Ring-fused compound as well as preparation and application thereof

Abstract

The invention relates to a ring-fused compound as well as preparation and application thereof. The invention belongs to the technical field of medicine, and relates to a class of ring-fused compounds shown in the formula (I ') and preparation and application thereof.The test result shows that the compounds can remarkably inhibit ATM kinase activity, have good selectivity to ATM target spots and have the medical application to cancer treatment. # imgabs0 #

Description

[0001] Citation of Related Applications

[0002] This application is a divisional application of an invention patent application, the parent case of which is a Chinese patent application with an application date of September 27, 2021, application number 202180066150.0, and invention name “A class of cyclopentadiene compounds and their preparation and application”; the Chinese patent application is an application for the entry into the Chinese national phase of a PCT international application with an application number of PCT / CN2021 / 121023, an application date of September 27, 2021, and invention name “A class of cyclopentadiene compounds and their preparation and application”. These applications claim priority to the invention patent application with the application number of 202011044828.9 filed in China on September 28, 2020 and the invention patent application with the application number of 202110905531.5 filed in China on August 5, 2021, respectively, and the invention patent application with the application number of 202110905531.5 filed in China on August 5, 2021. The entire contents of these patent applications are incorporated herein by reference. Technical Field

[0003] The present invention belongs to the field of medical technology, and in particular, relates to a new compound having ATM protein kinase inhibitory activity and the use of the compound or pharmaceutical composition in preparing medicines. Background Art

[0004] Hereditary ataxia-telangiectasia (AT) is an autosomal recessive genetic disease, which is clinically manifested by progressive cerebellar ataxia, facial telangiectasia, increased sensitivity to radiation, and a significant increase in the tendency to develop tumors (Taylor AM, Harnden DG, Arlett CF, et al. Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity. Nature, 1975, 258: 427-429). It is currently known that it is caused by a mutation in the ataxia telangiectasia mutated gene (ATM gene). The ATM gene is located on chromosome 11q22-23, is 150 kb in length, and has 66 exons. It is one of the human genes with the most exons discovered so far (Savitsky K, Bar Shira A, Gilad S, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science, 1995, 268(5218): 1749-1753).

[0005] ATM protein kinase is the encoded product of the ATM gene, a serine / threonine protein kinase, containing 3056 amino acids, with a relative molecular mass of about 350kDa (CHEN G, LEE E. The product of the ATM gene is a 370-kDa nuclear phosphoprotein. J Biol Chem, 1996, 271 (52): 33693-33697), and is a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family (Watters D, Khanna KK, Beamish H, et al. Cellular localisation of the ataxia-telangiectasia (ATM) gene product and discrimination between mutated and normal forms. Oncogene, 1997, 14: 1911-1921). It is distributed in the nucleus and cytoplasm, and is ubiquitous in the tissue cells of higher eukaryotic organisms, and is highly expressed in some tissue cells such as testis, spleen, thymus, etc.ATM participates in the regulation of cell cycle and the recognition and repair of DNA damage through its C-terminal functional domain. Its roles in cell signal transduction pathways include activating cell cycle checkpoints (Canman CE, Lim DS, Cimprich KA et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science, 1998, 281: 1677-1679), regulating the repair of DNA damage (matsuoka S, huang M, elledge SJ. linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 1998; 282: 1893-1897), and regulating telomeres (Kishi S, Lu KP. A critical role for Pin2 / TRF1 in ATM-dependent regulation. Inhibition of Pin2 / TRF1 function complements telomere shortening, radio sensitivity, and the G(2) / M checkpoint defect of ataxia-telangiectasia cells. Journal Bio Chem. 2002, 277(9): 7420-7429), regulation of cell apoptosis (Lee Y, Barnes DE, Lindahl T, et al. Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm. Genes Dev. 2000, 14: 2576-2580).

[0006] ATM protein kinase mainly acts on repairing DNA double-strand breaks, and maintains the stability of DNA by guiding downstream effector phosphorylation. When cells are damaged by DNA double strands due to ionization or ultraviolet radiation, DNA double-strand breaks (DSB) occur, and MRE11-RAD50-NBS1 (MRN) complex senses DSB and initiates DNA repair to recruit ATM protein kinase. ATM protein kinase, as the main sensor in the DSB repair process, recruits and acts with other proteins. ATM homodimers are separated into active monomers at the DSB site and activated by autophosphorylation and acetylation. Coordinate with other proteins to promote the repair of broken DNA (Lee JH, Paull TT, Activation and regulation of ATM kinase activity inresponse to DNA double-strand breaks. Oncogene. 2007, 26 (56): 7741-7748).

[0007] ATM can also regulate the cell cycle through the Chk2-p53 / AKT pathway, thereby affecting the proliferation and apoptosis of tumor cells (Lazzaro F, Giannattasio M, Puddu F, et al. Checkpoint mechanisms at the intersection between DNA damage and repair. DNA Repair, 2009, 8 (9): 1055-1067). At the same time, activated ATM can also affect the occurrence, migration and invasion of tumors through the ATM-Akt-GSK-3β pathway, transcriptional regulatory factors NF-κB and interleukin IL-8, and participate in DNA damage response through different mechanisms, thereby increasing the resistance and resistance of tumor cells to radiotherapy and chemotherapy (Bo Peng, Janice Ortega, et al. Phosphorylation of proliferating cell nuclear antigen promotes cancer progression by activating the ATM / AKT / GSK3β / Snail signaling pathway. JBC, 2019 (295) 9767).

[0008] Currently, most ATM inhibitors in clinical research are used in combination with radiotherapy and chemotherapy. Molecules under clinical research include AZD-1390 from AstraZeneca and M-3541 from Merck KGaA.

[0009] ATM kinase inhibitors can treat solid tumors or hematological tumors.

[0010] Summary of the invention

[0011] [Annular compounds]

[0012] The present invention provides a class of compounds with novel structures as ATM kinase inhibitors.

[0013] Specifically, the present invention provides a compound as shown in formula (I') or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, which has the following structure:

[0014]

[0015] in,

[0016] Y is

[0017] X 1 is selected from the group consisting of a bond, hydrogen, deuterium, halogen, hydroxyl, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more replaceable sites of the substituted group is independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond;

[0018] When X 1 When R is hydrogen, deuterium, halogen, hydroxyl, amino, nitro or cyano, 1 , X2 , R 2 and R 3 does not exist;

[0019] R 1 is selected from absence, a bond, hydrogen, deuterium or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not substituted or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 1a Replaced by; R 1a Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, nitro, thiol, cyano, oxo, -R 1b 、-OR 1b 、-SR 1b 、-S(O)R 1b 、-SO 2 (R 1b )、-C(O)R 1b 、-C(O)OR 1b 、-OC(O)R 1b 、-NH(R 1b )、-N(R 1b )(R 1c )、-C(O)NH(R 1b )、-C(O)N(R 1b )(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-S(O)N(R 1b )(R 1c ),-SO 2 NH(R 1b ),-SO 2 N(R 1b )(R 1c )、-NHS(O)(R 1b )、-N(R 1b )S(O)(R 1c ), -NHSO 2 (R 1b ) or -N(R 1b )SO 2 (R1c );R 1b , R 1c Each occurrence is independently selected from hydrogen, deuterium or optionally deuterated, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c and the nitrogen atom to which it is attached form a group optionally substituted with deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond;

[0020] When R 1 When X is hydrogen or deuterium, 2 , R 2 and R 3 does not exist;

[0021] X 2 is selected from the group consisting of absence, a bond, hydrogen, deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, -O-, -S-, -P-, -C(O)-, -C(S)-, -C(=NR 2x )-, -CH=N-, -C(O)O-, -C(O)C(O)-, -OC(O)-, -OC(S)-, -O-SO 2 -, -OP(O)-, -N=CH-, -C(O)N(R 2x )-、-N(R 2x )C(O)-、-N(R 2x )-、-S(O)-、-SO 2 -、-S(O)N(R2x )-、-SO 2 N(R 2x )-or-P(O)-;R 2x is selected from hydrogen, deuterium or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently selected from deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond;

[0022] When X 2 When R is hydrogen, deuterium, halogen, hydroxyl, amino, nitro, mercapto or cyano, 2 and R 3 does not exist;

[0023] R 2 is selected from absence, a bond, hydrogen, deuterium or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 aryl, 3-10 membered heterocycloalkyl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not substituted or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 2a Replaced by; R 2a Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, nitro, thiol, cyano, oxo, -R 2b 、-OR 2b 、-SR 2b 、-S(O)(R 2b ),-SO 2 (R 2b )、-C(O)R 2b 、-C(O)OR2b 、-OC(O)R 2b 、-NH(R 2b )、-N(R 2b )(R 2c )、-C(O)NH(R 2b )、-C(O)N(R 2b )(R 2c )、-NHC(O)(R 2b )、-N(R 2b )C(O)(R 2c )、-S(O)NH(R 2b )、-S(O)N(R 2b )(R 2c ),-SO 2 NH(R 2b ),-SO 2 N(R 2b )(R 2c )、-NHS(O)(R 2b )、-N(R 2b )S(O)(R 2c ), -NHSO 2 (R 2b ) or -N(R 2b )SO 2 (R 2c );R 2b , R 2c Each occurrence is independently selected from optionally deuterated, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 2b and R 2c When connected to the same nitrogen atom, R 2b and R 2c and the nitrogen atom to which it is attached form a group optionally substituted with deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond;

[0024] When R 2 When it is hydrogen or deuterium, R 3 does not exist;

[0025] R 3 is selected from the group consisting of absence, hydrogen, deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, -R 3b 、-OR 3b 、-SR 3b 、-S(O)(R 3b ),-SO 2 (R 3b )、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-NH(R 3b )、-N(R 3b )(R 3c )、-C(O)NH(R 3b )、-C(O)N(R 3b )(R 3c )、-NHC(O)(R 3b )、-N(R 3b )C(O)(R 3c )、-S(O)NH(R 3b )、-S(O)N(R 3b )(R 3c ),-SO 2 NH(R 3b ),-SO 2 N(R 3b )(R 3c )、-NHS(O)(R 3b )、-N(R 3b )S(O)(R 3c ), -NHSO 2 (R 3b ) or -N(R 3b )SO 2 (R 3c );R 3b , R 3c Each occurrence is independently selected from hydrogen, deuterium or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 3-20 membered heterocyclic group or a 5-12 membered heteroaryl group; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 3d Replaced by; R 3d Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, nitro, thiol, cyano, oxo, -R 3e 、-OR 3e 、-SR 3e 、-S(O)(R 3e ),-SO 2 (R 3e )、-C(O)R 3e 、-C(O)OR 3e 、-OC(O)R 3e 、-NH(R 3e )、-N(R 3e )(R 3f )、-C(O)NH(R 3e )、-C(O)N(R 3e )(R 3f )、-NHC(O)(R 3e )、-N(R 3e )C(O)(R 3f )、-S(O)NH(R 3e )、-S(O)N(R 3e )(R 3f ),-SO 2 NH(R 3e ),-SO 2 N(R 3e )(R 3f )、-NHS(O)(R 3e )、-N(R 3e )S(O)(R 3f ), -NHSO 2 (R 3e ) or -N(R 3e )SO 2 (R 3f );R 3e , R 3f Each occurrence is independently selected from hydrogen, deuterium or optionally substituted with halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached form a group optionally substituted with deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond;

[0026] R 4 Each occurrence is independently selected from hydrogen, deuterium, halogen, nitro, amino, cyano, hydroxyl, carboxyl, thiol or C optionally substituted with one or more deuterium, halogen, hydroxyl or amino. 1-6 Alkyl, C 1-6 Alkoxy or C 1-6 Alkylthio;

[0027] h is 1 or 2;

[0028] R 5 Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxyl or C optionally substituted with one or more deuterium, halogen, hydroxyl, amino or cyano groups. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-10 Cycloalkyl, C 6-14 Aryl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl;

[0029] L is C(R L ) or N;

[0030] R L Each occurrence is independently selected from hydrogen, deuterium, halogen, nitro, amino, cyano, hydroxyl, carboxyl, thiol, C1-6 Alkyl, C 1-6 Alkoxy or C 1-6 Alkylthio;

[0031] A is

[0032] in, Indicates a single bond or a double bond; Q 1 Connected with W;

[0033] t 1 ,t 2 ,t 3 ,t 4 ,t 5 ,t 6 independently 0 or 1;

[0034] n 1 、n 2 are independently 0, 1 or 2, and n 1 and n 2 Not all are 0, where n 1 Indicates n 1 Q 1 Sequentially connected, n 2 Indicates n 2 Q 2 Sequentially connected; two adjacent Q 1 They are connected by single or double bonds; two adjacent Q 2 They are connected by single or double bonds;

[0035] W.Q 1 , Q 2 independently selected from C, O, N or S;

[0036] Q 3 is C; when connected to Q 3 When one of the bonds is a double bond, R 10 or R 11 does not exist;

[0037] R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, cyano, nitro, -R 6a 、-OR 6a 、-SR 6a 、-S(O)(R 6a ),-SO 2 (R 6a)、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b )、-S(O)NH(R 6a )、-S(O)N(R 6a )(R 6b ),-SO 2 NH(R 6a ),-SO 2 N(R 6a )(R 6b )、-NHS(O)(R 6a )、-N(R 6a )S(O)(R 6b ), -NHSO 2 (R 6a ) or -N(R 6a )SO 2 (R 6b ); or R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Any two substituents attached to the same atom together form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group or heteromonospirocyclic group;

[0038] R 6a , R 6b Each occurrence is independently selected from hydrogen, deuterium or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or when R 6a and R 6b When connected to the same nitrogen atom, R 6a and R 6b and the nitrogen atom to which it is attached together form an optionally R 6c substituted 3-10 membered heterocyclyl or 5-12 membered heteroaryl;

[0039] R 6c Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, cyano, nitro, azido, oxo, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e 、-C(O)OR 6d 、-OC(O)R 6d 、-S(O)N(R 6d )(R 6e ),-SO 2 N(R 6d )(R 6e )、-N(R 6d )S(O)(R 6e )、-N(R 6d )SO 2 (R 6e ), =NR 6d or =CH-R 6d ; The oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond; the =NR 6dIt means that two H at the same substitution site are replaced by the same N to form a double bond, and N is replaced by R 6d Substitution; said =CH-R 6d It means that two H at the same substitution site are replaced by the same C to form a double bond, and C is replaced by R 6d replace;

[0040] R 6d , R 6e Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, cyano or optionally substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, monospirocyclic group, heteromonospirocyclic group, fused cyclic group or heterofused cyclic group; or when R 6d and R 6e When connected to the same nitrogen atom, R 6d and R 6e and the nitrogen atom to which it is attached form an optionally substituted 3-10 membered heterocyclic group or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 6f Replaced by; R 6f Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -C(O)C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH-C 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the oxo group means that two H at the same substitution site are replaced by the same O to form a double bond;

[0041] When a heterocycloalkyl group, a heteroaryl group, a heterocyclic group, a heteromonospirocyclic group, a heterocondensed cyclic group and / or a heterobridged cyclic group is present, the heteroatoms therein are independently selected from O, N or S, and the number of the heteroatoms is 1, 2, 3 or 4.

[0042] The present invention also provides a compound as shown in formula (I) or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, which has the following structure:

[0043]

[0044] in,

[0045] Y is

[0046] X 1 is selected from the group consisting of a bond, hydrogen, halogen, hydroxy, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more replaceable sites of the substituted group is independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond;

[0047] When X 1 When R is hydrogen, halogen, hydroxyl, amino, nitro or cyano, 1 , X 2 , R 2 and R 3 does not exist;

[0048] R 1 is selected from absence, a bond, hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not substituted or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 1a Replaced by; R 1a Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 1b 、-OR 1b 、-SR 1b 、-S(O)R 1b 、-SO 2 (R 1b )、-C(O)R 1b 、-C(O)OR 1b 、-OC(O)R 1b 、-NH(R 1b )、-N(R 1b )(R 1c )、-C(O)NH(R 1b )、-C(O)N(R 1b )(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-S(O)N(R 1b )(R 1c ),-SO 2 NH(R 1b ),-SO 2 N(R 1b )(R 1c )、-NHS(O)(R 1b )、-N(R 1b )S(O)(R 1c ), -NHSO 2 (R 1b ) or -N(R 1b )SO 2 (R 1c );R 1b , R 1c Each occurrence is independently selected from hydrogen or optionally substituted with halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c and the nitrogen atom to which it is attached form a group optionally substituted with halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond;

[0049] When R 1 When X is hydrogen, 2 , R 2 and R 3 does not exist;

[0050] X 2 is selected from the group consisting of absence, a bond, hydrogen, halogen, hydroxyl, amino, nitro, thiol, cyano, -O-, -S-, -P-, -C(O)-, -C(S)-, -C(=NR 2x )-, -CH=N-, -C(O)O-, -C(O)C(O)-, -OC(O)-, -OC(S)-, -O-SO 2 -, -OP(O)-, -N=CH-, -C(O)N(R 2x )-、-N(R 2x )C(O)-、-N(R 2x )-、-S(O)-、-SO 2 -、-S(O)N(R 2x )-、-SO 2 N(R 2x )-or-P(O)-;R 2x is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14Aryl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more replaceable sites of the substituted group is independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond;

[0051] When X 2 When R is hydrogen, halogen, hydroxyl, amino, nitro, mercapto or cyano, 2 and R 3 does not exist;

[0052] R 2 is selected from absence, a bond, hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 aryl, 3-10 membered heterocycloalkyl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not substituted or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 2a Replaced by; R 2a Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 2b 、-OR 2b 、-SR 2b 、-S(O)(R 2b ),-SO 2 (R 2b )、-C(O)R 2b 、-C(O)OR 2b 、-OC(O)R 2b 、-NH(R 2b )、-N(R 2b )(R 2c )、-C(O)NH(R 2b )、-C(O)N(R 2b )(R 2c )、-NHC(O)(R 2b )、-N(R 2b )C(O)(R2c )、-S(O)NH(R 2b )、-S(O)N(R 2b )(R 2c ),-SO 2 NH(R 2b ),-SO 2 N(R 2b )(R 2c )、-NHS(O)(R 2b )、-N(R 2b )S(O)(R 2c ), -NHSO 2 (R 2b ) or -N(R 2b )SO 2 (R 2c );R 2b , R 2c Each occurrence is independently selected from optionally substituted with halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 2b and R 2c When connected to the same nitrogen atom, R 2b and R 2c and the nitrogen atom to which it is attached form a group optionally substituted with halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond;

[0053] When R 2 When it is hydrogen, R 3 does not exist;

[0054] R 3is selected from the group consisting of absent, hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 3b 、-OR 3b 、-SR 3b 、-S(O)(R 3b ),-SO 2 (R 3b )、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-NH(R 3b )、-N(R 3b )(R 3c )、-C(O)NH(R 3b )、-C(O)N(R 3b )(R 3c )、-NHC(O)(R 3b )、-N(R 3b )C(O)(R 3c )、-S(O)NH(R 3b )、-S(O)N(R 3b )(R 3c ),-SO 2 NH(R 3b ),-SO 2 N(R 3b )(R 3c )、-NHS(O)(R 3b )、-N(R 3b )S(O)(R 3c ), -NHSO 2 (R 3b ) or -N(R 3b )SO 2 (R 3c );R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R3d Replaced by; R 3d Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 3e 、-OR 3e 、-SR 3e 、-S(O)(R 3e ),-SO 2 (R 3e )、-C(O)R 3e 、-C(O)OR 3e 、-OC(O)R 3e 、-NH(R 3e )、-N(R 3e )(R 3f )、-C(O)NH(R 3e )、-C(O)N(R 3e )(R 3f )、-NHC(O)(R 3e )、-N(R 3e )C(O)(R 3f )、-S(O)NH(R 3e )、-S(O)N(R 3e )(R 3f ),-SO 2 NH(R 3e ),-SO 2 N(R 3e )(R 3f )、-NHS(O)(R 3e )、-N(R 3e )S(O)(R 3f ), -NHSO 2 (R 3e ) or -N(R 3e )SO 2 (R 3f );R 3e , R 3f Each occurrence is independently selected from hydrogen or optionally substituted with halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached form a group optionally substituted with halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond;

[0055] R 4 is selected from hydrogen, halogen, nitro, amino, cyano, hydroxyl, carboxyl, mercapto or C optionally substituted by halogen, hydroxyl or amino 1-6 Alkyl, C 1-6 Alkoxy or C 1-6 Alkylthio;

[0056] R 5 is selected from hydrogen, halogen, hydroxyl or C optionally substituted by one or more halogen, hydroxyl, amino or cyano groups. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-10 Cycloalkyl, C 6-14 Aryl, 3-10 membered heterocycloalkyl and 5-12 membered heteroaryl;

[0057] L is C(R L ) or N;

[0058] R L is selected from hydrogen, halogen, nitro, amino, cyano, hydroxyl, carboxyl, thiol, C 1-6 Alkyl, C 1-6 Alkoxy or C 1-6 Alkylthio;

[0059] A is

[0060] in, Indicates a single bond or a double bond; Q 1 Connected with W;

[0061] t 1 ,t 2 ,t 3 ,t 4 ,t 5 ,t6 independently 0 or 1;

[0062] n 1 、n 2 are independently 0, 1 or 2, and n 1 and n 2 Not all are 0, where n 1 Indicates n 1 Q 1 Sequentially connected, n 2 Indicates n 2 Q 2 Sequentially connected; two adjacent Q 1 They are connected by single or double bonds; two adjacent Q 2 They are connected by single or double bonds;

[0063] W.Q 1 , Q 2 independently selected from C, O, N or S;

[0064] Q 3 is C; when connected to Q 3 When one of the bonds is a double bond, R 10 or R 11 does not exist;

[0065] R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, -R 6a 、-OR 6a 、-SR 6a 、-S(O)(R 6a ),-SO 2 (R 6a )、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b )、-S(O)NH(R 6a)、-S(O)N(R 6a )(R 6b ),-SO 2 NH(R 6a ),-SO 2 N(R 6a )(R 6b )、-NHS(O)(R 6a )、-N(R 6a )S(O)(R 6b ), -NHSO 2 (R 6a ) or -N(R 6a )SO 2 (R 6b ); or R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Any two substituents attached to the same atom together form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group or heteromonospirocyclic group;

[0066] R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or when R 6a and R 6b When connected to the same nitrogen atom, R 6a and R 6b and the nitrogen atom to which it is attached together form an optionally R 6c substituted 3-10 membered heterocyclyl or 5-12 membered heteroaryl;

[0067] R 6c Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, azido, oxo, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e 、-C(O)OR 6d 、-OC(O)R 6d 、-S(O)N(R 6d )(R 6e ),-SO 2 N(R 6d )(R 6e )、-N(R 6d )S(O)(R 6e )、-N(R 6d )SO 2 (R 6e ), =NR 6d or =CH-R 6d ; The oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond; the =NR 6d It means that two H at the same substitution site are replaced by the same N to form a double bond, and N is replaced by R 6d Substitution; said =CH-R 6d It means that two H at the same substitution site are replaced by the same C to form a double bond, and C is replaced by R 6d replace;

[0068] R 6d , R 6e Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, cyano or optionally substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, monospirocyclic group, heteromonospirocyclic group, fused cyclic group or heterofused cyclic group; or when R 6d and R 6e When connected to the same nitrogen atom, R 6d and R 6e and the nitrogen atom to which it is attached form an optionally substituted 3-10 membered heterocyclic group or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 6f Replaced by; R 6f Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -C(O)C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH-C 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the oxo group means that two H at the same substitution site are replaced by the same O to form a double bond;

[0069] When a heterocycloalkyl group, a heteroaryl group, a heterocyclic group, a heteromonospirocyclic group, a heterocondensed cyclic group and / or a heterobridged cyclic group is present, the heteroatoms therein are independently selected from O, N or S, and the number of the heteroatoms is 1, 2, 3 or 4.

[0070] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (Ia):

[0071]

[0072] Wherein, each substituent is as defined in formula (I') or the compound of formula (I).

[0073] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (Ib):

[0074]

[0075] Wherein, each substituent is as defined in formula (I') or the compound of formula (I).

[0076] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (Ic):

[0077]

[0078] Wherein, each substituent is as defined in formula (I') or the compound of formula (I).

[0079] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 1 is selected from the group consisting of a bond, hydrogen, halogen, hydroxy, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x Selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl.

[0080] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 1 is selected from the group consisting of a bond, hydrogen, halogen, hydroxy, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x Selected from hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl or 3-6 membered heterocycloalkyl.

[0081] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 1 is selected from a bond, hydrogen, halogen, hydroxyl, amino, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -NHC(O)-, -C(O)NH-, -NH- or -N(CH 3 )-.

[0082] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 1 is selected from a bond, hydrogen, -S-, -NHC(O)- or -C(O)NH-.

[0083] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 1 Select from keys.

[0084] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1 is selected from an optionally substituted 3-10 membered heterocyclic group; wherein the optionally substituted group is optionally replaced by R 1a replaced.

[0085] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from an optionally substituted 5-8 membered heterocyclic group, wherein the heteroatom is N and the number of heteroatoms is 1 or 2; the optional substitution refers to optionally being replaced by R 1a replaced.

[0086] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted dihydropyridinyl; wherein the optional substitution refers to being optionally replaced by R 1a replaced.

[0087] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from absence, a bond, hydrogen or optionally substituted C 1-6 Alkyl, C 1-6Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means optionally replaced by R 1a replaced.

[0088] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means optionally replaced by R 1a replaced.

[0089] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from optionally substituted C 1-6 Alkyl, C 2-6 Alkynyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means optionally replaced by R 1a replaced.

[0090] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from optionally substituted C 2-6 Alkynyl or 5-12 membered heteroaryl; the optional substitution means optionally replaced by R 1a replaced.

[0091] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from optionally substituted C 2-6 Alkynyl or 5-8 membered heteroaryl, wherein the heteroatom is N, and the number of heteroatoms is 1, 2 or 3; the optional substitution refers to the optional substitution of R 1a replaced.

[0092] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 Selected from optionally substituted C 2-6 Alkynyl; the optional substitution means optionally by R 1a replaced.

[0093] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted 5-12 membered heteroaryl; wherein the optional substitution refers to being optionally replaced by R 1a replaced.

[0094] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from an optionally substituted 5-8 membered heteroaryl group, wherein the heteroatom is N, and the number of heteroatoms is 1, 2 or 3; the optional substitution refers to optionally being replaced by R 1a replaced.

[0095] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from an optionally substituted 5-6 membered heteroaryl group, wherein the heteroatom is N and the number of heteroatoms is 1 or 2; the optional substitution refers to optionally being replaced by R 1a replaced.

[0096] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted ethynyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyrazolyl, imidazolyl or pyrrolyl; the optional substitution means that R 1a replaced.

[0097] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from ethynyl.

[0098] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted pyridyl, pyrimidinyl, pyrazinyl or pyrazolyl; the optional substitution means that R 1a replaced.

[0099] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted pyridyl; the optional substitution refers to optionally being R 1a replaced.

[0100] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1a Each occurrence is independently selected from halogen, hydroxy, amino, oxo, -R 1b 、-OR 1b 、-SR 1b 、-S(O)R 1b 、-SO 2 (R 1b )、-C(O)R 1b 、-C(O)OR 1b 、-OC(O)R 1b 、-NH(R 1b )、-N(R 1b )(R 1c )、-C(O)NH(R 1b )、-C(O)N(R 1b )(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-S(O)N(R 1b )(R 1c ),-SO 2 NH(R 1b ),-SO 2 N(R 1b )(R 1c )、-NHS(O)(R 1b )、-N(R 1b )S(O)(R 1c ), -NHSO 2 (R 1b ) or -N(R 1b )SO 2 (R 1c ); the oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond.

[0101] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1a Each occurrence is independently selected from halogen, hydroxy, amino, oxo, -R 1b 、-OR 1b 、-SO 2 (R 1b )、-C(O)R 1b 、-C(O)OR 1b 、-OC(O)R 1b 、-N(R 1b )(R 1c )、-C(O)N(R 1b )(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-S(O)N(R 1b )(R 1c ),-SO 2 NH(R 1b ),-SO 2 N(R 1b )(R 1c )、-NHS(O)(R 1b )、-N(R 1b )S(O)(R 1c ), -NHSO 2 (R 1b ) or -N(R 1b )SO 2 (R 1c ); the oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond.

[0102] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a Each occurrence is independently selected from halogen, hydroxy, amino, oxo, -R 1b 、-C(O)NH(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b ),-SO 2 NH(R 1b )、-NHS(O)(R 1b ), -NHSO 2 (R 1b ) or -N(R 1b )SO2 (R 1c ); the oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond.

[0103] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a Each occurrence is independently selected from halogen, amino, oxo, -R 1b 、-NHC(O)(R 1b ) or -NHSO 2 (R 1b ); the oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond.

[0104] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a Each occurrence is independently selected from -NHC(O)(R 1b ) or -NHSO 2 (R 1b ).

[0105] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from hydrogen or optionally substituted with halogen, hydroxy, amino, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-8 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c and the nitrogen atom to which it is attached together form an optionally substituted halogen, hydroxyl, amino, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-8 One or more arbitrarily substituted aryl or 5-8 membered heteroaryl groups are 3-10 membered heterocycloalkyl groups or 5-12 membered heteroaryl groups; the oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond.

[0106] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c Together with the nitrogen atom to which it is attached, it forms a 3-10 membered heterocycloalkyl.

[0107] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from C 1-6 Alkyl, 3-8 membered heterocycloalkyl or C 6-8 Aryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c Together with the nitrogen atom to which it is attached, it forms a 3-8 membered heterocycloalkyl.

[0108] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from C 1-6 Alkyl, C 3-10 Cycloalkyl or C 6-8 Aryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c Together with the nitrogen atom to which it is attached, it forms a 3-8 membered heterocycloalkyl.

[0109] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from C 1-6 Alkyl, C 3-8 Cycloalkyl or C 6-8 Aryl.

[0110] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from C 1-6 Alkyl, C 3-6 Cycloalkyl or C 6 Aryl (ie phenyl).

[0111] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from C 1-6 Alkyl or C 3-6 Cycloalkyl.

[0112] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from C 1-4 Alkyl or C 3-4 Cycloalkyl.

[0113] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from methyl, ethyl, cyclopropanyl, phenyl or tetrahydropyranyl.

[0114] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c Each occurrence is independently selected from methyl or cyclopropane.

[0115] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted pyrazolyl; wherein the optionally substituted refers to being optionally replaced by R 1a Replaced by; R 1a Independently selected from C 1-6 Alkyl or 3-8 membered heterocycloalkyl.

[0116] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted pyrazolyl; wherein the optionally substituted refers to being optionally replaced by R 1a Replaced by; R 1a Independently selected from C 1-4 Alkyl or 6-membered heterocycloalkyl.

[0117] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted pyrazolyl; wherein the optionally substituted refers to being optionally replaced by R 1a Replaced by; R 1a Independently selected from methyl, ethyl or tetrahydropyranyl.

[0118] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted pyridyl; the optional substitution refers to optionally being R 1a Replaced by; R 1a independently selected from amino, -NHC(O)(R 1b ) or -NHSO 2 (R 1b );R 1b Each occurrence is independently selected from C 1-6 Alkyl, C 3-6 Cycloalkyl or phenyl.

[0119] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 is selected from optionally substituted pyridyl; the optional substitution refers to optionally being R 1a Replaced by; R 1a independently selected from amino, -NHC(O)(R 1b ) or -NHSO2 (R 1b );R 1b Each occurrence is independently selected from C 1-4 Alkyl, C 3-4 Cycloalkyl or phenyl.

[0120] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from the following optionally substituted groups:

[0121]

[0122] Among them, the "*" end is connected to X 1 One end is connected to X 2 The optional substitution refers to optionally being R 1a replaced.

[0123] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from optionally substituted

[0124] Among them, the "*" end is connected to X 1 One end is connected to X 2 The optional substitution refers to optionally being R 1a replaced.

[0125] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from the following groups:

[0126]

[0127] Among them, the "*" end is connected to X 1 One end is connected to X 2 one end.

[0128] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from the following groups:

[0129]

[0130] Among them, the "*" end is connected to X 1One end is connected to X 2 one end.

[0131] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from the following groups:

[0132]

[0133] Among them, the "*" end is connected to X 1 One end is connected to X 2 one end.

[0134] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from the following groups:

[0135] Among them, the "*" end is connected to X 1 One end is connected to X 2 one end.

[0136] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from the following groups:

[0137]

[0138] Among them, the "*" end is connected to X 1 One end is connected to X 2 one end.

[0139] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1 Selected from the following groups:

[0140] Among them, the "*" end is connected to X 1 one end.

[0141] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 2 is selected from the group consisting of absence, a bond, hydrogen, halogen, hydroxyl, amino, -O-, -S-, -C(O)O-, -OC(O)-, -C(O)N(R2x )-、-N(R 2x )C(O)-or-N(R 2x )-;R 2x is selected from hydrogen or C optionally substituted by halogen, hydroxy or amino 1-6 alkyl.

[0142] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 2 is selected from the group consisting of absence, a bond, hydrogen, halogen, hydroxyl, amino, -O-, -S-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -NH-, -N(CH 3 )-or-N(CH 2 CH 3 )-.

[0143] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 2 is selected from absence, a bond, -O-, -NH- or -N(CH 3 )-.

[0144] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 2 Selected from absence, a bond, -O- or -N(CH 3 )-.

[0145] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 2 is selected from a bond, -O- or -NH-.

[0146] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 2 is selected from absence, a bond or -O-.

[0147] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X 2 Selected from -O-.

[0148] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 2 is selected from absence, a bond, hydrogen or optionally substituted by halogen, hydroxy, amino, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-8 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 aryl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl.

[0149] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 2 Selected from Absent, Hydrogen, C 1-6 Alkyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 aryl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl.

[0150] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 2 Select from non-existent, C 1-6 Alkyl, C 2-4 Alkynyl or 5-6 membered heterocycloalkyl, wherein the heteroatom is N or O, and the number of the heteroatoms is 1 or 2.

[0151] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 2 is selected from absent, methyl, ethyl, propyl (n-propyl, isopropyl), butyl (n-butyl, isobutyl, sec-butyl, tert-butyl), ethynyl, piperidinyl, tetrahydropyrrolyl or tetrahydropyranyl.

[0152] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 2 Selected from n-propyl.

[0153] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3 is selected from the group consisting of absent, hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 3b 、-OR 3b 、-SR 3b 、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-N(R 3b )(R 3c )、-C(O)N(R 3b )(R 3c )、-C(O)NH(R 3b )、-NHC(O)(R 3b )、-N(R 3b )C(O)(R 3c )、-S(O)N(R 3b )(R 3c ),-SO 2 N(R 3b )(R 3c )、-N(R 3b )S(O)(R 3c ) or -N(R 3b )SO 2 (R 3c ); the oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond.

[0154] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3 is selected from the group consisting of absent, hydrogen, halogen, hydroxy, amino, oxo, -R 3b 、-OR 3b 、-SR 3b 、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-N(R 3b )(R 3c )、-C(O)N(R 3b )(R 3c )、-C(O)NH(R 3b ) or -NHC(O)(R 3b ); the oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond.

