Nitrogen-containing tricyclic PRMT5 inhibitor, method for producing the same, and pharmaceutical use thereof

Abstract

The present invention relates to a nitrogen-containing tricyclic PRMT5 inhibitor, a method for producing the same, and a pharmaceutical use thereof. In particular, the present invention relates to a PRMT5 inhibitor having a structure represented by formula (I), a method for producing the same, a drug composition containing the same, and its use as a PRMT5 inhibitor and its use in the treatment and / or prevention of diseases mediated by PRMT5. Here, each substituent of formula (I) is the same as defined in the specification. 【Chemical 1】 TIFF2025516926000204.tif44144

Description

Detailed Description of the Invention

[0001] [Technical Field] The present invention belongs to the field of drug synthesis, and specifically relates to a nitrogen-containing tricyclic PRMT5 inhibitor, a method for producing the same, and a pharmaceutical use thereof.

[0002] [Background Art] Epigenetic gene regulation is an important biological control mechanism for protein synthesis and cell differentiation, and plays an important role in many human diseases.

[0003] Epigenetic control involves controlling inheritable genetic material without changing its nucleic acid sequence. Generally, epigenetic control controls the conversion between transcriptionally active and inactive states in chromatin conformation by selective and reversible modifications (such as methylation) to DNA and proteins (such as histones). These covalent modifications can be controlled by enzymes such as methyltransferases (such as PRMT5), and many methyltransferases are associated with specific genetic changes in many human pathogenic genes. PRMT5 plays an important role in many diseases such as tumors, metabolic diseases, and blood diseases.

[0004] Homozygous deletion of tumor suppressor genes is a driver of tumors and often results in deletion of passenger genes in the vicinity of the suppressor genes. Deletions of these passenger genes result in drawbacks of tumor cell specificity and can be targeted by targeted therapies. Homozygous deletion at the chromosomal 9p21 locus includes the well-known tumor suppressor gene CDKN2A, occurs in 15% of tumors, and often also includes deletion of the passenger gene MTAP. MTAP is an important enzyme in the methionine and adenine salvage pathways. Deletion of MTAP results in the accumulation of its substrate, MTA. MTA and S-adenosylmethionine (SAM) are structurally similar, while the latter is the methyl group donor for the type II methyltransferase PRMT5. The increase in MTA levels due to MTAP deletion selectively competes with the binding of SAM to PRMT5, rendering the methyltransferase non-functional and more susceptible to the effects of PRMT5 inhibition. Many different genome-wide shRNA screenings using a wide range of tumor cell lines have shown a correlation between MTAP deletion and the dependence of cell lines on PRMT5, and the impact of this metabolic sensitivity has attracted attention. However, as a gene that is very important for cells, any studies on conditional knockout of PRMT5 or siRNA knockout suggest that inhibition of PRMT5 in normal tissues has significant side effects. (For example, cytopenia, infertility, sarcopenia, myocardial hypertrophy, etc.). Therefore, new strategies are needed to apply and explore this metabolic sensitivity, selectively target PRMT5 in MTAP-deleted tumors, and avoid the action on PRMT5 in normal tissues (MTAP wild type).

[0005] Small molecule inhibitors targeting PRMT5 that co-act with MTA can selectively target only PRMT5 in the state bound to MTA, while such PRMT5 is concentrated only in MTAP-deleted tumor cells. Therefore, in normal cells with intact MTAP, when the MTA level is very low, PRMT5 is not targeted, and in this way, a better therapeutic window is obtained.

[0006] [Summary of the Invention] An object of the present invention is to provide a nitrogen-containing tricyclic PRMT5 inhibitor, a method for producing the same, and a pharmaceutical use thereof. A series of compounds of the present invention have a very strong inhibitory action on PRMT5 and can be widely used in the production of drugs for treating and / or preventing diseases mediated by PRMT5, thereby expecting the development of a new generation of PRMT5 inhibitors.

[0007] The first aspect of the present invention provides a compound represented by formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof:

[0008] [Chemical formula]

[0009] (wherein, "

