

[0559] In some embodiments, Z6 is selected from methyl, isopropyl.

[0560] In some embodiments, R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl.

[0561] In some embodiments, R 3 、R 4 、R 5 For hydrogen.

[0562] In the sixth aspect of the present invention, the present invention provides the following compounds of general formula:

[0563]

[0564] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0565] in:

[0566] R 1 Selected from:

[0567] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0568] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0569] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0570] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0571] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0572] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0573] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0574] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N , N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0575] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0576] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0577] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0578] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2- cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0579] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0580] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-5-amino 4-aminopiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0581] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0582] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0583] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0584] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0585] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0586] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0587] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0588] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0589] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0590] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0591] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0592] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0593] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0594] (16) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0595] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0596] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0597] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0598] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0599] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0600] R 2 Selected from:

[0601] 1) Wherein, Z1 and Z2 are each independently selected from C1-C6 alkyl, C3-C8 cycloalkyl;

[0602] 2) wherein Z3 and Z4 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, and Z4 is not hydrogen;

[0603] 3) Wherein, Z5 is selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0604] 4) wherein Z6 and Z7 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, or Z6, Z7 together with N form a substituted or unsubstituted 4-8 membered ring containing 1 to 2 heteroatoms, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0605] R 3 、R 4 、R 5 Each independently selected from:

[0606] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0607] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0608] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl;

[0609] Furthermore, the compound represented by formula (A) is not selected from

[0610] In some embodiments, R 1Selected from:

[0611] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0612] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0613] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0614] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0615] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0616] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0617] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl,

[0618] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0619] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0620] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0621] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0622] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0623] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0624] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0625] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0626] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0627] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0628] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0629] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0630] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0631] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0632] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0633] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0634] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0635] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido;

[0636] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0637] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0638] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0639] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0640] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0641] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0642] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0643] In some embodiments, R 1 Selected from:

[0644] 1) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0645] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0646] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C2-C6 alkenyl,

[0647] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,

[0648] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0649] (5) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0650] (6) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl,

[0651] (7) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl,

[0652] (8) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, 2-(N,N-dimethylamino)acetamido, cyclopropylsulfonamido, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0653] (9) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0654] (10) 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl, N-methylpiperazine-1-formyl, N-ethylpiperazine-1-formyl, N-isopropylpiperazine-1-formyl,

[0655] (11) cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0656] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl;

[0657] 2) Wherein Y1, Y3, Y4, Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time.

[0658] In some embodiments, R 1 Selected from:

[0659] 1) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time:

[0660] hydrogen, methyl, ethyl, methoxy, ethoxy, isopropoxy, trifluoromethyl, trifluoromethoxy, vinyl, N-methylpiperazinyl, morpholinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-hydroxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, N-methyl-4-piperidinyl, 2-(N,N-dimethylamino)acetamido, cyclopropylsulfonamido, N-methyl-N-(2-N,N-dimethylamino)ethylamino, 4-methyl-1-piperazinylmethylene, benzyl, cyclopropylmethylene, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, N-methylpiperazine-1-formyl, cyclopropylaminosulfonyl, N-methylpiperazine-1-sulfonyl;

[0661] 2) Wherein, Y1, Y3, Y4, and Y5 are each independently selected from hydrogen, methyl, ethyl, methoxy, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methylpiperazinyl, and 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, and Y5 are not hydrogen at the same time.

[0662] In some embodiments, Z1 and Z2 are each independently selected from C1-C6 alkyl.

[0663] In some embodiments, Z1 and Z2 are methyl.

[0664] In some embodiments, Z5 is selected from C1-C6 alkyl.

[0665] In some embodiments, Z5 is selected from methyl, isopropyl.

[0666] In some embodiments, Z3 and Z4 are each independently selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, and C3-C6 cycloalkyl.

[0667] In some embodiments, Z3 and Z4 are each independently selected from methyl, ethyl, isopropyl, cyclopropyl, and trifluoromethyl.

[0668] In some embodiments, R 3 、R 4 、R 5 Each independently selected from:

[0669] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl;

[0670] 2) substituted or unsubstituted aryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0671] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 Selected from hydrogen, C1-C6 alkyl.

[0672] In some embodiments, R 3 、R 4 、R 5 Each independently selected from:

[0673] 1) Hydrogen, methyl, ethoxy, cyclopropyl;

[0674] 2) phenyl;

[0675] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 For hydrogen.

[0676] In a seventh aspect of the present invention, the present invention provides a compound which is the following:

[0677]

[0678] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0679] in:

[0680] R 1 Selected from:

[0681] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0682] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0683] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0684] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0685] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0686] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0687] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0688] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N , N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0689] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0690] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0691] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0692] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2- cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0693] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0694] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-5-amino 4-aminopiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0695] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0696] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0697] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0698] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0699] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0700] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0701] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0702] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0703] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0704] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0705] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0706] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0707] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0708] (16) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0709] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0710] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0711] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0712] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0713] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0714] Z1 and Z2 are each independently selected from C1-C6 alkyl, C3-C8 cycloalkyl;

[0715] R 3 、R 4 、R 5 Each independently selected from:

[0716] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0717] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0718] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl;

[0719] Furthermore, the compound represented by formula (I) is not selected from

[0720] In some embodiments, R 1 Selected from:

[0721] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0722] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0723] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0724] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0725] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0726] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0727] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl,

[0728] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0729] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0730] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0731] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0732] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0733] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0734] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0735] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0736] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0737] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0738] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0739] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0740] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0741] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0742] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0743] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0744] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0745] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido;

[0746] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0747] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0748] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0749] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0750] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0751] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0752] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0753] In some embodiments, R 1 Selected from:

[0754] 1) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0755] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0756] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy,

[0757] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,

[0758] (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0759] (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl,

[0760] (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0761] 2) Wherein Y1, Y3, Y4, Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time.

[0762] In some embodiments, R 1 Selected from:

[0763] 1) in:

[0764] Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0765] hydrogen, methyl, ethyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl,

[0766] Preferably, Y1, Y2, Y4, Y5 are each independently selected from hydrogen, methyl, ethyl, methoxy, trifluoromethoxy, cyclopropylmethylene, Y3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl;

[0767] 2) in:

[0768] Y1, Y3, Y4, Y5 are each independently selected from hydrogen, ethyl, methoxy, 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time,

[0769] Preferably, Y1, Y4, and Y5 are each independently selected from hydrogen, ethyl, and methoxy, and Y3 is 4-(N-methylpiperazine-1-)piperidinyl.

[0770] In some embodiments, Z1 and Z2 are each independently selected from C1-C6 alkyl.

[0771] In some embodiments, Z1 and Z2 are methyl.

[0772] In some embodiments, R 3 、R 4 、R 5 Each independently selected from:

[0773] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl;

[0774] 2) substituted or unsubstituted aryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0775] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 Selected from hydrogen, C1-C6 alkyl.

[0776] In some embodiments, R 3 、R 4 、R 5 Each independently selected from:

[0777] 1) Hydrogen, methyl, ethoxy, cyclopropyl;

[0778] 2) phenyl;

[0779] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 For hydrogen.

[0780] In some embodiments, R 3 is hydrogen, R 4 Selected from methyl, ethoxy, cyclopropyl, phenyl, R 5 is selected from hydrogen, methyl; or, R 3 、R 4 Together with the carbon atoms to which they are attached, they form R 5 For hydrogen.

[0781] In an eighth aspect of the present invention, the present invention provides a compound which is the following:

[0782]

[0783] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0784] in:

[0785] R1 Selected from:

[0786] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0787] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0788] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0789] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0790] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0791] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0792] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0793] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N , N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0794] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0795] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0796] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0797] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2- cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0798] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0799] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-5-amino 4-aminopiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0800] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0801] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0802] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0803] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0804] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0805] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0806] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0807] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0808] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0809] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0810] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0811] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0812] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0813] (16) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0814] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0815] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0816] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0817] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0818] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0819] Z3 and Z4 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, and Z4 is not hydrogen;

[0820] R 3 、R 4 、R 5 Each independently selected from:

[0821] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0822] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0823] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl.

[0824] In some embodiments, R 1 Selected from:

[0825] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0826] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0827] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0828] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0829] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0830] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0831] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl,

[0832] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0833] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0834] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0835] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0836] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0837] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0838] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0839] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0840] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0841] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0842] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0843] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0844] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0845] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0846] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0847] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0848] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0849] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido;

[0850] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0851] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0852] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0853] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0854] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0855] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0856] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0857] In some embodiments, R 1 Selected from:

[0858] 1) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0859] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0860] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy,

[0861] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,

[0862] (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0863] (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl,

[0864] (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0865] 2) Wherein Y1, Y3, Y4, Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time.

[0866] In some embodiments, R 1 Selected from:

[0867] 1) in:

[0868] Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0869] hydrogen, methyl, ethyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl,

[0870] Preferably, Y1, Y2, Y4, Y5 are each independently selected from hydrogen, methyl, ethyl, methoxy, trifluoromethoxy, cyclopropylmethylene, Y3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl;

[0871] 2) in:

[0872] Y1, Y3, Y4, Y5 are each independently selected from hydrogen, ethyl, methoxy, 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, Y5 are not hydrogen at the same time,

[0873] Preferably, Y1, Y4, and Y5 are each independently selected from hydrogen, ethyl, and methoxy, and Y3 is 4-(N-methylpiperazine-1-)piperidinyl.

[0874] In some embodiments, Z3 and Z4 are each independently selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, and C3-C6 cycloalkyl.

[0875] In some embodiments, Z3 and Z4 are each independently selected from methyl, ethyl, isopropyl, cyclopropyl, and trifluoromethyl.

[0876] In some embodiments, Z3 is selected from methyl, ethyl, isopropyl, cyclopropyl, and Z4 is selected from methyl, ethyl, isopropyl, cyclopropyl, and trifluoromethyl.

[0877] In some embodiments, R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl.

[0878] In some embodiments, R 3 、R 4 、R 5 For hydrogen.

