Substituted quinazoline compounds, their preparation methods, pharmaceutical combinations and uses

Abstract

A substituted quinazoline compound, its preparation method, pharmaceutical combination and application; specifically, it relates to a class of substituted quinazoline compounds with BRK and / or BTK kinase inhibitory activity, pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof, its preparation method, a pharmaceutical composition containing the compound, and the use of these compounds in the preparation of drugs for preventing or treating diseases related to BRK, BTK kinase or both in vivo. #imgabs0#

Description

Technical Field

[0001] The present invention relates to the field of medicinal chemistry, and in particular, to a class of substituted quinazoline compounds having BRK and / or BTK kinase inhibitory activity, and pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof, a preparation method thereof, a pharmaceutical composition comprising the compound, and the use of these compounds in the preparation of drugs for preventing or treating diseases related to BRK, BTK kinase or both in vivo, especially in the preparation of drugs for preventing or treating tumor growth and metastasis. Background Art

[0002] BRK kinase (Breast tumor kinase) is a non-receptor tyrosine kinase related to various tumors. Research shows that BRK is highly expressed in more than 80% of breast cancer cells and 70% of higher-grade ovarian cancer cells (Barker et al, Oncogene, 1997, 15, 799 - 805; Schmandt et al, Cancer Biology and Therapy, 2006, 5, 1136 - 1141); in colon cancer cells, BRK also has a relatively high level of expression (Derry et al, Molecular and Cellular Biology, 2000, 20, 6114 - 6126); the expression of BRK has been detected in human oral squamous cell carcinoma, head and neck squamous cell carcinoma, and cutaneous T-cell lymphoma (Petro et al, Oral Oncology, 2004, 40, 1040 - 1047; Lin et al, Archives of Otolaryngology-Head & Neck Surgery, 2004, 130, 311 - 316; Kasprzycka et al, American Journal of Pathology, 2006, 168, 1631 - 1641). Moreover, small molecule inhibitors targeting BRK can effectively inhibit the growth of tumor cells with high BRK expression at the cellular and animal levels (Jiang et al, Cancer research, 2017, 77, 175 - 186). Therefore, the development of highly active and highly specific BRK inhibitors is beneficial to the development of targeted drugs for tumor treatment, especially breast cancer treatment.

[0003] BTK kinase (Bruton's tyrosine kinase) plays a very important role in the development, differentiation, and signal transduction of B cells, and is involved in and maintains the malignant phenotypes of B-cell lymphoma and B-cell leukemia (Hendriks et al, Nature Reviews Cancer, 2014, 14, 219-232). Treating B-cell malignancies by inhibiting the activity of BTK has also achieved good therapeutic effects. For example, Ibrutinib has been marketed in many countries and regions for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, and small lymphocytic lymphoma, etc. Other marketed BTK inhibitors include acalabrutinib and zanubrutinib. However, these inhibitors are all covalent inhibitors and largely rely on forming covalent bonds with the sulfhydryl group of cysteine at position 481 of BTK to produce drug effects, and are extremely prone to drug resistance due to the mutation of cysteine at position 481 (Woyachet al, New England Journal of Medicine, 2014, 370, 2286-2294). Therefore, the development of new non-covalent inhibitors is beneficial to overcoming drug resistance and meeting clinical needs. Summary of the Invention

[0004] Through extensive and in-depth research, the inventors of the present invention designed and synthesized a series of substituted quinazoline compounds with novel structures, high safety, and high inhibitory activity against BRK and / or BTK kinases, and studied the anti-tumor activities of these compounds.

[0005] The present invention provides compounds of the following general formula:

[0006]

[0007] Or stereoisomers, prodrugs, pharmaceutically acceptable salts, or pharmaceutically acceptable solvates of the above compounds.

[0008] More specifically, the present invention provides compounds of the following general formulas (I, II, III):

[0009]

[0010] The definitions of substituents and symbols are described in detail below.

[0011] One object of the present invention is to provide a class of compounds having inhibitory activity against BRK and / or BTK kinases, and their stereoisomers, prodrugs, pharmaceutically acceptable salts, or pharmaceutically acceptable solvates.

[0012] Another object of the present invention is to provide a preparation method of the above compounds.

[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 compound and the pharmaceutical composition comprising the above compound in the preparation of a medicament for the prevention and / or treatment of cancer or other diseases mediated by BRK, BTK kinase or both.

[0015] Another object of the present invention is to provide a method for treating cancer, the method comprising administering to a subject an effective amount of the compound or composition of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0017] Various specific embodiments, modes and examples are described herein, including exemplary embodiments and definitions employed for understanding the claimed invention. Although the following detailed description gives specific preferred embodiments, those skilled in the art will understand that these embodiments are merely exemplary and the invention may be practiced in other ways. For the purpose of determining infringement, the scope of the present invention will refer to any one or more of the appended claims, including their equivalents, and elements or limitations equivalent to those recited.

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

[0019] In a first aspect of the present invention, the present invention provides a compound of the following general formula:

[0020]

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

[0022] wherein:

[0023] R 1 is selected from:

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

[0025] 2) 2-N,N-dimethylaminoethyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinoethyl, 2-thiomorpholinoethyl, 2-piperidinoethyl, 2-hydroxyethyl, 2-methoxyethyl, 3-N,N-dimethylaminopropyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-acetyl-4-piperidyl, N-propionyl-4-piperidyl, N-isopropionyl-4-piperidyl, N-cyclopropylcarbonyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-ethylsulfonyl-4-piperidyl, N-propylsulfonyl-4-piperidyl, N-isopropylsulfonyl-4-piperidyl, N-cyclopropylsulfonyl-4-piperidyl, 3-N,N-dimethylaminocyclopentyl, 3-N,N-diethylaminocyclopentyl, 3-N,N-dipropylaminocyclopentyl, 3-N,N-diisopropylaminocyclopentyl, 4-aminocyclohexyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, 4-N,N-dipropylaminocyclohexyl, 4-N,N-diisopropylaminocyclohexyl, 4-acetamidocyclohexyl, 4-propionamidocyclohexyl, 4-isopropylformamidocyclohexyl, 4-methylsulfonamidocyclohexyl, 4-ethylsulfonamidocyclohexyl, 4-propylsulfonamidocyclohexyl, 4-isopropylsulfonamidocyclohexyl, 4-cyclopropylsulfonamidocyclohexyl, 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, 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-piperidyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0027] 4) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

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

[0029] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0030] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinoethoxy, 2-thiomorpholinoethoxy, 2-piperidinoethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinopropoxy, 3-thiomorpholinopropoxy, 3-piperidinopropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, mono-halogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, hetero-dihalogen-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, N-(N-methyl-4-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methanesulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0032] (5) Morpholino, 2,6-dimethylmorpholino, thiomorpholino,

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

[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-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methylsulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)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-methylsulfonyl-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-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-ylamino, N-ethylpiperidin-4-ylamino, N-n-propylpiperidin-4-ylamino, N-isopropylpiperidin-4-ylamino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0038] (11) Aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, pyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene,

[0039] (12) Carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0040] Pyrrolidin-1-ylcarbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylcarbonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylcarbonyl,

[0041] Morpholin-4-ylcarbonyl, thiomorpholin-4-ylcarbonyl, 2,6-dimethylmorpholin-4-ylcarbonyl,

[0042] Piperidin-1-ylcarbonyl, 4-hydroxypiperidin-1-ylcarbonyl, 4-(N,N-dimethylamino)piperidin-1-ylcarbonyl, 4-(N,N-diethylamino)piperidin-1-ylcarbonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonyl,

[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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl,

[0044] (13)hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl,

[0045] (14)hydroxy sulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylsulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0046] pyrrolidine-1-sulfonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylsulfonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylsulfonyl,

[0047] morpholine-4-sulfonyl, thiomorpholine-4-sulfonyl, 2,6-dimethylmorpholine-4-sulfonyl,

[0048] piperidin-1-sulfonyl, 4-hydroxypiperidine-1-sulfonyl, 4-(N,N-dimethylamino)piperidin-1-ylsulfonyl, 4-(N,N-diethylamino)piperidin-1-ylsulfonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylsulfonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylsulfonyl,

[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-piperidyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-sulfonyl,

[0050] (15) Carbamoylamino, methylcarbamoylamino, ethylcarbamoylamino, propylcarbamoylamino, isopropylcarbamoylamino, cyclopropylcarbamoylamino, cyclobutylcarbamoylamino, cyclopentylcarbamoylamino, piperidin-1-ylcarbonylamino, 4-hydroxypiperidin-1-ylcarbonylamino, 4-N,N-dimethylpiperidin-1-ylcarbonylamino, 4-N,N-diethylpiperidin-1-ylcarbonylamino, pyrrolidin-1-ylcarbonylamino, 3-N,N-dimethylpyrrolidin-1-ylcarbonylamino, 3-N,N-diethylpyrrolidin-1-ylcarbonylamino, N-methylpiperazin-1-ylcarbonylamino, N-ethylpiperazin-1-ylcarbonylamino, N-acetylpiperazin-1-ylcarbonylamino, N-tert-butoxycarbonylpiperazin-1-ylcarbonylamino, N-(2-hydroxyethyl)piperazin-1-ylcarbonylamino, N-(2-cyanoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-dimethylaminoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-diethylaminoethyl)piperazin-1-ylcarbonylamino, N-(3-hydroxypropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-dimethylpropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-diethylpropyl)piperazin-1-ylcarbonylamino, morpholin-1-ylcarbonylamino, 3,5-dimethylmorpholin-1-ylcarbonylamino, 4-(pyrrolidin-1-yl)piperidin-1-ylcarbonylamino, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-acetyl-1-piperazinyl)piperidin-1-ylcarbonylamino, N-(N-methyl-4-piperidyl)piperazin-1-ylcarbonylamino,

[0051] (16) Z3 and Z4 can form an oxygen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above substituents same as Z1,

[0052] (17) Z3 and Z4 can form a nitrogen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above substituents same as Z1;

[0053] 5) wherein Z2, Z3, Z4, Z5 are the same as defined in 4);

[0054] 6) wherein Z1, Z3, Z4, Z5 are the same as defined in 4);

[0055] 7) wherein Z1, Z2, Z4, Z5 are the same as defined in 4);

[0056] 8) wherein Z1, Z3, Z5 are the same as defined in 4);

[0057] R 2 Selected from:

[0058] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino;

[0059] R 3 Selected from:

[0060] 1)

[0061] wherein W1, W2, W3, W4, W5 are each independently selected from the following and not all hydrogen at the same time:

[0062] (1) hydrogen,

[0063] (2) fluorine, chlorine, bromine, iodine, nitro, cyano,

[0064] (3) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0065] (4) wherein R a , R b are each independently selected from:

[0066] hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0067] or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0068] (5) wherein R a , R b are as defined in (4);

[0069] (6) hydroxycarbonyl, C1-C6 alkoxycarbonyl;

[0070] (7)

[0071] wherein L is selected from a direct bond,

[0072] Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0073] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0074] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl, C1-C6 acyl,

[0075] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-ylmethylene, 4-aminopiperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-(N,N-diethylamino)-1-piperidinylmethylene, 4-(N,N-dipropylamino)-1-piperidinylmethylene, 4-(N,N-diisopropylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, 4-methoxypiperidin-1-ylmethylene, 4-ethoxypiperidin-1-ylmethylene, 4-propoxypiperidin-1-ylmethylene, 4-isopropoxypiperidin-1-ylmethylene, morpholin-4-ylmethylene, thiomorpholin-4-ylmethylene, 2,6-dimethylmorpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, 3-aminopyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene, 3-(N,N-diethylamino)-1-pyrrolidinylmethylene, 3-(N,N-dipropylamino)-1-pyrrolidinylmethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinylmethylene, azetidin-1-ylmethylene,

[0076] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0077] (8) wherein, L, Y2, Y3, Y4, Y5 are the same as defined in (7),

[0078] (9) wherein, L, Y1, Y3, Y4, Y5 are the same as defined in (7),

[0079] (10) wherein, L, Y1, Y2, Y4, Y5 are the same as defined in (7);

[0080] 2) Among them, W2, W3, W4, and W5 are the same as defined in 1), and can be hydrogen simultaneously;

[0081] 3) Among them, W1, W3, W4, and W5 are the same as defined in 1), and can be hydrogen simultaneously;

[0082] 4) Among them, W1, W2, W4, and W5 are the same as defined in 1), and can be hydrogen simultaneously.

[0083] In some embodiments, R 1 is selected from:

[0084] 1) Z1, Z2, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, and Z5 are not hydrogen simultaneously:

[0085] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0086] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0087] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0088] (4) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methylsulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0089] (5) 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-methylsulfonyl-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,

[0090] (6) 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-ylamino, N-ethylpiperidin-4-ylamino, N-n-propylpiperidin-4-ylamino, N-isopropylpiperidin-4-ylamino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0091] (7) Carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0092] Pyrrolidine-1-carbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylcarbonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylcarbonyl,

[0093] Morpholine-4-carbonyl, thiomorpholine-4-carbonyl, 2,6-dimethylmorpholine-4-carbonyl,

[0094] Piperidine-1-carbonyl, 4-hydroxypiperidine-1-carbonyl, 4-(N,N-dimethylamino)piperidine-1-carbonyl, 4-(N,N-diethylamino)piperidine-1-carbonyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidine-1-carbonyl,

[0095] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl;

[0096] 2) wherein Z1, Z3, Z4, Z5 are the same as defined in 1);

[0097] 3) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen simultaneously; R x1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0098] 4) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen simultaneously; R x2 and R y are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0099] 5) wherein: Z2, Z5 are the same as defined in 1) and can be hydrogen simultaneously; R x3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0100] 6) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen simultaneously; R x4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0101] 7) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl.

[0102] In some embodiments, R 1 is selected from:

[0103] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not hydrogen simultaneously:

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

[0105] (2) C1-C6 alkyl group, C1-C6 alkoxy group,

[0106] (3) piperazinyl group, N-methylpiperazinyl group, N-ethylpiperazinyl group, N-n-propylpiperazinyl group, N-isopropylpiperazinyl group, N-cyclopropylpiperazinyl group, N-(2-hydroxyethyl)piperazinyl group, N-(2-N,N-dimethylaminoethyl)piperazinyl group, N-(2-N,N-diethylaminoethyl)piperazinyl group, N-(2-cyanoethyl)piperazinyl group, N-cyanomethylpiperazinyl group, N-(3-hydroxypropyl)piperazinyl group, N-(3-N,N-dimethylaminopropyl)piperazinyl group, N-(3-N,N-diethylaminopropyl)piperazinyl group,

[0107] (4) piperidinyl group, 4-N,N-dimethylaminopiperidinyl group, 4-N,N-diethylaminopiperidinyl group, 4-N,N-diisopropylaminopiperidinyl group, 4-hydroxypiperidinyl group, 4-methoxypiperidinyl group, 4-ethoxypiperidinyl group, 4-(N-methylpiperazin-1-yl)piperidinyl group, 4-(N-ethylpiperazin-1-yl)piperidinyl group, 4-(N-isopropylpiperazin-1-yl)piperidinyl group, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl group, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl group, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl group, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl group, 4-(N-(2-N,N-diethylethyl)piperazin-1-yl)piperidinyl group, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl group, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl group, 4-(pyrrolidin-1-yl)piperidinyl group, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl group, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl group,

[0108] (5) piperidin-4-yl group, N-methyl-4-piperidinyl group, N-ethyl-4-piperidinyl group, N-isopropyl-4-piperidinyl group, N-(2-hydroxyethyl)-4-piperidinyl group, N-(2-N,N-dimethylaminoethyl)-4-piperidinyl group, N-(2-N,N-diethylaminoethyl)-4-piperidinyl group, N-(2-cyanoethyl)-4-piperidinyl group, N-(3-hydroxypropyl)-4-piperidinyl group, N-(3-N,N-dimethylaminopropyl)-4-piperidinyl group, N-(3-N,N-diethylaminopropyl)-4-piperidinyl group, N-(3-cyanopropyl)-4-piperidinyl group, N-cyanomethylene-4-piperidinyl group,

[0109] (6) acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido,

[0110] (7) 4-(N-methyl-1-piperazinyl)piperidin-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-carbonyl,

[0111] 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;

[0112] 2) Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0113] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0114] (2) C1-C6 alkyl, C1-C6 alkoxy,

[0115] (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,

[0116] (4) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl,

[0117] (5) N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino;

[0118] 3) wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkoxy; R x1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0119] 4) Wherein: Z1, Z2, and Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x2 , R y are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0120] 5) Wherein: Z2 and Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0121] 6) Wherein: Z1, Z2, and Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0122] 7) 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl.

[0123] In some embodiments, R 1 is selected from:

[0124] 1) Z1, Z2, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, and Z5 are not simultaneously hydrogen:

[0125] hydrogen, methyl, methoxy, ethoxy, isopropoxy, N-methylpiperazine-1-carbonyl, 4-hydroxypiperidinyl, N-methyl-4-piperidinyl, N-methylpiperazinyl, (N-methylpiperazine-1-)piperidinyl, 4-(pyrrolidin-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 2-(N,N-dimethylamino)acetamido;

[0126] 2) Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen:

[0127] hydrogen, methyl, methoxy, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-N,N-dimethylaminopiperidinyl, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-methylpiperazinyl;

[0128] 3) Wherein: Z1, Z2, and Z5 are each independently selected from hydrogen, fluorine, methoxy; Rx1 is methyl;

[0129] 4) wherein: Z1, Z2, Z5 are hydrogen; R x2 , R y is methyl;

[0130] 5) wherein: Z2, Z5 are hydrogen; R x3 is isopropyl;

[0131] 6) wherein: Z1, Z2, Z5 are hydrogen; R x4 is hydrogen;

[0132] 7) 1-methyl-3-pyrazolyl.

[0133] In some embodiments, R 3 is selected from:

[0134] 1)

[0135] wherein, W1, W4 are each independently selected from the following and are not both hydrogen:

[0136] (1) hydrogen,

[0137] (2) fluorine, chlorine, bromine, iodine, nitro, cyano,

[0138] (3) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0139] (4) wherein, R a , R b are each independently selected from:

[0140] hydrogen, C1-C6 alkyl,

[0141] or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl,

[0142] (5) wherein, R a , R b are defined the same as in (4),

[0143] (6) hydroxycarbonyl, C1-C6 alkoxycarbonyl,

[0144] (7)

[0145] L is selected from a direct bond,

[0146] Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0147] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0148] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl, C1-C6 acyl,

[0149] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-methylene, 4-aminopiperidin-1-methylene, 4-(N,N-dimethylamino)-1-piperidinomethylene, 4-(N,N-diethylamino)-1-piperidinomethylene, 4-(N,N-dipropylamino)-1-piperidinomethylene, 4-(N,N-diisopropylamino)-1-piperidinomethylene, 4-hydroxypiperidin-1-methylene, 4-methoxypiperidin-1-methylene, 4-ethoxypiperidin-1-methylene, 4-propoxypiperidin-1-methylene, 4-isopropoxypiperidin-1-methylene, morpholin-4-methylene, thiomorpholin-4-methylene, 2,6-dimethylmorpholin-4-methylene, pyrrolidin-1-methylene, 3-aminopyrrolidin-1-methylene, 3-(N,N-dimethylamino)-1-pyrrolidinomethylene, 3-(N,N-diethylamino)-1-pyrrolidinomethylene, 3-(N,N-dipropylamino)-1-pyrrolidinomethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinomethylene, azetidin-1-methylene,

[0150] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0151] (8) wherein, L, Y2, Y3, Y4, Y5 are as defined in (7),

[0152] (9) wherein, L, Y1, Y3, Y4, Y5 are as defined in (7),

[0153] (10) Among them, L, Y1, Y2, Y4, and Y5 are the same as defined in (7);

[0154] 2) Among them, W1 and W4 are the same as defined in 1), and can be hydrogen at the same time;

[0155] 3) Among them, W1 and W4 are the same as defined in 1), and can be hydrogen at the same time;

[0156] 4) Among them, W1 and W5 are the same as the definition of W1 in 1), and can be hydrogen at the same time.