[0155] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3 Select from non-existent, -R 3b 、-OR 3b or -N(R 3b )(R 3c ).

[0156] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3 Selected from -N(R 3b )(R 3c ).

[0157] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl, 4-12 membered bicyclic heterocyclyl or 5-12 membered heteroaryl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0158] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3cand the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0159] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy or 3-10 membered heterocycloalkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0160] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3 Select from non-existent, C 1-6 Alkyl, C 1-6 Alkoxy or -N(R 3b )(R 3c );R 3b , R 3c are independently selected from optionally substituted C 1-6 Alkyl, or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0161] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy or 3-10 membered heterocycloalkyl; the optional substitution means optionally replaced by R 3d replaced.

[0162] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl; the optional substitution means optionally replaced by R 3d replaced.

[0163] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0164] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 5-6 membered heterocycloalkyl or 6-10 membered bicyclic heterocyclic group, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1, 2, 3 or 4; the optional substitution refers to optionally being replaced by R 3d replaced.

[0165] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-6 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl or 4-12 membered bicyclic heterocyclyl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0166] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R3b , R 3c Each occurrence is independently selected from optionally substituted C 1-6 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 4-8 membered heterocycloalkyl or 6-10 membered bicyclic heterocyclyl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0167] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-4 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 5-6 membered heterocycloalkyl or 6-10 membered bicyclic heterocyclic group, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1, 2, 3 or 4; the optional substitution refers to optionally being replaced by R 3d replaced.

[0168] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-4 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3cand the nitrogen atom to which it is attached form an optionally substituted 5-6 membered heterocycloalkyl, a 3-membered / 4-membered heteromonospirocyclic radical, a 4-membered / 3-membered heteromonospirocyclic radical, a 3-membered / 5-membered heteromonospirocyclic radical, a 5-membered / 3-membered heteromonospirocyclic radical, a 3-membered / 6-membered heteromonospirocyclic radical, a 6-membered / 3-membered heteromonospirocyclic radical, a 4-membered / 5-membered heteromonospirocyclic radical, a 5-membered / 4-membered heteromonospirocyclic radical, a 4-membered / 6-membered heteromonospirocyclic radical, a 6-membered / 4-membered heteromonospirocyclic radical, a 4-membered / 4-membered heteromonospirocyclic radical, heteromonospirocyclic group, 5-membered / 5-membered heteromonospirocyclic group, 5-membered / 6-membered heteromonospirocyclic group, 6-membered / 5-membered heteromonospirocyclic group, 3-membered / 5-membered heterocyclic group, 5-membered / 3-membered heterocyclic group, 3-membered / 6-membered heterocyclic group, 6-membered / 3-membered heterocyclic group, 5-membered / 6-membered heterocyclic group or 6-membered / 5-membered heterocyclic group, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1, 2, 3 or 4; the optional substitution refers to the optional substitution of R 3d replaced.

[0169] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-4 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 5-6 membered heterocycloalkyl, a 3-membered / 6-membered heteromonospirocyclic group, a 6-membered / 3-membered heteromonospirocyclic group, a 4-membered / 6-membered heteromonospirocyclic group, a 6-membered / 4-membered heteromonospirocyclic group or a 4-membered / 4-membered heteromonospirocyclic group, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1 or 2; the optional substitution refers to optionally being replaced by R 3d replaced.

[0170] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted methyl, or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted piperidinyl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0171] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R3d Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, cyano, -R 3e 、-C(O)R 3e 、-C(O)OR 3e 、-N(R 3e )(R 3f ) or -C(O)NH(R 3e );R 3e , R 3f Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached together form an optionally substituted halogen, hydroxyl, amino, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 aryl or 5-12 membered heteroaryl, and one or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl.

[0172] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, cyano, -R 3e 、-C(O)R 3e 、-C(O)OR 3e 、-N(R 3e )(R 3f ) or -C(O)NH(R 3e );R 3e , R 3f Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6Cycloalkyl, 3-6 membered heterocycloalkyl, C 6 Aryl or 5-6 membered heteroaryl.

[0173] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, cyano, -CHO, -CO(C 1-6 alkyl), -COOH, -COO(C 1-6 Alkyl), -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 Alkyl), -C(O)NH 2 , C 1-6 Alkyl, C 1-6 Alkoxy or 3-6 membered heterocycloalkyl.

[0174] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from deuterium, hydroxyl, amino, -CHO, -CO(C 1-6 alkyl), -COOH, -COO(C 1-6 Alkyl), -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 Alkyl), -C(O)NH 2 , C 1-6 Alkyl, C 1-6 Alkoxy or 5-6 membered heterocycloalkyl.

[0175] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from deuterium, fluorine, hydroxyl, amino, cyano, -CHO, -COCH 3 、-COOH、-COOCH 3 、-NH(CH 3 )、-N(CH 3 )(CH 3 )、-C(O)NH 2 、-CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-OCH3 、-OCH 2 CH 3 、-OCH 2 CH 2 CH 3 , piperidinyl, piperazinyl or tetrahydropyrrolyl.

[0176] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from deuterium, fluorine, amino, cyano, -C(O)NH 2 、-CH 3 or piperidinyl.

[0177] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from halogen, hydroxy, amino, -R 3e or -N(R 3e )(R 3f );R 3e , R 3f Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached together form an optionally substituted halogen, hydroxyl, amino, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 aryl or 5-12 membered heteroaryl, and one or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl.

[0178] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from -R 3e or -N(R 3e )(R 3f);R 3e , R 3f Each occurrence is independently selected from C 1-6 Alkyl or 3-8 membered heterocycloalkyl, or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f Together with the nitrogen atom to which it is attached, it forms a 3-8 membered heterocycloalkyl.

[0179] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Selected from methyl, -N(methyl)(methyl) (ie dimethylamino) or piperidinyl.

[0180] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3 Selected from the following optionally substituted groups:

[0181] The optional substitution refers to optionally being replaced by R 3d replaced.

[0182] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3 Selected from the following groups:

[0183]

[0184] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3 Selected from the following groups:

[0185]

[0186] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (II-a):

[0187]

[0188] Among them, m 1-1 Selected from 0, 1 or 2, R 1a-1 For example, in the compound of formula (I') or formula (I), R 1a Defined by X2-1 For example, in the compound of formula (I') or formula (I), X 2 As defined, R 2-1 For example, in the compound of formula (I') or formula (I), R 2 As defined, R 3-1 For example, in the compound of formula (I') or formula (I), R 3 As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in the compound of formula (I).

[0189] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-a 1 ) shows the structure:

[0190]

[0191] Among them, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0192] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-a 2 ) shows the structure:

[0193]

[0194] Among them, R 3b-1 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-1 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0195] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (II-b):

[0196]

[0197] Among them, m 1-2 is selected from 0, 1, 2 or 3, R 1a-2 For example, in the compound of formula (I') or formula (I), R 1a Defined by X 2-2 For example, in the compound of formula (I') or formula (I), X 2 As defined, R 2-2 For example, in the compound of formula (I') or formula (I), R 2 As defined, R 3-2 For example, in the compound of formula (I') or formula (I), R 3 As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0198] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-b 1 ) shows the structure:

[0199]

[0200] Among them, m 1-3 is selected from 0, 1, 2 or 3, R 1a-3 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0201] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (II-c):

[0202]

[0203] Among them, m 1-4 is selected from 0, 1, 2 or 3, R 1a-4 For example, in the compound of formula (I') or formula (I), R 1a Defined by X 2-3 For example, in the compound of formula (I') or formula (I), X 2 As defined, R 2-3 For example, in the compound of formula (I') or formula (I), R 2 As defined, R 3-3 For example, in the compound of formula (I') or formula (I), R 3 As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0204] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-c 1 ) shows the structure:

[0205]

[0206] Among them, m 1-5 is selected from 0, 1, 2 or 3, R 1a-5 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3b-2 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-2 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0207] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (II-d):

[0208]

[0209] Among them, E 1 、E 2、E 3 、E 4 、E 5 、E 6 are independently selected from C or N, m 1-6 is selected from 0, 1, 2, 3 or 4, R 1a-6 For example, in the compound of formula (I') or formula (I), R 1a Defined by X 2-4 For example, in the compound of formula (I') or formula (I), X 2 As defined, R 2-4 For example, in the compound of formula (I') or formula (I), R 2 Definition, R 3-4 For example, in the compound of formula (I') or formula (I), R 3 As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0210] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-d 1 ) shows the structure:

[0211]

[0212] Among them, m 1-7 is selected from 0, 1, 2 or 3, R 1a-7 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3b-3 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-3 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0213] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-d 2 ) shows the structure:

[0214]

[0215] Among them, m 1-8 Selected from 0, 1 or 2, R 1a-8 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3b-4 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-4 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0216] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-d 3 ) shows the structure:

[0217]

[0218] Among them, m 1-9 Selected from 0, 1 or 2, R 1a-9 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3b-5 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-5 As R 3c As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0219] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-d 4 ) shows the structure:

[0220]

[0221] Among them, m 1-10 is selected from 0, 1, 2 or 3, R 1a-10For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3e-1 For example, in the compound of formula (I') or formula (I), R 3e As defined, R 3f-1 For example, in the compound of formula (I') or formula (I), R 3f As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0222] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-d 5 ) shows the structure:

[0223]

[0224] Among them, m 1-11 is selected from 0, 1, 2 or 3, R 1a-11 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0225] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-d 6 ) shows the structure:

[0226]

[0227] Among them, m 1-12 is selected from 0, 1, 2 or 3, R 1a-12 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3b-6 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-6 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 2x-1 For example, in the compound of formula (I') or formula (I), R 2xAs defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0228] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (II-e):

[0229]

[0230] Among them, E 7 、E 8 、E 9 、E 10 、E 11 、E 12 are independently selected from C or N, m 1-13 Selected from 0, 1, 2 or 3, m 2-1 is selected from 0, 1, 2, 3 or 4, R 1a-13 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 2a-1 For example, in the compound of formula (I') or formula (I), R 2a As defined, R 3-5 For example, in the compound of formula (I') or formula (I), R 3 As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0231] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (II-e 1 ) shows the structure:

[0232]

[0233] Among them, m 1-14 Selected from 0, 1, 2 or 3; m 2-2 is selected from 0, 1, 2, 3 or 4, R 1a-14 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 2a-2For example, in the compound of formula (I') or formula (I), R 2a As defined, R 3b-7 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-7 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0234] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (II-f):

[0235]

[0236] Among them, m 1-15 is selected from 0, 1, 2 or 3, R 1a-15 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3e-2 For example, in the compound of formula (I') or formula (I), R 3e As defined, R 3f-2 For example, in the compound of formula (I') or formula (I), R 3f As defined, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0237] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (II-g):

[0238]

[0239] Among them, R 3b-8 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-8 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 6, R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0240] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1a Independently selected from -H, -F, -Cl, -NH 2 , oxo, -CH 3 、-CH 2 CH 3 、-OCH 3 、-OCH 2 CH 3 、-NHC(O)CH 3 、-C(O)NHCH 3 , The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond.

[0241] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a Independently selected from -H, -NH 2 , oxo, -CH 3 、-CH 2 CH 3 、-NHC(O)CH 3 , The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond.

[0242] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, Y is selected from the following groups:

[0243]

[0244] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, Y is selected from the following groups:

[0245]

[0246] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R4 is selected from hydrogen, halogen, amino or C 1-6 Alkoxy.

[0247] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 4 Selected from hydrogen, halogen or C 1-3 Alkoxy.

[0248] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 4 is selected from hydrogen, fluorine or methoxy.

[0249] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 4 Selected from hydrogen or fluorine.

[0250] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 4 Selected from methoxy.

[0251] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 5 is selected from hydrogen, deuterium or C optionally substituted by one or more deuterium 1-6 alkyl.

[0252] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 5 C 1-6 alkyl.

[0253] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 5 C 1-3 alkyl.

[0254] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 5 It is methyl.

[0255] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, L is C(R L ) or N, R L Selected from hydrogen, halogen, amino, hydroxyl, C 1-6 Alkyl or C 1-6 Alkoxy.

[0256] More preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, L is C(R L ), R L is selected from hydrogen, halogen, amino, methyl or methoxy.

[0257] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, L is CH.

[0258] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, L is N.

[0259] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, W, Q 1 , Q 2 Independently selected from O, C, S or N; Q 3 is C; among them, Q 1 Connected to W.

[0260] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, W, Q 1 , Q 2 Independently selected from O, C or S; Q 3 is C; among them, Q 1 Connected to W.

[0261] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, W is selected from O or N; Q 1 C; Q 2 C; Q 3 is C; among them, Q 1 Connected to W.

[0262] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxyl, amino, cyano, -R 6a 、-OR 6a 、-SO 2 (R 6a )、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b ),-SO 2 NH(R 6a ),-SO 2 N(R 6a )(R 6b ), -NHSO 2 (R 6a ) or -N(R 6a )SO 2 (R 6b ); or R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group or heteromonospirocyclic group.

[0263] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, -R 6a 、-OR 6a 、-SO 2 (R 6a )、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b ),-SO 2 NH(R 6a ),-SO 2 N(R 6a )(R 6b ), -NHSO 2 (R 6a ) or -N(R 6a )SO 2 (R 6b ); or R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group or heteromonospirocyclic group.

[0264] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, -R 6a 、-OR 6a 、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a ) or -N(R 6a )C(O)(R 6b ); or R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl.

[0265] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, -R 6a 、-NH(R 6a ) or -N(R 6a )(R 6b ); or R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl.

[0266] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, -R 6a 、-NH(R 6a ) or -N(R 6a )(R 6b ); or R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 A carbocyclic group or a 3- to 10-membered heterocyclic group.

[0267] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, -R 6a 、-NH(R 6a ) or -N(R 6a )(R 6b ); or R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 aryl, 5-10 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 A carbocyclic group or a 3- to 10-membered heterocyclic group.

[0268] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen or -R 6a ; or R 6 , R 7, R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a ; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl or 5-12 membered heteroaryl; or W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 A carbocyclic group or a 3- to 10-membered heterocyclic group.

[0269] Preferably, in the compounds provided by the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic alkyl group, C 6-8 Aryl or 5-10 membered heteroaryl.

[0270] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-8 Aryl or 5-8 membered heteroaryl.

[0271] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, each occurrence of Q1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents connected thereto together form an optionally R 6c Substituted C 5-6 Cycloalkyl, 5-6 membered heterocycloalkyl, C 6 Aryl or 5-6 membered heteroaryl, wherein the heteroatom is selected from O or N, and the number of heteroatoms is 1 or 2.

[0272] Preferably, in the compounds provided by the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl.

[0273] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-6 Cycloalkyl or 3-7 membered heterocycloalkyl.

[0274] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C 3-4 Cycloalkyl or 3-6 membered heterocycloalkyl, wherein the heteroatom is selected from O or N, and the number of the heteroatoms is 1 or 2.

[0275] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form an optionally R 6c Substituted C3-4 Cycloalkyl.

[0276] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or when R 6a and R 6b When connected to the same nitrogen atom, R 6a and R 6b and the nitrogen atom to which it is attached together form an optionally R 6c Substituted 3-10 membered heterocyclyl or 5-12 membered heteroaryl.

[0277] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl or 5-10 membered heteroaryl.

[0278] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b Each occurrence is independently selected from hydrogen, deuterium or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 5-6 membered heterocycloalkyl, C 6-8 aryl, 5-6 membered heteroaryl, 9-10 membered bicyclic heterocyclyl or 9-10 membered bicyclic heteroaryl.

[0279] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6bEach occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-6 Alkyl or C 1-6 Alkoxy.

[0280] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-3 Alkyl or C 1-3 Alkoxy.

[0281] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy or isopropoxy.

[0282] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted methyl or ethyl.

[0283] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxyl, amino, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e or-C(O)OR 6d .

[0284] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6cEach occurrence is independently selected from hydrogen, halogen, hydroxy, amino, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e or-C(O)OR 6d .

[0285] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 6d , R 6e Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, cyano or optionally substituted with halogen, hydroxy, amino or C 1-6 Alkyl substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or when R 6d and R 6e When connected to the same nitrogen atom, R 6d and R 6e and the nitrogen atom to which it is attached together form an optionally substituted halogen, hydroxyl, amino or C 1-6 Alkyl-substituted 3- to 10-membered heterocyclic group or 5- to 12-membered heteroaryl group.

[0286] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6d , R 6e Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or when R 6d and R 6e When connected to the same nitrogen atom, R 6d and R 6eTogether with the nitrogen atom to which it is attached, it forms a 3-10 membered heterocyclyl or a 5-12 membered heteroaryl.

[0287] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6d , R 6e Each occurrence is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, fused ring group or heterofused ring group.

[0288] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6d , R 6e Each occurrence is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl or 5-10 membered heteroaryl.

[0289] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 6c Each occurrence is independently selected from hydrogen, fluorine, chlorine, hydroxyl, amino, -NH(C 1-6 alkyl), -N(CH 3 )(C 1-6 alkyl), -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl, 5-10 membered heteroaryl, fused ring group or heterofused ring group.

[0290] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c Each occurrence is independently selected from hydrogen, fluorine, chlorine, hydroxyl, amino, -NH(C 1-6 alkyl), -N(CH3 )(C 1-6 alkyl), -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl or 5-10 membered heteroaryl.

[0291] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c Each occurrence is independently selected from hydrogen, fluorine, chlorine, hydroxyl, amino, -NH(C 1-6 alkyl), -N(CH 3 )(C 1-6 alkyl), -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl or 5-10 membered heteroaryl, wherein the heteroatom is selected from N or S, and the number of heteroatoms is 1, 2 or 3.

[0292] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c Each occurrence is independently selected from hydrogen, fluorine, chlorine, hydroxyl, amino, -NH(C 1-6 alkyl), -N(CH 3 )(C 1-6 alkyl), -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C 6-8Aryl or 5-6 membered heteroaryl, wherein the heteroatom is selected from N or S, and the number of heteroatoms is 1, 2 or 3.

[0293] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxyl, amino, C 1-6 Alkyl or C 1-6 Alkoxy.

[0294] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c Each occurrence is independently selected from hydrogen, fluorine, chlorine, hydroxy, amino, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy or isopropoxy.

[0295] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, deuterium or optionally deuterated, halogen, hydroxyl, amino, C 1-6 Alkyl, C 1-6 Alkoxy, -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 3-6 C substituted with cycloalkyl, 5-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, 9-10 membered bicyclic heterocyclyl or 9-10 membered bicyclic heteroaryl 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 5-6 membered heterocycloalkyl, C 6-8 aryl, 5-6 membered heteroaryl, 9-10 membered bicyclic heterocyclyl or 9-10 membered bicyclic heteroaryl.

[0296] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 1-6 Alkoxy, -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 3-6 C substituted with cycloalkyl, 5-6 membered heterocycloalkyl, phenyl or 5-6 membered heteroaryl 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 5-6 membered heterocycloalkyl, C 6-8 Aryl or 5-6 membered heteroaryl.

[0297] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 1-6 Alkoxy, -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl) or -NHC(O)(C 1-6 Alkyl) substituted C 1-6 Alkyl or C 1-6 Alkoxy.

[0298] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C1-6 Alkyl, C 1-6 Alkoxy substituted C 1-6 Alkyl or C 1-6 Alkoxy.

[0299] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-3 Alkyl or C 1-3 Alkoxy substituted C 1-3 Alkyl or C 1-3 Alkoxy.

[0300] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from the following groups: -H, -F, -Cl, -OH, -NH 2 、-CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-CH(CH 3 )CH 3 、-CH 2 CH(CH 3 )CH 3 、-CH 2 OH, -CH 2 CH 2 OH, -OCH 3 、-OCH 2 CH 3 、-OCH 2 CH 2 CH 3 、-OCH(CH 3 )CH 3 、-CH2 OCH 3 、-CH 2 OCH 2 CH 3 、-CH 2 CH 2 OCH 3 、-CH 2 CH 2 CH 2 OCH 3 、-CH(CH 3 )CH 2 OCH 3 、-NHCH 3 、-N(CH 3 )CH 3 、-CH 2 N(CH 3 )CH 3 ,

[0301]

[0302] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from the following groups: -H, -F, -Cl, -OH, -NH 2 、-CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-CH(CH 3 )CH 3 、-CH 2 CH(CH 3 )CH 3 、-CH 2 OH, -CH 2 CH 2 OH, -OCH 3 、-OCH 2 CH 3 、-OCH 2 CH 2 CH 3 、-OCH(CH 3 )CH 3、-CH 2 OCH 3 、-CH 2 OCH 2 CH 3 、-CH 2 CH 2 OCH 3 、-NHCH 3 、-N(CH 3 )CH 3 、-CH 2 N(CH 3 )CH 3 ,

[0303]

[0304] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from the following groups: -H, -F, -Cl, -OH, -NH 2 、-CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-CH(CH 3 )CH 3 、-CH 2 OCH 3 、-CH 2 CH 2 OCH 3 、-CH 2 CH 2 CH 2 OCH 3 or -CH(CH 3 )CH 2 OCH 3 .

[0305] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 6 , R 7 , R 8 , R 9 , R10 , R 11 , R 12 and R 13 Any two groups attached to the same atom form =O or =CH 2 .

[0306] Preferably, in the compounds provided by the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any two adjacent atoms and the substituents they are connected to together form the following group:

[0307]

[0308] Preferably, in the compounds provided by the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form the following group:

[0309]

[0310] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form the following group:

[0311]

[0312] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, each occurrence of Q 1 , each time Q appears 2 and Q 3 Any atom and its attached substituent together form the following group:

[0313]

[0314] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a structure as shown in formula (III-a):

[0315]

[0316] Among them, m 1-16 is selected from 0, 1, 2 or 3, R 1a-16 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3b-9 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-9 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , W, L, t 1 ,t 2 As defined in formula (I') or in a compound of formula (I).

[0317] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (III-a 1 ) shows the structure:

[0318]

[0319] Among them, m 1-17 is selected from 0, 1, 2 or 3, R 1a-17 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3b-10 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-10 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 8 , R 9 , R 10 , R 11 , L are as defined in formula (I') or the compound of formula (I).

[0320] Preferably, the present invention provides a compound or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, wherein the compound has a formula (III-a 2 ) shows the structure:

[0321]

[0322] Among them, m 1-18 is selected from 0, 1, 2 or 3, R 1a-18 For example, in the compound of formula (I') or formula (I), R 1a As defined, R 3b-11 For example, in the compound of formula (I') or formula (I), R 3b As defined, R 3c-11 For example, in the compound of formula (I') or formula (I), R 3c As defined, R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 11 , L are as defined in formula (I') or the compound of formula (I).

[0323] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-6 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl; the optional substitution refers to optionally being replaced by R 3d replaced.

[0324] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-4 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3cand the nitrogen atom to which it is attached form an optionally substituted 5-6 membered heterocycloalkyl or 6-10 membered bicyclic heterocyclic group, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1, 2 or 3; the optional substitution refers to the optional substitution of R 3d replaced.

[0325] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-4 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 5-6 membered heterocycloalkyl, a 3-membered / 6-membered heteromonospirocyclic group, a 4-membered / 6-membered heteromonospirocyclic group or a 3-membered / 5-membered heterocyclic group, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1, 2 or 3; the optional substitution refers to the optional substitution of R 3d replaced.

[0326] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c Each occurrence is independently selected from optionally substituted methyl, or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted pyrrolidinyl, piperazinyl, piperidinyl, 2-oxa-7-azaspiro[3.5]nonyl (e.g., 2-oxa-7-azaspiro[3.5]non-7-yl), 3-azabicyclo[3.1.0]hexyl (e.g., 3-azabicyclo[3.1.0]hex-3-yl) or 6-azaspiro[2.5]octyl (e.g., 6-azaspiro[2.5]oct-6-yl); the optionally substituted refers to optionally replaced by R 3d replaced.

[0327] Preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from deuterium, fluorine, hydroxyl, amino, cyano, -NH(CH 3 )、-N(CH 3 )(CH 3 )、-C(O)NH2 、-CH 3 、-CH 2 CH 3 or -CH 2 CH 2 CH 3 .

[0328] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d Each occurrence is independently selected from deuterium, fluorine, cyano, -C(O)NH 2 or -CH 3 .

[0329] Further preferably, in the compound provided by the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b and R 3c and the nitrogen atom to which it is connected together form a group selected from the following groups:

[0330]

[0331] Preferably, the present invention provides compounds A-1 to A-212 and A-190-6 as described in the present application or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts.

[0332] [Synthetic intermediates and preparation methods]

[0333] With respect to the above compounds, the present invention also provides an intermediate for preparing a compound of formula (I') or formula (I), which has a structure as shown in formula (M-1):

[0334]

[0335] Among them, R x1 is selected from halogen or hydrogen; R 4 , R 6 , R 7 , A, W, L, t 1 ,t 2 , h are as defined in formula (I') or the compound of formula (I).

[0336] With respect to the above compounds, the present invention also provides an intermediate for preparing the compound of formula (I') or formula (I), which has a structure as shown in formula (M-2):

[0337]

[0338] Among them, R x1 is selected from halogen or hydrogen; R 4 , R 6 , R 7 , A, W, L, t 1 ,t 2 , h are as defined in formula (I') or the compound of formula (I).

[0339] With respect to the above compounds, the present invention also provides an intermediate for preparing a compound of formula (I') or formula (I), which has a structure as shown in formula (M-3):

[0340]

[0341] Among them, R x1 is selected from halogen or hydrogen, R 4 , R 6 , R 7 , A, W, L, t 1 ,t 2 , h are as defined in formula (I') or the compound of formula (I).

[0342] With respect to the above compounds, the present invention also provides an intermediate for preparing a compound of formula (I') or formula (I), which has a structure as shown in formula (M-4):

[0343]

[0344] Among them, R x2 is selected from halogen or hydrogen, R 4 , R 6 , R 7 , A, W, L, t 1 ,t 2 , h are as defined in formula (I') or the compound of formula (I).

[0345] With respect to the above compounds, the present invention also provides an intermediate for preparing a compound of formula (I') or formula (I), which has a structure as shown in formula (M-5):

[0346]

[0347] Among them, R x3 is selected from halogen or hydrogen, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 , h are as defined in formula (I') or the compound of formula (I).

[0348] With respect to the above compounds, the present invention also provides an intermediate for preparing a compound of formula (I') or formula (I), which has a structure as shown in formula (M-6):

[0349]

[0350] Among them, R x4 is selected from halogen or hydrogen, R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 , h are as defined in formula (I') or the compound of formula (I).

[0351] Preferably, the present invention provides synthetic intermediates M-1 to M-60, M-1-1, M-1-2, M-1-3, M-1-4, M-1-5, M-1-6, M-28-1, M-28-2, M-28-3, M-28-4, M-28-5, M-28-6, M-31-1, M-31-2, M-31-3, M-31-4, M-48-1, A-1-1, A-3- 1. A-5-1, A-6-1, A-7-1, A-8-1, A-9-1, A-10-1, A-11-1, A-12-1, A-13-1, A-14-1, A-15-1, A-16-1, A- 17-1, A-18-1, A-19-1, A-20-1, A-21-1, A-22-1, A-23-1, A-24-1, A-27-1, A-28-1, A-31-1, A-32-1, A- 41-1, A-41-2, A-42-1, A-43-1, A-49-1, A-52-1, A-56-1, A-67-1, A-67-2, A-146-1, A-146-2, A-148- 1. A-148-2, A-155-1, A-155-2, A-176-1, A-176-2, A-176-3, A-176-4, A-181-1, A-181-2, A-183-1, A -183-2, A-190-1, A-190-2, A-190-3, A-190-4, A-190-5, A-194-1, A-197-1, A-197-2, A-197-3, A-19 7-4, A-197-5, A-197-6, A-200-1, A-201-1, A-204-1, A-204-2, A-205-1, A-205-2, A-211-1, A-211-2.

[0352] The present invention also provides a method for preparing the compound of formula (I') or formula (I), which can be prepared by, for example, using the method shown in the following synthesis scheme 1, 2 or 3.

[0353] Synthesis Scheme 1:

[0354]

[0355] i) Compound I-a1 undergoes chemical transformation (such as substitution reaction) to obtain compound I-a2;

[0356] For example, compound I-a1 and thionyl chloride are used as basic raw materials to obtain compound I-a2;

[0357] ii) Compound I-a2 undergoes chemical transformation (such as substitution reaction and optional ring-closure reaction) to obtain compound I-a4;

[0358] For example, compounds I-a2 and I-a3 are used as basic raw materials and reacted under alkaline conditions to obtain un-ring-closed or ring-closed compound I-a4;

[0359] iii) Compound I-a4 undergoes chemical transformation (such as hydrolysis) to obtain compound I-a5;

[0360] For example, compound I-a4 is reacted under alkaline conditions to obtain compound I-a5;

[0361] iv) Compound I-a5 undergoes chemical transformation (such as ring-closing reaction) to obtain compound I-a6;

[0362] For example, compound I-a5 and diphenylphosphoryl azide are used as basic raw materials and reacted under alkaline conditions to obtain compound I-a6;

[0363] v) Compound I-a6 undergoes chemical transformation (such as alkylation reaction) to obtain compound I-a7;

[0364] For example, compound I-a6 and a halide (such as iodomethane) are used as basic raw materials and reacted under alkaline conditions to obtain compound I-a7;

[0365] vi) Compound I-a7 undergoes chemical transformation (such as coupling reaction) to obtain compound I-a8;

[0366] For example, compound I-a7 and a boronic acid derivative are used as basic raw materials, and a coupling reaction is performed to obtain compound I-a8;

[0367] vii) Compound I-a8 undergoes chemical transformation (such as substitution reaction) to obtain Compound I;

[0368] For example, compound I-a8 is used as the basic raw material and reacted under alkaline conditions to obtain compound I of the general formula.

[0369] Synthesis Scheme 2:

[0370]

[0371] i) using compound I-b1 and thionyl chloride as basic raw materials to obtain compound I-b2;

[0372] ii) using compounds I-b2 and I-b3 as basic raw materials, reacting under alkaline conditions to obtain compound I-b4;

[0373] iii) Compound I-b4 reacts under alkaline conditions to obtain compound I-b5;

[0374] iv) using compound I-b5 and a suitable reducing agent (such as iron powder, zinc powder, etc.), ammonium chloride, etc. as basic raw materials to obtain compound I-b6;

[0375] v) Using compound I-b6 and N,N-carbonyldiimidazole (CDI) as basic raw materials, compound I-b7 is obtained;

[0376] vi) using compound I-b7 and a halide (such as iodomethane) as basic raw materials, reacting under alkaline conditions to obtain compound I-b8;

[0377] vii) using compound I-b8 and a boronic acid derivative as basic raw materials, undergoing a coupling reaction to obtain compound I-b9;

[0378] viii) Compound I-b9 and amines or alcohols are used as basic raw materials and reacted under alkaline conditions to obtain compound I of the general formula.

[0379] Synthesis Scheme 3:

[0380]

[0381] i) using compound I-b1 and thionyl chloride as basic raw materials to obtain compound I-b2;

[0382] ii) using compounds I-b2 and I-b3 as basic raw materials, reacting under alkaline conditions to obtain compound I-b5;

[0383] iii) using compound I-b5 and a suitable reducing agent (such as iron powder, zinc powder, etc.), ammonium chloride, etc. as basic raw materials to obtain compound I-b6;

[0384] iv) using compound I-b6 and N,N-carbonyldiimidazole (CDI) as basic raw materials to obtain compound I-b7;

[0385] v) using compound I-b7 and a halide (such as iodomethane) as basic raw materials, reacting under alkaline conditions to obtain compound I-b8;

[0386] vi) using compound I-b8 and a boronic acid derivative as basic raw materials, undergoing a coupling reaction to obtain compound I-b9;

[0387] vii) Compound I-b9 and amines or alcohols are used as basic raw materials and reacted under alkaline conditions to obtain compound I of the general formula.

[0388] Preferably, in the preparation method of the present invention, R x1 is selected from halogen or hydrogen, X 1 , R 4 , R 5 , R 6 , R 7 , A, W, L, t 1 ,t 2 As defined in formula (I') or formula (I).

[0389] Preferably, in the preparation method of the present invention, the reaction is carried out in an organic solvent.

[0390] Further preferably, in the preparation method of the present invention, the organic solvent is selected from ethers, halogenated hydrocarbons, alcohols, alkanes, aromatic hydrocarbons, esters, acetonitrile, N,N-dimethylformamide and mixtures thereof; preferably, the ethers are selected from tetrahydrofuran, ethyl ether, ethylene glycol dimethyl ether and mixtures thereof, the halogenated hydrocarbons are selected from dichloromethane, chloroform, dichloroethane, tetrachloromethane and mixtures thereof, the alcohols are selected from methanol, ethanol, n-propanol, isopropanol and mixtures thereof, the alkanes are selected from petroleum ether, n-hexane and mixtures thereof, the aromatic hydrocarbons are selected from benzene, toluene, xylene and mixtures thereof, the esters are selected from ethyl acetate and the like.

[0391] Further preferably, in the preparation method of the present invention, the organic solvent is selected from one or more of acetonitrile, N,N-dimethylformamide, halogenated hydrocarbon, ether and ethyl acetate; preferably, the halogenated hydrocarbon is ethylene dichloride.

[0392] Preferably, in the preparation method of the present invention, the base is selected from one or more of potassium carbonate, sodium carbonate, magnesium carbonate, sodium bicarbonate, cesium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, lithium hydroxide, magnesium hydroxide, cesium hydroxide, triethylamine, diisopropylethylamine, piperidine, pyrrole, pyridine, lutidine and dimethylaminopyridine.

[0393] [Drug composition]

[0394] With respect to the above-mentioned compound, the present invention also provides a pharmaceutical composition comprising the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt.

[0395] Preferably, the pharmaceutical composition of the present invention comprises the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, and a pharmaceutically acceptable excipient.

[0396] [Medical Use]

[0397] The present invention also provides the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt or the pharmaceutical composition of the present invention, which is used as an ATM kinase inhibitor.

[0398] The present invention also provides a compound of the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof or a pharmaceutical composition of the present invention for use in preventing and / or treating a disease and / or condition at least partially mediated by ATM kinase. Preferably, the disease and / or condition at least partially mediated by ATM kinase is cancer.

[0399] Further, the present invention also provides a compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt or pharmaceutical composition of the present invention, which is used to prevent and / or treat cancer. Further, the cancer includes solid tumors and hematological tumors. Preferably, the cancer includes breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, small cell lung cancer, glioblastoma.

[0400] The present invention also provides use of the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt or the pharmaceutical composition of the present invention in the preparation of an ATM kinase inhibitor.

[0401] The present invention also provides the use of the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt or the pharmaceutical composition of the present invention in the preparation of a medicament for preventing and / or treating a disease and / or condition mediated at least in part by ATM kinase. Preferably, the disease and / or condition mediated at least in part by ATM kinase is cancer.