[0010] [Chemical formula] " is a double bond or a single bond,

[0011] X 1 is C or N, X 2 is C or N, provided that X 1 , X 2 at least one of which is N, X 3 is CR 5 or N, X 4 is CR 6 or N, X 5 is CR 7 or N, X 6 is CR 8 or N, X 7 is CR 9 or N, X 8 is CR 10 or N, R 1 is -(CR 11 R 12) m -R, or R 1 and R 2 together with the nitrogen atom directly linked thereto form a ring B, said ring B being a 4- to 10-membered nitrogen-containing heterocyclic group or a 5- to 10-membered nitrogen-containing heteroaryl group, said ring B being optionally further substituted by one or more substituents selected from R, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, =O, =S, -C 0-8 alkyl-SF 5 、-C 0-8 alkyl-O-S(O) 2 R 13 、-C 0-8 alkyl-S(O) r R 13 、-C 0-8 alkyl-O-R 14 、-C 0-8 alkyl-C(O)OR 14 、-C 0-8 alkyl-C(O)SR 14 、-C 0-8 alkyl-S-C(O)R 15 、-C 0-8 alkyl-C(O)R 15 、-C 0-8 alkyl-O-C(O)R 15 、-C 0-8 alkyl-P(O)(R 15 ) 2 、-C 0-8 alkyl-NR 16 R 17 、-C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 and is substituted by one or more substituents selected therefrom, R is -ring A-(R a ) n wherein, ring A is a C 3-12 cycloalkyl group, a 4- to 10-membered heterocyclic group, C 6-10Selected from an aryl group or a 5- to 10-membered heteroaryl group, said C 3-12 The cycloalkyl group or 4- to 10-membered heterocyclic group may optionally be further condensed with a C 6-10 Aryl group or 5- to 10-membered heteroaryl group, said C 6-10 The aryl group or 5- to 10-membered heteroaryl group may optionally be further condensed with a 5- to 10-membered heteroaryl group, C 3-12 Cycloalkyl group or 4- to 10-membered heterocyclic group, Each R a Is independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12 Cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 Aryl group, 5- to 10-membered heteroaryl group, -C 0-8 Alkyl-SF 5 、-C 0-8 Alkyl-O-S(O) 2 R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-O-R 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-S-C(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-O-C(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 ) 2 、-C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(O)NR 16 R 17 And -C 0-8 Alkyl-N(R 16 )-C(O)R15 selected from, or when n ≧ 2, two Rs at the same carbon a form C(O) together with the carbon atom to which they are directly attached, and the groups are independently optionally further deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 , -C 0-8 alkyl-O-S(O) 2 R 13 , -C 0-8 alkyl-S(O) r R 13 , -C 0-8 alkyl-O-R 14 , -C 0-8 alkyl-C(O)OR 14 , -C 0-8 alkyl-C(O)SR 14 , -C 0-8 alkyl-S-C(O)R 15 , -C 0-8 alkyl-C(O)R 15 , -C 0-8 alkyl-O-C(O)R 15 , -C 0-8 alkyl-P(O)(R 15 ) 2 , -C 0-8 alkyl-NR 16 R 17 , -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 substituted by one or more substituents selected from, R 2 is hydrogen, deuterium, C 1-10 alkyl group, C2-10 an alkenyl group, C 2-10 an alkynyl group, C 3-12 a cycloalkyl group, a 3- to 12-membered heterocyclic group, C 6-10 an aryl group, a 5- to 10-membered heteroaryl group, -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)R 15 and -C(O)NR 16 R 17 selected from, said C 3-12 the cycloalkyl group or the 3- to 12-membered heterocyclic group is optionally further condensed with a C 6-10 aryl group or a 5- to 10-membered heteroaryl group, said C 6-10 aryl group or a 5- to 10-membered heteroaryl group is optionally further condensed with a C 3-12 cycloalkyl group or a 4- to 10-membered heterocyclic group, said groups are independently optionally further deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, halogen-substituted C 3-6 cycloalkyl group, halogen-substituted 3- to 6-membered heterocyclic group, halogen-substituted C 6-8 aryl group, halogen-substituted 5- to 8-membered heteroaryl group, C 1-4 alkyl-substituted C 3-6 cycloalkyl group, C 1-4 alkyl-substituted 3- to 6-membered heterocyclic group, C 1-4 alkyl-substituted C 6-8 aryl group, C 1-4 alkyl-substituted 5- to 8-membered heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, =O, =S, -C 0-8 alkyl-SF 5 , -C 0-8 alkyl-O-S(O) 2 R 13 , -C 0-8Alkyl-S(O) r R 13 、-C 0-8 Alkyl-O-R 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-S-C(O)R 15 、-C 0-8 Alkyl-C(O)R 15 、-C 0-8 Alkyl-O-C(O)R 15 、-C 0-8 Alkyl-P(O)(R 15 ) 2 、-C 0-8 Alkyl-NR 16 R 17 、-C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 is substituted by one or more substituents selected from R 3 and R 4 are each independently hydrogen, deuterium, a hydroxy group, a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, a C 3-12 cycloalkyl group and a 3- to 12-membered heterocyclic group, or, R 3 and R 4 together with the nitrogen atom to which they are directly attached form a 4- to 10-membered nitrogen-containing heterocyclic group or a 5- to 10-membered nitrogen-containing heteroaryl group, and said groups are each independently optionally further deuterium, halogen, cyano group, hydroxy group, =O, =S, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deutero gen-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 1-10 alkoxy group, C 3-12 cycloalkyl group, C3-12 A cycloalkoxy group, a 3- to 12-membered heterocyclic group, a 3- to 12-membered heterocyclic oxy group, and -NR 16 R 17 substituted by one or more substituents selected from R 5 、R 6 and R 7 are each independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, -C 0-8 alkyl-SF 5 、-C 0-8 alkyl-O-S(O) 2 R 13 、-C 0-8 alkyl-S(O) r R 13 、-C 0-8 alkyl-O-R 14 、-C 0-8 alkyl-C(O)OR 14 、-C 0-8 alkyl-C(O)SR 14 、-C 0-8 alkyl-S-C(O)R 15 、-C 0-8 alkyl-C(O)R 15 、-C 0-8 alkyl-O-C(O)R 15 、-C 0-8 alkyl-P(O)(R 15 ) 2 、-C 0-8 alkyl-NR 16 R 17 、-C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 selected from, and the groups are each independently optionally further deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 , -C 0-8 alkyl-O-S(O) 2 R 13 , -C 0-8 alkyl-S(O) r R 13 , -C 0-8 alkyl-O-R 14 , -C 0-8 alkyl-C(O)OR 14 , -C 0-8 alkyl-C(O)SR 14 , -C 0-8 alkyl-S-C(O)R 15 , -C 0-8 alkyl-C(O)R 15 , -C 0-8 alkyl-O-C(O)R 15 , -C 0-8 alkyl-P(O)(R 15 ) 2 , -C 0-8 alkyl-NR 16 R 17 , -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 substituted by one or more substituents selected from R 8 , R 9 and R 10 are each independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10An aryl group, a 5- to 10-membered heteroaryl group, -C 0-8 alkyl-SF 5 、-C 0-8 alkyl-O-S(O) 2 R 13 、-C 0-8 alkyl-S(O) r R 13 