Fused ring compound and preparation and use thereof

Abstract

To provide a compound having a novel structure and being an ATM kinase inhibitor.SOLUTION: The present invention relates to a fused ring compound represented by the following formula (I') and to the preparation and use thereof. The compound can significantly inhibit ATM kinase activity, has excellent selectivity for the ATM target, and is useful as a therapeutic agent for cancer.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This invention claims priority to patent application No. 202011044828.9, entitled "Fused Ring Compounds and Their Preparation and Use," filed in China on September 28, 2020, and patent application No. 202110905531.5, entitled "Fused Ring Compounds and Their Preparation and Use," filed in China on August 5, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present invention falls within the field of pharmaceutical technology, and specifically relates to novel compounds having ATM protein kinase inhibitory activity and the use of said compounds or pharmaceutical compositions for producing medicaments. [Background technology]

[0003] Hereditary ataxia-telangiectasia (AT) is an autosomal recessive genetic disease. Its clinical symptoms include progressive cerebellar ataxia, facial telangiectasia, increased sensitivity to radiation exposure, and a significantly increased tendency to develop tumors (Non-Patent Document 1). It is currently known to be caused by mutations in the ataxia-telangiectasia mutated gene (ATM gene). The ATM gene, located on chromosome 11q22-23, is 150 kb long and contains 66 exons, making it one of the human genes with the largest number of exons discovered to date (Non-Patent Document 2). ATM protein kinase, encoded by the ATM gene, is a serine-threonine protein kinase containing 3,056 amino acids and a relative molecular mass of approximately 350 kDa (Non-Patent Document 3). It is a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family (Non-Patent Document 4). It is localized in the nucleus and cytoplasm and is widely present in tissues and cells of higher eukaryotes, and is highly expressed in tissues and cells such as the testis, spleen, and thymus. ATM is involved in cell cycle regulation and DNA damage recognition and repair via its C-terminal functional domain. Its functions in cell signaling pathways include cell cycle checkpoint activation (Non-Patent Document 5), regulation of DNA damage repair (Non-Patent Document 6), regulation of telomeres (Non-Patent Document 7), and regulation of apoptosis (Non-Patent Document 8).

[0004] ATM protein kinase primarily repairs DNA double-strand breaks and maintains DNA stability by inducing phosphorylation of downstream effectors. When cells are exposed to ionizing or ultraviolet radiation, resulting in DNA double-strand breaks (DSBs), the MRE11-RAD50-NBS1 (MRN) complex senses the DSBs, initiates DNA repair, and recruits ATM protein kinase. ATM protein kinase acts as a key sensor during DSB repair, recruiting and interacting with other proteins. ATM homodimers dissociate into active monomers at DSB sites and are catalytically activated by autophosphorylation and acetylation. It cooperates with other proteins to promote repair of broken DNA (Non-Patent Document 9).

[0005] ATM also regulates the cell cycle via the Chk2-p53 / AKT pathway, thereby affecting tumor cell proliferation and apoptosis (Non-Patent Document 10). Activated ATM also affects tumor development, metastasis, and invasion via the ATM-Akt-GSK-3β pathway, the transcriptional regulator NF-κB, and interleukin IL-8, and is involved in DNA damage responses through various mechanisms, thereby enhancing tumor cell drug resistance and resistance to radiation therapy and chemotherapy (Non-Patent Document 11).

[0006] Currently, ATM inhibitors in clinical trials are often used in combination with radiation therapy or chemotherapy. Investigational molecules include AstraZeneca's AZD-1390 and Merck's M-3541. The diseases that can be treated with ATM kinase inhibitors are solid tumors or hematological tumors. [ka] [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] Taylor AM, Harnden DG, Arlett CF, et al.Ataxia telangiectasia:ahumanmutation with abnormal radiation sensitivity.Nature,1975,258:427-429 [Non-patent document 2] Savitsky K, Bar Shira A, Gilad S, et al.A single ataxia telangiectasiagene with a product similar to PI-3 kinase.Science,1995,268 (5218):1749-1753 [Non-patent document 3] CHEN G,LEE E.The product of the ATMgene is a 370-kDa nuclear phosphoprotein.J Biol Chem,1996,271(52):33693-33697 [Non-patent document 4] Watters D,Khanna KK,Beamish H,et al.Cellular localization of the ataxia-telangiectasia (ATM) gene product and discrimination between mutated and normal forms.Oncogene,1997,14:1911-1921

Direct Environment 5

Outdoor Configuration6

Direct Environment 7

Outdoor Track 8

Outdoor Tools9

[0008] [Fused ring compounds] The present invention provides compounds that have a novel structure and are ATM kinase inhibitors. [Means for solving the problem]

[0009] Specifically, the present invention provides a compound represented by formula (I') having the following structure: or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof: [ka] (In the formula, Y is [ka] and X1 is a bond, hydrogen, deuterium, halogen, hydroxyl group, amino group, nitro group, cyano group, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-, -C(O)N(R 1x )- or -N(R 1x )-, and R 1x is hydrogen or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 The term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond; When X1 is hydrogen, deuterium, halogen, hydroxyl group, amino group, nitro group or cyano group, R1, X2, R2 and R3 are absent; R1 is absent, a bond, hydrogen, deuterium, or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10Cycloalkyl groups, 3-10 membered heterocyclic groups, C 6-14 The "optionally substituted" group is selected from an aryl group, a 5- to 12-membered heteroaryl group, a 4- to 12-membered bridged ring group, a 4- to 12-membered heterobridged ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, and a heterofused ring group, and the "optionally substituted" group means that a hydrogen atom in the substituted group is not substituted, or a hydrogen atom in one or more substitutable positions in the substituted group is independently substituted by R 1a means that it is replaced by R 1a are, when present, independently deuterium, halogen, hydroxyl, 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 ) and R 1b , R 1c are, when present, independently hydrogen, deuterium, or optionally deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 C optionally substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 1b and R 1c When R is attached to the same nitrogen atom, 1b and R 1c together with the nitrogen atom to which they are bonded, optionally deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted by one or more of an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means a group in which two H's at the same substitution position are replaced by one O to form a double bond; When R1 is hydrogen or deuterium, X2, R2 and R3 are absent; X2 is absent, a bond, hydrogen, deuterium, a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, -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 hydrogen, deuterium, or optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 The term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond; When X2 is hydrogen, deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group or cyano group, R2 and R3 are absent; R2 is absent, a bond, hydrogen, deuterium, or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, C 6-14The "optionally substituted" group is selected from an aryl group, a 3- to 10-membered heterocycloalkyl group, a 5- to 12-membered heteroaryl group, a 4- to 12-membered bridged ring group, a 4- to 12-membered heterobridged ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, and a heterofused ring group, and the "optionally substituted" group means that a hydrogen atom in the substituted group is not substituted, or that a hydrogen atom in one or more substitutable positions in the substituted group is independently substituted by R 2a means that it is replaced by R 2a are, when present, independently deuterium, halogen, hydroxyl, 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 ) and R 2b , R 2c are, when present, independently optionally deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, C 1-6 Alkyl group, C 1-6Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 hydrogen optionally substituted by one or more of an aryl group or a 5- to 12-membered heteroaryl group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5- to 12-membered heteroaryl group, or R 2b and R 2c When R is attached to the same nitrogen atom, 2b and R 2c together with the nitrogen atom to which they are bonded, optionally deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted by one or more of an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means a group in which two H's at the same substitution position are replaced by one O to form a double bond; When R2 is hydrogen or deuterium, R3 is absent; R3 is absent, hydrogen, deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, -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 )(R3c ), -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 ) and R 3b , R 3c When present, each independently represents hydrogen, deuterium, or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted 3- to 20-membered heterocyclic group or a 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with R 3d means that it is replaced by R 3d are, when present, independently deuterium, halogen, hydroxyl, 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 ) and R 3e , R 3f When present, each independently represents hydrogen, deuterium, or optionally a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 C optionally substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R3e and R 3f When R is attached to the same nitrogen atom, 3e and R 3f together with the nitrogen atom to which they are bonded, optionally deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted by one or more of an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means a group in which two H's at the same substitution position are replaced by one O to form a double bond; R4, when present, is independently hydrogen, deuterium, halogen, nitro group, amino group, cyano group, hydroxyl group, carboxy group, mercapto group, or C optionally substituted with one or more deuterium, halogen, hydroxyl group, or amino group. 1-6 Alkyl group, C 1-6 Alkoxy group or C 1-6 alkylmercapto groups, h is 1 or 2; R5, when present, is independently hydrogen, deuterium, halogen, hydroxyl, or C optionally substituted by one or more deuterium, halogen, hydroxyl, amino, or cyano groups. 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Alkylmercapto group, C 3-10 Cycloalkyl groups, C 6-14 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 12-membered heteroaryl group; L is C(R L ) or N, R L are, when present, independently hydrogen, deuterium, halogen, nitro group, amino group, cyano group, hydroxyl group, carboxy group, mercapto group, C 1-6 Alkyl group, C1-6 Alkoxy group or C 1-6 alkylmercapto groups, A is, [ka] and where: [ka] represents a single bond or a double bond, Q1 is bonded to W, t1, t2, t3, t4, t5, and t6 are independently 0 or 1; n1 and n2 are independently 0, 1 or 2, and n1 and n2 are not simultaneously 0, wherein n1 represents that n1 Q1s are bonded in sequence, n2 represents that n2 Q2s are bonded in sequence, two adjacent Q1s are bonded to each other by a single bond or a double bond, and two adjacent Q2s are bonded to each other by a single bond or a double bond; W, Q1, and Q2 are independently selected from C, O, N, or S; Q3 is C, and when one of the bonds in 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 are, when present, independently hydrogen, deuterium, halogen, hydroxyl, 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 bonded to the same atom are both =O and =NR 6a or =CH-R 6a or any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which it is bonded, optionally forms an aryl group, a 5- to 12-membered heteroaryl group, a 4- to 12-membered bridged ring group, a 4- to 12-membered heterobridged ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, or a fused heterocyclic ring group; 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 forming an aryl group, a 5- to 12-membered heteroaryl group, a monocyclic spiro ring group, or a monocyclic heterospiro ring group, R 6a , R 6b are, when present, independently hydrogen, deuterium, or optionally R 6c C may be substituted by 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 an aryl group, a 5- to 12-membered heteroaryl group, a 4- to 12-membered bridged ring group, a 4- to 12-membered heterobridged ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, or a heterofused ring group; or R 6a and R 6b When R is attached to the same nitrogen atom, 6a and R 6b together with the nitrogen atom to which they are attached, optionally R 6c and forming a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group optionally substituted by R 6c are, when present, independently hydrogen, deuterium, halogen, hydroxyl, 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 means that two H's at the same substitution position are replaced by one O to form a double bond, and the ═NR 6d means that two H's at the same substitution position are replaced by one N to form a double bond, and N is R 6d and the ═CH—R 6dmeans that two H's at the same substitution position are replaced by one C to form a double bond, and C is R 6d means replaced by R 6d , R 6e When present, each independently represents hydrogen, deuterium, halogen, hydroxyl, amino, nitro, cyano, or an optionally substituted C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 an aryl group, a 5- to 12-membered heteroaryl group, a monocyclic spirocyclic group, a monocyclic heterospirocyclic group, a fused ring group, or a heterofused ring group; or R 6d and R 6e When R is attached to the same nitrogen atom, 6d and R 6e together with the nitrogen atom to which they are bonded, form an optionally substituted 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with R 6f means that it is replaced by R 6f are, when present, independently hydrogen, deuterium, halogen, hydroxyl, 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 group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means a group in which two H's at the same substitution position are replaced by one O to form a double bond; When heterocycloalkyl, heteroaryl, heterocyclic, monocyclic heterospirocyclic, fused heterocyclic and / or bridged heterocyclic groups are present, the heteroatoms are independently selected from O, N or S, and the number of said heteroatoms is 1, 2, 3 or 4.

[0010] The present invention further provides a compound represented by formula (I) having the following structure: or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof: [ka] (In the formula, Y is [ka] and X1 is a bond, hydrogen, halogen, hydroxyl group, amino group, nitro group, cyano group, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -N(R 1x )C(O)-, -C(O)N(R 1x )- or -N(R 1x )-, and R 1x is hydrogen or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14The term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond; When X1 is hydrogen, halogen, a hydroxyl group, an amino group, a nitro group, or a cyano group, R1, X2, R2, and R3 are absent; R1 is absent, a bond, hydrogen, or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 The "optionally substituted" group is selected from an aryl group, a 5- to 12-membered heteroaryl group, a 4- to 12-membered bridged ring group, a 4- to 12-membered heterobridged ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, and a heterofused ring group, and the "optionally substituted" group means that a hydrogen atom in the substituted group is not substituted, or a hydrogen atom in one or more substitutable positions in the substituted group is independently substituted by R 1a means that it is replaced by R 1a When present, each independently represents a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, -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 ) and R 1b , R 1c When present, each independently represents hydrogen or optionally a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 C optionally substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 1b and R 1c When R is attached to the same nitrogen atom, 1b and R1c together with the nitrogen atom to which they are bonded, optionally a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted by one or more of an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means a group in which two H's at the same substitution position are replaced by one O to form a double bond; When R1 is hydrogen, X2, R2 and R3 are absent; X2 is absent, a bond, hydrogen, a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, -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 hydrogen or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 The term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl group, C1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond; When X2 is hydrogen, halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, or a cyano group, R2 and R3 are absent; R2 is absent, a bond, hydrogen, or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, C 6-14 The "optionally substituted" group is selected from an aryl group, a 3- to 10-membered heterocycloalkyl group, a 5- to 12-membered heteroaryl group, a 4- to 12-membered bridged ring group, a 4- to 12-membered heterobridged ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, and a heterofused ring group, and the "optionally substituted" group means that a hydrogen atom in the substituted group is not substituted, or that a hydrogen atom in one or more substitutable positions in the substituted group is independently substituted by R 2a means that it is replaced by R 2a When present, each independently represents a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, -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 ) and R 2b , R 2c When present, each independently represents an optional halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 hydrogen optionally substituted by one or more of an aryl group or a 5- to 12-membered heteroaryl group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5- to 12-membered heteroaryl group, or R 2b and R 2c When R is attached to the same nitrogen atom, 2b and R 2c together with the nitrogen atom to which they are bonded, optionally a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted by one or more of an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means a group in which two H's at the same substitution position are replaced by one O to form a double bond; When R2 is hydrogen, R3 is absent; R3 is absent, hydrogen, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, -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 ) and R 3b , R 3c are, when present, independently hydrogen or optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with R 3d means that it is replaced by R 3d When present, each independently represents a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, -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 ) and R 3e , R3f When present, each independently represents hydrogen or optionally a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 C optionally substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 3e and R 3f When R is attached to the same nitrogen atom, 3e and R 3f together with the nitrogen atom to which they are bonded, optionally a halogen, a hydroxyl group, an amino group, a nitro group, a mercapto group, a cyano group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted by one or more of an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means a group in which two H's at the same substitution position are replaced by one O to form a double bond; R4 is hydrogen, halogen, nitro group, amino group, cyano group, hydroxyl group, carboxy group, mercapto group, or C optionally substituted with halogen, hydroxyl group or amino group. 1-6 Alkyl group, C 1-6 Alkoxy group or C 1-6 alkylmercapto groups, R5 is hydrogen, halogen, hydroxyl, or C optionally substituted with one or more halogens, hydroxyl, amino, or cyano groups. 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Alkylmercapto group, C 3-10 Cycloalkyl groups, C 6-14 selected from an aryl group, a 3- to 10-membered heterocycloalkyl group, and a 5- to 12-membered heteroaryl group; L is C(R L ) or N, R L is hydrogen, halogen, nitro group, amino group, cyano group, hydroxyl group, carboxy group, mercapto group, C 1-6 Alkyl group, C 1-6 Alkoxy group or C 1-6 alkylmercapto groups, A is, [ka] and where: [ka] represents a single bond or a double bond, Q1 is bonded to W, t1, t2, t3, t4, t5, and t6 are independently 0 or 1; n1 and n2 are independently 0, 1 or 2, and n1 and n2 are not simultaneously 0, wherein n1 represents that n1 Q1s are bonded in sequence, n2 represents that n2 Q2s are bonded in sequence, two adjacent Q1s are bonded to each other by a single bond or a double bond, and two adjacent Q2s are bonded to each other by a single bond or a double bond; W, Q1, and Q2 are independently selected from C, O, N, or S; Q3 is C, and when one of the bonds in Q3 is a double bond, R 10 or R 11 does not exist, R6, R7, R8, R9, R 10 , R 11 , R 12 and R13 are, when present, independently hydrogen, halogen, hydroxyl, 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 bonded to the same atom are both =O and =NR 6a or =CH-R 6a or any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which it is bonded, optionally forms an aryl group, a 5- to 12-membered heteroaryl group, a 4- to 12-membered bridged ring group, a 4- to 12-membered heterobridged ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, or a fused heterocyclic ring group; 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 forming an aryl group, a 5- to 12-membered heteroaryl group, a monocyclic spiro ring group, or a monocyclic heterospiro ring group, R 6a , R 6b is, when present, independently hydrogen or optionally R 6c C may be substituted by 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 an aryl group, a 5- to 12-membered heteroaryl group, a 4- to 12-membered bridged ring group, a 4- to 12-membered heterobridged ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, or a heterofused ring group; or R 6a and R 6b When R is attached to the same nitrogen atom, 6a and R 6b together with the nitrogen atom to which they are attached, optionally R 6c and forming a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group optionally substituted by R 6c are, when present, independently hydrogen, halogen, hydroxyl, 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)R6d , -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 means that two H's at the same substitution position are replaced by one O to form a double bond, and the ═NR 6d means that two H's at the same substitution position are replaced by one N to form a double bond, and N is R 6d and the ═CH—R 6d means that two H's at the same substitution position are replaced by one C to form a double bond, and C is R 6d means replaced by R 6d , R 6e When present, each independently represents a hydrogen atom, a halogen atom, a hydroxyl group, an amino group, a nitro group, a cyano group, or an optionally substituted C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 an aryl group, a 5- to 12-membered heteroaryl group, a monocyclic spirocyclic group, a monocyclic heterospirocyclic group, a fused ring group, or a heterofused ring group; or R 6d and R 6e When R is attached to the same nitrogen atom, 6d and R 6e together with the nitrogen atom to which they are bonded, form an optionally substituted 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with R 6f means that it is replaced by R6f are, when present, independently hydrogen, halogen, hydroxyl, 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 group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means a group in which two H's at the same substitution position are replaced by one O to form a double bond; When heterocycloalkyl, heteroaryl, heterocyclic, monocyclic heterospirocyclic, fused heterocyclic and / or bridged heterocyclic groups are present, the heteroatoms are independently selected from O, N or S, and the number of said heteroatoms is 1, 2, 3 or 4.

[0011] Preferably, the present invention provides a compound having a structure represented by Formula (Ia) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (wherein each substituent is as defined in the compound of formula (I') or formula (I)).

[0012] Preferably, the present invention provides a compound having a structure represented by Formula (Ib), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (wherein each substituent is as defined in the compound of formula (I') or formula (I)).

[0013] Preferably, the present invention provides a compound having a structure represented by Formula (Ic) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (wherein each substituent is as defined in the compound of formula (I') or formula (I)).

[0014] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, X1 is a bond, hydrogen, halogen, a hydroxyl group, an amino group, a nitro group, a cyano group, —O—, —S—, —C(O)—, —C(O)O—, —OC(O)—, —N(R 1x )C(O)-, -C(O)N(R 1x )- or -N(R 1x )-, and R 1x is hydrogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 It is selected from an aryl group or a 5- to 12-membered heteroaryl group.

[0015] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, X1 is a bond, hydrogen, halogen, a hydroxyl group, an amino group, a nitro group, a cyano group, —O—, —S—, —C(O)—, —C(O)O—, —OC(O)—, —N(R 1x )C(O)-, -C(O)N(R 1x )- or -N(R1x )-, and R 1x is hydrogen, C 1-6 Alkyl group, C 3-6 It is selected from a cycloalkyl group or a 3- to 6-membered heterocycloalkyl group.

[0016] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, X1 is selected from a bond, hydrogen, halogen, a hydroxyl group, an amino group, -O-, -S-, -C(O)-, -C(O)O-, -OC(O)-, -NHC(O)-, -C(O)NH-, -NH- or -N(CH3)-.

[0017] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, X1 is selected from a bond, hydrogen, -S-, -NHC(O)- or -C(O)NH-.

[0018] More preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, X 1 is selected from a bond.

[0019] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R1 is selected from an optionally substituted 3- to 10-membered heterocyclic group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0020] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R1 is selected from an optionally substituted 5- to 8-membered heterocyclic group, wherein the heteroatom is N and the number of heteroatoms is 1 or 2. The term "optionally substituted" means that R 1a It means that it may be substituted by:

[0021] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted dihydropyridyl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0022] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R is absent, a bond, hydrogen, or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0023] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R is hydrogen or an optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6Alkenyl group, C 2-6 Alkynyl group, C 6-14 aryl group or 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0024] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R is an optionally substituted C 1-6 Alkyl group, C 2-6 Alkynyl group, C 6-14 aryl group or 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0025] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R is an optionally substituted C 2-6 alkynyl group or 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0026] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R is an optionally substituted C 2-6 an alkynyl group or a 5- to 8-membered heteroaryl group, wherein the heteroatom is N and the number of heteroatoms is 1, 2, or 3; and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0027] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R is an optionally substituted C 2-6 alkynyl, and the "optionally substituted" refers to an optionally substituted group selected from R 1a It means that it may be substituted by:

[0028] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R1 is selected from an optionally substituted 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0029] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R1 is selected from an optionally substituted 5- to 8-membered heteroaryl group, wherein the heteroatom is N and the number of heteroatoms is 1, 2 or 3, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0030] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R1 is selected from an optionally substituted 5- to 6-membered heteroaryl group, wherein the heteroatom is N and the number of heteroatoms is 1 or 2. The term "optionally substituted" means that R 1a It means that it may be substituted by:

[0031] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted ethynyl group, phenyl group, pyridyl group, pyrimidinyl group, pyrazinyl group, pyrazolyl group, imidazolyl group or pyrrolyl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0032] More preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is selected from ethynyl.

[0033] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted pyridyl group, pyrimidinyl group, pyrazinyl group or pyrazolyl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0034] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted pyridyl group, and the term "optionally substituted" means that R 1a It means that it may be substituted by:

[0035] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1a When present, each independently represents a halogen, a hydroxyl group, an amino group, an oxo group, -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 ) and the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond.

[0036] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1a When present, each independently represents a halogen, a hydroxyl group, an amino group, an oxo group, -R 1b , -OR 1b , -SO2(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)(R1c ), -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 ) and the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond.

[0037] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1a When present, each independently represents a halogen, a hydroxyl group, an amino group, an oxo group, -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 ) and the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond.

[0038] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1a are, when present, independently selected from halogen, amino, oxo, -R 1b , -NHC(O)(R 1b ) or -NHSO2(R1b ) and the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond.

[0039] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1a is, if present, independently —NHC(O)(R 1b ) or -NHSO2(R 1b ).

[0040] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c When present, each independently represents hydrogen or optionally a halogen, a hydroxyl group, an amino group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-8 Cycloalkyl groups, 3-8 membered heterocycloalkyl groups, C 6-8 C optionally substituted with one or more aryl groups or 5- to 8-membered heteroaryl groups 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 1b and R 1c When R is attached to the same nitrogen atom, 1b and R 1c together with the nitrogen atom to which they are bonded, optionally a halogen, a hydroxyl group, an amino group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-8Cycloalkyl groups, 3-8 membered heterocycloalkyl groups, C 6-8 It forms a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted by one or more of an aryl group or a 5- to 8-membered heteroaryl group, and the oxo group means that two H at the same substitution position are replaced by one O to form a double bond.

[0041] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c are, when present, independently hydrogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5- to 12-membered heteroaryl group, or R 1b and R 1c When R is attached to the same nitrogen atom, 1b and R 1c together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocycloalkyl group.

[0042] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c If present, independently, C 1-6 alkyl group, 3-8 membered heterocycloalkyl group or C 6-8 aryl groups, or R 1b and R 1c When R is attached to the same nitrogen atom, 1b and R 1c together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocycloalkyl group.

[0043] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c If present, independently, C 1-6 Alkyl group, C 3-10 Cycloalkyl group or C 6-8 aryl groups, or R 1b and R 1c When R is attached to the same nitrogen atom, 1b and R 1c together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocycloalkyl group.

[0044] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c If present, independently, C 1-6 Alkyl group, C 3-8 Cycloalkyl group or C 6-8 aryl groups.

[0045] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c If present, independently, C 1-6 Alkyl group, C 3-6 It is selected from a cycloalkyl group or a C6 aryl (i.e., a phenyl group). More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c If present, independently, C 1-6 Alkyl group or C 3-6 The group is selected from cycloalkyl groups.

[0046] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c If present, independently, C 1-4 Alkyl group or C 3-4 The group is selected from cycloalkyl groups.

[0047] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c When present, is independently selected from methyl, ethyl, cyclopropanyl, phenyl, or tetrahydropyranyl.