[0879] In the ninth aspect of the present invention, the present invention provides a compound which is the following:

[0880]

[0881] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof,

[0882] in:

[0883] R 1 Selected from:

[0884] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0885] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl- 4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N-cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-acetyl-4-piperidinyl, N-propionyl-4-piperidinyl, N-isopropionyl-4-piperidinyl, N-cyclopropylcarbonyl-4-piperidinyl, N-methylsulfonyl-4-piperidinyl, N-ethylsulfonyl-4-piperidinyl, N- Propylsulfonyl-4-piperidinyl, N-isopropylsulfonyl-4-piperidinyl, N-cyclopropylsulfonyl-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylamino 4-N,N-diisopropylaminocyclohexyl, 4-acetylaminocyclohexyl, 4-propionylaminocyclohexyl, 4-isopropylformylaminocyclohexyl, 4-methylsulfonylaminocyclohexyl, 4-ethylsulfonylaminocyclohexyl, 4-propylsulfonylaminocyclohexyl, 4-isopropylsulfonylaminocyclohexyl, 4-cyclopropylsulfonylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0886] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0887] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0888] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0889] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0890] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenantholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenantholinylpropoxy, 3-piperidinylpropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, heterodihalogen-substituted phenylmethoxy,

[0891] (4) Piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N , N-diethylaminopropyl)piperazinyl, N-(N-methyl-4-piperidinyl)piperazinyl, N-(N-ethyl-4-piperidinyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylformylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0892] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0893] (6) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0894] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0895] (8) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-acetylpiperazine-1-)piperidinyl, 4-(N-tert-butyloxycarbonylpiperazine-1-)piperidinyl, 4-(N-methylsulfonylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2- cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0896] (9) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-acetyl-4-piperidinyl, N-tert-butoxycarbonyl-4-piperidinyl, N-methanesulfonyl-4-piperidinyl, N-(2-hydroxyethyl)-4-piperidinyl, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl, N-(2-N,N-diethylaminoethyl)-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, N-(3-hydroxypropyl)-4-piperidinyl, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl, N-(3-N,N-diethylaminopropyl)-4-piperidinyl, N-(3-cyanopropyl)-4-piperidinyl, N-cyanomethylene-4-piperidinyl,

[0897] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(N-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(N-methylpiperazinyl)propylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-5-amino 4-aminopiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0898] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinemethylene, 4-ethyl-1-piperazinemethylene, 4-propyl-1-piperazinemethylene, 4-isopropyl-1-piperazinemethylene, 4-(2-hydroxyethyl)-1-piperazinemethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinemethylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene,

[0899] (12) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0900] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0901] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0902] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0903] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0904] (13) hydroxyformyl, methoxyformyl, ethoxyformyl, propoxyformyl, isopropoxyformyl, n-butoxyformyl, isobutoxyformyl, tert-butoxyformyl,

[0905] (14) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0906] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0907] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0908] piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-sulfonyl,

[0909] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-sulfonyl,

[0910] (15) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, cyclopropylaminocarboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, piperidinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N,N-dimethylpiperidinyl-1-carboxamido, 4-N,N-diethylpiperidinyl-1-carboxamido, tetrahydropyrrolyl -1-formylamino, 3-N,N-dimethyltetrahydropyrrolyl-1-formylamino, 3-N,N-diethyltetrahydropyrrolyl-1-formylamino, N-methylpiperazinyl-1-formylamino, N-ethylpiperazinyl-1-formylamino, N-acetylpiperazinyl-1-formylamino, N-tert-butoxycarbonylpiperazinyl-1-formylamino, N-(2-hydroxyethyl)piperazinyl-1-formylamino, N-(2-cyanoethyl)piperazinyl-1-formylamino )piperazinyl-1-formylamino, N-(2-N,N-dimethylaminoethyl)piperazinyl-1-formylamino, N-(2-N,N-diethylaminoethyl)piperazinyl-1-formylamino, N-(3-hydroxypropyl)piperazinyl-1-formylamino, N-(3-N,N-dimethylpropyl)piperazinyl-1-formylamino, N-(3-N,N-diethylpropyl)piperazinyl-1-formylamino, morpholinyl- 1-formylamino, 3,5-dimethylmorpholinyl-1-formylamino, 4-(tetrahydropyrrolyl)piperidinyl-1-formylamino, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formylamino, 4-(N-acetyl-1-piperazinyl)piperidinyl-1-formylamino, N-(N-methyl-4-piperidinyl)piperazinyl-1-formylamino,

[0911] (16) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing oxygen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0912] (17) Y3 and Y4 may form a substituted or unsubstituted five- to seven-membered ring containing nitrogen; the substituents may be selected from the same substituents as those mentioned above for Y1,

[0913] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0914] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0915] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0916] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0917] Z5 is selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0918] R 3 、R 4 、R 5 Each independently selected from:

[0919] 1) hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkyl, C1-C6 oxygen-containing alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, C3-C6 oxygen-containing cycloalkyl;

[0920] 2) substituted or unsubstituted aryl or heteroaryl, wherein the substituent is selected from halogen, C1-C6 alkyl, C3-C8 cycloalkyl;

[0921] 3) R 3 、R 4 Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted 5-7 membered ring, wherein the substituents are selected from halogen, C1-C6 alkyl, R 5 Selected from hydrogen, C1-C6 alkyl.

[0922] In some embodiments, R 1 Selected from:

[0923] 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0924] 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0925] 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0926] 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time:

[0927] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0928] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl,

[0929] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl,

[0930] (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0931] (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0932] (6) imidazolyl, 4-methyl-1-imidazolyl,

[0933] (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl,

[0934] (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl,

[0935] (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0936] (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene,

[0937] (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl,

[0938] Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl,

[0939] Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl,

[0940] Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl,

[0941] N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl,

[0942] (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0943] Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl,

[0944] Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl,

[0945] Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl,

[0946] N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl,

[0947] (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido;

[0948] 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time;

[0949] 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time;

[0950] 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time;

[0951] 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time;

[0952] 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1;

[0953] 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1;

[0954] 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1.

[0955] In some embodiments, R 1 for wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time:

[0956] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0957] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy,

[0958] (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl,

[0959] (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl,

[0960] (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl.

[0961] In some embodiments, R 1 for wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time:

[0962] Hydrogen, ethyl, methoxy, trifluoromethoxy, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl,

[0963] Preferably, Y1, Y2, Y4, Y5 are each independently selected from hydrogen, ethyl, methoxy, trifluoromethoxy, and Y3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, and 4-(N-methylpiperazine-1-)piperidinyl.

[0964] In some embodiments, Z5 is selected from C1-C6 alkyl.

[0965] In some embodiments, Z5 is selected from methyl, isopropyl.

[0966] In some embodiments, R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl.

[0967] In some embodiments, R 3 、R 4 、R 5 For hydrogen.

[0968] Unless otherwise specified, the above groups and substituents have the common meanings in the field of medicinal chemistry.

[0969] Throughout this specification, substituents of the compounds disclosed herein are disclosed by group class or range. It is specifically noted that the present invention includes each independent subcombination of the individual members of these group classes and ranges. For example, the term "C1-C6 alkyl" specifically refers to the independently disclosed methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl groups.

[0970] The term "C1-C6 alkyl" refers to any straight chain or branched chain group containing 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, tert-pentyl, n-hexyl, etc.

[0971] The term "C1-C3 alkyl" refers to any straight chain or branched chain group containing 1 to 3 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, and the like.

[0972] The term "oxyalkyl" refers to a group in which an alkyl skeleton is substituted by one or more alkoxy groups, for example, methoxyethyl, methoxyethoxymethyl, etc.

[0973] For example, a C1-C6 oxygen-containing alkyl group refers to a group in which a C1-C6 alkyl backbone is substituted by one or more C1-C6 alkoxy groups, such as methoxyethyl, methoxyethoxymethyl, etc. Similarly, a C1-C3 oxygen-containing alkyl group refers to a group in which a C1-C3 alkyl backbone is substituted by one or more C1-C6 alkoxy groups.

[0974] The term "C2-C6 alkenyl" refers to any straight-chain or branched group containing 2 to 6 carbon atoms and at least one carbon-carbon double bond, such as ethenyl, 1-propenyl, 2-propenyl, and the like.

[0975] The term "C3-C8 cycloalkyl" refers to a hydrocarbon having a 3-8 membered monocyclic ring system with a saturated ring. The C3-C8 cycloalkyl group may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or the like.

[0976] The term "C3-C6 cycloalkyl" refers to a hydrocarbon having a 3-6 membered monocyclic ring system with a saturated ring. The C3-C6 cycloalkyl group may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or the like.

[0977] The term "cyano" refers to a -CN residue.

[0978] The term "nitro" refers to a -NO2 group.

[0979] The term "heteroatom" refers to N, O or S.

[0980] The terms "alkoxy", "cyclyloxy" and their derivatives refer to any of the above-mentioned alkyl groups (e.g., C1-C6 alkyl, C1-C3 alkyl, etc.), cycloalkyl groups (e.g., C3-C6 cycloalkyl), which are connected to the rest of the molecule through an oxygen atom (-O-).

[0981] The term "heteroaryl" refers to an aromatic heterocycle, typically a 5-, 6-, 7-, or 8-membered heterocycle having 1 to 3 heteroatoms selected from N, O, or S; the heteroaryl ring may optionally be further fused or linked to aromatic and non-aromatic carbocyclic and heterocyclic rings. Non-limiting examples of such heteroaryl groups are, for example, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, imidazolyl, thiazolyl, isothiazolyl, thioxazolyl, pyrrolyl, phenyl-pyrrolyl, furanyl, phenyl-furanyl, oxazolyl, isoxazolyl, pyrazolyl, thienyl, benzofuranyl, benzothienyl, benzo-1,3-dioxolane (benzodioxole), isoindolinyl, benzimidazolyl, indazolyl, quinolyl, isoquinolyl, 1,2,3-triazolyl, 1-phenyl-1,2,3-triazolyl, 2,3-dihydroindolinyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, benzopyranyl, 2,3-dihydrobenzoxazinyl, 2,3-dihydroquinoxalinyl, and the like.