、-C 0-8 alkyl-O-R 14 、-C 0-8 alkyl-C(O)OR 14 、-C 0-8 alkyl-C(O)SR 14 、-C 0-8 alkyl-S-C(O)R 15 、-C 0-8 alkyl-C(O)R 15 、-C 0-8 alkyl-O-C(O)R 15 、-C 0-8 alkyl-P(O)(R 15 ) 2 、-C 0-8 alkyl-NR 16 R 17 、-C 0-8 alkyl-C(O)NR 16 R 17 および-C 0-8 alkyl-N(R 16 )-C(O)R 15 selected from, and said groups are independently optionally further deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 、-C 0-8 alkyl-O-S(O) 2 R 13 、-C 0-8 alkyl-S(O) r R 13 、-C0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 Alkyl-P(O)(R 15 ) 2 , -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 is substituted by one or more substituents selected from Each R 11 and R 12 are independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12 Cycloalkyl groups, 3-12 membered heterocyclic groups, C 6-10 Aryl groups, 5-10 membered heteroaryl groups, -C 0-8 Alkyl-SF 5 , -C 0-8 Alkyl-OS(O) 2 R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 Alkyl-P(O)(R 15 ) 2 , -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 or R 11 and R 12 are one C with the carbon atom directly connected to them. 3-12 Cycloalkyl groups, 4-10 membered heterocyclic groups, C 6-10 aryl or 5-10 membered heteroaryl groups, which may independently optionally further comprise deuterium, halogen, cyano, nitro, azide, C 1-10 Alkyl group, halogen-substituted C 1-10 Alkyl group, deuterium substituted C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12 Cycloalkyl groups, 3-12 membered heterocyclic groups, C 6-10 Aryl groups, 5-10 membered heteroaryl groups, =O, =S, -C 0-8 Alkyl-SF 5 , -C 0-8 Alkyl-OS(O) 2 R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C0-8 alkyl-O-C(O)R 15 , -C 0-8 alkyl-P(O)(R 15 ) 2 , -C 0-8 alkyl-NR 16 R 17 , -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 substituted by one or more substituents selected from each R 13 is independently hydrogen, deuterium, a hydroxy group, C 1-10 alkyl group, C 2-10 alkenyl group, C 3-12 cycloalkyl group, a 3- to 12-membered heterocyclic group, C 6-10 aryl group, a 5- to 10-membered heteroaryl group, and -NR 16 R 17 selected from, and said groups are independently optionally further deuterium, halogen, hydroxy group, =O, C 1-10 alkyl group, C 1-10 alkoxy group, C 3-12 cycloalkyl group, C 3-12 cycloalkoxy group, a 3- to 12-membered heterocyclic group, a 3- to 12-membered heterocyclic oxy group, C 6-10 aryl group, C 6-10 aryloxy group, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryloxy group, and -NR 16 R 17 selected from one or more substituents, each R 14 is independently hydrogen, deuterium, C 1-10 alkyl group, C 2-10 alkenyl group, C 3-12 cycloalkyl group, a 3- to 12-membered heterocyclic group, C 6-10 aryl group, and a 5- to 10-membered heteroaryl group selected from, and said groups are independently optionally further deuterium, halogen, hydroxy group, =O, cyano group, C 1-10 alkyl group, C 1-10 alkoxy group, C 3-12a cycloalkyl group, C 3-12 a cycloalkoxy group, a 3- to 12-membered heterocyclic group, a 3- to 12-membered heterocyclic oxy group, C 6-10 an aryl group, C 6-10 an aryloxy group, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryloxy group, and -NR 16 R 17 substituted by one or more substituents selected from each R 15 is independently hydrogen, deuterium, a hydroxy group, C 1-10 an alkyl group, C 1-10 an alkoxy group, C 2-10 an alkenyl group, C 2-10 an alkynyl group, C 3-12 a cycloalkyl group, C 3-12 a cycloalkoxy group, a 3- to 12-membered heterocyclic group, a 3- to 12-membered heterocyclic oxy group, C 6-10 an aryl group, C 6-10 an aryloxy group, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryloxy group, and -NR 16 R 17 selected from, and the groups are independently optionally further deuterium, halogen, hydroxy group, =O, cyano group, C 1-10 an alkyl group, C 1-10 an alkoxy group, C 3-12 a cycloalkyl group, C 3-12 a cycloalkoxy group, a 3- to 12-membered heterocyclic group, a 3- to 12-membered heterocyclic oxy group, C 6-10 an aryl group, C 6-10 an aryloxy group, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryloxy group, and -NR 16 R 17 substituted by one or more substituents selected from each R 16 and R 17 are each independently hydrogen, deuterium, hydroxy group, C 1-10 an alkyl group, C 2-10 an alkenyl group, C 2-10 an alkynyl group, C 3-12 a cycloalkyl group, a 3- to 12-membered heterocyclic group, C 6-10An aryl group, a 5- to 10-membered heteroaryl group, a sulfinyl group, a sulfonyl group, a methylsulfonyl group, an isopropylsulfonyl group, a cyclopropyl sulfonyl group, a p-toluenesulfonyl group, an aminosulfonyl group, a dimethylaminosulfonyl group, and a C 1-10 alkanoyl group, wherein said groups are each independently optionally further substituted with deuterium, halogen, a hydroxy group, =O, a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, a halogen-substituted C 1-10 alkyl group, a deuterium-substituted C 1-10 alkyl group, a C 1-10 alkoxy group, a C 3-12 cycloalkyl group, a C 3-12 cycloalkoxy group, a 3- to 12-membered heterocyclic group, a 3- to 12-membered heterocyclic oxy group, a C 6-10 aryl group, a C 6-10 aryloxy group, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryloxy group, an amino group, a C 1-10 alkylmonosubstituted amino group, a C 1-10 alkyldisubstituted amino group, and a C 1-10 alkanoyl group, or are substituted by one or more substituents selected from the group consisting of, or R 16 and R 17 together with the nitrogen atom directly connected thereto form a 4- to 10-membered heterocyclic group or a 5- to 10-membered heteroaryl group, and said 4- to 10-membered heterocyclic group or 5- to 10-membered heteroaryl group is optionally further substituted with deuterium, halogen, a hydroxy group, =O, a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, a halogen-substituted C 1-10 alkyl group, a deuterium-substituted C 1-10 alkyl group, a C 1-10 alkoxy group, a C 3-12 cycloalkyl group, a C 3-12 cycloalkoxy group, a 3- to 12-membered heterocyclic group, a 3- to 12-membered heterocyclic oxy group, a C 6-10 aryl group, a C 6-10An aryloxy group, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryloxy group, an amino group, C 1-10 An alkyl mono-substituted amino group, C 1-10 An alkyl di-substituted amino group and C 1-10 Substituted by one or more substituents selected from an alkanoyl group, m is 0, 1 or 2, n is 0, 1, 2, 3, 4, 5 or 6, Each r is independently 0, 1 or 2).