[0048] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1b , R 1c When present, is independently selected from a methyl group or a cyclopropanyl group.

[0049] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted pyrazolyl group, and the term "optionally substituted" means that R 1a R means that it may be substituted by 1a independently, C 1-6 It is selected from alkyl groups and 3- to 8-membered heterocycloalkyl groups.

[0050] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted pyrazolyl group, and the term "optionally substituted" means that R 1a R means that it may be substituted by 1a independently, C 1-4 It is selected from an alkyl group or a 6-membered heterocycloalkyl group.

[0051] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted pyrazolyl group, and the term "optionally substituted" means that R 1a R means that it may be substituted by 1a are independently selected from a methyl group, an ethyl group, or a tetrahydropyranyl group.

[0052] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted pyridyl group, and the term "optionally substituted" means that R 1a R means that it may be substituted by 1a are independently an amino group, -NHC(O)(R 1b ) or -NHSO2(R 1b ) and R 1b If present, independently, C 1-6 Alkyl group, C 3-6 It is selected from a cycloalkyl group or a phenyl group.

[0053] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R is selected from an optionally substituted pyridyl group, and the term "optionally substituted" means that R 1a R means that it may be substituted by 1a are independently an amino group, -NHC(O)(R 1b ) or -NHSO2(R 1b ) and R 1b If present, independently, C 1-4 Alkyl group, C 3-4 It is selected from a cycloalkyl group or a phenyl group.

[0054] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is selected from the following optionally substituted groups: [ka] (In the formula, the "*" end is bonded to X1, and the other end is bonded to X2. The term "optionally substituted" means that R 1a It means that it may be substituted by

[0055] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is an optionally substituted [ka] is selected from. (In the formula, the "*" end is bonded to X1, and the other end is bonded to X2. The term "optionally substituted" means that R 1a It means that it may be substituted by

[0056] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is selected from the following groups: [ka] (In the formula, the "*" end is bonded to X1, and the other end is bonded to X2.)

[0057] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is selected from the following groups: [ka] (In the formula, the "*" end is bonded to X1, and the other end is bonded to X2.)

[0058] Preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is selected from the following groups: [ka] (In the formula, the "*" end is bonded to X1, and the other end is bonded to X2.)

[0059] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is selected from the following groups: [ka] (In the formula, the "*" end is bonded to X1, and the other end is bonded to X2.)

[0060] Preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is selected from the following groups: [ka] (In the formula, the "*" end is bonded to X1, and the other end is bonded to X2.)

[0061] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R1 is selected from the following groups: [ka] (wherein the "*" end is the one that binds to X1.)

[0062] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, X2 is absent, a bond, hydrogen, halogen, a hydroxyl group, an amino group, -O-, -S-, -C(O)O-, -OC(O)-, -C(O)N(R 2x )-, -N(R 2x )C(O)- or -N(R 2x )-, and R 2x is hydrogen or C optionally substituted by halogen, hydroxyl group or amino group; 1-6 The alkyl group is selected from the group consisting of:

[0063] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, X2 is selected from absent, a bond, hydrogen, halogen, a hydroxyl group, an amino group, -O-, -S-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -NH-, -N(CH3)- or -N(CH2CH3)-.

[0064] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, X2 is selected from absent, a bond, -O-, -NH- or -N(CH3)-.

[0065] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, X2 is selected from absent, a bond, -O- or -N(CH3)-.

[0066] Preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, X2 is selected from a bond, -O- or -NH-.

[0067] Preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, X2 is selected from absent, a bond or -O-. More preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, X2 is selected from -O-.

[0068] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R2 is absent, a bond, hydrogen, or optionally halogen, a hydroxyl group, an amino group, an oxo group, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-8 Cycloalkyl groups, 3-8 membered heterocycloalkyl groups, C 6-8 C optionally substituted with one or more aryl groups or 5- to 8-membered heteroaryl groups1-6 Alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, C 6-14 It is selected from an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 12-membered heteroaryl group.

[0069] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R2 is absent, hydrogen, C 1-6 Alkyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, C 6-14 It is selected from an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 12-membered heteroaryl group.

[0070] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R2 is absent, C 1-6 Alkyl group, C 2-4 It is selected from an alkynyl group or a 5- to 6-membered heterocycloalkyl group, where the heteroatom is N or O, and the number of heteroatoms is 1 or 2.

[0071] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R2 is selected from absent, methyl, ethyl, propyl (n-propyl, isopropyl), butyl (n-butyl, isobutyl, s-butyl, t-butyl), ethynyl, piperidinyl, tetrahydropyrrolyl or tetrahydropyranyl.

[0072] More preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R2 is selected from n-propyl.

[0073] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R3 is absent, hydrogen, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, -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 ) and the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond.

[0074] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R3 is absent, hydrogen, halogen, hydroxyl group, amino group, oxo group, -R 3b , -OR 3b , -SR 3b , -C(O)R 3b , -C(O)OR 3b , -OC(O)R3b , -N(R 3b )(R 3c ), -C(O)N(R 3b )(R 3c ), -C(O)NH(R 3b ) or -NHC(O)(R 3b ) and the oxo group means that two H's at the same substitution position are replaced by one O to form a double bond.

[0075] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R3 is absent, -R 3b , -OR 3b or -N(R 3b )(R 3c ) is selected.

[0076] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R3 is -N(R 3b )(R 3c ) is selected.

[0077] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c are, when present, independently hydrogen or optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group, 5- to 12-membered heteroaryl group, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3ctogether with the nitrogen atom to which they are bonded, form an optionally substituted 3- to 10-membered heterocycloalkyl group, a 4- to 12-membered bicyclic heterocyclic group, or a 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0078] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c are, when present, independently hydrogen or optionally substituted C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0079] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c are, when present, independently hydrogen or optionally substituted C 1-6 Alkyl group, C 1-6 an alkoxy group or a 3- to 10-membered heterocycloalkyl group, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3ctogether with the nitrogen atom to which they are bonded form an optionally substituted 3- to 10-membered heterocycloalkyl group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0080] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c are, when present, independently hydrogen or optionally substituted C 1-6 Alkyl group, C 1-6 an alkoxy group or a 3- to 10-membered heterocycloalkyl group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0081] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c is, when present, independently an optionally substituted C 1-6 The term "optionally substituted" means that R 3d It means that it may be substituted by:

[0082] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded form an optionally substituted 3- to 10-membered heterocycloalkyl group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0083] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are attached, form an optionally substituted 5- to 6-membered heterocycloalkyl group or a 6- to 10-membered bicyclic heterocyclic group, in which the heteroatoms are independently O or N, and the number of heteroatoms is 1, 2, 3, or 4. The term "optionally substituted" as used herein means that R 3d It means that it may be substituted by:

[0084] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R3 is absent, C 1-6 Alkyl group, C 1-6 Alkoxy group or -N(R 3b )(R 3c ) and R 3b , R 3c are independently optionally substituted C 1-6 alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded form an optionally substituted 3- to 10-membered heterocycloalkyl group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0085] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3cis, when present, independently an optionally substituted C 1-6 alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted 3- to 10-membered heterocycloalkyl group or a 4- to 12-membered bicyclic heterocyclic group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0086] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c is, when present, independently an optionally substituted C 1-6 alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted 4- to 8-membered heterocycloalkyl group or a 6- to 10-membered bicyclic heterocyclic group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0087] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c is, when present, independently an optionally substituted C 1-4 alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3ctogether with the nitrogen atom to which they are attached, form an optionally substituted 5- to 6-membered heterocycloalkyl group or a 6- to 10-membered bicyclic heterocyclic group, in which the heteroatoms are independently O or N, and the number of heteroatoms is 1, 2, 3, or 4. The term "optionally substituted" as used herein means that R 3d It means that it may be substituted by:

[0088] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c is, when present, independently an optionally substituted C 1-4 alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c and together with the nitrogen atom to which they are bonded, represent an optionally substituted 5- to 6-membered heterocycloalkyl group, a 3-membered / 4-membered heteromonocyclic spiro ring group, a 4-membered / 3-membered heteromonocyclic spiro ring group, a 3-membered / 5-membered heteromonocyclic spiro ring group, a 5-membered / 3-membered heteromonocyclic spiro ring group, a 3-membered / 6-membered heteromonocyclic spiro ring group, a 6-membered / 3-membered heteromonocyclic spiro ring group, a 4-membered / 5-membered heteromonocyclic spiro ring group, a 5-membered / 4-membered heteromonocyclic spiro ring group, a 4-membered / 6-membered heteromonocyclic spiro ring group, a 6-membered / 4-membered heteromonocyclic spiro ring group, The term "optionally substituted" means that the heteromonocyclic spiro ring group is optionally substituted with R. 3d It means that it may be substituted by:

[0089] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c is, when present, independently an optionally substituted C 1-4 alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted 5- to 6-membered heterocycloalkyl group, a 3-membered / 6-membered heteromonocyclic spiro ring group, a 6-membered / 3-membered heteromonocyclic spiro ring group, a 4-membered / 6-membered heteromonocyclic spiro ring group, a 6-membered / 4-membered heteromonocyclic spiro ring group, or a 4-membered / 4-membered heteromonocyclic spiro ring group, in which the heteroatoms are independently O or N, and the number of heteroatoms is 1 or 2. The term "optionally substituted" as used herein means that R 3d It means that it may be substituted by:

[0090] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c are, when present, independently selected from optionally substituted methyl groups; or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are attached form an optionally substituted piperidinyl, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0091] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3dare, when present, independently deuterium, halogen, hydroxyl, amino, cyano, -R 3e , -C(O)R 3e , -C(O)OR 3e , -N(R 3e )(R 3f ) or -C(O)NH(R 3e ) and R 3e , R 3f When present, each independently represents hydrogen or, optionally, halogen, a hydroxyl group, an amino group, C 1-6 Alkyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 C optionally substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 3e and R 3f When R is attached to the same nitrogen atom, 3e and R 3f together with the nitrogen atom to which they are bonded, optionally a halogen, a hydroxyl group, an amino group, C 1-6 Alkyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 It forms a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups.

[0092] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3d are, when present, independently deuterium, halogen, hydroxyl, amino, cyano, -R 3e , -C(O)R 3e , -C(O)OR 3e , -N(R3e )(R 3f ) or -C(O)NH(R 3e ) and R 3e , R 3f When present, each independently represents hydrogen or, optionally, halogen, a hydroxyl group, an amino group, C 1-6 Alkyl group, C 3-6 C optionally substituted with one or more of a cycloalkyl group, a 3- to 6-membered heterocycloalkyl group, a C aryl group, or a 5- to 6-membered heteroaryl group 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 It is selected from a cycloalkyl group, a 3- to 6-membered heterocycloalkyl group, a C6 aryl group, or a 5- to 6-membered heteroaryl group.

[0093] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3d are, when present, independently deuterium, halogen, hydroxyl, 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 group, C 1-6 It is selected from an alkoxy group and a 3- to 6-membered heterocycloalkyl group.

[0094] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3d are, when present, independently deuterium, hydroxyl group, amino group, -CHO, -CO(C 1-6 alkyl), -COOH, -COO(C 1-6 alkyl), -NH(C 1-6 alkyl), -N(C 1-6 Alkyl)(C1-6 alkyl), -C(O)NH2, C 1-6 Alkyl group, C 1-6 It is selected from an alkoxy group or a 5- to 6-membered heterocycloalkyl group.

[0095] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3d When present, is independently selected from deuterium, fluorine, hydroxyl, amino, cyano, —CHO, —COCH3, —COOH, —COOCH3, —NH(CH3), —N(CH3)(CH3), —C(O)NH2, —CH3, —CH2CH3, —CH2CH2CH3, —OCH3, —OCH2CH3, —OCH2CH2CH3, piperidinyl, piperazinyl, or tetrahydropyrrolyl.

[0096] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3d When present, is independently selected from deuterium, fluorine, amino, cyano, —C(O)NH 2 , —CH 3 , or piperidinyl.

[0097] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3d are, when present, independently selected from halogen, hydroxyl, amino, -R 3e or -N(R 3e )(R 3f ) and R 3e , R 3f When present, each independently represents hydrogen or, optionally, halogen, a hydroxyl group, an amino group, C 1-6 Alkyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14C optionally substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups 1-6 Alkyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 aryl group or 5-12 membered heteroaryl group, or R 3e and R 3f When R is attached to the same nitrogen atom, 3e and R 3f together with the nitrogen atom to which they are bonded, optionally a halogen, a hydroxyl group, an amino group, C 1-6 Alkyl group, C 3-10 Cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C 6-14 It forms a 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group which may be substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups.

[0098] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3d is, if present, independently -R 3e or -N(R 3e )(R 3f ) and R 3e , R 3f If present, independently, C 1-6 alkyl group or a 3- to 8-membered heterocycloalkyl group, or R 3e and R 3f When R is attached to the same nitrogen atom, 3e and R 3f together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocycloalkyl group.

[0099] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3dis selected from a methyl group, —N(methyl)(methyl) (i.e., a dimethylamino group), or a piperidinyl group.

[0100] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R3 is selected from the following optionally substituted groups: [ka] The term "optionally substituted" means that R 3d It means that it may be substituted by:

[0101] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R3 is selected from the following groups: [ka]

[0102] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R3 is selected from the following groups: [ka]

[0103] Preferably, the present invention provides a compound having a structure represented by formula (II-a) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-1 is selected from 0, 1 or 2; R 1a-1 is R in the compound of formula (I') or formula (I) 1aAs defined by X 2-1 is as defined for X2 in the compound of formula (I') or formula (I), and R 2-1 is as defined for R in the compounds of formula (I') or formula (I), and R 3-1 is as defined for R3 in the compound of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compound of formula (I') or formula (I).

[0104] Preferably, the present invention provides a compound having a structure represented by formula (II-a1), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compound of formula (I') or formula (I).)

[0105] Preferably, the present invention provides a compound having a structure represented by formula (II-a2), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, R 3b-1 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-1 is R in the compound of formula (I') or formula (I) 3c and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0106] Preferably, the present invention provides a compound having a structure represented by formula (II-b) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-2 is selected from 0, 1, 2 or 3; R 1a-2 is R in the compound of formula (I') or formula (I) 1a As defined by X 2-2 is as defined for X2 in the compound of formula (I') or formula (I), and R 2-2 is as defined for R in the compounds of formula (I') or formula (I), and R 3-2 is as defined for R3 in the compound of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compound of formula (I') or formula (I).

[0107] Preferably, the present invention provides a compound having a structure represented by formula (II-b1), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-3 is selected from 0, 1, 2 or 3; R 1a-3 is R in the compound of formula (I') or formula (I) 1a and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0108] Preferably, the present invention provides a compound having a structure represented by formula (II-c), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-4 is selected from 0, 1, 2 or 3; R 1a-4 is R in the compound of formula (I') or formula (I) 1a As defined by X 2-3 is as defined for X2 in the compound of formula (I') or formula (I), and R2-3 is as defined for R in the compounds of formula (I') or formula (I), and R 3-3 is as defined for R3 in the compound of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compound of formula (I') or formula (I).

[0109] Preferably, the present invention provides a compound having a structure represented by formula (II-c1), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-5 is selected from 0, 1, 2 or 3; R 1a-5 is R in the compound of formula (I') or formula (I) 1a As defined by R 3b-2 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-2 is R in the compound of formula (I') or formula (I) 3c and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0110] Preferably, the present invention provides a compound having a structure represented by formula (II-d) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] wherein E1, E2, E3, E4, E5, and E6 are independently selected from C or N; 1-6 is selected from 0, 1, 2, 3 or 4; R 1a-6 is R in the compound of formula (I') or formula (I) 1a As defined by X 2-4 is as defined for X2 in the compound of formula (I') or formula (I), and R 2-4is the R definition in the compound of formula (I') or formula (I), R 3-4 is as defined for R3 in the compound of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compound of formula (I') or formula (I).

[0111] Preferably, the present invention provides a compound having a structure represented by formula (II-d1), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-7 is selected from 0, 1, 2 or 3; R 1a-7 is R in the compound of formula (I') or formula (I) 1a As defined by R 3b-3 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-3 is R in the compound of formula (I') or formula (I) 3c and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0112] Preferably, the present invention provides a compound having a structure represented by formula (II-d2), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-8 is selected from 0, 1 or 2; R 1a-8 is R in the compound of formula (I') or formula (I) 1a As defined by R 3b-4 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-4 is R in the compound of formula (I') or formula (I) 3cand R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0113] Preferably, the present invention provides a compound having a structure represented by formula (II-d3), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-9 is selected from 0, 1 or 2; R 1a-9 is R in the compound of formula (I') or formula (I) 1a As defined by R 3b-5 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-5 is R in the compound of formula (I') or formula (I) 3c and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0114] Preferably, the present invention provides a compound having a structure represented by formula (II-d4), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-10 is selected from 0, 1, 2 or 3; R 1a-10 is R in the compound of formula (I') or formula (I) 1a As defined by R 3e-1 is R in the compound of formula (I') or formula (I) 3e As defined by R 3f-1 is R in the compound of formula (I') or formula (I) 3f and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0115] Preferably, the present invention provides a compound having a structure represented by formula (II-d5), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-11 is selected from 0, 1, 2 or 3; R 1a-11 is R in the compound of formula (I') or formula (I) 1a and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0116] Preferably, the present invention provides a compound having a structure represented by formula (II-d6), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-12 is selected from 0, 1, 2 or 3; R 1a-12 is R in the compound of formula (I') or formula (I) 1a As defined by R 3b-6 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-6 is R in the compound of formula (I') or formula (I) 3c As defined by R 2x-1 is R in the compound of formula (I') or formula (I) 2x and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0117] Preferably, the present invention provides a compound having a structure represented by formula (II-e) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, E7, E8, E9, E 10 , E 11 , E 12 are independently selected from C or N, and m 1-13 is selected from 0, 1, 2 or 3; m 2-1 is selected from 0, 1, 2, 3 or 4; R 1a-13 is R in the compound of formula (I') or formula (I) 1a As defined by R 2a-1 is R in the compound of formula (I') or formula (I) 2a As defined by R 3-5 is as defined for R3 in the compound of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compound of formula (I') or formula (I).

[0118] Preferably, the present invention provides a compound having a structure represented by formula (II-e1), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-14 is selected from 0, 1, 2 or 3; m 2-2 is selected from 0, 1, 2, 3 or 4; R 1a-14 is R in the compound of formula (I') or formula (I) 1a As defined by R 2a-2 is R in the compound of formula (I') or formula (I) 2a As defined by R 3b-7 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-7 is R in the compound of formula (I') or formula (I) 3c and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0119] Preferably, the present invention provides a compound having a structure represented by formula (II-f) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-15 is selected from 0, 1, 2 or 3; R 1a-15 is R in the compound of formula (I') or formula (I) 1a As defined by R 3e-2 is R in the compound of formula (I') or formula (I) 3e As defined by R 3f-2 is R in the compound of formula (I') or formula (I) 3f and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0120] Preferably, the present invention provides a compound having a structure represented by formula (II-g) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, R 3b-8 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-8 is R in the compound of formula (I') or formula (I) 3c and R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0121] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1a are independently -H, -F, -Cl, -NH2, oxo group, -CH3, -CH2CH3, -OCH3, -OCH2CH3, -NHC(O)CH3, -C(O)NHCH3, [ka] is selected from The oxo group means that two H's at the same substitution position are replaced by one O to form a double bond.

[0122] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 1a are independently -H, -NH2, an oxo group, -CH3, -CH2CH3, -NHC(O)CH3, [ka] is selected from The oxo group means that two H's at the same substitution position are replaced by one O to form a double bond.

[0123] Preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, Y is selected from the following groups: [ka]

[0124] Preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, Y is selected from the following groups: [ka]

[0125] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R4 is hydrogen, halogen, amino group or C 1-6The alkoxy group is selected from the group consisting of alkoxy groups.

[0126] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R4 is hydrogen, halogen or C 1-3 The alkoxy group is selected from the group consisting of alkoxy groups.

[0127] More preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R4 is selected from hydrogen, fluorine or methoxy.

[0128] More preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R4 is selected from hydrogen or fluorine.

[0129] Preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R4 is selected from a methoxy group.

[0130] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R5 is hydrogen, deuterium, or C optionally substituted by one or more deuterium atoms. 1-6 The alkyl group is selected from the group consisting of:

[0131] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R5 is C 1-6 It is an alkyl group.

[0132] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R5 is C 1-3 It is an alkyl group.

[0133] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R5 is a methyl group. Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, L is C(R L ) or N, and R L is hydrogen, halogen, amino group, hydroxyl group, C 1-6 Alkyl group or C 1-6 The alkoxy group is selected from the group consisting of alkoxy groups.

[0134] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, L is C(R L ) and R L is selected from hydrogen, halogen, an amino group, a methyl group, or a methoxy group.

[0135] More preferably, in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, L is CH.

[0136] Preferably, L is N in the compounds according to the invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof.

[0137] Preferably, in the compounds according to the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts, W, Q1, Q2 are independently selected from O, C, S or N, and Q3 is C, wherein Q1 is bonded to W.

[0138] More preferably, in the compounds according to the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts, W, Q1, Q2 are independently selected from O, C or S, and Q3 is C, wherein Q1 is bonded to W.

[0139] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, W is selected from O or N, Q1 is C, Q2 is C and Q3 is C, wherein Q1 is bonded to W.

[0140] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 are, when present, independently hydrogen, deuterium, halogen, hydroxyl group, amino group, cyano group, -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 bonded to the same atom are =O, =NR 6a or =CH-R 6a or any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which they are attached, optionally forms an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group; 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 It forms an aryl group, a 5- to 12-membered heteroaryl group, a monocyclic spiro ring group, or a monocyclic heterospiro ring group.

[0141] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 are, when present, independently hydrogen, 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 bonded to the same atom are =O, =NR 6a or =CH-R 6a or any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which they are attached, optionally forms an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group; 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 It forms an aryl group, a 5- to 12-membered heteroaryl group, a monocyclic spiro ring group, or a monocyclic heterospiro ring group.

[0142] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 are, when present, independently hydrogen, halogen, hydroxyl, amino, cyano, -R 6a , -OR6a , -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 R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two groups bonded to the same atom are =O, =NR 6a or =CH-R 6a or any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which they are attached, optionally forms an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group; 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 It forms an aryl group or a 5- to 12-membered heteroaryl group.

[0143] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 are, when present, independently hydrogen, halogen, hydroxyl group, amino group, -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 bonded to the same atom are =O, =NR 6a or =CH-R 6a or any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which they are attached, optionally forms an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group; 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 It forms an aryl group or a 5- to 12-membered heteroaryl group.

[0144] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 are, when present, independently hydrogen, halogen, hydroxyl group, amino group, -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 bonded to the same atom are =O, =NR 6a or =CH-R 6aor any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which they are attached, optionally forms an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group; 6c C may be substituted by 3-10 It forms a carbocyclic group or a 3- to 10-membered heterocyclic group.

[0145] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 are, when present, independently hydrogen, halogen, hydroxyl group, amino group, -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 bonded to the same atom are =O, =NR 6a or =CH-R 6a or any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which they are bonded, optionally forms an aryl group, a 5- to 10-membered heteroaryl group, a fused ring group, or a heterofused ring group; 6cC may be substituted by 3-10 It forms a carbocyclic group or a 3- to 10-membered heterocyclic group.

[0146] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 is, when present, independently hydrogen, halogen or -R 6a Alternatively, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two groups bonded to the same atom are =O, =NR 6a or =CH-R 6a or any two adjacent atoms of W, Q1 when present, Q2 and Q3 when present, together with the substituents to which they are attached, optionally form R 6c C may be substituted by 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 or any one atom of W, Q1, if present, Q2, and Q3, together with the substituent to which they are attached, optionally forms an aryl group or a 5- to 12-membered heteroaryl group; 6c C may be substituted by 3-10 It forms a carbocyclic group or a 3- to 10-membered heterocyclic group.

[0147] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, any two adjacent atoms of W, Q1, if present, Q2 and Q3, together with the substituents to which they are attached, are optionally R 6c C may be substituted by 3-10 Carbocyclic groups, 3-10 membered heterocycloalkyl groups, C 6-8 It forms an aryl group or a 5- to 10-membered heteroaryl group.

[0148] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, any two adjacent atoms of W, Q1, if present, Q2 and Q3, together with the substituents to which they are attached, are optionally R 6c C may be substituted by 3-8 Cycloalkyl groups, 3-8 membered heterocycloalkyl groups, C 6-8 It forms an aryl group or a 5- to 8-membered heteroaryl group.

[0149] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, any two adjacent atoms of W, Q1, if present, Q2 and Q3, together with the substituents to which they are attached, are optionally R 6c C may be substituted by 5-6 It forms a cycloalkyl group, a 5- to 6-membered heterocycloalkyl group, a C6 aryl group, or a 5- to 6-membered heteroaryl group, wherein the heteroatom is selected from O or N, and the number of heteroatoms is 1 or 2.

[0150] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, any one atom of W, Q1, if present, Q2 and Q3, together with the substituent to which it is attached, is optionally R 6c C may be substituted by 3-10 It forms a cycloalkyl group or a 3- to 10-membered heterocycloalkyl group.

