Condensed ring compounds and their production and use

Abstract

This invention relates to a fused ring compound represented by formula (I') and its preparation and use in the field of pharmaceutical technology. Test results show that the compound can significantly inhibit ATM kinase activity, has excellent selectivity for ATM targets, and is useful as a cancer treatment drug. [Formula 1] JPEG2023542419000330.jpg54153

Description

[Technical Field]

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

[0002] The present invention falls under the field of pharmaceutical technology, and more specifically, relates to a novel compound having ATM protein kinase inhibitory activity, and to the use of said compound or pharmaceutical composition for manufacturing pharmaceuticals. [Background technology]

[0003] Hereditary ataxia-telangiectasia (AT) is an autosomal recessive genetic disorder. Its clinical symptoms mainly include progressive cerebellar ataxia that develops in childhood, facial telangiectasia, increased sensitivity to radiation exposure, and a significant increased tendency to develop tumors (Non-Patent Literature 1). It is currently known that the cause is a mutation in the ataxia telangiectasia mutated gene (ATM gene). The ATM gene is located on chromosome 11q22-23, is 150kb long, has 66 exons, and is one of the human genes with the most exons discovered to date (Non-Patent Literature 2). ATM protein kinase, encoded by the ATM gene, is a serine / threonine protein kinase containing 3056 amino acids with a relative molecular weight of approximately 350 kDa (Non-Patent Literature 3), and is a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family (Non-Patent Literature 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 testes, spleen, and thymus. ATM is involved in cell cycle regulation and DNA damage recognition and repair via its C-terminal functional region. Its actions in cellular signaling pathways include activation of cell cycle checkpoints (Non-Patent Literature 5), regulation of DNA damage repair (Non-Patent Literature 6), regulation of telomeres (Non-Patent Literature 7), and regulation of apoptosis (Non-Patent Literature 8).

[0004] ATM protein kinase primarily plays a role in repairing DNA double-strand breaks and maintaining DNA stability by inducing phosphorylation of downstream effectors. When cells are exposed to ionization radiation or ultraviolet radiation, DNA double-strand breaks (DSBs) occur. The MRE11-RAD50-NBS1 (MRN) complex senses the DSBs and initiates DNA repair, recruiting ATM protein kinase. ATM protein kinase functions as the primary sensor during DSB repair, recruiting and interacting with other proteins. ATM homodimers dissociate into active monomers at the DSB site and are catalytically activated by autophosphorylation and acetylation. They work in conjunction with other proteins to promote the repair of damaged DNA (Non-Patent Literature 9).

[0005] ATM further influences tumor cell proliferation and apoptosis by regulating the cell cycle via the Chk2-p53 / AKT pathway (Non-Patent Literature 10). Activated ATM also influences tumor development, metastasis, and invasion via the ATM-Akt-GSK-3β pathway, the transcription factor NF-κB, and the interleukin IL-8, and can enhance the drug resistance and resilience of tumor cells to radiotherapy and chemotherapy through various mechanisms in the DNA damage response (Non-Patent Literature 11).

[0006] Currently, ATM inhibitors undergoing clinical trials are often used in combination with radiotherapy or chemotherapy. Notable molecules currently in clinical trials 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 malignancies. [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

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Outdoor Configuration6

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[0008] [Fused ring compounds] The present invention provides a compound that is an ATM kinase inhibitor having a novel structure. [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 [Chemical] and X1 is selected from 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 ), where R 1x is hydrogen or a C 1-6 alkyl group, C 1-6 alkoxy group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 3-10 cycloalkyl group, 3- to 10-membered heterocycloalkyl group, C 6-14 aryl group or 5- to 12-membered heteroaryl group, and the "optionally substituted" means that the hydrogen in the substituent is unsubstituted or the hydrogen at one or more substitutable positions of the substituent is independently substituted by a substituent selected from 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 group, 3- to 10-membered heterocycloalkyl group, C 6-14 aryl group or 5- to 12-membered heteroaryl group, and the oxo group means that two Hs 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 do not exist. R1 is absent, a bond, hydrogen, deuterium, or a 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 Selected from aryl groups, 5-12 membered heteroaryl groups, 4-12 membered bridging ring groups, 4-12 membered heterobridging ring groups, monocyclic spiro ring groups, monocyclic heterospiro ring groups, fused ring groups, or heterofused ring groups, and "may be substituted as desired" means that the hydrogen in the substituent is unsubstituted, or that the hydrogen at one or more substituted positions of the substituent is independently R 1a This means that it is replaced by R 1a If present, independently include deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, and -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 ) is selected from, R 1b , R 1c If present, independently, hydrogen, deuterium, or optionally deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 C may be substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 1b and R 1c When R is bonded to the same nitrogen atom, 1b and R 1c These, along with the nitrogen atom to which they are bonded, optionally include deuterium, halogens, hydroxyl groups, amino groups, nitro groups, mercapto groups, cyano groups, oxo groups, and C. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 A 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group may be substituted with one or more aryl groups or 5-12 member heteroaryl groups, and the oxo group means a double bond formed by replacing two H atoms at the same substitution position with one O atom. If R1 is hydrogen or deuterium, then X2, R2, and R3 do not exist. X2 is absent, bonded, hydrogen, deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, 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)-, and R 2x is hydrogen, deuterium, or a C 1-6 alkyl group, C 1-6 alkoxy group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 3-10 cycloalkyl group, 3- to 10-membered heterocycloalkyl group, C 6-14 aryl group or 5- to 12-membered heteroaryl group, and "optionally substituted" means that the hydrogen in the substituent is unsubstituted or the hydrogen at one or more substitutable positions of the substituent is independently 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 group, 3- to 10-membered heterocycloalkyl group, C 6-14 aryl group or 5- to 12-membered heteroaryl group, and the oxo group means that two Hs 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 do not exist, R2 is absent, a bond, hydrogen, deuterium, or a C 1-6 alkyl group, C 1-6 alkoxy group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 3-10 cycloalkyl group, C 6-14Selected from aryl groups, 3-10 membered heterocycloalkyl groups, 5-12 membered heteroaryl groups, 4-12 membered crosslinking ring groups, 4-12 membered heterocrosslinking ring groups, monocyclic spiro ring groups, monocyclic heterospiro ring groups, fused ring groups, or heterofused ring groups, and "may be substituted as desired" means that the hydrogen in the substituent is unsubstituted, or that the hydrogens at one or more substituted positions of the substituent are independently R 2a This means that it is replaced by R 2a If present, independently include deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, and -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 ) is selected from, R 2b , R 2c If present, independently, as desired, deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl alkyl group, C 1-6Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Hydrogen, C which may be substituted with one or more aryl groups or 5-12 membered heteroaryl groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from aryl groups or 5-12 membered heteroaryl groups, or R 2b and R 2c When R is bonded to the same nitrogen atom, 2b and R 2c These, along with the nitrogen atom to which they are bonded, optionally include deuterium, halogens, hydroxyl groups, amino groups, nitro groups, mercapto groups, cyano groups, oxo groups, and C. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 A 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group may be substituted with one or more aryl groups or 5-12 member heteroaryl groups, and the oxo group means a double bond formed by replacing two H atoms at the same substitution position with one O atom. If R2 is hydrogen or deuterium, then R3 does not exist. 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 ) is selected from, R 3b , R 3c If present, C may independently be substituted with hydrogen, deuterium, or optionally. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c Together with the nitrogen atom to which these are bonded, they form a 3-20 membered heterocyclic group or a 5-12 membered heteroaryl group, which may optionally be substituted, and the phrase "may optionally be substituted" means that the hydrogen in the substituent is unsubstituted, or that the hydrogens at one or more substituted positions of the substituent are independently R 3d This means that it is replaced by R 3d If present, independently include deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, and -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 ) is selected from, R 3e , R 3f If present, independently of hydrogen, deuterium, or optionally a halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 C may be substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R3e and R 3f When R is bonded to the same nitrogen atom, 3e and R 3f These, along with the nitrogen atom to which they are bonded, optionally include deuterium, halogens, hydroxyl groups, amino groups, nitro groups, mercapto groups, cyano groups, oxo groups, and C. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 A 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group may be substituted with one or more aryl groups or 5-12 member heteroaryl groups, and the oxo group means a double bond formed by replacing two H atoms at the same substitution position with one O atom. If present, R4 may be independently substituted with hydrogen, deuterium, halogen, nitro group, amino group, cyano group, hydroxyl group, carboxyl group, mercapto group, or optionally one or more deuterium, halogen, hydroxyl group, or amino group. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group or C 1-6 Selected from alkyl mercapto groups, h is either 1 or 2. If present, R5 may be independently substituted with hydrogen, deuterium, halogen, hydroxyl group, or optionally one or more deuterium, halogen, hydroxyl group, amino group, or cyano group. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 1-6 Alkyl mercapto group, C 3-10 Cycloalkyl groups, C 6-14 Selected from an aryl group, a 3-10 membered heterocycloalkyl group, or a 5-12 membered heteroaryl group, L is C(R L ) or N, R L If present, they independently include hydrogen, deuterium, halogen, nitro group, amino group, cyano group, hydroxyl group, carboxyl group, mercapto group, and C. 1-6 Alkyl alkyl group, C1-6 Alkoxy group or C 1-6 Selected from alkyl mercapto groups, A is [ka] And, Here, [ka] represents a single or double bond, and Q1 is bonded to W. t1, t2, t3, t4, t5, and t6 are independently either 0 or 1. n1 and n2 are independently 0, 1, or 2, and n1 and n2 are not simultaneously 0, where n1 represents the sequential joining of n1 Q1s, n2 represents the sequential joining of n2 Q2s, two adjacent Q1s are joined by a single or double bond, and two adjacent Q2s are joined by a single or double bond. W, Q1, and Q2 are independently selected from C, O, N, or S. Q3 is C, and if one of the bonds in Q3 is a double bond, then R 10 or R 11 It does not exist. R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, independently of hydrogen, deuterium, halogen, hydroxyl group, amino group, cyano group, nitro group, -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 ) can be selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two substituents bonded to the same atom are both =O and =NR. 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 It forms an aryl group, a 5-12 membered heteroaryl group, a 4-12 membered bridging ring group, a 4-12 membered heterobridging ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, or a heterofused ring group, or W, one of the atoms of Q1 (if present), Q2 and Q3 (if present) together with the substituents to which they are bonded, optionally R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 Forming an aryl group, a 5-12 membered heteroaryl group, a monocyclic spiro ring group, or a monocyclic heterospiro ring group, R 6a , R 6b If present, independently of hydrogen, deuterium, or R as desired. 6c C may be substituted by 1-6 Alkyl alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 Selected from aryl groups, 5-12 membered heteroaryl groups, 4-12 membered bridging ring groups, 4-12 membered heterobridging ring groups, monocyclic spiro ring groups, monocyclic heterospiro ring groups, fused ring groups, or heterofused ring groups, or R 6a and R 6b When R is bonded to the same nitrogen atom, 6a and R 6b These, along with the nitrogen atom to which they bond, optionally include R 6c Forms a 3-10 member heterocyclic group or a 5-12 member heteroaryl group which may be substituted by R 6c If present, independently include hydrogen, deuterium, halogen, hydroxyl group, amino group, cyano group, nitro group, azide group, oxo group, and -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 Selected from, the oxo group means that two H atoms at the same substitution position are replaced by one O atom to form a double bond, and the =NR 6d This means that two H atoms at the same substitution position are replaced by one N atom to form a double bond, and N is R 6d This means that it is substituted by the aforementioned =CH-R 6dThis means that two H atoms at the same substitution position are replaced by one C atom to form a double bond, and the C atom is R 6d This means that it is replaced by R 6d , R 6e If present, C may be independently substituted with hydrogen, deuterium, halogen, hydroxyl group, amino group, nitro group, cyano group, or optionally. 1-6 Alkyl alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 Selected from aryl groups, 5-12 membered heteroaryl groups, monocyclic spiro ring groups, monocyclic heterospiro ring groups, fused ring groups, or heterofused ring groups, or R 6d and R 6e When R is bonded to the same nitrogen atom, 6d and R 6e Together with the nitrogen atom to which these are bonded, they form a optionally substituted 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group, where "optionally substituted" means that the hydrogen in the substituent is unsubstituted, or the hydrogens at one or more substituted positions of the substituent are independently R 6f This means that it is replaced by R 6f If present, they independently include hydrogen, deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, and -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 alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, the oxo group means that two H atoms at the same substitution position are replaced by one O atom to form a double bond. When heterocycloalkyl groups, heteroaryl groups, heterocyclic groups, monocyclic heterospirocyclic groups, heterofused ring groups, and / or heterobridged ring groups are present, the heteroatoms are independently selected from O, N, or S, and the number of such 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 )- Selected from, R 1x C is hydrogen, or optionally substituted. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14Selected from aryl groups or 5-12 membered heteroaryl groups, the phrase "may be substituted as desired" means that the hydrogen in the substituent is unsubstituted, or that one or more hydrogens at the substituted positions are independently a halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, or C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 This means that the group is substituted with a substituent selected from an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group means that two H atoms at the same substitution position are replaced by one O atom to form a double bond. If X1 is hydrogen, halogen, hydroxyl group, amino group, nitro group, or cyano group, then R1, X2, R2, and R3 are not present. R1 may be absent, bonded, hydrogen, or optionally substituted. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from aryl groups, 5-12 membered heteroaryl groups, 4-12 membered bridging ring groups, 4-12 membered heterobridging ring groups, monocyclic spiro ring groups, monocyclic heterospiro ring groups, fused ring groups, or heterofused ring groups, and "may be substituted as desired" means that the hydrogen in the substituent is unsubstituted, or that the hydrogen at one or more substituted positions of the substituent is independently R 1a This means that it is replaced by R 1a If present, they independently include halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, and -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 ) is selected from, R 1b , R 1c If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, or C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 C may be substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 1b and R 1c When R is bonded to the same nitrogen atom, 1b and R1c These, along with the nitrogen atom to which they are bonded, optionally include halogens, hydroxyl groups, amino groups, nitro groups, mercapto groups, cyano groups, oxo groups, and C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 A 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group may be substituted with one or more aryl groups or 5-12 member heteroaryl groups, and the oxo group means a double bond formed by replacing two H atoms at the same substitution position with one O atom. If R1 is hydrogen, then X2, R2, and R3 do not exist. X2 is absent, bonded, hydrogen, halogen, hydroxyl group, amino group, nitro group, mercapto group, 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)- is selected, R 2x C is hydrogen, or optionally substituted. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from aryl groups or 5-12 membered heteroaryl groups, the phrase "may be substituted as desired" means that the hydrogen in the substituent is unsubstituted, or that one or more hydrogens at the substituted positions are independently a halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, or C 1-6 Alkyl alkyl group, C1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 This means that the molecule is substituted with a substituent selected from an aryl group or a 5-12 membered heteroaryl group, and the oxo group means that two H atoms at the same substitution position are replaced by one O atom to form a double bond. If X2 is hydrogen, halogen, hydroxyl group, amino group, nitro group, mercapto group, or cyano group, then R2 and R3 are not present. R2 may be absent, bonded, hydrogen, or optionally substituted. 1-6 Alkyl 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 Selected from aryl groups, 3-10 membered heterocycloalkyl groups, 5-12 membered heteroaryl groups, 4-12 membered crosslinking ring groups, 4-12 membered heterocrosslinking ring groups, monocyclic spiro ring groups, monocyclic heterospiro ring groups, fused ring groups, or heterofused ring groups, and "may be substituted as desired" means that the hydrogen in the substituent is unsubstituted, or that the hydrogens at one or more substituted positions of the substituent are independently R 2a This means that it is replaced by R 2a If present, they independently include halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, and -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 ) is selected from, R 2b , R 2c If present, it can be independently, optionally, a halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, or C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Hydrogen, C which may be substituted with one or more aryl groups or 5-12 membered heteroaryl groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from aryl groups or 5-12 membered heteroaryl groups, or R 2b and R 2c When R is bonded to the same nitrogen atom, 2b and R 2c These, along with the nitrogen atom to which they are bonded, optionally include halogens, hydroxyl groups, amino groups, nitro groups, mercapto groups, cyano groups, oxo groups, and C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14A 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group may be substituted with one or more aryl groups or 5-12 member heteroaryl groups, and the oxo group means a double bond formed by replacing two H atoms at the same substitution position with one O atom. If R2 is hydrogen, then R3 does not exist. 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 ) is selected from, R 3b , R 3c If present, C may independently be hydrogen or optionally substituted. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c Together with the nitrogen atom to which these are bonded, they form a 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group which may be optionally substituted, and the phrase "may be optionally substituted" means that the hydrogen in the substituent is unsubstituted, or that the hydrogens at one or more substituted positions of the substituent are independently R 3d This means that it is replaced by R 3d If present, they independently include halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, and -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 ) is selected from, R 3e , R3f If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, or C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 C may be substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 3e and R 3f When R is bonded to the same nitrogen atom, 3e and R 3f These, along with the nitrogen atom to which they are bonded, optionally include halogens, hydroxyl groups, amino groups, nitro groups, mercapto groups, cyano groups, oxo groups, and C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 A 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group may be substituted with one or more aryl groups or 5-12 member heteroaryl groups, and the oxo group means a double bond formed by replacing two H atoms at the same substitution position with one O atom. R4 may be substituted with hydrogen, halogen, nitro group, amino group, cyano group, hydroxyl group, carboxyl group, mercapto group, or optionally with halogen, hydroxyl group or amino group. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group or C 1-6 Selected from alkyl mercapto groups, R5 may be substituted with hydrogen, a halogen, a hydroxyl group, or optionally one or more halogens, hydroxyl groups, amino groups, or cyano groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 1-6 Alkyl mercapto group, C 3-10 Cycloalkyl groups, C 6-14 Selected from aryl groups, 3-10 membered heterocycloalkyl groups, and 5-12 membered heteroaryl groups, L is C(R L ) or N, R L These are hydrogen, halogen, nitro group, amino group, cyano group, hydroxyl group, carboxyl group, mercapto group, C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group or C 1-6 Selected from alkyl mercapto groups, A is [ka] And, Here, [ka] represents a single or double bond, and Q1 is bonded to W. t1, t2, t3, t4, t5, and t6 are independently either 0 or 1. n1 and n2 are independently 0, 1, or 2, and n1 and n2 are not simultaneously 0, where n1 represents the sequential joining of n1 Q1s, n2 represents the sequential joining of n2 Q2s, two adjacent Q1s are joined by a single or double bond, and two adjacent Q2s are joined by a single or double bond. W, Q1, and Q2 are independently selected from C, O, N, or S. Q3 is C, and if one of the bonds in Q3 is a double bond, then R 10 or R 11 It does not exist. R6, R7, R8, R9, R 10 , R 11 , R 12 and R13 If present, they independently include hydrogen, halogen, hydroxyl group, amino group, cyano group, nitro group, and -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 ) can be selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two substituents bonded to the same atom are both =O and =NR. 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14It forms an aryl group, a 5-12 membered heteroaryl group, a 4-12 membered bridging ring group, a 4-12 membered heterobridging ring group, a monocyclic spiro ring group, a monocyclic heterospiro ring group, a fused ring group, or a heterofused ring group, or W, one of the atoms of Q1 (if present), Q2 and Q3 (if present) together with the substituents to which they are bonded, optionally R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 Forming an aryl group, a 5-12 membered heteroaryl group, a monocyclic spiro ring group, or a monocyclic heterospiro ring group, R 6a , R 6b If present, it independently provides hydrogen, or optionally R 6c C may be substituted by 1-6 Alkyl alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 Selected from aryl groups, 5-12 membered heteroaryl groups, 4-12 membered bridging ring groups, 4-12 membered heterobridging ring groups, monocyclic spiro ring groups, monocyclic heterospiro ring groups, fused ring groups, or heterofused ring groups, or R 6a and R 6b When R is bonded to the same nitrogen atom, 6a and R 6b These, along with the nitrogen atom to which they bond, optionally include R 6c Forms a 3-10 member heterocyclic group or a 5-12 member heteroaryl group which may be substituted by R 6c If present, they independently include hydrogen, halogen, hydroxyl group, amino group, cyano group, nitro group, azide group, oxo group, and -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 Selected from, the oxo group means that two H atoms at the same substitution position are replaced by one O atom to form a double bond, and the =NR 6d This means that two H atoms at the same substitution position are replaced by one N atom to form a double bond, and N is R 6d This means that it is substituted by the aforementioned =CH-R 6d This means that two H atoms at the same substitution position are replaced by one C atom to form a double bond, and the C atom is R 6d This means that it is replaced by R 6d , R 6e If present, C may be independently substituted with hydrogen, halogen, hydroxyl group, amino group, nitro group, cyano group, or optionally. 1-6 Alkyl alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 Selected from aryl groups, 5-12 membered heteroaryl groups, monocyclic spiro ring groups, monocyclic heterospiro ring groups, fused ring groups, or heterofused ring groups, or R 6d and R 6e When R is bonded to the same nitrogen atom, 6d and R 6e Together with the nitrogen atom to which these are bonded, they form a optionally substituted 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group, where "optionally substituted" means that the hydrogen in the substituent is unsubstituted, or the hydrogens at one or more substituted positions of the substituent are independently R 6f This means that it is replaced by R6f If present, these independently include hydrogen, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, and -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 alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, the oxo group means that two H atoms at the same substitution position are replaced by one O atom to form a double bond. When heterocycloalkyl groups, heteroaryl groups, heterocyclic groups, monocyclic heterospirocyclic groups, heterofused ring groups, and / or heterobridged ring groups are present, the heteroatoms are independently selected from O, N, or S, and the number of such heteroatoms is 1, 2, 3, or 4.