[0012] In a more preferred form, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, R 3 and R 4 are each independently hydrogen, deuterium, a hydroxy group, C 1-4 An alkyl group, C 2-4 An alkenyl group, C 2-4 An alkynyl group, C 3-6 Selected from a cycloalkyl group and a 3- to 6-membered heterocyclic group, and the said groups may independently be optionally further substituted by deuterium, a halogen, a cyano group, a hydroxy group, =O, =S, C 1-4 An alkyl group, a halogen-substituted C 1-4 An alkyl group, a deuterium-substituted C 1-4 An alkyl group, C 2-4 An alkenyl group, C 2-4 An alkynyl group, C 1-4 An alkoxy group, C 3-6 A cycloalkyl group, C 3-6 A cycloalkoxy group, a 3- to 6-membered heterocyclic group, a 3- to 6-membered heterocyclic oxy group and -NR 16 R 17 Selected from may be substituted by one or more substituents, Here, R 16 and R 17 are as described in the compound represented by the formula (I).

[0013] In an even more preferred form, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, R 3 and R 4is independently selected from hydrogen, deuterium, hydroxy group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group and 3- to 6-membered heterocyclic group.

[0014] In a more preferred form, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, R 5 , R 6 and R 7 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, -C 0-4 alkyl-SF 5 , -C 0-4 alkyl-O-S(O) 2 R 13 , -C 0-4 alkyl-S(O) r R 13 , -C 0-4 alkyl-O-R 14 , -C 0-4 alkyl-C(O)OR 14 , -C 0-4 alkyl-C(O)SR 14 , -C 0-4 alkyl-S-C(O)R 15 , -C 0-4 alkyl-C(O)R 15 , -C 0-4 alkyl-O-C(O)R 15 , -C 0-4 alkyl-P(O)(R 15 ) 2 , -C 0- 4 alkyl-NR 16 R 17 , -C 0-4Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 selected from, said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, =O, =S, -C 0-4 alkyl-SF 5 , -C 0-4 alkyl-O-S(O) 2 R 13 , -C 0-4 alkyl-S(O) r R 13 , -C 0-4 alkyl-O-R 14 , -C 0-4 alkyl-C(O)OR 14 , -C 0-4 alkyl-C(O)SR 14 , -C 0-4 alkyl-S-C(O)R 15 , -C 0-4 alkyl-C(O)R 15 , -C 0-4 alkyl-O-C(O)R 15 , -C 0-4 alkyl-P(O)(R 15 ) 2 , -C 0-4 alkyl-NR 16 R 17 , -C 0-4 alkyl-C(O)NR 16 R 17 and -C 0-4 alkyl-N(R 16 )-C(O)R 15 substituted by one or more substituents selected from, wherein, R 13 , R 14 , R 15, R 16 , R 17 and r are as described for the compound represented by formula (I).

[0015] Even more preferably, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, R 5 , R 6 and R 7 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 are selected from, and the groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen substituted C 1-4 alkyl group, deuterium substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, =O, =S, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R13 、 -O-R 14 、 -C(O)OR 14 、 -C(O)SR 14 、 -S-C(O)R 15 、 -C(O)R 15 、 -O-C(O)R 15 、 -P(O)(R 15 ) 2 、 -NR 16 R 17 、 -C(O)NR 16 R 17 および -N(R 16 )-C(O)R 15 are substituted by one or more substituents selected from: wherein R 13 、 R 14 、 R 15 、 R 16 、 R 17 and r are as described for the compounds of formula (I).

[0016] In a more preferred form, in the compound of formula (I), its stereoisomers or its pharmaceutically acceptable salts, R 8 、 R 9 and R 10 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -C 0-4 alkyl-SF 5 、 -C 0-4 alkyl-O-S(O) 2 R 13 、 -C 0-4 alkyl-S(O) r R 13 、 -C 0-4 alkyl-O-R 14 、 -C 0-4 alkyl-C(O)OR 14 、 -C 0-4 alkyl-C(O)SR 14 、 -C 0-4 alkyl-S-C(O)R15 、 -C 0-4 alkyl - C(O)R 15 、 -C 0-4 alkyl - O - C(O)R 15 、 -C 0-4 alkyl - P(O)(R 15 ) 2 、 -C 0-4 alkyl - NR 16 R 17 、 -C 0-4 alkyl - C(O)NR 16 R 17 and -C 0-4 alkyl - N(R 16 ) - C(O)R 15 selected from, and said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen - substituted C 1-4 alkyl group, deuterium - substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3 - 6 - membered heterocyclic group, C 6-8 aryl group, 5 - 8 - membered heteroaryl group, =O, =S, -C 0-4 alkyl - SF 5 、 -C 0-4 alkyl - O - S(O) 2 R 13 、 -C 0-4 alkyl - S(O) r R 13 、 -C 0-4 alkyl - O - R 14 、 -C 0-4 alkyl - C(O)OR 14 、 -C 0-4 alkyl - C(O)SR 14 、 -C 0-4 alkyl - S - C(O)R 15 、 -C 0-4 alkyl - C(O)R 15 、 -C 0-4 alkyl - O - C(O)R 15 、 -C 0-4 alkyl - P(O)(R 15 ) 2 、 -C 0-4 alkyl - NR16 R 17 、 -C 0-4 alkyl - C(O)NR 16 R 17 and - C 0-4 alkyl - N(R 16 ) - C(O)R 15 substituted by one or more substituents selected from wherein R 13 , R 14 , R 15 , R 16 , R 17 and r are as described for the compound represented by formula (I).

[0017] Even more preferably, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, R 8 , R 9 and R 10 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3 - 6 membered heterocyclic group, C 6-8 aryl group, 5 - 8 membered heteroaryl group, - SF 5 , - O - S(O) 2 R 13 , - S(O) r R 13 , - O - R 14 , - C(O)OR 14 , - C(O)SR 14 , - S - C(O)R 15 , - C(O)R 15 , - O - C(O)R 15 , - P(O)(R 15 ) 2 , - NR 16 R 17 , - C(O)NR 16 R 17 and - N(R 16 ) - C(O)R 15 selected from, and the said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen - substituted C1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, =O, =S, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 is substituted by one or more substituents selected from wherein R 13 , R 14 , R 15 , R 16 , R 17 and r are as described for the compound represented by formula (I).

[0018] In a more preferred form, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, each R 11 and R 12 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, -C 0-4 alkyl-SF 5 , -C 0-4 alkyl-O-S(O) 2R 13 、 -C 0-4 alkyl - S(O) r R 13 、 -C 0-4 alkyl - O - R 14 、 -C 0-4 alkyl - C(O)OR 14 、 -C 0-4 alkyl - C(O)SR 14 、 -C 0-4 alkyl - S - C(O)R 15 、 -C 0-4 alkyl - C(O)R 15 、 -C 0-4 alkyl - O - C(O)R 15 、 -C 0-4 alkyl - P(O)(R 15 ) 2 、 -C 0-4 alkyl - NR 16 R 17 、 -C 0-4 alkyl - C(O)NR 16 R 17 and -C 0-4 alkyl - N(R 16 ) - C(O)R 15 selected from, or, R 11 and R 12 together with the carbon atom directly connecting to them form one C 3-6 cycloalkyl group, 4 - 8 membered heterocyclic group, C 6-8 aryl group or 5 - 8 membered heteroaryl group, and said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen - substituted C 1-4 alkyl group, deuterium - substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3 - 6 membered heterocyclic group, C 6-8 aryl group, 5 - 8 membered heteroaryl group, =O, =S, -C 0-4 alkyl - SF 5 、 -C 0-4 alkyl - O - S(O) 2 R 13 、 -C 0-4 alkyl - S(O) r R13 、 -C 0-4 alkyl - O - R 14 、 -C 0-4 alkyl - C(O)OR 14 、 -C 0-4 alkyl - C(O)SR 14 、 -C 0-4 alkyl - S - C(O)R 15 、 -C 0-4 alkyl - C(O)R 15 、 -C 0-4 alkyl - O - C(O)R 15 、 -C 0-4 alkyl - P(O) (R 15 ) 2 、 -C 0-4 alkyl - NR 16 R 17 、 -C 0-4 alkyl - C(O)NR 16 R 17 and -C 0-4 alkyl - N(R 16 ) - C(O)R 15 is substituted by one or more substituents selected from wherein R 13 、 R 14 、 R 15 、 R 16 、 R 17 and r are as described for the compound represented by formula (I).