[0402] Further, the present invention also provides the use of the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt or the pharmaceutical composition of the present invention in the preparation of a medicament for preventing and / or treating cancer. Further, the cancer includes solid tumors and hematological tumors. More preferably, the cancer includes breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, small cell lung cancer, glioblastoma.

[0403] The present application also provides a method for preventing and / or treating a disease and / or condition at least partially mediated by ATM kinase, comprising administering to an individual in need thereof a preventive and / or therapeutically effective amount of a compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt or a pharmaceutical composition of the present invention; preferably, the disease and / or condition at least partially mediated by ATM kinase is cancer; more preferably, the cancer includes solid tumors and hematological tumors. More preferably, the cancer includes breast cancer, non-small cell lung cancer, brain glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, small cell lung cancer, glioblastoma.

[0404] Further, the present application also provides a method for preventing and / or treating cancer, which comprises administering to an individual in need thereof a preventive and / or therapeutically effective amount of a compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt or a pharmaceutical composition of the present invention; preferably, the cancer comprises solid tumors and hematological tumors. More preferably, the cancer comprises breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, small cell lung cancer, glioblastoma.

[0405] Furthermore, the use or method provided by the present invention, wherein the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt or the pharmaceutical composition of the present invention is used in combination with at least one additional anti-tumor agent or treatment method (such as radiotherapy); preferably, the anti-tumor agent is selected from doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan, bleomycin, cisplatin, oxaliplatin, carboplatin, valrubicin, idarubicin, pirarubicin, amrubicin, epirubicin, olaparib, MEDI4736, AZD1775 and AZD6738.

[0406] Furthermore, the present invention provides a use or method, wherein the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt or the pharmaceutical composition of the present invention is administered simultaneously, separately or sequentially with radiotherapy.

[0407] The present invention also provides a drug combination form (or drug combination composition, drug compound composition), which comprises a compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt or pharmaceutical composition of the present invention, and at least one additional anti-tumor agent or treatment method. Preferably, the anti-tumor agent is selected from doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan, bleomycin, cisplatin, oxaliplatin, carboplatin, valrubicin, idarubicin, pirarubicin, amrubicin, epirubicin, olaparib, MEDI4736, AZD1775 and AZD6738. Preferably, the treatment method is radiotherapy.

[0408] [Definition of terms]

[0409] The terms "optional", "optionally", "optionally" or "arbitrarily" mean that the subsequently described event or circumstance may but need not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0410] Accordingly, the term "optionally substituted" means that a group may be unsubstituted or substituted at its substitutable position by one or more substituents that are each independently present. When the group is substituted, the hydrogen at one or more substitutable positions of the substituted group is independently replaced by a substituent, which may be independently selected from deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, -C(O)C 1-6 Alkyl, -C(O)OC1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH-C 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the oxo group means that two H at the same substitution site are replaced by the same O to form a double bond.

[0411] Unless otherwise specified, the term "bond" refers to a chemical bond, including (but not limited to) a covalent bond (e.g., a carbon-carbon single bond, a carbon-nitrogen single bond, a carbon-oxygen single bond, a carbon-sulfur single bond, a carbon-carbon double bond, a carbon-nitrogen double bond, a carbon-oxygen double bond, a carbon-sulfur double bond, a carbon-carbon triple bond, a carbon-nitrogen triple bond, etc.), an ionic bond, a coordination bond, etc.; in the compounds of the present invention, the bond between the parent core and the substituent or between different substituents is essentially a covalent bond.

[0412] Unless otherwise specified, the term "carboxy" refers to a "-C(O)OH" group.

[0413] Unless otherwise specified, the term "hydroxy" refers to a "-OH" group.

[0414] Unless otherwise specified, the term "mercapto" refers to a "-SH" group.

[0415] Unless otherwise specified, the term "amino" refers to "-NH 2 In some embodiments, the amino group also includes a group in which one or two hydrogen atoms are replaced by an alkyl group (e.g., -NH(C 1-6 Alkyl), -N(C 1-6 alkyl) 2 wait).

[0416] Unless otherwise specified, the term "nitro" means "-NO 2 ” group.

[0417] Unless otherwise specified, the term "cyano" refers to a "-CN" group.

[0418] The term "oxo" refers to two hydrogen atoms at the same substitution position being replaced by the same oxygen atom to form a double bond (ie, "=O").

[0419] Unless otherwise specified, the term "alkyl" refers to a straight or branched, saturated, monovalent aliphatic hydrocarbon group, which may contain 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 8 carbon atoms, and more preferably 1 to 6 carbon atoms (i.e., C 1-6 For example, "C 1-6 "Alkyl" means that the group is an alkyl group, and the number of carbon atoms in the carbon chain is between 1 and 6 (specifically 1, 2, 3, 4, 5 or 6). Illustrative examples of alkyl groups include (but are not limited to) methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, n-heptyl, n-octyl, etc.

[0420] Unless otherwise specified, the term "alkoxy" refers to an -O-alkyl group, wherein the alkyl group is as defined above and may contain 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, further preferably 1 to 8 carbon atoms, and more preferably 1 to 6 carbon atoms (i.e., C 1-6 For example, "C 1-6 The term "alkoxy" means that the group is an alkoxy group and the number of carbon atoms in the carbon chain is between 1 and 6 (specifically 1, 2, 3, 4, 5 or 6). Illustrative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, tert-butoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, and the like.

[0421] Unless otherwise specified, the term "halogen" or "halo" refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0422] Unless otherwise specified, the term "haloalkyl" refers to a group formed by replacing one, two, more or all of the hydrogen atoms in an alkyl group as defined above with halogen. Illustrative examples of haloalkyl groups include, but are not limited to, -CCl 3 , -CF 3 , -CHCl 2 、-CH 2 Cl, -CH 2 Br, -CH 2 I. -CH 2 CF 3 , -CF 2 CF 3 wait.

[0423] Unless otherwise specified, the term "alkenyl" refers to a linear or branched, monovalent aliphatic hydrocarbon group containing one or more (e.g., 1, 2, 3 or 4) carbon-carbon double bonds, which may contain 2-20 carbon atoms, preferably 2-10 carbon atoms, further preferably 2-8 carbon atoms, and more preferably 2-6 carbon atoms (i.e., C 2-6 For example, "C 2-6 "Alkenyl" means that the group is an alkenyl group, and the number of carbon atoms in the carbon chain is between 2 and 6 (specifically 2, 3, 4, 5 or 6). Illustrative examples of alkenyl include (but are not limited to) ethenyl, n-propenyl, n-butenyl, n-pentenyl, etc.

[0424] Unless otherwise specified, the term "alkynyl" refers to a linear or branched, monovalent aliphatic hydrocarbon group containing one or more (e.g., 1, 2, 3 or 4) carbon-carbon triple bonds, which may contain 2-20 carbon atoms, preferably 2-10 carbon atoms, further preferably 2-8 carbon atoms, and more preferably 2-6 carbon atoms (i.e., C 2-6 For example, "C 2-6 "Alkynyl" means that the group is an alkynyl group, and the number of carbon atoms in the carbon chain is between 2 and 6 (specifically 2, 3, 4, 5 or 6). Illustrative examples of alkenyl include (but are not limited to) ethynyl, n-propynyl, n-butynyl, n-pentynyl, etc.

[0425] Unless otherwise specified, the term "carbocyclyl" or "carbocycle" refers to a monocyclic or polycyclic, saturated or partially unsaturated, monovalent non-aromatic hydrocarbon radical which may contain 3 to 14 ring carbon atoms (i.e., C 3-14 carbocyclic group), preferably containing 3 to 12 ring carbon atoms (i.e., C 3-12 Carbocyclic group), further preferably containing 4-12 ring carbon atoms (i.e. C 4-12 carbocyclic group) or 3-10 ring carbon atoms (i.e. C 3-10 In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms (“C 3-8 "Carbocyclyl"). Exemplary C 3-6 Carbocyclic groups include, but are not limited to, cyclopropyl (C 3 ), cyclopropenyl (C 3 ), cyclobutyl (C 4 ), cyclobutenyl (C 4 ), cyclopentyl (C 5 ), cyclopentenyl (C 5 ), cyclohexyl (C 6 ), cyclohexenyl (C 6 ), cyclohexadienyl (C 6 ) etc. Exemplary C 3-8 Carbocyclic groups include (but are not limited to) the aforementioned C3-6 Carbocyclic and cycloheptyl (C 7 ), cycloheptenyl (C 7 ), cycloheptadienyl (C 7 ), cycloheptatrienyl (C 7 ), cyclooctyl (C 8 ), cyclooctenyl (C 8 ), bicyclo[2.2.1]heptyl (C 7 ), bicyclo[2.2.2]octyl (C 8 ) etc. Exemplary C 3-10 Carbocyclic groups include (but are not limited to) the aforementioned C 3-8 Carbocyclic and cyclononyl (C 9 ), cyclononenyl (C 9 ), cyclodecyl (C 10 ), cyclodecenyl (C 10 ), octahydro-1H-indenyl (C 9 ), decahydronaphthyl (C 10 ), spiro[4.5]decyl (C 10 ) and the like. The carbocyclyl group can be a monocyclic (monocyclic carbocyclyl) ring system, a fused (fused cyclyl), a bridged (bridged cyclyl) or a spiro (spirocyclyl) ring system, such as a bicyclic system (bicyclic carbocyclyl), and can be saturated or partially unsaturated. In some embodiments, the carbocyclyl group also includes a carbocyclyl ring as defined above fused to one or more aryl / heteroaryl groups, wherein the point of attachment is on the carbocyclyl ring; or, in some embodiments, a carbocyclyl as defined above fused to one or more carbocyclyls as defined above, wherein the point of attachment is on any carbocyclyl ring. In the above case, the number of atoms of the carbocyclyl ring system is the number of ring carbon atoms of the ring system after fusion. In some embodiments, the carbocyclyl group is optionally substituted, for example, unsubstituted (unsubstituted carbocyclyl) or substituted by one or more substituents (substituted carbocyclyl). In some embodiments, the carbocyclyl group is an unsubstituted C 3-10 In some embodiments, the carbocyclyl is a substituted C 3-10 Carbocyclic group.

[0426] Unless otherwise specified, the term "cycloalkyl" refers to a monocyclic, saturated, monovalent aliphatic hydrocarbon group which may contain 3 to 12 carbon atoms (i.e., C 3-12 Cycloalkyl), preferably containing 3 to 10 carbon atoms (i.e., C 3-10 Cycloalkyl), further preferably containing 3 to 7 carbon atoms (i.e. C 3-7 Cycloalkyl), 4-6 carbon atoms (i.e. C 4-6 Cycloalkyl) or 5-6 carbon atoms (i.e. C 5-6 For example, "C 3-10"Cycloalkyl" means that the group is a cycloalkyl group, and the number of carbon atoms in the carbon ring is between 3 and 10 (specifically 3, 4, 5, 6, 7, 8, 9 or 10). Illustrative examples of cycloalkyl include (but are not limited to) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, 2-ethylcyclopentyl, dimethylcyclobutyl, etc.

[0427] Unless otherwise specified, the term "heterocyclyl" or "heterocycle" refers to a monocyclic or polycyclic, saturated or partially unsaturated, monovalent non-aromatic group having ring carbon atoms and 1 to 4 ring heteroatoms, which may contain 3-20 ring atoms, wherein 1, 2, 3 or more ring atoms are selected from N, O or S, and the remaining ring atoms are C, preferably containing 3-12 ring atoms (i.e. 3-12 membered heterocyclyl), further preferably containing 3-10 ring atoms (i.e. 3-10 membered heterocyclyl), 3-8 ring atoms (i.e. 3-8 membered heterocyclyl), 3-6 ring atoms (i.e. 3-6 membered heterocyclyl), 4-6 ring atoms (i.e. 4-6 membered heterocyclyl) or 5-6 ring atoms (i.e. 5-6 membered heterocyclyl), and the number of heteroatoms is 1-4, preferably 1-3 (i.e. 1, 2 or 3). Illustrative examples of monocyclic heterocyclyls include, but are not limited to, pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, dihydropyrrolyl, piperidinyl, piperazinyl, pyranyl, etc. Polycyclic heterocyclyls include paracyclic, spirocyclic, fused and bridged heterocyclyls. The heterocyclyl may be a monocyclic (monocyclic heterocyclyl) ring system, or a fused (fused heterocyclyl or heterofused), paracyclic (heterocyclic or paracyclic heterocyclyl), bridged (heterobridged or bridged heterocyclyl) or spiro (heterospiro or spiroheterocyclic) ring system, such as a bicyclic system (bicyclic heterocyclyl), and may be saturated or partially unsaturated. The bicyclic heterocyclyl may contain one or more heteroatoms in one or both rings. In some embodiments, heterocyclyl also includes a ring system in which a heterocyclyl as defined above is fused to one or more carbocyclyls, wherein the point of attachment is on the carbocyclyl or heterocyclyl ring; or, in some embodiments, a heterocyclyl as defined above is fused to one or more aryl / heteroaryl rings, wherein the point of attachment is on the aryl / heteroaryl or heterocyclyl ring; or, in some embodiments, a heterocyclyl as defined above is fused to one or more heterocyclyls as defined above, wherein the point of attachment is on either heterocyclyl ring. In the above cases, the number of members of the heterocyclyl ring system is the number of ring atoms in the ring system after fusion. In some embodiments, heterocyclyl is optionally substituted, for example, unsubstituted (unsubstituted heterocyclyl) or substituted with one or more substituents (substituted heterocyclyl). Exemplary 3-membered heterocyclyls containing 1 heteroatom include, but are not limited to, aziridinyl, oxiranyl, and thiorenyl. Exemplary 4-membered heterocyclyls containing 1 heteroatom include, but are not limited to, azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyls containing 1 heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, pyrrolidinyl, dihydropyrrolyl, and 2,5-dioxopyrrolidinyl.Exemplary 5-membered heterocyclic groups containing 2 heteroatoms include, but are not limited to, dioxolanyl, oxathiolanyl, dithiolanyl, and 2-oxoxazolidinyl. Exemplary 5-membered heterocyclic groups containing 3 heteroatoms include, but are not limited to, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclic groups containing 1 heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and tetrahydrothiopyranyl (thianyl). Exemplary 6-membered heterocyclic groups containing 2 heteroatoms include, but are not limited to, piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclic groups containing 3 heteroatoms include, but are not limited to, triazinanyl, oxadiazinanyl, thiadiazinanyl, oxathiazinanyl, and dioxazinanyl. Exemplary 7-membered heterocyclic groups containing 1 heteroatom include, but are not limited to, azepanyl, oxepane, and thiepanyl. Exemplary 8-membered heterocyclic groups containing 1 heteroatom include, but are not limited to, azocanyl, oxepane, and thiecanyl. Fused to one C. 6 Exemplary 5-membered heterocyclyl groups (also referred to herein as 5,6-bicyclic heterocyclyl groups) on the aryl ring include, but are not limited to, dihydroindolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinyl, and the like. 6 Exemplary 6-membered heterocyclyl groups (also referred to herein as 6,6-bicyclic heterocyclyl groups) on the aryl ring include, but are not limited to, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like.

[0428] Unless otherwise specified, "heterocycloalkyl" refers to a monocyclic, saturated, "heterocyclyl" or "heterocycle" as defined above, which may contain 3-20 ring atoms (i.e., 3-20-membered heterocycloalkyl), wherein 1, 2, 3 or more ring atoms are selected from N, O or S, and the remaining ring atoms are C, preferably containing 3-12 ring atoms (i.e., 3-12-membered heterocycloalkyl), further preferably containing 3-10 ring atoms (i.e., 3-10-membered heterocycloalkyl), 3-8 ring atoms (i.e., 3-8-membered heterocycloalkyl), 4-7 ring atoms (i.e., 4-7-membered heterocycloalkyl), 5-10 ring atoms (i.e., 5-10-membered heterocycloalkyl) or 5-6 ring atoms (i.e., 5-6-membered heterocycloalkyl), and the number of heteroatoms is 1-4, preferably 1-3 (1, 2 or 3). In some embodiments, heterocycloalkyl is optionally substituted, for example, unsubstituted (unsubstituted heterocycloalkyl) or substituted by one or more substituents (substituted heterocycloalkyl). Some exemplary "heterocycloalkyl" are given in the "heterocyclyl" or "heterocycle" section above, and also include (but are not limited to) aziridine, oxirane, thiirane, azetidine, oxetane, thiidine, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, oxathianyl, oxazolidinyl, dioxanyl, dithianyl, thiazolidinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, etc.

[0429] Unless otherwise specified, the term "paracyclic" refers to a non-aromatic, saturated or partially unsaturated ring system formed by two or more cyclic structures sharing two adjacent atoms, including paracarbocyclic groups and paraheterocyclic groups, wherein the ring atoms of the paraheterocyclic group contain one or more heteroatoms independently selected from oxygen, nitrogen and sulfur.

[0430] Unless otherwise specified, the term "monospirocyclic group" refers to a saturated, monovalent aliphatic hydrocarbon group containing only one spiro carbon atom, which may contain 6-14 ring carbon atoms, preferably 7-10 ring carbon atoms. Monospirocyclic groups include 3-membered / 5-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered and 5-membered / 6-membered monospirocyclic groups, wherein the spiro atom is counted in the number of members of each ring. Exemplary examples of monospirocyclic groups include (but are not limited to) wait.

[0431] Unless otherwise specified, the term "heteromonospirocyclic group" refers to a saturated, monovalent aliphatic group containing only one spiro carbon atom, which may contain 6-14 ring atoms, preferably 7-10 ring atoms, including 1-4 ring heteroatoms, preferably 1-3 (i.e., 1, 2 or 3) ring heteroatoms, and the heteroatoms are independently selected from N, O and S. Heteromonospirocyclic groups include 3-membered / 5-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 5-membered and 5-membered / 6-membered heteromonomonospirocyclic groups, etc., wherein the spiro atom is counted in the number of members of each ring respectively. Exemplary examples of heteromonomonospirocyclic groups include (but are not limited to) wait.

[0432] Unless otherwise specified, the term "bridged ring group" refers to a polycyclic, monovalent aliphatic hydrocarbon group in which any two rings share two ring carbon atoms that are not directly connected, which may contain 5-20 ring carbon atoms, preferably 6-14 ring carbon atoms, more preferably 7-10 ring carbon atoms, and may contain one or more double bonds, but no ring has a completely conjugated π electron system. Bridged ring groups include bicyclic, tricyclic, tetracyclic or polycyclic bridged ring groups, preferably bicyclic, tricyclic or tetracyclic bridged ring groups, more preferably bicyclic or tricyclic bridged ring groups. Exemplary examples of bridged ring groups include (but are not limited to)

[0433]

[0434] Unless otherwise specified, the term "heterobridged ring group" refers to a polycyclic, monovalent aliphatic group in which any two rings share two ring atoms that are not directly connected, which may contain 5-14 ring atoms, preferably 6-14 ring atoms, more preferably 7-10 ring atoms, wherein 1-4 ring heteroatoms, preferably 1-3 (i.e., 1, 2 or 3) ring heteroatoms, and the heteroatoms are independently selected from N, O and S, and may contain one or more double bonds, but none of the rings has a completely conjugated π electron system. Heterobridged ring groups include bicyclic, tricyclic, tetracyclic or polycyclic heterobridged ring groups, preferably bicyclic, tricyclic or tetracyclic heterobridged ring groups, more preferably bicyclic or tricyclic heterobridged ring groups. Exemplary examples of heterobridged ring groups include (but are not limited to)

[0435]

[0436] Unless otherwise specified, the term "aryl" or "aromatic ring group" refers to a monocyclic or polycyclic, monovalent aromatic hydrocarbon group which may contain 6 to 16 ring carbon atoms (i.e., C 6-16 Aryl), 6-14 ring carbon atoms (i.e. C 6-14 Aryl), 6-12 ring carbon atoms (i.e. C 6-12 Aryl) or 6-10 ring carbon atoms (i.e. C 6-10In some embodiments, the term "aryl" can be used interchangeably with the term "aromatic ring". Illustrative examples of aryl include (but are not limited to) phenyl, naphthyl, anthracenyl, phenanthrenyl, pyrenyl, etc.

[0437] Unless otherwise specified, the term "heteroaryl" or "heteroaromatic ring group" refers to a monocyclic or polycyclic, monovalent aromatic group, which may contain 5-14 ring atoms (i.e., 5-14-membered heteroaryl), 5-10 ring atoms (i.e., 5-10-membered heteroaryl), 5-8 ring atoms (i.e., 5-8-membered heteroaryl) or 5-6 ring atoms (i.e., 5-6-membered heteroaryl), wherein 1, 2, 3 or more ring atoms are heteroatoms independently selected from O, N or S, and the remaining ring atoms are C. In some embodiments, the term "heteroaryl" can be used interchangeably with the term "heteroaromatic ring". Illustrative examples of heteroaryl groups include, but are not limited to, furanyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, thiodiazolyl, triazinyl, phthalazinyl, quinolyl, isoquinolyl, pteridinyl, purinyl, indolyl, isoindolyl, indazolyl, benzofuranyl, benzothiophenyl, benzopyridinyl, benzopyrimidinyl, benzopyrazinyl, benzimidazolyl, benzophthalazinyl, pyrrolo[2,3-b]pyridinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl, [1,2,4]triazolo[1,5-a]pyridinyl, and the like.

[0438] Unless otherwise specified, the term "pharmaceutically acceptable salt" or "pharmaceutically acceptable salt" refers to salts that are suitable for contact with mammalian (especially human) tissues without excessive toxicity, irritation, allergic reaction, etc., and are commensurate with a reasonable benefit / risk ratio within the scope of reasonable medical judgment, such as amines, carboxylic acids and other types of pharmaceutically acceptable salts of compounds are well known in the art. The salts can be prepared in situ during the final isolation and purification of the compounds of the present invention, or separately by reacting the free base or free acid with a suitable reagent.

[0439] Unless otherwise specified, the term "isotopic derivative" means that the compounds of the present invention may exist in an isotopically traced or enriched form, containing one or more atoms whose atomic mass or mass number is different from the atomic mass or mass number of the atom with the greatest natural abundance. Isotopes may be radioactive or non-radioactive isotopes. Isotopes commonly used as isotopic labels include (but are not limited to) hydrogen isotopes: 2 H and 3 H; Carbon isotope: 13C and 14 C; Chlorine isotope: 35 Cl and 37 Cl; Fluorine isotope: 18 F; Iodine isotope: 123 I and 125 I; Nitrogen isotopes: 13 N and 15 N; oxygen isotope: 15 O. 17 O and 18 O; and sulfur isotopes: 35 S. These isotope-labeled compounds can be used to study the distribution of drug molecules in tissues. 2 H and 13 C, because they are easy to label and detect, they are more widely used.

[0440] Unless otherwise specified, the term "solvate" or "solvate" refers to a physical association of a compound of the invention with one or more solvent molecules, whether organic or inorganic. The physical association includes hydrogen bonding. In certain cases, such as when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid, the solvate will be capable of being separated. The solvent molecules in the solvate may exist in a regular arrangement and / or a disordered arrangement. The solvate may contain stoichiometric or non-stoichiometric amounts of solvent molecules. "Solvate" encompasses solution phases and separable solvates. Illustrative examples of solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Solvation methods are well known in the art.

[0441] Unless otherwise specified, the term "optical isomers" refers to isomers that have similar physical and chemical properties, the same atomic connection sequence in the molecules, but different optical rotations.

[0442] Unless otherwise specified, the term "geometric isomer" (particularly "cis / trans isomer") refers to isomers containing carbon-carbon or carbon-nitrogen double bonds of E or Z configuration, wherein the term "E" represents a higher order substituent on the opposite side of the carbon-carbon or carbon-nitrogen double bond, and the term "Z" represents a higher order substituent on the same side of the carbon-carbon or carbon-nitrogen double bond, and the order can be determined using the Cahn-Ingold-Prelog priority rules. The compounds of the present invention can also exist in the form of a mixture of "E" and "Z" isomers.

[0443] Unless otherwise specified, the term "tautomer" refers to isomers with different energies that are interconvertible via a low energy barrier. If tautomerism is possible (such as in solution), a chemical equilibrium of tautomers can be achieved. For example, proton tautomers (also known as prototropic tautomers) include tautomers that interconvert via proton migration, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers include tautomers that interconvert via reorganization of bonding electrons.

[0444] Unless otherwise specified, the structural formulas described in the present invention include all isomeric forms (such as enantiomers, diastereomers, geometric isomers (such as conformational isomers), tautomers, etc.). For example, R and S configurations containing asymmetric centers, (Z) and (E) isomers of double bonds, and (Z) and (E) conformational isomers. Therefore, single stereochemical isomers of the compounds of the present invention or mixtures of their enantiomers, diastereomers, geometric isomers (such as conformational isomers) or tautomers are all within the scope of the present invention.

[0445] Unless otherwise specified, the term "prodrug" refers to a drug that is converted into the parent drug in vivo. Prodrugs are generally useful and can improve some certain, undesirable physical or biological properties. Physical properties are generally related to solubility (too high or insufficient lipid or water solubility) or stability, while problematic biological properties include too rapid metabolism or poor bioavailability, which may themselves be related to physicochemical properties. For example, they can be bioavailable by oral administration, while the parent cannot. The solubility of the prodrug in the pharmaceutical composition is also improved compared to the parent drug. An illustrative example of a prodrug (but not limited to this) can be any compound of the present invention, which is administered as an ester ("prodrug") to facilitate transmission across the cell membrane, where water solubility is detrimental to mobility, but once inside the cell, water solubility is beneficial, which is subsequently hydrolyzed to the carboxylic acid, the active entity. Another illustrative example of a prodrug can be a short peptide (polyamino acid) bound to an acid group, where the peptide is metabolized to reveal the active portion.

[0446] [Beneficial Effects]

[0447] The present invention provides an ATM kinase inhibitor with a novel structure, a preparation method thereof and an application thereof in the medical field. In particular, the compound of the present invention has the use of treating cancer. The results of enzymatic tests show that the compound of the present invention has good selectivity for the ATM target and can significantly inhibit the activity of ATM kinase. In addition, the present invention adopts a specific synthesis method, which has a simple process, is easy to operate, and is conducive to large-scale industrial production and application. DETAILED DESCRIPTION

[0448] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0449] The experimental methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or conditions recommended by the manufacturer. In addition, any methods and materials similar or equivalent to those described herein can be applied to the methods of the present invention.

[0450] Unless otherwise specified, the professional terms and scientific terms used in the following examples have the meanings familiar to professionals in the field.

[0451] Abbreviations used in the Preparations, Examples and elsewhere herein have the following meanings:

[0452] DCM: dichloromethane; TEA: triethylamine; DIEA / DIPEA: N,N-diisopropylethylamine; DMF: N,N-dimethylformamide; EtOAc: ethyl acetate; h: hour; mL: milliliter; HATU: 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate; MeOH: methanol; TFA: trifluoroacetic acid; DMSO-d 6： Deuterated dimethyl sulfoxide.

[0453] [Intermediate Preparation Example]

[0454] Intermediate Preparation Example 1: Preparation of (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-1)

[0455]

[0456] Step 1: Synthesis of diethyl 2-((4-bromo-3,5-difluorophenyl)amino)methylene)malonate

[0457] 4-Bromo-3,5-difluoroaniline (5.00 g, 24 mmol), diethyl 2-ethoxymethylenemalonate (7.80 g, 36 mmol) and anhydrous ethanol (50 mL) were added to a 250 mL reaction bottle. The reaction solution was reacted under reflux conditions for 8 h. After the reaction was completed under TLC monitoring, the reaction solution was cooled to 10 ° C, and a white solid was precipitated. The solid was collected by suction filtration, and the solid was rinsed with n-hexane and dried to obtain diethyl 2-((4-bromo-3,5-difluorophenyl)amino)methylene)malonate (7.3 g, yield 80.3%). ESI-MS (m / z): 378.01 / 380.01 [M+H] + ; 1 H NMR (600 MHz, DMSO-d6 )δ:1.236-1.269(m,6H),4.137(q,2H),4.216(q,2H),7.483-7.506(t,2H),8.308(d,1H),10.613(d,1H).

[0458] Step 2: Synthesis of ethyl 6-bromo-5,7-difluoro-4-hydroxyquinoline-3-carboxylate

[0459] Add diphenyl ether (80 mL) to a 250 mL reaction bottle, heat to 240 ° C, and then add diethyl 2-((4-bromo-3,5-difluorophenyl)amino)methylene)malonate (7.30 g, 19.3 mmol) in batches. The reaction solution was reacted at 240 ° C for 1 h. After the reaction was completed by TLC monitoring, the reaction solution was cooled to 25 ° C, and a crystalline solid was precipitated. The mixture was diluted with ether (80 mL), and the solid was collected by suction filtration. The solid was rinsed with ether and dried to obtain 6-bromo-5,7-difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester (5.50 g, yield 85.8%). ESI-MS (m / z): 331.97 / 333.96 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.271(t,3H),4.208(q,2H),7.402(d,1H),8.528(s,1H),12.404(s,1H).

[0460] Step 3: Synthesis of ethyl 6-bromo-4-chloro-5,7-difluoroquinoline-3-carboxylate

[0461] Add thionyl chloride (20 mL) and 6-bromo-5,7-difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester (1.40 g, 4.2 mmol) to a 100 mL reaction bottle. The reaction solution was reacted at 80 ° C for 3 h. TLC monitored the completion of the reaction, and the reaction solution was cooled and concentrated to dryness to obtain a crude product of 6-bromo-4-chloro-5,7-difluoroquinoline-3-carboxylic acid ethyl ester (1.48 g, yield 100%). ESI-MS (m / z): 351.93 [M+H] + .

[0462] Step 4: Synthesis of (S)-ethyl 6-bromo-5,7-difluoro-4-((1-hydroxypropan-2-yl)amino)quinoline-3-carboxylate

[0463] DMF (20 mL), 6-bromo-4-chloro-5,7-difluoroquinoline-3-carboxylic acid ethyl ester (1.48 g, 4.2 mmol), L-aminopropanol (0.47 g, 6.3 mmol) and DIEA (1.09 g, 8.4 mmol) were added to a 100 mL reaction bottle in sequence, and the temperature was raised to 90 ° C for 3 h. After the reaction was completed by TLC monitoring, the reaction solution was cooled to room temperature, water was added to precipitate the solid, and the solid was collected by suction filtration. The solid was rinsed with water and dried to obtain (S)-6-bromo-5,7-difluoro-4-((1-hydroxypropyl-2-yl)amino)quinoline-3-carboxylic acid ethyl ester (1.2 g, yield was 73.4%). ESI-MS (m / z): 389.02 / 391.02 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 )δ:1.429(t,3H),1.555(d,3H),4.292-4.356(m,2H),4.420(q,2H),4.638(d,1H),8.010(s,1H),9.048(s,1H),11.557(s,1H).

[0464] Step 5: Synthesis of (S)-10-bromo-9-fluoro-3-methyl-3,4-dihydro-2H-[1,4]oxazepino[5,6,7-de]quinoline-5-carboxylic acid

[0465] THF (10 mL), (S)-6-bromo-5,7-difluoro-4-((1-hydroxypropyl-2-yl)amino)quinoline-3-carboxylic acid ethyl ester (1.20 g, 3.08 mmol), water (5 mL) and sodium hydroxide (0.37 g, 9.24 mmol) were added to a 100 mL reaction bottle in sequence, and the temperature was raised to 60°C for 3 h. After the reaction was completed by TLC monitoring, the reaction solution was cooled to room temperature, and the pH value was adjusted to 5 with 1N hydrochloric acid to precipitate a solid, which was collected by suction filtration, rinsed with water and dried to obtain (S)-10-bromo-9-fluoro-3-methyl-3,4-dihydro-2H-[1,4]oxazepin[5,6,7-de]quinoline-5-carboxylic acid (0.8 g, yield 76.1%). ESI-MS (m / z): 340.99 / 342.98 [M+H] + .

[0466] Step 6: Synthesis of (S)-7-bromo-6-fluoro-10-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0467] DMF (15 mL), (S)-10-bromo-9-fluoro-3-methyl-3,4-dihydro-2H-[1,4]oxazepine [5,6,7-de] quinoline-5-carboxylic acid (0.8 g, 2.35 mmol), DIEA (0.46 g, 3.53 mmol) and diphenylphosphoryl azide (0.78 g, 2.82 mmol) were added to a 100 mL reaction bottle in sequence, and the temperature was raised to 60°C for reaction for 3 h. The reaction was monitored by TLC, the reaction solution was cooled to room temperature, water was added to precipitate the solid, the solid was collected by suction filtration, the solid was rinsed with water and dried to obtain (S)-7-bromo-6-fluoro-10-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (0.7 g, yield was 88.1%). ESI-MS(m / z):337.99 / 339.98[M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.443(d,3H),4.593-4.616(m,2H),4.803-4.829(m,1H),7.594(d,1H),8.678(s,1H),11.681(s,1H).

[0468] Step 7: Synthesis of (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-1)

[0469] In a 100 mL reaction bottle, DMF (15 mL) and (S)-7-bromo-6-fluoro-10-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azule-1(2H)-one (0.7 g, 2.07 mmol) were added in sequence. After cooling to 0°C, NaH (0.124 g, 3.11 mmol) was added. The mixture was reacted at this temperature for 0.5 h. Then, iodomethane (0.441 g, 3.11 mmol) was added and the reaction was allowed to proceed at room temperature overnight. The reaction was completed by TLC monitoring, and water was added to the reaction solution to precipitate solids, which were collected by suction filtration, rinsed with water and dried to obtain (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (0.62 g, yield 85.1%). ESI-MS (m / z): 352.00 / 354.00 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:1.451(d,3H),3.536(s,3H),4.590-4.612(m,1H),4.651-4.665(m,1H),4.814-4.841(m,1H),7.635(d,1H),8.925(s,1H).

[0470] Intermediate Preparation Example 2: Preparation of (R)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-2)

[0471]

[0472] The synthesis method is the same as that of Preparation Example 1, except that D-aminopropanol is used instead of L-aminopropanol to obtain (R)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one with a yield of 75.4%. ESI-MS (m / z): 352.20 / 354.19 [M+H] + .

[0473] Intermediate Preparation Example 3: Preparation of 7-bromo-6-fluoro-9-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-3)

[0474]

[0475] The synthesis method is the same as that of Preparation Example 1, except that 2-amino-1-(4-fluorophenyl)ethanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-9-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 82.4%. ESI-MS (m / z): 432.01 / 434.01 [M+H] + .

[0476] Intermediate Preparation Example 4: Preparation of 7-bromo-6-fluoro-2,10,10-trimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-4)

[0477]

[0478] The synthesis method is the same as that of Preparation Example 1, except that 2-amino-2-methyl-propanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-2,10,10-trimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one with a yield of 82.4%. ESI-MS (m / z): 366.01 / 368.01 [M+H] + .

[0479] Intermediate Preparation Example 5: Preparation of 7-bromo-6-fluoro-2-methyl-9-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-5)

[0480]

[0481] The synthesis method is the same as that of Preparation Example 1, except that 2-amino-1-(pyridin-2-yl)ethanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-2-methyl-9-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one. ESI-MS (m / z): 415.01 / 417.01 [M+H] + .