[0011] Preferably, the present invention provides compounds having the structure represented by formula (Ia), or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, each substituent is defined as a compound of formula (I') or formula (I).)

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

[0013] Preferably, the present invention provides compounds having a structure represented by formula (Ic) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, each substituent is defined as a compound of formula (I') or formula (I).)

[0014] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, 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 )- Selected from, R 1x is hydrogen, C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group.

[0015] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, 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(R1x )- Selected from, R 1x is hydrogen, C 1-6 Alkyl alkyl group, C 3-6 Selected from cycloalkyl groups or 3- to 6-membered heterocycloalkyl groups.

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

[0018] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, X1 is selected from the bonds.

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

[0020] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from a 5- to 8-membered heterocyclic group which may optionally be substituted, where the heteroatom is N and the number of heteroatoms is one or two. The phrase "may optionally be substituted" means that R may optionally be substituted. 1a This means that it may be replaced by [another term].

[0021] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from optionally substituted dihydropyridyl groups, where " optionally substituted" means R 1a This means that it may be replaced by [another term].

[0022] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is absent, bonded, hydrogen, or optionally substituted C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, and the phrase "may be substituted as desired" means R 1a This means that it may be replaced by [another term].

[0023] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is hydrogen or optionally substituted C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6Alkenyl group, C 2-6 Alkynyl group, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, and the phrase "may be substituted as desired" means R 1a This means that it may be replaced by [another term].

[0024] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is optionally substituted with C 1-6 Alkyl alkyl group, C 2-6 Alkynyl group, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, and the phrase "may be substituted as desired" means R 1a This means that it may be replaced by [another term].

[0025] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is optionally substituted with C 2-6 Selected from an alkynyl group or a 5-12 membered heteroaryl group, and the phrase "may be substituted as desired" means R 1a This means that it may be replaced by [another term].

[0026] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is optionally substituted with C 2-6 Selected from an alkynyl group or a 5-8 membered heteroaryl group, where the heteroatom is N, and the number of heteroatoms is 1, 2, or 3, and the phrase "may be optionally substituted" means optionally R 1a This means that it may be replaced by [another term].

[0027] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is optionally substituted with C 2-6 Selected from alkynyl, and the phrase "may be substituted as desired" means R as desired 1a This means that it may be replaced by [another term].

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

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

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

[0031] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from an ethynyl group, phenyl group, pyridyl group, pyrimidinyl group, pyrazinyl group, pyrazolyl group, imidazolyl group or pyrrolyl group, which may be optionally substituted, and the phrase "may be optionally substituted" means that R 1a This means that it may be replaced by [another term].

[0032] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from ethynyl.

[0033] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from a pyridyl group, pyrimidinyl group, pyrazinyl group or pyrazolyl group, which may be optionally substituted, and the phrase "may be optionally substituted" means that R 1a This means that it may be replaced by [another term].

[0034] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from pyridyl groups which may be optionally substituted, and the phrase "which may be optionally substituted" means that R 1a This means that it may be replaced by [another term].

[0035] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a If present, they independently include halogen, hydroxyl group, amino group, oxo group, and -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 ) are selected from the above, and the oxo group refers to a group in which two H atoms at the same substitution position are replaced by one O atom to form a double bond.

[0036] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a If present, they independently include halogen, hydroxyl group, amino group, oxo group, and -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 ) are selected from the above, and the oxo group refers to a group in which two H atoms at the same substitution position are replaced by one O atom to form a double bond.

[0037] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a If present, they independently include halogen, hydroxyl group, amino group, oxo group, and -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 ) are selected from the above, and the oxo group refers to a group in which two H atoms at the same substitution position are replaced by one O atom to form a double bond.

[0038] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a If present, they independently include halogen, amino group, oxo group, and -R. 1b ,-NHC(O)(R 1b ) or -NHSO2(R1b ) are selected from the above, and the oxo group refers to a group in which two H atoms at the same substitution position are replaced by one O atom to form a double bond.

[0039] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a If present, independently, -NHC(O)(R 1b ) or -NHSO2(R 1b ).

[0040] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, oxo group, or C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-8 Cycloalkyl groups, 3- to 8-membered heterocycloalkyl groups, C 6-8 C may be substituted with one or more aryl groups or 5- to 8-membered heteroaryl groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 1b and R 1c When R is bonded to the same nitrogen atom, 1b and R 1c These, along with the nitrogen atom to which they are bonded, optionally include halogens, hydroxyl groups, amino groups, oxo groups, and C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-8A 3- to 10-membered heterocycloalkyl group or a 5- to 12-membered heteroaryl group, which may be substituted by one or more of a cycloalkyl group, a 3- to 8-membered heterocycloalkyl group, an aryl group or a 5- to 8-membered heteroaryl group, and the oxo group means that two Hs at the same substitution position are replaced by one O to form a double bond. 6-8 Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R

[0041] When present, are independently selected from hydrogen, C 1b R 1c alkyl group, C 1-6 alkoxy group, C 1-6 alkynyl group, C 2-6 cycloalkyl group, 3- to 10-membered heterocycloalkyl group, C 3-10 aryl group or 5- to 12-membered heteroaryl group, or when R 6-14 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 10-membered heterocycloalkyl group.

[0042] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R 1b R 1c When present, are independently selected from C 1-6 alkyl group, 3- to 8-membered heterocycloalkyl group or C 6-8 aryl group, or when 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.

[0043] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c If present, independently, C 1-6 Alkyl alkyl group, C 3-10 Cycloalkyl groups or C 6-8 Selected from aryl groups, or R 1b and R 1c When R is bonded to the same nitrogen atom, 1b and R 1c These, along with the nitrogen atom to which they bond, form a 3- to 8-membered heterocycloalkyl group.

[0044] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c If present, independently, C 1-6 Alkyl alkyl group, C 3-8 Cycloalkyl groups or C 6-8 Selected from aryl groups.

[0045] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c If present, independently, C 1-6 Alkyl alkyl group, C 3-6 Selected from cycloalkyl groups or C6 aryl groups (i.e., phenyl groups). More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c If present, independently, C 1-6 Alkyl alkyl group or C 3-6 Selected from cycloalkyl groups.

[0046] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c If present, independently, C 1-4 Alkyl alkyl group or C 3-4 Selected from cycloalkyl groups.

[0047] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c If present, the group is independently selected from a methyl group, an ethyl group, a cyclopropanyl group, a phenyl group, or a tetrahydropyranyl group.

[0048] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1b , R 1c If present, it is independently selected from a methyl group or a cyclopropanyl group.

[0049] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from pyrazolyl groups which may be optionally substituted, and the phrase "which may be optionally substituted" means that R 1a This means that it may be substituted by R 1a C 1-6 Selected from alkyl groups or 3- to 8-membered heterocycloalkyl groups.

[0050] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from pyrazolyl groups which may be optionally substituted, and the phrase "which may be optionally substituted" means that R 1a This means that it may be substituted by R 1a C 1-4 Selected from alkyl groups or six-membered heterocycloalkyl groups.

[0051] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from pyrazolyl groups which may be optionally substituted, and the phrase "which may be optionally substituted" means that R 1a This means that it may be substituted by R 1a The group is independently selected from a methyl group, an ethyl group, or a tetrahydropyranyl group.

[0052] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from pyridyl groups which may be optionally substituted, and the phrase "which may be optionally substituted" means that R 1a This means that it may be substituted by R 1a These are independently an amino group, -NHC(O)(R 1b ) or -NHSO2(R 1b ) is selected from, R 1b If present, independently, C 1-6 Alkyl alkyl group, C 3-6 Selected from a cycloalkyl group or a phenyl group.

[0053] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from pyridyl groups which may be optionally substituted, and the phrase "which may be optionally substituted" means that R 1a This means that it may be substituted by R 1a These are independently an amino group, -NHC(O)(R 1b ) or -NHSO2(R 1b ) is selected from, R 1b If present, independently, C 1-4 Alkyl alkyl group, C 3-4 Selected from a cycloalkyl group or a phenyl group.

[0054] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from the following groups, which may optionally be substituted. [ka] (In the formula, the "*" end connects to X1 and the other end connects to X2. The phrase "may be substituted as desired" means that R may be substituted as desired.) 1a (This means it may be replaced by [another term].)

[0055] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, R1 may be substituted as desired. [ka] Selected from. (In the formula, the "*" end connects to X1 and the other end connects to X2. The phrase "may be substituted as desired" means that R may be substituted as desired.) 1a (This means it may be replaced by [another term].)

[0056] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from the following groups. [ka] (In the formula, the "*" end connects to X1, and the other end connects to X2.)

[0057] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from the following groups. [ka] (In the formula, the "*" end connects to X1, and the other end connects to X2.)

[0058] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, R1 is selected from the following groups. [ka] (In the formula, the "*" end connects to X1, and the other end connects to X2.)

[0059] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R1 is selected from the following groups. [ka] (In the formula, the "*" end connects to X1, and the other end connects to X2.)

[0060] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R1 is selected from the following groups.

Chemical formula

[0061] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, R1 is selected from the following groups.

Chemical formula

[0062] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, 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 selected from hydrogen or a C 1-6 alkyl group which may optionally be substituted by halogen, a hydroxyl group or an amino group.

[0063] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt, X2 is 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 compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, X2 is selected from absent, bound, -O-, -NH- or -N(CH3)-.

[0065] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, X2 is selected from absent, bonded, -O- or -N(CH3)-.

[0066] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, X2 is selected from a bond, -O-, or -NH-.

[0067] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, X2 is selected from absent, bonded, or -O-. More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, X2 is selected from -O-.

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

[0069] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R2 is absent, hydrogen, C 1-6 Alkyl alkyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, C 6-14 Selected from an aryl group, a 3-10 membered heterocycloalkyl group, or a 5-12 membered heteroaryl group.

[0070] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R2 is absent, C 1-6 Alkyl alkyl group, C 2-4 Selected from an alkynyl group or a 5-6 membered heterocycloalkyl group, where the heteroatom is N or O, and the number of heteroatoms is one or two.

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

[0072] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R2 is selected from n-propyl.

[0073] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, 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 ) are selected from the above, and the oxo group refers to a group in which two H atoms at the same substitution position are replaced by one O atom to form a double bond.

[0074] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, 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 ) are selected from the above, and the oxo group refers to a group in which two H atoms at the same substitution position are replaced by one O atom to form a double bond.

[0075] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R3 is absent, -R 3b , -OR 3b or -N(R 3b )(R 3c ) will be selected from.

[0076] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R3 is -N(R 3b )(R 3c ) will be selected from.

[0077] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may independently be hydrogen or optionally substituted. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from aryl groups, 5-12 membered heteroaryl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3cTogether with the nitrogen atom to which these are bonded, they form a optionally substituted 3-10 membered heterocycloalkyl group, a 4-12 membered bicyclic heterocyclic group, or a 5-12 membered heteroaryl group, and the phrase "optionally substituted" means optionally R 3d This means that it may be replaced by [another term].

[0078] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may independently be hydrogen or optionally substituted. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c Together with the nitrogen atom to which these are bonded, they form a 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group, which may be optionally substituted, and the phrase "may be optionally substituted" means that R may be optionally substituted. 3d This means that it may be replaced by [another term].

[0079] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may independently be hydrogen or optionally substituted. 1-6 Alkyl alkyl group, C 1-6 Selected from an alkoxy group or a 3-10 member heterocycloalkyl group, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3cTogether with the nitrogen atom to which these are bonded, they form a 3- to 10-membered heterocycloalkyl group which may optionally be substituted, and the phrase "may optionally be substituted" means that R may optionally be substituted. 3d This means that it may be replaced by [another term].

[0080] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b 、R 3c If present, C may independently be hydrogen or optionally substituted. 1-6 Alkyl alkyl group, C 1-6 Selected from an alkoxy group or a 3- to 10-membered heterocycloalkyl group, and the phrase "may be optionally substituted" means optionally R 3d This means that it may be replaced by [another term].

[0081] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b 、R 3c If present, C may be independently and optionally substituted. 1-6 It is an alkyl group, and the phrase "may be substituted if desired" means that R may be substituted if desired. 3d This means that it may be replaced by [another term].

[0082] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c Together with the nitrogen atom to which these are bonded, they form a 3- to 10-membered heterocycloalkyl group which may optionally be substituted, and the phrase "may optionally be substituted" means that R may optionally be substituted. 3d This means that it may be replaced by [another term].

[0083] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c These, together with the nitrogen atom to which they are bonded, form a optionally substituted 5-6 membered heterocycloalkyl group or a 6-10 membered bicyclic heterocyclic group, wherein the heteroatoms are independently O or N, and the number of heteroatoms is 1, 2, 3, or 4. The phrase "optionally substituted" means optionally R 3d This means that it may be replaced by [another term].

[0084] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R3 is absent, C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group or -N(R 3b)(R 3c ) is selected from, R 3b , R 3c C may be substituted independently, as desired. 1-6 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c Together with the nitrogen atom to which these are bonded, they form a 3- to 10-membered heterocycloalkyl group which may optionally be substituted, and the phrase "may optionally be substituted" means that R may optionally be substituted. 3d This means that it may be replaced by [another term].

[0085] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may be independently and optionally substituted. 1-6 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c These, together with the nitrogen atom to which they are bonded, form a optionally substituted 3-10 member heterocycloalkyl group or a 4-12 member bicyclic heterocyclic group, and the phrase " optionally substituted" means optionally R 3d This means that it may be replaced by [another term].

[0086] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may be independently and optionally substituted. 1-6 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3cTogether with the nitrogen atom to which they are bonded, these form a 4-8 member heterocycloalkyl group or a 6-10 member bicyclic heterocyclic group, which may be optionally substituted, and the phrase "may be optionally substituted" means that R may be optionally substituted. 3d This means that it may be replaced by [another term].

[0087] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may be independently and optionally substituted. 1-4 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c These, together with the nitrogen atom to which they are bonded, form a optionally substituted 5-6 membered heterocycloalkyl group or a 6-10 membered bicyclic heterocyclic group, wherein the heteroatoms are independently O or N, and the number of heteroatoms is 1, 2, 3, or 4. The phrase "optionally substituted" means optionally R 3d This means that it may be replaced by [another term].

[0088] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may be independently and optionally substituted. 1-4 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3cThese, along with the nitrogen atom to which they are bonded, may optionally be substituted: 5-6 member heterocycloalkyl groups, 3- / 4 member heteromonocyclic spiro ring groups, 4- / 3 member heteromonocyclic spiro ring groups, 3- / 5 member heteromonocyclic spiro ring groups, 5- / 3 member heteromonocyclic spiro ring groups, 3- / 6 member heteromonocyclic spiro ring groups, 6- / 3 member heteromonocyclic spiro ring groups, 4- / 5 member heteromonocyclic spiro ring groups, 5- / 4 member heteromonocyclic spiro ring groups, 4- / 6 member heteromonocyclic spiro ring groups, 6- / 4 The heteroatoms are independently O or N, and the number of heteroatoms is 1, 2, 3, or 4. The phrase "may be substituted as desired" means that R may be substituted as desired. 3d This means that it may be replaced by [another term].

[0089] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may be independently and optionally substituted. 1-4 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c These, together with the nitrogen atom to which they are bonded, form optionally substituted 5-6 membered heterocycloalkyl groups, 3-membered / 6-membered heteromonocyclic spiro ring groups, 6-membered / 3-membered heteromonocyclic spiro ring groups, 4-membered / 6-membered heteromonocyclic spiro ring groups, 6-membered / 4-membered heteromonocyclic spiro ring groups, or 4-membered / 4-membered heteromonocyclic spiro ring groups, wherein the heteroatoms are independently O or N, and the number of heteroatoms is one or two. The phrase "optionally substituted" means optionally R 3d This means that it may be replaced by [another term].

[0090] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, it is independently selected from methyl groups which may be optionally substituted, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c Together with the nitrogen atom to which these are bonded, they form a piperidine which may be optionally substituted, and the phrase "may be optionally substituted" means that R may be optionally substituted 3d This means that it may be replaced by [another term].

[0091] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If present, independently include deuterium, halogen, hydroxyl group, amino group, cyano group, and -R. 3e , -C(O)R 3e , -C(O)OR 3e , -N(R 3e )(R 3f ) or -C(O)NH(R 3e ) is selected from, R 3e , R 3f If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, or C 1-6 Alkyl alkyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 C may be substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 3eand R 3f When R is bonded to the same nitrogen atom, 3e and R 3f These, along with the nitrogen atom to which they are bonded, optionally include halogens, hydroxyl groups, amino groups, and C 1-6 Alkyl alkyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 A 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group is formed, which may be substituted with one or more aryl groups or 5-12 member heteroaryl groups.

[0092] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If present, independently include deuterium, halogen, hydroxyl group, amino group, cyano group, and -R. 3e , -C(O)R 3e , -C(O)OR 3e , -N(R 3e )(R 3f ) or -C(O)NH(R 3e ) is selected from, R 3e , R 3f If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, or C 1-6 Alkyl alkyl group, C 3-6 C may be substituted with one or more of the following: a cycloalkyl group, a 3- to 6-membered heterocycloalkyl group, a C6 aryl group, or a 5- to 6-membered heteroaryl group. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-6 Selected from cycloalkyl groups, 3-6 membered heterocycloalkyl groups, C6 aryl groups, or 5-6 membered heteroaryl groups.