[0157] In some embodiments, R 3 is selected from:

[0158] 1)

[0159] Among them, W1 and W4 are each independently selected from the following and are not hydrogen at the same time:

[0160] (1) Hydrogen,

[0161] (2) Fluorine, chlorine, bromine, iodine, nitro group, cyano group,

[0162] (3) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0163] (4) Among them, R a , R b are each independently selected from:

[0164] Hydrogen, C1-C6 alkyl,

[0165] Or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0166] (5) Among them, R a , R b are the same as defined in (4);

[0167] (6) Hydroxycarbonyl, C1-C6 alkoxycarbonyl;

[0168] (7)

[0169] Among them, L is selected from a direct bond,

[0170] Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0171] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0172] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl, C1-C6 acyl,

[0173] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-methylene, 4-aminopiperidin-1-methylene, 4-(N,N-dimethylamino)-1-piperidinomethylene, 4-(N,N-diethylamino)-1-piperidinomethylene, 4-(N,N-dipropylamino)-1-piperidinomethylene, 4-(N,N-diisopropylamino)-1-piperidinomethylene, 4-hydroxypiperidin-1-methylene, 4-methoxypiperidin-1-methylene, 4-ethoxypiperidin-1-methylene, 4-propoxypiperidin-1-methylene, 4-isopropoxypiperidin-1-methylene, morpholin-4-methylene, thiomorpholinyl-4-methylene, 2,6-dimethylmorpholinyl-4-methylene, pyrrolidin-1-methylene, 3-aminopyrrolidin-1-methylene, 3-(N,N-dimethylamino)-1-pyrrolidinomethylene, 3-(N,N-diethylamino)-1-pyrrolidinomethylene, 3-(N,N-dipropylamino)-1-pyrrolidinomethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinomethylene, azetidin-1-methylene,

[0174] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0175] (8) Among them, L, Y2, Y3, Y4, Y5 are the same as defined in (7),

[0176] (9) Among them, L, Y1, Y3, Y4, Y5 are the same as defined in (7),

[0177] (10) Among them, L, Y1, Y2, Y4, and Y5 are the same as those defined in (7);

[0178] 2) Among them, W1 and W5 are the same as the definition of W1 in 1), and they can both be hydrogen at the same time.

[0179] In some embodiments, R 3 is selected from:

[0180] 1)

[0181] Among them, W1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy,

[0182] W4 is selected from:

[0183] (1) fluorine, chlorine, bromine, iodine, nitro, cyano,

[0184] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy,

[0185] (3) Among them, R a , R b are each independently selected from:

[0186] hydrogen, C1-C6 alkyl,

[0187] or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0188] (4) Among them, R a , R b are the same as those defined in (3);

[0189] (5) hydroxycarbonyl, C1-C6 alkoxycarbonyl;

[0190] (6)

[0191] Among them, L is selected from a direct bond,

[0192] Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0193] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0194] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl, C1-C6 acyl,

[0195] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-methylene, 4-aminopiperidin-1-methylene, 4-(N,N-dimethylamino)-1-piperidinomethylene, 4-(N,N-diethylamino)-1-piperidinomethylene, 4-(N,N-dipropylamino)-1-piperidinomethylene, 4-(N,N-diisopropylamino)-1-piperidinomethylene, 4-hydroxypiperidin-1-methylene, 4-methoxypiperidin-1-methylene, 4-ethoxypiperidin-1-methylene, 4-propoxypiperidin-1-methylene, 4-isopropoxypiperidin-1-methylene, morpholin-4-methylene, thiomorpholin-4-methylene, 2,6-dimethylmorpholin-4-methylene, pyrrolidin-1-methylene, 3-aminopyrrolidin-1-methylene, 3-(N,N-dimethylamino)-1-pyrrolidinomethylene, 3-(N,N-diethylamino)-1-pyrrolidinomethylene, 3-(N,N-dipropylamino)-1-pyrrolidinomethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinomethylene, azetidin-1-methylene,

[0196] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0197] (7) wherein, L, Y2, Y3, Y4, Y5 are the same as defined in (6),

[0198] (8) wherein, L, Y1, Y3, Y4, Y5 are the same as defined in (6),

[0199] (9) wherein, L, Y1, Y2, Y4, Y5 are the same as defined in (6);

[0200] 2) Among them, W1 and W5 have the same definition as W1 in 1) and can both be hydrogen at the same time.

[0201] In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, hydrogencarbonate and carbonate, sulfate or phosphate, and the organic acid salt is 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.

[0202] In a second aspect of the present invention, the present invention provides the following compounds:

[0203]

[0204] or stereoisomers of the compound, its prodrugs, its pharmaceutically acceptable salts or its pharmaceutically acceptable solvates,

[0205] Wherein:

[0206] R 1 is selected from:

[0207] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not all hydrogen at the same time:

[0208] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0209] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0210] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinoethoxy, 2-thiomorpholinoethoxy, 2-piperidinoethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinopropoxy, 3-thiomorpholinopropoxy, 3-piperidinopropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, mono-halogen-substituted phenylmethoxy, geminal-dihalogen-substituted phenylmethoxy, vicinal-dihalogen-substituted phenylmethoxy,

[0211] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0212] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0213] (6) pyrrolidinyl, 3-(N,N-dimethylamino)pyrrolidinyl, 3-(N,N-diethylamino)pyrrolidinyl,

[0214] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0215] (8) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazin-1-)piperidyl, 4-(N-ethylpiperazin-1-)piperidyl, 4-(N-isopropylpiperazin-1-)piperidyl, 4-(N-acetylpiperazin-1-)piperidyl, 4-(N-tert-butoxycarbonylpiperazin-1-)piperidyl, 4-(N-methylsulfonylpiperazin-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidyl, 4-(pyrrolidin-1-)piperidyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidyl,

[0216] (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-methylsulfonyl-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,

[0217] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino, 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-4-amino, N-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0218] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, pyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene,

[0219] (12) carbamoyl, methylaminocarbonyl, dimethylaminocarbonyl, ethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, cyclohexylaminocarbonyl,

[0220] Pyrrolidin-1-carbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-carbonyl, 3-(N,N-diethylamino)pyrrolidin-1-carbonyl,

[0221] Morpholin-4-carbonyl, thiomorpholin-4-carbonyl, 2,6-dimethylmorpholin-4-carbonyl,

[0222] Piperidin-1-carbonyl, 4-hydroxypiperidin-1-carbonyl, 4-(N,N-dimethylamino)piperidin-1-carbonyl, 4-(N,N-diethylamino)piperidin-1-carbonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-carbonyl,

[0223] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl,

[0224] (13) Hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl,

[0225] (14) Hydroxy-sulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylsulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0226] Pyrrolidin-1-sulfonyl, 3-(N,N-dimethylamino)pyrrolidin-1-sulfonyl, 3-(N,N-diethylamino)pyrrolidin-1-sulfonyl,

[0227] Morpholin-4-sulfonyl, thiomorpholin-4-sulfonyl, 2,6-dimethylmorpholin-4-sulfonyl,

[0228] Piperidin-1-sulfonyl, 4-hydroxypiperidin-1-sulfonyl, 4-(N,N-dimethylamino)piperidin-1-sulfonyl, 4-(N,N-diethylamino)piperidin-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-sulfonyl,

[0229] 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-piperidyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-sulfonyl,

[0230] (15) carbamoylamino, methylcarbamoylamino, ethylcarbamoylamino, propylcarbamoylamino, isopropylcarbamoylamino, cyclopropylcarbamoylamino, cyclobutylcarbamoylamino, cyclopentylcarbamoylamino, piperidin-1-ylformamido, 4-hydroxypiperidin-1-ylformamido, 4-N,N-dimethylpiperidin-1-ylformamido, 4-N,N-diethylpiperidin-1-ylformamido, pyrrolidin-1-ylformamido, 3-N,N-dimethylpyrrolidin-1-ylformamido, 3-N,N-diethylpyrrolidin-1-ylformamido, N-methylpiperazin-1-ylformamido, N-ethylpiperazin-1-ylformamido, N-acetylpiperazin-1-ylformamido, N-tert-butoxycarbonylpiperazin-1-ylformamido, N-(2-hydroxyethyl)piperazin-1-ylformamido, N-(2-cyanoethyl)piperazin-1-ylformamido, N-(2-N,N-dimethylaminoethyl)piperazin-1-ylformamido, N-(2-N,N-diethylaminoethyl)piperazin-1-ylformamido, N-(3-hydroxypropyl)piperazin-1-ylformamido, N-(3-N,N-dimethylpropyl)piperazin-1-ylformamido, N-(3-N,N-diethylpropyl)piperazin-1-ylformamido, morpholin-1-ylformamido, 3,5-dimethylmorpholin-1-ylformamido, 4-(pyrrolidinyl)piperidin-1-ylformamido, 4-(N-methyl-1-piperazinyl)piperidin-1-ylformamido, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylformamido, 4-(N-acetyl-1-piperazinyl)piperidin-1-ylformamido, N-(N-methyl-4-piperidyl)piperazin-1-ylformamido,

[0231] (16) Z3 and Z4 can form an oxygen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above-mentioned substituents same as Z1,

[0232] (17) Z3 and Z4 can form a nitrogen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above-mentioned substituents same as Z1;

[0233] 2) wherein Z2, Z3, Z4, Z5 are the same as defined in 1);

[0234] 3) wherein Z1, Z3, Z4, and Z5 are the same as defined in 1);

[0235] 4) wherein Z1, Z2, Z4, and Z5 are the same as defined in 1);

[0236] 5) wherein Z1, Z3, and Z5 are the same as defined in 1);

[0237] 6) 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-piperidyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0238] R 2 is selected from:

[0239] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino;

[0240] W1, W2, W3, and W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0241] R is selected from:

[0242] 1) hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0243] 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0244] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0245] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl, C1-C6 acyl,

[0246] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-ylmethylene, 4-aminopiperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-(N,N-diethylamino)-1-piperidinylmethylene, 4-(N,N-dipropylamino)-1-piperidinylmethylene, 4-(N,N-diisopropylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, 4-methoxypiperidin-1-ylmethylene, 4-ethoxypiperidin-1-ylmethylene, 4-propoxypiperidin-1-ylmethylene, 4-isopropoxypiperidin-1-ylmethylene, morpholin-4-ylmethylene, thiomorpholin-4-ylmethylene, 2,6-dimethylmorpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, 3-aminopyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene, 3-(N,N-diethylamino)-1-pyrrolidinylmethylene, 3-(N,N-dipropylamino)-1-pyrrolidinylmethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinylmethylene, azetidin-1-ylmethylene,

[0247] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0248] 3) wherein Y2, Y3, Y4, Y5 are the same as defined in 2),

[0249] 4) wherein Y1, Y3, Y4, Y5 are the same as defined in 2),

[0250] 5) wherein Y1, Y2, Y4, Y5 are the same as defined in 2),

[0251] 6) wherein Y1, Y2, Y3, Y4, Y5 are the same as defined in 2).

[0252] In some embodiments, R 1 is selected from:

[0253] 1) Z1, Z2, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, and Z5 are not simultaneously hydrogen:

[0254] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0255] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0256] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0257] (4) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methanesulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0258] (5) 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,

[0259] (6) 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-ylamino, N-ethylpiperidin-4-ylamino, N-n-propylpiperidin-4-ylamino, N-isopropylpiperidin-4-ylamino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0260] (7) Carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0261] Pyrrolidine-1-carbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylcarbonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylcarbonyl,

[0262] Morpholine-4-carbonyl, thiomorpholine-4-carbonyl, 2,6-dimethylmorpholine-4-carbonyl,

[0263] Piperidine-1-carbonyl, 4-hydroxypiperidine-1-carbonyl, 4-(N,N-dimethylamino)piperidine-1-carbonyl, 4-(N,N-diethylamino)piperidine-1-carbonyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidine-1-carbonyl,

[0264] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl;

[0265] 2) Among them, Z1, Z3, Z4, and Z5 are the same as defined in 1);

[0266] 3) Among them: Z1, Z2, and Z5 are the same as defined in 1), and can be hydrogen at the same time; R x1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0267] 4) Among them: Z1, Z2, and Z5 are the same as defined in 1), and can be hydrogen at the same time; R x2 and R y are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0268] 5) Among them: Z2 and Z5 are the same as defined in 1), and can be hydrogen at the same time; R x3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0269] 6) Among them: Z1, Z2, and Z5 are the same as defined in 1), and can be hydrogen at the same time; R x4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0270] 7) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl.

[0271] In some embodiments, R 1 is selected from:

[0272] 1) Z1, Z2, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, and Z5 are not hydrogen at the same time:

[0273] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0274] (2) C1-C6 alkyl, C1-C6 alkoxy,

[0275] (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,

[0276] (4) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-)piperidinyl, 4-(N-ethylpiperazin-1-)piperidinyl, 4-(N-isopropylpiperazin-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidinyl, 4-(pyrrolidin-1-)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidinyl,

[0277] (5) Piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-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-cyanomethylidene-4-piperidinyl,

[0278] (6) acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido,

[0279] (7) 4-(N-methyl-1-piperazinyl)piperidin-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-carbonyl,

[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;

[0281] 2) Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0282] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0283] (2) C1-C6 alkyl, C1-C6 alkoxy,

[0284] (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,

[0285] (4) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl,

[0286] (5) N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino;

[0287] 3) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkoxy; R x1Selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0288] 4) wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x2 and R y are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0289] 5) wherein: Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0290] 6) wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0291] 7) 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl.

[0292] In some embodiments, R 1 is selected from:

[0293] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0294] hydrogen, methyl, fluorine, methoxy, ethoxy, isopropoxy, N-methylpiperazine-1-carbonyl, 4-hydroxypiperidyl, N-methyl-4-piperidyl, N-methylpiperazinyl, 4-(N-methylpiperazine-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidyl, 4-(pyrrolidin-1-)piperidyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 2-(N,N-dimethylamino)acetamido,

[0295] Preferably, Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, methoxy, ethoxy, isopropoxy, and one of Z3, Z4 is selected from the following, and the other is selected from hydrogen, methyl, fluorine:

[0296] N-methylpiperazine-1-carbonyl, 4-hydroxypiperidinyl, N-methyl-4-piperidinyl, N-methylpiperazinyl, 4-(N-methylpiperazine-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazine-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazine-1-)piperidinyl, 4-(pyrrolidin-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 2-(N,N-dimethylamino)acetamido;

[0297] 2) Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0298] hydrogen, methyl, methoxy, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-N,N-dimethylaminopiperidinyl, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-methylpiperazinyl, 4-(N-methylpiperazine-1-)piperidinyl,

[0299] Preferably, Z1, Z5 are each independently selected from hydrogen, methoxy, and one of Z3, Z4 is selected from the following and the other is hydrogen:

[0300] methyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-N,N-dimethylaminopiperidinyl, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-methylpiperazinyl, 4-(N-methylpiperazine-1-)piperidinyl;

[0301] 3) wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, methoxy; R x1 is methyl;

[0302] 4) wherein: Z1, Z2, Z5 are hydrogen; R x2 , R y are methyl;

[0303] 5) wherein: Z2, Z5 are hydrogen; R x3 is isopropyl;

[0304] 6) wherein: Z1, Z2, Z5 are hydrogen; R x4 is hydrogen;

[0305] 7) 1-methyl-3-pyrazolyl.

[0306] In some embodiments, R 2 is selected from hydrogen, methyl, ethyl, isopropyl.

[0307] In some embodiments, each of W1, W2, W3, and W5 is independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

[0308] In some embodiments, each of W1, W2, W3, and W5 is independently selected from hydrogen and methyl.

[0309] In some embodiments, W2, W3, and W5 are hydrogen, and W1 is methyl.

[0310] In some embodiments, R is selected from:

[0311] 1) hydrogen, C1-C6 alkyl,

[0312] 2) wherein each of Y1, Y2, Y3, Y4, and Y5 is independently selected from:

[0313] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0314] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluoroalkyl, C1-C6 acyl,

[0315] (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene, N-cyclopropyl-1-piperazinylmethylene, N-(2-hydroxyethyl)-1-piperazinylmethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, N-(2-cyanoethyl)-1-piperazinylmethylene, morpholin-4-ylmethylene, thiomorpholin-4-ylmethylene, 2,6-dimethylmorpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, 3-amino-1-pyrrolidinylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene, 3-(N,N-diethylamino)-1-pyrrolidinylmethylene, 3-(N,N-dipropylamino)-1-pyrrolidinylmethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinylmethylene, azetidin-1-ylmethylene,

[0316] 3) wherein Y2, Y3, Y4, and Y5 are as defined in 2);

[0317] 4) wherein Y1, Y3, Y4, and Y5 are as defined in 2);

[0318] 5) wherein Y1, Y2, Y3, Y4, and Y5 are as defined in 2).

[0319] In some embodiments, R is selected from:

[0320] 1) Hydrogen,

[0321] 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0322] (a) Hydrogen, fluorine, chlorine, bromine, nitro,

[0323] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluoroalkyl,

[0324] (c) N-methyl-1-piperazinylmethylene, morpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, azetidin-1-ylmethylene,

[0325] (d) formyl, acetyl, propionyl, butyryl, 2-methylpropionyl,

[0326] 3) wherein Y2, Y3, Y4, and Y5 are each independently selected from:

[0327] (a) Hydrogen, fluorine, bromine,

[0328] (b) C1-C6 alkyl, C1-C6 fluoroalkyl;

[0329] 4) wherein Y1, Y3, Y4, and Y5 are each independently selected from:

[0330] Hydrogen, chlorine,

[0331] 5) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0332] Hydrogen, C1-C6 fluoroalkyl.

[0333] In some embodiments, R is selected from:

[0334] 1) Hydrogen,

[0335] 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0336] Hydrogen, fluorine, chlorine, bromine, nitro, methyl, methoxy, acetyl, trifluoromethyl, N-methyl-1-piperazinylmethylene, morpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, azetidin-1-ylmethylene,

[0337] 3) wherein Y2, Y3, Y4, and Y5 are each independently selected from:

[0338] Hydrogen, fluorine, bromine, trifluoromethyl,

[0339] 4) wherein Y1, Y3, Y4, Y5 are each independently selected from:

[0340] hydrogen, chlorine,

[0341] 5) wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0342] hydrogen, trifluoromethyl.

[0343] In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, hydrogencarbonate and carbonate, sulfate or phosphate, and the organic acid salt is 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.

[0344] In a third aspect of the present invention, the present invention provides the following compounds:

[0345]

[0346] or a stereoisomer thereof, a prodrug thereof, a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof,

[0347] wherein:

[0348] R 1 is selected from:

[0349] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0350] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0351] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0352] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinoethoxy, 2-thiomorpholinoethoxy, 2-piperidinoethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinopropoxy, 3-thiomorpholinopropoxy, 3-piperidinopropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, mono-halogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, hetero-dihalogen-substituted phenylmethoxy,

[0353] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0354] (5) morpholino, 2,6-dimethylmorpholino, thiomorpholino,

[0355] (6) pyrrolidinyl, 3-(N,N-dimethylamino)pyrrolidinyl, 3-(N,N-diethylamino)pyrrolidinyl,

[0356] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0357] (8) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methanesulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0358] (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,

[0359] (10) Amino, N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino, 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-ylamino, N-ethylpiperidin-4-ylamino, N-propylpiperidin-4-ylamino, N-isopropylpiperidin-4-ylamino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0360] (11) Aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, pyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene,

[0361] (12) Carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0362] Pyrrolidin-1-ylcarbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylcarbonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylcarbonyl,

[0363] Morpholin-4-ylcarbonyl, thiomorpholin-4-ylcarbonyl, 2,6-dimethylmorpholin-4-ylcarbonyl,

[0364] Piperidin-1-ylcarbonyl, 4-hydroxypiperidin-1-ylcarbonyl, 4-(N,N-dimethylamino)piperidin-1-ylcarbonyl, 4-(N,N-diethylamino)piperidin-1-ylcarbonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonyl,

[0365] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl,

[0366] (13)hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl,

[0367] (14)hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylsulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0368] pyrrolidine-1-sulfonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylsulfonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylsulfonyl,

[0369] morpholin-4-ylsulfonyl, thiomorpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl,

[0370] piperidin-1-ylsulfonyl, 4-hydroxypiperidine-1-sulfonyl, 4-(N,N-dimethylamino)piperidin-1-ylsulfonyl, 4-(N,N-diethylamino)piperidin-1-ylsulfonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylsulfonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylsulfonyl,

[0371] 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-piperidyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-sulfonyl,

[0372] (15) Carbamoylamino, methylcarbamoylamino, ethylcarbamoylamino, propylcarbamoylamino, isopropylcarbamoylamino, cyclopropylcarbamoylamino, cyclobutylcarbamoylamino, cyclopentylcarbamoylamino, piperidin-1-ylcarbonylamino, 4-hydroxypiperidin-1-ylcarbonylamino, 4-N,N-dimethylpiperidin-1-ylcarbonylamino, 4-N,N-diethylpiperidin-1-ylcarbonylamino, pyrrolidin-1-ylcarbonylamino, 3-N,N-dimethylpyrrolidin-1-ylcarbonylamino, 3-N,N-diethylpyrrolidin-1-ylcarbonylamino, N-methylpiperazin-1-ylcarbonylamino, N-ethylpiperazin-1-ylcarbonylamino, N-acetylpiperazin-1-ylcarbonylamino, N-tert-butoxycarbonylpiperazin-1-ylcarbonylamino, N-(2-hydroxyethyl)piperazin-1-ylcarbonylamino, N-(2-cyanoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-dimethylaminoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-diethylaminoethyl)piperazin-1-ylcarbonylamino, N-(3-hydroxypropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-dimethylpropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-diethylpropyl)piperazin-1-ylcarbonylamino, morpholin-1-ylcarbonylamino, 3,5-dimethylmorpholin-1-ylcarbonylamino, 4-(pyrrolidin-1-yl)piperidin-1-ylcarbonylamino, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-acetyl-1-piperazinyl)piperidin-1-ylcarbonylamino, N-(N-methyl-4-piperidyl)piperazin-1-ylcarbonylamino,

[0373] (16) Z3 and Z4 can form an oxygen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above-mentioned substituents the same as Z1,

[0374] (17) Z3 and Z4 can form a nitrogen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above-mentioned substituents the same as Z1;

[0375] 2) wherein Z2, Z3, Z4, Z5 are the same as defined in 1);

[0376] 3) wherein Z1, Z3, Z4, Z5 are the same as defined in 1);

[0377] 4) wherein Z1, Z2, Z4, Z5 are the same as defined in 1);

[0378] 5) wherein Z1, Z3, Z5 are the same as defined in 1);

[0379] R 2 Selected from:

[0380] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino;

[0381] W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0382] R' is selected from:

[0383] 1) wherein R a , R b are each independently selected from:

[0384] hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0385] or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0386] 2) hydroxy, C1-C6 alkoxy;

[0387] 3) wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0388] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0389] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0390] (c) Aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-ylmethylene, 4-aminopiperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-(N,N-diethylamino)-1-piperidinylmethylene, 4-(N,N-dipropylamino)-1-piperidinylmethylene, 4-(N,N-diisopropylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, 4-methoxypiperidin-1-ylmethylene, 4-ethoxypiperidin-1-ylmethylene, 4-propoxypiperidin-1-ylmethylene, 4-isopropoxypiperidin-1-ylmethylene, morpholin-4-ylmethylene, thiomorpholin-4-ylmethylene, 2,6-dimethylmorpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, 3-aminopyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene, 3-(N,N-diethylamino)-1-pyrrolidinylmethylene, 3-(N,N-dipropylamino)-1-pyrrolidinylmethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinylmethylene, azetidin-1-ylmethylene,

[0391] (d) Imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl.