[0482] Intermediate Preparation Example 6: Preparation of (R)-7-bromo-6-fluoro-10-isobutyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-6)

[0483]

[0484] The synthesis method is the same as that of Preparation Example 1, except that D-leucinol is used instead of L-aminopropanol to obtain (R)-7-bromo-6-fluoro-10-isobutyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 30.9%. ESI-MS (m / z): 394.05 / 396.05 [M+H] + .

[0485] Intermediate Preparation Example 7: Preparation of (S)-7-bromo-6-fluoro-10-isobutyl-2-methyl-9,10-dihydro-8-oxo-2,4,10a-triazaanthraquinone[2,1,8-cde]azulen-1(2H)-one (M-7)

[0486]

[0487] The synthesis method is the same as that of Preparation Example 1, except that L-leucinol is used instead of L-aminopropanol to obtain (S)-7-bromo-6-fluoro-10-isobutyl-2-methyl-9,10-dihydro-8-oxo-2,4,10a-triazaanthraquinone [2,1,8-cde] azulene-1(2H)-one with a yield of 51.0%. ESI-MS (m / z): 393.92 / 395.87 [M+H] + .

[0488] Intermediate Preparation Example 8: Preparation of 7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-8)

[0489]

[0490] The synthesis method is the same as that of Preparation Example 1, except that mercaptoethylamine is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one with a yield of 82.1%. ESI-MS (m / z): 353.96 / 355.97 [M+H] + .

[0491] Intermediate Preparation Example 9: Preparation of 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazinaphtho[2,1,8-cde]azulene-10,1-cyclopropane]-1-one (M-9)

[0492]

[0493] The synthesis method is the same as that of Preparation Example 1, except that 1-aminocyclopropylmethanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazinylnaphtho[2,1,8-cde]azulene-10,1-cyclopropane]-1-one with a yield of 43.7%. ESI-MS (m / z): 364.01 / 366.01 [M+H] + .

[0494] Intermediate Preparation Example 10: Preparation of 7-bromo-9-(ethoxymethyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazaanthraquinone[2,1,8-cde]azulene-1(2H)-one (M-10)

[0495]

[0496] The synthesis method is the same as that of Preparation Example 1, except that 1-amino-3-ethoxy-2-propanol is used instead of L-aminopropanol to obtain 7-bromo-9-(ethoxymethyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazaanthraquinone[2,1,8-cde]azulen-1(2H)-one in a yield of 49.3%. ESI-MS (m / z): 396.03 / 398.03 [M+H] + .

[0497] Intermediate Preparation Example 11: Preparation of (S)-10-benzyl-7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-11)

[0498]

[0499] The synthesis method is the same as that of Preparation Example 1, except that (S)-2-amino-3-phenylpropan-1-ol is used instead of L-aminopropanol to obtain (S)-10-benzyl-7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxo-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 53.2%. ESI-MS (m / z): 428.03 / 430.03 [M+H] + .

[0500] Intermediate Preparation Example 12: Preparation of (R)-10-benzyl-7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-12)

[0501]

[0502] The synthesis method is the same as that of Preparation Example 1, except that (R)-2-amino-3-phenylpropan-1-ol is used instead of L-aminopropanol to obtain (R)-10-benzyl-7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 32.6%. ESI-MS (m / z): 428.03 / 430.03 [M+H] + .

[0503] Intermediate Preparation Example 13: Preparation of 7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-13)

[0504]

[0505] The synthesis method is the same as that of Preparation Example 1, except that 2-aminoethanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one with a yield of 40.7%. ESI-MS (m / z): 337.99 / 339.99 [M+H] + .

[0506] Intermediate Preparation Example 14: Preparation of (S)-7-bromo-6-fluoro-10-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-14)

[0507]

[0508] The synthesis method is the same as that of Preparation Example 1, except that L-valinol is used instead of L-aminopropanol to obtain (S)-7-bromo-6-fluoro-10-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one with a yield of 52.3%. ESI-MS (m / z): 380.03 / 382.03 [M+H] + .

[0509] Intermediate Preparation Example 15: Preparation of (R)-7-bromo-6-fluoro-10-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-15)

[0510]

[0511] The synthesis method is the same as that of Preparation Example 1, except that D-valinol is used instead of L-aminopropanol to obtain (R)-7-bromo-6-fluoro-10-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 59.3%. ESI-MS (m / z): 380.03 / 382.03 [M+H] + .

[0512] Intermediate Preparation Example 16: Preparation of 7-bromo-6-fluoro-9-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-16)

[0513]

[0514] The synthesis method is the same as that of Preparation Example 1, except that 1-amino-3-methyl-butan-2-ol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-9-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 30.6%. ESI-MS (m / z): 380.03 / 382.03 [M+H]+.

[0515] Intermediate Preparation Example 17: Preparation of (S)-7-bromo-9-((dimethylamino)methyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-17)

[0516]

[0517] The synthesis method is the same as that of Preparation Example 1, except that (R)-1-amino-3-(dimethylamino)propan-2-ol is used instead of L-aminopropanol to obtain (S)-7-bromo-9-((dimethylamino)methyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 75.5%. ESI-MS (m / z): 395.04 / 397.04 [M+H] + .

[0518] Intermediate Preparation Example 18: Preparation of (S)-7-bromo-6-fluoro-2-methyl-9-(piperidin-1-ylmethyl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-18)

[0519]

[0520] The synthesis method is the same as that of Preparation Example 1, except that (R)-1-amino-3-(piperidin-1-yl)propan-2-ol is used instead of L-aminopropanol to obtain (S)-7-bromo-6-fluoro-2-methyl-9-(piperidin-1-ylmethyl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 72.1%. ESI-MS (m / z): 435.08 / 437.08 [M+H] + .

[0521] Intermediate Preparation Example 19: Preparation of 5-bromo-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadienyl[gh]pyroxene-11(12H)-one (M-19)

[0522]

[0523] The synthesis method is the same as that of Preparation Example 1, except that 2-aminocyclohexanol is used instead of L-aminopropanol to obtain 5-bromo-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadienyl[gh]pyro-11(12H)-one with a yield of 68.5%. ESI-MS (m / z): 392.03 / 394.03 [M+H] + .

[0524] Intermediate Preparation Example 20: Preparation of (R)-7-bromo-10-ethyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-20)

[0525]

[0526] The synthesis method is the same as that of Preparation Example 1, except that (R)-2-amino-1-butanol is used instead of L-aminopropanol to obtain (R)-7-bromo-10-ethyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 71.5%. ESI-MS (m / z): 366.02 / 368.02 [M+H] + .

[0527] Intermediate Preparation Example 21: Preparation of (S)-7-bromo-10-ethyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-21)

[0528]

[0529] The synthesis method is the same as that of Preparation Example 1, except that (S)-2-amino-1-butanol is used instead of L-aminopropanol to obtain (S)-7-bromo-10-ethyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 68.5%. ESI-MS (m / z): 366.02 / 368.02 [M+H] + .

[0530] Intermediate Preparation Example 22: Preparation of 7-bromo-6-fluoro-2,9-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-22)

[0531]

[0532] The synthesis method is the same as that of Preparation Example 1, except that 1-amino-2-propanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-2,9-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one with a yield of 82.4%. ESI-MS (m / z): 352.00 / 354.00 [M+H] + .

[0533] Intermediate Preparation Example 23: Preparation of 7-bromo-6-fluoro-9-(2-fluoropyridin-4-yl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-23)

[0534]

[0535] The synthesis method is the same as that of Preparation Example 1, except that 2-amino-1-(2-fluoro-pyridin-4-yl)ethanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-9-(2-fluoropyridin-4-yl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 32.5%. ESI-MS (m / z): 433.00 / 435.00 [M+H] + .

[0536] Intermediate Preparation Example 24: Preparation of 7-bromo-10-cyclopropyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-24)

[0537]

[0538] The synthesis method is the same as that of Preparation Example 1, except that 2-amino-2-cyclopropylethanol is used instead of L-aminopropanol to obtain 7-bromo-10-cyclopropyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 28.4%. ESI-MS (m / z): 378.02 / 380.02 [M+H] + .

[0539] Intermediate Preparation Example 25: Preparation of 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclobutane]-1-one (M-25)

[0540]

[0541] The synthesis method is the same as that of Preparation Example 1, except that (1-aminocyclobutyl)methanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazinylnaphtho[2,1,8-cde]azulene-10,1'-cyclobutane]-1-one with a yield of 37.5%. ESI-MS (m / z): 377.93 / 379.95 [M+H] + .

[0542] Intermediate Preparation Example 26: Preparation of (6aR, 10aS)-5-bromo-4-fluoro-12-methyl-11-oxo-6a,7,10,10a,11,12-hexahydro-6-oxa-2,8,10b,12-tetraazacyclopentadiene-8(9H)-carboxylic acid ethyl ester (M-26)

[0543]

[0544] The synthesis method is the same as that of Preparation Example 1, except that (3S,4R)-4-amino-3-hydroxypiperidine-1-carboxylic acid ethyl ester is used instead of L-aminopropanol to obtain (6aR,10aS)-5-bromo-4-fluoro-12-methyl-11-oxo-6a,7,10,10a,11,12-hexahydro-6-oxa-2,8,10b,12-tetraazacyclopentadiene-8(9H)-carboxylic acid ethyl ester in a yield of 37.5%. ESI-MS (m / z): 464.93 / 466.95 [M+H] + .

[0545] Intermediate Preparation Example 27: Preparation of 7-bromo-6-fluoro-10-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-27)

[0546]

[0547] The synthesis method is the same as that of Preparation Example 1, except that 2-amino-2-(4-fluorophenyl)ethanol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-10-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (100 mg, yield 32%). ESI-MS (m / z): 432.21 / 434.25 [M+H] + .

[0548] Intermediate Preparation Example 28: Preparation of 7-bromo-6-methoxy-2-methyl-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-28)

[0549]

[0550] Step 1: Synthesis of 4-bromo-3-fluoro-5-methoxyaniline

[0551] 3-Fluoro-5-methoxyaniline (4.1 g, 29.1 mmol) and DMF (50 mL) were added to a 250 mL reaction bottle in sequence, and NBS (5.2 g, 29.1 mmol) was added in batches at room temperature. The reaction was allowed to react for 1 h at room temperature. After the reaction solution was cooled, 100 mL of water and 100 mL of ethyl acetate were added, and the organic phase was separated and extracted. The organic phase was concentrated to dryness and purified by column chromatography (PE: EA = 10: 1 to 2: 1) to obtain 4.90 g of 4-bromo-3-fluoro-5-methoxyaniline. ESI-MS (m / z): 219.98 / 222.01 [M+H] + .

[0552] Step 2: Synthesis of diethyl 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene)malonate

[0553] 4-Bromo-3-fluoro-5-methoxyaniline (4.8 g, 21.8 mmol), diethyl 2-(ethoxymethylene)malonate (7.0 g, 32.4 mmol) and 50 mL of anhydrous ethanol were added to a 250 mL reaction bottle in sequence, the reaction solution was heated to reflux, reacted for 6 h, cooled to room temperature, 100 mL of n-hexane was added at room temperature, and 5.9 g of diethyl 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene)malonate was obtained by filtration. ESI-MS (m / z): 390.20 / 392.18 [M+H] + .

[0554] Step 3: Synthesis of ethyl 6-bromo-5-fluoro-4-hydroxy-7-methoxyquinoline-3-carboxylate

[0555] Add 40 mL of diphenyl ether to a 250 mL reaction bottle, heat to 240°C, add diethyl 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene)malonate (5.9 g, 15.1 mmol) in batches, maintain the temperature for 1 h, cool to room temperature, add 100 mL of n-hexane at room temperature, and filter to obtain 4.6 g of ethyl 6-bromo-5-fluoro-4-hydroxy-7-methoxyquinoline-3-carboxylate. ESI-MS (m / z): 344.14 / 346.18 [M+H] + .

[0556] Step 4: Synthesis of ethyl 6-bromo-4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate

[0557] Add 6-bromo-5-fluoro-4-hydroxy-7-methoxyquinoline-3-carboxylic acid ethyl ester (800 mg, 2.32 mmol) and 10 mL of thionyl chloride to a 100 mL reaction bottle, add two drops of DMF, reflux for 4 h, and evaporate to dryness under reduced pressure to obtain 840 mg of 6-bromo-4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylic acid ethyl ester. ESI-MS (m / z): 361.91 / 363.99 [M+H] + .

[0558] Step 5: Synthesis of ethyl 6-bromo-5-fluoro-4-((2-hydroxy-1-(pyridin-2-yl)ethyl)amino)-7-methoxyquinoline-3-carboxylate

[0559] 6-Bromo-4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylic acid ethyl ester (840 mg, 2.32 mmol), DMF 10 mL, DIPEA (1500 mg, 11.6 mmol), 2-amino-2-(pyridin-2-yl)ethanol (600 mg, 2.84 mmol) were added to a 100 mL reaction bottle in sequence, and the reaction solution was heated to 90°C for 2 h. After the reaction was completed by TLC monitoring, the reaction solution was cooled to room temperature, water was added, filtered, and the filter cake was dried to obtain 1.1 g of 6-Bromo-5-fluoro-4-((2-hydroxy-1-(pyridin-2-yl)ethyl)amino)-7-methoxyquinoline-3-carboxylic acid ethyl ester. ESI-MS (m / z): 464.29 / 466.30 [M+H] + .

[0560] Step 6: Synthesis of 10-bromo-9-methoxy-3-(pyridin-2-yl)-3,4-dihydro-2H-[1,4]oxaazepine[5,6,7-de]quinoline-5-carboxylic acid

[0561] In a 100 mL reaction bottle, add 6-bromo-5-fluoro-4-((2-hydroxy-1-(pyridin-2-yl)ethyl)amino)-7-methoxyquinoline-3-carboxylic acid ethyl ester (1100 mg, 2.37 mmol), THF10 mL, water 5 mL, sodium hydroxide (520 mg, 13.0 mmol), and heat the reaction solution to 60 ° C for 8 h. After the reaction is completed, THF is removed under reduced pressure, the pH value is adjusted to 3 with 6N hydrochloric acid, and 110-bromo-9-methoxy-3-(pyridin-2-yl)-3,4-dihydro-2H-[1,4]oxaza[5,6,7-de]quinoline-5-carboxylic acid 0.3 g is obtained by filtration. ESI-MS (m / z): 416.19 / 418.20 [M+H] +.

[0562] Step 7: Synthesis of 7-bromo-6-methoxy-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one. In a 100 mL reaction bottle, 10-bromo-9-methoxy-3-(pyridin-2-yl)-3,4-dihydro-2H-[1,4]oxaazepine[5,6,7-de]quinoline-5-carboxylic acid (300 mg, 0.72 mmol), 10 mL of DMF, triethylamine (150 mg, 1.48 mmol), and DPPA (300 mg, 1.09 mmol) were added in sequence, and the reaction solution was heated to 90°C for 2 h. The reaction was completed by TLC monitoring, the reaction solution was cooled to room temperature, water was added, solid precipitated, and filtered to obtain 0.3 g of 7-bromo-6-methoxy-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one. ESI-MS (m / z): 412.19 / 414.23 [M+H] + .

[0563] Step 8: Synthesis of 7-bromo-6-methoxy-2-methyl-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0564] 7-Bromo-6-methoxy-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (300 mg, 0.72 mmol), cesium carbonate (474 ​​mg, 1.45 mmol), DMF 10 mL were added to the reaction flask in sequence, and iodomethane (155 mg, 1.10 mmol) was added at room temperature, and the reaction was carried out at room temperature for 1.5 h. After the reaction was completed under TLC monitoring, the reaction solution was cooled to room temperature, water was added, and solids precipitated. After filtration, 0.2 g of 7-Bromo-6-methoxy-2-methyl-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one was obtained, and the yield was 64.5%. ESI-MS(m / z):427.03 / 429.03[M+H] + .

[0565] Intermediate Preparation Example 29: Preparation of (S)-7-bromo-6-methoxy-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-29)

[0566]

[0567] The synthesis method is the same as that of Preparation Example 1, except that 4-bromo-3-fluoro-5-methoxyaniline is used instead of 4-bromo-3,5-difluoroaniline to obtain (S)-7-bromo-6-methoxy-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 82.4%. ESI-MS (m / z): 364.02 / 366.02 [M+H] + .

[0568] Intermediate Preparation Example 30: Preparation of (R)-7-bromo-6-methoxy-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-30)

[0569]

[0570] The synthesis method is the same as that of Preparation Example 1, except that 4-bromo-3-fluoro-5-methoxyaniline is used instead of 4-bromo-3,5-difluoroaniline, and (R)-2-amino-1-propanol is used instead of (S)-2-amino-1-propanol to obtain (R)-7-bromo-6-methoxy-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 82.4%. ESI-MS (m / z): 364.02 / 366.02 [M+H] + .

[0571] Intermediate Preparation Example 31: Preparation of 5-bromo-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadienyl[gh]pyroxene-11(12H)-one (M-31)

[0572]

[0573] Step 1: Synthesis of ethyl 6-bromo-5-fluoro-4-((2-hydroxyphenyl)amino)-7-methoxyquinoline-3-carboxylate

[0574] 6-bromo-4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylic acid ethyl ester (840 mg, 2.32 mmol), 2-aminophenol (280 mg, 2.57 mmol), and 10 mL of glacial acetic acid were added to a 100 mL reaction bottle in sequence, and the reaction solution was heated to 60°C for 1 h. After the reaction was completed by TLC monitoring, the reaction solution was cooled to room temperature, water and ethyl acetate were added to the reaction solution, and the organic phase was washed twice with saturated sodium bicarbonate and concentrated to dryness under reduced pressure to obtain 1.0 g of 6-bromo-5-fluoro-4-((2-hydroxyphenyl)amino)-7-methoxyquinoline-3-carboxylic acid ethyl ester.

[0575] Step 2: Synthesis of 6-bromo-5-methoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylic acid

[0576] In a 100 mL reaction bottle, add 6-bromo-5-fluoro-4-((2-hydroxyphenyl)amino)-7-methoxyquinoline-3-carboxylic acid ethyl ester (1000 mg, 2.30 mmol), THF 10 mL, water 5 mL, sodium hydroxide (460 mg, 11.5 mmol), and heat the reaction solution to 60 ° C for 8 hours. After the reaction is completed, THF is removed under reduced pressure, and the pH value is adjusted to 3 with 6N hydrochloric acid, and filtered to obtain 0.86 g of 6-bromo-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylic acid.

[0577] Step 3: Synthesis of 5-bromo-4-methoxy-6-oxa-2,10b,12-triazacyclopentadien[gh]pyroxene-11(12H)-one

[0578] 6-Bromo-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylic acid (860 mg, 2.22 mmol), 10 mL of DMF, triethylamine (450 mg, 4.45 mmol), and DPPA (917 mg, 3.33 mmol) were added to a 100 mL reaction bottle in sequence, and the reaction solution was heated to 90°C for 2 h. After the reaction was completed under TLC monitoring, the reaction solution was cooled to room temperature, and water was added to precipitate solids, which were filtered to obtain 0.84 g of 5-bromo-4-methoxy-6-oxa-2,10b,12-triazacyclopentadien[gh]pyroxene-11(12H)-one.

[0579] Step 4: Synthesis of 5-bromo-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadien[gh]pyroxene-11(12H)-one

[0580] 5-Bromo-4-methoxy-6-oxa-2,10b,12-triazacyclopentadien[gh]pyro-11(12H)-one (840mg, 2.19mmol), cesium carbonate (1420mg, 4.36mmol), DMF10 mL were added to the reaction flask in sequence, and iodomethane (466mg, 3.28mmol) was added dropwise at room temperature. After the addition was completed, the reaction was allowed to react at room temperature for 1.5h. The reaction was monitored by TLC. Water was added to the reaction solution, and solids were precipitated. 5-Bromo-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadien[gh]pyro-11(12H)-one (0.76g) was obtained by filtration, and the yield was 87.3%. ESI-MS (m / z): 398.01 / 400.01 [M+H] + .

[0581] Intermediate Preparation Example 32: Preparation of 5-bromo-4-methoxy-12-methyl-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]pyroxene-11(12H)-one (M-32)

[0582]

[0583] The synthesis method is the same as that of Preparation Example 31, except that 3-amino-4-hydroxypyridine is used instead of 2-aminophenol to obtain 5-bromo-4-methoxy-12-methyl-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]pyroxene-11(12H)-one with a yield of 27.3%. ESI-MS (m / z): 398.99 / 400.96 [M+H] + .

[0584] Intermediate Preparation Example 33: Preparation of (6aS,9aR)-5-(6-bromopyridin-3-yl)-4-fluoro-11-methyl-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadien[h]naphtho[2,1,8-cde]azulene-10(11H)-one (M-33)

[0585]

[0586] The synthesis method is the same as that of Preparation Example 1, except that (3S,4R)-4-aminotetrahydrofuran-3-ol is used instead of L-aminopropanol to obtain (6aS,9aR)-5-bromo-4-fluoro-11-methyl-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopenta[h]naphtho[2,1,8-cde]azulen-10(11H)-one in a yield of 60.3%. ESI-MS (m / z): 379.94 / 381.95 [M+H] + .

[0587] Intermediate Preparation Example 34: Preparation of (6aR, 9aS)-5-bromo-4-fluoro-11-methyl-6a, 7, 9, 9a-tetrahydro-6, 8-dioxa-2, 9b, 11-triazacyclopenta[h]naphtho[2, 1, 8-cde]azulen-10(11H)-one (M-34)

[0588]

[0589] The synthesis method is the same as that of Preparation Example 1, except that (3R, 4S)-4-aminotetrahydrofuran-3-ol is used instead of L-aminopropanol to obtain (6aR, 9aS)-5-bromo-4-fluoro-11-methyl-6a, 7, 9, 9a-tetrahydro-6, 8-dioxa-2, 9b, 11-triazacyclopenta[h]naphtho[2, 1, 8-cde]azulen-10(11H)-one in a yield of 82.4%. ESI-MS (m / z): 380.00 / 382.00 [M+H] + .

[0590] Intermediate Preparation Example 35: Preparation of 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,3'-oxetanyl]-1-one (M-35)

[0591]

[0592] The synthesis method is the same as that of Preparation Example 1, except that 3-amino-3-hydroxymethyloxetane is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulene-10,3'-oxetane-1-one with a yield of 32.1%. ESI-MS (m / z): 380.00 / 381.99 [M+H] + .

[0593] Intermediate Preparation Example 36: Preparation of 7-bromo-6-methoxy-10-hydroxymethyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-36)

[0594]

[0595] The synthesis method is the same as that of Preparation Example 31, except that 2-amino-1,3-propanediol is used instead of 2-aminophenol to obtain 7-bromo-6-methoxy-10-hydroxymethyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 28.0%. ESI-MS (m / z): 380.02 / 382.02 [M+H] + .

[0596] Intermediate Preparation Example 37: Preparation of 7-bromo-6-fluoro-10-(hydroxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-37)

[0597]

[0598] The synthesis method is the same as that of Preparation Example 1, except that 2-amino-1,3-propanediol is used instead of L-aminopropanol to obtain 7-bromo-6-fluoro-10-(hydroxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one with a yield of 74.2%. ESI-MS (m / z): 367.96 / 370.02 [M+H] + .

[0599] Intermediate Preparation Example 38: Preparation of 5-bromo-8-fluoro-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadienyl[gh]pyroxene-11(12H)-one (M-38)

[0600]

[0601] The synthesis method is the same as that of Preparation Example 31, except that 2-amino-5-fluorophenol is used instead of 2-aminophenol to obtain 5-bromo-8-fluoro-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadienyl[gh]pyro-11(12H)-one with a yield of 74.5%. ESI-MS (m / z): 416.20 / 418.20 [M+H] + .

[0602] Intermediate Preparation Example 39: Preparation of 7-bromo-6-methoxy-2-methyl-9-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-39)

[0603]

[0604] The synthesis method is the same as that of Preparation Example 28, except that 2-amino-1-(pyridin-2-yl)ethanol is used instead of 2-amino-2-(pyridin-2-yl)ethanol to obtain 7-bromo-6-methoxy-2-methyl-9-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 63.8%. ESI-MS (m / z): 427.03 / 429.03 [M+H] + .

[0605] Intermediate Preparation Example 40: Preparation of (R)-7-bromo-6-methoxy-2-methyl-10-phenyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-40)

[0606]

[0607] The synthesis method is the same as that of Preparation Example 28, except that (R)-2-amino-2-phenylethanol is used instead of 2-amino-2-(pyridin-2-yl)ethanol to obtain (R)-7-bromo-6-methoxy-2-methyl-10-phenyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one in a yield of 67.2%. ESI-MS (m / z): 426.04 / 428.04 [M+H] + .

[0608] Intermediate Preparation Example 41: Preparation of ethyl 5-fluoro-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylate (M-41)

[0609]

[0610] In a 100 mL round-bottom flask, ethyl 4-chloro-5,7-difluoroquinoline-3-carboxylate (0.20 mmol), o-aminophenol (0.24 mmol), DIPEA (0.4 mmol) and DMF (20 mL) were added in sequence, and the reaction system was stirred at 90°C for 2.0 h. TLC monitoring showed that no raw material remained, and the heating was stopped. The reaction solution was cooled to room temperature, and water and ethyl acetate were added to the reaction solution. The organic phase was extracted, and the organic phase was concentrated under reduced pressure. The crude product was separated by column chromatography to obtain ethyl 5-fluoro-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate in a yield of 83.7%. 1 H NMR (600 MHz, CDCl 3)δ11.590(s,1H),9.130(s,1H),7.388(d,J=10.2Hz,1H),7.238-7.250(m,1H),7.105 -7.126(m,2H),7.025-7.061(m,2H),4.470(q,J=6.6Hz,2H),1.470(t,J=6.6Hz,3H); 13 C NMR (150 MHz, CDCl 3 )δ168.78,165.44,163.76,156.80(d,J=13.5Hz),153.05(d,J=13.5Hz),152.54,151.39,148.82,133.76,125.85,125.54,121.70,110.35(d,J=19.5Hz),107.28(d,J=27Hz),102.71,61.51,14.39; HR-MS(ESI)theoretical value C 18 H 14 FN 2 O 3 [M+H] + :325.1734, measured value 325.1732.

[0611] Intermediate Preparation Example 42: Preparation of ethyl 5-fluoro-12H-benzo[2,3][1,4]thiazino[5,6,7-de]quinoline-1-carboxylate (M-42)

[0612]

[0613] The synthesis method was the same as that in Preparation Example 41 to obtain 5-fluoro-12H-benzo[2,3][1,4]thiazino[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 81.6%. 1 HNMR (600MHz, CDCl 3 )δ11.885(s,1H),9.181(s,1H),7.549(d,J=7.2Hz,1H),7.500(d,J=7.8Hz,1H),7.429-7.442(m ,1H),7.295-7.320(m,1H),7.134-7.167(m,2H),4.495(q,J=7.2Hz,2H),1.484(t,J=6.6Hz,3H); 13 C NMR (150 MHz, CDCl 3)δ168.99,164.33,162.63,154.39,154.00(d,J=13.5Hz),152.55,144.81,135.7 5(d,J=9.0Hz),131.88,129.85,128.59,126.04,123.62,119.35(d,J=24Hz),113.95(d,J=21Hz),104.93,61.71,14.41; HR-MS(ESI)theoretical value C 18 H 14 FN 2 O 2 S[M+H] + :341.0957, measured value 341.0959.

[0614] Intermediate Preparation Example 43: Preparation of ethyl 5-fluoro-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate (M-43)

[0615]

[0616] The synthesis method was the same as that in Preparation Example 41 to obtain 5-fluoro-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 86.4%. 1 H NMR (600MHz, CD 3 OD+CF 3 COOH)δ9.040(s,1H),7.021-7.035(m,1H),6.958-6.976(m,1H),6.875-6.900(m,1H),6. 793-6.806(m,2H),6.757-6.778(m,1H),4.496(q,J=7.2Hz,2H),1.474(t,J=7.2Hz,3H); 13 C NMR (150MHz, CD 3 OD+CF 3 COOH)δ168.10,156.01,145.60,135.97,124.63,123.84,120.84,118.89,117.00,115.12,113.23,106.01(d,J=25.5Hz),104.73,102.73,99.08(d,J=25.5Hz),64.20,55.61,14.30; HR-MS(ESI)theoretical value C 18 H 15 FN 3 O 2 [M+H]+ :324.1171, measured value 324.1173.

[0617] Intermediate Preparation Example 44: Preparation of ethyl 5,9-difluoro-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylate (M-44)

[0618]

[0619] The synthesis method was the same as that in Preparation Example 41 to obtain 5,9-difluoro-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 80.3%. 1 H NMR (600 MHz, CDCl 3 )δ11.585(s,1H),9.161(s,1H),7.439(d,J=8.4Hz,1H),7.022-7.060(m, 3H), 6.888-6.899 (m, 1H), 4.476 (q, J = 7.2Hz, 2H), 1.475 (t, J = 7.2Hz, 3H); 13 C NMR (150 MHz, CDCl 3 )δ168.84,165.48,163.67,160.62,158.98,156.30(d,J=15Hz),156.05,152.63,151.25,130.27,122.36(d,J=9Hz),112.90(d,J=25.5Hz),110.76(d,J=19.5Hz),109.35(d,J=24Hz),107.48(d,J=25.5Hz),102.77,61.65,14.43; HR-MS(ESI)theoretical value C 18 H 13 F 2 N 2 O 3 [M+H] + :343.2013, measured value 343.2011.

[0620] Intermediate Preparation Example 45: Preparation of ethyl 5-fluoro-10-methoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylate (M-45)

[0621]

[0622] The synthesis method was the same as that of Preparation Example 41 to obtain 5-fluoro-10-methoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 85.6%. 1 H NMR (600 MHz, CDCl 3 )δ11.542(s,1H),9.124(s,1H),7.370-7.390(m,1H),7.136(d,J=9.0Hz,1H),6.987-7.006(m,1H) ,6.215-6.634(m,1H),6.536(m,1H),4.462(q,J=7.2Hz,2H),3.768(s,3H),1.467(t,J=7.2Hz,3H); 13 C NMR (150 MHz, CDCl 3 )δ168.82,165.52,163.84,157.39,157.20(d,J=13.5Hz),152.50(d,J=13.5Hz),152.42,151.62,142.84,134.35,122.24,111.14,110.51(d,J=3Hz),110.14(d,J=21Hz),107.10(d,J=25.5Hz),106.39,102.70,61.56,55.93,14.40; HR-MS(ESI)theoretical value C 19 H 16 FN 2 O 4 [M+H] + :355.0978, measured value 355.0980.

[0623] Intermediate Preparation Example 46: Preparation of ethyl 5-fluoro-12H-pyrido[3',4':2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylate (M-46)

[0624]

[0625] The synthesis method was the same as that of Preparation Example 41 to obtain 5-fluoro-12H-pyrido[3',4':2,3][1,4]oxaaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 95.8%. 1 H NMR (600MHz, CD 3OD)δ9.425(s,1H),8.932(s,1H),8.585(d,J=4.8Hz,1H),7.636-7.736(m,3H),4.619(q,J=6.6Hz,2H),1.528(t,J=6.6Hz,3H); 13 C NMR (150MHz, CD 3 OD+CF 3 COOH)δ168.23,166.68,156.40(d,J=15Hz),152.15,150.11,145.83(d,J=18Hz),142.15,139.35,119.32,117.80,116.99,115.89,111.65(d,J=28.5Hz),110.61,106.95,64.53,14.31; HR-MS(ESI)theoretical value C 17 H 13 FN 3 O 3 [M+H] + :326.0832, measured value 326.0830.

[0626] Intermediate Preparation Example 47: Preparation of ethyl 5-fluoro-12H-pyrido[4',3':2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylate (M-47)

[0627]

[0628] The synthesis method was the same as that of Preparation Example 41 to obtain 5-fluoro-12H-pyrido[4',3':2,3][1,4]oxaaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 94.5%. 1 H NMR (600 MHz, CF 3 COOH+CDCl 3 )δ13.144(s,1H),9.406(s,1H),8.799(s,1H),8.588(d,J=4.2Hz,1H),7.927(d,J=7.8Hz,1H), 7.584(d,J=5.4Hz,1H),7.422(d,J=7.8Hz,1H),4.571(q,J=7.2Hz,2H),1.485(t,J=7.2Hz,3H); 13 CNMR(150MHz,CF 3 COOH+CDCl 3)δ167.84,166.63,166.09,156.08,154.78(d,J=13.5Hz),153.43,146.80,144.71,140.78,129.00,118.64,116.56,117.69(d,J=27Hz),107.99,106.15(d,J=24Hz),104.00,64.24,13.93; HR-MS(ESI)theoretical value C 17 H 13 FN 3 O 3 [M+H] + :326.1438, measured value 326.1440.

[0629] Intermediate Preparation Example 48: Preparation of 5-methoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylic acid ethyl ester (M-48)

[0630]

[0631] Step 1: Synthesis of diethyl 2-(((3-fluoro-5-methoxyphenyl)amino)methylene)malonate

[0632] 3-Fluoro-5-methoxyaniline (1.41 g, 0.01 mol), diethyl 2-(ethoxymethylene)malonate (2.16 g, 0.01 mol) and 25 mL of anhydrous ethanol were added to a 100 mL reaction bottle in sequence, the reaction solution was heated to reflux, reacted for 6 h, cooled to room temperature, and the solvent was removed by rotary evaporation to obtain 2.76 g of diethyl 2-(((3-fluoro-5-methoxyphenyl)amino)methylene)malonate, a colorless transparent liquid, with a yield of 88.7%. HR-MS (ESI) theoretical value C 15 H 19 FNO 5 [M+H] + 312.0755, measured value 312.0756; 1 H NMR (600 MHz, CDCl 3 )δ:10.841~10.862(m,1H),8.322~8.344(m,1H),6.304-6.395(m,3H),4.165~4.239(m,4H),3.716~3.726(m,3H),1.243~1.316(m,6H).

[0633] Step 2: Synthesis of ethyl 5-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

[0634] 40 mL of diphenyl ether was added to a 100 mL reaction bottle, the temperature was raised to 240°C, 2-(((3-fluoro-5-methoxyphenyl)amino)methylene)malonic acid diethyl ester (3.11 g, 0.01 mol) was added, the temperature was maintained for 1 h, the reaction was cooled to room temperature, 100 mL of n-hexane was added at room temperature, and 5-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester was filtered to obtain 2.24 g of white solid. The yield was 84.4%, and the theoretical value of HR-MS (ESI) was C 13 H 12 FNO 4 [M+H] + 266.1326, measured value 266.1328; 1 HNMR (600 MHz, DMSO-d 6 )δ:12.071(s,1H),8.396(s,1H),6.833-6.844(m,1H),6.758~6.780(m,1H),4.155~4.201(m,2H),3.853(s,3H),1.244~1.286(m,3H).