[0093] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3dIf present, independently include deuterium, halogen, hydroxyl group, amino group, 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)NH2, C 1-6 Alkyl alkyl group, C 1-6 Selected from an alkoxy group or a 3- to 6-membered heterocycloalkyl group.

[0094] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If 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)(C 1-6 Alkyl), -C(O)NH2, C 1-6 Alkyl alkyl group, C 1-6 Selected from an alkoxy group or a 5-6 member heterocycloalkyl group.

[0095] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If present, these are independently selected from deuterium, fluorine, hydroxyl group, amino group, cyano group, -CHO, -COCH3, -COOH, -COOCH3, -NH(CH3), -N(CH3)(CH3), -C(O)NH2, -CH3, -CH2CH3, -CH2CH2CH3, -OCH3, -OCH2CH3, -OCH2CH2CH3, piperidinyl group, piperazinyl group, or tetrahydropyrrolyl group.

[0096] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If present, these are independently selected from deuterium, fluorine, an amino group, a cyano group, -C(O)NH2, -CH3, or a piperidinyl group.

[0097] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If present, they independently include halogen, hydroxyl group, amino group, and -R. 3e or -N(R 3e )(R 3f ) is selected from, R 3e , R 3f If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, or C 1-6 Alkyl alkyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 C may be substituted with one or more aryl groups or 5- to 12-membered heteroaryl groups. 1-6 Alkyl alkyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 Selected from an aryl group or a 5-12 membered heteroaryl group, or R 3e and R 3f When R is bonded to the same nitrogen atom, 3e and R 3f These, along with the nitrogen atom to which they are bonded, optionally include halogens, hydroxyl groups, amino groups, and C 1-6 Alkyl alkyl group, C 3-10 Cycloalkyl groups, 3-10 member heterocycloalkyl groups, C 6-14 A 3-10 member heterocycloalkyl group or a 5-12 member heteroaryl group is formed, which may be substituted with one or more aryl groups or 5-12 member heteroaryl groups.

[0098] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If present, independently, -R 3e or -N(R 3e )(R 3f ) is selected from, R 3e , R 3f If present, independently, C 1-6 Selected from alkyl groups or 3- to 8-membered heterocycloalkyl groups, or R 3e and R 3f When R is bonded to the same nitrogen atom, 3e and R 3f These, along with the nitrogen atom to which they bond, form a 3- to 8-membered heterocycloalkyl group.

[0099] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d The group is selected from a methyl group, -N(methyl)(methyl) (i.e., a dimethylamino group), or a piperidinyl group.

[0100] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, R3 is selected from the following groups, which may optionally be substituted. [ka] The phrase "may be substituted as desired" means that R may be substituted as desired. 3d This means that it may be replaced by [another term].

[0101] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R3 is selected from the following groups. [ka]

[0102] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R3 is selected from the following groups. [ka]

[0103] Preferably, the present invention provides compounds having the structure represented by formula (II-a) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, m 1-1 R is selected from 0, 1, or 2. 1a-1 R in compounds of formula (I') or formula (I) is 1a As defined, X 2-1 This is as defined for X2 in compounds of formula (I') or formula (I), and R 2-1 This is as defined for R2 in compounds of formula (I') or formula (I), and R 3-1 R3 is defined as such in compounds of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are defined as such in compounds of formula (I') or formula (I).

[0104] Preferably, the present invention provides compounds having a structure represented by formula (II-a1) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, R4, R5, R6, R7, A, W, L, t1, and t2 are defined as compounds of formula (I') or formula (I).)

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

[0106] Preferably, the present invention provides compounds having the structure represented by formula (II-b) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, m 1-2 R is selected from 0, 1, 2, or 3. 1a-2 R in compounds of formula (I') or formula (I) is 1a As defined, X 2-2 This is as defined for X2 in compounds of formula (I') or formula (I), and R 2-2 This is as defined for R2 in compounds of formula (I') or formula (I), and R 3-2 R3 is defined as such in compounds of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are defined as such in compounds of formula (I') or formula (I).

[0107] Preferably, the present invention provides compounds having a structure represented by formula (II-b1) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, m 1-3 R is selected from 0, 1, 2, or 3. 1a-3 R in compounds of formula (I') or formula (I) is 1a As defined, R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for compounds of formula (I') or formula (I).

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

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

[0110] Preferably, the present invention provides compounds having a structure represented by formula (II-d) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, E1, E2, E3, E4, E5, E6 are independently selected from C or N, m 1-6 R is selected from 0, 1, 2, 3 or 4. 1a-6 R in compounds of formula (I') or formula (I) is 1a As defined, X 2-4 This is as defined for X2 in compounds of formula (I') or formula (I), and R 2-4 R2 is defined in compounds of formula (I') or formula (I), R 3-4 R3 is defined as such in compounds of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are defined as such in compounds of formula (I') or formula (I).

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

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

[0113] Preferably, the present invention provides compounds having a structure represented by formula (II-d3) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, m 1-9 R is selected from 0, 1, or 2. 1a-9 R in compounds of formula (I') or formula (I) is 1a As defined, R 3b-5 R in compounds of formula (I') or formula (I) is 3b As defined, R 3c-5 R in claim 1 3cAs defined, R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for compounds of formula (I') or formula (I).

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

[0115] Preferably, the present invention provides compounds having a structure represented by formula (II-d5) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, m 1-11 R is selected from 0, 1, 2, or 3. 1a-11 R in compounds of formula (I') or formula (I) is 1a As defined, R4, R5, R6, R7, A, W, L, t1, and t2 are as defined for compounds of formula (I') or formula (I).

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

[0117] Preferably, the present invention provides compounds having a structure represented by formula (II-e) or prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. [ka] (In the formula, E7, E8, E9, E 10 , E 11 , E 12 It is independently selected from C or N, and m 1-13 is selected from 0, 1, 2, or 3, m 2-1 R is selected from 0, 1, 2, 3 or 4. 1a-13 R in compounds of formula (I') or formula (I) is 1a As defined, R 2a-1 R in compounds of formula (I') or formula (I) is 2a As defined, R 3-5 R3 is defined as such in compounds of formula (I') or formula (I), and R4, R5, R6, R7, A, W, L, t1, and t2 are defined as such in compounds of formula (I') or formula (I).

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

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

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

[0121] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a These are independently -H, -F, -Cl, -NH2, oxo group, -CH3, -CH2CH3, -OCH3, -OCH2CH3, -NHC(O)CH3, -C(O)NHCH3, [ka] Selected from, The aforementioned oxo group refers to a structure in which two hydrogen atoms at the same substitution position are replaced by one oxygen atom, forming a double bond.

[0122] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 1a These are independently -H, -NH2, oxo group, -CH3, -CH2CH3, -NHC(O)CH3, [ka] Selected from, The aforementioned oxo group refers to a structure in which two hydrogen atoms at the same substitution position are replaced by one oxygen atom, forming a double bond.

[0123] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, Y is selected from the following groups. [ka]

[0124] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, Y is selected from the following groups. [ka]

[0125] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R4 is hydrogen, halogen, amino group or C 1-6 Selected from alkoxy groups.

[0126] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R4 is hydrogen, halogen or C 1-3 Selected from alkoxy groups.

[0127] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, R4 is selected from hydrogen, fluorine, or methoxy.

[0128] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, R4 is selected from hydrogen or fluorine.

[0129] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, R4 is selected from a methoxy group.

[0130] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R5 may be substituted with hydrogen, deuterium, or optionally one or more deuterium atoms. 1-6 Selected from alkyl groups.

[0131] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R5 is C 1-6 It is an alkyl group.

[0132] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R5 is C 1-3 It is an alkyl group.

[0133] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, R5 is a methyl group. Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, L is C(R L ) or N, R L C is hydrogen, halogen, amino group, hydroxyl group, C 1-6 Alkyl alkyl group or C 1-6Selected from alkoxy groups.

[0134] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, L is C(R L ) and R L This is selected from hydrogen, halogen, amino group, methyl group, or methoxy group.

[0135] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, L is CH.

[0136] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, L is N.

[0137] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, Q1, and Q2 are independently selected from O, C, S, or N, and Q3 is C, where Q1 is bonded to W.

[0138] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W, Q1, and Q2 are independently selected from O, C, or S, and Q3 is C, where Q1 is bonded to W.

[0139] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, W is selected from O or N, Q1 is C, Q2 is C, Q3 is C, where Q1 is bonded to W.

[0140] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, they independently include hydrogen, deuterium, halogen, hydroxyl group, amino group, cyano group, and -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 ) can be selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two groups bonded to the same atom are =O, =NR 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 An aryl group, a 5-12 membered heteroaryl group, a fused ring group, or a heterofused ring group may be formed, or one of the atoms of W, Q1 (if present), Q2, and Q3 (if present) may be present together with the substituent to which they are bonded, optionally R6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 It forms an aryl group, a 5-12 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 its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, they independently include hydrogen, halogen, hydroxyl group, amino group, cyano group, and -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 ) can be selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two groups bonded to the same atom are =O, =NR 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R 6cC may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 An aryl group, a 5-12 membered heteroaryl group, a fused ring group, or a heterofused ring group may be formed, or one of the atoms of W, Q1 (if present), Q2, and Q3 (if present) may be present together with the substituent to which they are bonded, optionally R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 It forms an aryl group, a 5-12 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 its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, they independently include hydrogen, halogen, hydroxyl group, amino group, cyano group, and -R. 6a , -OR 6a , -C(O)R 6a , -C(O)OR 6a ,-OC(O)R 6a , -NH(R 6a ), -N(R 6a )(R 6b ), -C(O)NH(R 6a ), -C(O)N(R 6a )(R 6b ), -NHC(O)(R 6a ) or -N(R 6a )C(O)(R 6b ) can be selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two groups bonded to the same atom are =O, =NR 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 An aryl group, a 5-12 membered heteroaryl group, a fused ring group, or a heterofused ring group may be formed, or one of the atoms of W, Q1 (if present), Q2, and Q3 (if present) may be present together with the substituent to which they are bonded, optionally R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 It forms an aryl group or a 5-12 membered heteroaryl group.

[0143] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, they independently include hydrogen, halogen, hydroxyl group, amino group, and -R. 6a , -NH(R 6a ) or -N(R 6a )(R 6b ) can be selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two groups bonded to the same atom are =O, =NR 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 An aryl group, a 5-12 membered heteroaryl group, a fused ring group, or a heterofused ring group may be formed, or one of the atoms of W, Q1 (if present), Q2, and Q3 (if present) may be present together with the substituent to which they are bonded, optionally R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C6-14 It forms an aryl group or a 5-12 membered heteroaryl group.

[0144] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, they independently include hydrogen, halogen, hydroxyl group, amino group, and -R. 6a , -NH(R 6a ) or -N(R 6a )(R 6b ) can be selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two groups bonded to the same atom are =O, =NR 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 An aryl group, a 5-12 membered heteroaryl group, a fused ring group, or a heterofused ring group may be formed, or one of the atoms of W, Q1 (if present), Q2, and Q3 (if present) may be present together with the substituent to which they are bonded, optionally R 6c C may be substituted by 3-10 It forms a carbon ring group or a 3- to 10-membered heterocyclic group.

[0145] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13If present, they independently include hydrogen, halogen, hydroxyl group, amino group, and -R. 6a , -NH(R 6a ) or -N(R 6a )(R 6b ) can be selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two groups bonded to the same atom are =O, =NR 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R 6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-8 An aryl group, a 5-10 membered heteroaryl group, a fused ring group, or a heterofused ring group may be formed, or one of the atoms of W, Q1 (if present), Q2, and Q3 (if present) may be present together with the substituent to which they are bonded, and optionally R 6c C may be substituted by 3-10 It forms a carbon ring group or a 3- to 10-membered heterocyclic group.

[0146] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, independently of hydrogen, halogen, or -R 6a Selected from, or R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two groups bonded to the same atom are =O, =NR 6a Or =CH-R 6a Either W, Q1 (in the presence of Q2 and Q3), or any two adjacent atoms of Q1, Q2 and Q3 (in the presence of Q2 and Q3), together with the substituents to which they are bonded, optionally form R6c C may be substituted by 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-8 It forms an aryl group or a 5-12 membered heteroaryl group, or any one of the atoms of W, Q1 (if present), Q2 and Q3 (if present) together with the substituent to which they are bonded, optionally R 6c C may be substituted by 3-10 It forms a carbon ring group or a 3- to 10-membered heterocyclic group.

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

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

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

[0150] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, one of the atoms of W, Q1 in presence, Q2 and Q3 in presence, together with the substituent to which they are bonded, 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 compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, one of the atoms of W, Q1 in presence, Q2 and Q3 in presence, together with the substituent to which they are bonded, optionally R 6c C may be substituted by 3-6 It forms a cycloalkyl group or a 3- to 7-membered heterocycloalkyl group.

[0152] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, one of the atoms of W, Q1 in presence, Q2 and Q3 in presence, together with the substituent to which they are bonded, optionally R 6c C may be substituted by 3-4 It forms a cycloalkyl group or a 3- to 6-membered heterocycloalkyl group, where the heteroatom is selected from O or N, and the number of heteroatoms is one or two.

[0153] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, one of the atoms of W, Q1 in presence, Q2 and Q3 in presence, together with the substituent to which they are bonded, optionally R 6c C may be substituted by 3-4 It forms a cycloalkyl group.

[0154] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b If present, it independently provides hydrogen, or optionally R 6c C may be substituted by 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 Selected from aryl groups, 5-12 membered heteroaryl groups, fused ring groups, or heterofused ring groups, or R 6a and R 6b When R is bonded to the same nitrogen atom, 6a and R 6b These, along with the nitrogen atom to which they bond, optionally include R 6c It forms a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group, which may be substituted by the compound.

[0155] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b If present, it independently provides hydrogen, or optionally R 6c C may be substituted by 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-8 Selected from an aryl group or a 5-10 membered heteroaryl group.

[0156] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b If present, independently of hydrogen, deuterium, or R as desired. 6c C may be substituted by 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, 5-6 member heterocycloalkyl groups, C 6-8 The group is selected from an aryl group, a 5-6 membered heteroaryl group, a 9-10 membered bicyclic heterocyclic group, or a 9-10 membered bicyclic heteroaryl group.

[0157] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b If present, it independently provides hydrogen, or optionally R 6c C may be substituted by 1-6 Alkyl or C 1-6 Selected from alkoxy groups.

[0158] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b If present, it independently provides hydrogen, or optionally R 6c C may be substituted by 1-3 Alkyl or C 1-3 Selected from alkoxy groups.

[0159] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6bIf present, it independently provides hydrogen, or optionally R 6c A methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, ethoxy group, n-propoxy group, or isopropoxy group may be substituted by the following:

[0160] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6a , R 6b If present, it independently provides hydrogen, or optionally R 6c A methyl group or an ethyl group may be selected, which may be substituted by the methyl group or ethyl group.

[0161] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c If present, independently of hydrogen, deuterium, halogen, hydroxyl group, amino group, and -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 Selected from.

[0162] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c If present, they independently include hydrogen, halogen, hydroxyl group, amino group, and -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 Selected from.

[0163] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6d , R 6e If present, independently of hydrogen, halogen, hydroxyl group, amino group, nitro group, cyano group, or optionally halogen, hydroxyl group, amino group, or C 1-6 C may be substituted with an alkyl group. 1-6 Alkyl alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 Selected from aryl groups, 5-12 membered heteroaryl groups, fused ring groups, or heterofused ring groups, or R 6d and R 6e When R is bonded to the same nitrogen atom, 6d and R 6e These, along with the nitrogen atom to which they are bonded, optionally include halogens, hydroxyl groups, amino groups, or C 1-6 It forms a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group, which may be substituted with an alkyl group.

[0164] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6d , R 6e If present, they independently include hydrogen, halogen, hydroxyl group, amino group, nitro group, cyano group, and C. 1-6 Alkyl alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14Selected from aryl groups, 5-12 membered heteroaryl groups, fused ring groups, or heterofused ring groups, or R 6d and R 6e When R is bonded to the same nitrogen atom, 6d and R 6e These, together with the nitrogen atom to which they are bonded, form a 3- to 10-membered heterocyclic group or a 5- to 12-membered heteroaryl group.

[0165] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6d , R 6e If present, hydrogen and C are independently present. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-14 The group is selected from an aryl group, a 5-12 membered heteroaryl group, a fused ring group, or a heterofused ring group.

[0166] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6d , R 6e If present, hydrogen and C are independently present. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-8 Selected from an aryl group or a 5-10 membered heteroaryl group.

[0167] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c If present, they independently include hydrogen, fluorine, chlorine, hydroxyl group, amino group, and -NH(C). 1-6 Alkyl), -N(CH3)(C 1-6 Alkyl), -C(O)(C 1-6 Alkyl), -C(O)NH(C 1-6Alkyl), -NHC(O)(C 1-6 Alkyl), -C(O)O(C 1-6 Alkyl), C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-8 The group is selected from an aryl group, a 5-10 membered heteroaryl group, a fused ring group, or a heterofused ring group.

[0168] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c If present, they independently include hydrogen, fluorine, chlorine, hydroxyl group, amino group, and -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 alkyl group, C 1-6 Alkoxy group, C 3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-8 Selected from an aryl group or a 5-10 membered heteroaryl group.

[0169] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c If present, they independently include hydrogen, fluorine, chlorine, hydroxyl group, amino group, and -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 alkyl group, C 1-6 Alkoxy group, C3-10 Carbon ring group, 3-10 membered heterocyclic group, C 6-8 The group is selected from an aryl group or a 5- to 10-membered heteroaryl group, where the heteroatom is selected from N or S, and the number of heteroatoms is 1, 2, or 3.

[0170] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c If present, they independently include hydrogen, fluorine, chlorine, hydroxyl group, amino group, and -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 alkyl group, C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, 3-6 member heterocycloalkyl groups, C 6-8 The group is selected from an aryl group or a 5-6 membered heteroaryl group, where the heteroatom is selected from N or S, and the number of heteroatoms is 1, 2, or 3.

[0171] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6c If present, they independently include hydrogen, deuterium, halogen, hydroxyl group, amino group, and C. 1-6 Alkyl alkyl group or C 1-6 Selected from alkoxy groups.

[0172] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 6cIf present, the group is independently selected from hydrogen, fluorine, chlorine, hydroxyl group, amino group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, ethoxy group, n-propoxy group, or isopropoxy group.

[0173] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, independently of hydrogen, deuterium, or optionally deuterium, halogen, hydroxyl group, amino group, C 1-6 Alkyl 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 may be substituted with a cycloalkyl group, a 5-6 membered heterocycloalkyl group, a phenyl group, a 5-6 membered heteroaryl group, a 9-10 membered bicyclic heterocyclic group, or a 9-10 membered bicyclic heteroaryl group. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, 5-6 member heterocycloalkyl groups, C 6-8 The group is selected from an aryl group, a 5-6 membered heteroaryl group, a 9-10 membered bicyclic heterocyclic group, or a 9-10 membered bicyclic heteroaryl group.

[0174] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, or C 1-6Alkyl 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 may be substituted with a cycloalkyl group, a 5-6 member heterocycloalkyl group, a phenyl group, or a 5-6 member heteroaryl group. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, 5-6 member heterocycloalkyl groups, C 6-8 Selected from an aryl group or a 5-6 membered heteroaryl group.

[0175] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, or C 1-6 Alkyl 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 may be substituted with alkyl. 1-6 Alkyl or C 1-6 Selected from alkoxy groups.