[0392] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0393] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0394] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0395] (3) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methylsulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0396] (4) 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-methylsulfonyl-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.

[0397] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0398] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0399] (2) C1-C6 alkyl,

[0400] (3) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl.

[0401] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0402] Hydrogen, methyl, 4-N,N-dimethylaminopiperidinyl.

[0403] In some embodiments, R 2 is methyl.

[0404] In some embodiments, W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

[0405] In some embodiments, W1, W2, W3, W5 are each independently selected from hydrogen, methyl.

[0406] In some embodiments, W2, W3, W5 are hydrogen, and W1 is hydrogen or methyl.

[0407] In some embodiments, R' is selected from:

[0408] 1) Wherein, R a , R b are each independently selected from:

[0409] Hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0410] Or R a , R b and N form a substituted or unsubstituted piperazine ring, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0411] 2) Hydroxy, C1-C6 alkoxy;

[0412] 3) Wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0413] (a) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0414] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0415] (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene, N-cyclopropyl-1-piperazinylmethylene, N-(2-hydroxyethyl)-1-piperazinylmethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, N-(2-cyanoethyl)-1-piperazinylmethylene,

[0416] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl.

[0417] In some embodiments, R’ is selected from:

[0418] 1) wherein, R a , R b are each independently selected from:

[0419] hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0420] or R a , R b and N form a substituted or unsubstituted piperazine ring, and the substituent is C1-C6 alkyl;

[0421] 2) hydroxy, C1-C6 alkoxy;

[0422] 3) wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0423] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0424] (b) C1-C6 fluoroalkyl,

[0425] (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene,

[0426] (d) imidazolyl, 4-methylimidazolyl.

[0427] In some embodiments, R’ is selected from:

[0428] 1) wherein, R a , R b are each independently selected from hydrogen, methyl, ethyl, cyclopropyl,

[0429] or R a , R b and N form

[0430] 2) hydroxy, methoxy, ethoxy;

[0431] 3) wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0432] hydrogen, trifluoromethyl, N-methyl-1-piperazinylmethylene, 4-methylimidazolyl.

[0433] In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, hydrogencarbonate and carbonate, sulfate or phosphate, and the organic acid salt is 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.

[0434] In a fourth aspect of the present invention, the present invention provides the following compounds:

[0435]

[0436] or a stereoisomer of the compound, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate,

[0437] wherein:

[0438] R 1 is selected from:

[0439] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0440] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0441] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0442] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinoethoxy, 2-thiomorpholinoethoxy, 2-piperidinoethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinopropoxy, 3-thiomorpholinopropoxy, 3-piperidinopropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, mono-halogen-substituted phenylmethoxy, geminal-dihalogen-substituted phenylmethoxy, vicinal-dihalogen-substituted phenylmethoxy,

[0443] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methanesulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0444] (5) morpholino, 2,6-dimethylmorpholino, thiomorpholino,

[0445] (6) pyrrolidinyl, 3-(N,N-dimethylamino)pyrrolidinyl, 3-(N,N-diethylamino)pyrrolidinyl,

[0446] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0447] (8) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methylsulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0448] (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-methylsulfonyl-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,

[0449] (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-ylamino, N-ethylpiperidin-4-ylamino, N-n-propylpiperidin-4-ylamino, N-isopropylpiperidin-4-ylamino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0450] (11) Aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, pyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene,

[0451] (12) Carbamoyl, methylaminocarbonyl, dimethylaminocarbonyl, ethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, cyclohexylaminocarbonyl,

[0452] Pyrrolidin-1-ylcarbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylcarbonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylcarbonyl,

[0453] Morpholin-4-ylcarbonyl, thiomorpholin-4-ylcarbonyl, 2,6-dimethylmorpholin-4-ylcarbonyl,

[0454] Piperidin-1-ylcarbonyl, 4-hydroxypiperidin-1-ylcarbonyl, 4-(N,N-dimethylamino)piperidin-1-ylcarbonyl, 4-(N,N-diethylamino)piperidin-1-ylcarbonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonyl,

[0455] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl,

[0456] (13)hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl,

[0457] (14)hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylsulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0458] pyrrolidine-1-sulfonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylsulfonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylsulfonyl,

[0459] morpholin-4-ylsulfonyl, thiomorpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl,

[0460] piperidin-1-ylsulfonyl, 4-hydroxypiperidine-1-sulfonyl, 4-(N,N-dimethylamino)piperidin-1-ylsulfonyl, 4-(N,N-diethylamino)piperidin-1-ylsulfonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylsulfonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylsulfonyl,

[0461] 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-piperidyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-sulfonyl,

[0462] (15) Carbamoylamino, methylcarbamoylamino, ethylcarbamoylamino, propylcarbamoylamino, isopropylcarbamoylamino, cyclopropylcarbamoylamino, cyclobutylcarbamoylamino, cyclopentylcarbamoylamino, piperidin-1-ylcarbonylamino, 4-hydroxypiperidin-1-ylcarbonylamino, 4-N,N-dimethylpiperidin-1-ylcarbonylamino, 4-N,N-diethylpiperidin-1-ylcarbonylamino, pyrrolidin-1-ylcarbonylamino, 3-N,N-dimethylpyrrolidin-1-ylcarbonylamino, 3-N,N-diethylpyrrolidin-1-ylcarbonylamino, N-methylpiperazin-1-ylcarbonylamino, N-ethylpiperazin-1-ylcarbonylamino, N-acetylpiperazin-1-ylcarbonylamino, N-tert-butoxycarbonylpiperazin-1-ylcarbonylamino, N-(2-hydroxyethyl)piperazin-1-ylcarbonylamino, N-(2-cyanoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-dimethylaminoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-diethylaminoethyl)piperazin-1-ylcarbonylamino, N-(3-hydroxypropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-dimethylpropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-diethylpropyl)piperazin-1-ylcarbonylamino, morpholin-1-ylcarbonylamino, 3,5-dimethylmorpholin-1-ylcarbonylamino, 4-(pyrrolidin-1-yl)piperidin-1-ylcarbonylamino, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-acetyl-1-piperazinyl)piperidin-1-ylcarbonylamino, N-(N-methyl-4-piperidyl)piperazin-1-ylcarbonylamino,

[0463] (16) Z3 and Z4 can form an oxygen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above-mentioned substituents the same as Z1,

[0464] (17) Z3 and Z4 can form a nitrogen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above-mentioned substituents the same as Z1;

[0465] 2) wherein Z2, Z3, Z4, Z5 are the same as defined in 1);

[0466] 3) wherein Z1, Z3, Z4, Z5 are the same as defined in 1);

[0467] 4) wherein Z1, Z2, Z4, Z5 are the same as defined in 1);

[0468] 5) wherein Z1, Z3, Z5 are the same as defined in 1);

[0469] R 2 Selected from:

[0470] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino;

[0471] W1, W3, W4, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl.

[0472] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

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

[0474] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0475] (3) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-)piperidinyl, 4-(N-ethylpiperazin-1-)piperidinyl, 4-(N-isopropylpiperazin-1-)piperidinyl, 4-(N-acetylpiperazin-1-)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-)piperidinyl, 4-(N-methylsulfonylpiperazin-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidinyl, 4-(pyrrolidin-1-)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidinyl,

[0476] (4) 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-methylsulfonyl-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.

[0477] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0478] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0479] (2) C1-C6 alkyl,

[0480] (3) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl.

[0481] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen: hydrogen, 4-N,N-dimethylaminopiperidinyl.

[0482] In some embodiments, R 2 is isopropyl.

[0483] In some embodiments, W1, W3, W4, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

[0484] In some embodiments, W1, W3, W4, W5 are each independently selected from hydrogen, methyl.

[0485] In some embodiments, W1, W3, W4 are hydrogen, and W5 is hydrogen or methyl.

[0486] In the fifth aspect of the present invention, the present invention provides compounds of the following general formula:

[0487]

[0488] or a stereoisomer of said compound, a prodrug thereof, a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof,

[0489] wherein:

[0490] R 1 is selected from:

[0491] 1) hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C3-C8 cycloalkyl, C1-C6 heteroatom-containing alkyl, C3-C8 heteroatom-containing cycloalkyl;

[0492] 2) 2-N,N-dimethylaminoethyl, 2-(N-methylpiperazinyl)ethyl, 2-(N-acetylpiperazinyl)ethyl, 2-morpholinoethyl, 2-thiomorpholinoethyl, 2-piperidinoethyl, 2-hydroxyethyl, 2-methoxyethyl, 3-N,N-dimethylaminopropyl, N-methyl-4-piperidyl, N-ethyl-4-piperidyl, N-propyl-4-piperidyl, N-isopropyl-4-piperidyl, N-hydroxyethyl-4-piperidyl, N-cyanomethyl-4-piperidyl, N-(2-cyanoethyl)-4-piperidyl, N-acetyl-4-piperidyl, N-propionyl-4-piperidyl, N-isopropionyl-4-piperidyl, N-cyclopropylcarbonyl-4-piperidyl, N-methylsulfonyl-4-piperidyl, N-ethylsulfonyl-4-piperidyl, N-propylsulfonyl-4-piperidyl, N-isopropylsulfonyl-4-piperidyl, N-cyclopropylsulfonyl-4-piperidyl, 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-acetamidocyclohexyl, 4-propionamidocyclohexyl, 4-isopropylformamidocyclohexyl, 4-methylsulfonamidocyclohexyl, 4-ethylsulfonamidocyclohexyl, 4-propylsulfonamidocyclohexyl, 4-isopropylsulfonamidocyclohexyl, 4-cyclopropylsulfonamidocyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl, 4-ethoxycyclohexyl, 4-isopropoxycyclohexyl;

[0493] 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-piperidyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0494] 4) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0495] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0496] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0497] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinoethoxy, 2-thiomorpholinoethoxy, 2-piperidinoethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinopropoxy, 3-thiomorpholinopropoxy, 3-piperidinopropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, mono-halogen-substituted phenylmethoxy, geminal di-halogen-substituted phenylmethoxy, vicinal di-halogen-substituted phenylmethoxy,

[0498] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0499] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0500] (6) pyrrolidinyl, 3-(N,N-dimethylamino)pyrrolidinyl, 3-(N,N-diethylamino)pyrrolidinyl,

[0501] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0502] (8) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazin-1-)piperidyl, 4-(N-ethylpiperazin-1-)piperidyl, 4-(N-isopropylpiperazin-1-)piperidyl, 4-(N-acetylpiperazin-1-)piperidyl, 4-(N-tert-butoxycarbonylpiperazin-1-)piperidyl, 4-(N-methylsulfonylpiperazin-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidyl, 4-(pyrrolidin-1-)piperidyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidyl,

[0503] (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,

[0504] (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-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0505] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinomethylene, 4-ethyl-1-piperazinomethylene, 4-propyl-1-piperazinomethylene, 4-isopropyl-1-piperazinomethylene, 4-(2-hydroxyethyl)-1-piperazinomethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, piperidin-1-methylene, 4-(N,N-dimethylamino)-1-piperidinomethylene, 4-hydroxypiperidin-1-methylene, pyrrolidin-1-methylene, 3-(N,N-dimethylamino)-1-pyrrolidinomethylene,

[0506] (12) carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0507] Pyrrolidine-1-carbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-carbonyl, 3-(N,N-diethylamino)pyrrolidin-1-carbonyl,

[0508] Morpholine-4-carbonyl, Thiomorpholine-4-carbonyl, 2,6-dimethylmorpholine-4-carbonyl,

[0509] Piperidine-1-carbonyl, 4-hydroxypiperidine-1-carbonyl, 4-(N,N-dimethylamino)piperidine-1-carbonyl, 4-(N,N-diethylamino)piperidine-1-carbonyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidine-1-carbonyl,

[0510] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl,

[0511] (13)Hydroxycarbonyl, Methoxycarbonyl, Ethoxycarbonyl, Propoxycarbonyl, Isopropoxycarbonyl, n-Butoxycarbonyl, Isobutoxycarbonyl, tert-Butoxycarbonyl,

[0512] (14)Hydroxy sulfonyl, Amino sulfonyl, Methylamino sulfonyl, Ethylamino sulfonyl, Propylamino sulfonyl, Isopropylamino sulfonyl, Cyclopropylamino sulfonyl, Cyclobutyl sulfonyl, Cyclopentylamino sulfonyl, Cyclohexylamino sulfonyl,

[0513] Pyrrolidine-1-sulfonyl, 3-(N,N-dimethylamino)pyrrolidin-1-sulfonyl, 3-(N,N-diethylamino)pyrrolidin-1-sulfonyl,

[0514] Morpholine-4-sulfonyl, Thiomorpholine-4-sulfonyl, 2,6-dimethylmorpholine-4-sulfonyl,

[0515] Piperidine-1-sulfonyl, 4-hydroxypiperidine-1-sulfonyl, 4-(N,N-dimethylamino)piperidine-1-sulfonyl, 4-(N,N-diethylamino)piperidine-1-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidine-1-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidine-1-sulfonyl,

[0516] 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-piperidyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-sulfonyl,

[0517] (15) carbamoylamino, methylcarbamoylamino, ethylcarbamoylamino, propylcarbamoylamino, isopropylcarbamoylamino, cyclopropylcarbamoylamino, cyclobutylcarbamoylamino, cyclopentylcarbamoylamino, piperidin-1-ylformamido, 4-hydroxypiperidin-1-ylformamido, 4-N,N-dimethylpiperidin-1-ylformamido, 4-N,N-diethylpiperidin-1-ylformamido, pyrrolidin-1-ylformamido, 3-N,N-dimethylpyrrolidin-1-ylformamido, 3-N,N-diethylpyrrolidin-1-ylformamido, N-methylpiperazin-1-ylformamido, N-ethylpiperazin-1-ylformamido, N-acetylpiperazin-1-ylformamido, N-tert-butoxycarbonylpiperazin-1-ylformamido, N-(2-hydroxyethyl)piperazin-1-ylformamido, N-(2-cyanoethyl)piperazin-1-ylformamido, N-(2-N,N-dimethylaminoethyl)piperazin-1-ylformamido, N-(2-N,N-diethylaminoethyl)piperazin-1-ylformamido, N-(3-hydroxypropyl)piperazin-1-ylformamido, N-(3-N,N-dimethylpropyl)piperazin-1-ylformamido, N-(3-N,N-diethylpropyl)piperazin-1-ylformamido, morpholin-1-ylformamido, 3,5-dimethylmorpholin-1-ylformamido, 4-(pyrrolidinyl)piperidin-1-ylformamido, 4-(N-methyl-1-piperazinyl)piperidin-1-ylformamido, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylformamido, 4-(N-acetyl-1-piperazinyl)piperidin-1-ylformamido, N-(N-methyl-4-piperidyl)piperazin-1-ylformamido,

[0518] (16) Z3 and Z4 may form an oxygen-containing substituted or unsubstituted five- to seven-membered ring; the substituents may be selected from the above-mentioned substituents same as Z1,

[0519] (17) Z3 and Z4 may form a nitrogen-containing substituted or unsubstituted five- to seven-membered ring; the substituents may be selected from the above-mentioned substituents same as Z1;

[0520] 5) wherein Z2, Z3, Z4, Z5 are the same as defined in 4);

[0521] 6) wherein Z1, Z3, Z4, and Z5 are the same as defined in 4);

[0522] 7) wherein Z1, Z2, Z4, and Z5 are the same as defined in 4);

[0523] 8) wherein Z1, Z3, and Z5 are the same as defined in 4);

[0524] R 2 is selected from:

[0525] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino;

[0526] R 3 is selected from:

[0527] 1)

[0528] wherein W1, W2, W3, W4, and W5 are each independently selected from the following and not all hydrogen at the same time:

[0529] (1) hydrogen,

[0530] (2) fluorine, chlorine, bromine, iodine, nitro, cyano,

[0531] (3) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0532] (4) wherein R a , R b are each independently selected from:

[0533] hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0534] or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0535] (5) wherein R a , R b are the same as defined in (4);

[0536] (6) hydroxycarbonyl, C1-C6 alkoxycarbonyl;

[0537] (7)

[0538] Among them, L is selected from a direct bond,

[0539] Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0540] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0541] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0542] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-methylene, 4-aminopiperidin-1-methylene, 4-(N,N-dimethylamino)-1-piperidinomethylene, 4-(N,N-diethylamino)-1-piperidinomethylene, 4-(N,N-dipropylamino)-1-piperidinomethylene, 4-(N,N-diisopropylamino)-1-piperidinomethylene, 4-hydroxypiperidin-1-methylene, 4-methoxypiperidin-1-methylene, 4-ethoxypiperidin-1-methylene, 4-propoxypiperidin-1-methylene, 4-isopropoxypiperidin-1-methylene, morpholin-4-methylene, thiomorpholin-4-methylene, 2,6-dimethylmorpholin-4-methylene, pyrrolidin-1-methylene, 3-aminopyrrolidin-1-methylene, 3-(N,N-dimethylamino)-1-pyrrolidinomethylene, 3-(N,N-diethylamino)-1-pyrrolidinomethylene, 3-(N,N-dipropylamino)-1-pyrrolidinomethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinomethylene, azetidin-1-methylene,

[0543] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0544] (8) Among them, L, Y2, Y3, Y4, Y5 are the same as defined in (7),

[0545] (9) wherein, L, Y1, Y3, Y4, Y5 are the same as defined in (7);

[0546] (10) wherein, L, Y1, Y2, Y4, Y5 are the same as defined in (7);

[0547] 2) wherein, W2, W3, W4, W5 are the same as defined in 1), and can be hydrogen simultaneously;

[0548] 3) wherein, W1, W3, W4, W5 are the same as defined in 1), and can be hydrogen simultaneously;

[0549] 4) wherein, W1, W2, W4, W5 are the same as defined in 1), and can be hydrogen simultaneously.

[0550] In some embodiments, R 1 is selected from:

[0551] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not hydrogen simultaneously:

[0552] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0553] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0554] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methanesulfonylpiperazinyl, N-ethanesulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0555] (4) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methanesulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0556] (5) 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,

[0557] (6) 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-ylamino, N-ethylpiperidin-4-ylamino, N-n-propylpiperidin-4-ylamino, N-isopropylpiperidin-4-ylamino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0558] (7) Carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0559] Pyrrolidine-1-carbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylcarbonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylcarbonyl,

[0560] Morpholine-4-carbonyl, thiomorpholine-4-carbonyl, 2,6-dimethylmorpholine-4-carbonyl,

[0561] Piperidine-1-carbonyl, 4-hydroxypiperidine-1-carbonyl, 4-(N,N-dimethylamino)piperidine-1-carbonyl, 4-(N,N-diethylamino)piperidine-1-carbonyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidine-1-carbonyl,

[0562] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl;

[0563] 2) wherein Z1, Z3, Z4, Z5 are the same as defined in 1);

[0564] 3) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen at the same time; R x1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0565] 4) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen at the same time; R x2 and R y are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0566] 5) wherein: Z2, Z5 are the same as defined in 1) and can be hydrogen at the same time; R x3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0567] 6) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen at the same time; R x4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0568] 7) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl.