[0019] Even more preferably, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, each R 11 and R 12 is independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3 - 6 membered heterocyclic group, C 6-8 aryl group, 5 - 8 membered heteroaryl group, -SF 5 、 -O - S(O) 2 R 13 、 -S(O) r R 13 、 -O - R14 、 -C(O)OR 14 、 -C(O)SR 14 、 -S-C(O)R 15 、 -C(O)R 15 、 -O-C(O)R 15 、 -P(O)(R 15 ) 2 、 -NR 16 R 17 、 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 selected from, and said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, =O, =S, -SF 5 、 -O-S(O) 2 R 13 、 -S(O) r R 13 、 -O-R 14 、 -C(O)OR 14 、 -C(O)SR 14 、 -S-C(O)R 15 、 -C(O)R 15 、 -O-C(O)R 15 、 -P(O)(R 15 ) 2 、 -NR 16 R 17 、 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by one or more substituents selected from, wherein R 13 、 R 14 、 R 15 、 R 16 、 R 17 and r are as described for the compound represented by formula (I).

[0020] In a more preferred embodiment, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, R 1 is -(CR 11 R 12 ) m -R, or R 1 and R 2 together with the nitrogen atom directly connecting them form a ring B, and the ring B is a 4- to 10-membered nitrogen-containing heterocyclic group or a 5- to 10-membered nitrogen-containing heteroaryl group. The ring B is optionally further substituted with one or more substituents selected from R, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, =O, =S, -C 0-4 alkyl-SF 5 、-C 0-4 alkyl-O-S(O) 2 R 13 、-C 0-4 alkyl-S(O) r R 13 、-C 0-4 alkyl-O-R 14 、-C 0-4 alkyl-C(O)OR 14 、-C 0-4 alkyl-C(O)SR 14 、-C 0-4 alkyl-S-C(O)R 15 、-C 0-4 alkyl-C(O)R 15 、-C 0-4 alkyl-O-C(O)R 15 、-C 0-4 alkyl-P(O)(R 15 ) 2 、-C 0-4 alkyl-NR 16 R 17 、-C 0-4 alkyl-C(O)NR 16 R 17 and -C 0-4 alkyl-N(R 16 )-C(O)R 15 and is substituted by one or more substituents selected therefrom, R is -ring A-(R a )n and wherein ring A is selected from a C 3-6 cycloalkyl group, a 4- to 8-membered heterocyclic group, a C 6-8 aryl group or a 5- to 8-membered heteroaryl group, said C 3-6 cycloalkyl group or 4- to 8-membered heterocyclic group being optionally further fused to a C 6-8 aryl group or a 5- to 8-membered heteroaryl group, and said C 6-8 aryl group or 5- to 8-membered heteroaryl group being optionally fused to a 5- to 8-membered heteroaryl group, a C 3-6 cycloalkyl group or a 4- to 8-membered heterocyclic group, each R a is independently hydrogen, deuterium, halogen, cyano, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, a 3- to 6-membered heterocyclic group, C 6-8 aryl, 5- to 8-membered heteroaryl, -C 0-4 alkyl-SF 5 , -C 0-4 alkyl-O-S(O) 2 R 13 , -C 0-4 alkyl-S(O) r R 13 , -C 0-4 alkyl-O-R 14 , -C 0-4 alkyl-C(O)OR 14 , -C 0-4 alkyl-C(O)SR 14 , -C 0-4 alkyl-S-C(O)R 15 , -C 0-4 alkyl-C(O)R 15 , -C 0-4 alkyl-O-C(O)R 15 , -C 0-4 alkyl-P(O)(R 15 ) 2 , -C 0-4 alkyl-NR 16 R 17 , -C 0-4 alkyl-C(O)NR 16 R 17and -C 0-4 alkyl-N(R 16 )-C(O)R 15 selected from, said groups being independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, =O, =S, -C 0-4 alkyl-SF 5 , -C 0-4 alkyl-O-S(O) 2 R 13 , -C 0-4 alkyl-S(O) r R 13 , -C 0-4 alkyl-O-R 14 , -C 0-4 alkyl-C(O)OR 14 , -C 0-4 alkyl-C(O)SR 14 , -C 0-4 alkyl-S-C(O)R 15 , -C 0-4 alkyl-C(O)R 15 , -C 0-4 alkyl-O-C(O)R 15 , -C 0-4 alkyl-P(O)(R 15 ) 2 , -C 0-4 alkyl-NR 16 R 17 , -C 0-4 alkyl-C(O)NR 16 R 17 and -C 0-4 alkyl-N(R 16 )-C(O)R 15 substituted by one or more substituents selected from, R 2 is hydrogen, deuterium, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C3-6 A cycloalkyl group, a 3-6 membered heterocyclic group, C 6-8 An aryl group, a 5-8 membered heteroaryl group, -S(O) r R 13 、-O-R 14 、-C(O)OR 14 、-C(O)R 15 And -C(O)NR 16 R 17 Selected from, said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 An alkyl group, a halogen substituted C 1-4 An alkyl group, a deuterium substituted C 1-4 An alkyl group, C 2-4 An alkenyl group, C 2-4 An alkynyl group, C 3-6 A cycloalkyl group, a 3-6 membered heterocyclic group, C 6-8 An aryl group, a 5-8 membered heteroaryl group, a halogen substituted C 3-6 A cycloalkyl group, a halogen substituted 3-6 membered heterocyclic group, a halogen substituted C 6-8 An aryl group, a halogen substituted 5-8 membered heteroaryl group, C 1-4 An alkyl substituted C 3-6 A cycloalkyl group, C 1-4 An alkyl substituted 3-6 membered heterocyclic group, C 1-4 An alkyl substituted C 6-8 An aryl group, C 1-4 An alkyl substituted 5-8 membered heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, =O, =S, -C 0-4 An alkyl-SF 5 、-C 0-4 An alkyl-O-S(O) 2 R 13 、-C 0-4 An alkyl-S(O) r R 13 、-C 0-4 An alkyl-O-R 14 、-C 0-4 An alkyl-C(O)OR 14 、-C 0-4 An alkyl-C(O)SR 14 、-C 0-4 An alkyl-S-C(O)R 15 、-C 0-4 An alkyl-C(O)R 15, -C 0-4 alkyl - O - C(O)R 15 , -C 0-4 alkyl - P(O)(R 15 ) 2 , -C 0-4 alkyl - NR 16 R 17 , -C 0-4 alkyl - C(O)NR 16 R 17 and -C 0-4 alkyl - N(R 16 ) - C(O)R 15 substituted by one or more substituents selected from wherein R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , m, n and r are as described for the compound of formula (I).