[0635] Step 3: Synthesis of ethyl 4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate

[0636] In a 50 mL reaction bottle, add 5-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (1.30 g, 4.90 mmol), 10 mL of thionyl chloride, and dropwise add two drops of DMF. Reflux for 4 h. After the reaction is complete, evaporate to dryness under reduced pressure to obtain 1.21 g of 4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylic acid ethyl ester as a yellow solid with a yield of 87.1%. HR-MS (ESI) theoretical value C 13 H 12 ClFNO 3 [M+H] + 283.1184, measured value 283.1186; 1 H NMR (600 MHz, CDCl 3 )δ: 9.152 (s, 1H), 7.785 (m, 1H), 6.955-6.976 (m, 1H), 4.522 (q, J = 7.2Hz, 2H), 4.025 (s, 3H), 1.444 (t, J = 7.2Hz, 3H).

[0637] Step 4: Synthesis of ethyl 5-methoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylate

[0638] 4-Chloro-5-fluoro-7-methoxyquinoline-3-carboxylic acid ethyl ester (0.20mmol), o-aminophenol (0.24mmol), DIPEA (0.4mmol) and DMF (20mL) were added to a 100mL round-bottom flask in sequence, and the reaction system was stirred at 90°C for 2.0h. TLC monitoring showed that there was no residual raw material, and the heating was stopped. The reaction solution was cooled to room temperature, and water and ethyl acetate were added to the reaction solution. The organic phase was extracted, and the organic phase was concentrated under reduced pressure. The crude product was separated by column chromatography to obtain 5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 75.0%. 1 H NMR (600 MHz, CDCl 3 )δ11.535(s,1H),9.122(s,1H),7.276-7.290(m,1H),7.081-7.169(m,4H),6.9 37-6.941(m,1H),4.483(q,J=7.2Hz,2H),3.959(s,3H),1.494(t,J=7.2Hz,3H); 13 C NMR (150 MHz, CDCl 3 )δ168.99,163.05,156.11,153.64,152.18,151.32,149.00,134.20,125.58,125.24,121.79,121.61,108.68,107.97,105.52,101.94,61.27,55.91,14.46; HR-MS (ESI) theoretical value C 19 H 14 N 2 O 4 [M+H] + :337.1074, measured value 337.1076.

[0639] Intermediate Preparation Example 49: Preparation of ethyl 5-methoxy-12H-benzo[2,3][1,4]thiazino[5,6,7-de]quinoline-1-carboxylate (M-49)

[0640]

[0641] The synthesis method was the same as that of Preparation Example 48 to obtain 5-methoxy-12H-benzo[2,3][1,4]thiazino[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 64.0%. 1 H NMR (600 MHz, DMSO-d 6)δ11.565(s,1H),9.051(s,1H),7.611(d,J=7.2Hz,1H),7.399-7.422(m,1H),7.338(d,J=3.0Hz,2H),7. 279(d,J=3.0Hz,1H),7.197-7.242(m,2H),4.454(q,J=7.2Hz,2H),3.909(s,3H),1.417(t,J=7.2Hz,3H); 13 C NMR (150 MHz, CDCl 3 )δ169.10,161.96,154.33,154.13,151.90,145.07,134.17,131.88,129.59,128.77,125.74,123.49,121.56,116.46,108.45,104.12,61.50,55.87,14.45; HR-MS (ESI) theoretical value C 19 H 17 N 2 O 3 S[M+H] + :353.1283, measured value 353.1284.

[0642] Intermediate Preparation Example 50: Preparation of ethyl 5-methoxy-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate (M-50)

[0643]

[0644] The synthesis method was the same as that of Preparation Example 48 to obtain 5-methoxy-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 79.0%. 1 H NMR (600 MHz, CDCl 3 )δ11.641(s,1H),9.109(s,1H),6.899-6.963(m,4H),6.772-6.785(m,1H),6.406-6.4 09(m,1H),6.085(s,1H),4.431(q,J=7.2Hz,2H),3.878(s,3H),1.452(t,J=7.2Hz,3H); 13 C NMR (150 MHz, CDCl 3)δ169.20,162.68,153.63,152.28,151.58,144.79,135.46,131.39,124.64,122.84,121.62,119.15,105.33,104.62,102.77,101.68,61.20,55.61,14.41; HR-MS (ESI) theoretical value C 19 H 18 N 3 O 3 [M+H] + :336.0512, measured value 336.0513.

[0645] Intermediate Preparation Example 51: Preparation of ethyl 9-fluoro-5-methoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylate (M-51)

[0646]

[0647] The synthesis method was the same as that of Preparation Example 48 to obtain 9-fluoro-5-methoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 56.3%. 1 H NMR (600 MHz, CDCl 3 )δ11.481(s,1H),9.102(s,1H),7.169-7.173(m,1H),7.002-7.035(m,2H),6.902-6.906( m,1H),6.839-6.871(m,1H),4.458(q,J=6.6Hz,2H),3.942(s,3H),1.468(t,J=6.6Hz,3H); 13 C NMR (150 MHz, CDCl 3 )δ168.99,163.07,160.43,158.80,155.60,152.13,151.12,149.48(d,J=10.5Hz),130.61,122.18(d,J=10.5Hz),112.53(d,J=22.5Hz),109.34(d,J=24Hz),108.85,107.73,105.75,101.97,61.38,56.00,14.43; HR-MS(ESI)theoretical value C 19 H 16 FN 2 O 4 [M+H] + :355.1337, measured value 355.1338.

[0648] Intermediate Preparation Example 52: Preparation of ethyl 5,10-dimethoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylate (M-52)

[0649]

[0650] The synthesis method was the same as that of Preparation Example 48 to obtain 5,10-dimethoxy-12H-benzo[2,3][1,4]oxaazepine[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 59.4%. 1 H NMR (600 MHz, DMSO-d 6 )δ10.955(s,1H),9.766(s,1H),8.894(s,1H),8.582(s,1H),8.321(s,1H),7.165(m,1H),6.1 94-6.199(m,1H),4.435(q,J=7.2Hz,2H),3.939(s,3H),3.737(s,3H),1.408(t,J=7.2Hz,3H); 13 C NMR (150 MHz, CDCl 3 )δ168.98,163.32,157.24,156.53,153.29,151.88,151.63,143.03,134.70,122.35,111.01,108.57,108.09,106.30,105.11,101.93,61.38,55.96,14.46; HR-MS (ESI) theoretical value C 20 H 18 N 2 O 5 [M+H] + :367.1534, measured value 367.1535.

[0651] Intermediate Preparation Example 53: Preparation of ethyl 5-methoxy-12H-pyrido[4',3':2,3][1,4]oxaaza[5,6,7-de]quinoline-1-carboxylate (M-53)

[0652]

[0653] The synthesis method was the same as that of Preparation Example 48 to obtain 5-methoxy-12H-pyrido[4',3':2,3][1,4]oxaaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 81.2%. 1 H NMR (600 MHz, DMSO-d 6)δ11.456(s,1H),9.058(s,1H),8.493(s,1H),8.350(d,J=5.4Hz,1H),7.442(d,J=5.4Hz,1H),7.265( d,J=2.4Hz,1H),7.161(d,J=2.4Hz,1H),4.464(q,J=7.2Hz,2H),3.962(s,3H),1.427(t,J=7.2Hz,3H); 13 C NMR (150 MHz, CDCl 3 )δ175.53,158.63,163.25,153.84,152.10,151.08,150.34,145.88,142.68,130.14,116.44,109.87,106.14,105.17,102.37,61.81,56.12,14.34; HR-MS (ESI) theoretical value C 18 H 16 N 3 O 4 [M+H] + :338.1382, measured value 338.1382.

[0654] Intermediate Preparation Example 54: Preparation of ethyl 5-methoxy-12H-pyrido[3',4':2,3][1,4]oxaaza[5,6,7-de]quinoline-1-carboxylate (M-54)

[0655]

[0656] The synthesis method was the same as that of Preparation Example 48 to obtain 5-methoxy-12H-pyrido[3',4':2,3][1,4]oxaaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 89.4%. 1 H NMR (600 MHz, CDCl 3 )δ11.831(s,1H),9.145(s,1H),8.508(s,1H),8.273(s,1H),7.182(m,1H),6.9 48-6.988(m,2H),4.471(q,J=7.2Hz,2H),3.946(s,3H),1.473(t,J=7.2Hz,3H); 13 C NMR (150 MHz, CDCl 3)δ168.99,163.10,154.94,153.65,151.98,149.68,146.62,144.38,143.81,140.10,115.09,109.56,107.02,106.06,102.75,61.74,56.02,14.40; HR-MS (ESI) theoretical value C 18 H 16 N 3 O 4 [M+H] + :338.1438, measured value 338.1440.

[0657] Intermediate Preparation Example 55: Preparation of ethyl 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate (M-55)

[0658]

[0659] The synthesis method was the same as that in Preparation Example 41 to obtain 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 95.7%. 1 H NMR (600 MHz, CDCl 3 )δ10.086(s,1H),8.911(s,1H),6.860-6.880(m,1H),6.215-6.236(m,1H),4.485(s,1H),4.422(q,J=7.2Hz,2H),3.228- 3.267(m,1H),3.099-3.139(m,1H),2.189-2.212(m,1H),2.036-2.057(m,1H),1.807-1.814(m,2H),1.296-1.528(m,7H); 13 C NMR (150 MHz, CDCl 3 )δ169.38,165.53,163.38,156.22,154.47(d,J=15Hz),152.68,149.54(d,J=13.5Hz),105.52,103.58(d,J=21Hz),99.35,99.20,99.03,60.50(d,J=15Hz),59.35,32.89,32.39,23.79(d,J=6Hz),14.47; HR-MS(ESI)theoretical value C 18 H 20 FN3 O 2 [M+H] + :330.1237, measured value 330.1238.

[0660] Intermediate Preparation Example 56: Preparation of ethyl 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate (M-56)

[0661]

[0662] The synthesis method was the same as that in Preparation Example 41 to obtain 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 96.4%. 1 H NMR (600 MHz, CDCl 3 )δ10.637(s,1H),8.923(s,1H),6.909-6.928(m,1H),6.300-6.321(m,1H),5.383(s,1H), 4.349(q,J=6.6Hz,2H),3.708-3.722(m,2H),3.584-3.596(m,2H),1.401(t,J=6.6Hz,3H); 13 C NMR (150 MHz, CDCl 3 )δ169.81,169.25,165.82,164.05,157.74,151.56,104.78,102.76,99.41(d,J=21Hz),99.17,60.95,47.47,46.83,14.47; HR-MS(ESI)theoretical value C 14 H 15 FN 3 O 2 [M+H] + :276.0974, measured value 276.0973.

[0663] Intermediate Preparation Example 57: Preparation of ethyl 5-methoxy-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate (M-57)

[0664]

[0665] The synthesis method was the same as that of Preparation Example 48 to obtain 5-methoxy-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylic acid ethyl ester in a yield of 95.4%. 1 H NMR (600 MHz, CDCl 3 )δ10.333(s,1H),8.825(s,1H),6.827-6.830(m,1H),6.209-6.212(m,1H),4.782(s,1H),4.321(q,J=7.2Hz,2H),3.816(s,3H), 3.294-3.335(m,1H),3.287-3.127(m,1H),2.211-2.234(m,1H),2.139-2.160(m,1H),1.821-1.836(m,2H),1.315-1.528(m,7H); 13 C NMR (150 MHz, CDCl 3 )δ168.69,163.32,156.43,149.30,149.02,102.72,100.86,98.63,97.86,61.10,61.05,58.72,55.68,32.70,32.40,29.83,23.82,23.73,14.46; HR-MS (ESI) theoretical value C 19 H 24 N 3 O 3 [M+H] + :342.2013, measured value 342.2011.

[0666] Intermediate Preparation Example 58: Preparation of ethyl 9-methoxy-4,5,6,7-tetrahydro-[1,4]diaza[5,6,7-de]quinoline-3-carboxylate (M-58)

[0667]

[0668] The synthesis method was the same as that of Preparation Example 48 to obtain 9-methoxy-4,5,6,7-tetrahydro-[1,4]diaza[5,6,7-de]quinoline-3-carboxylic acid ethyl ester in a yield of 97.1%. 1 H NMR (600 MHz, DMSO-d 6)δ10.219(s,1H),8.664(s,1H),7.182(s,1H),6.487-6.492(m,1H),6.261-6.265(m,1H),4.461( q,J=7.2Hz,2H),3.771(s,3H),3.610-3.627(m,2H),3.374-3.390(m,2H),1.314(t,J=7.2Hz,3H); 13 CNMR (150MHz, DMSO-d 6 )δ168.38,161.84,156.80,154.00,151.06,150.82,101.75,99.14,98.06,97.11,59.93,54.97,47.07,45.79,14.31; HR-MS (ESI) theoretical value C 15 H 18 N 3 O 3 [M+H] + :288.0876, measured value 276.0878.

[0669] [Example]

[0670] Example 1: (S)-6-Fluoro-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-1)

[0671]

[0672] Step 1: Synthesis of (S)-6-fluoro-7-(6-fluoropyridin-3-yl)-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one

[0673] In a 100 mL reaction bottle, 1,4-dioxane (15 mL), (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (0.62 g, 1.76 mmol), 6-fluoropyridine-3-boric acid (0.315 g, 2.11 mmol), potassium carbonate (0.607 g, 4.4 mmol), water (1.5 mL) and tetrakis(triphenylphosphine)palladium (0.203 g, 0.18 mmol) were added in sequence. The temperature was raised to 90°C under nitrogen protection and the reaction was continued for 2.5 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM: MeOH = 60: 1) to obtain (S)-6-fluoro-7-(6-fluoropyridin-3-yl)-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one (0.43 g, yield 66.3%). ESI-MS (m / z): 369.11 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.541(d,3H),3.632(s,3H),4.525-4.660(m,2H),4.707-4.739(m,1H), 7.213-7.231(m,1H),7.565(d,1H),8.105(t,1H),8.343(s,1H),8.837(s,1H).

[0674] Step 2: Synthesis of (S)-6-fluoro-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0675] In a 100 mL reaction bottle, THF (4 mL) and 1-piperidinylpropanol (115 mg, 0.8 mmol) were added in sequence, and the temperature was lowered to 0°C before adding NaH (56 mg, 1.4 mmol). The mixture was reacted at this temperature for 0.5 h. Then, (S)-6-fluoro-7-(6-fluoropyridin-3-yl)-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (147 mg, 0.4 mmol) was added and the mixture was reacted at room temperature overnight. The reaction was completed by TLC monitoring, and the reaction solution was quenched with water, then concentrated to dryness, and the residue was purified by column chromatography (DCM: MeOH = 20: 1 to 15: 1) to obtain (S)-6-fluoro-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (63 mg, yield 32%). ESI-MS (m / z): 492.23 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.495-1.533(m,5H),1.620-1.657(m,4H),2.027-2.053(m,2H),2.507-2.577(m,6H),3.610(s,3H),4.373(t,J=6.0Hz,2H),4.467- 4.612(m,2H),4.630-4.701(m,1H),6.899(d,J=8.4Hz,1H),7.480(d,J=10.8Hz,1H),7.794(d,J=8.4Hz,1H),8.209(s,1H),8.767(s,1H).

[0676] Example 2: (S)-7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-2)

[0677]

[0678] The synthesis method was the same as in Example 1, except that 3-dimethylaminopropanol was used instead of 1-piperidinylpropanol to obtain (S)-7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (30 mg, yield 32.0%). ESI-MS (m / z): 452.20 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.526(d,J=7.2Hz,3H),2.040-2.066(m,2H),2.390(s,6H),2.662(t,J=7.8Hz,2H),3.610(s,3H),4.398(t,J=6.0Hz,2H),4.467-4 .632(m,2H),4.689-4.702(m,1H),6.912(d,J=8.4Hz,1H),7.476(d,J=11.4Hz,1H),7.800(d,J=9.0Hz,1H),8.215(s,1H),8.765(s,1H).

[0679] Example 3: (R)-7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-3)

[0680]

[0681] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (R)-7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (25 mg, yield 27.1%). ESI-MS (m / z): 452.20 [M+H] + ; 1 H NMR (600MHz, CD 3OD)δ:1.536(d,J=7.2Hz,3H),2.001-2.048(m,2H),2.310(s,6H),2.565(t,J=7.8Hz,2H),3.620(s,3H),4.388(t,J=6.0Hz,2H),4.484- 4.641(m,2H),4.698-4.712(m,1H),6.915(d,J=9.0Hz,1H),7.509(d,J=11.4Hz,1H),7.803-7.818(m,1H),8.226(s,1H),8.792(s,1H).

[0682] Example 4: (R)-6-Fluoro-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-4)

[0683]

[0684] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain (R)-6-fluoro-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (63 mg, yield 32%). ESI-MS (m / z): 492.20 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 )δ:1.577-1.588(m,4H),1.590-2.100(m,6H),2.211-3.199(m,7H),3.629(s,3H),4.366-4.388(m,1H),4.465(t,J=6.0Hz,2H),4.582- 4.608(m,1H),4.735-4.749(m,1H),6.848(d,J=8.4Hz,1H),7.607(d,J=10.8Hz,1H),7.732-7.746(m,1H),8.291(s,1H),8.691(s,1H).

[0685] Example 5: 7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-9-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-5)

[0686]

[0687] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-9-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (15 mg, yield 13.0%). ESI-MS (m / z): 532.21 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.230-1.236(m,2H),1.937(t,J=6.6Hz,2H),2.349(s,6H),2.610-2.618(m,2H),3.533(s,3H),4.220-4.242(m,1H),4.315(t, J=6.0Hz,2H),6.864(d,J=8.4Hz,1H),6.871-7.180(m,3H),7.501-7.522(m,2H),7.800-7.814(m,1H),8.234(s,1H),8.788(s,1H).

[0688] Example 6: 6-Fluoro-2,10,10-trimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-6)

[0689]

[0690] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain 6-fluoro-2,10,10-trimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (70 mg, yield 33.2%). ESI-MS (m / z): 506.25 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:1.383(s,2H),1.482-1.518(m,4H),1.639(s,6H),1.883-1.928(m,2H),2.348-2.405(m,4H),2.498-2.510(m,2H),3.503(s,3H),4 .335(t,J=6.6Hz,2H),4.441(s,2H),6.937-6.952(m,1H),7.560(d,J=10.8Hz,1H),7.824-7.844(m,1H),8.276(s,1H),8.899(s,1H).

[0691] Example 7: 6-Fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-7)

[0692]

[0693] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 6-fluoro-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (63 mg, yield 32.0%). ESI-MS (m / z): 555.2 [M+H] + ; 1 H NMR(600MHz,DMSO)δ:1.439(brs,2H),1.382-1.579(m,4H),1.970-1.997(m,2H),2.487-2.500(m,2H),2.520-2. 750(m,4H),3.581(s,3H),4.228-4.239(m,1H),4.332(d,J=6.6Hz,2H),4.887(d,J=13.8Hz,1H),5.858(d,J=9.6 Hz,1H),6.855(d,J=9.0Hz,1H),7.177(d,J=8.4Hz,1H),7.370-7.391(m,1H),7.663(d,J=10.8Hz,1H),7.733(d, J=7.2Hz,1H),7.711-7.752(m,1H),7.818(d,J=8.4Hz,1H),8.242(s,1H),8.600(d,J=4.2Hz,1H),8.963(s,1H).

[0694] Example 8: (R)-6-Fluoro-10-isobutyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-8)

[0695]

[0696] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (R)-6-fluoro-10-isobutyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (53 mg, yield 45.3%). ESI-MS (m / z): 534.28 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:0.980(s,3H),1.239(s,3H),1.395(s,2H),1.515(s,4H),1.567-1.616(m,1H),1.69 5-1.762(m,2H),1.921(s,2H),2.287-2.492(m,6H),3.550(s,3H),4.344(t,J=6.6Hz,2 H),4.516(d,J=13.2Hz,1H),4.595-4.701(m,1H),4.722(d,J=3.0Hz,1H),6.948(d,J=8 .4Hz,1H),7.594(d,J=10.8Hz,1H),7.837(d,J=8.4Hz,1H),8.278(s,1H),8.913(s,1H).

[0697] Example 9: (S)-6-Fluoro-10-isobutyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazinapho[2,1,8-cde]azulen-1(2H)-one (A-9)

[0698]

[0699] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain (S)-6-fluoro-10-isobutyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one (60 mg, yield 46.0%). ESI-MS (m / z): 534.28 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:0.920-0.930(d,J=6.0Hz,3H),0.970-0.980(d,J=6.0Hz,3H),1.400-1.402(m,2H),1.518-1.600(m,6H), 1.706-1.741(m,1H),1.918-1.924(m,2H),2.345-2.392(m,6H),3.550(s,3H),4.334-4.356(t,J=6.6Hz,J=6 .6Hz, 2H), 4.505-4.527 (d, J=13.2Hz, 1H), 4.606-4.615 (d, J=5.4Hz, 1H), 4.697-4.724 (m, 1H), 6.941-6.956 (d, J=9.0Hz, 1H), 7.586-7.604 (d, J=10.8Hz, 1H), 7.830-7.845 (d, J=9.0Hz, 1H), 8.279 (s, 1H), 8.914 (s, 1H).

[0700] Example 10: 6-Fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-10)

[0701]

[0702] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (90 mg, yield 45.2%). ESI-MS (m / z): 494.12 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:1.424-1.425(m,3H),1.560-1.562(m,5H),1.910-1.980(m,2H),2.420-2.421(m,2H),2.631-2.632(m,2H),3.350-3.353(m,2H), 3.565(s,3H),4.297-4.366(m,4H),6.952-6.966(d,J=8.4Hz,1H),7.719-7.774(m,2H),8.126-8.130(d,J=8.4Hz,1H),8.996(s,1H).

[0703] Example 11: 6-Fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1-cyclopropane]-1-one (A-11)

[0704]

[0705] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulene-10,1-cyclopropane]-1-one (50 mg, yield 21.2%). ESI-MS (m / z): 504.23 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.062-1.064(m,2H),1.425-1.557(m,2H),1.557-1.574(m,4H),1.915-2.207(m,4H),2.508-2.587(m,5H),3.90 -3.475(m,4H),4.33-4.354(t,J=6.6Hz,2H),4.464(s,2H),6.939(d,J=8.4Hz,1H),7.594(d,J=10.8Hz,1H),7.812(m 1H),8.254(s,1H),8.896(s,1H).

[0706] Example 12: 9-(Ethoxymethyl)-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-12)

[0707]

[0708] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain (9-(ethoxymethyl)-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one (86 mg, yield 51.0%). ESI-MS (m / z): 536.26 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.110-1.134(m,3H),1.594(s,2H),1.744-1.762(m,4H),2.145-1.17 2(m,2H),2.870-2.918(m,6H),3.423-3.489(m,2H),3.612-3.720(m,5H),3 .987-4.026(m,1H),4.419-4.439(m,2H),4.545(d,J=13.8Hz,1H),4.657(d ,J=9.6Hz,1H),6.921(d,J=8.4Hz,1H),7.513(d,J=10.8Hz,1H),7.884(dd,J 1＝ 1.2Hz,J 2 =8.4Hz,1H),8.285(s,1H),8.788(s,1H).

[0709] Example 13: (S)-10-Benzyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazinapho[2,1,8-cde]azulen-1(2H)-one (A-13)

[0710]

[0711] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (S)-10-benzyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one (30 mg, yield 20.2%). ESI-MS (m / z): 568.26 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:1.463-1.624(m,6H),2.055-2.103(m,2H),2.695-2.713(m,4H),3.104-3.190(m,4H),3.569(s,3H),4.297-4.440(m,4H),4.692-4. 714(m,1H),6.985(d,J=8.4Hz,1H),7.246-7.349(m,5H),7.626(d,J=11.4Hz,1H),7.928(d,J=8.4Hz,1H),8.343(s,1H),8.952(s,1H).

[0712] Example 14: (R)-10-Benzyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-14)

[0713]

[0714] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain (R)-10-benzyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (53 mg, yield 41.5%). ESI-MS (m / z): 568.26 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.463-1.624(m,6H),2.055-2.103(m,2H),2.695-2.713(m,4H),3.10 4-3.190(m,4H),3.569(s,3H),4.297-4.440(m,4H),4.692-4.714(m,1H) ,6.976-6.990(d,J=8.4Hz,1H),7.246-7.349(m,5H),7.616-7.635(d,J= 11.4Hz, 1H), 7.921-7.935 (d, J = 8.4Hz, 1H), 8.343 (s, 1H), 8.952 (s, 1H).

[0715] Example 15: 7-(6-(3-dimethylamino-propoxy)-pyridin-3-yl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-15)

[0716]

[0717] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 7-(6-(3-dimethylamino-propoxy)-pyridin-3-yl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (15 mg, yield 48.2%). ESI-MS (m / z): 438.42 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:2.076-2.102(m,2H),2.467(s,6H),2.747-2.773(m,2H),3.624(s,3H),4.325-4.330(m,2H),4.407-4.427(m,2H),4 .608-4.620(m,2H),6.939(d,J=8.4Hz,1H),7.534(d,J=16.8Hz,1H),7.832(d,J=14.4Hz,1H),8.236(s,1H),8.807(s,1H).

[0718] Example 16: (S)-6-Fluoro-10-isopropyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-16)

[0719]

[0720] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (S)-6-fluoro-10-isopropyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (50 mg, yield 24%). ESI-MS (m / z): 520.26 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:0.933(d,J=7.2Hz,3H),1.013(d,J=6.6Hz,3H),1.400-1.537(m,6H),1.922 -1.954(m,2H),2.221-2.258(m,1H),2.433-2.514(m,6H),3.558(s,3H),4.282 -4.351(m,3H),4.445-4.468(m,1H),4.828-4.856(m,1H),6.935(d,J=8.4Hz,1 H),7.566(d,J=10.8Hz,1H),7.828-7.813(m,1H),8.260(s,1H),8.909(s,1H).

[0721] Example 17: (R)-6-Fluoro-10-isopropyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-17)

[0722]

[0723] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain (R)-6-fluoro-10-isopropyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (45 mg, yield 24%). ESI-MS (m / z): 520.26 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:0.947(d,J=6.6Hz,3H),1.022(d,J=6.6Hz,3H),1.415-1.544(m,6H),1.933 -1.963(m,2H),2.240-2.261(m,1H),2.449-2.529(m,6H),3.560(s,3H),4.296 -4.365(m,3H),4.459-4.482(m,1H),4.839-4.867(m,1H),6.949(d,J=8.4Hz,1 H),7.579(d,J=10.8Hz,1H),7.840-7.825(m,1H),8.271(s,1H),8.920(s,1H).

[0724] Example 18: 6-Fluoro-9-isopropyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-18)

[0725]

[0726] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 6-fluoro-9-isopropyl-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (58 mg, yield 44.3%). ESI-MS (m / z): 519.26 [M+H] + ; 1 H NMR(600MHz,DMSO)δ:0.635(d,J=7.2Hz,3H),0.798(d,J=6.6Hz,3H),1.305-1.892 (m,6H),1.909-1.962(m,1H),2.012-2.198(m,2H),2.753-2.965(m,2H),3.137-3.3 26(m,4H),3.547(s,3H),3.994-4.032(m,1H),4.290-4.378(m,4H),6.961(d,J=8.4 Hz, 1H), 7.590 (d, J = 10.8Hz, 1H), 7.852-7.840 (m, 1H), 8.267 (s, 1H), 8.921 (s, 1H).

[0727] Example 19: (S)-9-((dimethylamino)methyl)-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-19)

[0728]

[0729] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (S)-9-((dimethylamino)methyl)-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (100 mg, yield 55.0%). ESI-MS (m / z): 535.28 [M+H] +; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.600(s,2H),1.746-1.763(m,4H),2.149-2.193(m,8H),2.650-2.6 71(m,2H),2.813-2.864(m,6H),3.648(s,3H),4.016-4.055(q,1H),4.44 8(t,J=6.0Hz,2H),4.660(d,J=13.2Hz,2H),6.960(d,J=9.0Hz,1H),7.55 0(d,J=10.8Hz,1H),7.797(d,J=8.4Hz,1H),8.290(s,1H),8.833(s,1H).

[0730] Example 20: (S)-6-Fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9-(piperidin-1-ylmethyl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-20)

[0731]

[0732] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (S)-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9-(piperidin-1-ylmethyl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (150 mg, yield 29.6%). ESI-MS (m / z): 575.31 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.396(s,2H),1.478-1.515(m,4H),1.550(s,2H),1.678-1.716(m,4H),2. 092-2.119(m,2H),2.329(s,4H),2.607-2.700(m,8H),3.627(s,3H),3.973-4 .013(m,1H),4.415-4.587(m,2H),4.611-4.915(m,2H),6.942(d,J=9.0Hz,1H ),7.521(d,J=10.8Hz,1H),7.902-7.921(m,1H),8.318(s,1H),8.785(s,1H).

[0733] Example 21: 4-Fluoro-12-methyl-5-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadienyl[GH]pyroxene-11(12H)-one (A-21)

[0734]

[0735] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 4-fluoro-12-methyl-5-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadienyl[gh]pyroxene-11(12H)-one (200 mg, yield 38.5%). ESI-MS (m / z): 532.26 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.635-1.693(m,4H),1.788-1.830(m,7H),2.120(d,J=12.0Hz,1H),2. 179-2.225(m,2H),2.954-2.999(m,7H),3.593(s,3H),3.691(d,J=13.2Hz ,1H),4.305-4.339(m,2H),4.456-4.476(m,2H),6.961(d,J=8.4Hz,1H),7 .517(d,J=10.8Hz,1H),7.852-7.869(m,1H),8.271(s,1H),8.794(s,1H).

[0736] Example 22: (R)-10-ethyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-22)

[0737]

[0738] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (R)-10-ethyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (150 mg, yield 14.3%). ESI-MS (m / z): 506.25 [M+H] + ;1 H NMR (600 MHz, DMSO-d 6 )δ:1.099-1.111(m,3H),1.560(s,2H),1.693-1.730(m,4H),1.942-1.979(m ,2H),2.091-2.138(m,2H),2.682-2.749(m,6H),3.640(s,3H),4.410-4.460 (m,3H),4.510-4.525(m,1H),4.815-4.842(m,1H),6.938(d,J=8.4Hz,1H),7 .505(d,J=10.8Hz,1H),7.825(d,J=8.4Hz,1H),8.238(s,1H),8.802(s,1H).

[0739] Example 23: (S)-10-ethyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-23)

[0740]

[0741] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (S)-10-ethyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (180 mg, yield 42.6%). ESI-MS (m / z): 506.25 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.099-1.111(m,3H),1.533(s,2H),1.663-1.701(m,4H),1.932-1.969(m,2H) ,2.065-2.112(m,2H),2.643-2.712(m,6H),3.625(s,3H),4.390-4.441(m,2H),4. 442(d,J=13.2Hz,1H),4.484-4.512(m,1H),4.798-4.825(m,1H),6.922(d,J=8.4H z, 1H), 7.512 (d, J = 10.8Hz, 1H), 7.807-7.824 (m, 1H), 8.229 (s, 1H), 8.802 (s, 1H).

[0742] Example 24: 6-Fluoro-2,9-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-24)

[0743]

[0744] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain 6-fluoro-2,9-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (68 mg, yield 33.2%). ESI-MS (m / z): 491.23 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.448(d,J=5.4Hz,3H),1.537(m,2H),1.663-1.701(m,4H),2.067-2.114(m,2H),2.579-2.654(m,6H),3.620(s,3H),3.932-3.9 71(m,1H),4.405-4.432(m,3H),4.677-4.702(m,1H),6.942(d,J=8.4Hz,1H),7.504(d,J=10.8Hz,1H),7.831-7.849(m,1H),8.245(s,1 H),8.777(s,1H),1.448(d,3H),1.537(m,2H),1.663-1.701(m,4H),2.067-2.114(m,2H),2.579-2.654(m,6H),3.620(s,3H),3.932-3 .971(m,1H),4.405-4.432(m,3H),4.677-4.702(m,1H),6.942(d,1H),7.504(d,1H),7.831-7.849(m,1H),8.245(s,1H),8.777(s,1H).

[0745] Example 25: 6-Fluoro-9-(2-fluoropyridin-4-yl)-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-25)

[0746]

[0747] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 6-fluoro-9-(2-fluoropyridin-4-yl)-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (85 mg, yield 26.8%). ESI-MS (m / z): 573.23 [M+H] + ; 1 H NMR(600MHz,MeOD)δ1.530-1.687(m,6H),2.025-2.089(m,2H),2.649-2.675(m,6H) ,3.645(s,3H),4.187-4.227(m,1H),4.365(t,J=6.6Hz,2H),4.646-4.669(m,1H),5 .808-5.824(m,1H),6.781(d,J=7.8Hz,1H),6.974(s,1H),7.305(d,J=4.8Hz,1H),7 .597(d,J=10.8Hz,1H),7.751(d,J=8.4Hz,1H),8.161-8.199(m,2H),8.860(s,1H).

[0748] Example 26: 6-Fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-26)

[0749]

[0750] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (25 mg, yield 19%). ESI-MS (m / z): 478.22 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:1.356-1.450(m,2H),1.514-1.532(m,4H),1.916-1.939(m,2H),2.4 06-2.461(m,6H),3.540(s,3H),4.204-4.212(m,2H),4.331-4.353(t,J= 6.6Hz,2H),4.607-4.619(t,J=3.6Hz,2H),6.943(d,J=8.4Hz,1H),7.58 5(d,J=10.8Hz,1H),7.821(d,J=8.4Hz,1H),8.257(s,1H),8.903(s,1H).

[0751] Example 27: 10-Cyclopropyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-27)

[0752]

[0753] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 10-cyclopropyl-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (40 mg, yield 39.0%). ESI-MS (m / z): 518.25 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ0.495-0.535(m,3H),0.863-0.901(m,1H),1.281-1.358(m,1H),1.388-1.490(m,2H),1.501 -1.592(m,4H),1.901-1.992(m,2H),2.385-2.502(m,6H),3.550(s,3H),3.924-3.943(m,1H), 4.336-4.358(t,J=6.6Hz,2H),4.535-4.557(d,J=13.2Hz,1H),4.698-4.725(m,1H),6.945-6. 960(m,1H),7.586-7.605(d,J=11.4Hz,1H),7.838-7.854(m,1H),8.285(s,1H),8.913(s,1H).

[0754] Example 28: 6-Fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclobutane]-1-one (A-28)

[0755]

[0756] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclobutane]-1-one (70 mg, yield 44.2%). ESI-MS (m / z): 518.25 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.410-1.541(m,8H),1.910-1.964(m,6H),2.466-2.508(m,6H),3.524(s,3H),4.344-4.365(t,J=6.6Hz,2H),4.647(m,2H ), 6.953-6.967 (d, J = 8.4Hz, 1H), 7.577-7.595 (d, J = 10.8Hz, 1H), 7.839-7.853 (d, J = 8.4Hz, 1H), 8.286 (s, 1H), 8.900 (s, 1H).