[0176] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, or C 1-6Alkyl alkyl group, C 1-6 C may be substituted with an alkoxy group. 1-6 Alkyl or C 1-6 Selected from alkoxy groups.

[0177] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, it independently contains hydrogen, or optionally a halogen, hydroxyl group, amino group, or C 1-3 Alkyl alkyl group or C 1-3 C may be substituted with an alkoxy group. 1-3 Alkyl or C 1-3 Selected from alkoxy groups.

[0178] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If 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] Selected from.

[0179] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If 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] Selected from.

[0180] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 If present, it 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 compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R6, R7, R8, R9, R 10 , R 11 , R 12 and R 13 Of these, any two groups bonded to the same atom form either =O or =CH2.

[0182] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, any two adjacent atoms of W, Q1 in the presence of Q2 and Q3 in the presence of Q3, together with the substituents to which they are bonded, form the following groups. [ka]

[0183] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, one of the atoms of W, Q1 in the presence of Q2, and Q3 in the presence of Q3, together with the substituents to which they are bonded, forms the following groups. [ka]

[0184] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, one of the atoms of W, Q1 in the presence of Q2, and Q3 in the presence of Q3, together with the substituents to which they are bonded, forms the following group. [ka]

[0185] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt, one of the atoms of W, Q1 in the presence of Q2, and Q3 in the presence of Q3, together with the substituents to which they are bonded, forms the following group. [ka]

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

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

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

[0189] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may be independently and optionally substituted. 1-6 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c Together with the nitrogen atom to which these are bonded, they form a 3- to 10-membered heterocycloalkyl group which may optionally be substituted, and the phrase "may optionally be substituted" means that R may optionally be substituted. 3d This means that it may be replaced by [another term].

[0190] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3cIf present, C may be independently and optionally substituted. 1-4 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c These, together with the nitrogen atom to which they are bonded, form a 5-6 membered heterocycloalkyl group or a 6-10 membered bicyclic heterocyclic group, which may optionally be substituted, and the heteroatoms are independently O or N, and the number of heteroatoms is 1, 2, or 3. The phrase "may optionally be substituted" means that R may optionally be substituted. 3d This means that it may be replaced by [another term].

[0191] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, C may be independently and optionally substituted. 1-4 Selected from alkyl groups, or R 3b and R 3c When R is bonded to the same nitrogen atom, 3b and R 3c These, together with the nitrogen atom to which they are bonded, form optionally substituted 5-6 membered heterocycloalkyl groups, 3- / 6 membered heteromonocyclic spiro ring groups, 4- / 6 membered heteromonocyclic spiro ring groups, or 3- / 5 membered fused heterocyclic groups, wherein the heteroatoms are independently O or N, and the number of heteroatoms is 1, 2, or 3. The phrase "optionally substituted" means optionally R 3d This means that it may be replaced by [another term].

[0192] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b , R 3c If present, it is independently selected from methyl groups which may be optionally substituted, or R 3band R 3c When R is bonded to the same nitrogen atom, 3b and R 3c Together with the nitrogen atom to which these are bonded, they form a 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]hexy-3-yl group), or 6-azaspiro[2.5]octyl group (e.g., 6-azaspiro[2.5]octa-6-yl group), which may be optionally substituted. 3d This means that it may be replaced by [another term].

[0193] Preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If present, these are independently selected from deuterium, fluorine, a hydroxyl group, an amino group, a cyano group, -NH(CH3), -N(CH3)(CH3), -C(O)NH2, -CH3, -CH2CH3, or -CH2CH2CH3.

[0194] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3d If present, it is independently selected from deuterium, fluorine, a cyano group, -C(O)NH2, or -CH3.

[0195] More preferably, in the compound according to the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, R 3b and R 3c These, together with the nitrogen atom to which they bond, form a group selected from the following groups. [ka]

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

[0197] [Intermediates for synthesis and manufacturing methods] With respect to the above-mentioned compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), having a structure represented by formula (M-1). [ka] (In the formula, R x1 (The elements are selected from halogens or hydrogen, and R4, R6, R7, A, W, L, t1, t2, and h are as defined for compounds of formula (I') or formula (I).)

[0198] With respect to the above-mentioned compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), having a structure represented by formula (M-2). [ka] (In the formula, R x1 (The elements are selected from halogens or hydrogen, and R4, R6, R7, A, W, L, t1, t2, and h are as defined for compounds of formula (I') or formula (I).)

[0199] With respect to the above-mentioned compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), having a structure represented by formula (M-3). [ka] (In the formula, R x1 (The elements are selected from halogens or hydrogen, and R4, R6, R7, A, W, L, t1, t2, and h are as defined for compounds of formula (I') or formula (I).)

[0200] With respect to the above-mentioned compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), having a structure represented by formula (M-4). [ka] (In the formula, R x2 R is selected from halogen or hydrogen, 4 、R 6 、R 7 A, W, L, t 1 、t 2 ,h is as defined for compounds of formula (I') or formula (I).

[0201] With respect to the above-mentioned compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), having a structure represented by formula (M-5). [ka] (In the formula, R x3 R is selected from halogen or hydrogen, 4 、R 6 、R 7 A, W, L, t 1 、t 2 ,h is as defined for compounds of formula (I') or formula (I).

[0202] With respect to the above-mentioned compounds, the present invention further provides an intermediate for producing a compound of formula (I') or formula (I), having a structure represented by formula (M-6). [ka] (In the formula, R x4 R is selected from halogen or hydrogen, 4 、R 6 、R 7 A, W, L, t 1 、t 2 ,h is as defined for compounds of formula (I') or formula (I).

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

[0204] The present invention further provides a method for producing a compound of formula (I') or formula (I). For example, the compound can be produced using the method represented by the following synthesis routes 1, 2, or 3. Synthesis Route 1

[0205] [ka] i) Compound I-a1 is subjected to a chemical transformation (e.g., substitution reaction) to obtain compound I-a2. For example, compound I-a2 is obtained using compound I-a1 and thionyl chloride as basic raw materials. ii) Compound I-a2 is subjected to chemical transformation (e.g., substitution reaction or desired ring-closing reaction) to obtain compound I-a4. For example, compounds I-a2 and I-a3 are used as basic starting materials and reacted under basic conditions to obtain an unclosed or closed compound I-a4. iii) Compound I-a4 is subjected to a chemical transformation (e.g., hydrolysis) to obtain compound I-a5. For example, compound I-a4 is reacted under basic conditions to obtain compound I-a5. iv) Compound I-a5 is subjected to a chemical transformation (e.g., a ring-closing reaction) to obtain compound I-a6. For example, compound I-a5 and diphenylphosphoryl azide are used as basic starting materials and reacted under basic conditions to obtain compound I-a6. v) Compound I-a6 is subjected to a chemical transformation (e.g., alkylation reaction) to obtain compound I-a7. For example, compound I-a6 and a halide (e.g., iodomethane) are used as basic raw materials and reacted under basic conditions to obtain compound I-a7. vi) Compound I-a7 is subjected to a chemical transformation (e.g., a coupling reaction) to obtain compound I-a8. For example, compound I-a7 and a boric acid derivative are used as basic raw materials in a coupling reaction to obtain compound I-a8. vii) Compound I is obtained by chemically transforming compound I-a8 (e.g., through a substitution reaction). For example, compound I-a8, etc., is used as a basic starting material and reacted under basic conditions to obtain compound I of the general formula. Synthesis Route 2

[0206] [ka] i) Compound I-b2 is obtained using compound I-b1 and thionyl chloride, etc., as basic raw materials. ii) Compound I-b4 is obtained by reacting compounds I-b2 and I-b3 as basic starting materials under basic conditions. iii) Compound I-b4 is reacted under basic conditions to obtain compound I-b5. iv) Compound I-b5 and a suitable reducing agent (e.g., iron powder, zinc powder, etc.), ammonium chloride, etc. are used as basic raw materials to obtain compound I-b6. v) Compound I-b7 is obtained using compound I-b6 and N,N-carbonyldiimidazole (CDI), etc., as basic raw materials. vi) Compound I-b7 and a halide (e.g., iodomethane) are used as basic raw materials and reacted under basic conditions to obtain compound I-b8. vii) Compound I-b8 and boric acid derivatives, etc., are used as basic raw materials in a coupling reaction to obtain compound I-b9. viii) Compound I-b9 is reacted with amines or alcohols, etc., as basic raw materials under basic conditions to obtain compound I of the general formula. Synthesis Route 3

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

[0208] Preferably, in the manufacturing method of the present invention, R x1 (The elements are selected from halogens 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 hydrocarbons, 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 above-mentioned compounds, the present invention further provides pharmaceutical compositions comprising the compound of the present invention or its prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts.

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

[0215] [Medical Use] The present invention further provides the use of the compounds of the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts or pharmaceutical compositions of the present invention as ATM kinase inhibitors.

[0216] The present invention further provides the use of the compounds of the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts or pharmaceutical compositions of the present invention for the prevention and / or treatment of diseases and / or disorders mediated at least partially by ATM kinase. Preferably, the diseases and / or disorders mediated at least partially by ATM kinase are cancer.

[0217] Furthermore, the present invention further provides the use of the compounds of the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts or pharmaceutical compositions of the present invention for the prevention and / or treatment of cancer. Furthermore, the cancers include solid tumors and hematological malignancies. Preferably, the cancers include breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, small cell lung cancer, and glioblastoma.

[0218] The present invention further provides the use of the compounds of the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts or pharmaceutical compositions of the present invention for the production of ATM kinase inhibitors.

[0219] The present invention further provides the use of the compounds of the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts or pharmaceutical compositions of the present invention for the production of pharmaceuticals for the prevention and / or treatment of diseases and / or disorders mediated at least partially by ATM kinase. Preferably, the diseases and / or disorders mediated at least partially by ATM kinase are cancer.

[0220] Furthermore, the present invention provides the use of the compounds of the present invention or their prodrugs, tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts or pharmaceutical compositions of the present invention for the manufacture of pharmaceuticals for the prevention and / or treatment of cancer. Furthermore, the cancers include solid tumors and hematological malignancies. More preferably, the cancers include breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, small cell lung cancer, and glioblastoma.

[0221] The present application further provides a method for the prevention and / or treatment of diseases and / or disorders mediated at least partially by ATM kinase, comprising administering a preventive and / or therapeutically effective amount of the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt or pharmaceutical composition of the present invention to a subject in need thereof. Preferably, the diseases and / or disorders mediated at least partially by ATM kinase are cancers. More preferably, the cancers include solid tumors and hematological malignancies. More preferably, the cancers include breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, small cell lung cancer, and glioblastoma.

[0222] Furthermore, the present application further provides a method for the prevention and / or treatment of cancer, comprising administering a preventive and / or therapeutically effective amount of the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt or pharmaceutical composition of the present invention to a subject in need thereof. Preferably, the cancers include solid tumors and hematological malignancies. More preferably, the cancers include breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, small cell lung cancer, and glioblastoma.

[0223] Furthermore, in the use or method of the present invention, the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt thereof or pharmaceutical composition of the present invention is administered together with at least one additional antitumor agent or therapeutic treatment (e.g., radiotherapy). Preferably, the antitumor agent is selected from doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan, bleomycin, cisplatin, oxaliplatin, carboplatin, barrubicin, idarubicin, pirarubicin, amrubicin, epirubicin, olaparib, MEDI4736, AZD1775, and AZD6738. Preferably, the therapeutic treatment is radiotherapy.

[0224] Furthermore, in the use or method of the present invention, the compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt thereof or pharmaceutical composition of the present invention may be administered simultaneously with, separately from, or sequentially with radiotherapy.

[0225] The present invention further includes a compound of the present invention or its prodrug, tautomer, optical isomer, geometric isomer, solvate, isotopic derivative or pharmaceutically acceptable salt, or a pharmaceutical composition of the present invention, and at least one additional antitumor agent. or therapeutic treatment The present invention provides a combination form of pharmaceuticals (or combination composition of pharmaceuticals, pharmaceutical complex composition) containing the above. Preferably, the antitumor agent is selected from doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan, bleomycin, cisplatin, oxaliplatin, carboplatin, barrubicin, idarubicin, pirarubicin, amrubicin, epirubicin, olaparib, MEDI4736, AZD1775, and AZD6738. Preferably, the therapeutic treatment is radiotherapy.

[0226] [Definition of Terms] The terms "may," "optional," "at will," or "at will" mean that the event or situation may occur, but is not guaranteed to occur, and include both cases in which such event or situation occurs and cases in which it does not occur. Thus, the term "may be substituted as desired" means that a specific group does not necessarily have to be substituted, but may be substituted at a position where it can be substituted by one or more independently existing substituents. When the group is substituted, the hydrogens at one or more substituted positions of the substituent are independently substituted by substituents, and these substituents can independently be deuterium, halogen, hydroxyl group, amino group, nitro group, mercapto group, cyano group, oxo group, -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 alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, C2-6 Alkenyl group, C 2-6 Alkynyl group, 3-10 member heterocycloalkyl group, C 6-14 The group may be selected from an aryl group or a 5- to 12-membered heteroaryl group, and the oxo group refers to a group in which two H atoms at the same substitution position are replaced by one O atom to form a double bond.

[0227] Unless otherwise specified, the term "bond" refers to a chemical bond, and includes, but is not limited to, covalent bonds (e.g., carbon-carbon single bond, carbon-nitrogen single bond, carbon-oxygen single bond, carbon-sulfur single bond, carbon-carbon double bond, carbon-nitrogen double bond, carbon-oxygen double bond, carbon-sulfur double bond, carbon-carbon triple bond, carbon-nitrogen triple bond, etc.), ionic bonds, and coordinate bonds. In the compounds of the present invention, the bonds between the core and the substituents or between each substituent are substantially covalent bonds.

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

[0229] Unless otherwise specified, the term "hydroxyl group" refers to the "-OH" group.

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

[0231] Unless otherwise specified, the term "amino group" refers to the "-NH2" group. In some embodiments, the amino group is a group in which one or two of its hydrogen atoms are substituted with alkyl (e.g., -NH(C) 1-6 Alkyl), -N(C 1-6 Includes alkyl (2, etc.).

[0232] Unless otherwise specified, the term "nitro group" refers to the "-NO2" group.

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

[0234] The term "oxo" refers to a compound where two hydrogen atoms at the same substitution position are replaced by one oxygen atom, forming a double bond (i.e., "=O").

[0235] Unless otherwise specified, the term "alkyl group" means a linear or branched saturated monovalent aliphatic hydrocarbon group which may contain 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 8 carbon atoms, and more preferably 1 to 6 carbon atoms (i.e., C 1-6 (Alkyl group). For example, "C 1-6 An alkyl group refers to an alkyl group in which the number of carbon atoms in the carbon chain ranges from 1 to 6 (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" means an -O-alkyl group, where the alkyl group may contain 1 to 20 carbon atoms as defined above, preferably 1 to 10 carbon atoms, more preferably 1 to 8 carbon atoms, and more preferably 1 to 6 carbon atoms (i.e., C 1-6 (alkoxy group). For example, "C 1-6An "alkoxy group" refers to an alkoxy group in which the number of carbon atoms in the carbon chain is in the range of 1 to 6 (specifically, 1, 2, 3, 4, 5, or 6). 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 terms "halogen" or "halogenation" refer to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

[0238] Unless otherwise specified, the term "halogenated alkyl group" refers to an alkyl group in which one, two, multiple, or all hydrogen atoms are substituted with a halogen, as defined above. Examples of halide alkyl groups include (but are not limited to) -CCl3, -CF3, -CHCl2, -CH2Cl, -CH2Br, -CH2I, -CH2CF3, and -CF2CF3.

[0239] Unless otherwise specified, the term "alkenyl group" means a linear or branched monovalent aliphatic hydrocarbon group containing one or more (e.g., one, two, three, or four) 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 more preferably 2 to 6 carbon atoms (i.e., C 2-6 (Alkenyl group). For example, "C 2-6 An "alkenyl group" refers to an alkenyl group in which the number of carbon atoms in the carbon chain ranges from 2 to 6 (specifically, 2, 3, 4, 5, or 6). Examples of alkenyl groups include (but are not limited to) vinyl groups, n-propenyl groups, n-butenyl groups, and n-pentenyl groups.

[0240] Unless otherwise specified, the term "alkynyl group" means a monovalent aliphatic hydrocarbon group containing one or more (e.g., one, two, three, or four) 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 more preferably 2 to 6 carbon atoms (i.e., C 2-6 (Alkynyl group). For example, "C 2-6 An "alkynyl group" refers to an alkynyl group in which the number of carbon atoms in the carbon chain is in the range of 2 to 6 (specifically, 2, 3, 4, 5, or 6). Examples of alkenyl groups include (but are not limited to) ethynyl, n-propynyl, n-butynyl, and n-pentynyl groups.

[0241] Unless otherwise specified, the terms "carbocyclic group" or "carbocyclic" mean a monocyclic or polycyclic, saturated or partially unsaturated monovalent non-aromatic hydrocarbon group, which may contain 3 to 14 ring carbon atoms (i.e., C 3-14 A carbocyclic group), preferably consisting of 3 to 12 ring carbon atoms (i.e., C 3-12 A carbocyclic group), more preferably 4 to 12 ring carbon atoms (i.e., C 4-12 (Carbocyclic group) or 3 to 10 ring carbon atoms (i.e., C 3-10 It may also contain a carbon ring group. In some examples, the carbon ring group contains 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 group (C3), cyclopropenyl group (C3), cyclobutyl group (C4), cyclobutenyl group (C4), cyclopentyl group (C5), cyclopentenyl group (C5), cyclohexyl group (C6), cyclohexenyl group (C6), and cyclohexadienyl group (C6). 3-8 Examples of carbocyclic groups include the above C 3-6Examples include (but are not limited to) carbocyclic groups and cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptyl (C7), bicyclo[2.2.2]octyl (C8), etc. 3-10 Examples of carbocyclic groups include the above C 3-8 Carbocyclic groups and cyclononyl groups (C9), cyclononenyl groups (C9), cyclodecyl groups (C9) 10 ), cyclodecenyl group (C 10 ), OctaHydro-1H-indenyl group (C9), Decalinyl group (C 10 )(decalinyl), spiro[4.5]decyl group (C 10 Examples include (but are not limited to) the following. The carbocyclic group may be a monocyclic (monocyclic carbocyclic group) ring system, or a condensed (condensed ring group), bridging (bridging ring group), or spiro-bonded (spiro ring group) ring system, such as a bicyclic (bicyclic carbocyclic group), and may be saturated or partially unsaturated. In some embodiments, the carbocyclic group further comprises a ring system formed by the condensation of a carbocyclic ring as defined above with one or more aryl / heteroaryl groups, with the bonding site located on the carbocyclic ring. Alternatively, in some embodiments, the carbocyclic group comprises a ring system formed by the condensation of a carbocyclic group as defined above with one or more carbocyclic groups as defined above, with the bonding site located on any of the carbocyclic rings. In these cases, the number of members in the carbocyclic ring system is the number of ring carbon atoms in the condensed ring system. In some embodiments, the carbocyclic group may optionally be substituted, for example, unsubstituted (unsubstituted carbocyclic group) or substituted with one or more substituents (substituted carbocyclic group). In some embodiments, the carbon ring group is unsubstituted C 3-10 It is a carbon ring group. In some embodiments, the carbon ring group is substituted C 3-10 It is a carbon ring group.