[0021] In a more preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, each R 13 is independently hydrogen, deuterium, hydroxy group, C 1-4 alkyl group, C 2-4 alkenyl group, C 3-6 cycloalkyl group, 3 - 6 membered heterocyclic group, C 6-8 aryl group, 5 - 8 membered heteroaryl group and -NR 16 R 17 selected from, and said groups are independently optionally further deuterium, halogen, hydroxy group, =O, C 1-4 alkyl group, C 1-4 alkoxy group, C 3-6 cycloalkyl group, C 3-6 cycloalkoxy group, 3 - 6 membered heterocyclic group, 3 - 6 membered heterocyclic oxy group, C 6-8 aryl group, C 6-8 aryloxy group, 5 - 8 membered heteroaryl group, 5 - 8 membered heteroaryloxy group and -NR 16 R 17 substituted by one or more substituents selected from each R14 is independently hydrogen, deuterium, C 1-4 alkyl group, C 2-4 alkenyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group and 5- to 8-membered heteroaryl group, and the groups are independently optionally further deuterium, halogen, hydroxy group, =O, cyano group, C 1-4 alkyl group, C 1-4 alkoxy group, C 3-6 cycloalkyl group, C 3-6 cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C 6- 8 aryl group, C 6-8 aryloxy group, 5- to 8-membered heteroaryl group, 5- to 8-membered heteroaryloxy group and -NR 16 R 17 and is substituted by one or more substituents selected from each R 15 is independently hydrogen, deuterium, hydroxy group, C 1-4 alkyl group, C 1-4 alkoxy group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, C 3-6 cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C 6-8 aryl group, C 6-8 aryloxy group, 5- to 8-membered heteroaryl group, 5- to 8-membered heteroaryloxy group and -NR 16 R 17 and the groups are independently optionally further deuterium, halogen, hydroxy group, =O, cyano group, C 1-4 alkyl group, C 1-4 alkoxy group, C 3-6 cycloalkyl group, C 3-6 cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C 6-8 aryl group, C 6-8 aryloxy group, 5- to 8-membered heteroaryl group, 5- to 8-membered heteroaryloxy group and -NR 16 R 17substituted by one or more substituents selected from each R 16 and R 17 is independently hydrogen, deuterium, a hydroxy group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, sulfinyl group, sulfonyl group, methylsulfonyl group, isopropylsulfonyl group, cyclopropylsulfonyl group, p-toluenesulfonyl group, aminosulfonyl group, dimethylaminosulfonyl group and C 1-4 alkanoyl group, and the groups are independently optionally further deuterium, halogen, hydroxy group, =O, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, halogen substituted C 1-4 alkyl group, deuterium substituted C 1-4 alkyl group, C 1-4 alkoxy group, C 3-6 cycloalkyl group, C 3-6 cycloalkoxy group, 3-6 membered heterocyclic group, 3-6 membered heterocyclic oxy group, C 6-8 aryl group, C 6-8 aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group, amino group, C 1-4 alkyl mono-substituted amino group, C 1-4 alkyl di-substituted amino group and C 1-4 alkanoyl group, and are substituted by one or more substituents selected from, or R 16 and R 17 together with the nitrogen atom directly connecting to them form a 4-8 membered heterocyclic group or a 5-8 membered heteroaryl group, and the 4-8 membered heterocyclic group or 5-8 membered heteroaryl group is optionally further deuterium, halogen, hydroxy group, =O, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, halogen substituted C 1-4 alkyl group, deuterium substituted C1-4 an alkyl group, C 1-4 an alkoxy group, C 3-6 a cycloalkyl group, C 3-6 a cycloalkoxy group, a 3- to 6-membered heterocyclic group, a 3- to 6-membered heterocyclic oxy group, C 6-8 an aryl group, C 6-8 an aryloxy group, a 5- to 8-membered heteroaryl group, a 5- to 8-membered heteroaryloxy group, an amino group, C 1-4 an alkyl mono-substituted amino group, C 1-4 an alkyl di-substituted amino group and C 1-4 is substituted by one or more substituents selected from an alkanoyl group.

[0022] More preferably, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound represented by the formula (I) has the structure of the compound represented by the following formula (II),

[0023]

Chemical formula

[0024] (wherein X 3 is CR 5 or N, X 4 is CR 6 or N, X 5 is CR 7 or N, X 6 is CR 8 or N, X 7 is CR 9 or N, R 1 is -(CR 11 R 12 ) m -R, or alternatively, R 1 and R 2 together with the nitrogen atom directly connecting them form a ring B, and the ring B is a 4- to 10-membered nitrogen-containing heterocyclic group or a 5- to 10-membered nitrogen-containing heteroaryl group, and the ring B is optionally further R, deuterium, halogen, cyano group, C 1-4 an alkyl group, C 2-4An alkenyl group, C 2-4 An alkynyl group, =O, =S, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 is substituted by one or more substituents selected from R has the following structure,