[0757] Example 29: 7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclopropane]-1-one (A-29)

[0758]

[0759] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulene-10,1'-cyclopropane]-1-one (47 mg, yield 39.1%). ESI-MS (m / z): 464.20 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:1.058-1.061(m,2H),1.962-2.194(m,4H),2.383(s,6H),2.660-2.663(m,2H),3.478(s,3H),4.338-4.359(t,J=6.6Hz,2H),4.46 8(m,2H),6.927-6.941(d,J=8.4Hz,1H),7.599-7.618(d,J=11.4Hz,1H),7.817-7.832(d,J=9.0Hz,1H),8.256(s,1H),8.916(s,1H).

[0760] Example 30: 6-methoxy-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-30)

[0761]

[0762] In a 100 mL reaction bottle, 7-bromo-6-methoxy-2-methyl-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (200 mg, 0.47 mmol), cesium carbonate (382 mg, 1.17 mmol), (1-methyl-1H-pyrazol-4-yl)boric acid (90 mg, 0.71 mmol), tetrakis(triphenylphosphine)palladium (55 mg, 0.05 mmol) and 20 mL of dioxane, N-[2,1,8-cde]azulen-1(2H)-one were added in sequence. 2 The reaction mixture was heated to 120°C for 4 h. The reaction mixture was cooled to room temperature, concentrated to dryness, and purified by column chromatography (DCM:MeOH=40:1-30:1) to obtain 6-methoxy-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-10-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (80 mg, yield 40.1%). ESI-MS (m / z): 429.16 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:3.525(s,3H),3.943-3.967(m,6H),4.867-4.916(m,2H),5.206(m,1H),7.039(s,1H),7.233-7.255(m,1H), 7.533(d,J=8.4Hz,1H),7.755-7.783(m,1H),8.234(s,1H),8.274(d,J=3.6Hz,1H),8.372(s,1H),8.669(s,1H).

[0763] Example 31: (S)-6-methoxy-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-31)

[0764]

[0765] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (S)-6-methoxy-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (68 mg, yield 33.2%). ESI-MS (m / z): 504.25 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.543(d,J=6.6Hz,3H),1.573-1.626(m,2H),1.781(m,4H),2.170- 2.196(m,2H),2.945(brs,6H),3.637(s,3H),3.925(s,3H),4.436(t,J=6. 0Hz,2H),4.465-4.571(m,2H),4.685-4.699(m,1H),6.916(d,J=9.0Hz,1H ),7.308(s,1H),7.749-7.767(m,1H),8.152-8.156(m,1H),8.743(s,1H).

[0766] Example 32: (R)-6-methoxy-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-32)

[0767]

[0768] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain (R)-6-methoxy-2,10-dimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (68 mg, yield 33.2%). ESI-MS (m / z): 504.25 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.509(d,J=6.6Hz,3H),1.597(brs,2H),1.739-1.776(m,4H),2.134 -2.181(m,2H),2.881-2.938(m,6H),3.604(s,3H),3.893(s,3H),4.407(t, J=6.0Hz,2H),4.426-4.538(m,2H),4.651-4.665(m,1H),6.878-6.893(m,1 H),7.268(s,1H),7.717-7.735(m,1H),8.119-8.123(m,1H),8.703(s,1H).

[0769] Example 33: 4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,10b,12-triazacyclopentadien[gh]pyroxene-11(12H)-one (A-33)

[0770]

[0771] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain 4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,10b,12-triazacyclopentadienyl[gh]pyroxene-11(12H)-one (120 mg, yield 31.5%). ESI-MS (m / z): 400.41 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:3.585(s,3H),3.970-3.998(m,6H),7.192-7.208(m,1H),7.271-7.299(m,1H),7 .316-7.344(m,2H),8.005(s,1H),8.251(s,1H),8.414-8.431(m,1H),8.866(s,1H).

[0772] Example 34: (S)-9-(dimethylamino)methyl)-6-fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-34)

[0773]

[0774] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain (S)-9-(dimethylamino)methyl)-6-fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (60 mg, yield 50%). ESI-MS (m / z): 397.17 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:2.235(s,6H),2.729-2.801(m,2H),3.533(s,3H),3.935(s,4H),4.523-4.546(m,1H),4.7 79-4.787(m,1H),7.555(d,J=13.2Hz,1H),7.996(d,J=2.4Hz,1H),8.488(s,1H),8.851(s,1H).

[0775] Example 35: 6-Fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-35)

[0776]

[0777] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain 6-fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (0.15 g, yield 50%). ESI-MS (m / z): 356.23 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:3.362(t,J=4.8Hz,2H),3.561(s,3H),3.954(s,3H),4.347(t,J=4.8Hz ,2H),7.589(s,1H),7.708(d,J=10.2Hz,1H),7.948(s,1H),8.952(s,1H).

[0778] Example 36: 6-Fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one 8-oxide (A-36)

[0779]

[0780] 6-Fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (0.05 g, 0.14 mmol) was dissolved in 20 mL of dichloromethane, and m-chloroperbenzoic acid (0.03 g, 0.17 mmol) was added under ice bath, and the system was stirred under ice bath for 1 h. A small amount of raw material remained after TLC monitoring. The reaction solution was washed with saturated sodium thiosulfate aqueous solution (10 mL × 2), saturated sodium chloride (10 mL × 2), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The final product was separated and purified by column chromatography (DCM: MeOH = 50: 1-25: 1) to obtain 6-fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one 8-oxide (0.04 g, yield 77%). ESI-MS (m / z): 372.23 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:3.651(m,3H),3.842-3.793(m,1H),3.994(s,3H),4.053-4.022(m,1H),4.541-4.530(m,1 H), 4.567-4.552 (m, 1H), 7.751 (s, 1H), 8.104 (d, J = 10.8Hz, 1H), 8.153 (s, 1H), 9.048 (s, 1H).

[0781] Example 37: 6-Fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one 8,8-dioxide (A-37)

[0782]

[0783] 6-Fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.05 g, 0.14 mmol) was dissolved in 20 mL of dichloromethane, and m-chloroperbenzoic acid (0.05 g, 0.28 mmol) was added under ice bath, and the system was stirred at room temperature for 24 h. No raw material remained after TLC monitoring. The reaction solution was washed with saturated sodium thiosulfate aqueous solution (10 mL × 2), saturated sodium chloride (10 mL × 2), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The product was separated and purified by column chromatography (DCM: MeOH = 50: 1-30: 1) to obtain 6-fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one 8,8-dioxide (0.015 g, yield 27.3%). ESI-MS (m / z): 388.34 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:3.590(s,3H),3.941(s,3H),4.202(t,J=4.8Hz,2H),4.423(t,J=4.8Hz ,2H),7.634(s,1H),7.974(s,1H),8.193(d,J=10.2Hz,1H),9.112(s,1H).

[0784] Example 38: (6aR, 10aS)-4-fluoro-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-11-oxo-6a,7,10,10a,11,12-hexahydro-6-oxa-2,8,10b,12-tetraazacyclopentadiene-8(9H)-carboxylic acid ethyl ester (A-38)

[0785]

[0786] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain (6aR, 10aS)-4-fluoro-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-11-oxo-6a,7,10,10a,11,12-hexahydro-6-oxa-2,8,10b,12-tetraazacyclopentadiene-8(9H)-carboxylic acid ethyl ester (0.10 g, yield 59%). ESI-MS (m / z): 467.2 [M+H] + .

[0787] Example 39: 6-Fluoro-10-(4-fluorophenyl)-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-39)

[0788]

[0789] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain 6-fluoro-10-(4-fluorophenyl)-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (0.05 g, yield 50%). ESI-MS (m / z): 434.2 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:3.561(s,3H),3.882(s,3H),4.833(d,J=13.2Hz,1H),5.134(d,J=13.2Hz,1H),5.820(s,1H),7.171- 7.141(m,2H),7.282-7.262(m,2H),7.603(d,J=12.6Hz,1H),7.774(s,1H),8.070(s,1H),8.941(s,1H).

[0790] Example 40: 4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]pyroxene-11(12H)-one (A-40)

[0791]

[0792] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain 4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]pyroxene-11(12H)-one (12 mg, yield 30%). ESI-MS (m / z): 401.11 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:3.597(s,3H),3.973(s,3H),4.001(s,3H),7.261(d,J=5.4Hz,1H),7.399(s,1 H),7.953(s,1H),8.230(s,1H),8.455(d,J=5.4Hz,1H),8.923(s,1H),9.714(s,1H).

[0793] Example 41: (6aS, 9aR)-4-fluoro-11-methyl-5-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadien[h]naphtho[2,1,8-cde]azulene-10(11H)-one (A-41)

[0794]

[0795] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (6aS, 9aR)-4-fluoro-11-methyl-5-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadien[h]naphtho[2,1,8-cde]azulene-10(11H)-one (40 mg, 33.6%). ESI-MS (m / z): 520.19 [M+H] + ; 1 HNMR (600 MHz, DMSO-d 6 )δ:1.590(s,2H),1.749(t,J=10.8Hz,4H),2.136-2.172(m,2H),2.855-2.913(m,6H),3.563(s,3H),3.791(t,J=16.8Hz,1H) ,4.144(t,J=19.8Hz,1H),4.209(t,J=16.8Hz,1H),4.420(t,J=12.0Hz,2H),4.628-4.671(m,1H),4.879(s,1H),5.194(dd,J 1 =8.4Hz,J2 =16.2Hz, 1H), 6.915 (d, J = 8.4Hz, 1H), 7.545 (d, J = 10.8Hz, 1H), 7.804 (d, J = 7.8Hz, 1H), 8.210 (s, 1H), 8.791 (s, 1H).

[0796] Example 42: (6aR, 9aS)-4-fluoro-11-methyl-5-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadien[h]naphtho[2,1,8-cde]azulene-10(11H)-one (A-42)

[0797]

[0798] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain (6aR, 9aS)-4-fluoro-11-methyl-5-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadien[h]naphtho[2,1,8-cde]azulene-10(11H)-one. ESI-MS (m / z): 520.23 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.550(brs,2H),1.674-1.711(m,4H),2.071-2.118(m,2H),2.679-2.743(m,6H),3.5 81(s,3H),3.807(t,J=8.4Hz,1H),4.148-4.180(m,1H),4.218(t,J=8.4Hz,1H),4.397(t,J =6.0Hz,2H),4.678-4.722(m,1H),4.910-4.937(m,1H),5.230(q,J=8.4Hz,1H),6.908(d,J =8.4Hz, 1H), 7.572 (d, J = 13.2Hz, 1H), 7.801 (d, J = 8.4Hz, 1H), 8.206 (s, 1H), 8.824 (s, 1H).

[0799] Example 43: 6-Fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,3'-oxetan-1-one (A-43)

[0800]

[0801] Except for the change of the starting material, the synthesis method was the same as Example 1 to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazinylnaphtho[2,1,8-cde]azulene-10,3'-oxacyclobutane]-1-one (74 mg, yield 40.4%). ESI-MS (m / z): 520.23 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.380-1.405(m,2H),1.500-1.589(m,4H),1.947-1.956(m,2H),2.465-2.73 7(m,6H),3.557(s,3H),4.348-4.370(t,J=6.6Hz,2H),4.348-4.500(m,2H),4.87 5-4.960(m,2H),5.424-5.592(m,2H),6.958-6.972(d,J=8.4Hz,1H),7.621-7.6 39(d,J=10.8Hz,1H),7.860-7.874(d,J=8.4Hz,1H),8.298(s,1H),8.952(s,1H).

[0802] Example 44: 6-Methoxy-10-hydroxymethyl-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-44)

[0803]

[0804] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain 6-methoxy-10-hydroxymethyl-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (180 mg, yield 90.2%). ESI-MS (m / z): 370.1 [M+H] + ; 1H NMR(600MHz,DMSO)δ:3.332(s,3H),3.718-3.740(m,2H),3.916(s,3H),3.945(s,3H),4.373-4.415(m,1 H),4.993-5.019(m,1H),5.326-5.345(m,1H),7.229(s,1H),7.924(s,1H),8.125(s,1H),8.729(s,1H).

[0805] Example 45: 6-methoxy-2,10,10-trimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-45)

[0806]

[0807] In a 100 mL reaction bottle, DMF (10 mL) and methanol (8 mg, 0.24 mmol) were added in sequence, and the temperature was lowered to 0°C before adding NaH (60%, 15 mg, 0.36 mmol). The mixture was reacted at this temperature for 0.5 h. Then, 6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (60 mg, 0.12 mmol) was added and the mixture was reacted at 65°C for 24 h. The reaction was completed by TLC monitoring, and the reaction solution was quenched with water, then concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=20:1-15:1) to obtain 6-methoxy-2,10,10-trimethyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (36 mg, yield 58.2%). ESI-MS (m / z): 518.27 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:1.370-1.405(m,2H),1.490-1.520(m,4H),1.609(s,6H),1.862-1.910(m,2H),2.356-2.410(m,6H),3.474(s,3H),3.383( s,3H),4.300-4.339(m,4H),6.871(d,J=8.4Hz,1H),7.269(s,1H),7.688-7.706(m,1H),8.138(d,J=1.8Hz,1H),8.784(s,1H).

[0808] Example 46: 7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-2,10,10-trimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-46)

[0809]

[0810] The synthesis method is the same as that of Example 1, except that 3-dimethylaminopropanol is used instead of 1-piperidinylpropanol to obtain 7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)-6-fluoro-2,10,10-trimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (40 mg, yield 41.5%). ESI-MS (m / z): 466.22 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.639(s,6H),1.874-1.898(m,2H),2.156(s,6H),2.366(t,J=7.2Hz,2H),3.504(s,3H),4.340(t,J=6.6Hz,2H) ,4.443(s,2H),6.948(d,J=8.4Hz,1H),7.598(d,J=11.4Hz,1H),7.827-7.843(m,1H),8.276(s,1H),8.901(s,1H).

[0811] Example 47: 6-Fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclopropane]-1-one (A-47)

[0812]

[0813] Except for the change of the starting material, the synthesis method was the same as Example 45 to obtain 6-methoxy-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazinonaphtho[2,1,8-cde]azulene-10,1'-cyclopropane]-1-one (25 mg, yield 49.2%). ESI-MS (m / z): 504.22 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:0.999-1.050(m,2H),1.130-1.283(m,2H),1.400-1.596(m,2H),1 .604-1.710(m,4H),2.067-2.174(m,4H),2.508-2.873(m,4H),3.451( s,3H),3.836(s,3H),4.327-4.348(m,4H),6.860(d,J=8.4Hz,1H),7.2 94(s,1H),7.680-7.697(m,1H),8.115(d,J=1.8Hz,1H),8.803(s,1H).

[0814] Example 48: 6-Fluoro-10-(hydroxymethyl)-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-48)

[0815]

[0816] Except for the change of the starting material, the synthesis method was the same as in Example 1 to obtain 6-fluoro-10-(hydroxymethyl)-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazinonaphtho[2,1,8-cde]azulen-1(2H)-one (0.10 g, yield 48.3%). ESI-MS (m / z): 508.21 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:1.427-1.568(m,6H),1.984-1.985(m,2H),2.500-2.506(m,6H),3.547(s,3H),3.630 -3.721(m,2H),4.350-4.371(t,J=6.6Hz,2H),4.438-4.444(m,1H),4.505-4.527(m,1H) ,4.820-4.846(m,1H),5.268-5.287(t,J=11.4Hz,1H),6.947-6.962(d,J=9.0Hz,1H),7. 590-7.609(d,J=11.4Hz,1H),7.844-7.858(d,J=8.4Hz,1H),8.288(s,1H),8.918(s,1H).

[0817] Example 49: 6-Fluoro-10-(methoxymethyl)-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-49)

[0818]

[0819] Step 1: Synthesis of 7-bromo-6-fluoro-10-(methoxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0820] In a 100 mL reaction bottle, THF (10 mL) and 7-bromo-6-fluoro-10-(hydroxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azule-1(2H)-one (0.10 g, 0.27 mmol) were added in sequence. After cooling to 0°C, NaH (0.03 g, 0.82 mmol) was added. The mixture was reacted at this temperature for 0.5 h. Then, iodomethane (0.08 g, 0.54 mmol) was added and the mixture was reacted at room temperature for 5 h. The reaction was completed by TLC monitoring, and the reaction solution was quenched with water, then concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=50:1-25:1) to obtain 7-bromo-6-fluoro-10-(methoxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (30 mg, yield 29.4%). ESI-M (m / z): 381.95 [M+H] + .

[0821] Step 2: Synthesis of 6-fluoro-10-(methoxymethyl)-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0822] In a 100 mL reaction bottle, 1,4-dioxane (15 mL), 7-bromo-6-fluoro-10-(methoxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (0.03 g, 0.08 mmol), (6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)boric acid (0.03 g, 0.12 mmol), cesium carbonate (0.05 g, 0.16 mmol), water (1.5 mL) and tetrakis(triphenylphosphine)palladium (0.02 g, 0.02 mmol) were added in sequence. The temperature was raised to 90°C under nitrogen protection and the reaction was carried out for 2.5 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=50:1-10:1) to obtain 6-fluoro-10-(methoxymethyl)-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (0.16 g, yield 39.2%). ESI-MS (m / z): 522.15 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.400-1.528(m,6H),1.926-1.947(m,2H),2.434-2.497(m,6H),3.307(s,3H),3 .570(s,3H),3.578-3.713(m,2H),4.330-4.351(t,J=6.6Hz,2H),4.526-4.548(m,1H ),4.647-4.734(m,1H),4.752-4.757(m,1H),6.939-6.953(d,J=8.4Hz,1H),7.593- 7.612(d,J=11.4Hz,1H),7.826-7.840(d,J=8.4Hz,1H),8.272(s,1H),8.920(s,1H).

[0823] Example 50: 6-methoxy-10-methoxymethyl-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-50)

[0824]

[0825] Anhydrous tetrahydrofuran (10 mL) and 10-hydroxymethyl-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (50 mg, 0.13 mmol) were added to a 50 mL reaction bottle in sequence, and sodium hydride (25 mg, 0.65 mmol) was added under ice bath, and iodomethane (22 mg, 0.15 mmol) was added after stirring under ice bath for 30 min. The reaction was carried out at room temperature under nitrogen protection for 2 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM: MeOH = 30: 1) to obtain 6-methoxy-10-methoxymethyl-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (20 mg, yield 40.4%). ESI-MS (m / z): 396.16 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:3.336(s,3H),3.501(s,3H),3.608-3.633(m,1H),3.733-3.764(m,1H),3.915(s,3H),3.941(s,3H),4.409-4 .431(m,1H),4.614-4.636(m,1H),4.904-4.926(m,1H),7.233(s,1H),7.780(s,1H),8.089(s,1H),8.734(s,1H).

[0826] Example 51: 6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-10-methylene-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-51)

[0827]

[0828] In a 50 mL reaction bottle, anhydrous tetrahydrofuran (2 mL), 10-hydroxymethyl-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (20 mg, 0.05 mmol) were added in sequence, and DMF (1 mL) was added. Sodium hydride (25 mg, 0.65 mmol) was added under ice bath, and p-toluenesulfonyl chloride (15 mg, 0.08 mmol) was added after stirring under ice bath for 30 min. The reaction was carried out at room temperature under nitrogen protection for 2 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM: MeOH = 30: 1) to obtain 6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-10-methylene-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (10 mg, yield 48.2%). ESI-MS (m / z): 364.13 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:3.352(s,3H),3.915(s,3H),3.962(s,3H),4.954(s,2H),5.396(s,1H ),6.182(s,1H),7.283(s,1H),7.925(s,1H),8.157(s,1H),8.835(s,1H).

[0829] Example 52: 10-((Dimethylamino)methyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-52)

[0830]

[0831] Step 1: Synthesis of 10-(aminomethyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0832] In a 50 mL reaction bottle, anhydrous N,N-dimethylformamide (2 mL), 6-methoxy-10-hydroxymethyl-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azule-1(2H)-one (50 mg, 0.13 mmol), triphenylphosphine (138 mg, 0.524 mmol), and phthalamide (29 mg, 0.19 mmol) were added in sequence, and diisopropyl azodicarboxylate (106 mg, 0.524 mmol) was added under nitrogen protection, and the reaction was carried out at room temperature under nitrogen protection for 2 h. The reaction was completed after TLC monitoring. The reaction solution was added with 50 mL of water, extracted with 30 mL of dichloromethane 4 times, the organic phases were combined, dried over anhydrous sodium sulfate, concentrated to dryness and directly proceeded to the next step. Methanol (15 mL) and hydrazine hydrate (2 mL) were added, and the reaction was carried out at room temperature for 2 h under nitrogen protection. The reaction was completed after TLC monitoring. Methanol was removed under reduced pressure, extracted with 30 mL of dichloromethane 4 times, the organic phases were combined, dried over anhydrous sodium sulfate, and purified by column chromatography (DCM: MeOH = 20: 1) to obtain 10-(aminomethyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (29 mg, yield 58.1%). ESI-MS (m / z): 381.16 [M+H] + .

[0833] Step 2: Synthesis of 10-((dimethylamino)methyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0834] In a 50 mL reaction bottle, anhydrous methanol (6 mL), 10-(aminomethyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (29 mg, 0.08 mmol), formaldehyde aqueous solution (2 mL), acetic acid (10 μL) were added in sequence, and sodium triacetoxyborohydride (49 mg, 0.23 mmol) was added after stirring at room temperature for 30 min. The reaction was carried out at room temperature for 12 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=15:1) to obtain 10-((dimethylamino)methyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrol-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (7 mg, yield 27.3%). ESI-MS (m / z): 409.19 [M+H] + ; 1 H NMR (600 MHz, CDCl 3 )δ:2.503(s,6H),2.694-2.712(d,J=10.8Hz,1H),3.121(s,1H),3.594(s,3H),4.007(s,3H),4.019(s,3H),4.269-4.290(d,J=12. 6Hz, 1H), 4.646-4.659 (d, J = 7.8Hz, 1H), 5.166-5.187 (d, J = 12.6Hz, 1H), 7.265 (s, 1H), 7.310 (s, 1H), 8.102 (s, 1H), 8.555 (s, 1H).

[0835] Example 53: 8-Fluoro-4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,10b,12-triaza[gh]pyroxene-11(12H)-one (A-53)

[0836]

[0837] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain 8-fluoro-4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,10b,12-triaza[gh]pyroxene-11(12H)-one (200 mg, yield 66.6%). ESI-MS (m / z): 418.12 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6)δ:3.577(s,3H),3.967-3.998(m,6H),6.934-6.943(m,1H),7.253(s,1H ),7.349(s,1H),7.972(s,1H),8.235(s,1H),8.475(s,1H),8.872(s,1H).

[0838] Example 54: 6-methoxy-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-54)

[0839]

[0840] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain 6-methoxy-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-9-(pyridin-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (230 mg, yield 63.9%). ESI-MS (m / z); 429.16 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:3.523(s,3H),3.773(s,3H),3.937(s,3H),4.369-4.406(m,1H),4.674-4.698(m,1H),5.734(d,J=9.0H z,1H),7.259(s,1H),7.435-7.446(m,2H),7.662(s,1H),7.849-7.906(m,2H),8.653(s,1H),8.763(s,1H).

[0841] Example 55: (R)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-10-phenyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-55)

[0842]

[0843] Except for the change of the starting material, the synthesis method was the same as Example 30 to obtain (R)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)-10-phenyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (130 mg, yield 43.3%). ESI-MS (m / z); 428.16 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:3.522(s,3H),3.830(s,3H),3.939(s,3H),4.747-4.769(m,1H),5.008-5.034(m,1H),5.746(s,1H),7 .174-7.187(m,2H),7.261-7.275(m,2H),7.296-7.321(m,2H),7.689(s,1H),7.945(s,1H),8.821(s,1H).

[0844] Example 56: (S)-6-Fluoro-2,10-dimethyl-7-(6-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-56)

[0845]

[0846] Step 1: Synthesis of (6-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-3-yl)boronic acid

[0847] Acetonitrile (20 mL), 1-(but-3-yn-1-yl)piperidine (1.37 g, 10.0 mmol), 2-bromopyridine-5-boric acid (2.01 g, 10.0 mmol), tetrakis(triphenylphosphine)palladium (0.40 g, 0.35 mmol), cuprous iodide (0.07 g, 0.35 mmol) and triethylamine (2 mL) were added to a 50 mL reaction bottle in sequence, and the mixture was reacted at room temperature for 6 h under nitrogen protection. The reaction was completed after TLC monitoring, and the reaction solution was concentrated to dryness. The residue was purified by column chromatography (DCM: MeOH = 30: 1) to obtain (6-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-3-yl)boric acid (1.26 g, yield 61.1%). ESI-MS (m / z): 259.15 [M+H] + .

[0848] Step 2: Synthesis of (S)-6-fluoro-2,10-dimethyl-7-(6-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0849] 1,4-dioxane (10 mL), (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (170 mg, 0.48 mmol), (6-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-3-yl)boric acid, potassium carbonate (132 mg, 0.96 mmol), water (1 mL) and tetrakis(triphenylphosphine)palladium (55 mg, 0.048 mmol) were added to a 50 mL reaction bottle in sequence. The mixture was heated to 90°C under nitrogen protection and reacted for 3 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=20:1-10:1) to obtain (S)-6-fluoro-2,10-dimethyl-7-(6-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (35 mg, yield 15%). ESI-MS (m / z): 486.22 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:1.532-1.543(m,6H),1.722(s,4H),2.775(s,2H),2.812-2.836(m,2H),2.931(s,2H),3.632(s,4H),4.531-4.553(m,1H),4.639-4 .661(m,1H),4.722-4.731(m,1H),7.569(d,J=11.4Hz,1H),7.630(d,J=8.4Hz,1H),7.981(d,J=7.8Hz,1H),8.622(s,1H),8.842(s,1H).

[0850] Example 57: 5-(6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-yl)-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadien[gh]pyroxene-11(12H)-one (A-57)

[0851]

[0852] Step 1: Synthesis of 4-fluoro-5-(6-fluoropyridin-3-yl)-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadien[gh]azulene-11(12H)-one

[0853] In a 100 mL reaction bottle, 1,4-dioxane (15 mL), 5-bromo-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadienyl[gh]pyroleum-11(12H)-one (0.69 g, 1.76 mmol), 6-fluoropyridine-3-boric acid (0.315 g, 2.23 mmol), potassium carbonate (0.607 g, 4.4 mmol), water (1.5 mL) and tetrakis(triphenylphosphine)palladium (0.203 g, 0.18 mmol) were added in sequence, and the temperature was raised to 90 °C under nitrogen protection and reacted for 2.5 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM: MeOH = 60: 1) to obtain 4-fluoro-5-(6-fluoropyridin-3-yl)-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadien[gh]azulen-11(12H)-one (0.35 g, yield 48.7%). ESI-MS (m / z): 409.31 [M+H] + .

[0854] Step 2: Synthesis of 5-(6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-yl)-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadien[gh]pyroxene-11(12H)-one (A-57)

[0855] In a 100 mL reaction bottle, 10 ml of DMSO, 3 ml of DIPEA, 170 mg of 4-fluoro-5-(6-fluoropyridin-3-yl)-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadienyl[gh]azulen-11(12H)-one and 167 mg of N,N-dimethylpiperidin-4-amine hydrochloride were added in sequence, the temperature was raised to 150°C, the reaction was carried out for 12 h, the reaction solution was cooled to room temperature, and the reaction solution was washed with ethyl acetate and The mixture was washed with saturated brine 2-3 times, and then the organic phase was dried and concentrated to obtain a crude product, which was purified by column chromatography (DCM: MeOH = 30: 1 to 6: 1) to obtain 5-(6-(4-(dimethylamino)piperidin-1-yl)pyridin-3-yl)-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadien[gh]pyro-11(12H)-one (30 mg, yield 13.9%). ESI-MS (m / z): 517.24 [M+H] + ; 1 H NMR (600 MHz, DMSO-d 6 )δ:1.280-1.353(m,2H),1.412-1.466(m,2H),1.533-1.641(m,1H),1.656-1.667(m,1H),1.71 3-1.728(m,1H),1.915(d,2H),2.098(d,1H),2.357(s,6H),2.615-2.636(m,1H),2.860(t,J=12 .6Hz,2H),3.491(s,3H),3.554-3.576(m,2H),4.218-4.259(m,1H),4.373-4.391(m,3H),6.973 (d, J = 9.0 Hz, 1H), 7.543 (d, J = 10.8 Hz, 1H), 7.647 (d, J = 8.4 Hz, 1H), 8.197 (s, 1H), 8.856 (s, 1H).

[0856] Example 58: (S)-6-Fluoro-2,10-dimethyl-7-(2-oxo-1-(3-piperidin-1-yl)propyl)-1,2-dihydropyridin-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-146)

[0857]

[0858] Step 1: Synthesis of 4-bromo-1-(3-(piperidin-1-yl)propyl)pyridin-2(1H)-one

[0859] Acetonitrile (30 mL), 1-(3-bromopropyl)piperidinyl hydrobromide (1.81 g, 6.32 mmol), 4-bromo-2-hydroxypyridine (1.0 g, 5.75 mmol) and potassium carbonate (1.98 g, 14.37 mmol) were added to a 100 mL reaction bottle in sequence and refluxed for 5 h. After the reaction was completed, the reaction solution was filtered by suction and the filtrate was concentrated to dryness. The residue was purified by column chromatography (DCM: MeOH = 20: 1-15: 1) to obtain 4-bromo-1-(3-(piperidin-1-yl)propyl)pyridin-2(1H)-one (1.24 g, yield 72.0%). ESI-M (m / z): 299.07 / 301.07 [M+H] + .

[0860] Step 2: Synthesis of 1-(3-(piperidin-1-yl)propyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxolan-2-yl)pyridin-2(1H)-one

[0861] 1,4-dioxane (25 mL), 4-bromo-1-(3-(piperidin-1-yl)propyl)pyridin-2(1H)-one (1.24 g, 4.14 mmol), biboronic acid pinacol ester (2.10 g, 8.28 mmol), potassium acetate (1.22 g, 12.42 mmol) and [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride (0.30 g, 0.41 mmol) were added to a 100 mL reaction bottle in sequence. The temperature was raised to 90°C under nitrogen protection and reacted for 3 h. The reaction was completed by TLC monitoring, and the reaction solution was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH=20:1-15:1) to obtain 1-(3-(piperidin-1-yl)propyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxolan-2-yl)pyridin-2(1H)-one (1.13 g, yield was 79%).

[0862] Step 3: Synthesis of (S)-6-fluoro-2,10-dimethyl-7-(2-oxo-1-(3-piperidin-1-yl)propyl)-1,2-dihydropyridin-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0863] 1,4-dioxane (5 mL), 1-(3-(piperidin-1-yl)propyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxolan-2-yl)pyridin-2(1H)-one (156 mg, 0.45 mmol), (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (106 mg, 0.3 mmol), potassium carbonate (83 mg, 0.6 mmol), water (0.5 mL) and tetrakis(triphenylphosphine)palladium (35 mg, 0.03 mmol) were added to a 50 mL reaction bottle in sequence. The mixture was heated to 90°C under nitrogen protection and reacted for 3 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=20:1-10:1) to obtain (S)-6-fluoro-2,10-dimethyl-7-(2-oxo-1-(3-piperidin-1-yl)propyl)-1,2-dihydropyridin-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (25 mg, yield 17%). ESI-M (m / z): 492.23 [M+H] + ; 1 H NMR (600 MHz, CD 3 OD)δ:1.561-1.572(m,5H),1.707-1.726(m,4H),2.100-2.148(m,2H),2. 665(brs,6H),3.657(s,3H),4.146(t,J=7.2Hz,2H),4.559-4.580(m,1H) ,4.689-4.715(m,1H),4.745-4.779(m,1H),6.582(d,J=6.6Hz,1H),6.72 7(s,1H),7.560(d,J=11.4Hz,1H),7.795(d,J=6.6Hz,1H),8.868(s,1H).

[0864] Example 59: (S)-6-Fluoro-2,10-dimethyl-7-(6-((2-(piperidin-1-yl)ethoxy)methyl)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-148)

[0865]

[0866] Step 1: Synthesis of 5-bromo-2-((2-(piperidin-1-yl)ethoxy)methyl)pyridine

[0867] THF (30 mL) and N-hydroxyethylpiperidine (1.0 g, 7.74 mmol) were added to a 100 mL reaction bottle in sequence, and NaH (0.62 g, 15.48 mmol) was added after cooling to 0°C. The reaction was allowed to react for 0.5 h at this temperature, and then 5-bromo-2-(bromomethyl)pyridine (1.94 g, 7.74 mmol) was added. The reaction was allowed to react at room temperature for 5 h. The reaction was completed after TLC monitoring, and the reaction solution was quenched with water, and then concentrated to dryness. The residue was purified by column chromatography (DCM: MeOH = 20: 1-15: 1) to obtain 5-bromo-2-((2-(piperidin-1-yl)ethoxy)methyl)pyridine (1.97 g, yield 85.0%). ESI-MS (m / z): 299.07 / 301.07 [M+H] + .

[0868] Step 2: Synthesis of 2-((2-(piperidin-1-yl)ethoxy)methyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)pyridine

[0869] 1,4-dioxane (25 mL), 5-bromo-2-((2-(piperidin-1-yl)ethoxy)methyl)pyridine (1.97 g, 6.58 mmol), biboronic acid pinacol ester (3.34 g, 13.16 mmol), potassium acetate (1.61 g, 16.45 mmol) and [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride (0.48 g, 0.66 mmol) were added to a 100 mL reaction bottle in sequence. The temperature was raised to 90 ° C under nitrogen protection and reacted for 3 h. The reaction was completed by TLC monitoring, and the reaction solution was concentrated to dryness to obtain a crude product of 2-((2-(piperidin-1-yl)ethoxy)methyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)pyridine, which was directly used in the next step.

[0870] Step 3: Synthesis of (S)-6-fluoro-2,10-dimethyl-7-(6-((2-(piperidin-1-yl)ethoxy)methyl)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one

[0871] 1,4-dioxane (5 mL), 2-((2-(piperidin-1-yl)ethoxy)methyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxane-2-yl)pyridine (156 mg, 0.45 mmol), (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (106 mg, 0.3 mmol), potassium carbonate (83 mg, 0.6 mmol), water (0.5 mL) and tetrakis(triphenylphosphine)palladium (35 mg, 0.03 mmol) were added to a 50 mL reaction bottle in sequence. The mixture was heated to 90°C under nitrogen protection and reacted for 3 h. The reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=20:1-10:1) to obtain (S)-6-fluoro-2,10-dimethyl-7-(6-((2-(piperidin-1-yl)ethoxy)methyl)pyridin-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (25 mg, yield 17%). ESI-MS (m / z): 492.23 [M+H] + ; 1 H NMR (600 MHz, CD 3 OD)δ:1.463-1.624(m,5H),1.693-1.711(m,4H),2.748(brs,4H),2.881 (brs,2H),3.622(s,3H),3.835(t,J=5.4Hz,2H),4.520-4.542(m,1H),4 .613-4.634(m,1H),4.711-4.726(m,3H),7.533(d,J=11.4Hz,1H),7.67 6(d,J=8.4Hz,1H),8.004(d,J=8.4Hz,1H),8.630(s,1H),8.811(s,1H).