[0569] In some embodiments, R 1 is selected from:

[0570] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not hydrogen at the same time:

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

[0572] (2) C1-C6 alkyl, C1-C6 alkoxy,

[0573] (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,

[0574] (4) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-)piperidinyl, 4-(N-ethylpiperazin-1-)piperidinyl, 4-(N-isopropylpiperazin-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidinyl, 4-(pyrrolidin-1-)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidinyl,

[0575] (5) Piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-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,

[0576] (6) acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido,

[0577] (7) 4-(N-methyl-1-piperazinyl)piperidin-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-carbonyl,

[0578] 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;

[0579] 2) Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0580] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0581] (2) C1-C6 alkyl, C1-C6 alkoxy,

[0582] (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,

[0583] (4) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl,

[0584] (5) N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino;

[0585] 3) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkoxy; R x1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0586] 4) Wherein: Z1, Z2, and Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x2 , R y are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0587] 5) Wherein: Z2 and Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0588] 6) Wherein: Z1, Z2, and Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0589] 7) 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl.

[0590] In some embodiments, R 1 is selected from:

[0591] 1) Z1, Z2, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, and Z5 are not simultaneously hydrogen:

[0592] Hydrogen, methyl, methoxy, ethoxy, isopropoxy, N-methylpiperazine-1-carbonyl, 4-hydroxypiperidinyl, N-methyl-4-piperidinyl, N-methylpiperazinyl, (N-methylpiperazine-1-)piperidinyl, 4-(pyrrolidin-1-)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 2-(N,N-dimethylamino)acetamido;

[0593] 2) Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen:

[0594] Hydrogen, methyl, methoxy, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-N,N-dimethylaminopiperidinyl, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-methylpiperazinyl;

[0595] 3) Wherein: Z1, Z2, and Z5 are each independently selected from hydrogen, fluorine, methoxy; Rx1 is methyl;

[0596] 4) wherein: Z1, Z2, Z5 are hydrogen; R x2 , R y is methyl;

[0597] 5) wherein: Z2, Z5 are hydrogen; R x3 is isopropyl;

[0598] 6) wherein: Z1, Z2, Z5 are hydrogen; R x4 is hydrogen;

[0599] 7) 1-methyl-3-pyrazolyl.

[0600] In some embodiments, R 3 is selected from:

[0601] 1)

[0602] wherein, W1, W4 are each independently selected from the following and are not both hydrogen:

[0603] (1) hydrogen,

[0604] (2) fluorine, chlorine, bromine, iodine, nitro, cyano,

[0605] (3) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0606] (4) wherein, R a , R b are each independently selected from:

[0607] hydrogen, C1-C6 alkyl,

[0608] or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl,

[0609] (5) wherein, R a , R b are as defined in (4),

[0610] (6) hydroxycarbonyl, C1-C6 alkoxycarbonyl,

[0611] (7)

[0612] L is selected from a direct bond,

[0613] Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0614] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0615] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0616] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-methylene, 4-aminopiperidin-1-methylene, 4-(N,N-dimethylamino)-1-piperidinomethylene, 4-(N,N-diethylamino)-1-piperidinomethylene, 4-(N,N-dipropylamino)-1-piperidinomethylene, 4-(N,N-diisopropylamino)-1-piperidinomethylene, 4-hydroxypiperidin-1-methylene, 4-methoxypiperidin-1-methylene, 4-ethoxypiperidin-1-methylene, 4-propoxypiperidin-1-methylene, 4-isopropoxypiperidin-1-methylene, morpholin-4-methylene, thiomorpholinyl-4-methylene, 2,6-dimethylmorpholinyl-4-methylene, pyrrolidin-1-methylene, 3-aminopyrrolidin-1-methylene, 3-(N,N-dimethylamino)-1-pyrrolidinomethylene, 3-(N,N-diethylamino)-1-pyrrolidinomethylene, 3-(N,N-dipropylamino)-1-pyrrolidinomethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinomethylene, azetidin-1-methylene,

[0617] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0618] (8) wherein, L, Y2, Y3, Y4, Y5 are as defined in (7),

[0619] (9) wherein, L, Y1, Y3, Y4, Y5 are as defined in (7),

[0620] (10) Among them, L, Y1, Y2, Y4, Y5 are the same as defined in (7);

[0621] 2) Among them, W1 and W4 are the same as defined in 1), and can be hydrogen at the same time;

[0622] 3) Among them, W1 and W4 are the same as defined in 1), and can be hydrogen at the same time;

[0623] 4) Among them, W1 and W5 are the same as the definition of W1 in 1), and can be hydrogen at the same time.

[0624] In some embodiments, R 3 is selected from:

[0625] 1)

[0626] Among them, W1 and W4 are each independently selected from the following and are not hydrogen at the same time:

[0627] (1) hydrogen,

[0628] (2) fluorine, chlorine, bromine, iodine, nitro, cyano,

[0629] (3) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0630] (4) Among them, R a , R b are each independently selected from:

[0631] hydrogen, C1-C6 alkyl,

[0632] or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0633] (5) Among them, R a , R b are the same as defined in (4);

[0634] (6) hydroxycarbonyl, C1-C6 alkoxycarbonyl;

[0635] (7)

[0636] Among them, L is selected from a direct bond,

[0637] Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0638] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0639] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0640] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-ylmethylene, 4-aminopiperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-(N,N-diethylamino)-1-piperidinylmethylene, 4-(N,N-dipropylamino)-1-piperidinylmethylene, 4-(N,N-diisopropylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, 4-methoxypiperidin-1-ylmethylene, 4-ethoxypiperidin-1-ylmethylene, 4-propoxypiperidin-1-ylmethylene, 4-isopropoxypiperidin-1-ylmethylene, morpholin-4-ylmethylene, thiomorpholin-4-ylmethylene, 2,6-dimethylmorpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, 3-aminopyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene, 3-(N,N-diethylamino)-1-pyrrolidinylmethylene, 3-(N,N-dipropylamino)-1-pyrrolidinylmethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinylmethylene, azetidin-1-ylmethylene,

[0641] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0642] (8) wherein L, Y2, Y3, Y4, and Y5 are as defined in (7),

[0643] (9) wherein L, Y1, Y3, Y4, and Y5 are as defined in (7),

[0644] (10) Among them, L, Y1, Y2, Y4, Y5 are the same as defined in (7);

[0645] 2) Among them, W1 and W5 are the same as the definition of W1 in 1), and can be hydrogen at the same time.

[0646] In some embodiments, R 3 is selected from:

[0647] 1)

[0648] Among them, W1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy,

[0649] W4 is selected from:

[0650] (1) Fluorine, chlorine, bromine, iodine, nitro, cyano,

[0651] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy,

[0652] (3) Among them, R a , R b are each independently selected from:

[0653] Hydrogen, C1-C6 alkyl,

[0654] Or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0655] (4) Among them, R a , R b are the same as defined in (3);

[0656] (5) Hydroxycarbonyl, C1-C6 alkoxycarbonyl;

[0657] (6)

[0658] Among them, L is selected from a direct bond,

[0659] Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0660] (a) Hydrogen, fluorine, chlorine, bromine, iodine, nitro group, cyano group,

[0661] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0662] (c) Aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-methylene, 4-aminopiperidin-1-methylene, 4-(N,N-dimethylamino)-1-piperidinomethylene, 4-(N,N-diethylamino)-1-piperidinomethylene, 4-(N,N-dipropylamino)-1-piperidinomethylene, 4-(N,N-diisopropylamino)-1-piperidinomethylene, 4-hydroxypiperidin-1-methylene, 4-methoxypiperidin-1-methylene, 4-ethoxypiperidin-1-methylene, 4-propoxypiperidin-1-methylene, 4-isopropoxypiperidin-1-methylene, morpholin-4-methylene, thiomorpholinyl-4-methylene, 2,6-dimethylmorpholinyl-4-methylene, pyrrolidin-1-methylene, 3-aminopyrrolidin-1-methylene, 3-(N,N-dimethylamino)-1-pyrrolidinomethylene, 3-(N,N-diethylamino)-1-pyrrolidinomethylene, 3-(N,N-dipropylamino)-1-pyrrolidinomethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinomethylene, azetidin-1-methylene,

[0663] (d) Imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0664] (7) Wherein, L, Y2, Y3, Y4, Y5 are the same as defined in (6),

[0665] (8) Wherein, L, Y1, Y3, Y4, Y5 are the same as defined in (6),

[0666] (9) Wherein, L, Y1, Y2, Y4, Y5 are the same as defined in (6);

[0667] 2) Among them, W1 and W5 have the same definition as W1 in 1) and can both be hydrogen at the same time.

[0668] In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, hydrogencarbonate and carbonate, sulfate or phosphate, and the organic acid salt is 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.

[0669] In the sixth aspect of the present invention, the present invention provides the following compounds:

[0670]

[0671] or stereoisomers of the compound, its prodrugs, its pharmaceutically acceptable salts or its pharmaceutically acceptable solvates,

[0672] wherein:

[0673] R 1 is selected from:

[0674] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not all hydrogen at the same time:

[0675] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0676] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0677] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinoethoxy, 2-thiomorpholinoethoxy, 2-piperidinoethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinopropoxy, 3-thiomorpholinopropoxy, 3-piperidinopropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, mono-halogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, hetero-dihalogen-substituted phenylmethoxy,

[0678] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0679] (5) morpholinyl, 2,6-dimethylmorpholinyl, thiomorpholinyl,

[0680] (6) pyrrolidinyl, 3-(N,N-dimethylamino)pyrrolidinyl, 3-(N,N-diethylamino)pyrrolidinyl,

[0681] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0682] (8) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazin-1-)piperidyl, 4-(N-ethylpiperazin-1-)piperidyl, 4-(N-isopropylpiperazin-1-)piperidyl, 4-(N-acetylpiperazin-1-)piperidyl, 4-(N-tert-butoxycarbonylpiperazin-1-)piperidyl, 4-(N-methylsulfonylpiperazin-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidyl, 4-(pyrrolidin-1-)piperidyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidyl,

[0683] (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-methylsulfonyl-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,

[0684] (10) amino, N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino, 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-4-amino, N-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, propanesulfonamido, isopropanesulfonamido, cyclopropanesulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0685] (11) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, pyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene,

[0686] (12) carbamoyl, methylaminocarbonyl, dimethylaminocarbonyl, ethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, cyclohexylaminocarbonyl,

[0687] Pyrrolidine-1-carbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-yl-carbonyl, 3-(N,N-diethylamino)pyrrolidin-1-yl-carbonyl,

[0688] Morpholine-4-carbonyl, Thiomorpholine-4-carbonyl, 2,6-dimethylmorpholine-4-carbonyl,

[0689] Piperidine-1-carbonyl, 4-Hydroxypiperidine-1-carbonyl, 4-(N,N-dimethylamino)piperidin-1-yl-carbonyl, 4-(N,N-diethylamino)piperidin-1-yl-carbonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-yl-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-yl-carbonyl,

[0690] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl,

[0691] (13) Hydroxycarbonyl, Methoxycarbonyl, Ethoxycarbonyl, Propoxycarbonyl, Isopropoxycarbonyl, n-Butoxycarbonyl, Isobutoxycarbonyl, tert-Butoxycarbonyl,

[0692] (14) Hydroxy-sulfonyl, Amino-sulfonyl, Methylamino-sulfonyl, Ethylamino-sulfonyl, Propylamino-sulfonyl, Isopropylamino-sulfonyl, Cyclopropylamino-sulfonyl, Cyclobutyl-sulfonyl, Cyclopentylamino-sulfonyl, Cyclohexylamino-sulfonyl,

[0693] Pyrrolidine-1-sulfonyl, 3-(N,N-dimethylamino)pyrrolidin-1-yl-sulfonyl, 3-(N,N-diethylamino)pyrrolidin-1-yl-sulfonyl,

[0694] Morpholine-4-sulfonyl, Thiomorpholine-4-sulfonyl, 2 6-dimethylmorpholine-4-sulfonyl,

[0695] Piperidine-1-sulfonyl, 4-Hydroxypiperidine-1-sulfonyl, 4-(N,N-dimethylamino)piperidin-1-yl-sulfonyl, 4-(N,N-diethylamino)piperidin-1-yl-sulfonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-yl-sulfonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-yl-sulfonyl,

[0696] 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-piperidyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-sulfonyl,

[0697] (15) carbamoylamino, methylcarbamoylamino, ethylcarbamoylamino, propylcarbamoylamino, isopropylcarbamoylamino, cyclopropylcarbamoylamino, cyclobutylcarbamoylamino, cyclopentylcarbamoylamino, piperidin-1-ylformamido, 4-hydroxypiperidin-1-ylformamido, 4-N,N-dimethylpiperidin-1-ylformamido, 4-N,N-diethylpiperidin-1-ylformamido, pyrrolidin-1-ylformamido, 3-N,N-dimethylpyrrolidin-1-ylformamido, 3-N,N-diethylpyrrolidin-1-ylformamido, N-methylpiperazin-1-ylformamido, N-ethylpiperazin-1-ylformamido, N-acetylpiperazin-1-ylformamido, N-tert-butoxycarbonylpiperazin-1-ylformamido, N-(2-hydroxyethyl)piperazin-1-ylformamido, N-(2-cyanoethyl)piperazin-1-ylformamido, N-(2-N,N-dimethylaminoethyl)piperazin-1-ylformamido, N-(2-N,N-diethylaminoethyl)piperazin-1-ylformamido, N-(3-hydroxypropyl)piperazin-1-ylformamido, N-(3-N,N-dimethylpropyl)piperazin-1-ylformamido, N-(3-N,N-diethylpropyl)piperazin-1-ylformamido, morpholin-1-ylformamido, 3,5-dimethylmorpholin-1-ylformamido, 4-(pyrrolidinyl)piperidin-1-ylformamido, 4-(N-methyl-1-piperazinyl)piperidin-1-ylformamido, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylformamido, 4-(N-acetyl-1-piperazinyl)piperidin-1-ylformamido, N-(N-methyl-4-piperidyl)piperazin-1-ylformamido,

[0698] (16) Z3 and Z4 can form an oxygen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above substituents same as Z1,

[0699] (17) Z3 and Z4 can form a nitrogen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above substituents same as Z1;

[0700] 2) wherein Z2, Z3, Z4, Z5 are the same as defined in 1);

[0701] 3) wherein Z1, Z3, Z4, and Z5 are the same as defined in 1);

[0702] 4) wherein Z1, Z2, Z4, and Z5 are the same as defined in 1);

[0703] 5) wherein Z1, Z3, and Z5 are the same as defined in 1);

[0704] 6) 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-piperidyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-piperidyl)-4-pyrazolyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl;

[0705] R 2 is selected from:

[0706] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino;

[0707] W1, W2, W3, and W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0708] R is selected from:

[0709] 1) hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0710] 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0711] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0712] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0713] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-ylmethylene, 4-aminopiperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-(N,N-diethylamino)-1-piperidinylmethylene, 4-(N,N-dipropylamino)-1-piperidinylmethylene, 4-(N,N-diisopropylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, 4-methoxypiperidin-1-ylmethylene, 4-ethoxypiperidin-1-ylmethylene, 4-propoxypiperidin-1-ylmethylene, 4-isopropoxypiperidin-1-ylmethylene, morpholin-4-ylmethylene, thiomorpholin-4-ylmethylene, 2,6-dimethylmorpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, 3-aminopyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene, 3-(N,N-diethylamino)-1-pyrrolidinylmethylene, 3-(N,N-dipropylamino)-1-pyrrolidinylmethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinylmethylene, azetidin-1-ylmethylene,

[0714] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl,

[0715] 3) wherein Y2, Y3, Y4, Y5 are the same as defined in 2),

[0716] 4) wherein Y1, Y3, Y4, Y5 are the same as defined in 2),

[0717] 5) wherein Y1, Y2, Y4, Y5 are the same as defined in 2).

[0718] In some embodiments, R 1 is selected from:

[0719] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0720] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0721] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0722] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0723] (4) piperidyl, 4-N,N-dimethylaminopiperidyl, 4-N,N-diethylaminopiperidyl, 4-N,N-diisopropylaminopiperidyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-ethoxypiperidyl, 4-(N-methylpiperazin-1-)piperidyl, 4-(N-ethylpiperazin-1-)piperidyl, 4-(N-isopropylpiperazin-1-)piperidyl, 4-(N-acetylpiperazin-1-)piperidyl, 4-(N-tert-butoxycarbonylpiperazin-1-)piperidyl, 4-(N-methylsulfonylpiperazin-1-)piperidyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidyl, 4-(pyrrolidin-1-)piperidyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidyl,

[0724] (5) 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,

[0725] (6) 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-4-amino, N-n-propylpiperidin-4-amino, N-isopropylpiperidin-4-amino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0726] (7) carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0727] pyrrolidine-1-carbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-carbonyl, 3-(N,N-diethylamino)pyrrolidin-1-carbonyl,

[0728] morpholine-4-carbonyl, thiomorpholine-4-carbonyl, 2,6-dimethylmorpholine-4-carbonyl,

[0729] Piperidin-1-ylcarbonyl, 4-hydroxypiperidin-1-ylcarbonyl, 4-(N,N-dimethylamino)piperidin-1-ylcarbonyl, 4-(N,N-diethylamino)piperidin-1-ylcarbonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonyl,

[0730] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl;

[0731] 2) wherein Z1, Z3, Z4, Z5 are the same as defined in 1);

[0732] 3) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen simultaneously; R x1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0733] 4) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen simultaneously; R x2 and R y each independently is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0734] 5) wherein: Z2, Z5 are the same as defined in 1) and can be hydrogen simultaneously; R x3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0735] 6) wherein: Z1, Z2, Z5 are the same as defined in 1) and can be hydrogen simultaneously; R x4Selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0736] 7) 1-methyl-3-pyrrolyl, 1-ethyl-3-pyrrolyl, 1-isopropyl-3-pyrrolyl, 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl, 1-methyl-4-imidazolyl, 3-methyl-5-isoxazolyl.

[0737] In some embodiments, R 1 is selected from:

[0738] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0739] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0740] (2) C1-C6 alkyl, C1-C6 alkoxy,

[0741] (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,

[0742] (4) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0743] (5) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-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,

[0744] (6) acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido,

[0745] (7) 4-(N-methyl-1-piperazinyl)piperidin-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-carbonyl,

[0746] 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;

[0747] 2) Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0748] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0749] (2) C1-C6 alkyl, C1-C6 alkoxy,

[0750] (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,

[0751] (4) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl,

[0752] (5) N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino;

[0753] 3) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkoxy; R x1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0754] 4) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x2 and R y are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0755] 5) Wherein: Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x3 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0756] 6) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x4Selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl;

[0757] 7) 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl.

[0758] In some embodiments, R 1 is selected from:

[0759] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0760] Hydrogen, methyl, methoxy, ethoxy, isopropoxy, N-methylpiperazine-1-carbonyl, 4-hydroxypiperidyl, N-methyl-4-piperidyl, N-methylpiperazinyl, (N-methylpiperazine-1-)piperidyl, 4-(pyrrolidin-1-)piperidyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 2-(N,N-dimethylamino)acetamido,

[0761] Preferably, Z1, Z2, Z5 are each independently selected from hydrogen, methoxy, ethoxy, isopropoxy, and one of Z3, Z4 is selected from the following and the other is selected from hydrogen, methyl:

[0762] N-methylpiperazine-1-carbonyl, 4-hydroxypiperidyl, N-methyl-4-piperidyl, N-methylpiperazinyl, (N-methylpiperazine-1-)piperidyl, 4-(pyrrolidin-1-)piperidyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 2-(N,N-dimethylamino)acetamido;

[0763] 2) Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0764] Hydrogen, methyl, methoxy, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-N,N-dimethylaminopiperidyl, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-methylpiperazinyl,

[0765] Preferably, Z1, Z5 are each independently selected from hydrogen, methoxy, and one of Z3, Z4 is selected from the following and the other is hydrogen:

[0766] Methyl, 4-hydroxypiperidyl, 4-methoxypiperidyl, 4-N,N-dimethylaminopiperidyl, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-methylpiperazinyl;

[0767] 3) wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, methoxy; R x1 is methyl;

[0768] 4) wherein: Z1, Z2, Z5 are hydrogen; R x2 , R y is methyl;

[0769] 5) wherein: Z2, Z5 are hydrogen; R x3 is isopropyl;

[0770] 6) wherein: Z1, Z2, Z5 are hydrogen; R x4 is hydrogen;

[0771] 7) 1-methyl-3-pyrazolyl.

[0772] In some embodiments, R 2 is selected from hydrogen, methyl, isopropyl.