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

[0243] Unless otherwise specified, the terms "heterocyclic group" or "heterocyclic" mean a monocyclic or polycyclic saturated or partially unsaturated monovalent non-aromatic group having a ring carbon atom and 1 to 4 heterocyclic atoms, which may include 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 C, preferably including 3 to 12 ring atoms (i.e., a 3 to 12-membered heterocyclic group), and more preferably 3 to 10. The heterocyclic group may contain ring atoms (i.e., a 3-10 membered heterocyclic group), 3-8 membered heterocyclic groups (i.e., a 3-8 membered heterocyclic group), 3-6 membered heterocyclic groups (i.e., a 3-6 membered heterocyclic group), 4-6 membered heterocyclic groups (i.e., a 4-6 membered heterocyclic group), or 5-6 membered heterocyclic groups (i.e., a 5-6 membered heterocyclic group), and the number of heteroatoms is 1-4, preferably 1-3 (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 rings, spiro rings, fused rings, and bridged ring heterocyclic groups. The heterocyclic group may be a monocyclic (monocyclic heterocyclic group) ring system, or a fused (fused heterocyclic group or heterofused ring group), fused ring (heterofused ring group or fused ring heterocyclic group), bridging bond (heterobridging ring group or bridging ring heterocyclic group), or spiro bond (heterospiro ring group or spiro ring heterocyclic group) ring system, such as a bicyclic system (bicyclic heterocyclic group), and may be saturated or partially unsaturated. The bicyclic heterocyclic group may have one or more heteroatoms in one or two rings. In some embodiments, the heterocyclic group further comprises a ring system in which a heterocyclic group as defined above is fused with one or more carbocyclic groups, and the bonding site is located in the carbocyclic group or heterocyclic ring. Alternatively, in some embodiments, the heterocyclic group further comprises a ring system formed by the fusion of a heterocyclic group as defined above with one or more aryl / heteroaryl groups, wherein the bond point is located in the aryl / heteroaryl group or the heterocyclic ring. Alternatively, in some embodiments, the ring system further comprises a heterocyclic group as defined above with one or more heterocyclic groups as defined above, wherein the bond point is located in any of the heterocyclic rings.In these cases, the number of members in the heterocyclic ring system is the number of ring atoms in the ring system after condensation. In some embodiments, the heterocyclic group may be optionally substituted, for example, unsubstituted (unsubstituted heterocyclic group) or substituted with one or more substituents (substituted heterocyclic group). Examples of three-membered heterocyclic groups containing one heteroatom include (but are not limited to) aziridinyl, oxiranyl, and thiorenyl groups. Examples of four-membered heterocyclic groups containing one heteroatom include (but are not limited to) azetidinyl, oxetanyl, and thietanyl groups. Examples of five-membered heterocyclic groups containing one heteroatom include (but are not limited to) tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, pyrrolidinyl, dihydropyrrolyl, and 2,5-dioxopyrrolidinyl groups. Examples of five-membered heterocyclic groups containing two heteroatoms include (but are not limited to) the dioxolyl group, oxathiolanyl group, dithiolanyl group, and 2-oxoxazolidinyl group. Examples of five-membered heterocyclic groups containing three heteroatoms include (but are not limited to) the triazolinyl group, oxadiazolinyl group, and thiadiazolinyl group. Examples of six-membered heterocyclic groups containing one heteroatom include (but are not limited to) the piperidinyl group, tetrahydropyranyl group, dihydropyridyl group, and tetrahydrothiopyranyl group (thianyl). Examples of six-membered heterocyclic groups containing two heteroatoms include (but are not limited to) the piperazinyl group, morpholinyl group, dithianyl group, and dioxanyl group. Examples of six-membered heterocyclic groups containing three heteroatoms include (but are not limited to) triazinanyl, oxadiazinanyl, thiadiazinanyl, oxathiazinanyl, and dioxazinanyl. Examples of seven-membered heterocyclic groups containing one heteroatom include (but are not limited to) azepanyl, oxepanyl, and thiepanyl.Examples of eight-membered heterocyclic groups containing one heteroatom include (but are not limited to) the azocanyl group, oxocanyl group, and thiecanyl group. Examples of five-membered heterocyclic groups fused to one C6 aryl ring (also referred to as 5,6-bicyclic heterocyclic groups) include (but are not limited to) the indolinyl group, isoindolinyl group, dihydrobenzofuryl group, dihydrobenzothienyl group, and benzoxazolinonyl group. Examples of six-membered heterocyclic groups fused to one C6 aryl ring (also referred to as 6,6-bicyclic heterocyclic groups) include (but are not limited to) the tetrahydroquinolinyl group and tetrahydroisoquinolinyl group.

[0244] Unless otherwise specified, "heterocycloalkyl group" means a monocyclic, saturated "heterocyclic group" or "heterocyclic ring" 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 C (i.e., a 3 to 20-membered heterocycloalkyl group), preferably containing 3 to 12 ring atoms (i.e., a 3 to 12-membered heterocycloalkyl group), and more preferably containing 3 to 10 ring atoms ( In other words, it may contain 3 to 10 member heterocycloalkyl groups, 3 to 8 ring atoms (i.e., 3 to 8 member heterocycloalkyl groups), 4 to 7 ring atoms (i.e., 4 to 7 member heterocycloalkyl groups), 5 to 10 ring atoms (i.e., 5 to 10 member heterocycloalkyl groups), or 5 to 6 ring atoms (i.e., 5 to 6 member heterocycloalkyl groups), with the number of heteroatoms being 1 to 4, preferably 1 to 3 (1, 2, or 3). In some embodiments, the heterocycloalkyl group may be optionally substituted, for example, unsubstituted (unsubstituted heterocycloalkyl group) or substituted with one or more substituents (substituted heterocycloalkyl group). While several examples of "heterocycloalkyl groups" are given in the aforementioned description of "heterocyclic groups" or "heterocycles," other examples (but not limited to these) include azilidinyl group, oxyranyl group, thiorenyl group, azetidinyl group, oxetanyl group, thietanyl group, tetrahydrofuranyl group, tetrahydropyranyl group, piperidinyl group, piperazinyl group, morpholinyl group, thiomorpholinyl group, oxathianyl group, oxazolidinyl group, dioxanyl group, dithianyl group, thiazolidinyl group, pyrrolidinyl group, pyrazolidinyl group, imidazolidinyl group, etc.

[0245] Unless otherwise specified, the term "condensed ring" refers to a non-aromatic saturated or partially unsaturated ring system formed by two or more ring structures that share two adjacent atoms, and includes condensed carbocyclic groups and condensed heterocyclic groups. Of these, the ring atoms of a condensed heterocyclic group independently contain one or more heteroatoms 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. 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. Here, each spiro atom is counted in the number of members of each ring. Examples of monocyclic spiro ring groups include: [ka] Examples include (but are not limited to) these.

[0247] Unless otherwise specified, the term "monocyclic heterospiro ring group" refers to a saturated monovalent aliphatic group containing only one spirocarbon atom, and may contain 6 to 14 ring atoms, preferably 7 to 10 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. Monocyclic heterospiro 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 heteromonocyclic spiro ring groups, etc. Here, each spiro atom is counted in the number of members of each ring. Examples of monocyclic heterospiro ring groups include: [ka] Examples include (but are not limited to) these.

[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. It may contain 5 to 20 ring carbon atoms, preferably 6 to 14, more preferably 7 to 10, and may also have one or more double bonds, but no rings with a fully 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) the following:

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

[0250] Unless otherwise specified, the terms "aryl group" or "aromatic ring group" refer to monocyclic or polycyclic monovalent aromatic hydrocarbon groups, which may contain 6 to 16 ring carbon atoms (i.e., C 6-16 Aryl group), 6 to 14 ring carbon atoms (i.e., C 6-14Aryl group), 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 It may contain an aryl group. 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, phenantrenyl, and pyrenyl groups.

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

[0252] Unless otherwise specified, the term “pharmaceutically acceptable salt” means a salt that, within the bounds of appropriate medical judgment, is suitable for use in contact with mammalian (especially human) tissues without excessive toxicity, irritation, or allergic reactions, and that is 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. The salts may be prepared directly during the final isolation and purification of the compounds of the present invention, or they may be prepared alone by reacting free bases or free acids with appropriate reagents.

[0253] Unless otherwise specified, the term "isotope derivative" means that the compounds of the present invention may exist in an isotope-labeled or isotope-rich form containing one or more atoms having atomic masses or mass numbers different from the most abundant atoms in nature. The isotopes may be radioactive or non-radioactive. Hydrogen isotopes are commonly used as isotope labels. 2 H and 3 H is a carbon isotope. 13 C and 14 C is a chlorine isotope. 35 Cl and 37 Cl is a fluorine isotope. 18 F is an isotope of iodine. 123 I and 125 I is a nitrogen isotope. 13 N and 15 N is an oxygen isotope. 15 O, 17 O and 18 O is a sulfur isotope. 35 Examples include (but are not limited to) S. Compounds labeled with these isotopes can be used to study the distribution of drug molecules in tissues. In particular, 2 H and 13 C is widely used because it is easy to label and detect.

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

[0255] Unless otherwise specified, the term "optical isomer" refers to isomers that have similar physical and chemical properties, the exact same order of atomic bonding within the molecule, but differ in optical rotation. Unless otherwise specified, the term "geometric isomer" (especially "cis-trans isomer") refers to isomers containing carbon-carbon or carbon-nitrogen double bonds in an E or Z configuration. The term "E" indicates that the higher-priority substituent is on the opposite side of the carbon-carbon or carbon-nitrogen double bond, and the term "Z" indicates that the higher-priority substituent is on the same side of the carbon-carbon or carbon-nitrogen double bond. The priority can be determined by the Kahn-Ingold-Prelogue rule. 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 can interconvert across a low-energy barrier. If 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 by proton transfer, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers include tautomers that interconvert by rearrangement of bonding electrons.

[0256] Unless otherwise specified, the structural formulas described in this invention encompass all isomeric forms (e.g., enantiomers, non-enantiomers, geometric isomers (e.g., conformational isomers), tautomers, etc.). Examples include the R,S configuration with an asymmetric center, the (Z), (E) isomers of a double bond, and the (Z), (E) conformational isomers. Therefore, all individual stereochemical isomers of the compounds of this invention, or mixtures thereof of their enantiomers, diastereomers, geometric isomers (e.g., conformational isomers), or tautomers, are within the scope of this invention.

[0257] Unless otherwise specified, the term “prodrug” refers to a drug that is converted into a parent drug in the body. Prodrugs are generally useful and can help improve certain undesirable physical or biological properties. Physical properties typically include the solubility (too high or insufficient lipid or water solubility) or stability of such drugs, while problematic biological properties include excessive metabolism or low bioavailability, which themselves may relate to physicochemical properties. For example, a prodrug may be orally bioavailable while the parent drug is not. Prodrugs may also have higher solubility in pharmaceutical compositions compared to their parent drugs. An example of a prodrug is one in which, if water solubility is detrimental to transport but beneficial once inside the cell, administering any compound of the present invention as an ester ("prodrug") promotes transport across the cell membrane, and once inside the cell, it is hydrolyzed to a carboxylic acid, which is the active substance. Another example of a prodrug is a short peptide (polyamino acid) that is activated by metabolism and has an acid group attached to it. [Effects of the Invention]

[0258] This invention provides an ATM kinase inhibitor having a novel structure, a method for producing the same, and its use in the pharmaceutical field. In particular, the compounds of this invention are useful for the treatment of cancer. Enzyme experiments have shown that the compounds of this invention have good selectivity for ATM target sites and can significantly inhibit ATM kinase activity. Furthermore, this invention employs a specific synthesis method that is simple and easy to operate, and advantageous for large-scale industrial production and application. [Modes for carrying out the invention]

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

[0260] Experimental methods in the following examples that do not specify detailed conditions are typically carried out under conventional conditions or manufacturer-recommended conditions. Furthermore, any methods or materials similar to or equivalent to those described can be applied to the methods of the present invention.

[0261] Unless otherwise specified, the technical terms and descriptions used in the following examples have meanings familiar to those skilled in the art. Abbreviations used in the manufacturing examples, examples, and elsewhere in the context have the following meanings. DCM Dichloromethane TEA (Triethylamine) DIEA / DIPEA N,N-diisopropylethylamine DMF (N,N-dimethylformamide) HCl 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] [Examples of intermediate production] (Example of intermediate preparation 1) Preparation of (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-1) [ka] (Step 1) Synthesis of 2-((4-bromo-3,5-difluorophenyl)amino)methylene)malonate diethyl 4-bromo-3,5-difluoroaniline (5.00 g, 24 mmol), 2-ethoxymethylene malonate diethyl (7.80 g, 36 mmol), and anhydrous ethanol (50 mL) were placed in a 250 mL flask. The reaction mixture was allowed to react under reflux for 8 hours. The completion of the reaction was confirmed by TLC, and the reaction mixture was cooled to 10°C to precipitate a white solid. The solid was collected by suction filtration, rinsed with N-hexane, and dried to obtain 2-((4-bromo-3,5-difluorophenyl)amino)methylene)malonate diethyl (7.3 g, yield 80.3%). 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. Then, 2-((4-bromo-3,5-difluorophenyl)amino)methylene)diethyl malonate (7.30 g, 19.3 mmol) was gradually added. The reaction mixture was allowed to react at 240 °C for 1 hour. The reaction was confirmed to be complete by TLC, and the reaction mixture was cooled to 25 °C to precipitate a crystalline solid. The mixture was diluted with ethyl ether (80 mL), the solid was collected by suction filtration, rinsed with ethyl ether, and dried to obtain 6-bromo-5,7-difluoro-4-hydroxyquinoline-3-carboxylate ethyl (5.50 g, yield 85.8%). 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 Thionyl chloride (20 mL) and ethyl 6-bromo-5,7-difluoro-4-hydroxyquinoline-3-carboxylate (1.40 g, 4.2 mmol) were added to a 100 mL flask. The reaction mixture was allowed to react at 80°C for 3 hours. 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 (S)-6-bromo-5,7-difluoro-4-((1-hydroxypropan-2-yl)amino)quinoline-3-carboxylate ethyl In a 100 mL flask, DMF (20 mL), 6-bromo-4-chloro-5,7-difluoroquinoline-3-carboxylate ethyl (1.48 g, 4.2 mmol), L-aminopropanol (0.47 g, 6.3 mmol), and DIEA (1.09 g, 8.4 mmol) were added sequentially, and the mixture was heated to 90 °C and reacted for 3 hours. The completion of the reaction was confirmed by TLC, and the reaction solution was cooled to room temperature. Water was added to precipitate the solid, which was recovered by suction filtration, rinsed with water, and dried to obtain (S)-6-bromo-5,7-difluoro-4-((1-hydroxypropan-2-yl)amino)quinoline-3-carboxylate ethyl (1.2 g, yield 73.4%). 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 In a 100 mL flask, THF (10 mL), (S)-6-bromo-5,7-difluoro-4-((1-hydroxypropan-2-yl)amino)quinoline-3-carboxylate ethyl (1.20 g, 3.08 mmol), water (5 mL), and sodium hydroxide (0.37 g, 9.24 mmol) were added sequentially, and the mixture was heated to 60 °C and reacted for 3 hours. The completion of the reaction was confirmed by TLC, and the reaction solution 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 obtain (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, yield 76.1%). 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]azulene-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 diphenyl phosphoryl azide (0.78 g, 2.82 mmol) were added sequentially to a 100 mL flask, and the mixture was heated to 60°C and reacted for 3 hours. The reaction was confirmed to be complete by TLC, the reaction mixture was cooled to room temperature, water was added, and the precipitated solid was collected by suction filtration. After rinsing with water and drying, (S)-7-bromo-6-fluoro-10-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.7g, yield 88.1%) was obtained. 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]azulene-1(2H)-one (M-1) In a 100 mL flask, DMF (15 mL) and (S)-7-bromo-6-fluoro-10-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.7 g, 2.07 mmol) were added sequentially. After cooling to 0°C, NaH (0.124 g, 3.11 mmol) was added, and the mixture was reacted at this temperature for 0.5 hours. Then, iodomethane (0.441 g, 3.11 mmol) was added, and the mixture was reacted overnight at room temperature. The reaction was confirmed to be complete by TLC, water was added to the reaction solution, and the precipitated solid was recovered by suction filtration. After rinsing with water and drying, (S)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.62 g, yield 85.1%) was obtained. 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] (Example of intermediate preparation 2) Preparation of (R)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-2) [ka] (R)-7-bromo-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 75.4% yield using the same synthesis method as in Production Example 1, except that D-aminopropanol was used instead of L-aminopropanol. ESI-MS (m / z): 352.20 / 354.19 [M+H] + .

[0270] (Example of intermediate preparation 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]azulene-1(2H)-one (M-3) [ka] 7-bromo-6-fluoro-9-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 82.4% yield using the same synthetic method as in Production Example 1, except that 2-amino-1-(4-fluorophenyl)ethanol was used instead of L-aminopropanol. ESI-MS(m / z):432.01 / 434.01 [M+H] + .

[0271] (Example of intermediate preparation 4) Preparation of 7-bromo-6-fluoro-2,10,10-trimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-4) [ka] Except for using 2-amino-2-methyl-propanol instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 7-bromo-6-fluoro-2,10,10-trimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one in 82.4% yield. ESI-MS(m / z):366.01 / 368.01 [M+H] + .

[0272] (Example of intermediate preparation 5) Preparation of 7-bromo-6-fluoro-2-methyl-9-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-5) [ka] 7-bromo-6-fluoro-2-methyl-9-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained using the same synthesis method as in Production Example 1, except that 2-amino-1-(pyridine-2-yl)ethanol was used instead of L-aminopropanol. ESI-MS (m / z): 415.01 / 417.01 [M+H] + .

[0273] (Example of intermediate preparation 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]azulene-1(2H)-one (M-6) [ka] (R)-7-bromo-6-fluoro-10-isobutyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 30.9% yield using the same synthesis method as in Production Example 1, except that D-leucinol was used instead of L-aminopropanol. ESI-MS (m / z): 394.05 / 396.05 [M+H] + .

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

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

[0276] (Example of intermediate preparation 9) Preparation of 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1-cyclopropane]-1-one (M-9) [ka] Except for using 1-aminocyclopropanemethanol instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 7-bromo-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1-cyclopropane]-1-one in 43.7% yield. ESI-MS (m / z): 364.01 / 366.01 [M+H] + .

[0277] (Example of intermediate preparation 10) Preparation of 7-bromo-9-(ethoxymethyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazantraquino[2,1,8-cde]azulene-1(2H)-one (M-10) [ka] Except for using 1-amino-3-ethoxy-2-propanol instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 7-bromo-9-(ethoxymethyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazantraquino[2,1,8-cde]azulene-1(2H)-one in 49.3% yield. ESI-MS(m / z):396.03 / 398.03 [M+H] + .

[0278] (Example of intermediate preparation 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]azulene-1(2H)-one (M-11) [ka] (S)-10-benzyl-7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxo-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 53.2% yield using the same synthesis method as in Production Example 1, except that (S)-2-amino-3-phenylpropan-1-ol was used instead of L-aminopropanol. ESI-MS (m / z): 428.03 / 430.03 [M+H] + .

[0279] (Example of intermediate preparation 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]azulene-1(2H)-one (M-12) [ka] (R)-10-benzyl-7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 32.6% yield using the same synthesis method as in Production Example 1, except that (R)-2-amino-3-phenylpropan-1-ol was used instead of L-aminopropanol. ESI-MS (m / z): 428.03 / 430.03 [M+H] + .