[0151] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, any one atom of W, Q1, if present, Q2 and Q3, together with the substituents to which they are attached, is optionally R 6cC may be substituted by 3-6 It forms a cycloalkyl group or a 3- to 7-membered heterocycloalkyl group.

[0152] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, any one atom of W, Q1, if present, Q2 and Q3, together with the substituents to which they are attached, is optionally R 6c C may be substituted by 3-4 It forms a cycloalkyl group or a 3- to 6-membered heterocycloalkyl group, in which the heteroatom is selected from O or N, and the number of heteroatoms is 1 or 2.

[0153] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, any one atom of W, Q1, if present, Q2 and Q3, together with the substituents to which they are attached, is optionally R 6c C may be substituted by 3-4 Forms a cycloalkyl group.

[0154] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6a , R 6b is, when present, independently hydrogen or optionally R 6c C may be substituted by 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group; or R 6a and R 6b When R is attached to the same nitrogen atom, 6a and R 6b together with the nitrogen atom to which they are attached, optionally R6c and forming a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group which may be substituted by:

[0155] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6a , R 6b is, when present, independently hydrogen or optionally R 6c C may be substituted by 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 It is selected from an aryl group or a 5- to 10-membered heteroaryl group.

[0156] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6a , R 6b are, when present, independently hydrogen, deuterium, or optionally R 6c C may be substituted by 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, 5-6 membered heterocycloalkyl groups, C 6-8 It is selected from an aryl group, a 5- to 6-membered heteroaryl group, a 9- to 10-membered bicyclic heterocyclic group, or a 9- to 10-membered bicyclic heteroaryl group.

[0157] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6a , R 6b is, when present, independently hydrogen or optionally R 6c C may be substituted by 1-6 Alkyl group or C 1-6 The alkoxy group is selected from the group consisting of alkoxy groups.

[0158] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6a , R 6b is, when present, independently hydrogen or optionally R 6c C may be substituted by 1-3 Alkyl group or C 1-3 The alkoxy group is selected from the group consisting of alkoxy groups.

[0159] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6a , R 6b is, when present, independently hydrogen or optionally R 6c The group is selected from a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a methoxy group, an ethoxy group, an n-propoxy group or an isopropoxy group, each of which may be substituted by

[0160] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6a , R 6b is, when present, independently hydrogen or optionally R 6c The alkyl group is selected from methyl or ethyl groups optionally substituted by:

[0161] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6c are, when present, independently hydrogen, deuterium, halogen, hydroxyl group, amino group, -R 6d , -OR 6d , -N(R 6d )R 6e , -C(O)R 6d , -C(O)N(R 6d )R6e , -N(R 6d )C(O)R 6e or -C(O)OR 6d is selected from.

[0162] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6c are, when present, independently hydrogen, halogen, hydroxyl group, amino group, -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 is selected from.

[0163] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6d , R 6e are, when present, independently hydrogen, halogen, hydroxyl, amino, nitro, cyano, or optionally halogen, hydroxyl, amino, or C 1-6 C optionally substituted by alkyl groups 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group; or R 6d and R 6e When R is attached to the same nitrogen atom, 6d and R 6e together with the nitrogen atom to which they are bonded, optionally a halogen, a hydroxyl group, an amino group or C 1-6It forms a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group which may be substituted by an alkyl group.

[0164] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6d , R 6e are, when present, independently hydrogen, halogen, hydroxyl, amino, nitro, cyano, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group; or R 6d and R 6e When R is attached to the same nitrogen atom, 6d and R 6e together with the nitrogen atom to which they are attached, form a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group.

[0165] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6d , R 6e are, when present, independently hydrogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-14 It is selected from an aryl group, a 5- to 12-membered heteroaryl group, a fused ring group, or a heterofused ring group.

[0166] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6d , R 6e are, when present, independently hydrogen, C1-6 Alkyl group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 It is selected from an aryl group and a 5- to 10-membered heteroaryl group.

[0167] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6c are, when present, independently hydrogen, fluorine, chlorine, a hydroxyl group, an amino group, -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 group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 It is selected from an aryl group, a 5- to 10-membered heteroaryl group, a fused ring group, or a heterofused ring group.

[0168] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6c are, when present, independently hydrogen, fluorine, chlorine, a hydroxyl group, an amino group, -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 group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8It is selected from an aryl group and a 5- to 10-membered heteroaryl group.

[0169] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6c are, when present, independently hydrogen, fluorine, chlorine, a hydroxyl group, an amino group, -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 group, C 1-6 Alkoxy group, C 3-10 Carbocyclic group, 3-10 membered heterocyclic group, C 6-8 It is selected from an aryl group or a 5-10 membered heteroaryl group, wherein the heteroatom is selected from N or S, and the number of heteroatoms is 1, 2 or 3.

[0170] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6c are, when present, independently hydrogen, fluorine, chlorine, a hydroxyl group, an amino group, -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 group, C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, 3-6 membered heterocycloalkyl groups, C 6-8It is selected from an aryl group or a 5- to 6-membered heteroaryl group, wherein the heteroatom is selected from N or S, and the number of heteroatoms is 1, 2 or 3.

[0171] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6c are, when present, independently hydrogen, deuterium, halogen, hydroxyl group, amino group, C 1-6 Alkyl group or C 1-6 The alkoxy group is selected from the group consisting of alkoxy groups.

[0172] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 6c When present, are independently selected from hydrogen, fluorine, chlorine, hydroxyl, amino, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, or isopropoxy.

[0173] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 When present, independently represent hydrogen, deuterium, or optionally deuterium, halogen, hydroxyl group, amino group, C 1-6 Alkyl group, C 1-6 Alkoxy group, -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 3-6C optionally substituted by a cycloalkyl group, a 5- to 6-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, a 9- to 10-membered bicyclic heterocyclic group, or a 9- to 10-membered bicyclic heteroaryl group 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, 5-6 membered heterocycloalkyl groups, C 6-8 It is selected from an aryl group, a 5- to 6-membered heteroaryl group, a 9- to 10-membered bicyclic heterocyclic group, or a 9- to 10-membered bicyclic heteroaryl group.

[0174] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 When present, each independently represents hydrogen or, optionally, halogen, a hydroxyl group, an amino group, C 1-6 Alkyl group, C 1-6 Alkoxy group, -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 optionally substituted by a cycloalkyl group, a 5- to 6-membered heterocycloalkyl group, a phenyl group, or a 5- to 6-membered heteroaryl group 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, 5-6 membered heterocycloalkyl groups, C 6-8 It is selected from an aryl group or a 5- to 6-membered heteroaryl group.

[0175] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12and R 13 When present, each independently represents hydrogen or, optionally, halogen, a hydroxyl group, an amino group, C 1-6 Alkyl group, C 1-6 Alkoxy group, -C(O)(C 1-6 alkyl), -C(O)NH(C 1-6 alkyl) or -NHC(O)(C 1-6 C optionally substituted by alkyl 1-6 Alkyl group or C 1-6 The alkoxy group is selected from the group consisting of alkoxy groups.

[0176] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 When present, each independently represents hydrogen or, optionally, halogen, a hydroxyl group, an amino group, C 1-6 Alkyl group, C 1-6 C optionally substituted by an alkoxy group 1-6 Alkyl group or C 1-6 The alkoxy group is selected from the group consisting of alkoxy groups.

[0177] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 When present, each independently represents hydrogen or, optionally, halogen, a hydroxyl group, an amino group, C 1-3 Alkyl group or C 1-3 C optionally substituted by an alkoxy group 1-3 Alkyl group or C 1-3 The alkoxy group is selected from the group consisting of alkoxy groups.

[0178] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 is, when present, independently: -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, [ka] is selected from.

[0179] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 is, when present, independently: -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, [ka] is selected from.

[0180] More preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 When present, is independently selected from -H, -F, -Cl, -OH, -NH2, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)CH3, -CH2OCH3, -CH2CH2OCH3, -CH2CH2CH2OCH3, or -CH(CH3)CH2OCH3.

[0181] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Any two groups bonded to the same atom form =O or =CH2.

[0182] Preferably, in the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, any two adjacent atoms of W, Q1, if present, and Q2 and Q3, if present, together with the substituents to which they are bound, form the following group: [ka]

[0183] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, any one atom of W, Q1, if present, Q2 and Q3 together with the substituents to which they are attached form the following group: [ka]

[0184] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, any one atom of W, Q1, if present, Q2 and Q3 together with the substituents to which they are attached form the following group: [ka]

[0185] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, any one atom of W, Q1, if present, Q2 and Q3 together with the substituents to which they are attached form the following group: [ka]

[0186] Preferably, the present invention provides a compound having a structure represented by formula (III-a) or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-16 is selected from 0, 1, 2 or 3; R 1a-16 is R in the compound of formula (I') or formula (I) 1a As defined by R 3b-9 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-9 is R in the compound of formula (I') or formula (I) 3c As defined in R4, R5, R6, R7, R8, R9, R 10 , R 11 , W, L, t1, and t2 are as defined for the compounds of formula (I') or formula (I).

[0187] Preferably, the present invention provides a compound having a structure represented by formula (III-a1), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-17 is selected from 0, 1, 2 or 3; R 1a-17 is R in the compound of formula (I') or formula (I) 1a As defined by R 3b-10 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-10 is R in the compound of formula (I') or formula (I) 3c As defined in R4, R5, R8, R9, R 10 , R 11 , L is as defined for the compounds of formula (I') or formula (I).

[0188] Preferably, the present invention provides a compound having a structure represented by formula (III-a2), or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof. [ka] (In the formula, m 1-18 is selected from 0, 1, 2 or 3; R 1a-18 is R in the compound of formula (I') or formula (I) 1a As defined by R 3b-11 is R in the compound of formula (I') or formula (I) 3b As defined by R 3c-11 is R in the compound of formula (I') or formula (I) 3c As defined in R4, R5, R7, R8, R9, R 10 , R 11 , L is as defined for the compounds of formula (I') or formula (I).

[0189] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c is, when present, independently an optionally substituted C 1-6 alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded form an optionally substituted 3- to 10-membered heterocycloalkyl group, and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0190] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c is, when present, independently an optionally substituted C 1-4 alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted 5- to 6-membered heterocycloalkyl group or a 6- to 10-membered bicyclic heterocyclic group, in which the heteroatoms are independently O or N, and the number of heteroatoms is 1, 2 or 3. The term "optionally substituted" as used herein means that R 3d It means that it may be substituted by:

[0191] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c is, when present, independently an optionally substituted C 1-4alkyl groups, or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted 5- to 6-membered heterocycloalkyl group, a 3- or 6-membered heteromonocyclic spiro ring group, a 4- or 6-membered heteromonocyclic spiro ring group, or a 3- or 5-membered fused heterocyclic ring group, in which the heteroatoms are independently O or N, and the number of heteroatoms is 1, 2, or 3. The term "optionally substituted" as used herein means that R 3d It means that it may be substituted by:

[0192] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b , R 3c are, when present, independently selected from optionally substituted methyl groups; or R 3b and R 3c When R is attached to the same nitrogen atom, 3b and R 3c together with the nitrogen atom to which they are bonded, form an optionally substituted pyrrolidinyl group, piperazinyl group, piperidinyl group, 2-oxa-7-azaspiro[3.5]nonyl group (e.g., 2-oxa-7-azaspiro[3.5]non-7-yl group), 3-azabicyclo[3.1.0]hexyl group (e.g., 3-azabicyclo[3.1.0]hex-3-yl group) or 6-azaspiro[2.5]octyl group (e.g., 6-azaspiro[2.5]oct-6-yl group), and the term "optionally substituted" means that R 3d It means that it may be substituted by:

[0193] Preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3dWhen present, is independently selected from deuterium, fluorine, hydroxyl, amino, cyano, —NH(CH), —N(CH)(CH), —C(O)NH, —CH, —CHCH, or —CHCHCH.

[0194] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3d When present, is independently selected from deuterium, fluorine, cyano, —C(O)NH 2 , or —CH 3 .

[0195] More preferably, in the compounds according to the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof, R 3b and R 3c together with the nitrogen atom to which they are attached form a group selected from the following groups: [ka]

[0196] Preferably, the present invention provides the following compounds or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts thereof: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0197] [Synthetic Intermediates and Manufacturing Methods] With respect to the above compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), which has a structure represented by formula (M-1). [ka] (In the formula, R x1 is selected from halogen or hydrogen, and R, R, R, A, W, L, t, t, and h are as defined for compounds of formula (I') or formula (I).

[0198] With respect to the above compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), which has a structure represented by formula (M-2). [ka] (In the formula, R x1 is selected from halogen or hydrogen, and R, R, R, A, W, L, t, t, and h are as defined for compounds of formula (I') or formula (I).

[0199] With respect to the above compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), which has a structure represented by formula (M-3). [ka] (In the formula, R x1 is selected from halogen or hydrogen, and R, R, R, A, W, L, t, t, and h are as defined for compounds of formula (I') or formula (I).

[0200] With respect to the above compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), which has a structure represented by formula (M-4). [ka] (In the formula, R x2 is selected from halogen or hydrogen, and R, R, R, A, W, L, t, t, and h are as defined for compounds of formula (I') or formula (I).

[0201] With respect to the above compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), which has a structure represented by formula (M-5). [ka] (In the formula, R x3 is selected from halogen or hydrogen, and R, R, R, A, W, L, t, t, and h are as defined for compounds of formula (I') or formula (I).

[0202] With respect to the above compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), which has a structure represented by formula (M-6). [ka] (In the formula, R x4 is selected from halogen or hydrogen, and R, R, R, A, W, L, t, t, and h are as defined for compounds of formula (I') or formula (I).

[0203] Preferably, the present invention provides the following synthetic intermediates for producing the target compounds: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0204] The present invention further provides a method for producing the compound of formula (I') or formula (I). The compound can be produced, for example, by the method represented by the following synthetic route 1, 2 or 3. Synthetic route 1

[0205] [ka] i) Compound I-a1 is subjected to a chemical transformation (for example, a substitution reaction) to give compound I-a2. For example, compound I-a2 is obtained using compound I-a1 and thionyl chloride or the like as basic materials. ii) Compound I-a2 is chemically transformed (for example, by substitution or, if desired, by ring closure) to give compound I-a4. For example, compounds I-a2 and I-a3 are used as basic materials and reacted under basic conditions to give uncyclized or cyclized compound I-a4. iii) Compound I-a4 is chemically transformed (for example, hydrolysis) to give compound I-a5. For example, compound I-a4 is reacted under basic conditions to give compound I-a5. iv) Compound I-a5 is chemically transformed (for example, by ring closure) to give compound I-a6. For example, compound I-a5 and diphenylphosphoryl azide or the like are used as basic materials and reacted under basic conditions to give compound I-a6. v) Compound I-a6 is chemically transformed (for example, by alkylation) to give compound I-a7. For example, compound I-a6 and a halide (eg, iodomethane) or the like are used as basic materials and reacted under basic conditions to give compound I-a7. vi) Compound I-a7 is chemically transformed (for example, by a coupling reaction) to give compound I-a8. For example, compound I-a7 and a boric acid derivative or the like are used as basic raw materials and subjected to a coupling reaction to obtain compound I-a8. vii) Compound I-a8 is subjected to a chemical transformation (eg, a substitution reaction) to give compound I. For example, compound I-a8 or the like can be used as a basic raw material and reacted under basic conditions to obtain compound I of the general formula.

[0206] [ka] i) Compound I-b2 is obtained using compound I-b1 and thionyl chloride or the like as basic raw materials. ii) Compound I-b2 and I-b3 are used as basic materials and reacted under basic conditions to give compound I-b4. iii) Compound I-b4 is reacted under basic conditions to give compound I-b5. iv) Compound I-b5 and an appropriate reducing agent (eg, iron powder, zinc powder, etc.), ammonium chloride, etc. are used as basic materials to obtain compound I-b6. v) Compound I-b7 is obtained using compound I-b6 and N,N-carbonyldiimidazole (CDI) or the like as basic materials. vi) Compound I-b7 and a halide (eg, iodomethane) or the like are used as basic materials and reacted under basic conditions to give compound I-b8. vii) Compound I-b8 and a boric acid derivative or the like are used as basic raw materials and subjected to a coupling reaction to obtain compound I-b9. viii) Compound I-b9 is reacted with amines or alcohols as basic raw materials under basic conditions to obtain compound I of the general formula.

[0207] [ka] i) Compound I-b2 is obtained using compound I-b1 and thionyl chloride or the like as basic raw materials. ii) Compound I-b2 and I-b3 are used as basic materials and reacted under basic conditions to give compound I-b5. iii) Compound I-b5 and an appropriate reducing agent (eg, iron powder, zinc powder, etc.), ammonium chloride, etc. are used as basic materials to obtain compound I-b6. iv) Compound I-b6 and N,N-carbonyldiimidazole (CDI) or the like are used as basic materials to obtain compound I-b7. v) Compound I-b7 and a halide (eg, iodomethane) or the like are used as basic materials and reacted under basic conditions to give compound I-b8. vi) Compound I-b8 and a boric acid derivative or the like are used as basic raw materials and subjected to a coupling reaction to obtain compound I-b9. vii) Compound I-b9 is reacted with amines or alcohols as basic raw materials under basic conditions to obtain compound I of the general formula.

[0208] Preferably, in the production method of the present invention, R x1 is selected from halogen or hydrogen, and X1, R4, R5, R6, R7, A, W, L, t1, and t2 are as defined in formula (I') or formula (I).

[0209] Preferably, in the production method of the present invention, the reaction is carried out in an organic solvent.

[0210] More preferably, in the production 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, and the esters are selected from ethyl acetate, etc.

[0211] More preferably, in the production method of the present invention, the organic solvent is one or more selected from acetonitrile, N,N-dimethylformamide, halogenated hydrocarbon, ethyl ether, and ethyl acetate. Preferably, the halogenated hydrocarbon is dichloroethane.

[0212] Preferably, in the production method of the present invention, the base is one or more selected from 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, dimethylpyridine, and dimethylaminopyridine.

[0213] [Pharmaceutical composition] With respect to the compounds described above, the present invention further provides pharmaceutical compositions comprising the compounds of the present invention or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof.

[0214] Preferably, the pharmaceutical composition of the present invention comprises a compound of the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0215] [Medicinal uses] The present invention further provides use of 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, as an ATM kinase inhibitor.

[0216] The present invention further provides use of 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 the prevention and / or treatment of a disease and / or disorder mediated at least in part by ATM kinase. Preferably, said disease and / or disorder mediated at least in part by ATM kinase is cancer.

[0217] The present invention further provides use of the compound of the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative, or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of the present invention, for the prevention and / or treatment of cancer. Furthermore, the cancer includes solid tumors and hematological tumors. 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, and glioblastoma.

[0218] The present invention further provides use of 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 the manufacture of an ATM kinase inhibitor.

[0219] The present invention further provides use of 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 the manufacture of a medicament for the prevention and / or treatment of a disease and / or disorder mediated at least in part by ATM kinase, preferably wherein said disease and / or disorder mediated at least in part by ATM kinase is cancer.

[0220] Furthermore, the present invention provides use of the compound of the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative, or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of the present invention, for the manufacture of a medicament for the prevention and / or treatment of cancer. Furthermore, 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, and glioblastoma.

[0221] The present application further provides a method for preventing and / or treating a disease and / or disorder mediated at least in part by ATM kinase, comprising administering a prophylactically and / or therapeutically effective amount of 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 to a subject in need thereof. Preferably, the disease and / or disorder mediated at least in part 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, and glioblastoma.

[0222] Furthermore, the present application further provides a method for preventing and / or treating cancer, comprising administering a prophylactically and / or therapeutically effective amount of 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 to a subject in need thereof. 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, and glioblastoma.

[0223] Furthermore, in the use or method according to the present invention, the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of the present invention is administered together with at least one additional antitumor agent or therapeutic treatment (e.g., radiation therapy). Preferably, the antitumor 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 therapeutic treatment is radiation therapy.

[0224] Furthermore, in the use or method according to the present invention, the compound according to the present invention or a prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of the present invention is administered simultaneously with, separately from, or sequentially with radiation therapy.

[0225] The present invention further provides a pharmaceutical combination form (or pharmaceutical combination composition, pharmaceutical composite composition) comprising 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, and at least one additional antitumor agent or therapeutic treatment. Preferably, the antitumor 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 therapeutic treatment is radiation therapy.

[0226] [Term definition] The terms "may," "optionally," "optionally," or "desirably" mean that the event or circumstance may occur, but does not necessarily occur, and encompass both the occurrence and non-occurrence of such event or circumstance. Thus, the term "optionally substituted" means that a particular group may be unsubstituted or may be substituted at any substitutable position with one or more independently occurring substituents. When a group is substituted, a hydrogen atom at one or more of the substitutable positions is independently replaced with a substituent, and the substituents are independently deuterium, halogen, hydroxyl, amino, nitro, mercapto, cyano, oxo, -C(O)C, or the like. 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 group, C 1-6 Alkoxy group, C 3-10Cycloalkyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, 3-10 membered heterocycloalkyl group, C 6-14 It may be selected from an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means that two H at the same substitution position are replaced by one O to form a double bond.

[0227] 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 coordinate bond, etc. In the compounds of the present invention, the bond between the core and the substituents or between each substituent is substantially a covalent bond.

[0228] Unless otherwise specified, the term "carboxy" refers to the group "-C(O)OH."

[0229] Unless otherwise specified, the term "hydroxyl group" means an "-OH" group.

[0230] Unless otherwise specified, the term "mercapto" refers to an "-SH" group.

[0231] Unless otherwise specified, the term "amino group" refers to an "-NH" group. In some embodiments, an amino group is a group in which one or two hydrogen atoms are replaced by alkyl (e.g., -NH(C 1-6 alkyl), -N(C 1-6 Also includes alkyl)2 etc.

[0232] Unless otherwise specified, the term "nitro group" means a "-NO2" group.

[0233] Unless otherwise specified, the term "cyano" refers to a "-CN" group.

[0234] The term "oxo" refers to two hydrogen atoms at the same substitution position replaced by one oxygen atom to form a double bond (ie, "=O").

[0235] Unless otherwise specified, the term "alkyl group" means a straight- or branched-chain 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 even more preferably 1 to 6 carbon atoms (i.e., C 1-6 alkyl group). For example, "C 1-6 The term "alkyl group" refers to an alkyl group having 1 to 6 carbon atoms in the carbon chain (specifically, 1, 2, 3, 4, 5, or 6). Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, s-butyl, n-pentyl, neopentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, n-heptyl, and n-octyl groups.

[0236] Unless otherwise specified, the term "alkoxy group" refers to an -O-alkyl group, where the alkyl group, as defined above, may contain 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 8 carbon atoms, and even more preferably 1 to 6 carbon atoms (i.e., C 1-6 alkoxy group). For example, "C 1-6The term "alkoxy group" refers to an alkoxy group having 1 to 6 carbon atoms in the carbon chain (specifically, 1, 2, 3, 4, 5, or 6 carbon atoms). Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, t-butoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, and 1-ethylpropoxy.

[0237] Unless otherwise specified, the term "halogen" or "halogenated" means fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0238] Unless otherwise specified, the term "halogenated alkyl group" means an alkyl group, as defined above, in which one, two, more than one, or all hydrogen atoms have been replaced with halogen. Examples of halogenated alkyl groups include, but are not limited to, -CCl3, -CF3, -CHCl2, -CH2Cl, -CH2Br, -CH2I, -CH2CF3, -CF2CF3, and the like.

[0239] Unless otherwise specified, the term "alkenyl group" means a straight- or branched-chain monovalent aliphatic hydrocarbon group containing one or more (e.g., 1, 2, 3, or 4) carbon-carbon double bonds, which may contain 2 to 20 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 8 carbon atoms, and even more preferably 2 to 6 carbon atoms (i.e., C 2-6 alkenyl group). For example, "C 2-6 The term "alkenyl group" refers to an alkenyl group having 2 to 6 carbon atoms in the carbon chain (specifically, 2, 3, 4, 5, or 6). Examples of alkenyl groups include, but are not limited to, vinyl, n-propenyl, n-butenyl, and n-pentenyl groups.

[0240] Unless otherwise specified, the term "alkynyl group" means a straight- or branched-chain monovalent aliphatic hydrocarbon group containing one or more (e.g., 1, 2, 3, or 4) carbon-carbon triple bonds, which may contain 2 to 20 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 8 carbon atoms, and even more preferably 2 to 6 carbon atoms (i.e., C 2-6 alkynyl group). For example, "C 2-6 The term "alkynyl group" refers to an alkynyl group having 2 to 6 carbon atoms in the carbon chain (specifically, 2, 3, 4, 5, or 6). Examples of alkenyl groups include, but are not limited to, an ethynyl group, an n-propynyl group, an n-butynyl group, an n-pentynyl group, and the like.