[0773] In some embodiments, W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

[0774] In some embodiments, W1, W2, W3, W5 are each independently selected from hydrogen, methyl.

[0775] In some embodiments, W2, W3, W5 are hydrogen and W1 is methyl.

[0776] In some embodiments, R is selected from:

[0777] 1) hydrogen, C1-C6 alkyl,

[0778] 2) wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0779] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0780] (b) C1-C6 alkyl, C1-C6 fluoroalkyl,

[0781] (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene, N-cyclopropyl-1-piperazinylmethylene, N-(2-hydroxyethyl)-1-piperazinylmethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, N-(2-cyanoethyl)-1-piperazinylmethylene, morpholin-4-ylmethylene, thiomorpholin-4-ylmethylene, 2,6-dimethylmorpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, 3-amino-1-pyrrolidinylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene, 3-(N,N-diethylamino)-1-pyrrolidinylmethylene, 3-(N,N-dipropylamino)-1-pyrrolidinylmethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinylmethylene, azetidin-1-ylmethylene,

[0782] 3) wherein Y2, Y3, Y4, and Y5 are as defined in 2).

[0783] In some embodiments, R is selected from:

[0784] 1) hydrogen,

[0785] 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0786] (a) hydrogen, fluorine,

[0787] (b) C1-C6 alkyl, C1-C6 fluoroalkyl,

[0788] (c) N-methyl-1-piperazinylmethylene, morpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, azetidin-1-ylmethylene,

[0789] 3) wherein Y2, Y3, Y4, and Y5 are each independently selected from:

[0790] (a) hydrogen,

[0791] (b) C1-C6 alkyl, C1-C6 fluoroalkyl.

[0792] In some embodiments, R is selected from:

[0793] 1) hydrogen,

[0794] 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from:

[0795] hydrogen, fluorine, methyl, trifluoromethyl, N-methyl-1-piperazinylmethylene, morpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, azetidin-1-ylmethylene,

[0796] 3) wherein Y2, Y3, Y4, Y5 are each independently selected from:

[0797] hydrogen, trifluoromethyl.

[0798] In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, hydrogencarbonate and carbonate, sulfate or phosphate, and the organic acid salt is 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.

[0799] In a seventh aspect of the present invention, the present invention provides the following compounds:

[0800]

[0801] or a stereoisomer, a prodrug, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate of the compound,

[0802] wherein:

[0803] R 1 is selected from:

[0804] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0805] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0806] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0807] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinoethoxy, 2-thiomorpholinoethoxy, 2-piperidinoethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinopropoxy, 3-thiomorpholinopropoxy, 3-piperidinopropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, monohalogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, hetero-dihalogen-substituted phenylmethoxy,

[0808] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0809] (5) morpholino, 2,6-dimethylmorpholino, thiomorpholino,

[0810] (6) pyrrolidinyl, 3-(N,N-dimethylamino)pyrrolidinyl, 3-(N,N-diethylamino)pyrrolidinyl,

[0811] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0812] (8) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methylsulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0813] (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-methylsulfonyl-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,

[0814] (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-ylamino, N-ethylpiperidin-4-ylamino, N-n-propylpiperidin-4-ylamino, N-isopropylpiperidin-4-ylamino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0815] (11) Aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, pyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene,

[0816] (12) Carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0817] Pyrrolidin-1-ylcarbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylcarbonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylcarbonyl,

[0818] Morpholin-4-ylcarbonyl, thiomorpholin-4-ylcarbonyl, 2,6-dimethylmorpholin-4-ylcarbonyl,

[0819] Piperidin-1-ylcarbonyl, 4-hydroxypiperidin-1-ylcarbonyl, 4-(N,N-dimethylamino)piperidin-1-ylcarbonyl, 4-(N,N-diethylamino)piperidin-1-ylcarbonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonyl,

[0820] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl,

[0821] (13)hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl,

[0822] (14)hydroxy-sulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylsulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0823] pyrrolidine-1-sulfonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylsulfonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylsulfonyl,

[0824] morpholin-4-ylsulfonyl, thiomorpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl,

[0825] piperidin-1-ylsulfonyl, 4-hydroxypiperidine-1-sulfonyl, 4-(N,N-dimethylamino)piperidin-1-ylsulfonyl, 4-(N,N-diethylamino)piperidin-1-ylsulfonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylsulfonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylsulfonyl,

[0826] 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-piperidyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-sulfonyl,

[0827] (15) Carbamoylamino, methylcarbamoylamino, ethylcarbamoylamino, propylcarbamoylamino, isopropylcarbamoylamino, cyclopropylcarbamoylamino, cyclobutylcarbamoylamino, cyclopentylcarbamoylamino, piperidin-1-ylcarbonylamino, 4-hydroxypiperidin-1-ylcarbonylamino, 4-N,N-dimethylpiperidin-1-ylcarbonylamino, 4-N,N-diethylpiperidin-1-ylcarbonylamino, pyrrolidin-1-ylcarbonylamino, 3-N,N-dimethylpyrrolidin-1-ylcarbonylamino, 3-N,N-diethylpyrrolidin-1-ylcarbonylamino, N-methylpiperazin-1-ylcarbonylamino, N-ethylpiperazin-1-ylcarbonylamino, N-acetylpiperazin-1-ylcarbonylamino, N-tert-butoxycarbonylpiperazin-1-ylcarbonylamino, N-(2-hydroxyethyl)piperazin-1-ylcarbonylamino, N-(2-cyanoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-dimethylaminoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-diethylaminoethyl)piperazin-1-ylcarbonylamino, N-(3-hydroxypropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-dimethylpropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-diethylpropyl)piperazin-1-ylcarbonylamino, morpholin-1-ylcarbonylamino, 3,5-dimethylmorpholin-1-ylcarbonylamino, 4-(pyrrolidin-1-yl)piperidin-1-ylcarbonylamino, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-acetyl-1-piperazinyl)piperidin-1-ylcarbonylamino, N-(N-methyl-4-piperidyl)piperazin-1-ylcarbonylamino,

[0828] (16) Z3 and Z4 can form an oxygen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above substituents the same as Z1,

[0829] (17) Z3 and Z4 can form a nitrogen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above substituents the same as Z1;

[0830] 2) wherein Z2, Z3, Z4, Z5 are the same as defined in 1);

[0831] 3) wherein Z1, Z3, Z4, Z5 are the same as defined in 1);

[0832] 4) wherein Z1, Z2, Z4, Z5 are the same as defined in 1);

[0833] 5) wherein Z1, Z3, Z5 are the same as defined in 1);

[0834] R 2 Selected from:

[0835] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino;

[0836] W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl;

[0837] R' is selected from:

[0838] 1) wherein, R a , R b are each independently selected from:

[0839] hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0840] or R a , R b and N form a substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0841] 2) hydroxyl, C1-C6 alkoxy;

[0842] 3) wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0843] (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0844] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0845] (c) aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, N-methyl-1-piperazinomethylene, N-ethyl-1-piperazinomethylene, N-propyl-1-piperazinomethylene, N-isopropyl-1-piperazinomethylene, N-cyclopropyl-1-piperazinomethylene, N-(2-hydroxyethyl)-1-piperazinomethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinomethylene, N-(2-cyanoethyl)-1-piperazinomethylene, piperidin-1-ylmethylene, 4-aminopiperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-(N,N-diethylamino)-1-piperidinylmethylene, 4-(N,N-dipropylamino)-1-piperidinylmethylene, 4-(N,N-diisopropylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, 4-methoxypiperidin-1-ylmethylene, 4-ethoxypiperidin-1-ylmethylene, 4-propoxypiperidin-1-ylmethylene, 4-isopropoxypiperidin-1-ylmethylene, morpholin-4-ylmethylene, thiomorpholin-4-ylmethylene, 2,6-dimethylmorpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, 3-aminopyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene, 3-(N,N-diethylamino)-1-pyrrolidinylmethylene, 3-(N,N-dipropylamino)-1-pyrrolidinylmethylene, 3-(N,N-diisopropylamino)-1-pyrrolidinylmethylene, azetidin-1-ylmethylene,

[0846] (d) imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl.

[0847] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0848] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0849] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0850] (3) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methylsulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0851] (4) 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-methylsulfonyl-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.

[0852] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0853] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0854] (2) C1-C6 alkyl,

[0855] (3) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl.

[0856] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0857] Hydrogen, methyl, 4-N,N-dimethylaminopiperidinyl.

[0858] In some embodiments, R 2 is methyl.

[0859] In some embodiments, W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

[0860] In some embodiments, W1, W2, W3, W5 are each independently selected from hydrogen, methyl.

[0861] In some embodiments, W2, W3, W5 are hydrogen, and W1 is hydrogen or methyl.

[0862] In some embodiments, R' is selected from:

[0863] 1) Wherein, R a , R b are each independently selected from:

[0864] Hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0865] Or R a , R b and N form a substituted or unsubstituted piperazine ring, and the substituents are halogen, C1-C6 alkyl or C3-C6 cycloalkyl;

[0866] 2) Hydroxy, C1-C6 alkoxy;

[0867] 3) Wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0868] (a) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0869] (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0870] (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene, N-cyclopropyl-1-piperazinylmethylene, N-(2-hydroxyethyl)-1-piperazinylmethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, N-(2-cyanoethyl)-1-piperazinylmethylene,

[0871] (d) Imidazolyl, 4-methylimidazolyl, pyrrolyl, pyrazolyl, 3-methylpyrazolyl, 4-methylpyrazolyl, 3-methyl-5-isoxazolyl.

[0872] In some embodiments, R’ is selected from:

[0873] 1) Wherein, R a , R b are each independently selected from:

[0874] Hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl,

[0875] Or R a , R b and N form a substituted or unsubstituted piperazine ring, and the substituent is C1-C6 alkyl;

[0876] 2) Hydroxy, C1-C6 alkoxy;

[0877] 3) Wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0878] (a) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0879] (b) C1-C6 fluoroalkyl,

[0880] (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene,

[0881] (d) Imidazolyl, 4-methylimidazolyl.

[0882] In some embodiments, R’ is selected from:

[0883] 1) Wherein, R a , R b are each independently selected from hydrogen, methyl, ethyl, cyclopropyl,

[0884] Or R a , R b and N form

[0885] 2) Hydroxy, methoxy, ethoxy;

[0886] 3) wherein Y1, Y2, Y3, Y4, Y5 are each independently selected from:

[0887] hydrogen, trifluoromethyl, N-methyl-1-piperazinylmethylene, 4-methylimidazolyl.

[0888] In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate and carbonate, sulfate or phosphate, and the organic acid salt is formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, α-glycerophosphate, alkyl sulfonate or aryl sulfonate; preferably, the alkyl sulfonate is methyl sulfonate or ethyl sulfonate; the aryl sulfonate is benzenesulfonate or p-toluenesulfonate.

[0889] In the eighth aspect of the present invention, the present invention provides the following compounds:

[0890]

[0891] or a stereoisomer of the compound, a prodrug thereof, a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof,

[0892] wherein:

[0893] R 1 is selected from:

[0894] 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen:

[0895] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0896] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0897] (3) 2-N,N-dimethylaminoethoxy, 3-N,N-dimethylaminopropoxy, 2-(N-methylpiperazinyl)ethoxy, 2-(N-acetylpiperazinyl)ethoxy, 2-morpholinoethoxy, 2-thiomorpholinoethoxy, 2-piperidinoethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(N-methylpiperazinyl)propoxy, 3-(N-acetylpiperazinyl)propoxy, 3-morpholinopropoxy, 3-thiomorpholinopropoxy, 3-piperidinopropoxy, 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy, phenylmethoxy, mono-halogen-substituted phenylmethoxy, gem-dihalogen-substituted phenylmethoxy, hetero-dihalogen-substituted phenylmethoxy,

[0898] (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-piperidyl)piperazinyl, N-(N-ethyl-4-piperidyl)piperazinyl, N-tert-butoxycarbonylpiperazinyl, N-acetylpiperazinyl, N-propionylpiperazinyl, N-isobutyrylpiperazinyl, N-cyclopropylcarbonylpiperazinyl, N-methylsulfonylpiperazinyl, N-ethylsulfonylpiperazinyl, N-n-propylsulfonylpiperazinyl, N-isopropylsulfonylpiperazinyl, N-cyclopropylsulfonylpiperazinyl, 2-oxo-piperazin-4-yl,

[0899] (5) morpholino, 2,6-dimethylmorpholino, thiomorpholino,

[0900] (6) pyrrolidinyl, 3-(N,N-dimethylamino)pyrrolidinyl, 3-(N,N-diethylamino)pyrrolidinyl,

[0901] (7) imidazolyl, 4-methyl-1-imidazolyl,

[0902] (8) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, 4-(N-acetylpiperazin-1-yl)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-yl)piperidinyl, 4-(N-methanesulfonylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-diethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-yl)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-yl)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-yl)piperidinyl,

[0903] (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,

[0904] (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-ylamino, N-ethylpiperidin-4-ylamino, N-n-propylpiperidin-4-ylamino, N-isopropylpiperidin-4-ylamino, acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, methanesulfonamido, ethanesulfonamido, n-propylsulfonamido, isopropylsulfonamido, cyclopropylsulfonamido, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino,

[0905] (11) Aminomethylene, N,N-dimethylaminomethylene, N,N-diethylaminomethylene, 4-methyl-1-piperazinylmethylene, 4-ethyl-1-piperazinylmethylene, 4-propyl-1-piperazinylmethylene, 4-isopropyl-1-piperazinylmethylene, 4-(2-hydroxyethyl)-1-piperazinylmethylene, 4-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, piperidin-1-ylmethylene, 4-(N,N-dimethylamino)-1-piperidinylmethylene, 4-hydroxypiperidin-1-ylmethylene, pyrrolidin-1-ylmethylene, 3-(N,N-dimethylamino)-1-pyrrolidinylmethylene,

[0906] (12) Carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, cyclopropylcarbamoyl, cyclobutylcarbamoyl, cyclopentylcarbamoyl, cyclohexylcarbamoyl,

[0907] Pyrrolidin-1-ylcarbonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylcarbonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylcarbonyl,

[0908] Morpholin-4-ylcarbonyl, thiomorpholin-4-ylcarbonyl, 2,6-dimethylmorpholin-4-ylcarbonyl,

[0909] Piperidin-1-ylcarbonyl, 4-hydroxypiperidin-1-ylcarbonyl, 4-(N,N-dimethylamino)piperidin-1-ylcarbonyl, 4-(N,N-diethylamino)piperidin-1-ylcarbonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonyl,

[0910] 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-piperidyl)piperazine-1-carbonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-carbonyl,

[0911] (13)hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl,

[0912] (14)hydroxy sulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylsulfonyl, cyclopentylaminosulfonyl, cyclohexylaminosulfonyl,

[0913] pyrrolidine-1-sulfonyl, 3-(N,N-dimethylamino)pyrrolidin-1-ylsulfonyl, 3-(N,N-diethylamino)pyrrolidin-1-ylsulfonyl,

[0914] morpholin-4-ylsulfonyl, thiomorpholin-4-ylsulfonyl, 2,6-dimethylmorpholin-4-ylsulfonyl,

[0915] piperidin-1-ylsulfonyl, 4-hydroxypiperidine-1-sulfonyl, 4-(N,N-dimethylamino)piperidin-1-ylsulfonyl, 4-(N,N-diethylamino)piperidin-1-ylsulfonyl, 4-(N-methyl-1-piperazinyl)piperidin-1-ylsulfonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylsulfonyl,

[0916] 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-piperidyl)piperazine-1-sulfonyl, 4-(N-ethyl-4-piperidyl)piperazine-1-sulfonyl,

[0917] (15) Carbamoylamino, methylcarbamoylamino, ethylcarbamoylamino, propylcarbamoylamino, isopropylcarbamoylamino, cyclopropylcarbamoylamino, cyclobutylcarbamoylamino, cyclopentylcarbamoylamino, piperidin-1-ylcarbonylamino, 4-hydroxypiperidin-1-ylcarbonylamino, 4-N,N-dimethylpiperidin-1-ylcarbonylamino, 4-N,N-diethylpiperidin-1-ylcarbonylamino, pyrrolidin-1-ylcarbonylamino, 3-N,N-dimethylpyrrolidin-1-ylcarbonylamino, 3-N,N-diethylpyrrolidin-1-ylcarbonylamino, N-methylpiperazin-1-ylcarbonylamino, N-ethylpiperazin-1-ylcarbonylamino, N-acetylpiperazin-1-ylcarbonylamino, N-tert-butoxycarbonylpiperazin-1-ylcarbonylamino, N-(2-hydroxyethyl)piperazin-1-ylcarbonylamino, N-(2-cyanoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-dimethylaminoethyl)piperazin-1-ylcarbonylamino, N-(2-N,N-diethylaminoethyl)piperazin-1-ylcarbonylamino, N-(3-hydroxypropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-dimethylpropyl)piperazin-1-ylcarbonylamino, N-(3-N,N-diethylpropyl)piperazin-1-ylcarbonylamino, morpholin-1-ylcarbonylamino, 3,5-dimethylmorpholin-1-ylcarbonylamino, 4-(pyrrolidin-1-yl)piperidin-1-ylcarbonylamino, 4-(N-methyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-ethyl-1-piperazinyl)piperidin-1-ylcarbonylamino, 4-(N-acetyl-1-piperazinyl)piperidin-1-ylcarbonylamino, N-(N-methyl-4-piperidyl)piperazin-1-ylcarbonylamino,

[0918] (16) Z3 and Z4 can form an oxygen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above substituents the same as Z1,

[0919] (17) Z3 and Z4 can form a nitrogen-containing substituted or unsubstituted five- to seven-membered ring; the substituents can be selected from the above substituents the same as Z1;

[0920] 2) wherein Z2, Z3, Z4, Z5 are the same as defined in 1);

[0921] 3) wherein Z1, Z3, Z4, Z5 are the same as defined in 1);

[0922] 4) wherein Z1, Z2, Z4, Z5 are the same as defined in 1);

[0923] 5) wherein Z1, Z3, Z5 are the same as defined in 1);

[0924] R 2 Selected from:

[0925] hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino;

[0926] W1, W3, W4, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl.

[0927] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0928] (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0929] (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl,

[0930] (3) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-)piperidinyl, 4-(N-ethylpiperazin-1-)piperidinyl, 4-(N-isopropylpiperazin-1-)piperidinyl, 4-(N-acetylpiperazin-1-)piperidinyl, 4-(N-tert-butoxycarbonylpiperazin-1-)piperidinyl, 4-(N-methylsulfonylpiperazin-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidinyl, 4-(pyrrolidin-1-)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidinyl,

[0931] (4)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-methylsulfonyl-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.

[0932] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen:

[0933] (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano,

[0934] (2) C1-C6 alkyl,

[0935] (3) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl.

[0936] In some embodiments, R 1 is Z1, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z3, Z4, Z5 are not simultaneously hydrogen: hydrogen, 4-N,N-dimethylaminopiperidinyl.

[0937] In some embodiments, R 2 is isopropyl.

[0938] In some embodiments, W1, W3, W4, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

[0939] In some embodiments, W1, W3, W4, W5 are each independently selected from hydrogen, methyl.

[0940] In some embodiments, W1, W3, W4 are hydrogen, and W5 is hydrogen or methyl.

[0941] In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, hydrogencarbonate and carbonate, sulfate or phosphate, and the organic acid salt is 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.

[0942] Unless otherwise specified, the above groups and substituents have the ordinary meanings in the field of medicinal chemistry.

[0943] 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.

[0944] 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, etc.

[0945] It should be noted that "oxygen-containing alkyl" refers to a group formed by substituting an alkyl skeleton with one or more alkoxy groups. For example, methoxyethyl, methoxyethoxymethyl, etc.

[0946] For example, C1-C6 oxygen-containing alkyl refers to a group formed by substituting a C1-C6 alkyl skeleton with one or more C1-C6 alkoxy groups, such as methoxyethyl, methoxyethoxymethyl, etc. Similarly, C1-C3 oxygen-containing alkyl refers to a group formed by substituting a C1-C3 alkyl skeleton with one or more C1-C6 alkoxy groups.

[0947] The term "C3-C8 cycloalkyl" refers to a hydrocarbon of a 3- to 8-membered monocyclic system with a saturated ring. C3-C8 cycloalkyl can be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0948] The term "C3-C6 cycloalkyl" refers to a hydrocarbon of a 3- to 6-membered monocyclic system with a saturated ring. C3-C6 cycloalkyl can be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0949] The term "cyano" refers to the -CN residue.

[0950] The term "nitro" refers to the -NO2 group.

[0951] The terms "alkoxy", "cyclalkyloxy" and their derivatives refer to any of the above 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-).