[0872] Example 60: N-(2-(3-(dimethylamino)propoxy)-5-(6'-fluoro-2'-methyl-1'-oxo-1',2'-dihydro-9'H-8'-oxa-2',4',10a'-triazaspiro[cyclobutane-1,10'-naphtho[2,1,8-cde]azulene]-2a',3',4a',4a1'(7a'),6'-pentan-7'-yl)pyridin-3-yl)cyclopropanecarboxamide (A-155)

[0873]

[0874] Step 1: Synthesis of 3-((5-bromo-3-nitropyridin-2-yl)oxy)-N,N-dimethylpropane-1-amine

[0875] Anhydrous THF (4 mL) and 3-(dimethylamino)propan-1-ol (1.7 g, 16.4 mmol) were added to a 250 mL reaction bottle, and NaH (0.66 g, 16.4 mmol) was added after cooling to 0°C, and the mixture was stirred at room temperature for 0.5 h. 2 After protection, cooling, slowly add 5-bromo-2-chloro-3-nitropyridine (3g, 12.6mmol) in THF (30mL) at -5°C, and after the addition is complete, return to room temperature and react for 3h. LC-MS shows that the reaction is complete, post-treatment, add saturated ammonium chloride solution to quench the reaction, then add water to dilute, add ethyl acetate, stir, separate, and concentrate the organic phase to dryness under reduced pressure. The residue is purified by column chromatography (DCM: MeOH = 40: 1 ~ 10: 1) to obtain 3-((5-bromo-3-nitropyridine-2-yl)oxy)-N,N-dimethylpropane-1-amine (2.1g, yield 54.5%). ESI-MS (m / z): 304.02 / 306.02 [M+H] + .

[0876] Step 2: Synthesis of 5-bromo-2-(3-(dimethylamino)propoxy)pyridin-3-amine

[0877] AcOH (50 mL), 3-((5-bromo-3-nitropyridin-2-yl)oxy)-N,N-dimethylpropane-1-amine (2.1 g, 6.9 mmol), and Fe powder (2.0 g, 35.7 mmol) were added to a 250 mL reaction bottle in sequence and reacted at room temperature for 2 h. LC-MS showed that the reaction was complete. After post-treatment, THF (50 mL) and DCM (100 mL) were added, filtered, and the filter cake was washed with DCM. The filtrate was concentrated to dryness under reduced pressure, and the residue was purified by column chromatography (DCM: MeOH = 80: 1 to 5: 1) to obtain 5-bromo-2-(3-(dimethylamino)propoxy)pyridin-3-amine (1.4 g, yield was 73.7%). ESI-MS (m / z): 274.05 / 276.02 [M+H] + .

[0878] Step 3: Synthesis of N-(5-bromo-2-(3-(dimethylamino)propoxy)pyridin-3-yl)cyclopropanecarboxamide

[0879] DCM (20 mL), 5-bromo-2-(3-(dimethylamino)propoxy)pyridin-3-amine (0.50 g, 1.8 mmol), and TEA (0.46 g, 4.5 mmol) were added to a 100 mL reaction bottle in sequence, and the temperature was lowered. Cyclopropanoyl chloride (0.25 g, 2.4 mol) was added dropwise at 0°C. After the addition was complete, the mixture was reacted at room temperature for 2 h. LC-MS showed that the reaction was complete. After post-treatment, water was added to quench the reaction, and the organic phase was concentrated to dryness under reduced pressure. The residue was purified by column chromatography (DCM: MeOH = 30: 1 to 10: 1) to obtain N-(5-bromo-2-(3-(dimethylamino)propoxy)pyridin-3-yl)cyclopropanecarboxamide (0.5 g, yield was 80.6%). ESI-MS (m / z): 342.07 / 344.07 [M+H] + .

[0880] Step 4: Synthesis of N-(2-(3-(dimethylamino)propoxy)-5-(6'-fluoro-2'-methyl-1'-oxo-1',2'-dihydro-9'H-8'-oxa-2',4',10a'-triazaspiro[cyclobutane-1,10'-naphtho[2,1,8-cde]azulene]-2a',3',4a',4a1'(7a'),6'-pentan-7'-yl)pyridin-3-yl)cyclopropanecarboxamide

[0881] In a 100 mL reaction bottle, DMF (20 mL), N-(5-bromo-2-(3-(dimethylamino)propoxy)pyridin-3-yl)cyclopropanecarboxamide (0.5 g, 1.5 mmol), biboric acid pinacol ester (0.76 g, 3.0 mmol), PdCl 2(dppf) (0.11 g, 0.15 mmol), potassium acetate (0.37 g, 3.8 mmol), react at 90 ° C for 4 h under nitrogen protection. Cool down, add 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclobutane]-1-one (0.57 g, 1.5 mmol), potassium carbonate (0.62 g, 4.5 mmol), water (1 mL) and tetrakis(triphenylphosphine)palladium (0.17 g, 0.15 mmol). Heat to 90 ° C for 4 h under nitrogen protection. After post-treatment, the reaction solution was concentrated to dryness, and the residue was purified by column chromatography (DCM: MeOH = 20: 1-5: 1) to obtain N-(2-(3-(dimethylamino)propoxy)-5-(6'-fluoro-2'-methyl-1'-oxo-1', 2'-dihydro-9'H-8'-oxa-2', 4', 10a'-triazaspiro[cyclobutane-1, 10'-naphtho[2, 1, 8-cde]azulene]-2a', 3', 4a', 4a1'(7a'), 6'-pentan-7'-yl)pyridin-3-yl)cyclopropanecarboxamide (35 mg, yield 4.3%). ESI-MS (m / z): 561.25 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:0.907-0.987(m,6H),1.318-1.329(m,5H),1.942-1.957(m,1H),1.995-2.009(m,1H),2.102-2.137(m,3H),2.367(s,6H) ,2.626-2.651(m,2H),3.589(s,3H),4.540-4.561(m,2H),7.491(d,J=10.8Hz,1H),7.973(s,1H),8.484(s,1H),8.769(s,1H).

[0882] Example 61: N-(5-(6'-fluoro-2'-methyl-1'-oxo-1',2'-dihydro-9'H-8'-oxa-2',4',10a'-triazaspiro[cyclobutane-1,10'-naphtho[2,1,8-cde]azulene]-2a',3',4a',4a1'(7a'),6'-pentan-7'-yl)-2-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)cyclopropanecarboxamide (A-156)

[0883]

[0884] Except for the change of the starting material, the synthesis method was the same as Example 60 to obtain N-(5-(6'-fluoro-2'-methyl-1'-oxo-1',2'-dihydro-9'H-8'-oxa-2',4',10a'-triazaspiro[cyclobutane-1,10'-naphtho[2,1,8-cde]azulene]-2a',3',4a',4a1'(7a'),6'-pentan-7'-yl)-2-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)cyclopropanecarboxamide (40 mg, yield 35.5%). ESI-MS (m / z): 601.29 [M+H] + ; 1 H NMR (600MHz, CD 3 OD)δ:0.897-0.985(m,6H),1.273-1.295(m,5H),1.629-1.639(m,2H),1.648-1.6 66(m,1H),1.891-1.995(m,1H),2.000-2.007(m,1H),2.014-2.139(m,4H),2.533 -2.579(m,4H),2.592-2.604(m,2H),3.582(s,3H),4.518-4.528(m,2H),4.539-4 .604(m,2H),7.468(d,J=10.8Hz,1H),7.958(s,1H),8.487(s,1H),8.749(s,1H).

[0885] Example 62: N-(2-(3-(dimethylamino)propoxy)-5-(6'-fluoro-2'-methyl-1'-oxo-1',2'-dihydro-9'H-8'-oxa-2',4',10a'-triazaspiro[cyclobutane-1,10'-naphtho[2,1,8-cde]azulene]-2a',3',4a',4a1'(7a'),6'-pentan-7'-yl)pyridin-3-yl)methanesulfonamide (A-157)

[0886]

[0887] Except for the change of the starting material, the synthesis method was the same as Example 60 to obtain N-(2-(3-(dimethylamino)propoxy)-5-(6'-fluoro-2'-methyl-1'-oxo-1',2'-dihydro-9'H-8'-oxa-2',4',10a'-triazaspiro[cyclobutane-1,10'-naphtho[2,1,8-cde]azulene]-2a',3',4a',4a1'(7a'),6'-pentan-7'-yl)pyridin-3-yl)methanesulfonamide (28 mg, yield 25.2%). ESI-MS (m / z): 571.21 [...

Claims

1. A compound of formula (I') or formula (I) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt thereof, having the following structure: In formula (I'), Y is X1 is selected from the group consisting of a bond, hydrogen, deuterium, halogen, hydroxyl, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more replaceable sites of the substituted group is independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond; When X1 is hydrogen, deuterium, halogen, hydroxyl, amino, nitro or cyano, R1, X2, R2 and R3 are absent; R1 is selected from absence, a bond, hydrogen, deuterium or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not substituted or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 1a Replaced by; R 1a Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, nitro, thiol, cyano, oxo, -R 1b 、-OR 1b 、-SR 1b 、-S(O)R 1b 、-SO2(R 1b )、-C(O)R 1b 、-C(O)OR 1b 、-OC(O)R 1b 、-NH(R 1b )、-N(R 1b )(R 1c )、-C(O)NH(R 1b )、-C(O)N(R 1b )(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-S(O)N(R 1b )(R 1c )、-SO2NH(R 1b )、-SO2N(R 1b )(R 1c )、-NHS(O)(R 1b )、-N(R 1b )S(O)(R 1c )、-NHSO2(R 1b ) or -N(R 1b )SO2(R 1c );R 1b , R 1c Each occurrence is independently selected from hydrogen, deuterium or optionally deuterated, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c and the nitrogen atom to which it is attached form a group optionally substituted with deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond; When R1 is hydrogen or deuterium, X2, R2 and R3 do not exist; X2 is selected from the group consisting of absence, a bond, hydrogen, deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, -O-, -S-, -P-, -C(O)-, -C(S)-, -C(=NR 2x )-, -CH=N-, -C(O)O-, -C(O)C(O)-, -OC(O)-, -OC(S)-, -O-SO2-, -OP(O)-, -N=CH-, -C(O)N(R 2x )-、-N(R 2x )C(O)-、-N(R 2x )-, -S(O)-, -SO2-, -S(O)N(R 2x )-、-SO2N(R 2x )-or-P(O)-;R 2x is selected from hydrogen, deuterium or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently selected from deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond; When X2 is hydrogen, deuterium, halogen, hydroxyl, amino, nitro, mercapto or cyano, R2 and R3 are absent; R2 is selected from absence, a bond, hydrogen, deuterium or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 aryl, 3-10 membered heterocycloalkyl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not substituted or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 2a Replaced by; R 2a Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, nitro, thiol, cyano, oxo, -R 2b 、-OR 2b 、-SR 2b 、-S(O)(R 2b )、-SO2(R 2b )、-C(O)R 2b 、-C(O)OR 2b 、-OC(O)R 2b 、-NH(R 2b )、-N(R 2b )(R 2c )、-C(O)NH(R 2b )、-C(O)N(R 2b )(R 2c )、-NHC(O)(R 2b )、-N(R 2b )C(O)(R 2c )、-S(O)NH(R 2b )、-S(O)N(R 2b )(R 2c )、-SO2NH(R 2b )、-SO2N(R 2b )(R 2c )、-NHS(O)(R 2b )、-N(R 2b )S(O)(R 2c )、-NHSO2(R 2b ) or -N(R 2b )SO2(R 2c );R 2b , R 2c Each occurrence is independently selected from optionally deuterated, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 2b and R 2c When connected to the same nitrogen atom, R 2b and R 2c and the nitrogen atom to which it is attached form a group optionally substituted with deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond; When R2 is hydrogen or deuterium, R3 is absent; R3 is selected from the group consisting of absent, hydrogen, deuterium, halogen, hydroxy, amino, nitro, thiol, cyano, oxo, -R 3b 、-OR 3b 、-SR 3b 、-S(O)(R 3b )、-SO2(R 3b )、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-NH(R 3b )、-N(R 3b )(R 3c )、-C(O)NH(R 3b )、-C(O)N(R 3b )(R 3c )、-NHC(O)(R 3b )、-N(R 3b )C(O)(R 3c )、-S(O)NH(R 3b )、-S(O)N(R 3b )(R 3c )、-SO2NH(R 3b )、-SO2N(R 3b )(R 3c )、-NHS(O)(R 3b )、-N(R 3b )S(O)(R 3c )、-NHSO2(R 3b ) or -N(R 3b )SO2(R 3c );R 3b , R 3c Each occurrence is independently selected from hydrogen, deuterium or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 3-20 membered heterocyclic group or a 5-12 membered heteroaryl group; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 3d Replaced by; R 3d Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, nitro, thiol, cyano, oxo, -R 3e 、-OR 3e 、-SR 3e 、-S(O)(R 3e )、-SO2(R 3e )、-C(O)R 3e 、-C(O)OR 3e 、-OC(O)R 3e 、-NH(R 3e )、-N(R 3e )(R 3f )、-C(O)NH(R 3e )、-C(O)N(R 3e )(R 3f )、-NHC(O)(R 3e )、-N(R 3e )C(O)(R 3f )、-S(O)NH(R 3e )、-S(O)N(R 3e )(R 3f )、-SO2NH(R 3e )、-SO2N(R 3e )(R 3f )、-NHS(O)(R 3e )、-N(R 3e )S(O)(R 3f )、-NHSO2(R 3e ) or -N(R 3e )SO2(R 3f );R 3e , R 3f Each occurrence is independently selected from hydrogen, deuterium or optionally substituted with halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached form a group optionally substituted with deuterium, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond; R4 is independently selected at each occurrence from hydrogen, deuterium, halogen, nitro, amino, cyano, hydroxyl, carboxyl, thiol or C optionally substituted with one or more deuterium, halogen, hydroxyl or amino. 1-6 Alkyl, C 1-6 Alkoxy or C 1-6 Alkylthio; h is 1 or 2; R5 is independently selected at each occurrence from hydrogen, deuterium, halogen, hydroxyl or C optionally substituted with one or more deuterium, halogen, hydroxyl, amino or cyano groups. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-10 Cycloalkyl, C 6-14 Aryl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; L is C(R L ) or N; R L Each occurrence is independently selected from hydrogen, deuterium, halogen, nitro, amino, cyano, hydroxyl, carboxyl, thiol, C 1-6 Alkyl, C 1-6 Alkoxy or C 1-6 Alkylthio; in, represents a single bond or a double bond; Q1 is connected to W; t1, t2, t3, t4, t5, t6 are independently 0 or 1; n1 and n2 are independently 0, 1 or 2, and n1 and n2 are not 0 at the same time, wherein n1 represents n1 Q1s connected in sequence, and n2 represents n2 Q2s connected in sequence; two adjacent Q1s are connected by a single bond or a double bond; two adjacent Q2s are connected by a single bond or a double bond; W, Q1, Q2 are independently selected from C, O, N or S; Q3 is C; when the bond connecting one side of Q3 is a double bond, R 10 or R 11 does not exist; R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, cyano, nitro, -R 6a 、-OR 6a 、-SR 6a 、-S(O)(R 6a )、-SO2(R 6a )、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b )、-S(O)NH(R 6a )、-S(O)N(R 6a )(R 6b )、-SO2NH(R 6a )、-SO2N(R 6a )(R 6b )、-NHS(O)(R 6a )、-N(R 6a )S(O)(R 6b )、-NHSO2(R 6a ) or -N(R 6a )SO2(R 6b ); or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two substituents attached to the same atom together form =O, =NR 6a or =CH-R 6a or W, each occurrence of Q1, each occurrence of Q2 and Q3, any two adjacent atoms and the substituents to which they are attached together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or W, each occurrence of Q1, each occurrence of Q2 and Q3 and any one of the substituents attached thereto together form an optionally replaced R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group or heteromonospirocyclic group; R 6a , R 6b Each occurrence is independently selected from hydrogen, deuterium or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or when R 6a and R 6b When connected to the same nitrogen atom, R 6a and R 6b and the nitrogen atom to which it is attached together form an optionally R 6c substituted 3-10 membered heterocyclyl or 5-12 membered heteroaryl; R 6c Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, cyano, nitro, azido, oxo, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e 、-C(O)OR 6d 、-OC(O)R 6d 、-S(O)N(R 6d )(R 6e )、-SO2N(R 6d )(R 6e )、-N(R 6d )S(O)(R 6e )、-N(R 6d )SO2(R 6e ), =NR 6d or =CH-R 6d ; The oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond; the =NR 6d It means that two H at the same substitution site are replaced by the same N to form a double bond, and N is replaced by R 6d Substitution; said =CH-R 6d It means that two H at the same substitution site are replaced by the same C to form a double bond, and C is replaced by R 6d replace; R 6d , R 6e Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, cyano or optionally substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, monospirocyclic group, heteromonospirocyclic group, fused cyclic group or heterofused cyclic group; or when R 6d and R 6e When connected to the same nitrogen atom, R 6d and R 6e and the nitrogen atom to which it is attached form an optionally substituted 3-10 membered heterocyclic group or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 6f Replaced by; R 6f Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -C(O)C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH-C 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the oxo group means that two H at the same substitution site are replaced by the same O to form a double bond; When there is a heterocycloalkyl group, a heteroaryl group, a heterocyclic group, a heteromonospirocyclic group, a heterofused cyclic group and / or a heterobridged cyclic group, the heteroatoms therein are independently selected from O, N or S, and the number of the heteroatoms is 1, 2, 3 or 4; In formula (I), Y is X1 is selected from the group consisting of a bond, hydrogen, halogen, hydroxy, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more replaceable sites of the substituted group is independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond; When X1 is hydrogen, halogen, hydroxy, amino, nitro or cyano, R1, X2, R2 and R3 are absent; R1 is selected from absence, a bond, hydrogen or an optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not substituted or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 1a Replaced by; R 1a Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 1b 、-OR 1b 、-SR 1b 、-S(O)R 1b 、-SO2(R 1b )、-C(O)R 1b 、-C(O)OR 1b 、-OC(O)R 1b 、-NH(R 1b )、-N(R 1b )(R 1c )、-C(O)NH(R 1b )、-C(O)N(R 1b )(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-S(O)N(R 1b )(R 1c )、-SO2NH(R 1b )、-SO2N(R 1b )(R 1c )、-NHS(O)(R 1b )、-N(R 1b )S(O)(R 1c )、-NHSO2(R 1b ) or -N(R 1b )SO2(R 1c );R 1b , R 1c Each occurrence is independently selected from hydrogen or optionally substituted with halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c and the nitrogen atom to which it is attached form a group optionally substituted with halogen, hydroxy, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond; When R1 is hydrogen, X2, R2 and R3 are absent; X2 is selected from the group consisting of absence, a bond, hydrogen, halogen, hydroxy, amino, nitro, thiol, cyano, -O-, -S-, -P-, -C(O)-, -C(S)-, -C(=NR 2x )-, -CH=N-, -C(O)O-, -C(O)C(O)-, -OC(O)-, -OC(S)-, -O-SO2-, -OP(O)-, -N=CH-, -C(O)N(R 2x )-、-N(R 2x )C(O)-、-N(R 2x )-, -S(O)-, -SO2-, -S(O)N(R 2x )-、-SO2N(R 2x )-or-P(O)-;R 2x is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more replaceable sites of the substituted group is independently selected from halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond; When X2 is hydrogen, halogen, hydroxyl, amino, nitro, mercapto or cyano, R2 and R3 are absent; R2 is selected from absent, a bond, hydrogen or an optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 aryl, 3-10 membered heterocycloalkyl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not substituted or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 2a Replaced by; R 2a Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 2b 、-OR 2b 、-SR 2b 、-S(O)(R 2b )、-SO2(R 2b )、-C(O)R 2b 、-C(O)OR 2b 、-OC(O)R 2b 、-NH(R 2b )、-N(R 2b )(R 2c )、-C(O)NH(R 2b )、-C(O)N(R 2b )(R 2c )、-NHC(O)(R 2b )、-N(R 2b )C(O)(R 2c )、-S(O)NH(R 2b )、-S(O)N(R 2b )(R 2c )、-SO2NH(R 2b )、-SO2N(R 2b )(R 2c )、-NHS(O)(R 2b )、-N(R 2b )S(O)(R 2c )、-NHSO2(R 2b ) or -N(R 2b )SO2(R 2c );R 2b , R 2c Each occurrence is independently selected from optionally substituted with halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 2b and R 2c When connected to the same nitrogen atom, R 2b and R 2c and the nitrogen atom to which it is attached form a group optionally substituted with halogen, hydroxy, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond; When R2 is hydrogen, R3 is absent; R3 is selected from the group consisting of absent, hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 3b 、-OR 3b 、-SR 3b 、-S(O)(R 3b )、-SO2(R 3b )、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-NH(R 3b )、-N(R 3b )(R 3c )、-C(O)NH(R 3b )、-C(O)N(R 3b )(R 3c )、-NHC(O)(R 3b )、-N(R 3b )C(O)(R 3c )、-S(O)NH(R 3b )、-S(O)N(R 3b )(R 3c )、-SO2NH(R 3b )、-SO2N(R 3b )(R 3c )、-NHS(O)(R 3b )、-N(R 3b )S(O)(R 3c )、-NHSO2(R 3b ) or -N(R 3b )SO2(R 3c );R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 3d Replaced by; R 3d Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 3e 、-OR 3e 、-SR 3e 、-S(O)(R 3e )、-SO2(R 3e )、-C(O)R 3e 、-C(O)OR 3e 、-OC(O)R 3e 、-NH(R 3e )、-N(R 3e )(R 3f )、-C(O)NH(R 3e )、-C(O)N(R 3e )(R 3f )、-NHC(O)(R 3e )、-N(R 3e )C(O)(R 3f )、-S(O)NH(R 3e )、-S(O)N(R 3e )(R 3f )、-SO2NH(R 3e )、-SO2N(R 3e )(R 3f )、-NHS(O)(R 3e )、-N(R 3e )S(O)(R 3f )、-NHSO2(R 3e ) or -N(R 3e )SO2(R 3f );R 3e , R 3f Each occurrence is independently selected from hydrogen or optionally substituted with halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached form a group optionally substituted with halogen, hydroxy, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-12 membered heteroaryl groups; the oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond; R4 is selected from hydrogen, halogen, nitro, amino, cyano, hydroxyl, carboxyl, mercapto or C 1-6 Alkyl, C 1-6 Alkoxy or C 1-6 Alkylthio; R5 is selected from hydrogen, halogen, hydroxyl or C optionally substituted by one or more halogen, hydroxyl, amino or cyano groups. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-10 Cycloalkyl, C 6-14 Aryl, 3-10 membered heterocycloalkyl and 5-12 membered heteroaryl; L is C(R L ) or N; R L is selected from hydrogen, halogen, nitro, amino, cyano, hydroxyl, carboxyl, thiol, C 1-6 Alkyl, C 1-6 Alkoxy or C 1-6 Alkylthio; A is in, represents a single bond or a double bond; Q1 is connected to W; t1, t2, t3, t4, t5, t6 are independently 0 or 1; n1 and n2 are independently 0, 1 or 2, and n1 and n2 are not 0 at the same time, wherein n1 represents n1 Q1s connected in sequence, and n2 represents n2 Q2s connected in sequence; two adjacent Q1s are connected by a single bond or a double bond; two adjacent Q2s are connected by a single bond or a double bond; W, Q1, Q2 are independently selected from C, O, N or S; Q3 is C; when the bond connecting one side of Q3 is a double bond, R 10 or R 11 does not exist; R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, -R 6a 、-OR 6a 、-SR 6a 、-S(O)(R 6a )、-SO2(R 6a )、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b )、-S(O)NH(R 6a )、-S(O)N(R 6a )(R 6b )、-SO2NH(R 6a )、-SO2N(R 6a )(R 6b )、-NHS(O)(R 6a )、-N(R 6a )S(O)(R 6b )、-NHSO2(R 6a ) or -N(R 6a )SO2(R 6b ); or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two substituents attached to the same atom together form =O, =NR 6a or =CH-R 6a or W, each occurrence of Q1, each occurrence of Q2 and Q3, any two adjacent atoms and the substituents to which they are attached together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or W, each occurrence of Q1, each occurrence of Q2 and Q3 and any one of the substituents attached thereto together form an optionally replaced R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group or heteromonospirocyclic group; R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or when R 6a and R 6b When connected to the same nitrogen atom, R 6a and R 6b and the nitrogen atom to which it is attached together form an optionally R 6c substituted 3-10 membered heterocyclyl or 5-12 membered heteroaryl; R 6c Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, azido, oxo, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e 、-C(O)OR 6d 、-OC(O)R 6d 、-S(O)N(R 6d )(R 6e )、-SO2N(R 6d )(R 6e )、-N(R 6d )S(O)(R 6e )、-N(R 6d )SO2(R 6e ), =NR 6d or =CH-R 6d ; The oxo group refers to two H groups at the same substitution site being replaced by the same O to form a double bond; the =NR 6d It means that two H at the same substitution site are replaced by the same N to form a double bond, and N is replaced by R 6d Substitution; said =CH-R 6d It means that two H at the same substitution site are replaced by the same C to form a double bond, and C is replaced by R 6d replace; R 6d , R 6e Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, cyano or optionally substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, monospirocyclic group, heteromonospirocyclic group, fused cyclic group or heterofused cyclic group; or when R 6d and R 6e When connected to the same nitrogen atom, R 6d and R 6e and the nitrogen atom to which it is attached form an optionally substituted 3-10 membered heterocyclic group or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or the hydrogen on one or more substitutable sites of the substituted group is independently replaced by R 6f Replaced by; R 6f Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -C(O)C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH-C 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; the oxo group means that two H at the same substitution site are replaced by the same O to form a double bond; When there is a heterocycloalkyl group, a heteroaryl group, a heterocyclic group, a heteromonospirocyclic group, a heterofused cyclic group and / or a heterobridged cyclic group, the heteroatoms therein are independently selected from O, N or S, and the number of the heteroatoms is 1, 2, 3 or 4; or In formula (I), Y is: X1 is selected from the group consisting of a bond, hydrogen, halogen, hydroxy, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or one or more substitutable sites of the substituted group are independently selected from halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The "oxo group" refers to two H groups at the same substitution position being replaced by the same O group to form a double bond; When X1 is hydrogen, halogen, hydroxyl, amino, nitro or cyano, R1, X2, R2 and R3 do not exist; R1 is selected from absent, a bond, hydrogen or an optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not replaced or one or more substitutable sites of the substituted group are independently replaced by R 1a replaced by, where R 1a Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 1b 、-OR 1b 、-SR 1b 、-S(O)R 1b 、-SO2(R 1b )、-C(O)R 1b 、-C(O)OR 1b 、-OC(O)R 1b 、-NH(R 1b )、-N(R 1b )(R 1c )、-C(O)NH(R 1b )、-C(O)N(R 1b )(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-S(O)N(R 1b )(R 1c )、-SO2NH(R 1b )、-SO2N(R 1b )(R 1c )、-NHS(O)(R 1b )、-N(R 1b )S(O)(R 1c )、-NHSO2(R 1b )、-N(R 1b )SO2(R 1c ), where R 1b , R 1c Each occurrence is independently selected from hydrogen or halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl, one or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c Together with the nitrogen atom to which they are attached, they form groups that are substituted by halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl, or one or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the "oxo group" means that two H at the same substitution position are replaced by the same O to form a double bond; When R1 is hydrogen, X2, R2, and R3 do not exist; X2 is selected from the group consisting of absence, a bond, hydrogen, halogen, hydroxy, amino, nitro, thiol, cyano, -O-, -S-, -P-, -C(O)-, -C(S)-, -C(=NR 2x )-, -CH=N-, -C(O)O-, -C(O)C(O)-, -OC(O)-, -OC(S)-, -O-SO2-, -OP(O)-, -N=CH-, -C(O)N(R 2x )-、-N(R 2x )C(O)-、-N(R 2x )-, -S(O)-, -SO2-, -S(O)N(R 2x )-、-SO2N(R 2x )-、-P(O)-;R 2x is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or one or more substitutable sites of the substituted group are independently selected from halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 The "oxo group" refers to two H groups at the same substitution position being replaced by the same O group to form a double bond; When X2 is hydrogen, halogen, hydroxyl, amino, nitro, mercapto or cyano, R2 and R3 do not exist; R2 is selected from absent, a bond, hydrogen, or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 aryl, 3-10 membered heterocycloalkyl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; the optional substitution means that the hydrogen on the substituted group is not replaced or one or more substitutable sites of the substituted group are independently replaced by R 2a replaced by, where R 2a Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 2b 、-OR 2b 、-SR 2b 、-S(O)(R 2b )、-SO2(R 2b )、-C(O)R 2b 、-C(O)OR 2b 、-OC(O)R 2b 、-NH(R 2b )、-N(R 2b )(R 2c )、-C(O)NH(R 2b )、-C(O)N(R 2b )(R 2c )、-NHC(O)(R 2b )、-N(R 2b )C(O)(R 2c )、-S(O)NH(R 2b )、-S(O)N(R 2b )(R 2c )、-SO2NH(R 2b )、-SO2N(R 2b )(R 2c )、-NHS(O)(R 2b )、-N(R 2b )S(O)(R 2c )、-NHSO2(R 2b )、-N(R 2b )SO2(R 2c ), where R 2b , R 2c Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl, one or more arbitrarily substituted hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; or when R 2b and R 2c When connected to the same nitrogen atom, R 2b and R 2c Together with the nitrogen atom to which they are attached, they form groups that are substituted by halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl, or one or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the "oxo group" means that two H at the same substitution position are replaced by the same O to form a double bond; When R2 is hydrogen, R3 is absent; R3 is selected from the group consisting of absent, hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 3b 、-OR 3b 、-SR 3b 、-S(O)(R 3b )、-SO2(R 3b )、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-NH(R 3b )、-N(R 3b )(R 3c )、-C(O)NH(R 3b )、-C(O)N(R 3b )(R 3c )、-NHC(O)(R 3b )、-N(R 3b )C(O)(R 3c )、-S(O)NH(R 3b )、-S(O)N(R 3b )(R 3c )、-SO2NH(R 3b )、-SO2N(R 3b )(R 3c )、-NHS(O)(R 3b )、-N(R 3b )S(O)(R 3c )、-NHSO2(R 3b )、-N(R 3b )SO2(R 3c ), where R 3b , R 3c Each occurrence is independently selected from optionally substituted hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c Together with the nitrogen atom to which they are attached, they form an optionally substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the optional substitution means that the hydrogen on the substituted group is not replaced or one or more substitutable positions of the substituted group are independently replaced by R 3d replaced by, where R 3d Each occurrence is independently selected from halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 3e 、-OR 3e 、-SR 3e 、-S(O)(R 3e )、-SO2(R 3e )、-C(O)R 3e 、-C(O)OR 3e 、-OC(O)R 3e 、-NH(R 3e )、-N(R 3e )(R 3f )、-C(O)NH(R 3e )、-C(O)N(R 3e )(R 3f )、-NHC(O)(R 3e )、-N(R 3e )C(O)(R 3f )、-S(O)NH(R 3e )、-S(O)N(R 3e )(R 3f )、-SO2NH(R 3e )、-SO2N(R 3e )(R 3f )、-NHS(O)(R 3e )、-N(R 3e )S(O)(R 3f )、-NHSO2(R 3e )、-N(R 3e )SO2(R 3f ), where R 3e , R 3f Each occurrence is independently selected from hydrogen or halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl, one or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f Together with the nitrogen atom to which they are attached, they form groups that are substituted by halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl, or one or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; the "oxo group" means that two H at the same substitution position are replaced by the same O to form a double bond; R4 is selected from hydrogen, halogen, nitro, amino, cyano, hydroxyl, carboxyl, mercapto or C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio; R5 is selected from hydrogen, halogen, hydroxyl or C substituted by one or more halogen, hydroxyl, amino, cyano 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-10 Cycloalkyl, C 6-14 Aryl, 3-10 membered heterocycloalkyl and 5-12 membered heteroaryl; L is C(R L ) or N; R L is selected from hydrogen, halogen, nitro, amino, cyano, hydroxyl, carboxyl, thiol, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio; A is: in, represents a single bond or a double bond; Q1 is connected to one end of W; t1, t2, t3, t4, t5, and t6 are each independently 0 or 1; n1 and n2 are each independently 0, 1 or 2, and n1 and n2 are not 0 at the same time, wherein n1 represents n1 Q1s connected in sequence, and n2 represents n2 Q2s connected in sequence; two adjacent Q1s are connected by a single bond or a double bond; two adjacent Q2s are connected by a single bond or a double bond; W, Q1, Q2 are each independently selected from C, O, N, S; Q3 is C; when the bond connecting one side of Q3 is a double bond, R 10 or R 11 One of them does not exist; R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, -R 6a 、-OR 6a 、-SR 6a 、-S(O)(R 6a )、-SO2(R 6a )、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b )、-S(O)NH(R 6a )、-S(O)N(R 6a )(R 6b )、-SO2NH(R 6a )、-SO2N(R 6a )(R 6b )、-NHS(O)(R 6a )、-N(R 6a )S(O)(R 6b )、-NHSO2(R 6a )、-N(R 6a )SO2(R 6b ); or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two substituents attached to the same atom together form =O, =NR 6a or =CR 6a or W, each occurrence of Q1, each occurrence of Q2 and Q3, any two adjacent atoms and the substituents to which they are connected together form a substituent group represented by R 6c Optionally substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or W, each occurrence of Q1, each occurrence of Q2 and Q3, any one atom and the substituents connected thereto together form a radical represented by R 6c Optionally substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group, heteromonospirocyclic group; R 6a , R 6b Each occurrence is independently selected from hydrogen, or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, 4-12 membered bridged ring group, 4-12 membered heterobridged ring group, monospiro ring group, heteromonospiro ring group, fused ring group or heterofused ring group; or when R 6a and R 6b When connected to the same nitrogen atom, R 6a and R 6b Together with the nitrogen atom to which they are attached, they form 6c substituted 3-10 membered heterocyclic group or optionally R 6c substituted 5-12 membered heteroaryl; The R 6c Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, nitro, azido, oxo, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e 、-C(O)OR 6d 、-OC(O)R 6d 、-S(O)N(R 6d )(R 6e )、-SO2N(R 6d )(R 6e )、-N(R 6d )S(O)(R 6e )、-N(R 6d )SO2(R 6e ), =NR 6d , =CR 6d ; The "oxo" refers to two H groups at the same substitution position being replaced by the same O to form a double bond; the "=NR 6d " means that two H at the same substitution position are replaced by the same N to form a double bond, and N is replaced by R 6d Replacement; said "=CR 6d " means that two H at the same substitution position are replaced by the same C to form a double bond, and C is replaced by R 6d replace; R 6d , R 6e Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, cyano, or optionally substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, monospirocyclic group, heteromonospirocyclic group, fused cyclic group or heterofused cyclic group; or when R 6d and R 6e When connected to the same nitrogen atom, R 6d and R 6e Together with the nitrogen atom to which they are attached, they can form an optionally substituted 3-10 membered heterocyclic group or an optionally substituted 5-12 membered heteroaryl group; the optional substitution means that the hydrogen on the substituted group is not replaced or one or more substitutable positions of the substituted group are independently replaced by R 6f replaced by, where R 6f Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -C(O)C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH-C 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; the "oxo group" means that two H at the same substitution position are replaced by the same O to form a double bond; Unless otherwise indicated, the term "optionally substituted" or "arbitrarily substituted" means that the substituents are independently selected from one or more hydroxyl, halogen, hydroxyl, amino, nitro, thiol, cyano, oxo, -C(O)C 1-6 Alkyl, -C(O)OC 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH-C 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl group, when the substituent is selected from "oxo" means that two hydrogen atoms at the same substitution position are replaced by oxygen atoms; Unless otherwise specified, the heteroatoms in the above heterocycloalkyl, heteroaryl, heteromonospirocyclic group and heterobridged ring group are independently selected from O, N or S, and the number of heteroatoms is 1, 2, 3 or 4.