[0280] (Example of intermediate preparation 13) Preparation of 7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-13) [ka] Except for using 2-aminoethanol instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 7-bromo-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one in 40.7% yield. ESI-MS(m / z):337.99 / 339.99 [M+H] + .

[0281] (Example of intermediate preparation 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]azulene-1(2H)-one (M-14) [ka] (S)-7-bromo-6-fluoro-10-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 52.3% yield using the same synthesis method as in Production Example 1, except that L-valinol was used instead of L-aminopropanol. ESI-MS (m / z): 380.03 / 382.03 [M+H] + .

[0282] (Example of intermediate preparation 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]azulene-1(2H)-one (M-15) [ka] (R)-7-bromo-6-fluoro-10-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 59.3% yield using the same synthesis method as in Production Example 1, except that D-valinol was used instead of L-aminopropanol. ESI-MS (m / z): 380.03 / 382.03 [M+H] + .

[0283] (Example of intermediate preparation 16) Preparation of 7-bromo-6-fluoro-9-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-16) [ka] 7-bromo-6-fluoro-9-isopropyl-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 30.6% yield using the same synthesis method as in Production Example 1, except that 1-amino-3-methyl-butan-2-ol was used instead of L-aminopropanol. ESI-MS (m / z): 380.03 / 382.03 [M+H]+.

[0284] (Example of intermediate preparation 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]azulene-1(2H)-one (M-17) [ka] (S)-7-bromo-9-((dimethylamino)methyl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 75.5% yield using the same synthesis method as in Production Example 1, except that (R)-1-amino-3-(dimethylamino)propan-2-ol was used instead of L-aminopropanol. ESI-MS (m / z): 395.04 / 397.04 [M+H] + .

[0285] (Example of intermediate preparation 18) Preparation of (S)-7-bromo-6-fluoro-2-methyl-9-(piperidine-1-ylmethyl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-18) [ka] (S)-7-bromo-6-fluoro-2-methyl-9-(piperidine-1-yl)propan-2-ol was used instead of L-aminopropanol in the same synthetic method as in Production Example 1 to obtain (S)-7-bromo-6-fluoro-2-methyl-9-(piperidine-1-ylmethyl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one in 72.1% yield. ESI-MS (m / z): 435.08 / 437.08 [M+H] + .

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

[0287] (Example of intermediate preparation 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]azulene-1(2H)-one (M-20) [ka] (R)-7-bromo-10-ethyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 71.5% yield using the same synthesis method as in Production Example 1, except that (R)-2-amino-1-butanol was used instead of L-aminopropanol. ESI-MS (m / z): 366.02 / 368.02 [M+H] + .

[0288] (Example of intermediate preparation 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]azulene-1(2H)-one (M-21) [ka] (S)-7-bromo-10-ethyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 68.5% yield using the same synthesis method as in Production Example 1, except that (S)-2-amino-1-butanol was used instead of L-aminopropanol. ESI-MS (m / z): 366.02 / 368.02 [M+H] + .

[0289] (Example of intermediate preparation 22) Preparation of 7-bromo-6-fluoro-2,9-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-22) [ka] Except for using 1-amino-2-propanol instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 7-bromo-6-fluoro-2,9-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one in 82.4% yield. ESI-MS (m / z): 352.00 / 354.00 [M+H] + .

[0290] (Example of intermediate preparation 23) Preparation of 7-bromo-6-fluoro-9-(2-fluoropyridine-4-yl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-23) [ka] Except for using 2-amino-1-(2-fluoropyridine-4-yl)ethanol instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 7-bromo-6-fluoro-9-(2-fluoropyridine-4-yl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one in 32.5% yield. ESI-MS (m / z): 433.00 / 435.00 [M+H] + .

[0291] (Example of intermediate preparation 24) Preparation of 7-bromo-10-cyclopropyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-24) [ka] Except for using 2-amino-2-cyclopropylethanol instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 7-bromo-10-cyclopropyl-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one in 28.4% yield. ESI-MS(m / z):378.02 / 380.02 [M+H] + .

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

[0293] (Example of intermediate preparation 26) Preparation of (6aR,10aS)-5-bromo-4-fluoro-12-methyl-11-oxo-6a,7,10,10a,11,12-hexahydro-6-oxa-2,8,10b,12-tetraazacyclopentadiene-8(9H)-ethyl carboxylate (M-26) [ka] (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)-ethyl carboxylate was obtained in 37.5% yield using the same synthetic method as in Preparation Example 1, except that (3S,4R)-4-amino-3-hydroxylpiperidine-1-carboxylate ethyl was used instead of L-aminopropanol. ESI-MS (m / z): 464.93 / 466.95 [M+H] + .

[0294] (Example of intermediate preparation 27) Preparation of 7-bromo-6-fluoro-10-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-27) [ka] Except for using 2-amino-2-(4-fluorophenyl)ethanol instead of L-aminopropanol, the same synthesis method as in Production Example 1 was used to obtain 7-bromo-6-fluoro-10-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (100 mg, yield 32%). ESI-MS (m / z): 432.21 / 434.25 [M+H] + .

[0295] (Example of intermediate preparation 28) Preparation of 7-bromo-6-methoxy-2-methyl-10-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-28) [ka] (Step 1) Synthesis of 4-bromo-3-fluoro-5-methoxyaniline 4.90 g of 4-bromo-3-fluoro-5-methoxyaniline was obtained by sequentially adding 3-fluoro-5-methoxyaniline (4.1 g, 29.1 mmol) and DMF (50 mL) to a 250 mL flask, and then gradually adding NBS (5.2 g, 29.1 mmol) at room temperature for 1 hour. After cooling the reaction mixture, 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 = 10:1~2:1) 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 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene)malonate diethyl 4-bromo-3-fluoro-5-methoxyaniline (4.8 g, 21.8 mmol), 2-(ethoxymethylene) diethyl malonate (7.0 g, 32.4 mmol), and 50 mL of anhydrous ethanol were sequentially added to a 250 mL flask. The reaction mixture was heated under reflux and allowed to react for 6 hours, 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 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene) diethyl malonate. ESI-MS (m / z): 390.20 / 392.18 [M+H] + .

[0297] (Step 3) Synthesis of 6-bromo-5-fluoro-4-hydroxyl-7-methoxyquinoline-3-carboxylate ethyl 40 mL of diphenyl ether was placed in a 250 mL flask and heated to 240 °C. Diethyl 2-(((4-bromo-3-fluoro-5-methoxyphenyl)amino)methylene)malonate (5.9 g, 15.1 mmol) was added gradually, and the reaction was maintained 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 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 800 mg (2.32 mmol) of ethyl 6-bromo-5-fluoro-4-hydroxyl-7-methoxyquinoline-3-carboxylate and 10 mL of thionyl chloride were placed in a 100 mL flask. Two drops of DMF were added dropwise, and the mixture was refluxed for 4 hours. After the reaction was complete, the mixture was evaporated to dryness under reduced pressure to obtain 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 6-bromo-5-fluoro-4-((2-hydroxyl-1-(pyridine-2-yl)ethyl)amino)-7-methoxyquinoline-3-carboxylate ethyl In a 100 mL flask, 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-(pyridine-2-yl)ethanol (600 mg, 2.84 mmol) were added sequentially. The reaction mixture was heated to 90°C and allowed to react for 2 hours. The completion of the reaction was confirmed by TLC, and the reaction mixture was cooled to room temperature. Water was added, the mixture was filtered, and the cake was dried to obtain 1.1 g of ethyl 6-bromo-5-fluoro-4-((2-hydroxyl-1-(pyridine-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-(pyridine-2-yl)-3,4-dihydro-2H-[1,4]oxaza[5,6,7-de]quinoline-5-carboxylic acid In a 100 mL flask, ethyl 6-bromo-5-fluoro-4-((2-hydroxyl-1-(pyridine-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) were added. The reaction mixture was heated to 60°C and allowed to react for 8 hours. After the reaction was complete, 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-(pyridine-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-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one In a 100 mL flask, 10-bromo-9-methoxy-3-(pyridine-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 added sequentially. The reaction mixture was heated to 90°C and allowed to react for 2 hours. After confirming the completion of the reaction by TLC, the reaction mixture was cooled to room temperature, water was added to precipitate the solid, and the mixture was filtered to obtain 0.3 g of 7-bromo-6-methoxy-10-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-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-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one 7-bromo-6-methoxy-10-(pyridine-2-yl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (300 mg, 0.72 mmol), cesium carbonate (474 ​​mg, 1.45 mmol), and 10 mL of DMF were sequentially added to a flask. Iodomethane (155 mg, 1.10 mmol) was then added at room temperature, and the mixture was reacted at room temperature for 1.5 hours. The reaction was confirmed to be complete by TLC, the reaction mixture was cooled to room temperature, water was added to precipitate the solid, and the mixture was filtered to obtain 0.2 g of 7-bromo-6-methoxy-2-methyl-10-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one in 64.5% yield. ESI-MS (m / z): 427.03 / 429.03 [M+H] + .

[0303] (Example of intermediate preparation 29) Preparation of (S)-7-bromo-6-methoxy-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-29) [ka] (S)-7-bromo-6-methoxy-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 82.4% yield using the same synthetic method as in Preparation Example 1, except that 4-bromo-3,5-difluoroaniline was used instead of 4-bromo-3,5-difluoroaniline. ESI-MS (m / z): 364.02 / 366.02 [M+H] + .

[0304] (Example of intermediate preparation 30) Preparation of (R)-7-bromo-6-methoxy-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-30) [ka] (R)-7-bromo-6-methoxy-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 82.4% yield using the same synthetic method as in Preparation Example 1, except that 4-bromo-3,5-difluoroaniline was used instead of 4-bromo-3,5-difluoroaniline and (R)-2-amino-1-propanol was used instead of (S)-2-amino-1-propanol. ESI-MS (m / z): 364.02 / 366.02 [M+H] + .

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

[0306] (Step 2) Synthesis of 6-bromo-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylic acid In a 100 mL flask, ethyl 6-bromo-5-fluoro-4-((2-hydroxylphenyl)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 added, and the reaction mixture was heated to 60°C and allowed to react for 8 hours. After the reaction was complete, the THF was removed under reduced pressure, the pH was adjusted to 3 with 6N hydrochloric acid, and the mixture was filtered to obtain 0.86 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 In a 100 mL flask, 6-bromo-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylic acid (860 mg, 2.22 mmol), 10 mL of DMF, triethylamine (450 mg, 4.45 mmol), and DPPA (917 mg, 3.33 mmol) were added sequentially. The reaction mixture was heated to 90°C and allowed to react for 2 hours. After confirming the completion of the reaction by TLC, the reaction mixture was cooled to room temperature, water was added to precipitate the solid, and the mixture was filtered to obtain 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]preiaden-11(12H)-one 840 mg, 2.19 mmol of 5-bromo-4-methoxy-6-oxa-2,10b,12-triazacyclopentadiene [gh]preiaden-11(12H)-one, 1420 mg, 4.36 mmol of cesium carbonate, and 10 mL of DMF were sequentially added to a flask. Iodomethane (466 mg, 3.28 mmol) was added dropwise at room temperature, and the mixture was allowed to react at room temperature for 1.5 hours after the addition was complete. After confirming the completion of the reaction by TLC, water was added to the reaction mixture to precipitate the solid, and the mixture was filtered to obtain 0.76 g of 5-bromo-4-methoxy-12-methyl-6-oxa-2,10b,12-triazacyclopentadiene [gh]preiaden-11(12H)-one in 87.3% yield. ESI-MS (m / z): 398.01 / 400.01 [M+H] + .

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

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

[0311] (Example of intermediate preparation 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]azulene-10(11H)-one (M-34) [ka] (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]azulene-10(11H)-one was obtained in 82.4% yield using the same synthetic method as in Preparation Example 1, except that (3R,4S)-4-aminotetrahydrofuran-3-ol was used instead of L-aminopropanol. ESI-MS (m / z): 380.00 / 382.00 [M+H] + .

[0312] (Example of intermediate preparation 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] Except for using 3-amino-3-hydroxymethyloxetane instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 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 in 32.1% yield. ESI-MS (m / z): 380.00 / 381.99 [M+H] + .

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

[0314] (Example of intermediate preparation 37) Preparation of 7-bromo-6-fluoro-10-(hydroxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-37) [ka] Except for using 2-amino-1,3-propanediol instead of L-aminopropanol, the same synthetic method as in Production Example 1 was used to obtain 7-bromo-6-fluoro-10-(hydroxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one in 74.2% yield. ESI-MS(m / z):367.96 / 370.02 [M+H] + .

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

[0316] (Example of intermediate preparation 39) Preparation of 7-bromo-6-methoxy-2-methyl-9-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (M-39) [ka] 7-bromo-6-methoxy-2-methyl-9-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 63.8% yield using the same synthetic method as in Production Example 28, except that 2-amino-2-(pyridine-2-yl)ethanol was used instead of 2-amino-2-(pyridine-2-yl)ethanol. ESI-MS (m / z): 427.03 / 429.03 [M+H] + .

[0317] (Example of intermediate preparation 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]azulene-1(2H)-one (M-40) [ka] (R)-7-bromo-6-methoxy-2-methyl-10-phenyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one was obtained in 67.2% yield using the same synthetic method as in Production Example 28, except that (R)-2-amino-2-phenylethanol was used instead of 2-amino-2-(pyridine-2-yl)ethanol. ESI-MS (m / z): 426.04 / 428.04 [M+H] + .

[0318] (Example of intermediate preparation 41) Preparation of 5-fluoro-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-41) [ka] 4-chloro-5,7-difluoroquinoline-3-carboxylate ethyl (0.20 mmol), o-aminophenol (0.24 mmol), DIPEA (0.4 mmol), and DMF (20 mL) were sequentially added to a 100 mL round-bottom flask, and the reaction system was stirred at 90 °C for 2.0 hours. After confirming the disappearance of the starting materials by TLC, heating was stopped, and the mixture was 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 5-fluoro-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 325.1732.

[0319] (Example of intermediate preparation 42) Preparation of 5-fluoro-12H-benzo[2,3][1,4]thiadino[5,6,7-de]quinoline-1-carboxylate ethyl (M-42) [ka] Using the same synthesis method as in Production Example 41, 5-fluoro-12H-benzo[2,3][1,4]thiadino[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 341.0959.

[0320] (Example of intermediate preparation 43) Preparation of 5-fluoro-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-43) [ka] Using the same synthesis method as in Production Example 41, 5-fluoro-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 324.1173.

[0321] (Example of intermediate preparation 44) Preparation of 5,9-difluoro-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-44) [ka] Using the same synthesis method as in Production Example 41, 5,9-difluoro-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl was obtained in 80.3% yield. 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, measured value 343.2011.

[0322] (Example of intermediate preparation 45) Preparation of 5-fluoro-10-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-45) [ka] Using the same synthesis method as in Production Example 41, 5-fluoro-10-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 355.0980.

[0323] (Example of intermediate preparation 46) Preparation of 5-fluoro-12H-pyrido[3',4':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-46) [ka] Using the same synthesis method as in Production Example 41, 5-fluoro-12H-pyrido[3',4':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 326.0830.

[0324] (Example of intermediate preparation 47) Preparation of 5-fluoro-12H-pyrido[4',3':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-47) [ka] Using the same synthesis method as in Production Example 41, 5-fluoro-12H-pyrido[4',3':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl was obtained in 94.5% yield. 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, measured value 326.1440.

[0325] (Example of intermediate preparation 48) Preparation of 5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-48) [ka] (Step 1) Synthesis of 2-(((3-fluoro-5-methoxyphenyl)amino)methylene)malonate diethyl 3-fluoro-5-methoxyaniline (1.41 g, 0.01 mol), 2-(ethoxymethylene) diethyl malonate (2.16 g, 0.01 mol), and 25 mL of anhydrous ethanol were sequentially added to a 100 mL flask. The reaction mixture was heated under reflux and allowed to react for 6 hours, then cooled to room temperature. By removing the solvent using a rotary evaporator, 2.76 g of 2-(((3-fluoro-5-methoxyphenyl)amino)methylene) diethyl malonate was obtained as a colorless, transparent liquid in 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 40 mL of diphenyl ether was placed in a 100 mL flask and heated to 240 °C. Diethyl 2-(((3-fluoro-5-methoxyphenyl)amino)methylene)malonate (3.11 g, 0.01 mol) was added, and the reaction was maintained 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 84.4% yield. HR-MS (ESI) theoretical value: C 13 H 12 FNO4[M+H] + 266.1326, measured 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 1.30 g, 4.90 mmol of ethyl 5-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate and 10 mL of thionyl chloride were added to a 50 mL flask. Two drops of DMF were added dropwise, and the mixture was refluxed for 4 hours. After the reaction was complete, the mixture was evaporated to dryness under reduced pressure to obtain 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, measured 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 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 ethyl (0.20 mmol), o-aminophenol (0.24 mmol), DIPEA (0.4 mmol), and DMF (20 mL) were sequentially added to a 100 mL round-bottom flask, and the reaction system was stirred at 90 °C for 2.0 hours. After confirming the disappearance of the starting materials by TLC, heating was stopped, and the mixture was 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 5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl 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] (Example of intermediate preparation 49) Preparation of 5-methoxy-12H-benzo[2,3][1,4]thiadino[5,6,7-de]quinoline-1-carboxylate ethyl (M-49) [ka] Using the same synthesis method as in Production Example 48, 5-methoxy-12H-benzo[2,3][1,4]thiadino[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 353.1284.

[0330] (Example of intermediate preparation 50) Preparation of 5-methoxy-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-50) [ka] Using the same synthetic method as in Production Example 48, 5-methoxy-7,12-dihydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 336.0513.

[0331] (Example of intermediate preparation 51) Preparation of 9-fluoro-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-51) [ka] Using the same synthesis method as in Production Example 48, 9-fluoro-5-methoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 355.1338.

[0332] (Example of intermediate preparation 52) Preparation of 5,10-dimethoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-52) [ka] Using the same synthesis method as in Production Example 48, 5,10-dimethoxy-12H-benzo[2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 367.1535.

[0333] (Example of intermediate preparation 53) Preparation of 5-methoxy-12H-pyrido[4',3':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-53) [ka] Using the same synthetic method as in Production Example 48, 5-methoxy-12H-pyrido[4',3':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl was obtained in 81.2% yield. 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, measured value 338.1382.

[0334] (Example of intermediate preparation 54) Preparation of 5-methoxy-12H-pyrido[3',4':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-54) [ka] Using the same synthetic method as in Production Example 48, 5-methoxy-12H-pyrido[3',4':2,3][1,4]oxaza[5,6,7-de]quinoline-1-carboxylate ethyl was obtained in 89.4% yield. 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, measured value 338.1440.

[0335] (Example of intermediate preparation 55) Preparation of 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-55) [ka] Using the same synthesis method as in Production Example 41, 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl 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, measured value 330.1238.

[0336] (Example of intermediate preparation 56) Preparation of 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-56) [ka] Using the same synthesis method as in Production Example 41, 5-fluoro-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl was obtained in 96.4% yield. 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, measured value 276.0973.

[0337] (Example of intermediate preparation 57) Preparation of 5-methoxy-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl (M-57) [ka] Using the same synthetic method as in Production Example 48, 5-methoxy-7,7a,8,9,10,11,11a,12-octahydrobenzo[2,3][1,4]diaza[5,6,7-de]quinoline-1-carboxylate ethyl was obtained in 95.4% yield. 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, measured value 342.2011.