[0241] Unless otherwise specified, the terms "carbocyclic group" or "carbocycle" mean a monocyclic or polycyclic, saturated or partially unsaturated, monovalent non-aromatic hydrocarbon group, which may contain from 3 to 14 ring carbon atoms (i.e., C 3-14 carbocyclic groups), preferably 3 to 12 ring carbon atoms (i.e., C 3-12 carbocyclic groups), more preferably 4 to 12 ring carbon atoms (i.e., C 4-12 carbocyclic groups) or 3 to 10 ring carbon atoms (i.e., C 3-10 In some embodiments, carbocyclic groups contain 3 to 8 ring carbon atoms ("C 3-8 carbocyclic group). C 3-6 Examples of carbocyclic groups include, but are not limited to, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like. 3-8 Examples of carbocyclic groups include the above C 3-6Examples of carbocyclic groups include, but are not limited to, cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptyl (C7), bicyclo[2.2.2]octyl (C8), and the like. 3-10 Examples of carbocyclic groups include the above C 3-8 Carbocyclic groups and cyclononyl groups (C9), cyclononenyl groups (C9), cyclodecyl groups (C 10 ), cyclodecenyl group (C 10 ), octahydro-1H-indenyl group (C9), decalinyl group (C 10 )(decalinyl), spiro[4.5]decyl group (C 10 Carbocyclic groups include, but are not limited to, monocyclic (monocyclic carbocyclic group) ring systems or fused (fused ring groups), bridged (bridged ring groups), or spiro-bonded (spirocyclic group) ring systems, such as, for example, bicyclic (bicyclic carbocyclic group) systems, and may be saturated or partially unsaturated. In some embodiments, carbocyclic groups further include ring systems in which a carbocyclic ring, as defined above, is fused with one or more aryl / heteroaryl groups, and the point of attachment is on the carbocyclic ring. Alternatively, in some embodiments, carbocyclic groups, as defined above, are fused with one or more carbocyclic groups, as defined above, and the point of attachment is on either carbocyclic ring. In these cases, the number of members in the carbocyclic ring system is the number of ring carbon atoms in the fused ring system. In some embodiments, carbocyclic groups are optionally substituted, for example, unsubstituted (unsubstituted carbocyclic group) or substituted with one or more substituents (substituted carbocyclic group). In some embodiments, the carbocyclic group is an unsubstituted C 3-10 In some embodiments, the carbocyclic group is a substituted C 3-10 It is a carbocyclic group.

[0242] Unless otherwise specified, the term "cycloalkyl group" means a monocyclic saturated monovalent aliphatic hydrocarbon group, which may contain 3 to 12 carbon atoms (i.e., C 3-12cycloalkyl group), and preferably contains 3 to 10 carbon atoms (i.e., C 3-10 cycloalkyl groups), and more preferably may contain 3 to 7 carbon atoms (i.e., C 3-7 cycloalkyl groups), and may contain 4 to 6 carbon atoms (i.e., C 4-6 cycloalkyl groups), or may contain 5 to 6 carbon atoms (i.e., C 5-6 cycloalkyl groups). For example, "C 3-10 The term "cycloalkyl group" refers to a cycloalkyl group having 3 to 10 carbon atoms in the carbon ring (specifically, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms). Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, 2-ethylcyclopentyl, dimethylcyclobutyl, and the like.

[0243] Unless otherwise specified, the term "heterocyclic group" or "heterocycle" means a monocyclic or polycyclic saturated or partially unsaturated monovalent non-aromatic group having ring carbon atoms and 1 to 4 hetero ring atoms, and may contain 3 to 20 ring atoms, consisting of 1, 2, 3 or more ring atoms selected from N, O, or S, and the remaining ring atoms being C (i.e., a 3- to 12-membered heterocyclic group), and more preferably 3 to 10 ring atoms. The heterocyclic group may contain 1 to 4 ring atoms (i.e., a 3- to 10-membered heterocyclic group), 3 to 8 ring atoms (i.e., a 3- to 8-membered heterocyclic group), 3 to 6 ring atoms (i.e., a 3- to 6-membered heterocyclic group), 4 to 6 ring atoms (i.e., a 4- to 6-membered heterocyclic group), or 5 to 6 ring atoms (i.e., a 5- to 6-membered heterocyclic group), and the number of heteroatoms is 1 to 4, preferably 1 to 3 (i.e., 1, 2, or 3). Examples of monocyclic heterocyclic groups include, but are not limited to, pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, dihydropyrrolyl, piperidinyl, piperazinyl, and pyranyl groups. Examples of polycyclic heterocyclic groups include fused-ring, spiro-ring, fused-ring, and bridged-ring heterocyclic groups. Heterocyclic groups can be monocyclic (monocyclic heterocyclic groups) ring systems or can be fused (fused heterocyclic groups or heterofused ring groups), fused-ring (heterofused ring groups or fused-ring heterocyclic groups), bridged (heterobridged ring groups or bridged-ring heterocyclic groups), or spiro-connected (heterospirocyclic groups or spirocyclic heterocyclic groups), such as, for example, bicyclic systems (bicyclic heterocyclic groups), and can be saturated or partially unsaturated. Bicyclic heterocyclic groups can have one or more heteroatoms in one or both rings. In some embodiments, heterocyclic groups further include ring systems in which a heterocyclic group, as defined above, is fused with one or more carbocyclic groups, and the point of attachment is at the carbocyclic or heterocyclic ring. Alternatively, in some embodiments, heterocyclic groups further include ring systems in which a heterocyclic group, as defined above, is fused with one or more aryl / heteroaryl groups, where the point of attachment is at the aryl / heteroaryl group or the heterocyclic ring. Alternatively, in some embodiments, heterocyclic groups, as defined above, are fused with one or more heterocyclic groups, as defined above, where the point of attachment is at either the heterocyclic ring.In these cases, the number of members of the heterocyclic ring system refers to the number of ring atoms in the fused ring system. In some embodiments, the heterocyclic group may be optionally substituted, e.g., unsubstituted (unsubstituted heterocyclic group) or substituted with one or more substituents (substituted heterocyclic group). Examples of 3-membered heterocyclic groups containing one heteroatom include, but are not limited to, aziridinyl, oxiranyl, and thiorenyl. Examples of 4-membered heterocyclic groups containing one heteroatom include, but are not limited to, azetidinyl, oxetanyl, and thietanyl. Examples of 5-membered heterocyclic groups containing one heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, pyrrolidinyl, dihydropyrrolyl, and 2,5-dioxopyrrolidinyl. Examples of 5-membered heterocyclic groups containing two heteroatoms include, but are not limited to, dioxolyl, oxathiolanyl, dithiolanyl, and 2-oxooxazolidinyl groups. Examples of 5-membered heterocyclic groups containing three heteroatoms include, but are not limited to, triazolinyl, oxadiazolinyl, and thiadiazolinyl groups. Examples of 6-membered heterocyclic groups containing one heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridyl, and tetrahydrothiopyranyl (thianyl) groups. Examples of 6-membered heterocyclic groups containing two heteroatoms include, but are not limited to, piperazinyl, morpholinyl, dithianyl, and dioxanyl groups. Examples of 6-membered heterocyclic groups containing three heteroatoms include, but are not limited to, triazinanyl, oxadiazinanyl, thiadiazinanyl, oxathiazinanyl, and dioxazinanyl. Examples of 7-membered heterocyclic groups containing one heteroatom include, but are not limited to, azepanyl, oxepanyl, and thiepanyl.Examples of 8-membered heterocyclic groups containing one heteroatom include, but are not limited to, azocanyl, oxocanyl, and thiecanyl. Examples of 5-membered heterocyclic groups fused to one C6 aryl ring (also referred to herein as 5,6-bicyclic heterocyclic groups) include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuryl, dihydrobenzothienyl, benzoxazolinonyl, etc. Examples of 6-membered heterocyclic groups fused to one C6 aryl ring (also referred to herein as 6,6-bicyclic heterocyclic groups) include, but are not limited to, tetrahydroquinolinyl, tetrahydroisoquinolinyl, etc.

[0244] Unless otherwise specified, the term "heterocycloalkyl group" refers to a monocyclic, saturated, "heterocyclic group" or "heterocycle" as defined above, which may contain 3 to 20 ring atoms consisting of 1, 2, 3, or more ring atoms selected from N, O, or S, and the remaining ring atom(s) being C (i.e., a 3-20-membered heterocycloalkyl group), preferably 3 to 12 ring atoms (i.e., a 3-12-membered heterocycloalkyl group), and more preferably 3 to 10 ring atoms (i.e., a 3-12-membered heterocycloalkyl group). The heterocycloalkyl group may contain 3 to 8 ring atoms (i.e., a 3- to 10-membered heterocycloalkyl group), 4 to 7 ring atoms (i.e., a 4- to 7-membered heterocycloalkyl group), 5 to 10 ring atoms (i.e., a 5- to 10-membered heterocycloalkyl group), or 5 to 6 ring atoms (i.e., a 5- to 6-membered heterocycloalkyl group), with 1 to 4, preferably 1 to 3 (1, 2, or 3) heteroatoms. In some embodiments, a heterocycloalkyl group is optionally substituted, e.g., unsubstituted (unsubstituted heterocycloalkyl group) or substituted with one or more substituents (substituted heterocycloalkyl group). Several examples of "heterocycloalkyl groups" are mentioned in the above description of "heterocyclic group" or "heterocycle," and examples include, but are not limited to, an aziridinyl group, an oxiranyl group, a thiorenyl group, an azetidinyl group, an oxetanyl group, a thietanyl group, a tetrahydrofuranyl group, a tetrahydropyranyl group, a piperidinyl group, a piperazinyl group, a morpholinyl group, a thiomorpholinyl group, an oxathianyl group, an oxazolidinyl group, a dioxanyl group, a dithianyl group, a thiazolidinyl group, a pyrrolidinyl group, a pyrazolidinyl group, and an imidazolidinyl group.

[0245] Unless otherwise specified, the term "fused ring" means a non-aromatic saturated or partially unsaturated ring system formed by two or more ring structures that share two adjacent atoms, and includes fused carbocyclic groups and fused heterocyclic groups, the ring atoms of which contain one or more heteroatoms independently selected from oxygen, nitrogen, and sulfur.

[0246] Unless otherwise specified, the term "monocyclic spiro ring group" refers to a saturated monovalent aliphatic hydrocarbon group containing only one spiro carbon atom, which may contain 6 to 14 ring carbon atoms, preferably 7 to 10 ring carbon atoms. Monocyclic spiro ring 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 monocyclic spiro ring groups, etc., where each spiro atom is counted as a member in each ring. Examples of monocyclic spiro ring groups include: [ka] These include (but are not limited to):

[0247] Unless otherwise specified, the term "monocyclic heterospirocyclic group" refers to a saturated monovalent aliphatic group containing only one spiro carbon atom, and may contain 6 to 14 ring atoms, preferably 7 to 10 ring atoms, including 1 to 4 heteroatoms independently selected from N, O, and S, preferably 1 to 3 (i.e., 1, 2, or 3) heteroatoms. Monocyclic heterospirocyclic 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 heteromonocyclic spirocyclic groups, etc., where each spiro atom is counted in the number of members of each ring. Examples of monocyclic heterospirocyclic groups include: [ka] These include (but are not limited to):

[0248] 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 bonded, and may contain 5 to 20 ring carbon atoms, preferably 6 to 14 ring carbon atoms, and more preferably 7 to 10 ring carbon atoms, and may further 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. Bicyclic, tricyclic, or tetracyclic bridged ring groups are preferred, and bicyclic or tricyclic bridged ring groups are more preferred. Examples of bridged ring groups include: [ka] These include (but are not limited to):

[0249] Unless otherwise specified, the term "heterobridged cyclic group" refers to a polycyclic monovalent aliphatic group in which any two rings share two ring atoms that are not directly bonded, and may contain 5 to 14 ring atoms, including 1 to 4 heterocyclic atoms independently selected from N, O, and S, preferably 1 to 3 (i.e., 1, 2, or 3) heterocyclic atoms, and preferably 6 to 14 ring atoms, more preferably 7 to 10 ring atoms, and may further contain one or more double bonds, but no ring has a completely conjugated π-electron system. Heterobridged cyclic groups include bicyclic, tricyclic, tetracyclic, or polycyclic heterobridged cyclic groups. Bicyclic, tricyclic, or tetracyclic heterobridged cyclic groups are preferred, and bicyclic or tricyclic heterobridged cyclic groups are more preferred. Examples of heterobridged cyclic groups include: [ka] These include (but are not limited to):

[0250] Unless otherwise specified, the term "aryl group" or "aromatic ring group" means a monovalent aromatic hydrocarbon group, which may be monocyclic or polycyclic, and may contain from 6 to 16 ring carbon atoms (i.e., C 6-16 aryl groups), 6 to 14 ring carbon atoms (i.e., C 6-14aryl groups), 6 to 12 ring carbon atoms (i.e., C 6-12 aryl group) or 6 to 10 ring carbon atoms (i.e., C 6-10 In some embodiments, the terms "aryl group" and "aromatic ring" are used interchangeably. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl, phenanthrenyl, pyrenyl, and the like.

[0251] Unless otherwise specified, the term "heteroaryl group" or "heteroaromatic ring group" means a monocyclic or polycyclic monovalent aromatic group that may contain 5 to 14 ring atoms, consisting of one, two, three, or more ring atoms independently selected from O, N, or S, and the remaining ring atoms being C (i.e., a 5-14-membered heteroaryl group), 5 to 10 ring atoms (i.e., a 5-10-membered heteroaryl group), 5 to 8 ring atoms (i.e., a 5-8-membered heteroaryl group), or 5 to 6 ring atoms (i.e., a 5-6-membered heteroaryl group). In some embodiments, the terms "heteroaryl group" and "heteroaromatic ring" are used interchangeably. Examples of heteroaryl groups include furanyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thiodiazolyl, triazinyl, phthalazinyl, quinolinyl, isoquinolinyl, pteridyl, purinyl, indolyl, isoindolyl, indazolyl, benzofuranyl, benzothienyl, and benzo Examples of such alkyl groups include, but are not limited to, a pyridyl group, a benzopyrimidinyl group, a benzopyrazinyl group, a benzimidazolyl group, a benzophthalazinyl group, a pyrrolo[2,3-b]pyridyl group, an imidazo[1,2-a]pyridyl group, a pyrazolo[1,5-a]pyridyl group, a pyrazolo[1,5-a]pyrimidinyl group, an imidazo[1,2-b]pyridazinyl group, a [1,2,4]triazolo[4,3-b]pyridazinyl group, a [1,2,4]triazolo[1,5-a]pyrimidinyl group, and a [1,2,4]triazolo[1,5-a]pyridyl group.

[0252] Unless otherwise specified, the term "pharmaceutically acceptable salt" or "pharmaceutically acceptable salt" means, within the scope of sound medical judgment, a salt that is suitable for use in contact with the tissues of mammals (particularly humans) without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit / risk ratio. For example, pharmaceutically acceptable salts of amines, carboxylic acids, and other types of compounds are well known in the art. Such salts may be prepared directly during the final isolation and purification of the compounds of this invention, or may be prepared separately by reacting the free base or free acid with appropriate reagents.

[0253] Unless otherwise specified, the term "isotopically-derived" means that the compounds of the present invention may exist in isotopically-labeled or isotopically-enriched form containing one or more atoms having an atomic mass or mass number different from the atom most abundant in nature. The isotope may be a radioactive or non-radioactive isotope. Typically, the isotope used for isotopic labeling is a hydrogen isotope. 2 H and 3 H, a carbon isotope 13 C and 14 C, a chlorine isotope 35 Cl and 37 Cl, a fluorine isotope 18 F, an iodine isotope 123 I and 125 I, a nitrogen isotope 13 N and 15 N, an oxygen isotope 15 O. 17 O and 18 O, a sulfur isotope 35 These isotopically labeled compounds can be used to study the distribution of pharmaceutical molecules in tissues. 2 H and 13 C is widely used because it is easy to label and detect.

[0254] Unless otherwise specified, the term "solvate" or "solvate" refers to a physical association of a compound of the present invention with one or more solvent molecules (whether organic or inorganic). This physical association includes hydrogen bonding. In some cases, the solvate may be isolated, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. The solvent molecules in a solvate may be present in a regular and / or irregular arrangement. The solvate may contain stoichiometric or non-stoichiometric solvent molecules. "Solvate" encompasses both solution-phase and isolatable solvates. Examples of solvates include, but are not limited to, hydrates, ethanol solvates, methanol solvates, and isopropanol solvates. Solvation methods are well known in the art.

[0255] Unless otherwise specified, the term "optical isomers" refers to isomers that have similar physical and chemical properties, identical bonding sequences of atoms in their molecules, but different optical rotations. Unless otherwise specified, the term "geometric isomer" (especially "cis-trans isomer") refers to isomers containing carbon-carbon or carbon-nitrogen double bonds in the E or Z configuration. The term "E" denotes that higher priority substituents are on opposite sides of the carbon-carbon or carbon-nitrogen double bond, and the term "Z" denotes that higher priority substituents are on the same side of the carbon-carbon or carbon-nitrogen double bond. Priority can be determined by the Cahn-Ingold-Prelog priority rules. The compounds of the present invention may also exist as mixtures of "E" and "Z" isomers. Unless otherwise specified, the term "tautomer" refers to isomers with different energies that are interconvertible via a low energy barrier. When tautomerization is possible (e.g., in solution), a chemical equilibrium of tautomers can be reached. For example, proton tautomers (also known as prototropic tautomers) include tautomers that interconvert via migration of a proton, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers include tautomers that interconvert via rearrangement of bonding electrons.

[0256] Unless otherwise specified, the structural formulae depicted in the present invention encompass all isomeric forms (e.g., enantiomeric, non-enantiomeric, geometric (e.g., conformational) isomers, tautomeric forms, etc.) including asymmetric centers, such as R, S configurations, (Z), (E) isomers of double bonds, and (Z), (E) conformational isomers. Thus, all individual stereochemical isomers of the compounds of the present invention or mixtures of their enantiomers, diastereomers, geometric (e.g., conformational) or tautomers are within the scope of the present invention.

[0257] Unless otherwise specified, the term "prodrug" refers to a drug that is converted into the parent drug in the body. Prodrugs are generally useful and can help improve certain undesirable physical or biological properties. Physical properties typically include the drug's solubility (too high or insufficient lipid or water solubility) or stability, while problematic biological properties include rapid metabolism or low bioavailability, which themselves may be related to physicochemical properties. For example, a prodrug may be orally bioavailable, whereas the parent drug is not. A prodrug may also have enhanced solubility in pharmaceutical compositions compared to the parent drug. An example of a prodrug includes, but is not limited to, administering any compound of the present invention as an ester ("prodrug") to facilitate transport across cell membranes, where water solubility is detrimental to transport but beneficial once inside cells, and which is then hydrolyzed to the active carboxylic acid once inside the cells. Another example of a prodrug is a short peptide (polyamino acid) attached to an acid group that is activated by metabolism. [Effects of the Invention]

[0258] The present invention provides ATM kinase inhibitors with novel structures, methods for preparing the same, and uses in the pharmaceutical field. In particular, the compounds of the present invention are useful for the treatment of cancer. Enzyme experiments show that the compounds of the present invention have good selectivity for the ATM target site and can significantly inhibit ATM kinase activity. Furthermore, the present invention employs a specific synthetic method that is simple, easy to operate, and advantageous for large-scale industrial production and application. DETAILED DESCRIPTION OF THE INVENTION

[0259] The present invention will be further described below through specific examples, which are merely for illustrative purposes and are not intended to limit the scope of the present invention.

[0260] In the following examples, experimental methods for which no detailed conditions are given are generally carried out under conventional conditions or under conditions recommended by the manufacturer. Furthermore, any methods or materials similar or equivalent to those described can be applied to the methods of the present invention.

[0261] Unless otherwise specified, technical and technical terms used in the following examples have the meanings familiar to those skilled in the art. Abbreviations used in the Preparations, Examples and elsewhere in the context have the following meanings: DCM dichloromethane TEA Triethylamine DIEA / DIPEA N,N-Diisopropylethylamine DMF N,N-dimethylformamide EtOAc ethyl acetate h time mL milliliter HATU 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate MeOH Methanol TFA trifluoroacetic acid DMSO-d6 Deuterated Dimethyl Sulfoxide

[0262] [Example of intermediate production] (Intermediate Production 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) [ka] (Step 1) Synthesis of diethyl 2-((4-bromo-3,5-difluorophenyl)amino)methylene)malonate A 250 mL flask was charged with 4-bromo-3,5-difluoroaniline (5.00 g, 24 mmol), diethyl 2-ethoxymethylenemalonate (7.80 g, 36 mmol), and absolute ethanol (50 mL). The reaction mixture was refluxed for 8 hours. After confirming the completion of the reaction by TLC, the mixture was cooled to 10 °C, and a white solid precipitated. The solid was collected by suction filtration, rinsed with n-hexane, and dried to give diethyl 2-((4-bromo-3,5-difluorophenyl)amino)methylene)malonate (7.3 g, 80.3% yield). ESI-MS (m / z): 378.01 / 380.01 [M+H] + ; 1 H NMR (600MHz,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).

[0263] (Step 2) Synthesis of ethyl 6-bromo-5,7-difluoro-4-hydroxyquinoline-3-carboxylate Diphenyl ether (80 mL) was placed in a 250 mL flask and heated to 240 °C. Diethyl 2-((4-bromo-3,5-difluorophenyl)amino)methylene)malonate (7.30 g, 19.3 mmol) was added portionwise. The reaction mixture was allowed to react at 240 °C for 1 h. After completion of the reaction was confirmed by TLC, the reaction mixture was cooled to 25 °C to precipitate a crystalline solid. The mixture was diluted with ethyl ether (80 mL), and the solid was collected by suction filtration, rinsed with ethyl ether, and dried to give ethyl 6-bromo-5,7-difluoro-4-hydroxyquinoline-3-carboxylate (5.50 g, 85.8% yield). ESI-MS (m / z): 331.97 / 333.96 [M+H] + ; 1 H NMR (600MHz, DMSO-d6) δ: 1.271 (t, 3H), 4.208 (q, 2H), 7.402 (d, 1H), 8.528 (s, 1H), 12.404 (s, 1H).

[0264] (Step 3) Synthesis of ethyl 6-bromo-4-chloro-5,7-difluoroquinoline-3-carboxylate A 100 mL flask was charged with thionyl chloride (20 mL) and ethyl 6-bromo-5,7-difluoro-4-hydroxyquinoline-3-carboxylate (1.40 g, 4.2 mmol). The reaction mixture was incubated at 80 °C for 3 h. After confirming the completion of the reaction by TLC, the reaction mixture was cooled and concentrated to dryness to obtain the crude product, ethyl 6-bromo-4-chloro-5,7-difluoroquinoline-3-carboxylate (1.48 g, 100% yield). ESI-MS (m / z): 351.93 [M+H] + .

[0265] (Step 4) Synthesis of ethyl (S)-6-bromo-5,7-difluoro-4-((1-hydroxypropan-2-yl)amino)quinoline-3-carboxylate A 100 mL flask was charged with DMF (20 mL), ethyl 6-bromo-4-chloro-5,7-difluoroquinoline-3-carboxylate (1.48 g, 4.2 mmol), L-aminopropanol (0.47 g, 6.3 mmol), and DIEA (1.09 g, 8.4 mmol), and the mixture was heated to 90 °C for 3 h. After confirming completion of the reaction by TLC, the reaction mixture was cooled to room temperature. Water was added to precipitate a solid, which was then collected by suction filtration, rinsed with water, and dried to give ethyl (S)-6-bromo-5,7-difluoro-4-((1-hydroxypropan-2-yl)amino)quinoline-3-carboxylate (1.2 g, 73.4% yield). ESI-MS (m / z): 389.02 / 391.02 [M+H]. + ; 1 H NMR (600MHz,CDCl3)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).

[0266] (Step 5) Synthesis of (S)-10-bromo-9-fluoro-3-methyl-3,4-dihydro-2H-[1,4]oxazepine[5,6,7-de]quinoline-5-carboxylic acid A 100 mL flask was charged with THF (10 mL), (S)-6-bromo-5,7-difluoro-4-((1-hydroxypropan-2-yl)amino)ethyl quinoline-3-carboxylate (1.20 g, 3.08 mmol), water (5 mL), and sodium hydroxide (0.37 g, 9.24 mmol), and the mixture was heated to 60 °C and reacted for 3 h. Completion of the reaction was confirmed by TLC, and the reaction mixture was cooled to room temperature. The pH was adjusted to 5 with 1 N hydrochloric acid, and the precipitated solid was collected by suction filtration, rinsed with water, and dried to give (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, 76.1% yield). ESI-MS(m / z):340.99 / 342.98 [M+H] + .

[0267] (Step 6) Synthesis of (S)-7-bromo-6-fluoro-10-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one 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 sequentially placed in a 100 mL flask, heated to 60 °C, and reacted for 3 h. After confirming the completion of the reaction by TLC, the reaction mixture was cooled to room temperature, water was added, and the precipitated solid was collected by suction filtration, rinsed with water, and dried to give (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, 88.1% yield). ESI-MS (m / z): 337.99 / 339.98 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0268] (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]azulen-1(2H)-one (M-1) DMF (15 mL) and (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, 2.07 mmol) were sequentially placed in a 100 mL flask, and after cooling to 0 °C, NaH (0.124 g, 3.11 mmol) was added and the mixture was allowed to react at this temperature for 0.5 h. After that, iodomethane (0.441 g, 3.11 mmol) was added and the mixture was allowed to react at room temperature overnight. After confirming the completion of the reaction by TLC, water was added to the reaction mixture, and the precipitated solid was collected by suction filtration, rinsed with water, and dried to give (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, 85.1% yield). ESI-MS (m / z): 352.00 / 354.00 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0269] (Intermediate Production 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) [ka] Using the same synthesis method as in Preparation Example 1, except for using D-aminopropanol instead of L-aminopropanol, (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 was obtained in a yield of 75.4%. ESI-MS (m / z): 352.20 / 354.19 [M+H] + .