[0025] [Chemical formula] and

[0026] where Y 1 , Y 2 , Y 4 , Y 5 , Y 6 , Y 7 , Y 8 , Y 9 , Y 10 , Y 11 , Y 12 , Y 13 is each independently CR a or N, Y 3 is -O-, -S- or -NR a3 -, Z is -O-, -S-, -CR a1 R a2 -, -CR a1 R a2 -O- or -NR a3 -, p is 0, 1, 2 or 3, Each R ais independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 selected from, and said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, =O, =S, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , - P(O)(R 15 ) 2 , -NR 16 R17 、 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by one or more substituents selected from each R a1 and R a2 is independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 selected from, and said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen substituted C 1-4 alkyl group, deuterium substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, =O, =S, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14, -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 substituted by one or more substituents selected from each R a3 is independently hydrogen, deuterium, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 , -C(O)OR 14 , -C(O)SR 14 , -C(O)R 15 and -C(O)NR 16 R 17 selected from, and said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen substituted C 1-4 alkyl group, deuterium substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, =O, =S, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR16 R 17 and -N(R 16 )-C(O)R 15 substituted by one or more substituents selected from each R 2 is, independently of one another, hydrogen, deuterium, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group and 5- to 8-membered heteroaryl group, where said groups are, independently of one another, optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, halogen-substituted C 3-6 cycloalkyl group, halogen-substituted 3- to 6-membered heterocyclic group, halogen-substituted C 6-8 aryl group, halogen-substituted 5- to 8-membered heteroaryl group, C 1-4 alkyl-substituted C 3-6 cycloalkyl group, C 1-4 alkyl-substituted 3- to 6-membered heterocyclic group, C 1-4 alkyl-substituted C 6-8 aryl group, C 1-4 alkyl-substituted 5- to 8-membered heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, =O, =S, -SF 5 、-O-S(O) 2 R 13 、-S(O) r R 13 、-O-R 14 、-C(O)OR 14 、-C(O)SR 14 、-S-C(O)R 15 、-C(O)R 15 、-O-C(O)R 15 、-P(O)(R 15 ) 2 、-NR 16 R 17 、-C(O)NR 16 R17 and -N(R 16 )-C(O)R 15 substituted by one or more substituents selected from R 5 ,R 6 and R 7 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 ,-O-S(O) 2 R 13 ,-S(O) r R 13 ,-O-R 14 ,-C(O)OR 14 ,-C(O)SR 14 ,-S-C(O)R 15 ,-C(O)R 15 ,-O-C(O)R 15 ,-P(O)(R 15 ) 2 ,-NR 16 R 17 ,-C(O)NR 16 R 17 and -N(R 16 )-C(O)R 1 5 selected from R 8 and R 9 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 ,-O-S(O)2 R 13 、 -S(O) r R 13 、 -O-R 14 、 -C(O)OR 14 、 -C(O)SR 14 、 -S-C(O)R 15 、 -C(O)R 15 、 -O-C(O)R 15 、 -P(O)(R 15 ) 2 、 -NR 16 R 17 、 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 selected from each R 11 and R 12 is independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 、 -O-S(O) 2 R 13 、 -S(O) r R 13 、 -O-R 14 、 -C(O)OR 14 、 -C(O)SR 14 、 -S-C(O)R 15 、 -C(O)R 15 、 -O-C(O)R 15 、 -P(O)(R 15 ) 2 、 -NR 16 R 17 、 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 selected from wherein R 13 、 R 14 、 R 15 、 R16 , R 17 , r and m are as described for the compounds represented by formula (I)).

[0027] In a more preferred form, in the compound represented by formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound represented by formula (I) has the structure of the following formula (III 1 ) or formula (III 2 ), and

[0028] [Chemical formula]

[0029] (where each X 3 is independently CR 5 or N, and each X 4 is independently CR 6 or N, and each X 5 is independently CR 7 or N, and each X 6 is independently CR 8 or N, and In the structure of the compound represented by formula (III 2 ), ring B is a 4- to 10-membered nitrogen-containing heterocyclic group, and the 4- to 10-membered nitrogen-containing heterocyclic group is optionally further hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 1-4 alkoxy group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, -SF 5 and -NR 16 R 17 substituted by one or more substituents selected from, and each R is independently the following structure:

[0030] [Chemical formula] and

[0031] where Y 1 、Y 2 、Y 6 、Y 7 、Y 8 、Y 9 、Y 10 and Y 11 are each independently CR a or N, Y 3 is -O- or -S-, Z is -O-, -S-, -CH 2 - or -CH 2 -O-, p is 0, 1, 2 or 3, each R a is independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 、-O-R 14 、-C(O)OR 14 、-C(O)SR 14 、-C(O)R 15 、-O-C(O)R 15 and -NR 16 R 17 selected from, and said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen substituted C 1-4 alkyl group, deuterium substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, =O, =S, -SF 5 、-O-R 14 、-C(O)OR 14 、-C(O)R 15 、-O-C(O)R 15 and -NR16 R 17 substituted by one or more substituents selected from R 2 is hydrogen, deuterium, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group and 5-8 membered heteroaryl group, and said groups are each independently optionally further substituted by deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, halogen-substituted C 3-6 cycloalkyl group, halogen-substituted 3-6 membered heterocyclic group, halogen-substituted C 6-8 aryl group, halogen-substituted 5-8 membered heteroaryl group, C 1-4 alkyl-substituted C 3-6 cycloalkyl group, C 1-4 alkyl-substituted 3-6 membered heterocyclic group, C 1-4 alkyl-substituted C 6-8 aryl group, C 1-4 alkyl-substituted 5-8 membered heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, =O, =S, -SF 5 , -O-R 14 , -C(O)OR 14 , -C(O)R 15 , -O-C(O)R 15 and -NR 16 R 17 and may be substituted by one or more substituents selected from each R 5 , R 6 and R 7 is each independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C 1-4 alkyl group, C 1-4 alkoxy group, halogen-substituted C 1-4 alkyl group, halogen-substituted C 1-4An alkoxy group, deuterium-substituted C 1-4 An alkyl group, deuterium-substituted C 1-4 An alkoxy group, C 2-4 An alkenyl group, C 2-4 An alkynyl group, C 3-6 A cycloalkyl group, C 3-6 A cycloalkoxy group, a 3- to 6-membered heterocyclic group, a 3- to 6-membered heterocyclic oxy group, C 6-8 An aryl group, C 6-8 An aryloxy group, a 5- to 8-membered heteroaryl group, a 5- to 8-membered heteroaryloxy group, -SF 5 And -NR 16 R 17 Selected from Each R 8 Is independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C 1-4 An alkyl group, C 1-4 An alkoxy group, halogen-substituted C 1-4 An alkyl group, halogen-substituted C 1-4 An alkoxy group, deuterium-substituted C 1-4 An alkyl group, deuterium-substituted C 1-4 An alkoxy group, C 2-4 An alkenyl group, C 2-4 An alkynyl group, C 3-6 A cycloalkyl group, C 3-6 A cycloalkoxy group, a 3- to 6-membered heterocyclic group, a 3- to 6-membered heterocyclic oxy group, C 6-8 An aryl group, C 6-8 An aryloxy group, a 5- to 8-membered heteroaryl group, a 5- to 8-membered heteroaryloxy group, -SF 5 And -NR 16 R 17 Selected from Each R 11 And R 12 Is independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C 1-4 An alkyl group, C 1-4 An alkoxy group, halogen-substituted C 1-4 An alkyl group, halogen-substituted C 1-4 An alkoxy group, deuterium-substituted C 1-4 An alkyl group, deuterium substituted C 1-4 An alkoxy group, C 2-4An alkenyl group, C 2-4 An alkynyl group, C 3-6 A cycloalkyl group, C 3-6 A cycloalkoxy group, a 3- to 6-membered heterocyclic group, a 3- to 6-membered heterocyclic oxy group, C 6-8 An aryl group, C 6-8 An aryloxy group, a 5- to 8-membered heteroaryl group, a 5- to 8-membered heteroaryloxy group, -SF 5 And -NR 16 R 17 Selected from Here, R 14 、R 15 、R 16 And R 17 Is as described in the compound represented by formula (I)).