[0982] The term "heterocyclyl" (also referred to as "heterocycloalkyl") refers to a 3-, 4-, 5-, 6-, and 7-membered saturated or partially unsaturated carbocyclic ring in which one or more carbon atoms are replaced by heteroatoms such as nitrogen, oxygen, and sulfur. Non-limiting examples of heterocyclyl groups are, for example, pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, thiazoline, thiazolidine, dihydrofuran, tetrahydrofuran, 1,3-dioxolane, piperidine, piperazine, morpholine, morpholinyl, tetrahydropyrrolyl, thiomorpholinyl, and the like.

[0983] For example, "6-membered heterocyclyl" refers to a 6-membered saturated or partially unsaturated carbocyclic ring in which one or more carbon atoms are replaced by heteroatoms such as nitrogen, oxygen, and sulfur. Non-limiting examples of 6-membered heterocyclyls are, for example, pyran, piperidine, piperazine, morpholine, morpholinyl, thiomorpholinyl, etc.

[0984] "5-membered heterocyclyl" refers to a 5-membered saturated or partially unsaturated carbocyclic ring in which one or more carbon atoms are replaced by heteroatoms such as nitrogen, oxygen, and sulfur. Non-limiting examples of 5-membered heterocyclyls are, for example, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, thiazoline, thiazolidine, 1,3-dioxolane, and the like.

[0985] The term "optionally substituted heterocyclic group" means that the above-mentioned "heterocyclic group" is substituted by one or more "C1-C6 alkyl groups", "C1-C3 alkyl groups", "C3-C6 cycloalkyl groups" and the like.

[0986] The "fluorinated alkyl group" refers to a group in which the alkyl backbone is substituted by one or more fluorinated groups, for example, monofluoromethyl, difluoroethyl, trifluoromethyl, etc.

[0987] The term "C1-C6 fluorinated alkyl group" refers to a group in which a C1-C6 alkyl skeleton is substituted by one or more fluorinated groups, for example, monofluoromethyl, difluoroethyl, trifluoromethyl, and the like.

[0988] Similarly, the term "C1-C3 fluorinated alkyl group" refers to a group in which the C1-C3 alkyl skeleton is substituted by one or more fluorinated groups, for example, monofluoromethyl, difluoroethyl, trifluoromethyl, etc.

[0989] The term "C1-C6 heteroatom-containing alkyl" refers to a group in which one or more carbon atoms in the C1-C6 alkyl skeleton are replaced by one or more heteroatoms such as nitrogen, oxygen and sulfur, for example, wait.

[0990] The term "C3-C8 heteroatom-containing cycloalkyl" refers to a group in which one or more carbon atoms in the C3-C8 cycloalkyl skeleton are replaced by one or more heteroatoms such as nitrogen, oxygen and sulfur, such as pyrrolidine, imidazolidine, pyrazolidine, thiazolidine, piperidine, piperazine, morpholine, morpholinyl, thiomorpholinyl and the like.

[0991] The term "C1-C6 acyl" refers to -C(=O)-H and -C(=O)-C1-C5 alkyl, such as formyl, acetyl, propionyl, butyryl and the like.

[0992] The term "sulfonyl" refers to -S(=O)2-.

[0993] The term "C1-C6 alkylsulfonyl" refers to -S(=O)2-C1-C6 alkyl, such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl and the like.

[0994] From all of the above descriptions, it will be apparent to those skilled in the art that any group whose name is a composite name, such as "fluorine-containing oxyalkyl," should refer to a conventional moiety derived therefrom, such as a moiety constructed from an oxyalkyl group substituted with a fluorine group, wherein the alkyl group is as defined above. Similarly, there is also a "fluorine-containing alkoxy group." For another example, "arylamino" should refer to a conventional moiety derived therefrom, such as a moiety constructed from an amino group substituted with an aryl group, wherein the aryl group is as defined above. Similarly, the meaning of "heteroarylamino" should be understood. Similarly, the meaning of "hydroxysulfonyl," "aminosulfonyl," and the like should be understood.

[0995] Likewise, any of the terms such as alkylamino, dialkylamino, alkoxycarbonyl, alkoxycarbonylamino, heterocyclylcarbonyl, heterocyclylcarbonylamino, cycloalkyloxycarbonyl, alkoxyformyl and the like composite groups, wherein the alkyl, alkoxy and the like portions are as defined above.

[0996] The term "R 3 、R 4 、R5 Each independently selected from " represents R 3 、R 4 and R 5 The groups represented by R can be the same or different and are not restricted to each other. 3 、R 4 、R 5 are independently selected from hydrogen or methyl, which means that R 3 is selected from hydrogen or methyl, R 4 is selected from hydrogen or methyl, R 5 is selected from hydrogen or methyl.

[0997] According to the present invention and unless otherwise provided, any of the above groups may be optionally substituted at any free position thereof by one or more groups, for example by 1 to 6 groups, which are independently selected from: halogen atoms, nitro, oxo (=O), cyano, C1-C6 alkyl, polyfluorinated alkyl, polyfluorinated alkoxy, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkylamino, hydroxyheterocyclyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclyl, heterocyclyl-alkyl, C3-C7 cycloalkyl, cycloalkyl-alkyl, alkyl-aryl, alkyl- heteroaryl, alkyl-heterocyclyl, alkyl-cycloalkyl, alkyl-aryl-alkyl, alkyl-heteroaryl-alkyl, alkyl-heterocyclyl-alkyl, alkyl-cycloalkyl-alkyl, alkyl-heterocyclyl-heterocyclyl, heterocyclyl-heterocyclyl, heterocyclyl-alkyl-heterocyclyl, heterocyclyl-alkylamino, alkyl-heterocyclyl-alkyl-amino, hydroxy, alkoxy, aryloxy, heterocyclyloxy, alkyl-heterocyclyloxy, methylenedioxy, alkylcarbonyloxy, arylcarbonyloxy, cycloalkenyloxy, heterocyclylcarbonyloxy, alkyleneaminooxy, carboxyl, alkoxycarbonyl yl, aryloxycarbonyl, cycloalkyloxycarbonyl, heterocyclyloxycarbonyl, amino, urea, alkylamino, amino-alkylamino, dialkylamino, dialkylamino-heterocyclyl, dialkylamino-alkylamino, arylamino, arylalkylamino, diarylamino, heterocyclylamino, alkyl-heterocyclylamino, alkyl-heterocyclylcarbonyl, formylamino, alkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, alkyl-heterocyclylcarbonylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl The invention also includes but is not limited to: alkyl, alkyloxy ...

[0998] Furthermore, each of the above-mentioned substituents may be further substituted with one or more of the above-mentioned groups, if appropriate.

[0999] The term "oxygen-containing substituted or unsubstituted five- to seven-membered ring" or "nitrogen-containing substituted or unsubstituted five- to seven-membered ring" refers to a 5-, 6-, or 7-membered saturated or partially unsaturated carbon ring in which one or more carbon atoms are replaced by oxygen or nitrogen. Non-limiting examples include pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, dihydrofuran, tetrahydrofuran, 1,3-dioxolane, piperidine, piperazine, morpholine, tetrahydropyrrolyl, hexamethyleneimine, and the like.

[1000] The term "substituted or unsubstituted five- to seven-membered ring" refers to a 5-, 6-, or 7-membered saturated or partially unsaturated carbon ring. Non-limiting examples include, for example, cyclopentane, cyclohexane, cyclopentene, cyclopentadiene, cyclohexene, cyclohexadiene (cyclohexa-1,3-diene, cyclohex-1,4-diene), and the like.

[1001] The term "substituted or unsubstituted 4- to 8-membered ring containing 1 to 2 heteroatoms" refers to a 4-, 5-, 6-, 7-, or 8-membered saturated or partially unsaturated carbon ring in which one or two carbon atoms are replaced by heteroatoms such as nitrogen, oxygen, and sulfur. Non-limiting examples include pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, dihydrofuran, tetrahydrofuran, 1,3-dioxolane, piperidine, piperazine, morpholine, tetrahydropyrrolyl, hexamethyleneimine, and the like.

[1002] As used herein, unless otherwise indicated, the term "prodrug" refers to a derivative that can be hydrolyzed, oxidized, or otherwise reacted under biological conditions (in vitro or in vivo) to provide a compound of the present invention. Prodrugs become active compounds only through this reaction under biological conditions, or they are inactive in their unreactive form. Prodrugs can generally be prepared using known methods, such as those described in Burger's Medicinal Chemistry and Drug Discovery (1995) 172-178, 949-982 (Manfred E. Wolff, 5th edition).

[1003] As used herein, the term "pharmaceutically acceptable salt of a compound of Formula (A), (I), (II), (III), (IV), (A'), (I'), (II') or (III')" is exemplified by organic acid addition salts formed with organic acids that form pharmaceutically acceptable anions, including but not limited to formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, α-glycerophosphate, alkylsulfonate or arylsulfonate; preferably, the alkylsulfonate is methylsulfonate or ethylsulfonate; the arylsulfonate is benzenesulfonate or p-toluenesulfonate. Suitable inorganic salts may also be formed, including but not limited to hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate and carbonate, sulfate or phosphate, etc.

[1004] Pharmaceutically acceptable salts can be obtained using standard procedures well known in the art, for example, by reacting a sufficient amount of a basic compound with a suitable acid affording a pharmaceutically acceptable anion.

[1005] As used herein, the term "treat" generally refers to obtaining a desired pharmacological and / or physiological effect. The effect may be prophylactic, in terms of completely or partially preventing a disease or its symptoms; and / or therapeutic, in terms of partially or completely stabilizing or curing a disease and / or causing side effects due to the disease. As used herein, "treat" encompasses any treatment of a disease in a patient, including: (a) preventing the onset of a disease or symptom in a patient who is susceptible to the disease or symptom but has not yet been diagnosed with the disease; (b) suppressing the symptoms of a disease, i.e., arresting its development; or (c) relieving the symptoms of a disease, i.e., causing regression of the disease or symptom.