[0270] (Intermediate Production 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) [ka] Using the same synthesis method as in Preparation Example 1, except for using 2-amino-1-(4-fluorophenyl)ethanol instead of L-aminopropanol, 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 was obtained in 82.4% yield. ESI-MS (m / z): 432.01 / 434.01 [M+H] + .

[0271] (Intermediate Production 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) [ka] Using the same synthesis method as in Preparation Example 1, except for using 2-amino-2-methyl-propanol instead of L-aminopropanol, 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 was obtained in 82.4% yield. ESI-MS (m / z): 366.01 / 368.01 [M+H] + .

[0272] (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) [ka] Using the same synthesis method as in Preparation Example 1, except for using 2-amino-1-(pyridin-2-yl)ethanol instead of L-aminopropanol, 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 was obtained. ESI-MS (m / z): 415.01 / 417.01 [M+H] + .

[0273] (Intermediate Production 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) [ka] Using the same synthesis method as in Preparation Example 1, except for using D-leucinol instead of L-aminopropanol, (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 was obtained in a yield of 30.9%. ESI-MS (m / z): 394.05 / 396.05 [M+H] + .

[0274] (Intermediate Preparation Example 7) Preparation of (S)-7-bromo-6-fluoro-10-isobutyl-2-methyl-9,10-dihydro-8-oxo-2,4,10a-triazanthrachino[2,1,8-cde]azulen-1(2H)-one (M-7) [ka] Using the same synthesis method as in Preparation Example 1, except for using L-leucinol instead of L-aminopropanol, (S)-7-bromo-6-fluoro-10-isobutyl-2-methyl-9,10-dihydro-8-oxo-2,4,10a-triazanthrachino[2,1,8-cde]azulen-1(2H)-one was obtained in a 51.0% yield. ESI-MS (m / z): 393.92 / 395.87 [M+H] + .

[0275] (Intermediate Production 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) [ka] Using the same synthesis method as in Preparation Example 1, except for using mercaptoethylamine instead of L-aminopropanol, 7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one was obtained in 82.1% yield. ESI-MS (m / z): 353.96 / 355.97 [M+H] + .

[0276] (Intermediate Production Example 9) Preparation of 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-10,1-cyclopropan]-1-one (M-9) [ka] Using the same synthesis method as in Preparation 1, except for using 1-aminocyclopropanemethanol instead of L-aminopropanol, 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-10,1-cyclopropane]-1-one was obtained in 43.7% yield. ESI-MS (m / z): 364.01 / 366.01 [M+H] + .

[0277] (Intermediate Production Example 10) Preparation of 7-bromo-9-(ethoxymethyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanthrachino[2,1,8-cde]azulen-1(2H)-one (M-10) [ka] Using the same synthesis method as in Preparation Example 1, except for using 1-amino-3-ethoxy-2-propanol instead of L-aminopropanol, 7-bromo-9-(ethoxymethyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanthrachino[2,1,8-cde]azulen-1(2H)-one was obtained in 49.3% yield. ESI-MS (m / z): 396.03 / 398.03 [M+H] + .

[0278] (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) [ka] Using the same synthetic method as in Preparation 1, except for using (S)-2-amino-3-phenylpropan-1-ol instead of L-aminopropanol, (S)-10-benzyl-7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxo-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one was obtained in 53.2% yield. ESI-MS (m / z): 428.03 / 430.03 [M+H] + .

[0279] (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) [ka] Using the same synthesis method as in Preparation 1, except for using (R)-2-amino-3-phenylpropan-1-ol instead of L-aminopropanol, (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 was obtained in a yield of 32.6%. ESI-MS (m / z): 428.03 / 430.03 [M+H] + .

[0280] (Intermediate Production 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) [ka] Using the same synthesis method as in Preparation Example 1, except for using 2-aminoethanol instead of L-aminopropanol, 7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one was obtained in a yield of 40.7%. ESI-MS (m / z): 337.99 / 339.99 [M+H] + .

[0281] (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) [ka] Using the same synthesis method as in Preparation 1, except for using L-valinol instead of L-aminopropanol, (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 was obtained in a yield of 52.3%. ESI-MS (m / z): 380.03 / 382.03 [M+H] + .

[0282] (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) [ka] Using the same synthesis method as in Preparation 1, except for using D-valinol instead of L-aminopropanol, (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 was obtained in 59.3% yield. ESI-MS (m / z): 380.03 / 382.03 [M+H] + .

[0283] (Intermediate Production 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) [ka] Using the same synthesis method as in Preparation 1, except for using 1-amino-3-methyl-butan-2-ol instead of L-aminopropanol, 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 was obtained in 30.6% yield. ESI-MS (m / z): 380.03 / 382.03 [M+H]+.

[0284] (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) [ka] Using the same synthetic method as in Preparation Example 1, except for using (R)-1-amino-3-(dimethylamino)propan-2-ol instead of L-aminopropanol, (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 was obtained in 75.5% yield. ESI-MS (m / z): 395.04 / 397.04 [M+H] + .

[0285] (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) [ka] Using the same synthesis method as in Preparation Example 1, except for using (R)-1-amino-3-(piperidin-1-yl)propan-2-ol instead of L-aminopropanol, (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 was obtained in a yield of 72.1%. ESI-MS (m / z): 435.08 / 437.08 [M+H] + .

[0286] (Intermediate Production Example 19) Preparation of 5-bromo-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one (M-19) [ka] Using the same synthesis method as in Preparation 1, except for using 2-aminocyclohexanol instead of L-aminopropanol, 5-bromo-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one was obtained in 68.5% yield. ESI-MS (m / z): 392.03 / 394.03 [M+H] + .

[0287] (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) [ka] Using the same synthesis method as in Preparation Example 1, except for using (R)-2-amino-1-butanol instead of L-aminopropanol, (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 was obtained in 71.5% yield. ESI-MS (m / z): 366.02 / 368.02 [M+H] + .

[0288] (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) [ka] Using the same synthesis method as in Preparation Example 1, except for using (S)-2-amino-1-butanol instead of L-aminopropanol, (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 was obtained in 68.5% yield. ESI-MS (m / z): 366.02 / 368.02 [M+H] + .

[0289] (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) [ka] Using the same synthesis method as in Preparation Example 1, except for using 1-amino-2-propanol instead of L-aminopropanol, 7-bromo-6-fluoro-2,9-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one was obtained in 82.4% yield. ESI-MS (m / z): 352.00 / 354.00 [M+H] + .

[0290] (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) [ka] Using the same synthesis method as in Preparation Example 1, except that 2-amino-1-(2-fluoro-pyridin-4-yl)ethanol was used instead of L-aminopropanol, 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 was obtained in a yield of 32.5%. ESI-MS (m / z): 433.00 / 435.00 [M+H] + .

[0291] (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) [ka] Using the same synthesis method as in Preparation 1, except for using 2-amino-2-cyclopropylethanol instead of L-aminopropanol, 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 was obtained in a yield of 28.4%. ESI-MS (m / z): 378.02 / 380.02 [M+H] + .

[0292] (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]azulen-10,1'-cyclobutan]-1-one (M-25) [ka] Using the same synthesis method as in Preparation 1, except for using (1-aminocyclobutyl)methanol instead of L-aminopropanol, 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-10,1'-cyclobutan]-1-one was obtained in 37.5% yield. ESI-MS (m / z): 377.93 / 379.95 [M+H] + .

[0293] (Intermediate Preparation Example 26) Preparation of ethyl (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)-carboxylate (M-26) [ka] Using the same synthetic method as in Preparation 1, except for using ethyl (3S,4R)-4-amino-3-hydroxylpiperidine-1-carboxylate instead of L-aminopropanol, ethyl (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)-carboxylate was obtained in 37.5% yield. ESI-MS (m / z): 464.93 / 466.95 [M+H] + .

[0294] (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]azulen-1(2H)-one (M-27) [ka] Using the same synthesis method as in Preparation 1, except for using 2-amino-2-(4-fluorophenyl)ethanol instead of L-aminopropanol, 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, 32% yield) was obtained. ESI-MS (m / z): 432.21 / 434.25 [M+H] + .

[0295] (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) [ka] (Step 1) Synthesis of 4-bromo-3-fluoro-5-methoxyaniline 3-Fluoro-5-methoxyaniline (4.1 g, 29.1 mmol) and DMF (50 mL) were sequentially placed in a 250 mL flask, and NBS (5.2 g, 29.1 mmol) was added portionwise at room temperature. The reaction mixture was allowed to react for 1 h. After cooling, 100 mL of water and 100 mL of ethyl acetate were added, and the mixture was separated. The extracted 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] + .

[0296] (Step 2) Synthesis of diethyl 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene)malonate A 250 mL flask was charged with 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 absolute ethanol. The reaction mixture was heated to reflux and reacted for 6 h. The mixture was then cooled to room temperature. 100 mL of n-hexane was added at room temperature, and the mixture was filtered to obtain 5.9 g of diethyl 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene)malonate. ESI-MS (m / z): 390.20 / 392.18 [M+H]. + .

[0297] (Step 3) Synthesis of ethyl 6-bromo-5-fluoro-4-hydroxyl-7-methoxyquinoline-3-carboxylate A 250 mL flask was charged with 40 mL of diphenyl ether and heated to 240 °C. Diethyl 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene)malonate (5.9 g, 15.1 mmol) was added in small portions, and the mixture was allowed to react at this temperature for 1 h. The mixture was then cooled to room temperature. 100 mL of n-hexane was added at room temperature, and the mixture was filtered to give 4.6 g of ethyl 6-bromo-5-fluoro-4-hydroxyl-7-methoxyquinoline-3-carboxylate. ESI-MS (m / z): 344.14 / 346.18 [M+H]. + .

[0298] (Step 4) Synthesis of ethyl 6-bromo-4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate Ethyl 6-bromo-5-fluoro-4-hydroxyl-7-methoxyquinoline-3-carboxylate (800 mg, 2.32 mmol) and 10 mL of thionyl chloride were placed in a 100 mL flask, and two drops of DMF were added. The mixture was refluxed for 4 hours. After completion of the reaction, the mixture was evaporated to dryness under reduced pressure to give 840 mg of ethyl 6-bromo-4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate. ESI-MS (m / z): 361.91 / 363.99 [M+H] + .

[0299] (Step 5) Synthesis of ethyl 6-bromo-5-fluoro-4-((2-hydroxyl-1-(pyridin-2-yl)ethyl)amino)-7-methoxyquinoline-3-carboxylate Ethyl 6-bromo-4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate (840 mg, 2.32 mmol), 10 mL of DMF, DIPEA (1500 mg, 11.6 mmol), and 2-amino-2-(pyridin-2-yl)ethanol (600 mg, 2.84 mmol) were sequentially placed in a 100 mL flask, and the reaction mixture was heated to 90 °C for 2 h. Completion of the reaction was confirmed by TLC, and the mixture was cooled to room temperature. Water was added, and the mixture was filtered. The cake was dried to obtain 1.1 g of ethyl 6-bromo-5-fluoro-4-((2-hydroxyl-1-(pyridin-2-yl)ethyl)amino)-7-methoxyquinoline-3-carboxylate. ESI-MS (m / z): 464.29 / 466.30 [M+H] + .

[0300] (Step 6) Synthesis of 10-bromo-9-methoxy-3-(pyridin-2-yl)-3,4-dihydro-2H-[1,4]oxaza[5,6,7-de]quinoline-5-carboxylic acid A 100 mL flask was charged with ethyl 6-bromo-5-fluoro-4-((2-hydroxyl-1-(pyridin-2-yl)ethyl)amino)-7-methoxyquinoline-3-carboxylate (1100 mg, 2.37 mmol), 10 mL of THF, 5 mL of water, and sodium hydroxide (520 mg, 13.0 mmol). The reaction mixture was heated to 60 °C and reacted for 8 h. After completion of the reaction, the THF was removed under reduced pressure, the pH was adjusted to 3 with 6N hydrochloric acid, and the mixture was filtered to obtain 0.3 g of 110-bromo-9-methoxy-3-(pyridin-2-yl)-3,4-dihydro-2H-[1,4]oxaza[5,6,7-de]quinoline-5-carboxylic acid. ESI-MS (m / z): 416.19 / 418.20 [M+H] + .

[0301] (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 flask, 10-bromo-9-methoxy-3-(pyridin-2-yl)-3,4-dihydro-2H-[1,4]oxaza[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 sequentially added, and the reaction mixture was heated to 90 ° C. and reacted for 2 h. After confirming the completion of the reaction by TLC, the reaction mixture was cooled to room temperature, and water was added to precipitate a solid. The solid was then 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] + .

[0302] (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]azulen-1(2H)-one 7-Bromo-6-methoxy-10-(pyridin-2-yl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (300 mg, 0.72 mmol), cesium carbonate (474 ​​mg, 1.45 mmol), and 10 mL of DMF were sequentially placed in a flask, and iodomethane (155 mg, 1.10 mmol) was added at room temperature. The mixture was allowed to react at room temperature for 1.5 hours. After confirming the completion of the reaction by TLC, the reaction mixture was cooled to room temperature, and water was added to precipitate a solid. The solid was filtered to obtain 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 in 64.5% yield. ESI-MS (m / z): 427.03 / 429.03 [M+H] + .

[0303] (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) [ka] Using the same synthesis method as in Preparation Example 1, except for using 4-bromo-3-fluoro-5-methoxyaniline instead of 4-bromo-3,5-difluoroaniline, (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 was obtained in 82.4% yield. ESI-MS (m / z): 364.02 / 366.02 [M+H] + .

[0304] (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) [ka] Using the same synthetic method as in Preparation Example 1, except for using 4-bromo-3-fluoro-5-methoxyaniline instead of 4-bromo-3,5-difluoroaniline and (R)-2-amino-1-propanol instead of (S)-2-amino-1-propanol, (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 was obtained in 82.4% yield. ESI-MS (m / z): 364.02 / 366.02 [M+H] + .

[0305] (Intermediate Production Example 31) Preparation of 5-bromo-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one (M-31) [ka] (Step 1) Synthesis of ethyl 6-bromo-5-fluoro-4-((2-hydroxyphenyl)amino)-7-methoxyquinoline-3-carboxylate Ethyl 6-bromo-4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate (840 mg, 2.32 mmol), 2-aminophenol (280 mg, 2.57 mmol), and 10 mL of glacial acetic acid were sequentially placed in a 100 mL flask, and the reaction solution was heated to 60 ° C. and reacted for 1 hour. After confirming the completion of the reaction by TLC, the reaction solution was cooled to room temperature, and water and ethyl acetate were added to the reaction solution. The mixture was separated, and the organic phase was washed twice with saturated sodium bicarbonate and then concentrated under reduced pressure to dryness, yielding 1.0 g of ethyl 6-bromo-5-fluoro-4-((2-hydroxyphenyl)amino)-7-methoxyquinoline-3-carboxylate.

[0306] (Step 2) Synthesis of 6-bromo-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylic acid Ethyl 6-bromo-5-fluoro-4-((2-hydroxyphenyl)amino)-7-methoxyquinoline-3-carboxylate (1000 mg, 2.30 mmol), 10 mL of THF, 5 mL of water, and sodium hydroxide (460 mg, 11.5 mmol) were placed in a 100 mL flask, and the reaction mixture was heated to 60 °C and reacted for 8 h. After completion of the reaction, the THF was removed under reduced pressure, the pH was adjusted to 3 with 6N hydrochloric acid, and the residue was 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.

[0307] (Step 3) Synthesis of 5-bromo-4-methoxy-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one A 100 mL flask was charged with 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), and the reaction mixture was heated to 90 °C for 2 h. After confirming completion of the reaction by TLC, the reaction mixture was cooled to room temperature, and water was added to precipitate the solid. The solid was then filtered, yielding 0.84 g of 5-bromo-4-methoxy-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one.

[0308] (Step 4) Synthesis of 5-bromo-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one A flask was charged with 5-bromo-4-methoxy-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one (840 mg, 2.19 mmol), cesium carbonate (1420 mg, 4.36 mmol), and 10 mL of DMF. Iodomethane (466 mg, 3.28 mmol) was added dropwise at room temperature. After the addition was complete, the reaction was allowed to proceed for 1.5 h at room temperature. After confirming completion of the reaction by TLC, water was added to the reaction mixture to precipitate a solid. This solid was then filtered, yielding 0.76 g of 5-bromo-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one in 87.3% yield. ESI-MS (m / z): 398.01 / 400.01 [M+H] + .

[0309] (Intermediate Preparation Example 32) Preparation of 5-bromo-4-methoxy-12-methyl-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]pleiaden-11(12H)-one (M-32) [ka] Using the same synthetic method as in Preparation 31, except for using 3-amino-4-hydroxypyridine instead of 2-aminophenol, 5-bromo-4-methoxy-12-methyl-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]pleiaden-11(12H)-one was obtained in 27.3% yield. ESI-MS (m / z): 398.99 / 400.96 [M+H] + .

[0310] (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-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulen-10(11H)-one (M-33) [ka] Using the same synthetic method as in Preparation 1, except for using (3S,4R)-4-aminotetrahydrofuran-3-ol instead of L-aminopropanol, (6aS,9aR)-5-bromo-4-fluoro-11-methyl-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulen-10(11H)-one was obtained in 60.3% yield. ESI-MS (m / z): 379.94 / 381.95 [M+H] + .

[0311] (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-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulen-10(11H)-one (M-34) [ka] Using the same synthetic method as in Preparation 1, except for using (3R,4S)-4-aminotetrahydrofuran-3-ol instead of L-aminopropanol, (6aR,9aS)-5-bromo-4-fluoro-11-methyl-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulen-10(11H)-one was obtained in 82.4% yield. ESI-MS (m / z): 380.00 / 382.00 [M+H] + .

[0312] (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) [ka] Using the same synthesis method as in Preparation 1, except for using 3-amino-3-hydroxymethyloxetane instead of L-aminopropanol, 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 was obtained in a yield of 32.1%. ESI-MS (m / z): 380.00 / 381.99 [M+H] + .

[0313] (Intermediate Preparation Example 36) Preparation of 7-bromo-6-methoxy10-hydroxymethyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (M-36) [ka] Using the same synthetic method as in Preparation 31, except for using 2-amino-1,3-propanediol instead of 2-aminophenol, 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 was obtained in 28.0% yield. ESI-MS (m / z): 380.02 / 382.02 [M+H] + .

[0314] (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) [ka] Using the same synthesis method as in Preparation Example 1, except for using 2-amino-1,3-propanediol instead of L-aminopropanol, 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 was obtained in 74.2% yield. ESI-MS (m / z): 367.96 / 370.02 [M+H] + .

[0315] (Intermediate Preparation Example 38) Preparation of 5-bromo-8-fluoro-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one (M-38) [ka] Using the same synthesis method as in Preparation 31, except for using 2-amino-5-fluorophenol instead of 2-aminophenol, 5-bromo-8-fluoro-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one was obtained in 74.5% yield. ESI-MS (m / z): 416.20 / 418.20 [M+H]+ .

[0316] (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) [ka] Using the same synthetic method as in Preparation 28, except for using 2-amino-1-(pyridin-2-yl)ethanol instead of 2-amino-2-(pyridin-2-yl)ethanol, 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 was obtained in 63.8% yield. ESI-MS (m / z): 427.03 / 429.03 [M+H] + .

[0317] (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) [ka] Using the same synthetic method as in Preparation 28, except for using (R)-2-amino-2-phenylethanol instead of 2-amino-2-(pyridin-2-yl)ethanol, (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 was obtained in 67.2% yield. ESI-MS (m / z): 426.04 / 428.04 [M+H] + .

[0318] (Intermediate Preparation Example 41) Preparation of ethyl 5-fluoro-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-41) [ka] 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 sequentially placed in a 100 mL round-bottom flask and stirred at 90 °C for 2.0 h. After confirming the disappearance of the starting materials by TLC, the reaction mixture was turned off and cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, and the organic phase was extracted. The organic phase was concentrated under reduced pressure, and the crude product was separated by column chromatography to obtain ethyl 5-fluoro-12H-benzo[2,3][1,4]oxaaza[5,6,7-de]quinoline-1-carboxylate in 83.7% yield. 1 H NMR (600MHz,CDCl3)δ 11.590(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 (150MHz,CDCl3)δ 168.78,165.44,163.76,156.80(d,J=13.5Hz),153.05(d,J=13.5Hz),152.54,151.39,148.82,1 33.76,125.85,125.54,121.70,110.35(d,J=19.5Hz),107.28(d,J=27Hz),102.71,61.51,14.39; HR-MS (ESI) theoretical value C 18 H 14 FN2O3[M+H] + :325. 1734, Actual value 325.1732.

[0319] (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) [ka] Using the same synthetic method as in Preparation Example 41, ethyl 5-fluoro-12H-benzo[2,3][1,4]thiazino[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 81.6%. 1 H NMR (600MHz,CDCl3)δ 11.885(s,1H),9.181(s,1H),7.549(d,J=7.2Hz,1H),7.500(d,J=7.8Hz,1 H),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 (150MHz,CDCl3)δ 168.99,164.33,162.63,154.39,154.00(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 FN2O2S [M+H] + :341.0957, Actual value 341.0959.

[0320] (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) [ka] Using the same synthetic method as in Preparation Example 41, ethyl 5-fluoro-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 86.4%. 1H NMR (600MHz,CD3OD+CF3COOH)δ 9.040(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,CD3OD+CF3COOH)δ 168.10,156.01,145.60,135.97,124.63,123.84,120.84,118.89,117.00,115.12,113 .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 FN3O2[M+H] + :324.1171, Actual value 324.1173.

[0321] (Intermediate Preparation Example 44) Preparation of ethyl 5,9-difluoro-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-44) [ka] Using the same synthetic method as in Preparation Example 41, ethyl 5,9-difluoro-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 80.3%. 1 H NMR (600MHz,CDCl3)δ 11.585(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); 13C NMR (150MHz,CDCl3)δ 168.84,165.48,163.67,160.62,158.98,156.30(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 F2N2O3[M+H] + :343.2013, Actual value 343.2011.

[0322] (Intermediate Preparation Example 45) Preparation of ethyl 5-fluoro-10-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-45) [ka] Using the same synthetic method as in Preparation Example 41, ethyl 5-fluoro-10-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 85.6%. 1 H NMR (600MHz,CDCl3)δ 11.542(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); 13C NMR (150MHz,CDCl3)δ 168.82,165.52,163.84,157.39,157.20(d,J=13.5Hz),152.50(d,J=13.5Hz),152.42,151.62,142.84,134.35,12 2.24,111.14,110.51(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 FN2O4[M+H] + :355.0978, Actual value 355.0980.

[0323] (Intermediate Preparation Example 46) Preparation of ethyl 5-fluoro-12H-pyrido[3',4':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-46) [ka] Using the same synthetic method as in Preparation Example 41, ethyl 5-fluoro-12H-pyrido[3',4':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 95.8%. 1 H NMR (600MHz,CD3OD)δ 9.425(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,CD3OD+CF3COOH)δ 168.23,166.68,156.40(d,J=15Hz),152.15,150.11,145.83(d,J=18Hz),142.15,139.3 5,119.32,117.80,116.99,115.89,111.65(d,J=28.5Hz),110.61,106.95,64.53,14.31; HR-MS (ESI) theoretical value C 17 H 13 FN3O3[M+H] + :326. 0832, Actual value 326.0830.

[0324] (Intermediate Preparation Example 47) Preparation of ethyl 5-fluoro-12H-pyrido[4',3':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-47) [ka] Using the same synthetic method as in Preparation Example 41, ethyl 5-fluoro-12H-pyrido[4',3':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 94.5%. 1 H NMR (600MHz,CF3COOH+CDCl3)δ 13.144(s,1H),9.406(s,1H),8.799(s,1H),8.588(d,J=4.2Hz,1H),7.92 7(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 C NMR (150MHz,CF3COOH+CDCl3)δ 167.84,166.63,166.09,156.08,154.78(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 FN3O3[M+H] + :326. 1438, Actual value 326.1440.

[0325] (Intermediate Preparation Example 48) Preparation of ethyl 5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-48) [ka] (Step 1) Synthesis of diethyl 2-(((3-fluoro-5-methoxyphenyl)amino)methylene)malonate 3-Fluoro-5-methoxyaniline (1.41 g, 0.01 mol), diethyl 2-(ethoxymethylene)malonate (2.16 g, 0.01 mol), and 25 mL of absolute ethanol were added sequentially to a 100 mL flask. The reaction mixture was heated to reflux and reacted for 6 hours. The mixture was then cooled to room temperature. The solvent was removed using a rotary evaporator, yielding 2.76 g of diethyl 2-(((3-fluoro-5-methoxyphenyl)amino)methylene)malonate as a colorless, transparent liquid in an 88.7% yield. HR-MS (ESI) theoretical value: C 15 H 19 FNO5[M+H] + 312. 0755, measured value 312.0756; 1 H NMR (600MHz, CDCl3)δ:10.841~10.862(m,1H),8.322~8.344(m,1H),6.304-6.3 95(m, 3H), 4.165~4.239(m, 4H), 3.716~3.726(m, 3H), 1.243~1.316(m, 6H).