[0952] The term "heteroaryl" refers to an aromatic heterocycle, usually a 5-, 6-, 7-, 8-membered heterocycle having 1 to 3 heteroatoms selected from N, O or S; the heteroaryl ring may optionally be further fused or attached to aromatic and non-aromatic carbocyclic and heterocyclic rings. Non-limiting examples of said heteroaryl are, for example, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, imidazolyl, thiazolyl, isothiazolyl, thiazoxazolyl, pyrrolyl, phenyl-pyrrolyl, furyl, phenyl-furyl, oxazolyl, isoxazolyl, pyrazolyl, thienyl, benzofuryl, benzothienyl, benzo-1,3-dioxole (benzodioxol), isoindolinyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, 1,2,3-triazolyl, 1-phenyl-1,2,3-triazolyl, 2,3-dihydroindolyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, benzopyranyl, 2,3-dihydrobenzoxazinyl, 2,3-dihydroquinoxalinyl, etc.

[0953] The term "heterocyclic group" (also referred to as "heterocycloalkyl") refers to 3-, 4-, 5-, 6- and 7-membered saturated or partially unsaturated carbocycles, wherein one or more carbon atoms are replaced by heteroatoms such as nitrogen, oxygen and sulfur. Non-limiting examples of heterocyclic groups are, for example, pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, thiazoline, thiazolidine, dihydrofuran, tetrahydrofuran, 1,3-dioxolane, piperidine, piperazine, morpholine, morpholinyl, pyrrolidinyl, thiomorpholinyl, etc.

[0954] For example, "6-membered heterocyclic group" refers to a 6-membered saturated or partially unsaturated carbocycle, wherein one or more carbon atoms are replaced by heteroatoms such as nitrogen, oxygen and sulfur. Non-limiting examples of 6-membered heterocyclic groups are, for example, pyran, piperidine, piperazine, morpholine, morpholinyl, thiomorpholinyl, etc.

[0955] "5-membered heterocyclic group" refers to a 5-membered saturated or partially unsaturated carbocycle, wherein one or more carbon atoms are replaced by heteroatoms such as nitrogen, oxygen and sulfur. Non-limiting examples of 5-membered heterocyclic groups are, for example, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, thiazoline, thiazolidine, 1,3-dioxolane, etc.

[0956] The term "optionally substituted heterocyclic group" refers to the above "heterocyclic group" substituted by one or more "C1-C6 alkyl", "C1-C3 alkyl", "C3-C6 cycloalkyl", etc.

[0957] "Fluoroalkyl" refers to a group formed by substituting one or more fluorine groups for the alkyl backbone. For example, monofluoromethyl, difluoroethyl, trifluoromethyl, etc.

[0958] The term "C1-C6 fluoroalkyl" refers to a group formed by substituting one or more fluorine groups for the C1-C6 alkyl backbone. For example, monofluoromethyl, difluoroethyl, trifluoromethyl, etc.

[0959] Similarly, the term "C1-C3 fluoroalkyl" refers to a group formed by substituting one or more fluorine groups for the C1-C3 alkyl backbone. For example, monofluoromethyl, difluoroethyl, trifluoromethyl, etc.

[0960] The term "C1-C6 heteroatom-containing alkyl" refers to a group formed by substituting one or more carbon atoms in the C1-C6 alkyl backbone with one or more heteroatoms. For example, etc.

[0961] The term "C3-C8 heteroatom-containing cycloalkyl" refers to a group formed by substituting one or more carbon atoms in the C3-C8 cycloalkyl backbone with one or more heteroatoms. For example, pyrrolidine, imidazolidine, pyrazolidine, thiazolidine, piperidine, piperazine, morpholine, morpholinyl, thiomorpholinyl, etc.

[0962] The term "C1-C6 acyl" refers to -C(=O)-H and -C(=O)-C1-C5 alkyl. For example, formyl, acetyl, propionyl, butyryl, etc.

[0963] The term "sulfonyl" refers to -S(=O)2-.

[0964] The term "C1-C6 alkylsulfonyl" refers to -S(=O)2-C1-C6 alkyl. For example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, etc.

[0965] The terms "alkoxy", "cycloalkyloxy" and their derivatives refer to any of the above alkyl groups (such as C1-C6 alkyl, C1-C3 alkyl, etc.), cycloalkyl groups (such as C3-C6 cycloalkyl), which are connected to the rest of the molecule through an oxygen atom (-O-).

[0966] From all of the above descriptions, it is obvious to those skilled in the art that any group with a compound name, such as "fluorooxyalkyl", should be constructed conventionally from the derived part, for example, from an oxyalkyl substituted with a fluorine group, where the alkyl is as defined above. Similarly, there is also "fluoroalkoxy". For another example, "arylamino" should be constructed conventionally from the derived part, for example, from an amino group substituted with an aryl group, where the aryl is as defined above. Similarly, the meaning of "heteroarylamino" can be understood. Similarly, the meanings of "hydroxysulfonyl", "aminosulfonyl", etc. can be understood.

[0967] Similarly, any terms such as alkylamino, dialkylamino, alkoxycarbonyl, alkoxycarbonylamino, heterocycliccarbonyl, heterocycliccarbonylamino, cycloalkyloxycarbonyl, alkoxyformyl, etc. include groups in which the alkyl, alkoxy, aryl, C3-C7 cycloalkyl, and heterocyclic moieties are as defined above.

[0968] According to the present invention and unless otherwise provided, any of the above groups may optionally be substituted at any of their free positions by one or more groups, such as being substituted by 1-6 groups, which are independently selected from: halogen atoms, nitro, oxo (=O), cyano, C1-C6 alkyl, polyfluoroalkyl, polyfluoroalkoxy, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkylamino, hydroxyheterocycle, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocycle, heterocycle-alkyl, C3-C7 cycloalkyl, cycloalkyl-alkyl, alkyl-aryl, alkyl-heteroaryl, alkyl-heterocycle, alkyl-cycloalkyl, alkyl-aryl-alkyl, alkyl-heteroaryl-alkyl, alkyl-heterocycle-alkyl, alkyl-cycloalkyl-alkyl, alkyl-heterocycle-heterocycle, heterocycle-heterocycle, heterocycle-alkyl-heterocycle, heterocycle-alkylamino, alkyl-heterocycle-alkyl-amino, hydroxy, alkoxy, aryloxy, heterocyclyloxy, alkyl-heterocyclyloxy, methylenedioxy, alkylcarbonyloxy, arylcarbonyloxy, cycloalkenyloxy, heterocycliccarbonyloxy, alkylenaminooxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl, heterocyclyloxycarbonyl, amino, ureido, alkylamino, amino-alkylamino, dialkylamino, dialkylamino-heterocycle, dialkylamino-alkylamino, arylamino, arylalkylamino, diarylamino, heterocyclicamino, alkyl-heterocyclicamino, alkyl-heterocycliccarbonyl, formylamino, alkylcarbonylamino, arylcarbonylamino, heterocycliccarbonylamino, alkyl-heterocycliccarbonylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, heterocyclicaminocarbonyl, alkoxycarbonylamino, alkoxycarbonylamino-alkylamino, alkoxycarbonylheterocycle-alkylamino, alkoxy-aryl-alkyl, hydroxyaminocarbonyl, alkoxyimino, alkylsulfonylamino, arylsulfonylamino, heterocyclicsulfonylamino, formyl, alkylcarbonyl, arylcarbonyl, cycloalkylcarbonyl, heterocycliccarbonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, heterocyclicaminosulfonyl, arylthio, alkylthio, phosphonate, and alkylphosphonate.

[0969] Furthermore, if appropriate, each of the above substituents may further be substituted by one or more of the groups listed above.

[0970] 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 carbocyclic ring in which one or more carbon atoms are replaced by oxygen or nitrogen. Non-limiting examples are, for example, pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, dihydrofuran, tetrahydrofuran, 1,3-dioxolane, piperidine, piperazine, morpholine, pyrrolidinyl, hexamethyleneimine, etc.

[0971] The term "substituted or unsubstituted 3- to 7-membered ring containing 1 to 2 heteroatoms" refers to a 3-, 4-, 5-, 6- or 7-membered saturated or partially unsaturated carbocyclic ring in which one or more carbon atoms are replaced by heteroatoms. Non-limiting examples are, for example, pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, dihydrofuran, tetrahydrofuran, 1,3-dioxolane, piperidine, piperazine, morpholine, pyrrolidinyl, hexamethyleneimine, etc.

[0972] The heteroatoms are N, O or S.

[0973] As used herein, unless otherwise indicated, the term "prodrug" refers to a derivative of a compound of the present invention that can be hydrolyzed, oxidized or undergo other reactions under biological conditions (in vitro or in vivo) to provide the compound of the present invention. Prodrugs become active compounds only after such reactions under biological conditions, or they are active in their non-reactive forms. Prodrugs can generally be prepared using well-known methods, such as those described in Burger's Medicinal Chemistry and Drug Discovery (1995) 172 - 178, 949 - 982 (edited by Manfred E. Wolff, 5th edition).

[0974] Examples of the term "pharmaceutically acceptable salts of the compounds of formula (O), (I), (II), (III), (O'), (I'), (II'), (III')" as used herein are organic acid addition salts formed by 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, alkyl sulfonate or aryl sulfonate; preferably, the alkyl sulfonate is methyl sulfonate or ethyl sulfonate; the aryl sulfonate is benzenesulfonate or p-toluenesulfonate. Suitable inorganic salts can also be formed, including but not limited to hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate and carbonate, sulfate or phosphate, etc.

[0975] 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 that provides a pharmaceutically acceptable anion.

[0976] As used herein, the term "treatment" generally refers to obtaining the desired pharmacological and / or physiological effect. This effect can be prophylactic, based on completely or partially preventing a disease or its symptoms; and / or therapeutic, based on partially or completely stabilizing or curing a disease and / or the side effects resulting from the disease. "Treatment" as used herein encompasses any treatment of a patient's disease, including: (a) preventing the occurrence of a disease or symptoms in a patient susceptible to the disease or symptoms but not yet diagnosed as having the disease; (b) inhibiting the symptoms of a disease, i.e., preventing its progression; or (c) alleviating the symptoms of a disease, i.e., causing regression of the disease or symptoms.

[0977] 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.

[0978] On the other hand, the present invention provides a pharmaceutical composition comprising the compound, its stereoisomer, its prodrug, or its pharmaceutically acceptable salt or pharmaceutically acceptable solvate according to any of the above technical solutions, and a pharmaceutically acceptable carrier, diluent, or excipient.

[0979] Methods for preparing various pharmaceutical compositions containing a certain amount of the active ingredient are known or will be apparent to those skilled in the art from the disclosure of the present invention. As described in REMINGTON’S PHARMACEUTICAL SCIENCES, Martin, E.W., ed., Mack Publishing Company, 19th ed. (1995), the methods for preparing the pharmaceutical compositions include incorporating appropriate pharmaceutical excipients, carriers, diluents, etc.

[0980] The pharmaceutical preparations of the present invention are manufactured by known methods, including conventional mixing, dissolving, or lyophilization methods. The compounds of the present invention can be formulated into pharmaceutical compositions and administered to patients by various routes suitable for the selected mode of administration, for example, orally or parenterally (by intravenous, intramuscular, topical, or subcutaneous routes).

[0981] Thus, the compounds of the present invention, in combination with a pharmaceutically acceptable carrier (such as an inert diluent or an assimilable edible carrier), can be administered systemically, for example, orally. They can be enclosed in hard or soft shell gelatin capsules and can be compressed into tablets. For oral therapeutic administration, the active compounds 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% of the active compound. The proportion of such compositions and preparations can of course vary and can be about 1% to about 99% of the weight of the given unit dosage form. In such therapeutically useful compositions, the amount of the active compound is such that an effective dosage level can be obtained.

[0982] Tablets, lozenges, pills, capsules, etc. can also contain: binders such as gum tragacanth, gum arabic, corn starch or gelatin; excipients such as dibasic calcium phosphate; disintegrants such as corn starch, potato starch, alginic acid, etc.; lubricants such as magnesium stearate; and sweetening agents such as sucrose, fructose, lactose or aspartame; or flavoring agents such as peppermint, wintergreen oil or cherry flavor. When the unit dosage form is a capsule, in addition to materials of the above types, it can also contain a liquid carrier such as a vegetable oil or polyethylene glycol. Various other materials can be present, as coatings, or otherwise to alter the physical form of the solid unit dosage form. For example, tablets, pills or capsules can be coated with gelatin, wax, shellac or sugar, etc. Syrups or elixirs can contain the active compound, sucrose or fructose as a sweetening agent, methylparaben or propylparaben as a preservative, and dyes and flavoring agents (such as cherry flavor or orange flavor). Of course, any material used in the preparation of any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. In addition, the active compounds can be incorporated into sustained-release preparations and devices.

[0983] The active compounds can also be administered intravenously or intraperitoneally by infusion or injection. An aqueous solution of the active compound or its salt can be prepared, optionally mixed with a non-toxic surfactant. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, triacetin and their mixtures, and in oils. Under ordinary storage and use conditions, these preparations contain preservatives to prevent the growth of microorganisms.

[0984] A pharmaceutical dosage form suitable for injection or infusion may include a sterile aqueous solution or dispersion or sterile powder containing an active ingredient (optionally encapsulated in liposomes) of an immediate preparation comprising a sterile injectable or infusible solution or dispersion. In all cases, the final dosage form must be sterile, liquid, and stable under production and storage conditions. The liquid carrier may be a solvent or a 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 may be maintained, for example, by the formation of liposomes, by maintaining the desired particle size in the case of a dispersion, or by the use of surfactants. The prevention of microorganisms may be effected 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 may be effected by the use of compositions that retard absorption, such as aluminum monostearate and gelatin.

[0985] A sterile injectable solution is prepared by combining the required amount of the active compound in a suitable solvent with the various other ingredients required above, followed by filtration sterilization. In the case of a sterile powder for the preparation of a sterile injectable solution, the preferred methods of preparation are vacuum drying and freeze-drying techniques, which yield a powder of the active ingredient plus any additional ingredients present in the previously sterile filtered solution that are required.

[0986] Useful solid carriers include comminuted solids such as talc, clay, microcrystalline cellulose, silica, alumina, etc. Useful liquid carriers include water, ethanol, or ethylene glycol or water-ethanol / ethylene glycol mixtures, in which the compounds of the present invention may be dissolved or dispersed in an effective amount, optionally with the aid of a non-toxic surfactant. Adjuvants such as flavors and additional antimicrobial agents may be added to optimize the properties for a given use.

[0987] Thickening agents such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified celluloses, or modified inorganic materials may also be used with the liquid carrier to form coatable pastes, gels, ointments, soaps, etc., for direct application to the skin of the user.

[0988] The therapeutically effective amount of the compound or its active salt or derivative depends not only on the particular salt selected, but also on the mode of administration, the nature of the disease to be treated, the age and condition of the patient, and ultimately on the decision of the attending physician or clinician.

[0989] The above-mentioned preparation can exist in unit dosage forms, which are physical dispersion units containing a unit dose and are suitable for administration to the human body and other mammalian bodies. The unit dosage form can be a capsule or a tablet, or a plurality of capsules or tablets. Depending on the specific treatment involved, the amount of the unit dose of the active ingredient can vary or be adjusted between approximately 0.1 and approximately 1000 milligrams or more.

[0990] In addition, it also includes the application of various new drug dosage forms such as milk liposomes, microspheres and nanospheres, such as medicaments prepared using particulate dispersion systems including polymeric micelles, nanoemulsion, submicroemulsion, microcapsule, microsphere, liposomes and niosomes (also known as nonionic surfactant vesicles), etc.

[0991] On the other hand, the present invention also provides a preparation method of the compound described in any of the above technical solutions, including the following steps:

[0992]

[0993] Among them, the definitions of R 1 , R 2 , R 3 are as described in the previous description.

[0994] Reaction conditions:

[0995] (a) A coupling reaction catalyzed by palladium metal;

[0996] (b) A coupling reaction catalyzed by palladium metal, or a nucleophilic substitution reaction under acidic conditions, or a nucleophilic substitution reaction under basic conditions;

[0997] (c) A nucleophilic substitution reaction under acidic conditions, or a nucleophilic substitution reaction under basic conditions;

[0998] The palladium metal catalyst is selected from palladium acetate, tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium, tris(dibenzylideneacetone)dipalladium;

[0999] The basic conditions refer to the conditions in the presence of any of the following substances: triethylamine, diisopropylethylamine, pyridine, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride;

[1000] The acidic conditions refer to the conditions in the presence of any of the following substances: acetic acid, trifluoroacetic acid, hydrochloric acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid.

[1001] On the other hand, the present invention also provides a preparation method of the compound according to any one of the above technical solutions, including the following steps:

[1002]

[1003] Reaction conditions: (a) A carbon-carbon bond formation coupling reaction of a heteroaryl chloride or bromide with boric acid or borate catalyzed by palladium metal; (b) A carbon-nitrogen bond formation coupling reaction of a heteroaryl chloride with an amine compound catalyzed by palladium metal, or a nucleophilic substitution reaction of an amine compound with a heteroaryl chloride under acidic conditions, or a nucleophilic substitution reaction of an amine compound with a heteroaryl chloride under basic conditions; (c) A nucleophilic substitution reaction of an amine compound with a heteroaryl chloride under acidic conditions, or a nucleophilic substitution reaction of an amine compound with a heteroaryl chloride under basic conditions;

[1004] Among them, the heteroaryl chloride or bromide includes the following types:

[1005]

[1006] The boric acid or borate is selected from substituted or unsubstituted phenylboric acid or borate and their derivatives; the amine compounds are selected from substituted or unsubstituted five- or six-membered heterocyclic amines, aniline and its derivatives, C1-C6 alkylamines, C3-C7 cycloalkylamines, C1-C6 oxygen-containing alkylamines, C3-C7 oxygen-containing cycloalkylamines, as described in detail above;

[1007] The palladium metal catalyst is selected from palladium acetate, tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)dichloropalladium, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium, tris(dibenzylideneacetone)dipalladium; the basic conditions refer to the conditions in the presence of any of the following substances: 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 the presence of any of the following substances: acetic acid, trifluoroacetic acid, hydrochloric acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid.

[1008] On the other hand, the present invention provides a pharmaceutical composition, which comprises the compound according to any one of the above technical solutions, its stereoisomers, its prodrugs, or its pharmaceutically acceptable salts or pharmaceutically acceptable solvates, and a pharmaceutically acceptable carrier, diluent or excipient.

[1009] On the other hand, the present invention also provides the use of the compound described in any of the above technical solutions, its stereoisomers, its prodrugs, or its pharmaceutically acceptable salts or pharmaceutically acceptable solvates, and the pharmaceutical composition containing the compound in the preparation of a drug for the prevention and / or treatment of cancers and other diseases mediated by BRK, BTK kinase or both, especially in the preparation of a drug for the prevention and / or treatment of breast cancer and B-cell malignancies.

[1010] On the other hand, the present invention provides a method for preventing and / or treating cancers and other diseases mediated by BRK, BTK kinase or both, which comprises administering to a subject in need thereof a prophylactically and / or therapeutically effective amount of the compound described in any of the above technical solutions or its stereoisomers, its prodrugs, its pharmaceutically acceptable salts or its pharmaceutically acceptable solvates, or the above pharmaceutical composition.

[1011] In some embodiments, the method is used for preventing and / or treating breast cancer and B-cell malignancies.

[1012] On the other hand, the present invention provides the compound described in any of the above technical solutions or its stereoisomers, its prodrugs, its pharmaceutically acceptable salts or its pharmaceutically acceptable solvates, or the above pharmaceutical composition, which is used for preventing and / or treating diseases mediated by BRK, BTK kinase or both in a living organism, especially for preventing and / or treating breast cancer and B-cell malignancies.

[1013] 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 cows), pets (such as cats, dogs, and horses), primates, mice, and rats. In certain embodiments, the mammal refers to a human.

[1014] In the present invention, "effective amount" refers to an amount that is effective to achieve the desired therapeutic or prophylactic effect at the required dose and time. The "therapeutically effective amount" of the substance / molecule of the present invention may vary depending on factors such as the disease state, age, sex, and body weight of the individual and the ability of the substance / molecule to elicit the desired response in the individual. The therapeutically effective amount also encompasses an amount in which the therapeutic beneficial effect of the substance / molecule outweighs any toxic or harmful consequences. "Prophylactically effective amount" refers to an amount that is effective to achieve the desired prophylactic effect at the required dose and time. Generally but not necessarily, since the prophylactic dose is used in a subject before the onset of the disease or in the early stage of the disease, the prophylactically effective amount will be lower than the therapeutically effective amount. In the case of cancer, the therapeutically effective amount of the drug can reduce the number of cancer cells; shrink the tumor volume; inhibit (i.e., slow down to a certain extent, preferably stop) the infiltration of cancer cells 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.

[1015] Experimental Section

[1016] For the following described embodiments, the compounds of the present invention were synthesized using the methods described herein or other methods well known in the art.