[1006] According to a specific technical solution of the present invention, the compound, its stereoisomer, its prodrug, or its pharmaceutically acceptable salt or pharmaceutically acceptable solvate, wherein the compound is one of the compounds described in the following examples.

[1007] On the other hand, the present invention provides a pharmaceutical composition comprising the compound described in any of the above technical solutions, its stereoisomers, its prodrugs, or its pharmaceutically acceptable salts or pharmaceutically acceptable solvates, and optionally a pharmaceutically acceptable carrier, diluent or excipient.

[1008] In some embodiments, the pharmaceutical composition further comprises an EGFR monoclonal antibody.

[1009] In some embodiments, the EGFR monoclonal antibody is cetuximab or a biosimilar thereof.

[1010] The term "biosimilar" refers to an antibody product that has the same sequence as cetuximab and has the same physicochemical properties, biological activity, clinical safety and efficacy as cetuximab.

[1011] Methods for preparing various pharmaceutical compositions containing a certain amount of active ingredient are known or will be apparent to those skilled in the art based on the disclosure of the present invention. As described in REMINGTON'S PHARMACEUTICAL SCIENCES, Martin, EW, ed., Mack Publishing Company, 19th ed. (1995), the method for preparing the pharmaceutical composition includes incorporating appropriate pharmaceutical excipients, carriers, diluents, etc.

[1012] The pharmaceutical preparations of the present invention are manufactured by known methods, including conventional mixing, dissolving or lyophilizing methods. The compounds of the present invention can be prepared into pharmaceutical compositions and administered to the patient in various ways suitable for the selected mode of administration, for example, orally or parenterally (by intravenous, intramuscular, topical or subcutaneous routes).

[1013] Therefore, the compounds of the present invention can be systemically administered, for example, orally, in combination with a pharmaceutically acceptable carrier (such as an inert diluent or an assimilable edible carrier). They can be enclosed in hard or soft shell gelatin capsules and can be compressed into tablets. For oral therapeutic administration, the active compound can be combined with one or more excipients and used in the form of swallowable tablets, buccal tablets, lozenges, capsules, elixirs, suspensions, syrups, wafers, etc. Such compositions and preparations should contain at least 0.1% active compound. The proportions of such compositions and preparations can of course vary and can account for about 1% to about 99% of the weight of a given unit dosage form. In such therapeutically useful compositions, the amount of active compound is such that an effective dosage level can be achieved.

[1014] Tablets, lozenges, pills, capsules, etc. may also contain: binders such as gum tragacanth, gum arabic, corn starch, or gelatin; excipients such as dicalcium phosphate; disintegrants such as corn starch, potato starch, alginic acid, etc.; lubricants such as magnesium stearate; and sweeteners such as sucrose, fructose, lactose, or aspartame; or flavorings such as mint, wintergreen oil, or cherry flavor. When the unit dosage form is a capsule, it may contain, in addition to the above types of materials, a liquid carrier such as a vegetable oil or polyethylene glycol. Various other materials may be present as a coating or otherwise modify the physical form of the solid unit dosage form. For example, tablets, pills, or capsules may be coated with gelatin, wax, shellac, or sugar. Syrups or elixirs may contain the active compound, sucrose or fructose as a sweetener, methylparaben or propylparaben as a preservative, a dye, and a flavoring (such as cherry flavor or orange flavor). Of course, any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. Additionally, the active compound can be incorporated into sustained-release preparations and devices.

[1015] The active compound can also be administered intravenously or intraperitoneally by infusion or injection. Aqueous solutions of the active compound or its salts can be prepared, optionally mixed with a nontoxic surfactant. Dispersions in glycerol, liquid polyethylene glycol, triacetin, and mixtures thereof, and oils can also be prepared. Under ordinary storage and use conditions, these formulations contain a preservative to prevent microbial growth.

[1016] Pharmaceutical dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersants or sterile powders containing active ingredients (optionally encapsulated in liposomes) suitable for instant preparations of sterile injectable or infusible solutions or dispersants. In all cases, the final dosage form must be sterile, liquid and stable under production and storage conditions. The liquid carrier can be a solvent or liquid dispersion medium, including, for example, water, ethanol, polyols (e.g., glycerol, propylene glycol, liquid polyethylene glycol, etc.), vegetable oils, non-toxic glycerides and suitable mixtures thereof. Suitable fluidity can be maintained, for example, by the formation of liposomes, by maintaining the required particle size in the case of dispersants, or by the use of surfactants. The effect of preventing microorganisms can be produced by various antibacterial and antifungal agents (such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, etc.). In many cases, it is preferred to include isotonic agents, such as sugars, buffers or sodium chloride. Prolonged absorption of injectable compositions can be produced by using compositions that delay absorption (e.g., aluminum monostearate and gelatin).

[1017] Sterile injectable solutions are prepared by combining the active compound in the required amount in an appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze drying techniques, which yield a powder of the active ingredient plus any additional desired ingredient present in a previously sterile-filtered solution.

[1018] Useful solid carriers include pulverized solids (such as talc, clay, microcrystalline cellulose, silicon dioxide, aluminum oxide, etc.). Useful liquid carriers include water, ethanol or ethylene glycol or water-ethanol / ethylene glycol mixtures, in which the compounds of the present invention can be dissolved or dispersed in an effective amount, optionally with the aid of non-toxic surfactants. Adjuvants (such as flavors) and additional antimicrobial agents can be added to optimize the properties for a given use.

[1019] Thickeners (such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified celluloses or modified inorganic materials) can also be used with liquid carriers to form spreadable pastes, gels, ointments, soaps, etc., for application directly to the user's skin.

[1020] The therapeutically required amount of the compound or its active salt or derivative will depend not only on the particular salt selected but also on the mode of administration, the nature of the disease to be treated and the age and condition of the patient and will ultimately be determined by the attending physician or clinician.

[1021] The above-mentioned formulations can be presented in unit dosage form, which is a physically discrete unit containing a unit dose suitable for administration to humans and other mammals. The unit dosage form can be a capsule or tablet, or a plurality of capsules or tablets. Depending on the specific treatment involved, the amount of the active ingredient in a unit dose can be varied or adjusted from about 0.1 to about 1000 mg or more.

[1022] In addition, it also includes the application of various new drug dosage forms such as emulsion liposomes, microspheres and nanospheres, such as drugs prepared using particulate dispersion systems including polymeric micelles, nanoemulsions, submicroemulsions, microcapsules, microspheres, liposomes and lipid vesicles (niosomes) (also known as non-ionic surfactant vesicles).

[1023] On the other hand, the present invention also provides a method for preparing the compound described in any of the above technical solutions, comprising the following steps (X represents a halogen):

[1024]

[1025] Reaction conditions:

[1026] (a) Nucleophilic substitution reaction under acidic or basic conditions;

[1027] (b) palladium-catalyzed coupling reactions or nucleophilic substitution reactions under acidic conditions;

[1028] (c) coupling reaction catalyzed by palladium metal;

[1029] in:

[1030] The metal palladium catalyst is selected from palladium acetate, tetrakis(triphenylphosphine)palladium, bistriphenylphosphine palladium dichloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride, and tris(dibenzylideneacetone)dipalladium;

[1031] The alkaline conditions refer to the conditions in which any of the following substances exist: triethylamine, diisopropylethylamine, pyridine, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride;

[1032] The acidic conditions refer to conditions in which any of the following substances are present: acetic acid, trifluoroacetic acid, hydrochloric acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid;

[1033] R 1 、R 2 、R 3 、R 4 and R 5 The definition of is as described above.

[1034] On the other hand, the present invention also provides the use of a compound described in any of the above technical solutions, its stereoisomers, its prodrugs, or its pharmaceutically acceptable salts or pharmaceutically acceptable solvates, and a pharmaceutical composition containing the compound in the preparation of a medicament for the prevention and / or treatment of EGFR kinase-mediated cancers and other diseases, especially in the preparation of a medicament for the prevention and / or treatment of lung cancer (preferably non-small cell lung cancer), especially in the preparation of a medicament for the prevention and / or treatment of EGFR kinase 19Del, L858R, T790M, C797S or a combination thereof mutant lung cancer (preferably non-small cell lung cancer), most preferably in the preparation of a medicament for the prevention and / or treatment of EGFR kinase 19Del single mutation, L858R single mutation, 19Del / T790M double mutation, L858R / T790M double mutation, 19Del / T790M / C797S triple mutation or L858R / T790M / C797S triple mutation lung cancer (preferably non-small cell lung cancer).

[1035] On the other hand, the present invention also provides a method for preventing and / or treating EGFR kinase-mediated cancer and other diseases, which comprises administering to a subject in need thereof an effective amount of the above-mentioned compound or its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate or the above-mentioned pharmaceutical composition.

[1036] In some embodiments, the method is used to prevent and / or treat lung cancer (preferably non-small cell lung cancer).

[1037] In some embodiments, the method is used to prevent and / or treat lung cancer (preferably non-small cell lung cancer) harboring EGFR kinase 19Del, L858R, T790M, C797S, or a combination thereof mutations.

[1038] In some embodiments, the method is used to prevent and / or treat EGFR kinase 19Del single mutation, L858R single mutation, 19Del / T790M double mutation, L858R / T790M double mutation, 19Del / T790M / C797S triple mutation or L858R / T790M / C797S triple mutation lung cancer (preferably non-small cell lung cancer).