[0326] (Step 2) Synthesis of ethyl 5-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate A 100 mL flask was charged with 40 mL of diphenyl ether and heated to 240°C. Diethyl 2-(((3-fluoro-5-methoxyphenyl)amino)methylene)malonate (3.11 g, 0.01 mol) was added, and the mixture was allowed to react at this temperature for 1 hour. The mixture was then cooled to room temperature. 100 mL of n-hexane was added at room temperature, and the mixture was filtered to obtain 2.24 g of ethyl 5-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate as a white solid in a yield of 84.4%. HR-MS (ESI) theoretical value: C 13 H 12 FNO4[M+H] + 266. 1326, Actual value 266.1328; 1H NMR (600MHz,DMSO-d6)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).

[0327] (Step 3) Synthesis of ethyl 4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate Ethyl 5-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (1.30 g, 4.90 mmol) and 10 mL of thionyl chloride were added to a 50 mL flask, and two drops of DMF were added. The mixture was refluxed for 4 hours. After completion of the reaction, the mixture was evaporated to dryness under reduced pressure to give 1.21 g of ethyl 4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate as a yellow solid in 87.1% yield. HR-MS (ESI) theoretical value: C 13 H 12 ClFNO3[M+H] + 283.1184, Actual value 283.1186; 1 H NMR (600MHz, CDCl3)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).

[0328] (Step 4) Synthesis of ethyl 5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate Ethyl 4-chloro-5-fluoro-7-methoxyquinoline-3-carboxylate (0.20 mmol), o-aminophenol (0.24 mmol), DIPEA (0.4 mmol), and DMF (20 mL) were added sequentially to a 100 mL round-bottom flask, and the reaction mixture was stirred at 90 °C for 2.0 h. After confirming the disappearance of the starting materials by TLC, the mixture was turned off and cooled to room temperature. Water and ethyl acetate were added to the reaction mixture, and the organic phase was extracted. The organic phase was concentrated under reduced pressure, and the crude product was separated by column chromatography to obtain ethyl 5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate in 75.0% yield. 1 H NMR (600MHz,CDCl3)δ 11.535(s,1H),9.122(s,1H),7.276-7.290(m,1H),7.081-7.169(m,4H),6.937-6.941(m,1H),4.483 (q,J=7.2Hz,2H),3.959(s,3H),1.494(t,J=7.2Hz,3H); 13 C NMR (150MHz,CDCl3)δ 168.99,163.05,156.11,153.64,152.18,151.32,149.00,134.20,125.58,12 5.24,121.79,121.61,108.68,107.97,105.52,101.94,61.27,55.91,14.46; HR-MS (ESI) theoretical value C 19 H 14 N2O4[M+H] + :337. 1074, measured value 337.1076.

[0329] (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) [ka] Using the same synthetic method as in Preparation Example 48, ethyl 5-methoxy-12H-benzo[2,3][1,4]thiazino[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 64.0%. 1H NMR (600MHz,DMSO-d6)δ 11.565(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 (150MHz,CDCl3)δ 169.10,161.96,154.33,154.13,151.90,145.07,134.17,131.88,129.59,12 8.77,125.74,123.49,121.56,116.46,108.45,104.12,61.50,55.87,14.45; HR-MS (ESI) theoretical value C 19 H 17 N2O3S [M+H] + :353.1283, Actual value 353.1284.

[0330] (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) [ka] Using the same synthetic method as in Preparation Example 48, ethyl 5-methoxy-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 79.0%. 1 H NMR (600MHz,CDCl3)δ 11.641(s,1H),9.109(s,1H),6.899-6.963(m,4H),6.772-6.785(m,1H),6.406-6.409(m,1H),6.085(s,1H),4.431 (q,J=7.2Hz,2H),3.878(s,3H),1.452(t,J=7.2Hz,3H); 13C NMR (150MHz,CDCl3)δ 169.20,162.68,153.63,152.28,151.58,144.79,135.46,131.39,124.64,12 2.84,121.62,119.15,105.33,104.62,102.77,101.68,61.20,55.61,14.41; HR-MS (ESI) theoretical value C 19 H 18 N3O3[M+H] + :336.0512, Actual value 336.0513.

[0331] (Intermediate Preparation Example 51) Preparation of ethyl 9-fluoro-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-51) [ka] Using the same synthetic method as in Preparation Example 48, ethyl 9-fluoro-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 56.3%. 1 H NMR (600MHz,CDCl3)δ 11.481(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 (150MHz,CDCl3)δ 168.99,163.07,160.43,158.80,155.60,152.13,151.12,149.48(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 FN2O4[M+H] +:355.1337, Actual value 355.1338.

[0332] (Intermediate Preparation Example 52) Preparation of ethyl 5,10-dimethoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-52) [ka] Using the same synthetic method as in Preparation Example 48, ethyl 5,10-dimethoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 59.4%. 1 H NMR (600MHz,DMSO-d6)δ 10.955(s,1H),9.766(s,1H),8.894(s,1H),8.582(s,1H),8.321(s,1H),7.165(m,1H),6.194-6.199(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 (150MHz,CDCl3)δ 168.98,163.32,157.24,156.53,153.29,151.88,151.63,143.03,134.70,12 2.35,111.01,108.57,108.09,106.30,105.11,101.93,61.38,55.96,14.46; HR-MS (ESI) theoretical value C 20 H 18 N2O5[M+H] + :367.1534, Actual value 367.1535.

[0333] (Intermediate Preparation Example 53) Preparation of ethyl 5-methoxy-12H-pyrido[4',3':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-53) [ka] Using the same synthetic method as in Preparation Example 48, ethyl 5-methoxy-12H-pyrido[4',3':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 81.2%. 1 H NMR (600MHz,DMSO-d6)δ 11.456(s,1H),9.058(s,1H),8.493(s,1H),8.350(d,J=5.4Hz,1H),7.44 2(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 (150MHz,CDCl3)δ 175.53,158.63,163.25,153.84,152.10,151.08,150.34,145.88,142.6 8,130.14,116.44,109.87,106.14,105.17,102.37,61.81,56.12,14.34; HR-MS (ESI) theoretical value C 18 H 16 N3O4[M+H] + :338.1382, Actual value 338.1382.

[0334] (Intermediate Preparation Example 54) Preparation of ethyl 5-methoxy-12H-pyrido[3',4':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate (M-54) [ka] Using the same synthetic method as in Preparation Example 48, ethyl 5-methoxy-12H-pyrido[3',4':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 89.4%. 1 H NMR (600MHz,CDCl3)δ 11.831(s,1H),9.145(s,1H),8.508(s,1H),8.273(s,1H),7.182(m,1H),6.948-6.988(m,2H),4.471 (q,J=7.2Hz,2H),3.946(s,3H),1.473(t,J=7.2Hz,3H); 13C NMR (150MHz,CDCl3)δ 168.99,163.10,154.94,153.65,151.98,149.68,146.62,144.38,143.8 1,140.10,115.09,109.56,107.02,106.06,102.75,61.74,56.02,14.40; HR-MS (ESI) theoretical value C 18 H 16 N3O4[M+H] + :338.1438, Actual value 338.1440.

[0335] (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) [ka] Using the same synthetic method as in Preparation Example 41, ethyl 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 95.7%. 1 H NMR (600MHz,CDCl3)δ 10.086(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),2.189-2.21 2(m,1H),2.036-2.057(m,1H),1.807-1.814(m,2H),1.296-1.528(m,7H); 13 C NMR (150MHz,CDCl3)δ 169.38,165.53,163.38,156.22,154.47(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 C18 H 20 FN3O2[M+H] + :330.1237, Actual value 330.1238.

[0336] (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) [ka] Using the same synthetic method as in Preparation Example 41, ethyl 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 96.4%. 1 H NMR (600MHz,CDCl3)δ 10.637(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 (150MHz,CDCl3)δ 169.81,169.25,165.82,164.05,157.74,151.56,104.78,102.76,99.41(d,J=21Hz),99.17,60.95,47.47,46.83,14.47; HR-MS (ESI) theoretical value C 14 H 15 FN3O2[M+H] + :276.0974, Actual value 276.0973.

[0337] (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) [ka] Using the same synthetic method as in Preparation Example 48, ethyl 5-methoxy-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate was obtained in a yield of 95.4%. 1 H NMR (600MHz,CDCl3)δ 10.333(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),2.21 1-2.234(m,1H),2.139-2.160(m,1H),1.821-1.836(m,2H),1.315-1.528(m,7H); 13 C NMR (150MHz,CDCl3)δ 168.69,163.32,156.43,149.30,149.02,102.72,100.86,98.63,97.86 ,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 N3O3[M+H] + :342.2013, Actual value 342.2011.

[0338] (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) [ka] Using the same synthetic method as in Preparation Example 48, ethyl 9-methoxy-4,5,6,7-tetrahydro-[1,4]diaza[5,6,7-de]quinoline-3-carboxylate was obtained in a yield of 97.1%. 1H NMR (600MHz,DMSO-d6)δ 10.219(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 HR-MS (ESI) Theoretical value C 15 H 18 N3O3[M+H] + :288.0876, Actual value 276.0878. [Example]

[0339] 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) [ka] (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 A 100 mL flask was charged with 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-boronic 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). The mixture was heated to 90 °C under a nitrogen atmosphere and reacted for 2.5 h. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH = 60:1) to give (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 (0.43 g, 66.3% yield). ESI-MS (m / z): 369.11 [M+H] + ; 1 H NMR (600MHz,CD3OD)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).

[0340] (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]azulen-1(2H)-one A 100 mL flask was charged with THF (4 mL) and 1-piperidinepropanol (115 mg, 0.8 mmol), cooled to 0 °C, and then NaH (56 mg, 1.4 mmol) was added. The mixture was then allowed to react at this temperature for 0.5 h. (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 then added and the mixture was allowed to react at room temperature overnight. After confirming the completion of the reaction by TLC, the reaction mixture was quenched by adding water and then concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1 to 15:1) to give (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, 32% yield). ESI-MS (m / z): 492.23 [M+H] + ; 1 H NMR (600MHz,CD3OD)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).

[0341] 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) [ka] Using the same synthesis method as in Example 1, except for using 3-dimethylaminopropanol instead of 1-piperidinepropanol, (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, 32.0% yield) was obtained. ESI-MS (m / z): 452.20 [M+H] + ; 1 H NMR (600MHz,CD3OD)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).

[0342] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 27.1% yield) was obtained. ESI-MS (m / z): 452.20 [M+H] + ; 1H NMR (600MHz,CD3OD)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),7.5 09(d,J=11.4Hz,1H),7.803-7.818(m,1H),8.226(s,1H),8.792(s,1H).

[0343] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 32% yield) was obtained. ESI-MS (m / z): 492.20 [M+H] + ; 1 H NMR (600MHz, CDCl3)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),7.6 07(d,J=10.8Hz,1H),7.732-7.746(m,1H),8.291(s,1H),8.691(s,1H).

[0344] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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, 13.0% yield) was obtained. ESI-MS (m / z): 532.21 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0345] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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, 33.2% yield) was obtained. ESI-MS (m / z): 506.25 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0346] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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, 32.0% yield) was obtained. ESI-MS (m / z): 555.2 [M+H] + ; 1H 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=9.6Hz,1H),6.855(d,J=9.0Hz,1H),7.177(d,J=8.4 Hz,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).

[0347] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 45.3% yield) was obtained. ESI-MS (m / z): 534.28 [M+H] + ; 1H NMR (600MHz,DMSO-d6)δ:0.980(s,3H),1.239(s,3H),1.395(s,2H),1.515(s,4 H),1.567-1.616(m,1H),1.695-1.762(m,2H),1.921(s,2H),2.287-2.492(m ,6H),3.550(s,3H),4.344(t,J=6.6Hz,2H),4.516(d,J=13.2Hz,1H),4.595-4.701(m,1H),4.722(d,J=3.0H) z,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).

[0348] 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-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-9) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (60 mg, 46.0% yield) was obtained. ESI-MS (m / z): 534.28 [M+H] + ; 1H NMR (600MHz, DMSO-d6)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).

[0349] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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%) was obtained. ESI-MS (m / z): 494.12 [M+H] + ; 1H NMR (600MHz, DMSO-d6)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).

[0350] (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]azulen-10,1-cyclopropan]-1-one (A-11) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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]azulen-10,1-cyclopropan]-1-one (50 mg, 21.2% yield) was obtained. ESI-MS (m / z): 504.23 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0351] (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) [ka] The same synthesis method as in Example 1 was used except for changing the starting material, 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-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (86 mg, 51.0% yield). ESI-MS (m / z): 536.26 [M+H] + ; 1 H NMR (600MHz,CD3OD)δ:1.110-1.134(m,3H),1.594(s,2H),1.744-1.762(m,4H),2. 145-1.172(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, J2=8.4Hz, 1H), 8.285(s, 1H), 8.788(s, 1H).

[0352] (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-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-13) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (30 mg, 20.2% yield) was obtained. ESI-MS (m / z): 568.26 [M+H] + ; 1 H NMR (600MHz, DMSO-d6)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),7.62 6(d,J=11.4Hz, 1H),7.928(d,J=8.4Hz, 1H),8.343(s,1H),8.952(s,1H).

[0353] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 41.5% yield) was obtained. ESI-MS (m / z): 568.26 [M+H] + ; 1H NMR (600MHz,DMSO-d6)δ:1.463-1.624(m,6H),2.055-2.103(m,2H),2.695-2.71 3(m,4H),3.104-3.190(m,4H),3.569(s,3H),4.297-4.440(m,4H),4.692-4.7 14(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).

[0354] (Example 15) 7-(6-(3-dimethylamino-propoxy)-pyridin-3yl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-15) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 7-(6-(3-dimethylamino-propoxy)-pyridin-3yl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (15 mg, 48.2% yield) was obtained. ESI-MS (m / z): 438.42 [M+H] + ; 1 H NMR (600MHz,CD3OD)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,1 H),7.832(d,J=14.4Hz,1H),8.236(s,1H),8.807(s,1H).

[0355] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 24% yield) was obtained. ESI-MS (m / z): 520.26 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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,3 H),4.282-4.351(m,3H),4.445-4.468(m,1H),4.828-4.856(m,1H),6.935(d,J=8.4 Hz,1H),7.566(d,J=10.8Hz,1H),7.828-7.813(m,1H),8.260(s,1H),8.909(s,1H).

[0356] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 24% yield) was obtained. ESI-MS (m / z): 520.26 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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,3 H),4.296-4.365(m,3H),4.459-4.482(m,1H),4.839-4.867(m,1H),6.949(d,J=8.4 Hz,1H),7.579(d,J=10.8Hz,1H),7.840-7.825(m,1H),8.271(s,1H),8.920(s,1H).

[0357] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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 was synthesized (58 mg, yield 44.3%). ESI-MS (m / z): 519.26 [M+H] + ; 1H 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),3.137-3.326 (m,4H),3.547(s,3H),3.994-4.032(m,1H),4.290-4.378(m,4H),6.961(d,J=8.4H z,1H),7.590(d,J=10.8Hz,1H),7.852-7.840(m,1H),8.267(s,1H),8.921(s,1H).

[0358] Example 19: (S)-9-((Dimethylamino)methyl)-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-19) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (S)-9-((dimethylamino)methyl)-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (100 mg, 55.0% yield) was obtained. ESI-MS (m / z): 535.28 [M+H] + ; 1H NMR (600MHz,DMSO-d6)δ:1.600(s,2H),1.746-1.763(m,4H),2.149-2.193(m, 8H),2.650-2.671(m,2H),2.813-2.864(m,6H),3.648(s,3H),4.016-4.055 (q,1H),4.448(t,J=6.0Hz,2H),4.660(d,J=13.2Hz,2H),6.960(d,J=9.0Hz,1H ),7.550(d,J=10.8Hz,1H),7.797(d,J=8.4Hz,1H),8.290(s,1H),8.833(s,1H).

[0359] 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-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (A-20) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (S)-6-fluoro-2-methyl-7-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-9-(piperidin-1-ylmethyl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulen-1(2H)-one (150 mg, 29.6% yield) was obtained. ESI-MS (m / z): 575.31 [M+H] + ; 1H NMR (600MHz,DMSO-d6)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=9.0H z,1H),7.521(d,J=10.8Hz,1H),7.902-7.921(m,1H),8.318(s,1H),8.785(s,1H).

[0360] 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-triazacyclopentadiene [GH]pleiaden-11(12H)-one (A-21) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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-triazacyclopentadiene[gh]pleiaden-11(12H)-one (200 mg, 38.5% yield) was obtained. ESI-MS (m / z): 532.26 [M+H] + ; 1H NMR (600MHz,DMSO-d6)δ:1.635-1.693(m,4H),1.788-1.830(m,7H),2.120(d,J=1 2.0Hz,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,1 H),7.517(d,J=10.8Hz,1H),7.852-7.869(m,1H),8.271(s,1H),8.794(s,1H).

[0361] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 14.3% yield) was obtained. ESI-MS (m / z): 506.25 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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),4.4 10-4.460(m,3H),4.510-4.525(m,1H),4.815-4.842(m,1H),6.938(d,J=8.4Hz,1 H),7.505(d,J=10.8Hz,1H),7.825(d,J=8.4Hz,1H),8.238(s,1H),8.802(s,1H).

[0362] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 42.6% yield) was obtained. ESI-MS (m / z): 506.25 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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= 8.4Hz, 1H), 7.512 (d, J=10.8Hz, 1H), 7.807-7.824 (m, 1H), 8.229 (s, 1H), 8.802 (s, 1H).

[0363] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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, 33.2% yield) was obtained. ESI-MS (m / z): 491.23 [M+H] + ; 1 H NMR (600MHz,CD3OD)δ:1.448(d,J=5.4Hz,3H),1.537(m,2H),1.663-1.701(m,4H),2.067-2.114(m,2 H),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,J=8.4Hz,1H),7.504(d,J=10.8Hz,1H),7.831-7.849(m,1H),8.245(s,1H),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).

[0364] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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%) was synthesized. ESI-MS (m / z): 573.23 [M + H] + ; 1 H NMR (600MHz, MeOD)δ 1.530-1.687(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),5.808-5.8 24(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).

[0365] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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, 19% yield) was obtained. ESI-MS (m / z): 478.22 [M+H] + ; 1H NMR (600MHz,DMSO-d6)δ:1.356-1.450(m,2H),1.514-1.532(m,4H),1.916-1.93 9(m,2H),2.406-2.461(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), 7.585(d,J=10.8Hz,1H),7.821(d,J=8.4Hz,1H),8.257(s,1H),8.903(s,1H).

[0366] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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%) was obtained. ESI-MS (m / z): 518.25 [M+H] + ; 1H NMR (600MHz,DMSO-d6)δ 0.495-0.535(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).

[0367] 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]azulen-10,1′-cyclobutan]-1-one (A-28) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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]azulen-10,1'-cyclobutan]-1-one (70 mg, 44.2% yield) was obtained. ESI-MS (m / z): 518.25 [M+H] + ; 1H NMR (600MHz, DMSO-d6)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).

[0368] 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]azulen-10,1′-cyclopropan]-1-one (A-29) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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]azulen-10,1'-cyclopropan]-1-one (47 mg, 39.1% yield) was obtained. ESI-MS (m / z): 464.20 [M+H] + ; 1 H NMR (600MHz, DMSO-d6)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),4.468(m,2H),6.927-6.941(d,J=8.4Hz,1H),7.599-7.618(d,J=1 1.4Hz, 1H), 7.817-7.832 (d, J=9.0Hz, 1H), 8.256 (s, 1H), 8.916 (s, 1H).

[0369] (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) [ka] A 100 mL flask was charged with 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)boronic acid (90 mg, 0.71 mmol), tetrakis(triphenylphosphine)palladium (55 mg, 0.05 mmol), and 20 mL of dioxane, in that order. The reaction mixture was heated to 120° C. under a N atmosphere and reacted for 4 hours. The reaction mixture was cooled to room temperature, concentrated to dryness, and purified by column chromatography (DCM:MeOH = 40:1 to 30:1) to give 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, 40.1% yield). ESI-MS (m / z): 429.16 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0370] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 33.2% yield) was obtained. ESI-MS (m / z): 504.25 [M+H] + ; 1 H NMR (600MHz,CD3OD)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).

[0371] 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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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, 33.2% yield) was obtained. ESI-MS (m / z): 504.25 [M+H] + ; 1 H NMR (600MHz,CD3OD)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,1H),7.268(s,1H),7.717-7.735(m,1H),8.119-8.123(m,1H),8.703(s,1H).

[0372] (Example 33) 4-Methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one (A-33) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, 4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one (120 mg, 31.5% yield) was obtained. ESI-MS (m / z): 400.41 [M+H] + ; 1H NMR (600MHz,DMSO-d6)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).

[0373] (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]azulen-1(2H)-one (A-34) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, (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, 50% yield) was obtained. ESI-MS (m / z): 397.17 [M+H] + ; 1 H NMR (600MHz,CD3OD)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),4.779-4.787(m ,1H),7.555(d,J=13.2Hz,1H),7.996(d,J=2.4Hz,1H),8.488(s,1H),8.851(s,1H).

[0374] (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) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, 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, 50% yield) was obtained. ESI-MS (m / z): 356.23 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0375] (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) [ka] 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, m-chloroperbenzoic acid (0.03 g, 0.17 mmol) was added in an ice bath, and the mixture was stirred in an ice bath for 1 h. TLC confirmed that a small amount of starting material remained. The reaction mixture was washed with saturated aqueous sodium thiosulfate (10 mL x 2), saturated sodium chloride (10 mL x 2), dried over anhydrous sodium sulfate, the solvent removed under reduced pressure, and the mixture was purified by column chromatography (DCM:MeOH = 50:1 to 25:1) to obtain the final product, 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, 77% yield). ESI-MS (m / z): 372.23 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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,1H),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).

[0376] (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) [ka] 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, m-chloroperbenzoic acid (0.05 g, 0.28 mmol) was added in an ice bath, and the mixture was stirred at room temperature for 24 h. The disappearance of the starting material was confirmed by TLC. The reaction mixture was washed with saturated aqueous sodium thiosulfate (10 mL x 2), saturated sodium chloride (10 mL x 2), dried over anhydrous sodium sulfate, the solvent removed under reduced pressure, and the residue was purified by column chromatography (DCM:MeOH = 50:1 to 30:1) to give 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, 27.3% yield). ESI-MS (m / z): 388.34 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0377] (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)-carboxylate ethyl (A-38) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, ethyl (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)-carboxylate (0.10 g, 59% yield) was obtained. ESI-MS (m / z): 467.2 [M+H] + .

[0378] (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) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, 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, 50% yield) was obtained. ESI-MS (m / z): 434.2 [M+H] + ; 1 H NMR ( 600MHz, DMSO-d6)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).

[0379] (Example 40) 4-Methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]pleiaden-11(12H)-one (A-40) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, 4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]pleiaden-11(12H)-one (12 mg, 30% yield) was obtained. ESI-MS (m / z): 401.11 [M+H] + ; 1 H NMR (600MHz,CD3OD)δ:3.597(s,3H),3.973(s,3H),4.001(s,3H),7.261(d,J=5.4Hz,1H),7.39 9(s,1H),7.953(s,1H),8.230(s,1H),8.455(d,J=5.4Hz,1H),8.923(s,1H),9.714(s,1H).

[0380] (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-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulen-10(11H)-one (A-41) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulen-10(11H)-one (40 mg, 33.6%) was obtained. ESI-MS (m / z): 520.19 [M+H] + ; 1H NMR (600MHz,DMSO-d6)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),4.4 20(t,J=12.0Hz,2H),4.628-4.671(m,1H),4.879(s,1H),5.194(dd,J1=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).

[0381] (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-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulen-10(11H)-one (A-42) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, (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-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulen-10(11H)-one was obtained. ESI-MS (m / z): 520.23 [M+H] + ; 1H NMR (600MHz,CD3OD)δ:1.550 (brs,2H),1.674-1.711(m,4H),2.071-2.118(m,2H),2.679-2.743(m,6H),3.581(s,3H),3.807(t,J=8.4Hz,1 H),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).

[0382] (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]azulen-10,3′-oxetan]-1-one (A-43) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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 (74 mg, 40.4% yield) was obtained. ESI-MS (m / z): 520.23 [M+H] + ; 1H NMR (600MHz, DMSO-d6)δ:1.380-1.405(m,2H),1.500-1.589(m,4H),1.947-1.956(m,2H) ,2.465-2.737(m,6H),3.557(s,3H),4.348-4.370(t,J=6.6Hz,2H),4.348-4.500(m, 2H),4.875-4.960(m,2H),5.424-5.592(m,2H),6.958-6.972(d,J=8.4Hz,1H),7.621 -7.639(d,J=10.8Hz,1H),7.860-7.874(d,J=8.4Hz,1H),8.298(s,1H),8.952(s,1H).