[1017] General purification and analysis methods:

[1018] Thin layer chromatography was performed on silica gel GF254 pre-coated plates (Qingdao Ocean Chemical Factory). Column chromatography was carried out under medium pressure over silica gel (300 - 400 mesh, Huangwu Silica Gel Development Reagent Factory, Zhifu District, Yantai City) or by using an ISCO CombiflashRf200 rapid purification system with pre-packed silica cartridges (ISCO or Welch). Components were visualized by UV light (wavelength 254 nm) and by iodine vapor. When necessary, the compounds were purified by preparative HPLC over a Waters Symmetry C18 (19 x 50 mm, 5 μm) column or over a Waters X Terra RP 18 (30 x 150 mm, 5 μm) column, detected using a Waters preparative HPLC 600 equipped with a 996 Waters PDA detector and a Micromass mod.ZMD single quadrupole mass spectrometer (electrospray ionization, positive ion mode). Method 1: Phase A: 0.1% TFA / MeOH 95 / 5; Phase B: MeOH / H2O 95 / 5. Gradient: 10 to 90% B for 8 min, hold at 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 for 8 min, hold at 100% B for 2 min; flow rate 20 mL / min.

[1019] 1 1H-NMR spectra were recorded on a Bruker Avance 600 nuclear magnetic resonance spectrometer at 600 MHz. Chemical shifts (δ) are reported in parts per million (ppm) and coupling constants (J) are 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 of doublets.

[1020] Electrospray (ESI) mass spectra were obtained on a Finnigan LCQ ion trap.

[1021] Unless otherwise stated, all final compounds are homogeneous (purity not less than 95%), as determined by high performance liquid chromatography (HPLC). HPLC-UV-MS analysis for evaluating compound purity is carried out by combining an ion trap MS device with an HPLC system SSP4000 (Thermo Separation Products), and the HPLC system is equipped with an autosampler LC Pal (CTC Analytics) and a UV6000LP diode array detector (UV detection at 215 - 400 nm). Device control, data acquisition and processing are performed using Xcalibur 1.2 software (Finnigan). HPLC chromatography is carried out 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 is 5 mM ammonium acetate buffer (pH 5.5 adjusted with acetic acid): acetonitrile 90:10, and mobile phase B is 5 mM ammonium acetate buffer (pH 5.5 adjusted with acetic acid): acetonitrile 10:90; the gradient is from 0 to 100% B for 7 minutes, and then 100% B is maintained for 2 minutes before re-equilibration.

[1022] Purification of reagents refers to Purification of Laboratory Chemicals (Perrin, D.D., Armarego, W.L.F. and Perrins Eds, D.R.; Pergamon Press: Oxford, 1980). Petroleum ether is the fraction of 60 - 90 °C, and ethyl acetate, methanol, and dichloromethane are all of analytical grade. Detailed Description of the Invention

[1023] The embodiments of the present invention are described in detail below through specific examples, but in no way can they be construed as limiting the present invention.

[1024] Compounds can be divided into the following major categories:

[1025]

[1026]

[1027]

[1028] Among them, the definitions of R1, R, R', and W5 are as described above.

[1029] Some of the raw materials and intermediates involved in the synthesis process are described as follows:

[1030] 1. 5-Amino-2-methylphenylboronic acid pinacol ester (cas: 882670-69-1, Shuya, Shanghai);

[1031] 2. 3-(Trifluoromethyl)benzoyl chloride (cas: 2251-65-2, Energy Chemical, Shanghai);

[1032] 3. 2-Chloro-6-bromoquinazoline (cas: 882672-05-1, Bidepharm, Shanghai);

[1033] 4. Obtained by reacting 2-fluoro-5-nitropyridine (cas: 456-24-6, Bidepharm, Shanghai) with 4-hydroxypiperidine (cas: 5382-16-1, Energy Chemical, Shanghai) And then reducing the nitro group;

[1034] The following intermediates are obtained by similar methods:

[1035]

[1036] The raw materials involved are: 4-methoxypiperidine (cas: 4045-24-3, Bidepharm, Shanghai), 4-dimethylaminopiperidine (cas: 50533-97-6, Shyuan Chemical, Shanghai), 1-methyl-4-(piperidin-4-yl)piperazine (cas: 53617-36-0, Alchem Pharmtech, Jiangsu), 5-fluoro-2-nitroanisole (cas: 448-19-1, Bidepharm, Shanghai), 2-methoxy-3-nitro-6-chloropyridine (cas: 40851-91-0, Bidepharm, Shanghai), p-fluoronitrobenzene (cas: 350-46-9, Energy Chemical, Shanghai); 4-(pyrrolidin-1-yl)piperidine (cas: 5004-07-9, Shyuan Chemical, Shanghai), N,N'-dimethylpyrrolidin-3-amine (cas: 64021-83-6, TCI, Shanghai), 2-ethoxy-4-fluoro-1-nitrobenzene (cas: 28987-44-2, Bidepharm, Shanghai), N-methylpiperazine (cas: 109-01-3, Energy Chemical, Shanghai), 3,4,5-trifluoronitrobenzene (cas: 66684-58-0, Bidepharm, Shanghai), 2,3,4-trifluoronitrobenzene (cas: 771-69-7, Bidepharm, Shanghai);

[1037] Obtained by reacting 1-benzyloxycarbonyl-4-piperidone (cas: 19099-93-5, Bidepharm, Shanghai) with 1-(2-dimethylaminoethyl)piperazine (cas: 3644-18-6, Bidepharm, Shanghai) And then removing the protecting group to obtain And then reacting with p-fluoronitrobenzene (cas: 350-46-9, Energy Chemical, Shanghai) by the above similar method to obtain Replace 1-(2-dimethylaminoethyl)piperazine with 1-(2-hydroxyethyl)piperazine (cas: 103-76-4, Bidepharm, Shanghai), and the following can be obtained through a similar method

[1038] 5. It is obtained by reacting 4-methoxy-3-nitrobenzoic acid (cas: 89-41-8, Bidepharm, Shanghai) with N-methylpiperazine (cas: 109-01-3, Energy Chemical, Shanghai) and then reducing the nitro group;

[1039] The following intermediates are obtained through a similar method:

[1040]

[1041] The raw materials involved are: 3-ethoxy-4-nitrobenzoic acid (cas: 367501-32-4, Bidepharm, Shanghai), 4-methoxy-3-nitrobenzoic acid (cas: 89-41-8, Bidepharm, Shanghai), m-nitrobenzoic acid (cas: 121-92-6, Bidepharm, Shanghai), 1-methyl-4-(4-piperidyl)piperazine (cas: 53617-36-0, Alcon, Jiangsu), N-methylpiperazine (cas: 109-01-3, Energy Chemical, Shanghai);

[1042] 6. It is obtained by reacting m-bromonitrobenzene (cas: 585-79-5, Energy Chemical, Shanghai) with 4-hydroxypiperidine (cas: 5382-16-1, Energy Chemical, Shanghai) and then reducing the nitro group;

[1043] The following intermediates are obtained through a similar method:

[1044]

[1045] The raw materials involved are: 4-bromo-2-nitroanisole (cas: 33696-00-3, Shuya, Shanghai), 4-hydroxypiperidine (cas: 5382-16-1, Energy Chemical, Shanghai), 1-methyl-4-(4-piperidyl)piperazine (cas: 53617-36-0, Alcon, Jiangsu), 4-(1-pyrrolidino)piperidine (cas: 5004-07-9, Shoyuan, Shanghai), N-methylpiperazine (cas: 109-01-3, Energy Chemical, Shanghai);

[1046] 7. 2-Nitro-4-methyl-5-chlorophenol (cas: 100278-74-8, Bidepharm, Shanghai) reacts with methyl iodide (cas: 74-88-4, Xiya Reagent, Shandong) to obtain 2-nitro-4-methyl-5-chloroanisole, which then reacts with 4-pyridineboronic acid (cas: 4-pyridineboronic acid, Shuya, Shanghai) to obtain It further reacts with methyl iodide (cas: 74-88-4, Xiya Reagent, Shandong) to obtain Finally, the nitro group and the pyridine ring are reduced to obtain; replacing methyl iodide with isopropyl bromide (cas: 75-26-3, Macklin, Shanghai), the following can be obtained through a similar method

[1047] 8. 4-Nitrophenethyl alcohol (cas: 100-27-6, Bidepharm, Shanghai) reacts with 1,3-dibromo-5,5-dimethylhydantoin (cas: 77-48-5, Bidepharm, Shanghai) to obtain 2-bromo-4-nitrophenethyl alcohol, which then reacts with methanesulfonyl chloride (cas: 124-63-0, Xiya Reagent, Shandong) to obtain 2-bromo-4-nitrophenethyl alcohol methanesulfonate. Continuing to react with methallylamine (cas: 627-37-2, Aladdin, Shanghai) to obtain It is further converted through the Heck reaction to Finally, the nitro group and the double bond are reduced to obtain;

[1048] 9. 6-Fluoro-3,4-dihydro-2H-isoquinolin-1-one (cas: 214045-84-8, Bidepharm, Shanghai) reacts with methyl iodide (cas: 74-88-4, Xiya Reagent, Shandong) to obtain 2-methyl-6-fluoro-3,4-dihydro-2H-isoquinolin-1-one, which then reacts with fuming nitric acid (cas: 7697-37-2, Shanghai Reagent, Shanghai) to obtain 2-methyl-6-fluoro-7-nitro-3,4-dihydro-2H-isoquinolin-1-one. Further reduction of the carbonyl group gives 2-methyl-6-fluoro-7-nitro-1,2,3,4-tetrahydroisoquinoline, and finally the nitro group is reduced to obtain; 2-methyl-6-fluoro-7-nitro-3,4-dihydro-2H-isoquinolin-1-one reacts with methanol (cas: 67-56-1, Shanghai Reagent, Shanghai) to obtain 2-methyl-6-methoxy-7-nitro-3,4-dihydro-2H-isoquinolin-1-one, and the following can be obtained through a similar method

[1049] 10. 1-Isopropyl-6-chloro-1H-pyrazolo[4,3-c]pyridine was obtained by reacting 6-chloro-1H-pyrazolo[4,3-c]pyridine (cas: 1206979-33-0, Bidepharm, Shanghai) with isopropyl bromide (cas: 75-26-3, Macklin, Shanghai), and then reacting with benzophenone imine (cas: 1013-88-3, Bidepharm, Shanghai); It was further obtained by reducing the imine;

[1050] 11. 7-Amino-3,4-dihydro-1H-quinolin-2-one (cas: 22246-07-7, Bidepharm, Shanghai);

[1051] 12. It was obtained by reacting m-nitroaniline (cas: 99-09-2, Energy Chemical, Shanghai) with bromoacetyl bromide (cas: 598-21-0, Energy Chemical, Shanghai), and then further reacting with dimethylamine (cas: 124-40-3, Merck, Shanghai); It was further obtained by reducing the nitro group; It was obtained by a similar method from 3-nitro-4-methoxyaniline (cas: 577-72-0, Bidepharm, Shanghai);

[1052] 13. 2-Chloro-6-bromo-8-methylquinazoline (cas: 1388046-71-6), 2-Amino-6-bromo-8-methylquinazoline was cyclized from 5-bromo-2-fluoro-3-methylbenzaldehyde (cas: 903875-64-9, Bidepharm, Shanghai) and guanidine carbonate (cas: 593-85-1, Bidepharm, Shanghai), and then obtained by reacting with antimony trichloride (cas: 10025-91-9, Aladdin, Shanghai) and tert-butyl nitrite (cas: 540-80-7, Aladdin, Shanghai);

[1053] 2-Fluoro-3-ethyl-5-bromobenzaldehyde was obtained by reacting 4-bromo-2-ethyl-1-fluorobenzene (cas: 627463-25-6, Bidepharm, Shanghai) with lithium diisopropylamide (cas: 4111-54-0, Aladdin, Shanghai) and N,N-dimethylformamide (cas: 68-12-2, Titan Scientific, Shanghai), and then 2-chloro-6-bromo-8-ethylquinazoline was obtained by the same method;

[1054] 2-(2-Fluoro-5-bromophenyl)propan-2-ol was obtained by reacting 1-(2-fluoro-5-bromophenyl)ethanone (cas: 198477-89-3, Bidepharm, Shanghai) with methylmagnesium bromide (cas: 75-16-1, Aladdin, Shanghai), and then 1-fluoro-2-isopropyl-4-bromobenzene (cas: 112611-93-5) was obtained by reducing the hydroxyl group. Subsequently, 2-chloro-6-bromo-8-isopropylquinazoline was obtained by the same method;

[1055] 14. 2-Fluoro-3-methyl-5-bromobenzaldehyde (cas: 903875-64-9, Bidepharm, Shanghai);

[1056] 15. 3-Amino-6-methylpyridine; (cas: 3430-14-6, Bidepharm, Shanghai);

[1057] 16. 5-Amino-2-methylphenylboronic acid pinacol ester (cas: 882670-69-1, Shuya, Shanghai);

[1058] 17. 4-(Trifluoromethyl)benzoyl chloride (cas: 329-15-7, Energy Chemical, Shanghai);

[1059] 18. 3-(Trifluoromethyl)-4-(bromomethyl)benzoic acid (cas: 859213-39-1, J&K Scientific, Beijing);

[1060] 19. 2-(Trifluoromethyl)benzoyl chloride (cas: 312-94-7, Bidepharm, Shanghai);

[1061] 20. 3-Fluorobenzoyl chloride (cas: 1711-07-5, Energy Chemical, Shanghai);

[1062] 21. m-Toluoyl chloride (cas: 1711-06-4, Bidepharm, Shanghai);

[1063] 22. m-Methoxycarbonylphenylboronic acid (cas: 99769-19-4, Bidepharm, Shanghai);

[1064] 23. 4-Methoxycarbonyl-2-methylphenylboronic acid (cas: 158429-38-0, Bidepharm, Shanghai);

[1065] 24. m-Aminobenzotrifluoride (cas: 98-16-8, Energy Chemical, Shanghai);

[1066] 25. 3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline (cas: 641571-11-1, Bidepharm, Shanghai);

[1067] 26. 3-(4-Methylpiperazin-1-ylmethylene)-5-(trifluoromethyl)aniline (cas: 853296-94-3, Alcon, Jiangsu);

[1068] 27. 3-(Trifluoromethyl)-4-(4-methylpiperazin-1-ylmethylene)aniline (cas: 694499-26-8, Shuya, Shanghai);

[1069] 28. Dichlorobis(benzonitrile)palladium(II) (cas: 95464-05-4, Bidepharm, Shanghai);

[1070] 29. Tris(dibenzylideneacetone)dipalladium(0) (cas: 51364-51-3, Energy Chemical, Shanghai);

[1071] 30. 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (cas: 564483-18-7, Energy Chemical, Shanghai);

[1072] 31. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (cas: 7084-11-9, Energy Chemical, Shanghai);

[1073] 32. 4-Dimethylaminopyridine (cas: 1122-58-3, Energy Chemical, Shanghai);

[1074] 33. 1-Methyl-3-aminopyrazole (cas: 1904-31-0, Bidepharm, Shanghai);

[1075] 34. 6-(Trifluoromethyl)picolinic acid (cas: 131747-42-7, Bidepharm, Shanghai);

[1076] 35. 4-(Trifluoromethyl)picolinic acid (cas: 588702-62-9, Bidepharm, Shanghai);

[1077] 36. 4-Methylpyridine-3-boronic acid (cas: 148546-82-1, Aladdin, Shanghai);

[1078] 37. Pyridine-3-boronic acid (cas: 1692-25-7, Bidepharm, Shanghai);

[1079] 38. Benzoyl chloride (cas: 98-88-4, TCI, Shanghai);

[1080] 39. Nicotinic acid (cas: 59-67-6, Energy Chemical, Shanghai);

[1081] 40. 3-(Trifluoromethyl)benzenesulfonyl chloride (cas: 777-44-6, Energy Chemical, Shanghai);

[1082] 41. 4-Chloro-2-fluorobenzoic acid (cas: 446-30-0, Energy Chemical, Shanghai);

[1083] 42. 5-Chloro-2-methoxybenzoic acid (cas: 3438-16-2, Energy Chemical, Shanghai);

[1084] 43. 2-Chloronicotinic acid (cas: 2942-59-8, Bidepharm, Shanghai);

[1085] 44. 2-Chloro-3-nitrobenzoic acid (cas: 3970-35-2, Bidepharm, Shanghai);

[1086] 45. 3-Chloro-2-fluorobenzoic acid (cas: 161957-55-7, Energy Chemical, Shanghai);

[1087] 46. o-Chlorobenzoyl chloride (cas: 609-65-4, Energy Chemical, Shanghai);

[1088] 47. 5-Chloro-2-fluorobenzoic acid (cas: 394-30-9, Energy Chemical, Shanghai);

[1089] 48. 4-Chloro-3-nitrobenzoic acid (cas: 96-99-1, Bidepharm, Shanghai);

[1090] 49. 4-Bromobenzoic acid (cas: 586-76-5, Energy Chemical, Shanghai);

[1091] 50. 4-Bromo-2-fluorobenzoic acid (cas: 112704-79-7, Energy Chemical, Shanghai);

[1092] 51. 5-Bromo-2-fluorobenzoic acid (cas: 146328-85-0, Energy Chemical, Shanghai);

[1093] 52. 3-Bromo-2-fluorobenzoic acid (cas: 161957-56-8, Energy Chemical, Shanghai);

[1094] 53. 2,4-Dichlorobenzoic acid (cas: 50-84-0, Bidepharm, Shanghai);

[1095] 54. 3,4-Dichlorobenzoic acid (cas: 51-44-5, Bidepharm, Shanghai);

[1096] 55. 6-Fluoro-2-pyridinecarboxylic acid (cas: 402-69-7, Energy Chemical, Shanghai);

[1097] 56. 5-Bromo-2-pyridinecarboxylic acid (cas: 30766-11-1, Energy Chemical, Shanghai);

[1098] 57. 3-Acetylbenzoic acid (cas: 586-42-5, Bidepharm, Shanghai);

[1099] 58. 4-Acetylbenzoic acid (cas: 586-89-0, Energy Chemical, Shanghai).

[1100] The embodiments of the present invention will be described in detail below by specific examples, but in any case, they cannot be construed as limiting the present invention.

[1101] Synthesis of Compound IA:

[1102]

[1103] Preparation of Compound 3:

[1104] Compound 1 (2 mmol, 466 mg) and DIEA were dissolved in 40 mL of dichloromethane. Under ice bath conditions, a solution of Compound 2 (2.4 mmol, 499 mg) in dichloromethane (40 mL) was added dropwise using a constant pressure dropping funnel. The reaction was carried out at room temperature for 5 hours. After the reaction was completed as detected by TLC and LC-MS, it was washed successively with dilute hydrochloric acid, saturated sodium bicarbonate solution, and saturated brine once (30 mL each), dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and purified by silica gel column chromatography to obtain Compound 3 as a white powdery solid (500 mg), which was directly used for the next reaction.

[1105] Preparation of Compound 5:

[1106] In a 50 ml round-bottom flask, Compound 3 (1 mmol, 405 mg), Compound 4 (2 mmol, 480 mg), PdCl2(dppf)·CH2Cl2 (0.1 mmol, 82 mg), and Na2CO3 (5 mmol, 530 mg) were added. Using 1,4-dioxane (20 mL) and water (10 mL) as a mixed solvent, the reaction system was heated at 50 °C for 4 h under nitrogen protection. After the reaction was completed as detected by TLC and LC-MS, the reaction system was diluted with 50 mL of water and extracted with DCM. The organic phase was concentrated and purified by silica gel column chromatography to obtain Compound 5 as a colorless powdery solid (209 mg).

[1107] Preparation of Compound IA:

[1108] Compound 5 (22.0 mg, 0.05 mmol) and amine R1NH2 (0.05 mmol) were dissolved in 1 mL of tert-butanol. Then, 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (7.7 mg, 0.016 mmol), tris(dibenzylideneacetone)dipalladium (9.9 mg, 0.011 mmol), and potassium carbonate (37 mg, 0.27 mmol) were added to the solution. Under nitrogen protection, the resulting reaction solution was placed in an oil bath preheated to 90 °C and heated with stirring until the aromatic amine reaction was complete (monitored by LCMS and TLC), and then the reaction was stopped. Methanol and dichloromethane were added to the reaction solution, and it was filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (dichloromethane / methanol), and then further purified by preparative HPLC (using an aqueous solution containing 0.35% trifluoroacetic acid and methanol as the mobile phase) to obtain Compound IA.

[1109] Compound IB was synthesized by a similar method.

[1110] The following table lists the specific compounds and structure identification data.