[1039] On the other hand, the present invention also provides the above-mentioned compound or its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate or the above-mentioned pharmaceutical composition, which is used for preventing and / or treating cancer and other diseases mediated by EGFR kinase, preferably for preventing and / or treating lung cancer (preferably non-small cell lung cancer), more preferably for preventing and / or treating EGFR kinase 19Del, L858R, T790M, C797S or a combination thereof mutant lung cancer (preferably non-small cell lung cancer), and most preferably for preventing and / or treating EGFR kinase 19Del single mutation, L858R single mutation, 19Del / T790M double mutation, L858R / T790M double mutation, 19Del / T790M / C797S triple mutation or L858R / T790M / C797S triple mutation lung cancer (preferably non-small cell lung cancer).

[1040] In the present invention, "subject" refers to a vertebrate. In certain embodiments, the vertebrate refers to a mammal. Mammals include, but are not limited to, livestock (such as cattle), pets (such as cats, dogs, and horses), primates, mice, and rats. In certain embodiments, the mammal refers to a human.

[1041] In the present invention, an "effective amount" refers to an amount that is effective at the necessary dosage and time to achieve the desired therapeutic or preventive effect. The "therapeutically effective amount" of the substance / molecule of the present invention may vary according to factors such as the disease state, age, sex and weight of the individual and the ability of the substance / molecule to elicit the desired response in the individual. A therapeutically effective amount also encompasses an amount in which the therapeutically beneficial effects of the substance / molecule outweigh any toxic or deleterious consequences. A "prophylactically effective amount" refers to an amount that is effective at the necessary dosage and time to achieve the desired preventive effect. Typically, but not necessarily, a prophylactic dose is used in subjects before the onset of disease or in the early stages of the disease, so the prophylactic effective amount will be lower than the therapeutically effective amount. In the case of cancer, a therapeutically effective amount of a drug can reduce the number of cancer cells; reduce tumor size; inhibit (i.e., slow down to a certain extent, preferably stop) cancer cell infiltration into surrounding organs; inhibit (i.e., slow down to a certain extent, preferably stop) tumor metastasis; inhibit tumor growth to a certain extent; and / or alleviate one or more symptoms associated with cancer to a certain extent.

[1042] Experimental part

[1043] With respect to the examples referred to below, compounds of the invention were synthesized using the methods described herein or other methods well known in the art.

[1044] General purification and analytical methods:

[1045] On silica gel GF254 pre-coating plate (Qingdao Ocean Chemical Plant), carry out thin layer chromatography.Under medium pressure, carry out column chromatography separation through silica gel (300-400 mesh, Huangwu Silica Gel Development Reagent Factory, Zhifu District, Yantai City) or by using ISCO CombiflashRf200 rapid purification system, carry out column chromatography separation with preloaded silica gel cartridge (ISCO or Welch).Composition is by UV light (wavelength 254nm) and by iodine vapor development.When necessary, compound is passed through preparative HPLC through Waters Symmetry C18 (19x50mm, 5 μm) post or through Waters X Terra RP 18 (30x150mm, 5 μm) column purification, use the Waters preparative HPLC 600 that is equipped with 996Waters PDA detector and Micromass mod.ZMD single quadruple mass spectrum (electrospray ionization, positive ion mode) detection. Method 1: Phase A: 0.1% TFA / MeOH 95 / 5; Phase B: MeOH / H₂O 95 / 5. Gradient: 10 to 90% B over 8 min, hold 90% B for 2 min; flow rate 20 mL / min. Method 2: Phase A: 0.05% NH₄OH / MeOH 95 / 5; Phase B: MeOH / H₂O 95 / 5. Gradient: 10 to 100% B over 8 min, hold 100% B for 2 min; flow rate 20 mL / min.

[1046] 1 H-NMR spectra were recorded on a 600 MHz Bruker Avance 600 nuclear magnetic resonance spectrometer. Chemical shifts (δ) are reported in parts per million (ppm) and coupling constants (J) are reported in Hz. The tetramethylsilane signal was used as a reference (δ = 0 ppm). The following abbreviations are used for peak splitting: s = singlet; br.s. = broad signal; d = doublet; t = triplet; m = multiplet; dd = doublet.

[1047] Electrospray ionization (ESI) mass spectra were acquired using a Finnigan LCQ ion trap.

[1048] Unless otherwise stated, all final compounds were homogeneous (purity not less than 95%) as determined by high performance liquid chromatography (HPLC). HPLC-UV-MS analysis for evaluating compound purity was performed using a combined ion trap MS instrument and an HPLC system SSP4000 (Thermo Separation Products) equipped with an autosampler LC Pal (CTC Analytics) and a UV6000LP diode array detector (UV detection 215-400 nm). Instrument control, data acquisition, and processing were performed using Xcalibur 1.2 software (Finnigan). HPLC chromatography was performed at room temperature and a flow rate of 1 mL / min using a Waters X Terra RP 18 column (4.6 x 50 mm; 3.5 μm). Mobile phase A was ammonium acetate 5 mM buffer (pH 5.5 with acetic acid): acetonitrile 90:10, mobile phase B was ammonium acetate 5 mM buffer (pH 5.5 with acetic acid): acetonitrile 10:90; gradient was 0 to 100% B in 7 minutes, then held at 100% B for 2 minutes before re-equilibration.

[1049] Reagents were purified according to Purification of Laboratory Chemicals (Perrin, DD, Armarego, WL F, and Perrins Eds, DR; Pergamon Press: Oxford, 1980). Petroleum ether (60-90°C fraction), ethyl acetate, methanol, and dichloromethane were all analytical grade. DETAILED DESCRIPTION

[1050] The embodiments of the present invention are described in detail below through specific examples, but they are not to be construed as limiting the present invention in any way.

[1051] Compounds can be divided into four main categories:

[1052]

[1053] Among them, R 1 、R 3 、R 4 、R 5 , Z1, Z2, Z3, Z4, and Z5 are as described above.

[1054] Some of the raw materials and intermediates involved in the synthesis process are described as follows:

[1055] 1. Prepared by the reaction of 5-fluoro-2-nitroanisole (cas: 448-19-1, Bidex, Shanghai) and 1-methyl-4-(4-piperidinyl)piperazine (cas: 53617-36-0, Aikon, Jiangsu) Then reduce the nitro group to obtain.

[1056] The following intermediates were obtained by similar methods:

[1057]

[1058] The raw materials involved are: 1-fluoro-5-methoxy-2-methyl-4-nitrobenzene (CAS: 314298-13-0, Bidex, Shanghai), 3,4,5-trifluoronitrobenzene (CAS: 66684-58-0, Bidex, Shanghai), 2,3,4-trifluoronitrobenzene (CAS: 771-69-7, Bidex, Shanghai), 1-methyl-4-(4-piperidinyl)piperazine (CAS: 53617-36-0, Aikon, Jiangsu).

[1059] 2. 2-Fluoro-4-hydroxyacetophenone (cas: 98619-07-9, Bidler, Shanghai) was reduced with palladium on carbon and hydrogen to obtain 3-fluoro-4-ethylphenol, which was then nitrated to obtain 3-fluoro-4-ethyl-6-nitrophenol. The 3-fluoro-4-ethyl-6-nitrophenol was further reacted with iodomethane (cas: 74-88-4, Xiya Reagent, Shandong) to obtain 3-fluoro-4-ethyl-6-nitroanisole, which was then reacted with N-methylpiperazine (cas: 109-01-3, Anaiji, Shanghai) to obtain 3-(N-methylpiperazinyl)-4-ethyl-6-nitroanisole, and the nitro group was finally reduced to obtain the product.

[1060] 3-Fluoro-4-ethyl-6-nitroanisole can be obtained by reducing the nitro group

[1061] The following intermediates were obtained by similar methods:

[1062]

[1063] The raw materials involved are: 3-N,N-dimethylaminopyrrolidine (cas: 64021-83-6, TCI, Shanghai), 4-dimethylaminopiperidine (cas: 50533-97-6, Shaoyuan, Shanghai), ethanolamine (cas: 141-43-5, Aladdin, Shanghai), N,N-dimethylethylenediamine (cas: 108-00-9, Bidex, Shanghai), N,N,N'-trimethylethylenediamine (cas: 142-25-6, Bidex, Shanghai), 2-oxa-6-azaspiro[3.3]heptane (cas: 174-78-7, Bidex, Shanghai), 2-methyl-2,6-diazaspiro[3.3]heptane (cas: 120 3567-11-6, Bidex, Shanghai), 1-methyl-4-(4-piperidinyl)piperazine (cas: 53617-36-0, Aikon, Jiangsu), tert-butyl 4-(piperidin-4-yl)piperazine-1-carboxylate (cas: 205059-24-1, Bidex, Shanghai), 1-(1-methylpiperidin-4-yl)piperazine (cas: 23995-88-2, J&K, Shanghai), 2-methyl-2,7-diazaspiro[3.5]nonane dihydrochloride (cas: 1610028-42-6, Bidex, Shanghai), 1-(1-methylazetidin-3-yl)piperazine (cas: 864350-81-2, J&K, Shanghai).

[1064] 3. Obtained by the reaction of tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate (cas: 203661-69-2, Bidex, Shanghai) with dimethylamine (cas: 124-40-3, Aladdin, Shanghai) After removing the tert-butyloxycarbonyl group, it reacts with 3-fluoro-4-ethyl-6-nitroanisole in (2) to obtain Then reduce the nitro group to obtain.

[1065] 4. 2-Methoxy-3-nitro-6-chloropyridine was obtained by reacting 2,6-dichloro-3-nitropyridine with sodium methoxide (cas: 124-41-4, Anaiji, Shanghai), and then reacted with 1-methyl-4-(4-piperidinyl)piperazine (cas: 53617-36-0, Aikang, Jiangsu) to obtain Then reduce the amino group to obtain.

[1066] Obtained from 2,6-dichloro-3-nitro-5-methylpyridine by a similar method.

[1067] 5. From (3) Reaction with liquid bromine (cas: 7726-95-6, Sinopharm Group, Shanghai) to obtain Then react with vinyl pinacol borate (cas: 75927-49-0, Bidler, Shanghai) to obtain Then reduce the nitro group and double bond to obtain.