2. The compound according to claim 1 or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, characterized in that: The compound has a structure as shown in formula (Ia), formula (Ib) or (Ic): wherein each substituent is as defined in claim 1.

3. The compound according to any one of claims 1 to 2, or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, characterized in that: X1 is selected from the group consisting of a bond, hydrogen, halogen, hydroxy, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x Selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; Preferably, X1 is selected from a bond, hydrogen, halogen, hydroxyl, amino, nitro, cyano, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-、-C(O)N(R 1x )-or-N(R 1x )-;R 1x Selected from hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl or 3-6 membered heterocycloalkyl; More preferably, X1 is selected from a bond, hydrogen, halogen, hydroxyl, amino, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -NHC(O)-, -C(O)NH-, -NH- or -N(CH3)-; or X1 is selected from a bond, hydrogen, -S-, -NHC(O)- or -C(O)NH-; or X1 is selected from a bond; and / or R1 is selected from absence, a bond, hydrogen or an optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; Preferably, R1 is selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-14 Aryl or 5-12 membered heteroaryl; More preferably, R1 is selected from optionally substituted C 1-6 Alkyl, C 2-6 Alkynyl, C 6-14 Aryl or 5-12 membered heteroaryl; The optional substitution refers to optionally being replaced by R 1a replaced by; or R1 is selected from optionally substituted C 2-6 Alkynyl or 5-12 membered heteroaryl; Preferably, R1 is selected from optionally substituted 5-12 membered heteroaryl; The optional substitution refers to optionally being replaced by R 1a replaced by; or R1 is selected from optionally substituted C 2-6 Alkynyl or 5-8 membered heteroaryl, wherein the heteroatom is N and the number of heteroatoms is 1, 2 or 3; Preferably, R1 is selected from an optionally substituted 5-6 membered heteroaryl group, wherein the heteroatom is N and the number of heteroatoms is 1 or 2; More preferably, R1 is selected from optionally substituted ethynyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyrazolyl, imidazolyl or pyrrolyl; More preferably, R1 is selected from optionally substituted pyridinyl; The optional substitution refers to optionally being replaced by R 1a replaced by; or R1 is selected from an optionally substituted 3-10 membered heterocyclyl; Preferably, R1 is selected from an optionally substituted 5-8 membered heterocyclic group, wherein the heteroatom is N and the number of heteroatoms is 1 or 2; More preferably, R1 is selected from optionally substituted dihydropyridinyl; The optional substitution refers to optionally being replaced by R 1a replaced by; and / or R 1a Each occurrence is independently selected from halogen, hydroxy, amino, oxo, -R 1b 、-OR 1b 、-SR 1b 、-S(O)R 1b 、-SO2(R 1b )、-C(O)R 1b 、-C(O)OR 1b 、-OC(O)R 1b 、-NH(R 1b )、-N(R 1b )(R 1c )、-C(O)NH(R 1b )、-C(O)N(R 1b )(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-S(O)N(R 1b )(R 1c )、-SO2NH(R 1b )、-SO2N(R 1b )(R 1c )、-NHS(O)(R 1b )、-N(R 1b )S(O)(R 1c )、-NHSO2(R 1b ) or -N(R 1b )SO2(R 1c ); The oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond; or R 1a Each occurrence is independently selected from halogen, hydroxy, amino, oxo, -R 1b 、-C(O)NH(R 1c )、-NHC(O)(R 1b )、-N(R 1b )C(O)(R 1c )、-S(O)NH(R 1b )、-SO2NH(R 1b )、-NHS(O)(R 1b )、-NHSO2(R 1b ) or -N(R 1b )SO2(R 1c ); The oxo group means that two H groups at the same substitution site are replaced by the same O group to form a double bond; or R 1a Each occurrence is independently selected from halogen, amino, oxo, -R 1b 、-NHC(O)(R 1b ) or -NHSO2(R 1b ); The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond; Preferably, R 1a Each occurrence is independently selected from -NHC(O)(R 1b ) or -NHSO2(R 1b ); and / or R 1b , R 1c Each occurrence is independently selected from hydrogen or optionally substituted with halogen, hydroxy, amino, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-8 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 1b and R 1c When connected to the same nitrogen atom, R 1b and R 1c and the nitrogen atom to which it is attached together form an optionally substituted halogen, hydroxyl, amino, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-8 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups among aryl or 5-8 membered heteroaryl groups; The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond; Preferably, R 1b , R 1c Each occurrence is independently selected from C 1-6 Alkyl, C 3-8 Cycloalkyl or C 6-8 Aryl; More preferably, R 1b , R 1c Each occurrence is independently selected from C 1-4 Alkyl or C 3-4 Cycloalkyl; or R 1b , R 1c is independently selected at each occurrence from methyl, ethyl, cyclopropanyl, phenyl or tetrahydropyranyl; Preferably, R 1b , R 1c is independently selected at each occurrence from methyl or cyclopropane; and / or R1 is selected from the following optionally substituted groups: Preferably, R1 is selected from optionally substituted Wherein, the "*" end is one end connected to X1, and the other end is one end connected to X2; the optional substitution means that R 1a replaced by; or R1 is selected from the following groups: Among them, the "*" end is the end connected to X1, and the other end is the end connected to X2; and / or X2 is selected from the group consisting of absence, a bond, hydrogen, halogen, hydroxyl, amino, -O-, -S-, -C(O)O-, -OC(O)-, -C(O)N(R 2x )-、-N(R 2x )C(O)-or-N(R 2x )-;R 2x is selected from hydrogen or C optionally substituted by halogen, hydroxy or amino 1-6 Alkyl; or X2 is selected from absence, a bond, hydrogen, halogen, hydroxyl, amino, -O-, -S-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -NH-, -N(CH3)- or -N(CH2CH3)-; or X2 is selected from absence, a bond, -O- or -N(CH3)-; and / or R2 is selected from absence, a bond, hydrogen or optionally substituted by halogen, hydroxy, amino, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, 3-8 membered heterocycloalkyl, C 6-8 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; Preferably, R2 is selected from the group consisting of absent, hydrogen, C 1-6 Alkyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 aryl, 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; or R2 is selected from the group consisting of not present, C 1-6 Alkyl, C 2-4 Alkynyl or 5-6 membered heterocycloalkyl, wherein the heteroatom is N or O, and the number of heteroatoms is 1 or 2; or R2 is selected from absent, methyl, ethyl, propyl, butyl, ethynyl, piperidinyl, tetrahydropyrrolyl or tetrahydropyranyl; Preferably, R2 is selected from n-propyl; and / or R3 is selected from the group consisting of absent, hydrogen, halogen, hydroxy, amino, nitro, mercapto, cyano, oxo, -R 3b 、-OR 3b 、-SR 3b 、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-N(R 3b )(R 3c )、-C(O)N(R 3b )(R 3c )、-C(O)NH(R 3b )、-NHC(O)(R 3b )、-N(R 3b )C(O)(R 3c )、-S(O)N(R 3b )(R 3c )、-SO2N(R 3b )(R 3c )、-N(R 3b )S(O)(R 3c ) or -N(R 3b )SO2(R 3c ); Preferably, R3 is selected from the group consisting of absent, hydrogen, halogen, hydroxy, amino, oxo, -R 3b 、-OR 3b 、-SR 3b 、-C(O)R 3b 、-C(O)OR 3b 、-OC(O)R 3b 、-N(R 3b )(R 3c )、-C(O)N(R 3b )(R 3c )、-C(O)NH(R 3b ) or -NHC(O)(R 3b ); The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond; More preferably, R3 is selected from the group consisting of absent, -R 3b 、-OR 3b or -N(R 3b )(R 3c ); More preferably, R3 is selected from -N(R 3b )(R 3c ); and / or R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl, 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl, 4-12 membered bicyclic heterocyclyl, or 5-12 membered heteroaryl; Preferably, R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl; More preferably, R 3b , R 3c Each occurrence is independently selected from hydrogen or optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy or 3-10 membered heterocycloalkyl; More preferably, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-6 alkyl; or, More preferably, when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl; More preferably, when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 5-6 membered heterocycloalkyl or 6-10 membered bicyclic heterocyclyl, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1, 2, 3 or 4; The optional substitution refers to optionally being replaced by R 3d replaced by; or R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-4 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 5-6-membered heterocycloalkyl, 3-membered / 6-membered heteromonospirocyclic group, 6-membered / 3-membered heteromonospirocyclic group, 4-membered / 6-membered heteromonospirocyclic group, 6-membered / 4-membered heteromonospirocyclic group or 4-membered / 4-membered heteromonospirocyclic group, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1 or 2; The optional substitution refers to optionally being replaced by R 3d replaced by; and / or R 3d Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, cyano, -R 3e 、-C(O)R 3e 、-C(O)OR 3e 、-N(R 3e )(R 3f ) or -C(O)NH(R 3e );R 3e , R 3f Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached together form an optionally substituted halogen, hydroxyl, amino, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups; Preferably, R 3d Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, cyano, -R 3e 、-C(O)R 3e 、-C(O)OR 3e 、-N(R 3e )(R 3f ) or -C(O)NH(R 3e );R 3e , R 3f Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 3-6 One or more of cycloalkyl, 3-6 membered heterocycloalkyl, C6 aryl or 5-6 membered heteroaryl optionally substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 3-6 membered heterocycloalkyl, C6 aryl or 5-6 membered heteroaryl; More preferably, R 3d Each occurrence is independently selected from deuterium, halogen, hydroxy, amino, cyano, -CHO, -CO(C 1-6 alkyl), -COOH, -COO(C 1-6 Alkyl), -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy or 3-6 membered heterocycloalkyl; More preferably, R 3d Each occurrence is independently selected from deuterium, hydroxyl, amino, -CHO, -CO(C 1-6 alkyl), -COOH, -COO(C 1-6 Alkyl), -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), -C(O)NH2, C 1-6 Alkyl, C 1-6 Alkoxy or 5-6 membered heterocycloalkyl; More preferably, R 3d Each occurrence is independently selected from deuterium, fluorine, hydroxy, amino, cyano, -CHO, -COCH3, -COOH, -COOCH3, -NH(CH3), -N(CH3)(CH3), -C(O)NH2, -CH3, -CH2CH3, -CH2CH2CH3, -OCH3, -OCH2CH3, -OCH2CH2CH3, piperidinyl, piperazinyl or tetrahydropyrrolyl; More preferably, R 3d is independently selected at each occurrence from deuterium, fluorine, amino, cyano, -C(O)NH2, -CH3 or piperidinyl; or R 3d Each occurrence is independently selected from halogen, hydroxy, amino, -R 3e or -N(R 3e )(R 3f );R 3e , R 3f Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 Aryl or 5-12 membered heteroaryl; or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached together form an optionally substituted halogen, hydroxyl, amino, C 1-6 Alkyl, C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-14 One or more arbitrarily substituted 3-10 membered heterocycloalkyl or 5-12 membered heteroaryl groups; Preferably, R 3d Each occurrence is independently selected from -R 3e or -N(R 3e )(R 3f );R 3e , R 3f Each occurrence is independently selected from C 1-6 Alkyl or 3-8 membered heterocycloalkyl, or when R 3e and R 3f When connected to the same nitrogen atom, R 3e and R 3f and the nitrogen atom to which it is attached together form a 3-8 membered heterocycloalkyl group; More preferably, R 3d is selected from methyl, -N(methyl)(methyl) or piperidinyl; and / or R3 is selected from the following optionally substituted groups: The optional substitution refers to optionally being replaced by R 3d replaced by; More preferably, R3 is selected from the following groups: More preferably, R3 is selected from the following groups:

4. The compound according to any one of claims 1 to 3 or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, characterized in that: The compound has a structure as shown in formula (II-a): Among them, m 1-1 Selected from 0, 1 or 2, R 1a-1 As claimed in claim 1, R 1a Defined by X 2-1 As defined in X2 of claim 1, R 2-1 As defined in R2 of claim 1, R 3-1 R3 is as defined in claim 1, and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined in claim 1; Preferably, the compound has a structure as shown in formula (II-a1): wherein R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or Preferably, the compound has a structure as shown in formula (II-a2): Among them, R 3b-1 As claimed in claim 1, R 3b As defined, R 3c-1 As claimed in claim 1, R 3c R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or The compound has a structure as shown in formula (II-b): Among them, m 1-2 is selected from 0, 1, 2 or 3, R 1a-2 As claimed in claim 1, R 1a Defined by X 2-2 As defined in X2 of claim 1, R 2-2 As defined in R2 of claim 1, R 3-2 R3 is as defined in claim 1, and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined in claim 1; Preferably, the compound has a structure as shown in formula (II-b1): Among them, m 1-3 is selected from 0, 1, 2 or 3, R 1a-3 As claimed in claim 1, R 1a R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or The compound has a structure as shown in formula (II-c): Among them, m 1-4 is selected from 0, 1, 2 or 3, R 1a-4 As claimed in claim 1, R 1a Defined by X 2-3 As defined in X2 of claim 1, R 2-3 As defined in R2 of claim 1, R 3-3 R3 is as defined in claim 1, and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined in claim 1; Preferably, the compound has a structure as shown in formula (II-c1): Among them, m 1-5 is selected from 0, 1, 2 or 3, R 1a-5 As claimed in claim 1, R 1a As defined, R 3b-2 As claimed in claim 1, R 3b As defined, R 3c-2 As claimed in claim 1, R 3c R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or The compound has a structure as shown in formula (II-d): Wherein, E1, E2, E3, E4, E5, E6 are independently selected from C or N, m 1-6 is selected from 0, 1, 2, 3 or 4, R 1a-6 As claimed in claim 1, R 1a Defined by X 2-4 As defined in X2 of claim 1, R 2-4 As defined in R2 of claim 1, R 3-4 R3 is as defined in claim 1, and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined in claim 1; Preferably, the compound has a structure as shown in formula (II-d1): Among them, m 1-7 is selected from 0, 1, 2 or 3, R 1a-7 As claimed in claim 1, R 1a As defined, R 3b-3 As claimed in claim 1, R 3b As defined, R 3c-3 As claimed in claim 1, R 3c R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or Preferably, the compound has a structure as shown in formula (II-d2): Among them, m 1-8 Selected from 0, 1 or 2, R 1a-8 As claimed in claim 1, R 1a As defined, R 3b-4 As claimed in claim 1, R 3b As defined, R 3c-4 As claimed in claim 1, R 3c R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or Preferably, the compound has a structure as shown in formula (II-d3): Among them, m 1-9 Selected from 0, 1 or 2, R 1a-9 As claimed in claim 1, R 1a As defined, R 3b-5 As claimed in claim 1, R 3b As defined, R 3c-5 As claimed in claim 1, R 3c R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or Preferably, the compound has a structure as shown in formula (II-d4): Among them, m 1-10 is selected from 0, 1, 2 or 3, R 1a-10 As claimed in claim 1, R 1a As defined, R 3e-1 As claimed in claim 1, R 3e As defined, R 3f-1 As claimed in claim 1, R 3f R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or Preferably, the compound has a structure as shown in formula (II-d5): Among them, m 1-11 is selected from 0, 1, 2 or 3, R 1a-11 As claimed in claim 1, R 1a R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or Preferably, the compound has a structure as shown in formula (II-d6): Among them, m 1-12 is selected from 0, 1, 2 or 3, R 1a-12 As claimed in claim 1, R 1a As defined, R 3b-6 As claimed in claim 1, R 3b As defined, R 3c-6 As claimed in claim 1, R 3c R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or The compound has a structure as shown in formula (II-e): Among them, E7, E8, E9, E 10 、E 11 、E 12 are independently selected from C or N, m 1-13 Selected from 0, 1, 2 or 3, m 2-1 is selected from 0, 1, 2, 3 or 4, R 1a-13 As claimed in claim 1, R 1a As defined, R 2a-1 As claimed in claim 1, R 2a As defined, R 3-5 R3 is as defined in claim 1, and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined in claim 1; Preferably, the compound has a structure as shown in formula (II-e1): Among them, m 1-14 Selected from 0, 1, 2 or 3; m 2-2 is selected from 0, 1, 2, 3 or 4, R 1a-14 As claimed in claim 1, R 1a As defined, R 2a-2 As claimed in claim 1, R 2a As defined, R 3b-7 As claimed in claim 1, R 3b As defined, R 3c-7 As claimed in claim 1, R 3c R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or The compound has a structure as shown in formula (II-f): Among them, m 1-15 is selected from 0, 1, 2 or 3, R 1a-15 As claimed in claim 1, R 1a As defined, R 3e-2 As claimed in claim 1, R 3e As defined, R 3f-2 As claimed in claim 1, R 3f R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or The compound has a structure as shown in formula (II-g): Among them, R 3b-8 As claimed in claim 1, R 3b As defined, R 3c-8 As claimed in claim 1, R 3c R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; or The compound has a structure as shown in formula (III-a): Among them, m 1-16 is selected from 0, 1, 2 or 3, R 1a-16 As claimed in claim 1, R 1a As defined, R 3b-9 As claimed in claim 1, R 3b As defined, R 3c-9 As claimed in claim 1, R 3c As defined, R4, R5, R6, R7, R8, R9, R 10 , R 11 , W, L, t1, t2 as defined in claim 1; Preferably, the compound has a structure as shown in formula (III-a1): Among them, m 1-17 is selected from 0, 1, 2 or 3, R 1a-17 As claimed in claim 1, R 1a As defined, R 3b-10 As claimed in claim 1, R 3b As defined, R 3c-10 As claimed in claim 1, R 3c As defined, R4, R5, R8, R9, R 10 , R 11 , L as defined in claim 1; Preferably, the compound has a structure as shown in formula (III-a2): Among them, m 1-18 is selected from 0, 1, 2 or 3, R 1a-18 As claimed in claim 1, R 1a As defined, R 3b-11 As claimed in claim 1, R 3b As defined, R 3c-11 As claimed in claim 1, R 3c As defined, R4, R5, R7, R8, R9, R 10 , R 11 , L as defined in claim 1.

5. The compound according to any one of claims 1 to 4, or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, characterized in that: R 1a independently selected from -H, -F, -Cl, -NH2, oxo, -CH3, -CH2CH3, -OCH3, -OCH2CH3, -NHC(O)CH3, -C(O)NHCH3, The oxo group refers to two H groups at the same substitution site being replaced by the same O group to form a double bond; and / or Y is selected from the following groups: Preferably, Y is selected from the following groups: and / or R4 is selected from hydrogen, halogen, amino or C 1-6 Alkoxy; or R4 is selected from hydrogen, fluorine or methoxy; and / or R5 is selected from hydrogen, deuterium or C optionally substituted by one or more deuterium 1-6 alkyl; Preferably, R5 is C 1-6 Alkyl; or R5 is methyl; and / or L is C(R L ) or N, R L Selected from hydrogen, halogen, amino, hydroxyl, C 1-6 Alkyl or C 1-6 Alkoxy; or L is C(R L ), R L is selected from hydrogen, halogen, amino, methyl or methoxy; Preferably, L is CH; and / or W, Q1, Q2 are independently selected from O, C, S or N; Q3 is C; wherein Q1 is connected to W; Preferably, W, Q1, Q2 are independently selected from O, C or S; Q3 is C; wherein Q1 is connected to W; More preferably, W is selected from O or N; Q1 is C; Q2 is C; Q3 is C; wherein Q1 is connected to W; and / or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxyl, amino, cyano, -R 6a 、-OR 6a 、-SO2(R 6a )、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b )、-SO2NH(R 6a )、-SO2N(R 6a )(R 6b )、-NHSO2(R 6a ) or -N(R 6a )SO2(R 6b ); or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a or W, each occurrence of Q1, each occurrence of Q2 and Q3, any two adjacent atoms and the substituents to which they are attached together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q1, each occurrence of Q2 and Q3 and any one of the substituents attached thereto together form an optionally substituted R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group or heteromonospirocyclic group; Preferably, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, cyano, -R 6a 、-OR 6a 、-SO2(R 6a )、-C(O)R 6a 、-C(O)OR 6a 、-OC(O)R 6a 、-NH(R 6a )、-N(R 6a )(R 6b )、-C(O)NH(R 6a )、-C(O)N(R 6a )(R 6b )、-NHC(O)(R 6a )、-N(R 6a )C(O)(R 6b )、-SO2NH(R 6a )、-SO2N(R 6a )(R 6b )、-NHSO2(R 6a ) or -N(R 6a )SO2(R 6b ); or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a or W, each occurrence of Q1, each occurrence of Q2 and Q3, any two adjacent atoms and the substituents to which they are attached together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q1, each occurrence of Q2 and Q3 and any one of the substituents attached thereto together form an optionally substituted R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, monospirocyclic group or heteromonospirocyclic group; or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, -R 6a 、-NH(R 6a ) or -N(R 6a )(R 6b ); or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a or W, each occurrence of Q1, each occurrence of Q2 and Q3, any two adjacent atoms and the substituents to which they are attached together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q1, each occurrence of Q2 and Q3 and any one of the substituents attached thereto together form an optionally substituted R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl; or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, -R 6a 、-NH(R 6a ) or -N(R 6a )(R 6b ); or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O, =NR 6a or =CH-R 6a or W, each occurrence of Q1, each occurrence of Q2 and Q3, any two adjacent atoms and the substituents to which they are attached together form an optionally R 6c Substituted C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or W, each occurrence of Q1, each occurrence of Q2 and Q3 and any one of the substituents attached thereto together form an optionally substituted R 6c Substituted C 3-10 Carbocyclic group or 3-10 membered heterocyclic group; Preferably, W, each occurrence of Q1, each occurrence of Q2 and any one of Q3 and the substituents attached thereto together form an optionally R 6c Substituted C 3-6 Cycloalkyl or 3-7 membered heterocycloalkyl; More preferably, W, each occurrence of Q1, each occurrence of Q2 and Q3 and any one of the substituents attached thereto together form a 6c Substituted C 3-4 Cycloalkyl; and / or R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or when R 6a and R 6b When connected to the same nitrogen atom, R 6a and R 6b and the nitrogen atom to which it is attached together form an optionally R 6c substituted 3-10 membered heterocyclyl or 5-12 membered heteroaryl; or R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl or 5-10 membered heteroaryl; Preferably, R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c Substituted C 1-3 Alkyl or C 1-3 Alkoxy; More preferably, R 6a , R 6b Each occurrence is independently selected from hydrogen or optionally replaced by R 6c a substituted methyl or ethyl group; and / or R 6c Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxyl, amino, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e or-C(O)OR 6d ; Preferably, R 6c Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, -R 6d 、-OR 6d 、-N(R 6d )R 6e 、-C(O)R 6d 、-C(O)N(R 6d )R 6e 、-N(R 6d )C(O)R 6e or-C(O)OR 6d ; and / or R 6d , R 6e Each occurrence is independently selected from hydrogen, halogen, hydroxy, amino, nitro, cyano or optionally substituted with halogen, hydroxy, amino or C 1-6 Alkyl substituted C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 aryl, 5-12 membered heteroaryl, fused cyclic group or heterofused cyclic group; or when R 6d and R 6e When connected to the same nitrogen atom, R 6d and R 6e and the nitrogen atom to which it is attached together form an optionally substituted halogen, hydroxyl, amino or C 1-6 Alkyl-substituted 3-10 membered heterocyclic group or 5-12 membered heteroaryl group; and / or R 6d , R 6e Each occurrence is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl or 5-10 membered heteroaryl; and / or R 6c Each occurrence is independently selected from hydrogen, fluorine, chlorine, hydroxyl, amino, -NH(C 1-6 alkyl), -N(CH3)(C 1-6 alkyl), -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 Aryl or 5-10 membered heteroaryl; Preferably, R 6c Each occurrence is independently selected from hydrogen, deuterium, halogen, hydroxyl, amino, C 1-6 Alkyl or C 1-6 Alkoxy; More preferably, R 6c is independently selected at each occurrence from hydrogen, fluorine, chlorine, hydroxy, amino, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy or isopropoxy; and / or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen, deuterium or optionally deuterated, halogen, hydroxyl, amino, C 1-6 Alkyl, C 1-6 Alkoxy, -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 3-6 C substituted with cycloalkyl, 5-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, 9-10 membered bicyclic heterocyclyl or 9-10 membered bicyclic heteroaryl 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 5-6 membered heterocycloalkyl, C 6-8 Aryl, 5-6 membered heteroaryl, 9-10 membered bicyclic heterocyclyl or 9-10 membered bicyclic heteroaryl; Preferably, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 1-6 Alkoxy, -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 Alkyl), -NHC(O)(C 1-6 alkyl), -C(O)O(C 1-6 Alkyl), C 3-6 C substituted with cycloalkyl, 5-6 membered heterocycloalkyl, phenyl or 5-6 membered heteroaryl 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 5-6 membered heterocycloalkyl, C 6-8 Aryl or 5-6 membered heteroaryl; More preferably, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-6 Alkyl, C 1-6 Alkoxy substituted C 1-6 Alkyl or C 1-6 Alkoxy; More preferably, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from hydrogen or optionally substituted by halogen, hydroxy, amino, C 1-3 Alkyl or C 1-3 Alkoxy substituted C 1-3 Alkyl or C 1-3 Alkoxy; More preferably, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from the following groups: -H, -F, -Cl, -OH, -NH2, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)CH3, -CH2CH(CH3)CH3, -CH2OH, -CH2CH2OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)CH3, -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3, -CH2CH2CH2OCH3, -CH(CH3)CH2OCH3, -NHCH3, -N(CH3)CH3, -CH2N(CH3)CH3, More preferably, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Each occurrence is independently selected from the following groups: -H, -F, -Cl, -OH, -NH2, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)CH3, -CH2CH(CH3)CH3, -CH2OH, -CH2CH2OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH(CH3)CH3, -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3, -NHCH3, -N(CH3)CH3, -CH2N(CH3)CH3, More preferably, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 is independently selected at each occurrence from the group consisting of -H, -F, -Cl, -OH, -NH2, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)CH3, -CH2OCH3, -CH2CH2OCH3, -CH2CH2CH2OCH3, or -CH(CH3)CH2OCH3; or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two groups connected to the same atom form =O or =CH2; and / or W, each occurrence of Q1, each occurrence of Q2 and Q3, any two adjacent atoms and the substituents to which they are attached together form the following group: or W, each occurrence of Q1, each occurrence of Q2 and any one of Q3 and the substituents attached thereto together form the following group: Preferably, W, each occurrence of Q1, each occurrence of Q2 and any one of Q3 and the substituents attached thereto together form the following group:

6. The compound according to any one of claims 1 to 5, or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, characterized in that: R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-6 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 3-10 membered heterocycloalkyl; Preferably, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-4 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached together form an optionally substituted 5-6 membered heterocycloalkyl or 6-10 membered bicyclic heterocyclyl, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1, 2 or 3; More preferably, R 3b , R 3c Each occurrence is independently selected from optionally substituted C 1-4 Alkyl; or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted 5-6-membered heterocycloalkyl, a 3-membered / 6-membered heteromonospirocyclic group, a 4-membered / 6-membered heteromonospirocyclic group or a 3-membered / 5-membered heterocyclic group, wherein the heteroatoms are independently selected from O or N, and the number of heteroatoms is 1, 2 or 3; The optional substitution refers to optionally being replaced by R 3d replaced by; or R 3b , R 3c Each occurrence is independently selected from optionally substituted methyl, or when R 3b and R 3c When connected to the same nitrogen atom, R 3b and R 3c and the nitrogen atom to which it is attached form an optionally substituted pyrrolidinyl, piperazinyl, piperidinyl, 2-oxa-7-azaspiro[3.5]nonyl, 3-azabicyclo[3.1.0]hexyl or 6-azaspiro[2.5]octyl; The optional substitution refers to optionally being replaced by R 3d replaced by; Optionally, R 3d Each occurrence is independently selected from deuterium, fluorine, hydroxyl, amino, cyano, -NH(CH3), -N(CH3)(CH3), -C(O)NH2, -CH3, -CH2CH3 or -CH2CH2CH3; preferably, R 3d is independently selected at each occurrence from deuterium, fluorine, cyano, -C(O)NH2 or -CH3; or R 3b and R 3c and the nitrogen atom to which it is connected together form a group selected from the following groups:

7. The following compound or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt:

8. A pharmaceutical composition comprising the compound according to any one of claims 1 to 7 or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt.

9. Use of the compound according to any one of claims 1 to 7 or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt or the pharmaceutical composition according to claim 8 in the preparation of a medicament for preventing and / or treating cancer; Preferably, the cancer includes solid tumors and hematological tumors; more preferably, the cancer includes breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, small cell lung cancer, glioblastoma.

10. A drug combination composition or a drug compound composition or a drug combination form, wherein the pharmaceutical combination composition or pharmaceutical compound composition comprises a compound according to any one of claims 1 to 7 or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof or a pharmaceutical composition according to claim 8 and at least one additional anti-tumor agent; and the pharmaceutical combination form comprises a compound according to any one of claims 1 to 7 or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof or a pharmaceutical composition according to claim 8, and at least one additional anti-tumor agent or therapeutic means; Preferably, the anti-tumor agent is selected from doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan, bleomycin, cisplatin, oxaliplatin, carboplatin, valrubicin, idarubicin, pirarubicin, amrubicin, epirubicin, olaparib, MEDI4736, AZD1775 and AZD6738; Preferably, the treatment is radiotherapy.

11. An intermediate compound selected from the compounds represented by formula (M-1), (M-2), (M-3), (M-4), (M-5), and (M-6), or selected from the compounds represented by formula I-a1, I-b1, I-a2, I-b2, I-a3, I-a4, I-a4', I-b4, I-a5, I-b5, I-a6, I-b6, I-a7, and I-a8;or selected from intermediate compounds M-1, M-2, M-3, M-4, M-5, M-6, M-7, M-8, M-9, M-10, M-11, M-12, M-13, M-14, M-15, M-16, M-17, M-18, M-19, M-20, M-21, M-22, M-23, M-24, M-25, M-26, M-27, M-28, M-29, M-30, M-31, M-32, M-33, M-34, M-35, M-36, M-37, M-38, M-39, M-40, M-1-1, M-1-2, M-1-3, M-1-4, M-1-5, M-1-6, M-28-1, M-28-2, M-28-3, M-28-4, M-28-5, M-28-6, M-31-1, M-31-2, M-31-3, M-31-4, M-48-1, M-41, M-42, M-43, M-44, M-45, M-46, M-47, M-48, M-49, M-50, M-51, M-52, M-53, M-54, M-55, M-56, M-57, M-58, M-59, M-60, A-1-1, A-3-1, A-5-1, A-6-1, A-7-1, A-8-1, A-9-1, A-10-1, A-11-1, A-12-1, A-13-1, A-14-1, A-15-1, A-16-1, A-17-1, A-18-1, A-19-1, A-20-1, A-21-1, A-22-1, A-23-1, A-24-1, A-27-1, A-28-1, A-31-1, A-32-1, A-41-1, A-41-2, A-42-1, A-43-1, A-49-1, A-52-1, A-56-1, A-67-1, A-67-2, A-146-1, A-146-2, A-148-1, A-148-2, A-155-1, A-155-2, A-176-1, A-176-2, A-176-3, A-176-4, A-181-1, A-181-2, A-183-1, A-183-2, A-190-1, A-190-2, A-190-3, A-190-4, A-190-5, A-194-1, A-197-1, A-197-2, A-197-3, A-197-4, A-197-5, A-197-6, A-200-1, A-201-1, A-204-1, A-204-2, A-205-1, A-205-2, A-211-1, and A-211-2:; in, R x1 is selected from halogen or hydrogen, R4, R6, R7, A, W, L, t1, t2, h are as defined in any one of claims 1 to 8; Among them, R x2 is selected from halogen or hydrogen, R4, R6, R7, A, W, L, t1, t2, h are as defined in any one of claims 1 to 8; Among them, R x3 is selected from halogen or hydrogen, R4, R5, R6, R7, A, W, L, t1, t2, h are as defined in any one of claims 1 to 8; Among them, R x4 is selected from halogen or hydrogen, R4, R5, R6, R7, A, W, L, t1, t2, h are as defined in any one of claims 1 to 8; Among them, R x1 is selected from halogen or hydrogen, X1, R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1; 12. A method for preparing the compound of formula (I) according to claim 1, which is selected from any one of the following synthesis schemes: Synthesis Scheme 1: i) Compound I-a1 undergoes chemical conversion to obtain compound I-a2; ii) Compound I-a2 undergoes chemical conversion to obtain compound I-a4; iii) Compound I-a4 undergoes chemical transformation to obtain Compound I-a5; iv) Compound I-a5 undergoes chemical transformation to obtain Compound I-a6; v) Compound I-a6 undergoes chemical transformation to obtain compound I-a7; vi) Compound I-a7 is chemically transformed to obtain compound I-a8; vii) Compound I-a8 is chemically transformed to obtain a compound of formula I; Synthesis Scheme 2: i) using compound I-b1 as the basic raw material to obtain compound I-b2; ii) using compounds I-b2 and I-b3 as basic raw materials to obtain compound I-b4; iii) using compound I-b4 as a basic raw material to obtain compound I-b5; iv) using compound I-b5 as the basic raw material to obtain compound I-b6; v) using compound I-b6 as the basic raw material to obtain compound I-b7; vi) using compound I-b7 as the basic raw material to obtain compound I-b8; vii) using compound I-b8 as a basic raw material to obtain compound I-b9; viii) using compound I-b9 as a basic raw material to obtain a compound of formula I; Synthesis Scheme 3: i) using compound I-b1 as the basic raw material to obtain compound I-b2; ii) using compounds I-b2 and I-b3 as basic raw materials to obtain compound I-b5; iii) using compound I-b5 as a basic raw material to obtain compound I-b6; iv) using compound I-b6 as the basic raw material to obtain compound I-b7; v) using compound I-b7 as the basic raw material to obtain compound I-b8; vi) using compound I-b8 as the basic raw material to obtain compound I-b9; vii) using compound I-b9 as a basic raw material to obtain a compound of formula I; Among them, R x1 is selected from halogen or hydrogen, and X1, R4, R5, R6, R7, A, W, L, t1, t2 are as defined in claim 1.

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