[1111]

[1112]

[1113]

[1114]

[1115]

[1116]

[1117]

[1118]

[1119]

[1120]

[1121] Synthesis of Compounds IC-1, IC-2, and IC-3:

[1122]

[1123] Preparation of Compound 8:

[1124] Compound 6 (1 mmol, 256 mg), compound 7 (1.5 mmol, 162 mg), and p-toluenesulfonic acid (3 mmol, 270 mg) were dissolved in 10 mL of acetonitrile and reacted under microwave at 125 °C for 6 h. The reaction was monitored by TLC and LC-MS until completion. The reaction system was concentrated to obtain a brown oil, which was dissolved in EA and washed with saturated sodium bicarbonate and saturated brine. The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain compound 8 (316 mg), which was a brown solid and directly used in the next step of the reaction.

[1125] Preparation of Compound IC-1:

[1126] In a 50 mL round-bottom flask, compound 1 (0.96 mmol, 223.7 mg), compound 8 (0.96 mmol, 316 mg), PdCl2(dppf)·CH2Cl2 (0.1 mmol, 82 mg), and Na2CO3 (5 mmol, 530 mg) were added. Using 1,4-dioxane (20 mL) and water (10 mL) as a mixed solvent, under nitrogen protection, the reaction system was refluxed at 50 °C for 4 h. After the reaction was completed as detected by TLC and LC-MS, the reaction system was diluted with 50 mL of water and then extracted with DCM. The organic phase was concentrated and purified by silica gel column chromatography to obtain compound IC-1 (265 mg), which was a brown powdery solid.

[1127] Preparation of compound IC-2:

[1128] At room temperature, compound IC-1 (0.05 mmol, 17.75 mg) and DIEA (0.2 mmol, 25.8 mg) were stirred in 1 mL of DMF. After adding 4-trifluoromethylbenzoyl chloride (0.06 mmol, 8.7 μL), the reaction was monitored by LCMS. After completion, methanol and dichloromethane (10 / 10 mL) were added to the reaction solution. After concentration, it was purified by silica gel column chromatography (dichloromethane / methanol) and then by preparative HPLC to obtain compound IC-2.

[1129] Preparation of compound IC-3:

[1130] Compound 10 (0.2 mmol, 56.4 mg) was dissolved in 1 mL of thionyl chloride and refluxed at 90 °C for 4 h. After the reaction system was concentrated, a colorless oily liquid was obtained. It was dissolved in DCM (1 mL) and added to a solution of compound IC-1 (0.1 mmol, 35.5 mg) and DIEA (0.4 mmol, 52 mg) in DCM (4 mL), and the reaction was carried out at room temperature. After the reaction was completed as detected by LCMS, N-methylpiperazine (0.1 mmol) was added to the reaction system and the reaction continued. After the reaction was completed as detected by TLC and LCMS, the system was concentrated and purified by silica gel column chromatography (dichloromethane / methanol) and then by preparative HPLC to obtain compound IC-3.

[1131] Compounds IC-4 - IC-9 can be synthesized using similar methods.

[1132] Compound ID can also be synthesized using a similar method.

[1133] The following table lists the specific compounds and structure identification data.

[1134]

[1135]

[1136]

[1137]

[1138] Compound IE is obtained by a method similar to that for preparing compound IA, and compound IF is obtained by a method similar to that for preparing compound IC.

[1139] The following table lists specific compounds and structure identification data.

[1140]

[1141]

[1142]

[1143]

[1144]

[1145]

[1146]

[1147]

[1148]

[1149]

[1150]

[1151]

[1152] Compound IG is obtained by a method similar to that for preparing compound IA, and compound IH is obtained by a method similar to that for preparing compound IC.

[1153] The following table lists specific compounds and structure identification data.

[1154]

[1155]

[1156]

[1157] Synthesis of compounds IID-1 to IID-4:

[1158]

[1159] Preparation of compound IID-1:

[1160] In a 50 mL round-bottom flask, compound 8 (1 mmol, 328 mg), compound 11 (1 mmol, 194 mg), PdCl2(dppf)·CH2Cl2 (0.1 mmol, 82 mg), and Na2CO3 (5 mmol, 530 mg) were added. Using 1,4-dioxane (20 mL) and water (10 mL) as the mixed solvent, under nitrogen protection, the reaction system was refluxed at 50 °C for 4 h. After the reaction was completed as detected by TLC and LC-MS, the reaction system was diluted with 50 mL of water and then extracted with DCM. The organic phase was concentrated and purified by silica gel column chromatography to obtain compound IID-1 (280 mg), which was a colorless powdery solid.

[1161] Preparation of compound IID-2:

[1162] Compound IID-1 (0.16 mmol, 63 mg) and lithium hydroxide (0.48 mmol, 20 mg) were added to a 20 mL round-bottom flask, and THF / MeOH / H2O was used as the mixed solvent, and the mixture was stirred at room temperature. After the reaction was completed as detected by TLC and LC-MS, dilute hydrochloric acid was added to adjust the pH to 7, and a large amount of yellow solid precipitated. The solid was collected by filtration and dried to obtain compound IID-2 (45.5 mg).

[1163] Preparation of compound IID-3:

[1164] Compound IID-2 (0.06 mmol, 25 mg), iodoethane (0.06 mmol, 4.8 μL), sodium bicarbonate (0.24 mmol, 20 mg), and 2 mL of DMF were added to a round-bottom flask, and the reaction was carried out at room temperature. After the reaction was completed as detected by TLC and LCMS, the mixture was concentrated and purified by silica gel column chromatography (dichloromethane / methanol) and then by preparative HPLC to obtain compound IID-3.

[1165] Preparation of compound IID-4:

[1166] Compound IID-2 (0.06 mmol, 25 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.18 mmol, 34.5 mg), and 4-dimethylaminopyridine (0.18 mmol, 22.4 mg) were dissolved in DMF (2 mL) and stirred. After methylamine (0.12 mmol, 2 M THF solution) was added, the reaction was carried out at room temperature. After the reaction was completed as detected by TLC and LC-MS, the mixture was concentrated and purified by silica gel column chromatography (dichloromethane / methanol) and then by preparative HPLC to obtain compound IID-4.

[1167] Other IID, IIE, IIF, and IIG compounds were synthesized by similar methods.

[1168] The following table lists specific compounds and structure identification data.

[1169]

[1170]

[1171]

[1172]

[1173]

[1174]

[1175]

[1176]

[1177]

[1178]

[1179] Compound IIIA was obtained by a method similar to that for preparing compound IC.

[1180] The following table lists specific compounds and structure identification data.

[1181]

[1182] Biological activity test.

[1183] Growth inhibitory activity of the compound against kinase stably transfected cell lines.

[1184] The activity of the compound against kinases BRK, BTK and BTK kinase with cysteine at position 481 mutated to serine (BTK-C481S) can be evaluated by its inhibition of the growth of kinase stably transfected BaF3 cell lines BRK-BaF3, BTK-BaF3, BTK-C481S-BaF3 and wild-type BaF3 cells. The growth of kinase stably transfected cell lines depends on their kinase activity, while the growth of wild-type BaF3 cells does not depend on this kinase activity. Measuring the effect of the compound on the growth of BaF3 can evaluate its broad-spectrum toxicity. The larger the ratio of the half-maximal inhibitory concentration (IC 50 ) of the compound between BaF3 and BRK-BaF3, BTK-BaF3, BTK-C481S-BaF3, the better the targeting of the compound.

[1185] The specific test method is as follows:

[1186] 1) Culture medium: DMEM (Dulbecco's modified eagle medium) or RPMI1640 (containing 10% fetal bovine serum, 100 μg / mL ampicillin, 100 μg / mL streptomycin).

[1187] 2) Reagents: MTS reaction solution (containing 2 mg / mL of MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt); 100 μg / mL of PES (phenazine methosulfate).

[1188] 3) Compound testing: Seed the cells into a 96-well culture plate with a cell suspension volume of 90 μL, then add 10 μL of each gradient concentration of the compound with the highest concentration of 10 μM, and sequentially dilute stepwise by 1 / 3. A total of 8 concentration points are set, and the system contains 0.1% DMSO (dimethyl sulfoxide). Mix the cell plates with the compounds and place them in a cell culture incubator (37 °C; 5% CO2) for 48 h. Then add 20 μL of the MTS reaction solution, mix well and place it in a cell culture incubator (37 °C; 5% CO2) for incubation for 1 - 4 h; measure the OD value at a wavelength of 490 nm using an enzyme-linked immunosorbent assay (ELISA) reader (VARIOSKAN FLASH, Thermo). Set two parallels for each group of experiments, use 0.1% DMSO at the final concentration as the negative control, and use the culture medium without cells and compounds as the blank control. The cell growth inhibition rate is calculated by the following formula:

[1189] Cell inhibition rate % = 1 - (ODexperimental group - ODblank group) / (ODnegative control group - ODblank group) * 100%

[1190] 4) IC 50 value calculation: Calculate the half-inhibitory concentration of the compound acting on the cells using GradPad Prism 5 software based on the measured cell inhibition rate.

[1191] The following table lists the growth inhibition activities of the compounds on the kinase stable transfected cell lines:

[1192]

[1193]

[1194]

[1195]

[1196] Note: ++++ represents IC 50≤500 nM; +++ represents 500 nM <IC 50 ≤2000 nM; ++ represents 2000 nM <IC 50 ≤10000 nM; + represents IC 50 >10000 nM; ND represents not tested.

Claims

1. The following general formula compounds: or a pharmaceutically acceptable salt of the compound, wherein: the compound is a compound represented by Formula I, Formula II or Formula III, wherein: In Formula I: R 1 Selected from: 1) Z1, Z2, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, and Z5 are not simultaneously hydrogen: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, (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) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-)piperidinyl, 4-(N-ethylpiperazin-1-)piperidinyl, 4-(N-isopropylpiperazin-1-)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-)piperidinyl, 4-(N-(2-cyanoethyl)piperazin-1-)piperidinyl, 4-(N-(3-hydroxypropyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-)piperidinyl, 4-(N-(2-N,N-diethylethyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-dimethylpropyl)piperazin-1-)piperidinyl, 4-(N-(3-N,N-diethylpropyl)piperazin-1-)piperidinyl, 4-(pyrrolidin-1-)piperidinyl, 4-(3-N,N-dimethylaminopyrrolidin-1-)piperidinyl, 4-(3-N,N-diethylaminopyrrolidin-1-)piperidinyl, (5) piperidin-4-yl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-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, (6) acetamido, propionamido, 2-(N,N-dimethylamino)acetamido, 2-hydroxyacetamido, 2-methoxyacetamido, (7) 4-(N-methyl-1-piperazinyl)piperidin-1-carbonyl, 4-(N-ethyl-1-piperazinyl)piperidin-1-carbonyl, 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; 2) Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, (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) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-ethylpiperazin-1-yl)piperidinyl, 4-(N-isopropylpiperazin-1-yl)piperidinyl, (5) N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-(N-methyl-3-pyrrolidinyl)amino, N-methyl-N-(2-N,N-dimethylamino)ethylamino; 3) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkoxy; R x1 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; 4) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x2 and R y are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; 5) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; R x4 is selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl; (6) 1-methyl-3-pyrazolyl, 1-ethyl-3-pyrazolyl, 1-isopropyl-3-pyrazolyl, 1-methyl-4-pyrazolyl, 1-ethyl-4-pyrazolyl, 1-isopropyl-4-pyrazolyl; R 2 Selected from: hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino; W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl; R is selected from: (1) hydrogen, 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: (a) hydrogen, fluorine, chlorine, bromine, nitro, (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluoroalkyl, (c) N-methyl-1-piperazinylmethylene, morpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, azetidin-1-ylmethylene, (d) formyl, acetyl, propionyl, butyryl, 2-methylpropionyl, 3) wherein Y2, Y3, Y4, and Y5 are each independently selected from: (a) hydrogen, fluorine, bromine, (b) C1-C6 alkyl, C1-C6 fluoroalkyl; 4) wherein Y1, Y3, Y4, and Y5 are each independently selected from: hydrogen, chlorine, 5) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: hydrogen, C1-C6 fluoroalkyl; In formula II: R 1 For Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, (3) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl; R 2 Selected from: hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino; W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl; R’ is selected from: 1) wherein, R a , R b are each independently selected from: hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, Or R a , R b and N form a substituted or unsubstituted piperazine ring, and the substituent is halogen, C1-C6 alkyl or C3-C6 cycloalkyl; 2) hydroxy, C1-C6 alkoxy; 3) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: (a) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl, (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene, N-cyclopropyl-1-piperazinylmethylene, N-(2-hydroxyethyl)-1-piperazinylmethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, N-(2-cyanoethyl)-1-piperazinylmethylene; In formula III: R 1 is Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, (3) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl; R 2 Selected from: hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino; W1, W3, W4, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl.

2. The compound according to claim 1, which is the following: or a pharmaceutically acceptable salt of the compound, wherein: R 1 Selected from: 1) Z1, Z2, Z3, Z4, Z5 are each independently selected from the following, and Z1, Z2, Z3, Z4, Z5 are not simultaneously hydrogen: hydrogen, methyl, fluorine, methoxy, ethoxy, isopropoxy, N-methylpiperazine-1-carbonyl, 4-hydroxypiperidinyl, N-methyl-4-piperidinyl, N-methylpiperazinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 2-(N,N-dimethylamino)acetamido, 2) Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen: hydrogen, methyl, methoxy, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-N,N-dimethylaminopiperidinyl, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-methylpiperazinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 3) Wherein: Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, and methoxy; R x1 is methyl; 4) wherein: Z1, Z2, Z5 are hydrogen; R x2 , R y is methyl; 5) wherein: Z1, Z2, Z5 are hydrogen; R x4 is hydrogen; 6) 1-methyl-3-pyrazolyl; R 2 Selected from: hydrogen, methyl, ethyl, isopropyl, cyclopropyl, methoxy, ethoxy, isopropoxy, methylamino, ethylamino, cyclopropylamino, N,N-dimethylamino, methylethylamino, N,N-diethylamino, N,N-diisopropylamino; W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl; R is selected from: 1) hydrogen, 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: (a) hydrogen, fluorine, chlorine, bromine, nitro, (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 fluoroalkyl, (c) N-methyl-1-piperazinylmethylene, morpholine-4-ylmethylene, pyrrolidin-1-ylmethylene, azetidin-1-ylmethylene, (d) formyl, acetyl, propionyl, butyryl, 2-methylpropionyl, 3) wherein Y2, Y3, Y4, and Y5 are each independently selected from: (a) hydrogen, fluorine, bromine, (b) C1-C6 alkyl, C1-C6 fluoroalkyl; 4) wherein Y1, Y3, Y4, and Y5 are each independently selected from: hydrogen, chlorine, 5) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: hydrogen, C1-C6 fluoroalkyl.

3. The compound according to claim 2, wherein R 1 selected from when, Z1, Z2, Z5 are each independently selected from hydrogen, fluorine, methoxy, ethoxy, isopropoxy, and one of Z3 and Z4 is selected from the following, and the other is selected from hydrogen, methyl, fluorine: N-methylpiperazine-1-carbonyl, 4-hydroxypiperidinyl, N-methyl-4-piperidinyl, N-methylpiperazinyl, 4-(N-methylpiperazin-1-yl)piperidinyl, 4-(N-(2-hydroxyethyl)piperazin-1-yl)piperidinyl, 4-(N-(2-N,N-dimethylaminoethyl)piperazin-1-yl)piperidinyl, 4-(pyrrolidin-1-yl)piperidinyl, 4-(N-methyl-1-piperazinyl)piperidine-1-carbonyl, 2-(N,N-dimethylamino)acetamido.

4. The compound according to claim 2, wherein, R 1 selected from when, Z1 and Z5 are each independently selected from hydrogen and methoxy, and one of Z3 and Z4 is selected from the following and the other is hydrogen: methyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-N,N-dimethylaminopiperidinyl, N-methyl-N-(N-methyl-3-pyrrolidinyl)amino, N-methylpiperazinyl, 4-(N-methylpiperazin-1-yl)piperidinyl.

5. The compound according to claim 2, wherein R 2 Selected from hydrogen, methyl, ethyl, isopropyl.

6. The compound according to claim 2, wherein, W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

7. The compound according to claim 2, wherein W1, W2, W3, W5 are each independently selected from hydrogen, methyl.

8. The compound according to claim 2, wherein, W2, W3, W5 are hydrogen, and W1 is methyl.

9. The compound according to claim 2, wherein, R is selected from: 1) hydrogen, 2) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: Hydrogen, fluorine, chlorine, bromine, nitro, methyl, methoxy, acetyl, trifluoromethyl, N-methyl-1-piperazinylmethylene, morpholin-4-ylmethylene, pyrrolidin-1-ylmethylene, azetidin-1-ylmethylene, 3) wherein Y2, Y3, Y4, and Y5 are each independently selected from: Hydrogen, fluorine, bromine, trifluoromethyl, 4) wherein Y1, Y3, Y4, Y5 are each independently selected from: Hydrogen, chlorine, 5) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: Hydrogen, trifluoromethyl.

10. The compound according to claim 1, which is as follows: or a pharmaceutically acceptable salt of the compound, wherein: R 1 is Z1, Z3, Z4, and Z5 are each independently selected from the following, provided that Z1, Z3, Z4, and Z5 are not simultaneously hydrogen: (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, (3) Piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl; R 2 Selected from: Hydrogen, methyl, ethyl, isopropyl; W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl; R' is selected from: 1) wherein, R a , R b are each independently selected from: Hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, or R a ,R b and N form a substituted or unsubstituted piperazine ring, and the substituent is halogen, C1-C6 alkyl or C3-C6 cycloalkyl; 2) Hydroxy, C1-C6 alkoxy; 3) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: (a) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (b) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl, (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene, N-cyclopropyl-1-piperazinylmethylene, N-(2-hydroxyethyl)-1-piperazinylmethylene, N-(2-N,N-dimethylaminoethyl)-1-piperazinylmethylene, N-(2-cyanoethyl)-1-piperazinylmethylene.

11. The compound according to claim 10, wherein, R 1 For Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen: Hydrogen, methyl, 4-N,N-dimethylaminopiperidinyl.

12. The compound according to claim 10, wherein, R 2 is methyl.

13. The compound according to claim 10, wherein, W1, W2, W3, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

14. The compound according to claim 10, wherein, W1, W2, W3, W5 are each independently selected from hydrogen, methyl.

15. The compound according to claim 10, wherein, W2, W3, W5 are hydrogen, and W1 is hydrogen or methyl.

16. The compound according to claim 10, wherein, R' is selected from: 1) wherein, R a , R b each independently selected from: Hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, Or R a , R b and N form a substituted or unsubstituted piperazine ring, and the substituent is a C1-C6 alkyl group; 2) Hydroxy, C1-C6 alkoxy; 3) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: (a) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (b) C1-C6 fluoroalkyl, (c) N-methyl-1-piperazinylmethylene, N-ethyl-1-piperazinylmethylene, N-propyl-1-piperazinylmethylene, N-isopropyl-1-piperazinylmethylene.

17. The compound according to claim 10, wherein, R' is selected from: 1) wherein, R a , R b each independently selected from hydrogen, methyl, ethyl, cyclopropyl, Or R a , R b and N form 2) Hydroxy, methoxy, ethoxy; 3) wherein Y1, Y2, Y3, Y4, and Y5 are each independently selected from: Hydrogen, trifluoromethyl, N-methyl-1-piperazinylmethylene.

18. The compound according to claim 1, which is as follows: or a pharmaceutically acceptable salt of the compound, wherein: R 1 is Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen: (1) Hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, (3) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, 4-methoxypiperidinyl, 4-ethoxypiperidinyl; R 2 Selected from: hydrogen, methyl, ethyl, isopropyl; W1, W3, W4, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxyalkyl, C1-C6 fluoroalkyl, C1-C6 fluoroalkoxy, C3-C6 cycloalkyl.

19. The compound according to claim 18, wherein R 1 For Z1, Z3, Z4, and Z5 are each independently selected from the following, and Z1, Z3, Z4, and Z5 are not simultaneously hydrogen: hydrogen, 4-N,N-dimethylaminopiperidinyl.

20. The compound according to claim 18, wherein, R 2 is isopropyl.

21. The compound according to claim 18, wherein W1, W3, W4, W5 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, C1-C6 alkyl.

22. The compound according to claim 18, wherein W1, W3, W4, W5 are each independently selected from hydrogen, methyl.

23. The compound according to claim 18, wherein, W1, W3, W4 are hydrogen, and W5 is hydrogen or methyl.

24. The compound according to any one of claims 1-23, selected from the following: or a pharmaceutically acceptable salt of the above compound.

25. A pharmaceutical composition comprising the compound according to any one of claims 1-24 or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable excipient.

26. Use of the compound according to any one of claims 1-24 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition according to claim 25 in the preparation of a drug for preventing and / or treating diseases mediated by BRK, BTK kinase or both in an organism.

27. Use of the compound according to any one of claims 1-24 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition according to claim 25 in the preparation of a drug for preventing and / or treating breast cancer, B-cell malignancies.

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