[1068] 6. 1-Bromo-2-fluoro-4-trifluoromethoxybenzene (cas: 168971-68-4, Bidler, Shanghai) was nitrated to obtain 2-trifluoromethoxy-4-fluoro-5-bromonitrobenzene, which was then reacted with 1-methyl-4-(4-piperidinyl)piperazine (cas: 53617-36-0, Aikon, Jiangsu) to obtain Further reacted with vinyl pinacol borate (cas: 75927-49-0, Bidler, Shanghai) to obtain Then reduce the nitro group and double bond to obtain.

[1069] 7. Prepared by the reaction of 1-bromo-2-fluoro-4-methoxy-5-nitrobenzene (cas: 1352244-77-9, Bidex, Shanghai) and 1-methyl-4-(4-piperidinyl)piperazine (cas: 53617-36-0, Aikon, Jiangsu) Then coupled with isopropenylboronic acid pinacol ester (cas: 126726-62-3, Bidler, Shanghai) to obtain The following intermediates were obtained by similar methods:

[1070]

[1071] The raw materials involved are: 3-bromo-4-fluoronitrobenzene (CAS: 701-45-1, Bidler, Shanghai), cyclopropylboronic acid pinacol ester (CAS: 126689-01-8, Bidler, Shanghai), and vinylboronic acid pinacol ester (CAS: 75927-49-0, Bidler, Shanghai).

[1072] 8. 2-Fluoro-4-methoxybenzaldehyde (cas: 331-64-6) was nitrated to give 2-fluoro-4-methoxy-5-nitrobenzaldehyde, which was then reduced to give 2-fluoro-4-methoxy-5-nitrobenzyl alcohol, which was further brominated to give 2-fluoro-4-methoxy-5-nitrobenzyl bromide, which was then reacted with cyclopropylboronic acid (cas: 411235-57-9, Bidler, Shanghai) to give Then react with 1-methyl-4-(4-piperidinyl)piperazine (cas: 53617-36-0, Aikang, Jiangsu) to obtain Finally, it is obtained by reducing the nitro group.

[1073] Cyclopropylboronic acid was replaced with phenylboronic acid (cas: 98-80-6, Anaiji, Shanghai), and a similar method was used to obtain

[1074] 9. 1-Bromo-2-methyl-4-methoxy-5-nitrobenzene (cas: 89978-56-3, Jiuding Chemical, Shanghai) was oxidized to 2-bromo-4-nitro-5-methoxybenzoic acid, and then condensed with 1-methyl-4-(4-piperidinyl)piperazine (cas: 53617-36-0, Aikon, Jiangsu) to obtain Further coupled with potassium trifluoroborate (cas: 13682-77-4, Bidler, Shanghai) to obtain Then restored.

[1075] 10. Prepared by the reaction of m-bromonitrobenzene (cas: 585-79-5, Aladdin, Shanghai) with 4-pyridineboronic acid (cas: 1692-15-5, Shuya, Shanghai) Further react with iodomethane (cas: 74-88-4, Xiya reagent, Shandong) to obtain Finally, the nitro group and the pyridine ring are reduced to obtain the product.

[1076] It was obtained from 4-bromo-2-nitroanisole (cas: 33696-00-3, Bidler, Shanghai) by a similar method.

[1077] 11. 6-aminoquinoxaline (cas: 6298-37-9, Bidler, Shanghai) reacts with iodine monochloride (cas: 7790-99-0, Aladdin, Shanghai) to obtain Then it reacts with dimethylphosphine oxide (cas: 7211-39-4, Bidler, Shanghai) to obtain the product.

[1078] 12. 5-amino-6-nitroquinoxaline was obtained by reacting 6-nitroquinoxaline (CAS: 6639-87-8, Bidex, Shanghai) and hydroxylamine hydrochloride (CAS: 5470-11-1, Anaiji, Shanghai), which was then converted into 5-chloro-6-nitroquinoxaline and further reacted with methanesulfonylmethylamine (CAS: 1184-85-6, Bidex, Shanghai) to obtain Finally, the nitro group is reduced to obtain the following intermediates:

[1079]

[1080] The raw materials involved are: methylamine (cas: 74-89-5, Anage, Shanghai), ethylamine (cas: 75-04-7, Aladdin, Shanghai), isopropylamine (cas: 75-31-0, Anage, Shanghai), cyclopropylamine (cas: 765-30-0, Anage, Shanghai), trifluoromethanesulfonyl chloride (cas: 421-83-0, Aladdin, Shanghai), ethylsulfonyl chloride (cas: 594-44-5, Anage, Shanghai), isopropylsulfonyl chloride (cas: 10147-37-2, TCI, Shanghai), cyclopropylsulfonyl chloride (cas: 139631-62-2, Anage, Shanghai), methylsulfonamide (cas: 3144-09-0, Bidex, Shanghai), and isopropylsulfonamide (cas: 81363-76-0, Bidex, Shanghai).

[1081] 13. The 5-chloro-6-nitroquinoxaline in (7) was reacted with sodium methanesulfinate (cas: 20277-69-4, Bidler, Shanghai) to obtain Then react with 2,4-dimethoxybenzylamine (cas: 20781-20-8, Bidler, Shanghai) to obtain Then remove the 2,4-dimethoxybenzyl group to obtain.

[1082] 14. The 5-chloro-6-nitroquinoxaline in (7) was reacted with isopropyl mercaptan (cas: 75-33-2, Aladdin, Shanghai) to obtain Reoxidation to obtain Finally, it is obtained by reducing the nitro group.

[1083] 15. Obtained by the reaction of 6-amino-5-bromoquinoxaline (cas: 50358-63-9, Bidex, Shanghai) with di-tert-butyl dicarbonate (cas: 24424-99-5, Bidex, Shanghai) Removal of a tert-butyloxycarbonyl group converts to Reaction with benzyl mercaptan (cas: 100-53-8, Aladdin, Shanghai) to obtain Then react with 1,3-dichloro-5,5-dimethylhydantoin (cas: 118-52-5, Bidler, Shanghai) to obtain Then react with methylamine (cas: 74-89-5, Anaiji, Shanghai) to convert Finally, the tert-butyloxycarbonyl group is removed to obtain the product.

[1084] Methylamine was replaced with isopropylamine (cas: 75-31-0, Anaiji, Shanghai), and a similar method was used to obtain

[1085] 16. 2-Bromo-4-nitrophenylethanol was obtained by reacting 4-nitrophenylethanol (CAS: 100-27-6, Bidler, Shanghai) with 1,3-dibromo-5,5-dimethylhydantoin (CAS: 77-48-5, Bidler, Shanghai), and then reacted with methylsulfonyl chloride (CAS: 124-63-0, Xiya Reagent, Shandong) to obtain 2-bromo-4-nitrophenylethanol methanesulfonate, which was further reacted with methylallylamine (CAS: 627-37-2, Anaiji, Shanghai) to obtain Then it is further converted into Finally, the nitro group and the double bond are reduced to obtain.

[1086] 17. Obtained by the reaction of 2,3,4,5-tetrahydro-1H-benzo[d]azepine (cas: 4424-20-8, Bidler, Shanghai) with formaldehyde Renitrification Finally, it is obtained by reducing the nitro group.

[1087] 18. 2-Methyl-6-fluoro-3,4-dihydro-2H-isoquinolin-1-one was obtained by the reaction of 6-fluoro-3,4-dihydro-2H-isoquinolin-1-one (cas: 214045-84-8, Bidler, Shanghai) and iodomethane (cas: 74-88-4, Xiya Reagent, Shandong). The reaction was then reacted with fuming nitric acid (cas: 7697-37-2, Shanghai Test, Shanghai) to obtain 2-methyl-6-fluoro-7-nitro-3,4-dihydro-2H-isoquinolin-1-one. The carbonyl group was further reduced to obtain 2-methyl-6-fluoro-7-nitro-1,2,3,4-tetrahydroisoquinoline, and the nitro group was finally reduced to obtain the product.

[1088] It was obtained from 6-chloro-3,4-dihydro-2H-isoquinolin-1-one (cas: 22246-02-2, Bidex, Shanghai) by a similar method.

[1089] It was obtained from 6-methyl-3,4-dihydro-2H-isoquinolin-1-one (cas: 1082041-78-8, Bidex, Shanghai) by a similar method.

[1090] 2-(3-trifluoromethoxyphenyl)ethylamine was reduced with 3-(trifluoromethoxy)benzylacetonitrile (cas: 108307-56-8, Bidex, Shanghai), and then reacted with ethyl chloroformate (cas: 541-41-3, Xiya Reagent, Shandong) to obtain 2-(3-trifluoromethoxyphenyl)ethylcarbamate. 6-trifluoromethoxy-3,4-dihydro-2H-isoquinolin-1-one was further obtained by a similar method under the action of trifluoromethanesulfonic anhydride (cas: 358-23-6, Anaiji, Shanghai).

[1091] From m-trifluoromethylbenzeneacetonitrile (cas: 2338-76-3, Bidler, Shanghai) a similar method can be obtained

[1092] 2-Methyl-6-fluoro-7-nitro-3,4-dihydro-2H-isoquinolin-1-one reacts with methanol (cas: 67-56-1, Shanghai trial, Shanghai) to obtain 2-methyl-6-methoxy-7-nitro-3,4-dihydro-2H-isoquinolin-1-one, which can then be obtained by a similar method.

[1093] 19.1,2,3,4-Tetrahydro-2-methyl-7-isoquinolinamine (cas: 14097-40-6, Aikon, Jiangsu).

[1094] 20. Vinylboronic acid pinacol ester (cas: 75927-49-0, Bidler, Shanghai).

[1095] 21. Isopropenylboronic acid pinacol ester (cas: 126726-62-3, Bidex, Shanghai)

[1096] 22. (E)-2-Cyclopropylvinylboronic acid pinacol ester (cas: 849061-99-0, Bidler, Shanghai).