[0383] (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) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, 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, 90.2% yield) was obtained. ESI-MS (m / z): 370.1 [M+H] + ; 1 H 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,1H ),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).

[0384] (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) [ka] A 100 mL flask was charged with DMF (10 mL) and methanol (8 mg, 0.24 mmol), cooled to 0 °C, and then NaH (60%, 15 mg, 0.36 mmol) was added. The mixture was then allowed to react at this temperature for 0.5 h. 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 then added and the mixture was allowed to react at 65 °C for 24 h. After confirming the completion of the reaction by TLC, the reaction mixture was quenched with water and concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1 to 15:1) to give 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, 58.2% yield). ESI-MS (m / z): 518.27 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)δ:1.370-1.405(m,2H),1.490-1.520(m,4H),1.609(s,6H),1.8 62-1.910(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).

[0385] (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) [ka] Using the same synthesis method as in Example 1, except for using 3-dimethylaminopropanol instead of 1-piperidinepropanol, 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, 41.5% yield) was obtained. ESI-MS (m / z): 466.22 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0386] 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]azulen-10,1′-cyclopropan]-1-one (A-47) [ka] Using the same synthetic method as in Example 45, except for changing the starting material, 6-methoxy-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]azulen-10,1'-cyclopropan]-1-one (25 mg, 49.2% yield) was obtained. ESI-MS (m / z): 504.22 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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) ,7.294(s,1H),7.680-7.697(m,1H),8.115(d,J=1.8Hz,1H),8.803(s,1H).

[0387] (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) [ka] Using the same synthesis method as in Example 1, except for changing the starting material, 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 (0.10 g, 48.3% yield) was obtained. ESI-MS (m / z): 508.21 [M+H] + ; 1H NMR (600MHz,DMSO-d6)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),4.505-4.52 7(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).

[0388] 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]azulen-1(2H)-one (A-49) [ka] (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]azulen-1(2H)-one A 100 mL flask was charged with 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]azulen-1(2H)-one (0.10 g, 0.27 mmol), cooled to 0 °C, added with NaH (0.03 g, 0.82 mmol), and reacted at this temperature for 0.5 h. Further, iodomethane (0.08 g, 0.54 mmol) was added, and the mixture was reacted at room temperature for 5 h. After confirming the completion of the reaction by TLC, the reaction mixture was quenched by adding water, concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH = 50:1 to 25:1) to give 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, 29.4% yield). ESI-M (m / z): 381.95 [M+H] + .

[0389] (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]azulen-1(2H)-one A 100 mL flask was charged with 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)boronic 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) in a nitrogen atmosphere at 90 °C for 2.5 h. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 50:1 to 10:1) to give 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, 39.2% yield). ESI-MS (m / z): 522.15 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)δ:1.400-1.528(m, 6H),1.926-1.947(m, 2H),2.434-2.497(m,6H),3.30 7(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).

[0390] (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) [ka] 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 flask, followed by the addition of sodium hydride (25 mg, 0.65 mmol) in an ice bath. The mixture was stirred for 30 minutes in an ice bath, and then iodomethane (22 mg, 0.15 mmol) was added. The mixture was allowed to react for 2 hours at room temperature under a nitrogen atmosphere. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 30:1) to give 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, 40.4% yield). ESI-MS (m / z): 396.16 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0391] (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) [ka] Anhydrous tetrahydrofuran (2 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 (20 mg, 0.05 mmol) were added to a 50 mL flask, followed by DMF (1 mL). Sodium hydride (25 mg, 0.65 mmol) was added in an ice bath, and the mixture was stirred for 30 min in an ice bath. After that, p-toluenesulfonyl chloride (15 mg, 0.08 mmol) was added. The mixture was allowed to react for 2 h at room temperature under a nitrogen atmosphere. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 30:1) to give 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, 48.2% yield). ESI-MS (m / z): 364.13 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)δ:3.352(s,3H),3.915(s,3H),3.962(s,3H),4.954(s,2H),5.3 96(s,1H),6.182(s,1H),7.283(s,1H),7.925(s,1H),8.157(s,1H),8.835(s,1H).

[0392] (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) [ka] (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]azulen-1(2H)-one 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]azulen-1(2H)-one (50 mg, 0.13 mmol), triphenylphosphine (138 mg, 0.524 mmol), and phthalamide (29 mg, 0.19 mmol) were sequentially placed in a 50 mL flask. Diisopropyl azodicarboxylate (106 mg, 0.524 mmol) was added under a nitrogen atmosphere and the mixture was incubated at room temperature for 2 h under a nitrogen atmosphere. After completion of the reaction by TLC, the reaction mixture was added with 50 mL of water and extracted four times with 30 mL of dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, concentrated to dryness, and used directly in the next step. Methanol (15 mL) and hydrazine hydrate (2 mL) were added and the mixture was incubated at room temperature under a nitrogen atmosphere for 2 hours. Completion of the reaction was confirmed by TLC. The methanol was removed under reduced pressure, and the mixture was extracted four times with 30 mL of dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate, and purified by column chromatography (DCM:MeOH = 20:1) to give 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, 58.1% yield). ESI-MS (m / z): 381.16 [M+H] + .

[0393] (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]azulen-1(2H)-one Anhydrous methanol (6 mL) and 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, 0.08 mmol) were sequentially placed in a 50 mL flask, followed by aqueous formaldehyde (2 mL) and acetic acid (10 μL). The mixture was stirred at room temperature for 30 min, and then sodium triacetoxyborohydride (49 mg, 0.23 mmol) was added. The mixture was allowed to react at room temperature for 12 h. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 15:1) to give 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, 27.3% yield). ESI-MS (m / z): 409.19 [M+H] + ; 1 H NMR (600MHz,CDCl3)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).

[0394] (Example 53) 8-Fluoro-4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,10b,12-triaza[gh]pleiaden-11(12H)-one (A-53) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, 8-fluoro-4-methoxy-12-methyl-5-(1-methyl-1H-pyrazol-4-yl)-6-oxa-2,10b,12-triaza[gh]pleiaden-11(12H)-one (200 mg, 66.6% yield) was obtained. ESI-MS (m / z): 418.12 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)δ:3.577(s,3H),3.967-3.998(m,6H),6.934-6.943(m,1H),7.2 53(s,1H),7.349(s,1H),7.972(s,1H),8.235(s,1H),8.475(s,1H),8.872(s,1H).

[0395] (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) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, 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, 63.9% yield) was obtained. ESI-MS (m / z): 429.16 [M+H] + ; 1H NMR (600MHz,DMSO-d6)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=9.0Hz,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).

[0396] (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) [ka] Using the same synthesis method as in Example 30, except for changing the starting material, (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, 43.3% yield) was obtained. ESI-MS (m / z): 428.16 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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).

[0397] (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]azulen-1(2H)-one (A-56) [ka] (Step 1) Synthesis of (6-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-3-yl)boronic acid A 50 mL flask was charged with acetonitrile (20 mL), 1-(but-3-yn-1-yl)piperidine (1.37 g, 10.0 mmol), 2-bromopyridine-5-boronic 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). The mixture was reacted at room temperature for 6 h under a nitrogen atmosphere. After confirming completion of the reaction by TLC, the reaction mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 30:1) to give (6-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-3-yl)boronic acid (1.26 g, 61.1% yield). ESI-MS (m / z): 259.15 [M+H] + .

[0398] (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]azulen-1(2H)-one A 50 mL flask was charged with 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)boronic acid, potassium carbonate (132 mg, 0.96 mmol), water (1 mL), and tetrakis(triphenylphosphine)palladium (55 mg, 0.048 mmol) in that order, and the mixture was heated to 90° C. under a nitrogen gas atmosphere and reacted for 3 hours. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1 to 10:1) to give (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, 15% yield). ESI-MS (m / z): 486.22 [M+H] + ; 1 H NMR (600MHz,CD3OD)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).

[0399] (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-triazacyclopentadiene[gh]pleiaden-11(12H)-one (A-57) [ka] (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-triazacyclopentadiene[gh]azulen-11(12H)-one In a 100 mL flask, 1,4-dioxane (15 mL), 5-bromo-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]pleiaden-11(12H)-one (0.69 g, 1.76 mmol), 6-fluoropyridine-3-boronic 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 sequentially placed, and the mixture was heated to 90 ° C. under a nitrogen gas atmosphere and reacted for 2.5 h. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH = 60:1) to give 4-fluoro-5-(6-fluoropyridin-3-yl)-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]azulen-11(12H)-one (0.35 g, 48.7% yield). ESI-MS (m / z): 409.31 [M+H] + .

[0400] (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-triazacyclopentadiene[gh]pleiaden-11(12H)-one (A-57) A 100 mL flask was charged with 10 mL of DMSO, 3 mL of DIPEA, 4-fluoro-5-(6-fluoropyridin-3-yl)-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]azulen-11(12H)-one (170 mg, 0.417 mmol), and N,N-dimethylpiperidin-4-amine hydrochloride (167 mg, 0.834 mmol), and the mixture was heated to 150 °C for 12 hours. The reaction mixture was cooled to room temperature and washed with ethyl acetate and saturated brine two to three times. The organic phase was then dried and concentrated to give the crude product. The crude product was purified by column chromatography (DCM:MeOH = 30:1 to 6:1) to give 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-triazacyclopentadiene[gh]pleiaden-11(12H)-one (30 mg, 13.9% yield). ESI-MS (m / z): 517.24 [M+H] + ; 1 H NMR (600MHz,DMSO-d6)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),1.713-1.728(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=9.0Hz,1H),7.543(d,J=10.8Hz,1H),7.647(d,J=8.4Hz,1H),8.197(s,1H),8.856(s,1H).

[0401] (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]azulen-1(2H)-one (A-146) [ka] (Step 1) Synthesis of 4-bromo-1-(3-(piperidin-1-yl)propyl)pyridin-2(1H)-one A 100 mL flask was charged with acetonitrile (30 mL), 1-(3-bromopropyl)piperidine 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), and the mixture was refluxed for 5 h. After confirming completion of the reaction by TLC, the reaction mixture was filtered under suction, and the filtrate was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1 to 15:1) to give 4-bromo-1-(3-(piperidin-1-yl)propyl)pyridin-2(1H)-one (1.24 g, 72.0% yield). ESI-M (m / z): 299.07 / 301.07 [M+H] + .

[0402] (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 A 100 mL flask was charged with 1,4-dioxane (25 mL), 4-bromo-1-(3-(piperidin-1-yl)propyl)pyridin-2(1H)-one (1.24 g, 4.14 mmol), bis(pinacolato)diboron (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) in that order, and the mixture was heated to 90°C under a nitrogen gas atmosphere and reacted for 3 hours. The completion of the reaction was confirmed by TLC, and the reaction solution was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1 to 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 79%).

[0403] (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]azulen-1(2H)-one In a 50 mL flask, 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 sequentially placed, and the mixture was heated to 90 ° C. under a nitrogen gas atmosphere and reacted for 3 h. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1 to 10:1) to give (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, 17% yield). ESI-M (m / z): 492.23 [M+H] + ; 1 H NMR (600MHz, CD3OD)δ:1.561-1.572(m,5 H),1.707-1.726(m,4 H),2.100-2.148(m,2 H),2.665 (brs,6 H),3.657(s,3H),4.146(t,J=7.2Hz,2 H),4.559-4.580(m,1 H),4.689-4.715(m,1 H),4.745-4.779(m,1 H),6.582(d,J=6.6Hz,1 H),6.727(s,1H),7.560(d,J=11.4Hz,1 H),7.795(d,J=6.6Hz,1 H),8.868(s,1 H).

[0404] (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]azulen-1(2H)-one (A-148) [ka] (Step 1) Synthesis of 5-bromo-2-((2-(piperidin-1-yl)ethoxy)methyl)pyridine A 100 mL flask was charged with THF (30 mL) and N-hydroxyethylpiperidine (1.0 g, 7.74 mmol), cooled to 0 °C, and then NaH (0.62 g, 15.48 mmol) was added. The mixture was then incubated at this temperature for 0.5 h. After this, 5-bromo-2-(bromomethyl)pyridine (1.94 g, 7.74 mmol) was added and incubated at room temperature for 5 h. After confirming completion of the reaction by TLC, the reaction mixture was quenched with water and concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1 to 15:1) to give 5-bromo-2-((2-(piperidin-1-yl)ethoxy)methyl)pyridine (1.97 g, 85.0% yield). ESI-MS (m / z): 299.07 / 301.07 [M+H] + .

[0405] (Step 2) Synthesis of 2-((2-(piperidin-1-yl)ethoxy)methyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxan-2-yl)pyridine A 100 mL flask was charged with 1,4-dioxane (25 mL), 5-bromo-2-((2-(piperidin-1-yl)ethoxy)methyl)pyridine (1.97 g, 6.58 mmol), bis(pinacolato)diboron (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), and the mixture was heated to 90 °C under a nitrogen atmosphere for 3 h. After confirming completion of the reaction by TLC, the reaction mixture was concentrated to dryness to give the crude product, 2-((2-(piperidin-1-yl)ethoxy)methyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxan-2-yl)pyridine, which was used directly in the next step.

[0406] (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]azulen-1(2H)-one In a 50 mL flask, 1,4-dioxane (5 mL), 2-((2-(piperidin-1-yl)ethoxy)methyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxan-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 sequentially placed, and the mixture was heated to 90 ° C. under a nitrogen gas atmosphere and reacted for 3 h. After confirming the completion of the reaction by TLC, the reaction mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1 to 10:1) to give (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, 17% yield). ESI-MS (m / z): 492.23 [M+H] + ; 1 H NMR (600MHz, CD3OD)δ:1.463-1.624(m,5 H),1.693-1.711(m,4 H),2.748 (brs,4 H),2.881 (brs,2 H),3.622(s,3H),3.835(t,J=5.4Hz,2 H),4.520-4.542(m,1 H),4.613-4.634(m,1 H),4.711-4.726(m,3 H),7.533(d,J=11.4Hz,1 H),7.676(d,J=8.4Hz,1 H),8.004(d,J=8.4Hz,1 H),8.630(s,1 H),8.811(s,1 H).

[0407] (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'-pent-7'-yl)pyridin-3-yl)cyclopropanecarboxamide (A-155) [ka] (Step ...

Claims

1. Formula (I') having the following structure: 【Chemistry 1】 (In the formula, Y is, 【Chemistry 2】 and X １ is selected from the group consisting of a bond, hydrogen, deuterium, and a halogen; X １ is hydrogen, deuterium and halogen, R １ , X ２ , R ２ and R ３ does not exist, R １ is absent or an optionally substituted C ２－６ is selected from the group consisting of an alkenyl group, a 5- to 8-membered heterocyclic group, and a 5- to 6-membered heteroaryl group, wherein the heteroatom is N and the number of heteroatoms is 1 or 2; １ａ means that it has been replaced by R １ａ When present, each independently represents deuterium, halogen, hydroxyl, amino, oxo, -R １ｂ , -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 ) and -N(R １ｂ ) SO ２ (R １ｃ ) selected from the group consisting of R １ｂ and R １ｃ each occurrence independently represents hydrogen, C １－６ Alkyl group, C ３－６ cycloalkyl groups, 3- to 8-membered heterocycloalkyl groups, and phenyl groups; or R １ｂ and R １ｃ are attached to the same nitrogen atom, R １ｂ and R １ｃ together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocycloalkyl group; X ２ represents absence, a bond, hydrogen, deuterium, halogen, —O—, —S—, and —N(R ２ｘ )-, and R ２ｘ is hydrogen, deuterium and C １－６ alkyl groups, X ２ is hydrogen, deuterium or halogen, R ２ and R ３ does not exist, R ２ is non-existent or C １－６ Alkyl group, C ２－４ selected from the group consisting of alkynyl groups and 5-6 membered heterocycloalkyl groups, wherein the heteroatoms are N or O, and the number of the heteroatoms is 1 or 2; R ３ is absent or -R ３ｂ , -OR ３ｂ , -SR ３ｂ , and −N(R ３ｂ ) (R ３ｃ ) selected from the group consisting of R ３ｂ and R ３ｃ each, if present, independently represents hydrogen, deuterium, and C １－６ alkyl groups, or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached, form an optionally substituted 3- to 10-membered heterocyclic group or a 4- to 12-membered bicyclic heterocyclic group, and the term "optionally substituted" means that hydrogen atoms in the substituted group are not substituted, or that hydrogen atoms in one or more substitutable positions of the substituted group are independently substituted with R ３ｄ means that it has been replaced by R ３ｄ When present, each independently represents deuterium, a halogen, a hydroxyl group, an amino group, a cyano group, -R ３ｅ , -C(O)R ３ｅ , -C(O)OR ３ｅ , -N(R ３ｅ ) (R ３ｆ ), -C(O)N(R ３ｅ ) (R ３ｆ ) and -N(R ３ｅ ) C(O)(R ３ｆ ) selected from the group consisting of R ３ｅ and R ３ｆ each, when present, independently represents hydrogen, deuterium, and optionally halogen, hydroxyl group, amino group, C １－６ Alkyl group, C ３－６ Cycloalkyl groups, 3- to 6-membered heterocycloalkyl groups, C ６ C optionally substituted with one or more selected from the group consisting of an aryl group and a 5- to 6-membered heteroaryl group １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, 3- to 6-membered heterocycloalkyl groups, C ６ selected from the group consisting of aryl groups and 5- to 6-membered heteroaryl groups; R ４ When present, C is independently selected from the group consisting of hydrogen, deuterium, halogen, nitro group, amino group, cyano group, hydroxyl group, and C which may be optionally substituted with one or more selected from the group consisting of deuterium, halogen, hydroxyl group, and amino group. １－６ Alkyl group and C １－６ selected from the group consisting of alkoxy groups; h is 1 or 2; R ５ is hydrogen or C １－６ is an alkyl group, L is C(R Ｌ ) or N, R Ｌ is, if present, independently selected from the group consisting of hydrogen, deuterium, halogen, methyl, and methoxy; A is one of the following: 【Transformation 3】 where: 【Chemistry 4】 represents a single bond or a double bond, Q １ binds to W, t １ , t ２ , t ３ , t ４ , t ５ and t ６ are each independently 0 or 1, n １ and n ２ are independently 0 or 1, but are not simultaneously 0; W is selected from the group consisting of C, O, N and S; Q １ is C and Q ２ is C, Q ３ is C and Q ３ When one of the bonds in is a double bond, R １０ or R １１ does not exist, R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ each, when present, independently represents hydrogen, deuterium, halogen, hydroxyl group, amino group, cyano group, nitro group, -R ６ａ , -NH(R ６ａ ) and -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 substituents bonded to the same atom are both ═O and ═N—R ６ａ or =CH-R ６ａ or W, Q １ , Q ２ and Q ３ Any two adjacent atoms among these may optionally be R ６ｃ C may be replaced by ３－１０ Carbocyclic group, 3- to 10-membered heterocyclic group, C ６－１４ or W, Q form an aryl group or a 5- to 12-membered heteroaryl group. １ , Q ２ and Q ３ Any one atom of these, together with the substituent to which it is attached, may optionally be R ６ｃ C may be replaced by ３－１０ forming a carbocyclic group or a 3- to 10-membered heterocyclic group, R ６ａ and R ６ｂ each occurrence independently represents hydrogen, deuterium, and optionally R ６ｃ C may be replaced by １－６ Alkyl group, C １－６ Alkoxy group, C ３－１０ Carbocyclic group, 3- to 10-membered heterocyclic group, C ６－１４ aryl groups and 5- to 12-membered heteroaryl groups, or R ６ａ and R ６ｂ are attached to the same nitrogen atom, R ６ａ and R ６ｂ together with the nitrogen atom to which they are attached, optionally R ６ｃ forming a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group optionally substituted by R ６ｃ are, when present, independently hydrogen, deuterium, halogen, hydroxyl group, amino group, -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 and -C(O)OR ６ｄ selected from the group consisting of R ６ｄ and R ６ｅ each, if present, independently represents hydrogen, deuterium, C １－６ Alkyl group, C １－６ Alkoxy group, C ３－１０ Carbocyclic group, 3- to 10-membered heterocyclic group, C ６－１４ aryl groups and 5- to 12-membered heteroaryl groups; When heterocycloalkyl, heteroaryl, heterocyclic, heteromonocyclic spirocyclic, hetero(hetero)fused and / or hetero(hetero)bridged ring groups are present, the heteroatoms are independently selected from the group consisting of O, N and S, and the number of said heteroatoms is 1, 2, 3 or 4. or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof.

2. The compound has the formula (Ia) 【Transformation 5】 (wherein each substituent is as defined in claim 1) or the compound has a structure represented by formula (I-b) or (I-c) 【Transformation 6】 (wherein each substituent is as defined in claim 1) 10. The compound of claim 1, having the structure:

3. X １ is a bond or halogen, or X １ 3. The compound of claim 1 or 2, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, wherein: is a bond.

4. R １ is an optionally substituted 5- to 6-membered heteroaryl group, wherein the heteroatom is N and the number of the heteroatoms is 1 or 2, and the term "optionally substituted" means that R １ａ or R １ is selected from the group consisting of an optionally substituted ethynyl group, a phenyl group, a pyridyl group, a pyrimidinyl group, a pyrazinyl group, a pyrazolyl group, an imidazolyl group, and a pyrrolyl group, and the term "optionally substituted" means that R １ａ or R １ is selected from the group consisting of an optionally substituted pyridyl group, a pyrimidinyl group, a pyrazinyl group, and a pyrazolyl group, and the term "optionally substituted" means that R １ａ or R １ is selected from the group consisting of optionally substituted pyridyl groups, and the term "optionally substituted" means that R １ａ or R １ is selected from the group consisting of optionally substituted dihydropyridyl groups, and the term "optionally substituted" means that R １ａ or R １ is an optionally substituted group as follows: 【Transformation 7】 (wherein the "*" end is X １ The other end is X ２ and the term "optionally substituted" means that R １ａ (meaning that it may be replaced by selected from the group consisting of Or, R １ optionally, 【Transformation 8】 (wherein the "*" end is X １ The other end is X ２ and the term "optionally substituted" means that R １ａ or R １ Below is the: 【Chemistry 9】 (wherein the "*" end is X １ The other end is connected to X ２ (which binds to selected from the group consisting of groups 4. The compound according to any one of claims 1 to 3, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

5. R １ａ When present, each independently represents a halogen, an amino group, an oxo group, -R １ｂ , -NHC(O)(R １ｂ ) and -NHSO ２ (R １ｂ or R １ａ is, if present, independently —NHC(O)(R １ｂ ) and -NHSO ２ (R １ｂ or R １ａ are independently —H, —F, —Cl, —NH ２ , oxo group, —CH ３ , -CH ２ CH ３ , -OCH ３ , -OCH ２ CH ３ , -NHC(O)CH ３ , -C(O)NHCH ３ , 【Chemistry 10】 Selected from:

5. The compound according to any one of claims 1 to 4, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

6. R １ｂ and R １ｃ each, if present, independently represents C １－６ Alkyl group or C ３－６ is a cycloalkyl group, or R １ｂ and R １ｃ each, if present, independently represents C １－４ Alkyl group or C ３－４ is a cycloalkyl group, or R １ｂ and R １ｃ is, each occurrence independently selected from the group consisting of methyl, ethyl, cyclopropanyl, phenyl, and tetrahydropyranyl; or R １ｂ and R １ｃ each, if present, is independently a methyl group or a cyclopropanyl group; 6. The compound according to any one of claims 1 to 5, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

7. X ２ represents absence, a bond, hydrogen, a halogen, a hydroxyl group, an amino group, —O—, —S—, —NH—, —N(CH ３ )- and -N(CH ２ CH ３ )- or X ２ represents absence, a bond, —O—, and —N(CH ３ ) - selected from 7. The compound according to any one of claims 1 to 6, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

8. R ２ is selected from the group consisting of absent, methyl, ethyl, propyl, butyl, ethynyl, piperidinyl, tetrahydropyrrolyl, and tetrahydropyranyl, or R ２ is selected from the group consisting of absent, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, ethynyl, piperidinyl, tetrahydropyrrolyl, and tetrahydropyranyl, or R ２ is an n-propyl group; 8. The compound according to any one of claims 1 to 7, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

9. R ３ is non-existent, -R ３ｂ , -OR ３ｂ and -N(R ３ｂ ) (R ３ｃ or R ３ HA-N(R ３ｂ ) (R ３ｃ ) or R ３ is an optionally substituted group as follows: 【Chemistry 11】 and the term "optionally substituted" means that R ３ｄ or R ３ is the following group: 【Chemistry 12】 or selected from the group consisting of R ３ is the following group: 【Chemistry 13】 Selected from:

9. The compound according to any one of claims 1 to 8, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

10. R ３ｂ and R ３ｃ each occurrence independently represents an optionally substituted C １－６ is an alkyl group, or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached, form an optionally substituted 4- to 8-membered heterocycloalkyl group or a 6- to 10-membered bicyclic heterocyclic group, and the term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ each occurrence independently represents an optionally substituted C １－６ The term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached, form an optionally substituted 5- to 6-membered heterocycloalkyl group or a 6- to 10-membered bicyclic heterocyclic group, the heteroatoms of which are independently O or N, the number of said heteroatoms being 1, 2, 3 or 4, and the term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ each occurrence independently represents an optionally substituted C １－４ is an alkyl group, or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached, form an optionally substituted 5- to 6-membered heterocycloalkyl group, a 3-membered / 6-membered heteromonocyclic spiro ring group, a 6-membered / 3-membered heteromonocyclic spiro ring group, a 4-membered / 6-membered heteromonocyclic spiro ring group, a 6-membered / 4-membered heteromonocyclic spiro ring group or a 4-membered / 4-membered heteromonocyclic spiro ring group, in which the heteroatoms are independently O or N, the number of the heteroatoms is 1 or 2, and the term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ each occurrence independently represents an optionally substituted C １－４ is an alkyl group, or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached, form an optionally substituted 5- to 6-membered heterocycloalkyl group or a 6- to 10-membered bicyclic heterocyclic group, the heteroatoms of which are independently O or N, the number of said heteroatoms being 1, 2 or 3, and the term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ each occurrence independently represents an optionally substituted C １－４ is an alkyl group, or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached, form an optionally substituted 5- to 6-membered heterocycloalkyl group, a 3-membered / 4-membered heteromonocyclic spirocyclic group, or a 4-membered / 3-membered heteromonocyclic spirocyclic group, a 3-membered / 5-membered heteromonocyclic spirocyclic group, a 5-membered / 3-membered heteromonocyclic spirocyclic group, a 3-membered / 6-membered heteromonocyclic spirocyclic group, a 6-membered / 3-membered heteromonocyclic spirocyclic group, a 4-membered / 5-membered heteromonocyclic spirocyclic group, a 5-membered / 4-membered heteromonocyclic spirocyclic group, a 4-membered / 6-membered heteromonocyclic spirocyclic group, a 6-membered / 4-membered heteromonocyclic spirocyclic group, a 4-membered / and the heterocyclic group is selected from the group consisting of a 4-membered heteromonocyclic spirocyclic group, a 5-membered / 5-membered heteromonocyclic spirocyclic group, a 5-membered / 6-membered heteromonocyclic spirocyclic group, a 6-membered / 5-membered heteromonocyclic spirocyclic group, a 3-membered / 5-membered fused heterocyclic group, a 5-membered / 3-membered fused heterocyclic group, a 3-membered / 6-membered fused heterocyclic group, a 6-membered / 3-membered fused heterocyclic group, a 5-membered / 6-membered fused heterocyclic group, and a 6-membered / 5-membered fused heterocyclic group, wherein the heteroatoms are independently O or N, the number of the heteroatoms is 1, 2, 3, or 4, and the term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ each occurrence independently represents an optionally substituted C １－４ is an alkyl group, or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached, form an optionally substituted 5- to 6-membered heterocycloalkyl group, a 3- or 6-membered heteromonocyclic spiro ring group, a 4- or 6-membered heteromonocyclic spiro ring group, or a 3- or 5-membered fused heterocyclic ring group, the heteroatoms of which are independently O or N, the number of the heteroatoms being 1, 2, or 3, and the term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ each occurrence is independently an optionally substituted methyl group; or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are bonded, form an optionally substituted pyrrolidinyl group, piperazinyl group, piperidinyl group, 2-oxa-7-azaspiro[3.5]nonyl group, 3-azabicyclo[3.1.0]hexyl group or 6-azaspiro[2.5]octyl group, and the term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ each occurrence is independently an optionally substituted methyl group; or R ３ｂ and R ３ｃ are attached to the same nitrogen atom, R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached form an optionally substituted piperidinyl group, and the term "optionally substituted" means that R ３ｄ or R ３ｂ and R ３ｃ together with the nitrogen atom to which they are attached form the following group: 【Chemistry 14】 forming a group selected from the group consisting of 10. The compound according to any one of claims 1 to 9, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

11. R ３ｄ When present, each independently represents deuterium, a halogen, a hydroxyl group, an amino group, a cyano group, —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 group, C １－６ selected from the group consisting of alkoxy groups and 3- to 6-membered heterocycloalkyl groups; or R ３ｄ When present, each independently represents deuterium, a hydroxyl group, an amino group, —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 group, C １－６ selected from the group consisting of alkoxy groups and 5-6 membered heterocycloalkyl groups; or R ３ｄ When present, each independently represents deuterium, fluorine, a hydroxyl group, an amino group, a cyano group, —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 , -OCH ３ , -OCH ２ CH ３ , -OCH ２ CH ２ CH ３ , piperidinyl, piperazinyl and tetrahydropyrrolyl groups, or R ３ｄ When present, each independently represents deuterium, fluorine, an amino group, a cyano group, or —C(O)NH ２ , -CH ３ and piperidinyl groups; or R ３ｄ is a methyl group, —N(methyl)(methyl) or piperidinyl group, or R ３ｄ When present, each independently represents deuterium, fluorine, a hydroxyl group, an amino group, a cyano group, —NH(CH ３ ), -N(CH ３ ) (CH ３ ), —C(O)NH ２ , -CH ３ , -CH ２ CH ３ and -CH ２ CH ２ CH ３ or selected from the group consisting of R ３ｄ When present, each independently represents deuterium, fluorine, a cyano group, or —C(O)NH ２ and -CH ３ Selected from:

11. The compound according to any one of claims 1 to 10, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

12. The compound has the formula (II-a) 【Chemistry 15】 (In the formula, m １－１ is selected from the group consisting of 0, 1 or 2; R １ａ－１ is R in claim 1 １ａ As defined by X ２－１ is X in claim 1 ２ is as defined by R ２－１ is R in claim 1 ２ is as defined by R ３－１ is R in claim 1 ３ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) Alternatively, the compound has a structure represented by formula (II-b): 【Chemistry 16】 (In the formula, m １－２ is selected from the group consisting of 0, 1, 2, or 3; R １ａ－２ is R in claim 1 １ａ As defined by X ２－２ is X in claim 1 ２ is as defined by R ２－２ is R in claim 1 ２ is as defined by R ３－２ is R in claim 1 ３ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) Alternatively, the compound has a structure represented by formula (II-c): 【Chemistry 17】 (In the formula, m １－４ is selected from the group consisting of 0, 1, 2, or 3; R １ａ－４ is R in claim 1 １ａ As defined by X ２－３ is X in claim 1 ２ is as defined by R ２－３ is R in claim 1 ２ is as defined by R ３－３ is R in claim 1 ３ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) Alternatively, the compound has a structure represented by formula (II-d): [Chemistry 18] (In the formula, E １ , E ２ , E ３ , E ４ , E ５ and E ６ are independently selected from the group consisting of C or N, and m １－６ is selected from the group consisting of 0, 1, 2, 3, or 4; R １ａ－６ is R in claim 1 １ａ As defined by X ２－４ is X in claim 1 ２ is as defined by R ２－４ is R in claim 1 ２ is as defined by R ３－４ is R in claim 1 ３ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) Alternatively, the compound has a structure represented by formula (II-e): 【Chemistry 19】 (In the formula, E ７ , E ８ , E ９ , E １０ , E １１ and E １２ are independently selected from the group consisting of C or N, and m １－１３ is selected from the group consisting of 0, 1, 2, or 3; m ２－１ is selected from the group consisting of 0, 1, 2, 3, or 4; R １ａ－１３ is R in claim 1 １ａ is as defined by R ２ａ－１ is R in claim 1 ２ａ is as defined by R ３－５ is R in claim 1 ３ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) Alternatively, the compound has a structure represented by formula (II-f): 【Chemistry 20】 (In the formula, m １－１５ is selected from the group consisting of 0, 1, 2, or 3; R １ａ－１５ is R in claim 1 １ａ is as defined by R ３ｅ－２ is R in claim 1 ３ｅ is as defined by R ３ｆ－２ is R in claim 1 ３ｆ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) Alternatively, the compound has a structure represented by formula (II-g): 【Chemistry 21】 (In the formula, R ３ｂ－８ is claim 1R ３ｂ is as defined by R ３ｃ－８ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, according to any one of claims 1 to 11, having a structure represented by the following formula:

13. The compound has the formula (II-a １ ) 【Chemistry 22】 (In the formula, R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-a ２ ) 【Chemistry 23】 (In the formula, R ３ｂ－１ is R in claim 1 ３ｂ is as defined by R ３ｃ－１ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-b １ ) 【Chemistry 24】 (In the formula, m １－３ is selected from the group consisting of 0, 1, 2, or 3; R １ａ－３ is R in claim 1 １ａ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-c １ ) 【Chemistry 25】 (In the formula, m １－５ is selected from the group consisting of 0, 1, 2 or 3; R １ａ－５ is R in claim 1 １ａ is as defined by R ３ｂ－２ is R in claim 1 ３ｂ is as defined by R ３ｃ－２ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-d １ ) 【Chemistry 26】 (In the formula, m １－７ is selected from the group consisting of 0, 1, 2 or 3; R １ａ－７ is R in claim 1 １ａ is as defined by R ３ｂ－３ is R in claim 1 ３ｂ is as defined by R ３ｃ－３ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-d ２ ) 【Chemistry 27】 (In the formula, m １－８ is selected from the group consisting of 0, 1 or 2; R １ａ－８ is R in claim 1 １ａ is as defined by R ３ｂ－４ is R in claim 1 ３ｂ is as defined by R ３ｃ－４ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-d ３ ) 【Chemistry 28】 (In the formula, m １－９ is selected from the group consisting of 0, 1 or 2; R １ａ－９ is R in claim 1 １ａ is as defined by R ３ｂ－５ is R in claim 1 ３ｂ is as defined by R ３ｃ－５ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-d ４ ) 【Chemistry 29】 (In the formula, m １－１０ is selected from the group consisting of 0, 1, 2, or 3; R １ａ－１０ is R in claim 1 １ａ is as defined by R ３ｅ－１ is R in claim 1 or 2 ３ｅ is as defined by R ３ｆ－１ is R in claim 1 ３ｆ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-d ５ ) 【Transformation 30】 (In the formula, m １－１１ is selected from the group consisting of 0, 1, 2 or 3; R １ａ－１１ is R in claim 1 １ａ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (II-d ６ ) 【Chemistry 31】 (In the formula, m １－１２ is selected from the group consisting of 0, 1, 2, or 3; R １ａ－１２ is R in claim 1 １ａ is as defined by R ３ｂ－６ is R in claim 1 ３ｂ is as defined by R ３ｃ－６ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) Alternatively, the compound has a structure represented by formula (II-e １ ) 【Chemistry 32】 (In the formula, m １－１４ is selected from the group consisting of 0, 1, 2, or 3; m ２－２ is selected from the group consisting of 0, 1, 2, 3, or 4; R １ａ－１４ is R in claim 1 １ａ is as defined by R ２ａ－２ is R in claim 1 ２ａ is as defined by R ３ｂ－７ is R in claim 1 ３ｂ is as defined by R ３ｃ－７ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1) Alternatively, the compound has a structure represented by formula (III-a): 【Transformation 33】 (In the formula, m １－１６ is selected from the group consisting of 0, 1, 2, or 3; R １ａ－１６ is R in claim 1 １ａ is as defined by R ３ｂ－９ is R in claim 1 ３ｂ is as defined by R ３ｃ－９ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ６ , R ７ , R ８ , R ９ , R １０ , R １１ ,W,L,t １ and t ２ is as defined in claim 1) or the compound has a structure represented by formula (III-a １ ) 【Transformation 34】 (In the formula, m １－１７ is selected from the group consisting of 0, 1, 2 or 3; R １ａ－１７ is R in claim 1 １ａ is as defined by R ３ｂ－１０ is R in claim 1 ３ｂ is as defined by R ３ｃ－１０ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ８ , R ９ , R １０ , R １１ and L is as defined in claim 1). or the compound has a structure represented by formula (III-a ２ ) 【Chemistry 35】 (In the formula, m １－１８ is selected from the group consisting of 0, 1, 2 or 3; R １ａ－１８ is R in claim 1 １ａ is as defined by R ３ｂ－１１ is R in claim 1 ３ｂ is as defined by R ３ｃ－１１ is R in claim 1 ３ｃ is as defined by R ４ , R ５ , R ７ , R ８ , R ９ , R １０ , R １１ and L is as defined in claim 1).

13. The compound of claim 12, having the structure:

14. Y is selected from the group consisting of: 【Transformation 36】 Alternatively, Y is selected from the following groups: 【Chemistry 37】 14. The compound according to any one of claims 1 to 13, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

15. R ４ is hydrogen, halogen, amino group or C １－６ alkoxy groups; or R ４ is selected from hydrogen, fluorine, or a methoxy group, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

16. R ５ is C １－３ is an alkyl group or a methyl group; 16. The compound according to any one of claims 1 to 15, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

17. W, Q １ , Q ２ and Q ３ Any one atom of these, together with the substituent to which it is attached, may optionally be R ６ｃ C may be replaced by ３－６ forming a cycloalkyl group or a 3- to 7-membered heterocycloalkyl group; or W, Q １ , Q ２ and Q ３ Any one atom of these, together with the substituent to which it is attached, may optionally be R ６ｃ C may be replaced by ３－４ forming a cycloalkyl group or a 3- to 6-membered heterocycloalkyl group, the heteroatoms of which are independently O or N, and the number of said heteroatoms is 1 or 2; or W, Q １ , Q ２ and Q ３ Any one atom of these, together with the substituent to which it is attached, may optionally be R ６ｃ C may be replaced by ３－４ forming a cycloalkyl group, or W, Q １ , Q ２ and Q ３ Any two adjacent atoms of the group, together with the substituents to which they are attached, may optionally be R ６ｃ C may be replaced by ３－１０ Carbocyclic groups, 3- to 10-membered heterocycloalkyl groups, C ６－８ forming an aryl group or a 5- to 10-membered heteroaryl group, or W, Q １ , Q ２ and Q ３ Any two adjacent atoms of the group, together with the substituents to which they are attached, may optionally be R ６ｃ C may be replaced by ３－８ Cycloalkyl groups, 3- to 8-membered heterocycloalkyl groups, C ６－８ forming an aryl group or a 5- to 8-membered heteroaryl group; or W, Q １ , Q ２ and Q ３ Any two adjacent atoms of the group, together with the substituents to which they are attached, may optionally be R ６ｃ C may be replaced by ５－６ Cycloalkyl groups, 5- to 6-membered heterocycloalkyl groups, C ６ an aryl group or a 5- to 6-membered heteroaryl group, the heteroatoms of which are independently O or N, and the number of said heteroatoms is 1 or 2; or R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ each, when present, independently represents hydrogen, deuterium, and optionally deuterium, halogen, hydroxyl group, amino group, C １－６ Alkyl group, C １－６ Alkoxy group, —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 optionally substituted by a cycloalkyl group, a 5- to 6-membered heterocycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group, a 9- to 10-membered bicyclic heterocyclic group, or a 9- to 10-membered bicyclic heteroaryl group. １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, 5- to 6-membered heterocycloalkyl groups, C ６－８ selected from the group consisting of an aryl group, a 5- to 6-membered heteroaryl group, a 9- to 10-membered bicyclic heterocyclic group, and a 9- to 10-membered bicyclic heteroaryl group; or R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ each, when present, independently represents hydrogen, and optionally halogen, hydroxyl group, amino group, C １－６ Alkyl group, C １－６ Alkoxy group, —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 optionally substituted by a cycloalkyl group, a 5- to 6-membered heterocycloalkyl group, a phenyl group, or a 5- to 6-membered heteroaryl group １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, 5- to 6-membered heterocycloalkyl groups, C ６－８ selected from the group consisting of aryl groups and 5- to 6-membered heteroaryl groups; or R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ each, when present, independently represents hydrogen, and optionally halogen, hydroxyl group, amino group, C １－６ Alkyl group, C １－６ Alkoxy group, —C(O)(C １－６ alkyl), —C(O)NH(C １－６ alkyl) or —NHC(O)(C １－６ C optionally substituted by alkyl １－６ Alkyl group and C １－６ alkoxy groups; or R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ each, when present, independently represents hydrogen, and optionally halogen, hydroxyl group, amino group, C １－６ Alkyl group or C １－６ C optionally substituted by an alkoxy group １－６ Alkyl group and C １－６ alkoxy groups; or R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ each, when present, independently represents hydrogen, and optionally halogen, hydroxyl group, amino group, C １－３ Alkyl group or C １－３ C optionally substituted by an alkoxy group １－３ Alkyl group and C １－３ alkoxy groups; or R ６ 、R ７ 、R ８ 、R ９ 、R １０ 、R １１ 、R １２ and R １３ when each exists, independently, -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 、-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 、 【Transformation 38】 or selected from the group consisting of R ６ 、R ７ 、R ８ 、R ９ 、R １０ 、R １１ 、R １２ and R １３ are, when present, independently, -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 、 【Chemistry 39】 or selected from the group consisting of R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ is, if present, independently —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 and -CH(CH ３ ) CH ２ OCH ３ or selected from the group consisting of R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ Any two groups bonded to the same atom are ═O or ═CH ２ or W, Q １ , Q ２ and Q ３ Any two adjacent atoms in the formula (I) together with the substituents to which they are bonded may form the following group: 【Chemistry 40】 or form a group selected from the group consisting of W, Q １ , Q ２ and Q ３ Any one atom of these, together with the substituent to which it is attached, can be one of the following groups: 【Chemistry 41】 or form a group selected from the group consisting of W, Q １ , Q ２ and Q ３ Any one atom of these, together with the substituent to which it is attached, can be one of the following groups: 【Chemistry 42】 or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof, according to any one of claims 1 to 16, which forms a group selected from the group consisting of:

18. R ６ａ and R ６ｂ each occurrence independently represents hydrogen, and optionally R ６ｃ C may be replaced by １－６ Alkyl group, C １－６ Alkoxy group, C ３－１０ Carbocyclic group, 3- to 10-membered heterocyclic group, C ６－８ selected from the group consisting of aryl groups and 5-10 membered heteroaryl groups; or R ６ａ and R ６ｂ each occurrence independently represents hydrogen, deuterium, and optionally R ６ｃ C may be replaced by １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, 5- to 6-membered heterocycloalkyl groups, C ６－８ selected from the group consisting of an aryl group, a 5- to 6-membered heteroaryl group, a 9- to 10-membered bicyclic heterocyclic group, and a 9- to 10-membered bicyclic heteroaryl group; or R ６ａ and R ６ｂ each occurrence independently represents hydrogen, and optionally R ６ｃ C may be replaced by １－６ Alkyl group and C １－６ alkoxy groups; or R ６ａ and R ６ｂ is, when present, independently hydrogen or optionally R ６ｃ C may be replaced by １－３ Alkyl group or C １－３ alkoxy groups; or R ６ａ and R ６ｂ each occurrence independently represents hydrogen, and optionally R ６ｃ or selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy and isopropoxy, optionally substituted by R ６ａ and R ６ｂ each occurrence independently represents hydrogen, and optionally R ６ｃ selected from the group consisting of methyl and ethyl groups, optionally substituted by 18. The compound according to any one of claims 1 to 17, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

19. R ６ｃ When present, each independently represents hydrogen, fluorine, chlorine, a hydroxyl group, an amino group, —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 group, C １－６ Alkoxy group, C ３－１０ Carbocyclic group, 3- to 10-membered heterocyclic group, C ６－８ selected from the group consisting of aryl groups and 5-10 membered heteroaryl groups; or R ６ｃ When present, each independently represents hydrogen, fluorine, chlorine, a hydroxyl group, an amino group, —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 group, C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, 3- to 6-membered heterocycloalkyl groups, C ６－８ an aryl group or a 5- to 6-membered heteroaryl group, the heteroatoms of which are N or S, and the number of said heteroatoms is 1, 2 or 3; or R ６ｃ are, if present, independently hydrogen, deuterium, halogen, hydroxyl group, amino group, C １－６ Alkyl group and C １－６ alkoxy groups; or R ６ｃ is, if present, independently selected from the group consisting of hydrogen, fluorine, chlorine, hydroxyl, amino, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy and isopropoxy; 19. The compound according to any one of claims 1 to 18, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

20. R ６ｄ and R ６ｅ each occurrence independently represents hydrogen, C １－６ Alkyl group, C １－６ Alkoxy group, C ３－１０ Carbocyclic group, 3- to 10-membered heterocyclic group, C ６－８ 20. The compound of any one of claims 1 to 19, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of an aryl group and a 5- to 10-membered heteroaryl group.

21. The following 【Chemistry 43】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof selected from the group consisting of:

22. A pharmaceutical composition comprising the compound according to any one of claims 1 to 21, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof.

23. A compound according to any one of claims 1 to 21 or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof or a pharmaceutical composition according to claim 22 for use as an ATM kinase inhibitor or for the prevention and / or treatment of diseases and / or disorders mediated at least in part by ATM kinase, said disease and / or disorder mediated at least in part by ATM kinase is cancer; The cancer is selected from the group consisting of solid tumors and blood tumors, 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, and glioblastoma, or the compound, or a tautomer, optical isomer, geometric isomer, solvate, isotope derivative, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

24. A compound according to any one of claims 1 to 21, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 22, for the prevention and / or treatment of cancer, The cancer is selected from the group consisting of solid tumors and blood tumors, 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, and glioblastoma, or the compound, or a tautomer, optical isomer, geometric isomer, solvate, isotope derivative, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

25. A pharmaceutical composition comprising the compound of any one of claims 1 to 21, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 22, and at least one additional antitumor agent, The pharmaceutical composition, wherein the antitumor agent is selected from the group consisting of 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.

26. A compound according to any one of claims 1 to 21 or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof or a pharmaceutical composition according to claim 22, and at least one additional anti-tumor agent or therapeutic treatment for the prevention and / or treatment of cancer, the antitumor agent is selected from the group consisting of 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; or The therapeutic treatment is radiation therapy, the compound or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt or pharmaceutical composition thereof and at least one additional anti-tumor agent or therapeutic treatment.

27. A compound represented by formula (M-1), (M-2) or (M-3) for producing a compound according to any one of claims 1 to 21. 【Chemistry 44】 (In the formula, R ｘ１ is selected from the group consisting of halogen or hydrogen, and R ４ , R ６ , R ７ ,A,W,L,t １ , t ２ and h are as defined in claim 1. or has a structure represented by formula (M-4) 【Chemistry 45】 (In the formula, R ｘ２ is selected from the group consisting of halogen or hydrogen, and R ４ , R ６ , R ７ ,A,W,L,t １ , t ２ and h are as defined in claim 1. or has a structure represented by formula (M-5) 【Chemistry 46】 (In the formula, R ｘ３ is selected from the group consisting of halogen or hydrogen, and R ４ , R ６ , R ７ ,A,W,L,t １ , t ２ and h are as defined in claim 1. or has a structure represented by formula (M-6) 【Chemistry 47】 (In the formula, R ｘ４ is selected from the group consisting of halogen or hydrogen, and R ４ , R ６ , R ７ ,A,W,L,t １ , t ２ and h are as defined in claim 1. An intermediate having a structure represented by the formula:

28. The following intermediates for preparing the compounds according to any one of claims 1 to 21: 【Chemistry 48】 【change】 【change】 【change】 【change】 【change】 【change】

29. A method for producing the compound of claim 1, comprising the steps of: 【Chemistry 49】 i) chemically converting compound I-a1 to obtain compound I-a2; ii) chemically converting compound I-a2 to give compound I-a4; iii) chemically converting compound I-a4 to give compound I-a5; iv) chemically converting compound I-a5 to give compound I-a6; v) chemically converting compound I-a6 to give compound I-a7; vi) chemically converting compound I-a7 to give compound I-a8; vii) Synthetic Route 1, in which compound I-a8 is chemically transformed to give a compound of formula I; [Transformation 50] i) using compound I-b1 as a basic material to obtain compound I-b2; ii) using compounds I-b2 and I-b3 as basic materials to obtain compound I-b4; iii) compound I-b4 is used as a starting material to obtain compound I-b5; iv) compound I-b5 is used as a starting material to obtain compound I-b6, v) compound I-b6 is used as a starting material to obtain compound I-b7, vi) compound I-b7 is used as a starting material to obtain compound I-b8, vii) using compound I-b8 as a starting material to obtain compound I-b9; viii) Synthetic Route 2, which uses compound I-b9 as a basic material to obtain compounds of formula I; 【Chemistry 51】 i) using compound I-b1 as a basic material to obtain compound I-b2; ii) using compounds I-b2 and I-b3 as basic materials to obtain compound I-b5; iii) compound I-b5 is used as a starting material to obtain compound I-b6; iv) compound I-b6 is used as a starting material to obtain compound I-b7, v) using compound I-b7 as a starting material to obtain compound I-b8, vi) using compound I-b8 as a starting material to obtain compound I-b9; vii) Synthetic Route 3 for obtaining Compound I of the general formula using Compound I-b9 as a basic material One of the following is selected from In these formulas, R ｘ１ is selected from the group consisting of halogen or hydrogen, and X １ , R ４ , R ５ , R ６ , R ７ ,A,W,L,t １ and t ２ is as defined in claim 1.

Images