[0338] (Example of intermediate preparation 58) Preparation of 9-methoxy-4,5,6,7-tetrahydro-[1,4]diaza[5,6,7-de]quinoline-3-carboxylate ethyl (M-58) [ka] Using the same synthetic method as in Production Example 48, 9-methoxy-4,5,6,7-tetrahydro-[1,4]diaza[5,6,7-de]quinoline-3-carboxylate ethyl was obtained in 97.1% yield. 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, measured value 276.0878. [Examples]

[0339] (Example 1) (S)-6-fluoro-2,10-dimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-1) [ka] (Step 1) Synthesis of (S)-6-fluoro-7-(6-fluoropyridine-3-yl)-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one 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]azulene-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) were sequentially added to a 100 mL flask. The mixture was heated to 90°C under a nitrogen atmosphere and reacted for 2.5 hours. The reaction was confirmed to be complete by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=60:1) to obtain (S)-6-fluoro-7-(6-fluoropyridine-3-yl)-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.43g, yield 66.3%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one In a 100 mL flask, THF (4 mL) and 1-piperidinepropanol (115 mg, 0.8 mmol) were added sequentially, and after cooling to 0°C, NaH (56 mg, 1.4 mmol) was added, and the reaction was carried out at this temperature for 0.5 hours. Then, (S)-6-fluoro-7-(6-fluoropyridine-3-yl)-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (147 mg, 0.4 mmol) was added, and the reaction was carried out overnight at room temperature. After confirming the completion of the reaction by TLC, water was added to the reaction mixture to stop the reaction, and the mixture was concentrated to dryness. The residue was then purified by column chromatography (DCM:MeOH=20:1~15:1) to obtain (S)-6-fluoro-2,10-dimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (63 mg, yield 32%). 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)pyridine-3-yl)-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-2) [ka] (S)-7-(6-(3-(dimethylamino)propoxy)pyridine-3-yl)-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (30 mg, yield 32.0%) was obtained using the same synthesis method as in Example 1, except that 3-dimethylaminopropanol was used instead of 1-piperidinepropanol. 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)pyridine-3-yl)-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-3) [ka] (R)-7-(6-(3-(dimethylamino)propoxy)pyridine-3-yl)-6-fluoro-2,10-dimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (25 mg, yield 27.1%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-4) [ka] (R)-6-fluoro-2,10-dimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (63 mg, yield 32%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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)pyridine-3-yl)-6-fluoro-9-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-5) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 7-(6-(3-(dimethylamino)propoxy)pyridine-3-yl)-6-fluoro-9-(4-fluorophenyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (15 mg, yield 13.0%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-6) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-2,10,10-trimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (70 mg, yield 33.2%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-7) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-2,10-dimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (63 mg, yield 32.0%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-8) [ka] (R)-6-fluoro-10-isobutyl-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (53 mg, yield 45.3%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-9) [ka] (S)-6-fluoro-10-isobutyl-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (60 mg, yield 46.0%) was obtained using the same synthesis method as in Example 1, except for a change in the starting materials. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-10) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (90 mg, yield 45.2%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1-cyclopropane]-1-one (A-11) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1-cyclopropane]-1-one (50 mg, yield 21.2%). ESI-MS (m / z): 504.23 [M+H] + ; 1 H-NMR (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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-12) [ka] (9-(ethoxymethyl)-6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (86 mg, yield 51.0%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-13) [ka] (S)-10-benzyl-6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (30 mg, yield 20.2%) was obtained using the same synthesis method as in Example 1, except for a change in the starting materials. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-14) [ka] (R)-10-benzyl-6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (53 mg, yield 41.5%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-dimethylaminopropoxy)-pyridine-3yl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-15) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 7-(6-(3-dimethylamino-propoxy)-pyridine-3yl)-6-fluoro-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (15 mg, yield 48.2%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-16) [ka] (S)-6-fluoro-10-isopropyl-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (50 mg, yield 24%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-17) [ka] (R)-6-fluoro-10-isopropyl-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (45 mg, yield 24%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-18) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to synthesize 6-fluoro-9-isopropyl-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-19) [ka] (S)-9-((dimethylamino)methyl)-6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (100 mg, yield 55.0%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9-(piperidine-1-ylmethyl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-20) [ka] (S)-6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9-(piperidine-1-ylmethyl)-9,10-dihydro-8-oxa2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (150 mg, yield 29.6%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-6a,7,8,9,10,10a-Hexahydro-6-oxa-2,10b,12-Triazacyclopentadiene[GH]preiaden-11(12H)-one(A-21) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 4-fluoro-12-methyl-5-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]preiaden-11(12H)-one (200 mg, yield 38.5%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-22) [ka] (R)-10-ethyl-6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (150 mg, yield 14.3%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-23) [ka] (S)-10-ethyl-6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (180 mg, yield 42.6%) was obtained using the same synthesis method as in Example 1, except for a change in the starting materials. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-24) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-2,9-dimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (68 mg, yield 33.2%). 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-fluoropyridine-4-yl)-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-25) [ka] 6-Fluoro-9-(2-fluoropyridine-4-yl)-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (85 mg, yield 26.8%) was synthesized using the same synthesis method as in Example 1, except for a change in the starting materials. ESI-MS(m / z):573.23 [M+H] + ; 1 1H 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-26) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (25 mg, yield 19%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-27) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 10-cyclopropyl-6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (40 mg, yield 39.0%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclobutan]-1-one (A-28) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclobutan]-1-one (70 mg, yield 44.2%). 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)pyridine-3-yl)-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclopropane]-1-one (A-29) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 7-(6-(3-(dimethylamino)propoxy)pyridine-3-yl)-6-fluoro-2-methyl-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclopropane]-1-one (47 mg, yield 39.1%). 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-pyrazole-4-yl)-10-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-30) [ka] 7-bromo-6-methoxy-2-methyl-10-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (200 mg, 0.47 mmol), cesium carbonate (382 mg, 1.17 mmol), (1-methyl-1H-pyrazole-4-yl)boronic acid (90 mg, 0.71 mmol), tetrakis(triphenylphosphine)palladium (55 mg, 0.05 mmol), and 20 mL of dioxane were sequentially added to a 100 mL flask. The reaction mixture was heated to 120 °C and allowed to react for 4 hours under an N2 atmosphere. The reaction mixture was cooled to room temperature, concentrated to dryness, and purified by column chromatography (DCM:MeOH = 40:1 to 30:1) to obtain 6-methoxy-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-10-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (80 mg, yield 40.1%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-31) [ka] (S)-6-methoxy-2,10-dimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (68 mg, yield 33.2%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-32) [ka] (R)-6-methoxy-2,10-dimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (68 mg, yield 33.2%) was obtained using the same synthesis method as in Example 1, except for a change in the starting material. 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-pyrazole-4-yl)-6-oxa-2,10b,12-triazacyclopentadiene[gh]preiaden-11(12H)-one(A-33) [ka] Except for a change in the starting materials, the same synthesis method as in Example 30 was used to obtain 4-methoxy-12-methyl-5-(1-methyl-1H-pyrazole-4-yl)-6-oxa-2,10b,12-triazacyclopentadiene[gh]preiaden-11(12H)-one (120 mg, yield 31.5%). 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-pyrazole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-34) [ka] (S)-9-(dimethylamino)methyl)-6-fluoro-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (60 mg, yield 50%) was obtained using the same synthesis method as in Example 30, except for a change in the starting material. 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-pyrazole-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-35) [ka] Except for a change in the starting materials, the same synthesis method as in Example 30 was used to obtain 6-fluoro-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.15 g, yield 50%). 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-pyrazole-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one 8-oxide(A-36) [ka] 6-Fluoro-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.05 g, 0.14 mmol) was dissolved in 20 mL of dichloromethane, and m-chloroperbenzoic acid (0.03 g, 0.17 mmol) was added under ice bath conditions. The system was stirred under ice bath conditions for 1 hour. TLC confirmed that a small amount of the starting material remained. The reaction mixture was washed with saturated sodium thiosulfate aqueous solution (10 mL x 2), then with saturated sodium chloride (10 mL x 2), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Separation and purification were performed by column chromatography (DCM:MeOH = 50:1~25:1) to obtain the final product, 6-fluoro-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one 8-oxide (0.04 g, yield 77%). 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-pyrazole-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one 8,8-dioxide (A-37) [ka] 6-Fluoro-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.05 g, 0.14 mmol) was dissolved in 20 mL of dichloromethane, and m-chloroperbenzoic acid (0.05 g, 0.28 mmol) was added under ice bath conditions. The system was stirred at room temperature for 24 hours. The disappearance of the starting material was confirmed by TLC. The reaction mixture was washed with saturated sodium thiosulfate aqueous solution (10 mL x 2), then with saturated sodium chloride (10 mL x 2), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Separation and purification were performed by column chromatography (DCM:MeOH = 50:1~30:1) to obtain 6-fluoro-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9,10-dihydro-8-thia-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one 8,8-dioxide (0.015 g, yield 27.3%). 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-pyrazole-4-yl)-11-oxo-6a,7,10,10a,11,12-hexahydro-6-oxa-2,8,10b,12-tetraazacyclopentadiene-8(9H)-ethylcarboxylate (A-38) [ka] Except for a change in the starting materials, the same synthesis method as in Example 30 was used to obtain (6aR,10aS)-4-fluoro-12-methyl-5-(1-methyl-1H-pyrazole-4-yl)-11-oxo-6a,7,10,10a,11,12-hexahydro-6-oxa-2,8,10b,12-tetraazacyclopentadiene-8(9H)-ethyl carboxylate (0.10 g, yield 59%). ESI-MS (m / z): 467.2 [M+H] + .

[0378] (Example 39) 6-Fluoro-10-(4-fluorophenyl)-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-39) [ka] Except for a change in the starting materials, the same synthesis method as in Example 30 was used to obtain 6-fluoro-10-(4-fluorophenyl)-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.05 g, yield 50%). 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-pyrazole-4-yl)-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]preiaden-11(12H)-one(A-40) [ka] Except for a change in the starting material, the same synthesis method as in Example 30 was used to obtain 4-methoxy-12-methyl-5-(1-methyl-1H-pyrazole-4-yl)-6-oxa-2,9,10b,12-tetraazacyclopenta[gh]preiaden-11(12H)-one (12 mg, yield 30%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulene-10(11H)-one(A-41) [ka] (6aS,9aR)-4-fluoro-11-methyl-5-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulene-10(11H)-one (40 mg, 33.6%) was obtained using the same synthesis method as in Example 1, except for a change in the starting materials. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulene-10(11H)-one(A-42) [ka] (6aR,9aS)-4-fluoro-11-methyl-5-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-6a,7,9,9a-tetrahydro-6,8-dioxa-2,9b,11-triazacyclopentadiene[h]naphtho[2,1,8-cde]azulene-10(11H)-one was obtained using the same synthesis method as in Example 1, except for a change in the starting materials. 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,3'-oxetane]-1-one (A-43) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,3'-oxetane]-1-one (74 mg, yield 40.4%). 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-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-44) [ka] Except for a change in the starting materials, the same synthesis method as in Example 30 was used to obtain 6-methoxy-10-hydroxymethyl-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (180 mg, yield 90.2%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-45) [ka] DMF (10 mL) and methanol (8 mg, 0.24 mmol) were sequentially added to a 100 mL flask, cooled to 0°C, and then NaH (60%, 15 mg, 0.36 mmol) was added. The reaction was carried out at this temperature for 0.5 hours. Furthermore, 6-fluoro-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (60 mg, 0.12 mmol) was added, and the reaction was carried out at 65°C for 24 hours. After confirming the completion of the reaction by TLC, water was added to the reaction mixture to stop the reaction, and the mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1~15:1) to obtain 6-methoxy-2,10,10-trimethyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (36 mg, yield 58.2%). 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)pyridine-3-yl)-6-fluoro-2,10,10-trimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-46) [ka] Except for using 3-dimethylaminopropanol instead of 1-piperidinepropanol, the same synthetic method as in Example 1 was used to obtain 7-(6-(3-(dimethylamino)propoxy)pyridine-3-yl)-6-fluoro-2,10,10-trimethyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (40 mg, yield 41.5%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclopropane]-1-one (A-47) [ka] Except for a change in the starting materials, the same synthesis method as in Example 45 was used to obtain 6-methoxy-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-2,9-dihydro-1H-spiro[8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-10,1'-cyclopropane]-1-one (25 mg, yield 49.2%). ESI-MS(m / z):504.22 [M+H] + ; 1 H-NMR (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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-48) [ka] Except for a change in the starting materials, the same synthesis method as in Example 1 was used to obtain 6-fluoro-10-(hydroxymethyl)-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxy-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.10 g, yield 48.3%). 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-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-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]azulene-1(2H)-one In a 100 mL flask, 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]azulene-1(2H)-one (0.10 g, 0.27 mmol) were added sequentially. After cooling to 0°C, NaH (0.03 g, 0.82 mmol) was added, and the reaction was carried out at this temperature for 0.5 hours. Furthermore, iodomethane (0.08 g, 0.54 mmol) was added, and the reaction was carried out at room temperature for 5 hours. After confirming the completion of the reaction by TLC, water was added to the reaction mixture to stop the reaction, and the mixture was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 50:1 to 25:1) to obtain 7-bromo-6-fluoro-10-(methoxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (30 mg, yield 29.4%). ESI-M(m / z):381.95 [M+H] + .

[0389] (Step 2) Synthesis of 6-fluoro-10-(methoxymethyl)-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one 1,4-Dioxane (15 mL), 7-Bromo-6-Fluoro-10-(methoxymethyl)-2-methyl-9,10-dihydro-8-oxa-2,4,10a-Triazanafto[2,1,8-cde]azulene-1(2H)-one (0.03 g, 0.08 mmol), (6-(3-(piperidine-1-yl)propoxy)pyridine-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) were sequentially added to a 100 mL flask. The mixture was heated to 90 °C under a nitrogen atmosphere and reacted for 2.5 hours. The reaction was confirmed to be complete by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH = 50:1~10:1) to obtain 6-fluoro-10-(methoxymethyl)-2-methyl-7-(6-(3-(piperidine-1-yl)propoxy)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (0.16 g, yield 39.2%). 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-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-50) [ka] In a 50 mL flask, anhydrous tetrahydrofuran (10 mL) and 10-hydroxymethyl-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (50 mg, 0.13 mmol) were added sequentially. Sodium hydride (25 mg, 0.65 mmol) was added under an ice bath, and the mixture was stirred under an ice bath for 30 minutes. Then, iodomethane (22 mg, 0.15 mmol) was added. The mixture was allowed to react at room temperature for 2 hours under a nitrogen atmosphere. The reaction was confirmed to be complete by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=30:1) to obtain 6-methoxy-10-methoxymethyl-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (20 mg, yield 40.4%). 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-pyrrole-4-yl)-10-methylene-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-51) [ka] In a 50 mL flask, anhydrous tetrahydrofuran (2 mL) and 10-hydroxymethyl-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (20 mg, 0.05 mmol) were added sequentially, followed by the addition of DMF (1 mL), sodium hydride (25 mg, 0.65 mmol) under an ice bath, and after stirring under an ice bath for 30 minutes, p-toluenesulfonyl chloride (15 mg, 0.08 mmol) was added. The mixture was allowed to react at room temperature for 2 hours under a nitrogen atmosphere. The reaction was confirmed to be complete by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=30:1) to obtain 6-methoxy-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-10-methylene-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (10 mg, yield 48.2%). 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-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-52) [ka] (Step 1) Synthesis of 10-(aminomethyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one In a 50 mL flask, add anhydrous N,N-dimethylformamide (2 mL), 6-methoxy-10-hydroxymethyl-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (50 mg, 0.13 mmol), triphenylphosphine (138 mg, 0.524 mmol), and phthalamide (29 mg, 0.19 mmol) in sequence under a nitrogen atmosphere. Diisopropyl azodicarboxylate (106 mg, 0.524 mmol) was added and the reaction was carried out at room temperature for 2 hours under a nitrogen atmosphere. After confirming the completion of the reaction by TLC, 50 mL of water was added to the reaction solution, and extraction with 30 mL of dichloromethane was performed four times. The organic phases were combined, dried over anhydrous sodium sulfate, and the concentrated dry solution was used directly in the next step. Methanol (15 mL) and hydrazine hydrate (2 mL) were added and the reaction was carried out at room temperature for 2 hours under a nitrogen atmosphere, and the completion of the reaction was confirmed by TLC. 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 obtain 10-(aminomethyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (29 mg, yield 58.1%). ESI-MS (m / z): 381.16 [M+H] + .

[0393] (Step 2) Synthesis of 10-((dimethylamino)methyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one In a 50 mL flask, anhydrous methanol (6 mL) and 10-(aminomethyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (29 mg, 0.08 mmol) were added sequentially. Then, aqueous formaldehyde (2 mL) and acetic acid (10 μL) were added, and the mixture was stirred at room temperature for 30 minutes. After that, sodium triacetoxyborohydride (49 mg, 0.23 mmol) was added. The mixture was allowed to react at room temperature for 12 hours. The reaction was confirmed to be complete by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=15:1) to obtain 10-((dimethylamino)methyl)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrrole-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (7 mg, yield 27.3%). 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-pyrazole-4-yl)-6-oxa-2,10b,12-triaz[gh]preiaden-11(12H)-one (A-53) [ka] Except for a change in the starting materials, the same synthesis method as in Example 30 was used to obtain 8-fluoro-4-methoxy-12-methyl-5-(1-methyl-1H-pyrazole-4-yl)-6-oxa-2,10b,12-triaz[gh]preiaden-11(12H)-one (200 mg, yield 66.6%). 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-pyrazole-4-yl)-9-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-54) [ka] Except for a change in the starting materials, the same synthesis method as in Example 30 was used to obtain 6-methoxy-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-9-(pyridine-2-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (230 mg, yield 63.9%). 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-pyrazole-4-yl)-10-phenyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (A-55) [ka] (R)-6-methoxy-2-methyl-7-(1-methyl-1H-pyrazole-4-yl)-10-phenyl-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (130 mg, yield 43.3%) was obtained using the same synthesis method as in Example 30, except for a change in the starting materials. 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-(piperidine-1-yl)buta-1-in-1-yl)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-56) [ka] (Step 1) Synthesis of (6-(4-(piperidine-1-yl)buta-1-in-1-yl)pyridine-3-yl)boronic acid In a 50 mL flask, acetonitrile (20 mL), 1-(buta-3-in-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) were sequentially added and reacted at room temperature for 6 hours under a nitrogen atmosphere. 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=30:1) to obtain (6-(4-(piperidine-1-yl)buta-1-in-1-yl)pyridine-3-yl)boronic acid (1.26 g, yield 61.1%). ESI-MS (m / z): 259.15 [M+H] + .