[1097] 23. (E)-1-ethoxyethylene-2-boronic acid pinacol ester (cas: 1201905-61-4, Bidex, Shanghai).

[1098] 24. 2-Methyl-1-propenylboronic acid pinacol ester (cas: 126689-00-7, Bidler, Shanghai).

[1099] 25.1-Cyclopentenylboronic acid pinacol ester (cas: 287944-10-9, Bidler, Shanghai).

[1100] 26. (E)-2-phenylvinylboronic acid pinacol ester (cas: 83947-56-2, Bidex, Shanghai).

[1101] 27.2,4-Dichloro-5-bromopyrimidine (cas: 36082-50-5, Bidex, Shanghai).

[1102] 28. [1,1'-Bis(diphenylphosphino)ferrocene]palladium dichloride dichloromethane complex (CAS: 95464-05-4, Bis(II), Shanghai).

[1103] 29. Sodium hydride (cas: 7646-69-7, TCI, Shanghai).

[1104] 30.3-Aminopyrazole (cas: 1820-80-0, Bidex, Shanghai).

[1105] 31.1-Ethyl-3-aminopyrazole (cas: 55361-49-4, Bidler, Shanghai).

[1106] 32. 1-Isopropyl-3-aminopyrazole (cas: 857267-04-0, Bidler, Shanghai).

[1107] 33.1,5-Dimethyl-3-aminopyrazole (CAS: 35100-92-6, Bidex, Shanghai).

[1108] 34. It is obtained by reacting 3-oxopentanonitrile (cas: 33279-01-5, Bidex, Shanghai) with methylhydrazine (cas: 60-34-4, West Asia, Shandong).

[1109] 35.4-Aminopyrazole (cas: 28466-26-4, Bidex, Shanghai).

[1110] 36. 1-Methyl-4-aminopyrazole (cas: 69843-13-6, Bidler, Shanghai).

[1111] 37.1-Ethyl-4-aminopyrazole (cas: 876343-24-7, Bidex, Shanghai)

[1112] 38.1-Isopropyl-4-aminopyrazole (cas: 97421-16-4, Bidex, Shanghai)

[1113] 39. 1-Ethyl-3-methyl-4-aminopyrazole (cas: 947763-34-0, Bidler, Shanghai).

[1114] The embodiments of the present invention are described in detail below through specific examples, but they are not to be construed as limiting the present invention in any way.

[1115] Synthesis of compound I-1:

[1116]

[1117] Step 1: Dissolve compound 1 (442 mg, 2 mmol) in DMF (5 mL). Add NaH (60% content, dispersed in liquid paraffin, 160 mg, 4 mmol) in portions at 0°C. After 5 minutes, add 2,4-dichloro-5-bromopyrimidine (479 mg, 2.1 mmol). Allow to autothermally react for 1 hour. TLC and LCMS confirm the reaction is complete. Add 100 mL of water, and a solid precipitates. Filter and drain to obtain compound 2 (339 mg), which is used directly in the next step.

[1118] Step 2: Compound 2 (41.3 mg, 0.1 mmol), compound 3 (33.2 mg, 0.1 mmol), and methanesulfonic acid (19 μL, 0.3 mmol) were heated in t-BuOH (2 mL) at 100°C for 4 h. The reaction was complete as determined by TLC and LCMS. After cooling, the reaction mixture was concentrated and purified on a silica gel column (eluted with dichloromethane / methanol) to afford compound 4 (50 mg).

[1119] Step 3: Compound 4 (0.042 mmol, 30 mg), vinylboronic acid pinacol ester (0.126 mmol, 21 μL), PdCl2(dppf)·CH2Cl2 (0.0042 mmol, 3.4 mg), and Na2CO3 (0.126 mmol, 13.4 mg) were dispersed in 1,4-dioxane (1 mL) and water (0.5 mL). After nitrogen displacement, the reaction system was heated at 100°C for 4 h. TLC and LC-MS confirmed the completion of the reaction. The reaction system was diluted with 50 mL of water and extracted with DCM. The organic phase was concentrated and purified on a silica gel column (eluted with dichloromethane / methanol). It was then purified by preparative HPLC (using water and methanol containing 0.35% trifluoroacetic acid as the mobile phase) to afford compound I-1 (15.3 mg).

[1120] Other compounds were obtained by similar methods.

[1121] The following table lists the specific compounds and their structural identification data:

[1122]

[1123]

[1124]

[1125]

[1126]

[1127]

[1128]

[1129]

[1130]

[1131]

[1132]

[1133]

[1134]

[1135]

[1136]

[1137]

[1138]

[1139]

[1140]

[1141]

[1142]

[1143]

[1144]

[1145]

[1146]

[1147]

[1148]

[1149]

[1150] Biological activity test.

[1151] Growth inhibitory activity of compounds against kinase-stable cell lines.

[1152] The activity of the compounds against various mutants of the EGFR kinase was evaluated by inhibiting the growth of the kinase-stable BaF3 cell line. The specific test method is as follows:

[1153] 1) Culture medium: Dulbecco's modified eagle medium (DMEM) or RPMI1640 (containing 10% fetal bovine serum, 100 μg / mL ampicillin, and 100 μg / mL streptomycin).

[1154] 2) Reagents: MTS reaction solution (containing 2 mg / mL MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt); 100 μg / mL PES (phenazine methosulfate).

[1155] 3) Compound testing: Cells were plated in a 96-well culture plate with a cell volume of 90 μL. 10 μL of each compound was then added at a gradient concentration, with the highest concentration being 10 μM. The mixture was diluted in 1 / 3 increments for a total of 8 concentration points. The system contained 0.1% DMSO (dimethyl sulfoxide). The cell plate containing the mixed compound was placed in a cell culture incubator (37°C; 5% CO2) and cultured for 48 hours. 20 μL of MTS reaction solution was then added, mixed, and placed in a cell culture incubator (37°C; 5% CO2) for 1-4 hours. The OD value at a wavelength of 490 nm was measured using a microplate reader (VARIOSKAN FLASH, Thermo). Two parallel experiments were performed for each group of experiments. A final concentration of 0.1% DMSO was used as a negative control, and a culture medium without cells or compound was used as a blank control. The cell growth inhibition rate was calculated using the following formula:

[1156] Cell inhibition rate % = 1-(OD experimental group-OD blank group) / (OD negative group-OD blank group)*100%

[1157] 4)IC 50 Calculation of inhibitory concentrations: The half-inhibitory concentrations of the compounds on cells were calculated based on the measured cell inhibition rates using GradPad Prism 5 software.

[1158] The following table lists the growth inhibitory activities of the compounds against kinase stably transfected cell lines:

[1159]

[1160]

[1161]

[1162]

[1163] Note: ++++ represents IC 50 ≤50nM; +++ represents 50nM <IC 50 ≤500nM; ++ represents 500nM <IC 50 ≤2500nM.

[1164] The remaining compounds also had excellent inhibitory activity against the growth of the above kinase stably transfected cell lines.