[0398] (Step 2) Synthesis of (S)-6-fluoro-2,10-dimethyl-7-(6-(4-(piperidine-1-yl)buta-1-in-1-yl)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one 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]azulene-1(2H)-one (170 mg, 0.48 mmol), (6-(4-(piperidine-1-yl)buta-1-in-1-yl)pyridine-3-yl)boronic acid, potassium carbonate (132 mg, 0.96 mmol), water (1 mL), and tetrakis(triphenylphosphine)palladium (55 mg, 0.048 mmol) were sequentially added to a 50 mL flask and heated to 90 °C under a nitrogen atmosphere for 3 hours. The reaction was confirmed to be complete by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH = 20:1 to 10:1) to obtain (S)-6-fluoro-2,10-dimethyl-7-(6-(4-(piperidine-1-yl)buta-1-in-1-yl)pyridine-3-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one (35 mg, yield 15%). 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)piperidine-1-yl)pyridine-3-yl)-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]preiaden-11(12H)-one(A-57) [ka] (Step 1) Synthesis of 4-fluoro-5-(6-fluoropyridine-3-yl)-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]azulene-11(12H)-one 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]preiaden-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 added to a 100 mL flask and heated to 90 °C under a nitrogen atmosphere for 2.5 hours. The reaction was confirmed to be complete by TLC, the reaction mixture was concentrated to dryness, and the residue was purified by column chromatography (DCM:MeOH=60:1) to obtain 4-fluoro-5-(6-fluoropyridine-3-yl)-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]azulene-11(12H)-one (0.35 g, yield 48.7%). ESI-MS (m / z): 409.31 [M+H] + .

[0400] (Step 2) Synthesis of 5-(6-(4-(dimethylamino)piperidine-1-yl)pyridine-3-yl)-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]preiaden-11(12H)-one (A-57) In a 100 mL flask, 10 mL of DMSO, 3 mL of DIPEA, 4-fluoro-5-(6-fluoropyridine-3-yl)-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]azulene-11(12H)-one (170 mg, 0.417 mmol), and N,N-dimethylpiperidine-4-amine hydrochloride (167 mg, 0.834 mmol) were added sequentially, and the mixture was heated to 150 °C and reacted for 12 hours. The reaction mixture was cooled to room temperature, washed 2-3 times with ethyl acetate and saturated brine, and the organic phase was dried and concentrated to obtain the crude product. The crude product was purified by column chromatography (DCM:MeOH = 30:1 to 6:1) to obtain 5-(6-(4-(dimethylamino)piperidine-1-yl)pyridine-3-yl)-4-fluoro-12-methyl-6a,7,8,9,10,10a-hexahydro-6-oxa-2,10b,12-triazacyclopentadiene[gh]preiaden-11(12H)-one (30 mg, yield 13.9%). 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-piperidine-1-yl)propyl)-1,2-dihydropyridine-4-yl)-9,10-dihydro-8-oxa-2,4,10a-triazanaphtho[2,1,8-cde]azulene-1(2H)-one(A-146) [ka] (Step 1) Synthesis of 4-bromo-1-(3-(piperidine-1-yl)propyl)pyridine-2(1H)-one In a 100 mL flask, 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) were added sequentially, and the mixture was refluxed for 5 hours. After confirming the completion of the reaction by TLC, the reaction mixture was filtered by suction, and the filtrate was concentrated to dryness. The residue was purified by column chromatography (DCM:MeOH = 20:1~15:1) t...

Claims

1. Formula (I') having the following structure: 【Chemistry 1】 (In the formula, Y is, 【Chemistry 2】 And, X １ It is selected from the group consisting of bonds, hydrogen, and halogens. X １ If R is hydrogen or halogen, １ , X ２ , R ２ and R ３ It does not exist. R １ The following 【Transformation 3】 (wherein, “*” indicates that one end is bonded to X １ and the other end is bonded to X ２ ). X ２ is absent, or the bond, hydrogen, halogen, -O-, -NH- and -N(CH) ３ Selected from the group consisting of ) X ２ If R is hydrogen or halogen, ２ and R ３ It does not exist. R ２ This is selected from the group consisting of methyl group, ethyl group, propyl group, butyl group, ethynyl group, piperidinyl group, tetrahydropyrrolyl group and tetrahydropyranyl group. R ３ The following may be replaced as desired: 【Chemistry 4】 Selected from the group consisting of groups, where "may be substituted as desired" means that the hydrogen in the substituent is unsubstituted, or that the hydrogens at one or more substituted positions of the substituent are independently R ３ｄ This means that it is replaced by R ３ｄ If present, independently include deuterium, halogen, hydroxyl group, amino group, 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, R ４ It is selected from the group consisting of hydrogen, fluorine, and methoxy groups. h is 1, R ５ It is a methyl group, L is CH, A is, 【Transformation 5】 And here, 【Transformation 6】 represents a single bond or a double bond, t １ ,t ２ ,t ３ ,t ４ ,t ５ and t ６ These are independently 0 or 1, n １ and n ２ It is independently 0 or 1 and simultaneously not 0. W is selected from the group consisting of O, N, and S, Q １ is C and Q ２ is C, Q ３ is C, and here Q １ It is combined with W, Q ３ If one of the bonds is a double bond, R １０ or R １１ It does not exist. R ６ and R ７ Each of them, when present, is hydrogen. R ８ , R ９ , R １０ , R １１ , R １２ and R １３ If present, each independently comprises hydrogen, deuterium, halogen, hydroxyl group, amino group, and -R. ６ａ Selected from the group consisting of R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ and R １３ Of these, any two substituents bonded to the same atom are either =O, =NH, or =CH ２ To form, or Q １ Q ２ and Q ３ Any two adjacent atoms among them, along with the substituents to which they are bonded, can optionally be R ６ｃ C may be replaced by ３－１０ Carbon ring group, 3-10 membered heterocyclic group, C ６－１４ It forms an aryl group or a 5- to 12-membered heteroaryl group, or Q １ Q ２ and Q ３ Any one of these atoms, together with the substituent to which they are bonded, optionally forms R ６ｃ C may be replaced by ３－１０ Forming a carbon ring group or a 3- to 10-membered heterocyclic group, R ６ａ It independently contains hydrogen, deuterium, and, if desired, R ６ｃ C may be replaced by １－６ alkyl group, C １－６ Alkoxy group, C ３－１０ Carbon ring group, 3-10 membered heterocyclic group, C ６－１４ Selected from the group consisting of aryl groups and 5- to 12-membered heteroaryl groups, R ６ｃ is independently selected from the group consisting of hydrogen, fluorine, chlorine, hydroxyl group, 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 aryl group and 5- to 10-membered heteroaryl group, If heterocycloalkyl groups, heteroaryl groups, and / or heterocyclic groups are present, the heteroatoms are independently selected from the group consisting of O, N, and S, and the number of heteroatoms is 1, 2, 3, or 4. A compound represented by or its tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts.

2. The aforementioned compound is given by formula (I-a) 【Transformation 7】 (Each substituent is defined as in Claim 1.) The compound has a structure represented by formula (I-b) or (I-c) 【Transformation 8】 (Each substituent is defined as in Claim 1.) A compound according to claim 1, or a tautomer, optical isomer, geometric isomer, solvate, isotopic derivative, or pharmaceutically acceptable salt thereof, having the structure represented by .

3. R ２ It is an n-propyl group. The compound according to claim 1 or 2, or its tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts.

4. R ３ The following are the basis: 【Chemistry 9】 Selected from the group consisting of, Or, R ３ The following are the basis: 【Chemistry 10】 Selected from the group consisting of, A 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 ３ｄ is independently selected from the group consisting of deuterium, fluorine, hydroxyl group, amino group, 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 [[ID=3,2]] -OCH ２ CH ２ CH ３ , piperidinyl group, piperazinyl group and tetrahydropyrrolyl group, or R ３ｄ These are independently deuterium, fluorine, amino group, cyano group, and -C(O)NH ２ ien-CH ３ Selected from the group consisting of and piperidinyl groups, R ３ｄ The group is selected from the group consisting of a methyl group, -N(methyl)(methyl), and a piperidinyl group, or R ３ｄ These are independently deuterium, fluorine, hydroxyl group, amino group, cyano group, -NH(CH ３ ), -N(CH ３ ) (CH ３ ), -C(O)NH ２ ien-CH ３ ien-CH ２ CH ３ and -CH ２ CH ２ CH ３ Selected from the group consisting of, A 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. Y is based on the following: 【Chemistry 11】 Selected from the group consisting of, Alternatively, Y is based on the following: 【Chemistry 12】 A compound according to any one of claims 1 to 5, or a tautomer, optical isomer, geometric isomer, solvate, isotope derivative, or pharmaceutically acceptable salt thereof, selected from the group consisting of the above.

7. Q １ Q ２ and Q ３ Any one of these atoms, together with the substituent to which they are bonded, optionally forms R ６ｃ C may be replaced by ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocycloalkyl group, or Q １ Q ２ and Q ３ Any one of these atoms, together with the substituent to which they are bonded, optionally forms R ６ｃ C may be replaced by ３－４ A cycloalkyl group or a 3- to 6-membered heterocycloalkyl group is formed, wherein the heteroatoms are independently O or N, and the number of heteroatoms is 1 or 2, or Q １ Q ２ and Q ３ Any one of these atoms, together with the substituent to which they are bonded, optionally forms R ６ｃ C may be replaced by ３－４ Forms a cycloalkyl group, or, Q １ Q ２ and Q ３ Any two of these adjacent atoms, along with the substituents to which they are bonded, optionally form R ６ｃ C may be replaced by ３－８ Cycloalkyl groups, 3- to 8-membered heterocycloalkyl groups, C ６－８ It forms an aryl group, or a 5- to 8-membered heteroaryl group, or Q １ Q ２ and Q ３ Any two of these adjacent atoms, along with the substituents to which they are bonded, optionally form R ６ｃ C may be replaced by ５－６ Cycloalkyl groups, 5-6 member heterocycloalkyl groups, C ６ An aryl group or a 5-6 membered heteroaryl group is formed, wherein the heteroatoms are independently O or N, and the number of such heteroatoms is 1 or 2, or R ８ , R ９ , R １０ , R １１ , R １２ and R １３ If present, each independently contains hydrogen, deuterium, and optionally fluorine, chlorine, hydroxyl group, amino group, and 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 may be substituted with a cycloalkyl group, a 5-6 membered heterocycloalkyl group, a phenyl group, a 5-6 membered heteroaryl group, a 9-10 membered bicyclic heterocyclic group, or a 9-10 membered bicyclic heteroaryl group. １－６ alkyl group, C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, 5-6 member heterocycloalkyl groups, C ６－８ Selected from the group consisting of aryl groups, 5-6 membered heteroaryl groups, 9-10 membered bicyclic heterocyclic groups, and 9-10 membered bicyclic heteroaryl groups, or R ８ , R ９ , R １０ , R １１ , R １２ and R １３ If present, each independently contains hydrogen, or optionally fluorine, chlorine, 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 may be substituted with a cycloalkyl group, a 5-6 member heterocycloalkyl group, a phenyl group, or a 5-6 member heteroaryl group. １－６ alkyl group, C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, 5-6 member heterocycloalkyl groups, C ６－８ Selected from the group consisting of aryl groups and 5-6 membered heteroaryl groups, R ８ , R ９ , R １０ , R １１ , R １２ and R １３ If present, each independently contains hydrogen, or optionally fluorine, chlorine, 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 C may be substituted with alkyl. １－６ Alkyl and C １－６ Selected from the group consisting of alkoxy groups, or, R ８ , R ９ , R １０ , R １１ , R １２ and R １３ If present, each independently contains hydrogen, and optionally fluorine, chlorine, hydroxyl group, amino group, and C １－６ alkyl group, C １－６ C may be substituted with an alkoxy group. １－６ Alkyl and C １－６ Selected from the group consisting of alkoxy groups, or, R ８ , R ９ , R １０ , R １１ , R １２ and R １３ If present, each independently contains hydrogen, and optionally fluorine, chlorine, hydroxyl group, amino group, and C １－３ Alkyl alkyl group or C １－３ C may be substituted with an alkoxy group. １－３ Alkyl and C １－３ Selected from the group consisting of alkoxy groups, or, R ８ 、R ９ 、R １０ 、R １１ 、R １２ and R １３ are, when each 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<000L 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 , 【Chemistry 13】 Selected from a group consisting of, R ８ , R ９ , R １０ , R １１ , R １２ and R １３ If each exists, independently, -H, -F, -Cl, -OH, -NH ２ ien-CH ３ ien-CH ２ CH ３ ien-CH ２ CH ２ CH ３ , -CH(CH ３ )CH ３ ien-CH ２ OCH ３ ien-CH ２ CH ２ OCH ３ ien-CH ２ CH ２ CH ２ OCH ３ and -CH(CH ３ )CH ２ OCH ３ Selected from the group consisting of, Q １ Q ２ and Q ３ Any two adjacent atoms among them, together with the substituents to which they are bonded, form the following group: 【Chemistry 14】 They form a group selected from the group consisting of, or, Q １ Q ２ and Q ３ Any one of these atoms, together with the substituent to which they are bonded, forms one of the following groups: 【Chemistry 15】 A compound according to any one of claims 1 to 6, or a tautomer, optical isomer, geometric isomer, solvate, isotope derivative, or pharmaceutically acceptable salt thereof, which forms a group selected from the group consisting of the above.

8. R ６ａ It independently contains hydrogen, and optionally R ６ｃ C may be replaced by １－６ alkyl group, C １－６ Alkoxy group, C ３－１０ Carbon ring group, 3-10 membered heterocyclic group, C ６－８ Selected from the group consisting of aryl groups and 5- to 10-membered heteroaryl groups, R ６ａ It independently contains hydrogen, deuterium, and optionally R ６ｃ C may be replaced by １－６ alkyl group, C １－６ Alkoxy group, C ３－６ Carbon ring group, 5-6 membered heterocyclic group, C ６－８ Selected from the group consisting of aryl groups, 5-6 membered heteroaryl groups, 9-10 membered bicyclic heterocyclic groups, and 9-10 membered bicyclic heteroaryl groups, or R ６ａ It independently contains hydrogen, and optionally R ６ｃ C may be replaced by １－６ Alkyl alkyl group or C １－６ It is an alkoxy group, or, R ６ａ It independently uses hydrogen, or R if desired. ６ｃ C may be replaced by １－３ Alkyl alkyl group or C １－３ Selected from alkoxy groups, or, R ６ａ It independently contains hydrogen, and optionally R ６ｃ A selection from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy and isopropoxy, which may be substituted by, R ６ａ It independently uses hydrogen, or R if desired. ６ｃ A methyl group or an ethyl group which may be substituted by, A 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 ６ｃ These are independently hydrogen, fluorine, chlorine, hydroxyl group, amino group, and -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 Carbon ring group, 3-6 membered heterocyclic group, C ６－８ Selected from an aryl group or a 5-6 membered heteroaryl group, the heteroatom is N or S, and the number of heteroatoms is 1, 2, or 3, or R ６ｃ These are independently hydrogen, halogen, hydroxyl group, amino group, and C １－６ Alkyl alkyl group or C １－６ Selected from alkoxy groups, or, R ６ｃ These are independently selected from hydrogen, fluorine, chlorine, hydroxyl group, amino group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, ethoxy group, n-propoxy group, or isopropoxy group. A 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. The following 【Chemistry 16】 【Chemistry 17】 [Chemistry 18] 【Chemistry 19】 【Chemistry 20】 【Chemistry 21】 【Chemistry 22】 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 A compound selected from the group consisting of the above, or its tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts.

11. A pharmaceutical composition comprising a 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. A compound according to any one of claims 1 to 10, or a tautomer, optical isomer, geometric isomer, solvate, isotope derivative or pharmaceutically acceptable salt thereof, for use as an ATM kinase inhibitor, or for the prevention and / or treatment of diseases and / or disorders mediated at least partially by ATM kinase, The disease and / or disorder mediated by ATM kinase, said to be cancer, said cancer including solid tumors and hematological malignancies, or said compound or its tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts, said to include breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, small cell lung cancer, glioblastoma.

13. A pharmaceutical composition according to claim 11, for use as an ATM kinase inhibitor, or for the prevention and / or treatment of diseases and / or disorders mediated at least partially by ATM kinase, The disease and / or disorder mediated by ATM kinase, at least partially, is cancer, and the cancer includes solid tumors and hematological malignancies, or a pharmaceutical composition including breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, small cell lung cancer, and glioblastoma.

14. A 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, for the prevention and / or treatment of cancer, The aforementioned cancers include solid tumors and hematological malignancies, or include breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, small cell lung cancer, glioblastoma, the aforementioned compound or its tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts.

15. A pharmaceutical composition according to claim 11 for the prevention and / or treatment of cancer, The cancers mentioned above include solid tumors and hematological malignancies, or the pharmaceutical composition includes breast cancer, non-small cell lung cancer, glioma, colon cancer, rectal cancer, malignant glioma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, small cell lung cancer, and glioblastoma.

16. A pharmaceutical composition comprising a compound according to any one of claims 1 to 10 or its tautomer, optical isomer, geometric isomer, solvate, or isotopic derivative, and at least one additional antitumor agent, The aforementioned antitumor agent is a pharmaceutical composition selected from doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan, bleomycin, cisplatin, oxaliplatin, carboplatin, barrubicin, idarubicin, pirarubicin, amrubicin, epirubicin, olaparib, MEDI4736, AZD1775, and AZD6738.

17. The use of a compound according to any one of claims 1 to 10 or its tautomers, optical isomers, geometric isomers, solvates, isotopic derivatives or pharmaceutically acceptable salts, or the pharmaceutical composition according to claim 11, in the preparation of a pharmaceutical for the prevention and / or treatment of cancer, wherein the pharmaceutical is used in combination with at least one additional antitumor agent or therapeutic treatment. The aforementioned antitumor agent is selected from doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan, bleomycin, cisplatin, oxaliplatin, carboplatin, barrubicin, idarubicin, pirarubicin, amrubicin, epirubicin, olaparib, MEDI4736, AZD1775, and AZD6738, or The therapeutic treatment is radiation therapy, used.

18. A method for producing the compound described in claim 1, 【Chemistry 26】 i) Chemically transform compound I-a1 to obtain compound I-a2, ii) Chemically transform compound I-a2 to obtain compound I-a4, iii) Compound I-a4 is chemically transformed to obtain compound I-a5, iv) Compound I-a5 is chemically transformed to obtain compound I-a6, v) Chemically transform compound I-a6 to obtain compound I-a7, vi) Chemically transform compound I-a7 to obtain compound I-a8, vii) Synthetic route 1 to obtain compound I by chemically transforming compound I-a8, 【Chemistry 27】 i) Using compound I-b1 as a basic raw material, compound I-b2 is obtained. ii) Compound I-b4 is obtained using compounds I-b2 and I-b3 as basic raw materials. iii) Using compound I-b4 as a basic raw material, compound I-b5 is obtained. iv) Compound I-b5 is used as the basic raw material to obtain compound I-b6. v) Using compound I-b6 as a basic raw material, compound I-b7 is obtained. vi) Using compound I-b7 as a basic raw material, compound I-b8 is obtained. vii) Using compound I-b8 as a basic raw material, compound I-b9 is obtained. viiii) Synthetic route 2 for obtaining compound I using compound I-b9 as a basic raw material, 【Chemistry 28】 i) Using compound I-b1 as a basic raw material, compound I-b2 is obtained. ii) Compound I-b5 is obtained using compounds I-b2 and I-b3 as basic raw materials. iii) Using compound I-b5 as a basic raw material, compound I-b6 is obtained. iv) Using compound I-b6 as a basic raw material, compound I-b7 is obtained. v) Using compound I-b7 as a basic raw material, compound I-b8 is obtained. vi) Using compound I-b8 as a basic raw material, compound I-b9 is obtained. vii) Synthesis route 3 for obtaining compound I of general formula using compound I-b9 as a basic raw material It is one of the following that can be selected. In these formulas, R ｘ１ X is selected from halogen or hydrogen, １ , R ４ , R ５ , R ６ , R ７ A, W, L, t １ and t ２ A manufacturing method, wherein the method is as defined in claim 1.

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