Claims

1. The following compounds of the general formula: or a pharmaceutically acceptable salt of said compound, in: The compound has a structure represented by formula (II) or formula (III), In formula (II): R 1 Selected from: 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time: (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (6) imidazolyl, 4-methyl-1-imidazolyl, (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl, (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl, (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene, (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl, Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl, N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl, (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl, Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido, 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time; 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time; 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time; 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time; 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1; 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1; 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1; Z3 and Z4 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, and Z4 is not hydrogen; R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl; In formula (III): R 1 Selected from: 1) Hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl; 2) 2-N,N-dimethylaminoethyl, 3-N,N-dimethylaminopropyl, 2-N,N-diethylaminoethyl, 3-N,N-diethylaminopropyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinylethyl, 2-thiomorpholinylethyl, 2-piperidinylethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-propyl-4-piperidinyl, N-isopropyl-4-piperidinyl, N-hydroxyethyl-4-piperidinyl, N -cyanomethyl-4-piperidinyl, N-(2-cyanoethyl)-4-piperidinyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-isopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl; 3) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-cyclopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-cyclopropyl-3-pyrazolyl, 1-hydroxyethyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-cyclopropyl-4-pyrazolyl, 1-hydroxyethyl-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl; 4) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time: (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorinated alkyl, C1-C6 fluorinated alkoxy, C3-C6 cycloalkyl, C2-C6 alkenyl, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, N-cyclopropylpiperazinyl, N-(2-hydroxyethyl)piperazinyl, N-(2-N,N-dimethylaminoethyl)piperazinyl, N-(2-N,N-diethylaminoethyl)piperazinyl, N-(2-cyanoethyl)piperazinyl, N-cyanomethylpiperazinyl, N-(3-hydroxypropyl)piperazinyl, N-(3-N,N-dimethylaminopropyl)piperazinyl, N-(3-N,N-diethylaminopropyl)piperazinyl, (4) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl, (5) tetrahydropyrrolyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (6) imidazolyl, 4-methyl-1-imidazolyl, (7) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazine-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperidinyl)piperidinyl piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazine-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazine-1-)piperidinyl, 4-(tetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrol-1-)piperidinyl, 4-(3-N,N-diethylaminotetrahydropyrrol-1-)piperidinyl, (8) Piperidin-4-yl, N-methyl-4-piperidin-yl, N-ethyl-4-piperidin-yl, N-isopropyl-4-piperidin-yl, N-(2-hydroxyethyl)-4-piperidin-yl, N-(2-N,N-dimethylaminoethyl)-4-piperidin-yl, N-(2-N,N-diethylaminoethyl)-4-piperidin-yl, N-(2-cyanoethyl)-4-piperidin-yl, N-(3-hydroxypropyl)-4-piperidin-yl, N-(3-N,N-dimethylaminopropyl)-4-piperidin-yl, N-(3-N,N-diethylaminopropyl)-4-piperidin-yl, N-(3-cyanopropyl)-4-piperidin-yl, N-cyanomethylene-4-piperidin-yl, (9) amino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, N-methylpiperidin-4-amino, N-ethylpiperidin-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin -4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethylsulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-tetrahydropyrrolyl)amino, N-(N-methyl-3-tetrahydropyrrolyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino, (10) 4-methyl-1-piperazine methylene, 4-ethyl-1-piperazine methylene, 4-propyl-1-piperazine methylene, 4-isopropyl-1-piperazine methylene, 4-(2-hydroxyethyl)-1-piperazine methylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazine methylene, piperidine-1-methylene, 4-(N,N-dimethylamino)-1-piperidinyl methylene, 4-hydroxypiperidin-1-methylene, tetrahydropyrrol-1-methylene, 3-(N,N-dimethylamino)-1-tetrahydropyrrol-1-methylene, benzyl, cyclopropyl methylene, cyclobutyl methylene, cyclopentyl methylene, cyclohexyl methylene, (11) Carbamoyl, methylcarbamoyl, N,N-dimethylcarbamoyl, ethylcarbamoyl, aminoacetyl, methylaminoacetyl, 2-(N,N-dimethylamino)acetyl, ethylaminoacetyl, Tetrahydropyrrol-1-carbonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-carbonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-carbonyl, Morpholinyl-4-formyl, thiomorpholinyl-4-formyl, 2,6-dimethylmorpholinyl-4-formyl, Piperidinyl-1-formyl, 4-hydroxypiperidinyl-1-formyl, 4-(N,N-dimethylamino)piperidinyl-1-formyl, 4-(N,N-diethylamino)piperidinyl-1-formyl, 4-(N-methyl-1-piperazinyl)piperidinyl-1-formyl, 4-(N-ethyl-1-piperazinyl)piperidinyl-1-formyl, N-methylpiperazine-1-carbonyl, N-ethylpiperazine-1-carbonyl, N-isopropylpiperazine-1-carbonyl, N-(2-hydroxyethyl)piperazine-1-carbonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-carbonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-carbonyl, 4-(N-methyl-4-piperidinyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidinyl)piperazine-1-carbonyl, (12) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl, Tetrahydropyrrol-1-sulfonyl, 3-(N,N-dimethylamino)tetrahydropyrrol-1-sulfonyl, 3-(N,N-diethylamino)tetrahydropyrrol-1-sulfonyl, Morpholinyl-4-sulfonyl, thiomorpholinyl-4-sulfonyl, 2,6-dimethylmorpholinyl-4-sulfonyl, Piperidinyl-1-sulfonyl, 4-hydroxypiperidinyl-1-sulfonyl, 4-(N,N-dimethylamino)piperidinyl-1-sulfonyl, 4-(N,N-diethylamino)piperidinyl-1-sulfonyl, N-methylpiperazine-1-sulfonyl, N-ethylpiperazine-1-sulfonyl, N-isopropylpiperazine-1-sulfonyl, N-(2-hydroxyethyl)piperazine-1-sulfonyl, N-(2-N,N-dimethylaminoethyl)piperazine-1-sulfonyl, N-(2-N,N-diethylaminoethyl)piperazine-1-sulfonyl, (13) aminocarboxamido, methylaminocarboxamido, ethylaminocarboxamido, propylaminocarboxamido, isopropylaminocarboxamido; 5) wherein Y2, Y3, Y4, and Y5 are the same as those defined in 4), and Y2, Y3, Y4, and Y5 are not hydrogen at the same time; 6) wherein Y1, Y3, Y4, and Y5 are the same as those defined in 4), and Y1, Y3, Y4, and Y5 are not hydrogen at the same time; 7) wherein Y1, Y2, Y4, and Y5 are the same as those defined in 4), and Y1, Y2, Y4, and Y5 may be hydrogen at the same time; 8) wherein Y1, Y3, and Y5 are the same as those defined in 4), and Y1, Y3, and Y5 are not hydrogen at the same time; 9) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R x is selected from the same substituents as Y1; 10) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R y is selected from the same substituents as Y1; 11) Wherein Y1, Y2, Y5 are the same as those defined in 4), and Y1, Y2, Y5 can be hydrogen at the same time, R z , R are each independently selected from the same substituents as Y1; Z5 is selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl; R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl.

2. The compound according to claim 1, which is: or a pharmaceutically acceptable salt of said compound, in: R 1 Selected from: 1) Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time: (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, (6) cyclopropylmethylene, cyclobutylmethylene, cyclopentylmethylene, cyclohexylmethylene; 2) wherein Y1, Y3, Y4, and Y5 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, and 4-(N-isopropylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, and Y5 are not hydrogen at the same time; Z3 and Z4 are each independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C6 cycloalkyl, C3-C6 fluorinated cycloalkyl, and Z4 is not hydrogen; R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl.

3. The compound according to claim 2, wherein R 1 Selected from: 1) in: Y1, Y2, Y3, Y4, Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, Y5 are not hydrogen at the same time: Hydrogen, methyl, ethyl, methoxy, trifluoromethoxy, cyclopropylmethylene, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl; 2) in: Y1, Y3, Y4, and Y5 are each independently selected from hydrogen, ethyl, methoxy, and 4-(N-methylpiperazine-1-)piperidinyl, and Y1, Y3, Y4, and Y5 are not hydrogen at the same time.

4. The compound according to claim 3, wherein R 1 for When, Y1, Y2, Y4, Y5 are each independently selected from hydrogen, methyl, ethyl, methoxy, trifluoromethoxy, cyclopropylmethylene; Y3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl.

5. The compound according to claim 3, wherein R 1 for When Y1, Y4, and Y5 are each independently selected from hydrogen, ethyl, and methoxy, and Y3 is 4-(N-methylpiperazine-1-)piperidinyl.

6. The compound according to claim 2, wherein Z3 and Z4 are each independently selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, and C3-C6 cycloalkyl.

7. The compound according to claim 2, wherein Z3 and Z4 are each independently selected from methyl, ethyl, isopropyl, cyclopropyl, and trifluoromethyl.

8. The compound according to claim 2, wherein Z3 is selected from methyl, ethyl, isopropyl, cyclopropyl, and Z4 is selected from methyl, ethyl, isopropyl, cyclopropyl, and trifluoromethyl.

9. The compound according to claim 2, wherein R 3 、R 4 、R 5 For hydrogen.

10. The compound according to claim 1, which is the following: or a pharmaceutically acceptable salt of said compound, in: R 1 for: wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time: (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluorinated alkoxy, (3) piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, N-n-propylpiperazinyl, N-isopropylpiperazinyl, (4) 3-(N,N-dimethylamino)tetrahydropyrrolyl, 3-(N,N-diethylamino)tetrahydropyrrolyl, (5) 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-ethylpiperazine-1-)piperidinyl, 4-(N-isopropylpiperazine-1-)piperidinyl, Z5 is selected from C1-C6 alkyl, C1-C6 fluorinated alkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl; R 3 、R 4 、R 5 Each is independently selected from hydrogen, C1-C6 alkyl.

11. The compound according to claim 10, wherein R 1 for: wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from the following, and Y1, Y2, Y3, Y4, and Y5 are not hydrogen at the same time: Hydrogen, ethyl, methoxy, trifluoromethoxy, N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl.

12. The compound according to claim 11, wherein Y1, Y2, Y4, Y5 are each independently selected from hydrogen, ethyl, methoxy, trifluoromethoxy; Y3 is selected from N-methylpiperazinyl, 3-(N,N-dimethylamino)tetrahydropyrrolyl, 4-N,N-dimethylaminopiperidinyl, 4-(N-methylpiperazine-1-)piperidinyl.

13. The compound according to claim 10, wherein Z5 is selected from C1-C6 alkyl.

14. The compound according to claim 10, wherein Z5 is selected from methyl and isopropyl.

15. The compound according to claim 10, wherein R 3 、R 4 、R 5 For hydrogen.

16. The compound according to claim 1, selected from the group consisting of: or a pharmaceutically acceptable salt of the above compound.

17. A method for preparing the compound according to claim 1, comprising the steps of: in, R 2 for R 1 , Z3, Z4, Z5, R 3 、R 4 and R 5 As defined in claim 1, X is halogen, Reaction conditions: (a) Nucleophilic substitution reaction under acidic or basic conditions; (b) palladium-catalyzed coupling reactions or nucleophilic substitution reactions under acidic conditions; (c) coupling reaction catalyzed by palladium metal; in: The metal palladium catalyst is selected from palladium acetate, tetrakis(triphenylphosphine)palladium, bistriphenylphosphine palladium dichloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride, and tris(dibenzylideneacetone)dipalladium; The alkaline conditions refer to the conditions in which any of the following substances exist: triethylamine, diisopropylethylamine, pyridine, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride; The acidic conditions refer to the conditions in which any of the following substances exist: acetic acid, trifluoroacetic acid, hydrochloric acid, methanesulfonic acid, p-toluenesulfonic acid, and camphorsulfonic acid.

18. A pharmaceutical composition comprising the compound according to any one of claims 1 to 16 or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable excipient.

19. The pharmaceutical composition according to claim 18, wherein The pharmaceutical composition further comprises EGFR monoclonal antibody.

20. The pharmaceutical composition according to claim 19, wherein The EGFR monoclonal antibody is cetuximab.

21. Use of the compound according to any one of claims 1 to 16 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to any one of claims 18 to 20, in the preparation of a medicament for preventing and / or treating cancer and other diseases mediated by EGFR kinase.

22. The use according to claim 21, wherein The medicine is used for preventing and / or treating lung cancer.

23. The use according to claim 21, wherein The drug is used for preventing and / or treating lung cancer with EGFR kinase 19Del, L858R, T790M, C797S or a combination thereof mutations.

24. The use according to claim 21, wherein The drug is used to prevent and / or treat EGFR kinase 19Del single mutation, L858R single mutation, 19Del / T790M double mutation, L858R / T790M double mutation, 19Del / T790M / C797S triple mutation or L858R / T790M / C797S triple mutation lung cancer.

25. The use according to any one of claims 22 to 24, wherein The lung cancer is non-small cell lung cancer.

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