[0032] In a more preferred form, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, the "

[0033]

Chemical formula

[0034]

Chemical formula

[0035] Selected from Each X 6 Is independently CR 8 Or N, Each R 5 、R 6 And R 7 Are each independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C 1-4 An alkyl group, C 1-4 An alkoxy group, a halogen-substituted C 1-4 An alkyl group, a halogen-substituted C 1-4 An alkoxy group, a deuterium-substituted C 1-4 An alkyl group, a deuterium-substituted C 1-4 An alkoxy group, C 2-4 An alkenyl group, C2-4 alkynyl group, C 3-6 cycloalkyl group, C 3-6 cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C 6-8 aryl group, C 6-8 aryloxy group, 5- to 8-membered heteroaryl group, 5- to 8-membered heteroaryloxy group, -SF 5 , amino group, mono-C 1-4 alkyl-substituted amino group and bis-C 1-4 alkyl-substituted amino group selected from, each R 8 is independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C 1-4 alkyl group, C 1-4 alkoxy group, halogen-substituted C 1-4 alkyl group, halogen-substituted C 1-4 alkoxy group, deuterium-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkoxy group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, C 3-6 cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C 6-8 aryl group, C 6-8 aryloxy group, 5- to 8-membered heteroaryl group, 5- to 8-membered heteroaryloxy group, -SF 5 , amino group, mono-C 1-4 alkyl-substituted amino group and bis-C 1-4 alkyl-substituted amino group selected from.

[0036] In a more preferred form, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound represented by the formula (I) has the structure of the compound represented by the following formula (IV 1-1 ), (IV 1-2 ), (IV 2-1 ) or (IV 2-2 ), and

[0037]

Chemical formula

[0038] (Here, each X 4 is independently CR 6 or N, and each X 5 is independently CR 7 or N, each Y 6 and each Y 7 is independently CH or N, Z is O or CH 2 and p is 1 or 2, In the structure of the compound represented by formula (IV 2-1 ) or (IV 2-2 ), ring B together with the substituents thereon has the following structure:

[0039]

Chemical formula

[0040] each R' is independently hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxy group, methyl group, ethyl group, n-propyl group, isopropyl group, trifluoromethyl group, trideuteromethyl group, methoxy group, ethoxy group, cyclopropyl group and -SF 5 selected from, each R'' is independently hydrogen, deuterium, hydroxy group, methyl group, ethyl group, n-propyl group, isopropyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group selected from, each R 2 is independently hydrogen, deuterium, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azetidinyl group, tetrahydrofuranyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group and t Selected from a riazinyl group, said group may optionally further independently be deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteriomethyl group, dideuteriomethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azacyclopentyl group, tetrahydrofuranyl group, phenyl group, pyrazolyl group, 2-(trimethylsilyl)ethoxy group, methyl-substituted pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyridyl group, fluorine-substituted pyridyl group, pyridazinyl group, pyrimidinyl group, triazinyl group, =O, =S, -SF 5 substituted by one or more substituents selected from hydroxy group, methoxy group, ethoxy group, cyclopropoxy group, cyclobutoxy group, amino group, methylamino group and dimethylamino group, each R a is independently hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, methoxy group, ethoxy group, trifluoromethyl group, difluoromethyl group, trideuteriomethyl group, dideuteriomethyl group, trifluoromethoxy group, trideuteromethoxy group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, methyl-substituted cyclopropyl group, methyl-substituted cyclobutyl group, cyclopropoxy group, cyclobutoxy group, oxetanyl group, azetidinyl group, tetrahydropyrrolyl group, piperidinyl group, methyl-substituted piperidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyrimidinyl group, methyl-substituted pyrazolyl group, -SF 5 hydroxy group, amino group, methylamino group, dimethylamino group, dimethylaminomethyl group and dimethylaminoethyl group, each R 6is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxy group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, trideuteriomethyl group, trideuteromethoxy group and cyclopropyl group, each R 7 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxy group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, trideuteriomethyl group, trideuteromethoxy group and cyclopropyl group, each R 8 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxy group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, trideuteriomethyl group, trideuteromethoxy group and cyclopropyl group, R 11 and R 12 are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteriomethyl group and cyclopropyl group).

[0041] In a more preferred form, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, the structure contains

[0042]

Chemical formula

[0043]

Chemical formula

[0044] R 7 is selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteriomethyl group and cyclopropyl group, R 8 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group.

[0045] In a more preferred form, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, the formula (IV 1-2 ) and (IV 2-1 ) in the structure of the compound represented by "",

[0046]

Chemical Structure

[0047]

Chemical Structure

[0048] In the structure of the compound represented by the formula (IV 1-1 ), "",

[0049]

Chemical Structure

[0050]

Chemical Structure

[0051] Each R a is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, isopropyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group and -SF 5 selected from.

[0052] More preferably, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, each R 2 is independently selected from hydrogen, deuterium, methyl group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azetidinyl group, tetrahydrofuranyl group, pyrazolyl group, imidazolyl group, thiazolyl group, pyridyl group and pyrimidinyl group, and the group is independently optionally further substituted with one or more substituents selected from deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, trifluoromethyl group, difluoromethyl group, trideuteriomethyl group, dideuteriomethyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azetidinyl group, tetrahydrofuranyl group, pyrazolyl group, (2-(trimethylsilyl)ethoxy)methyl-substituted pyrazolyl group, imidazolyl group, thiazolyl group, pyridyl group, fluorine-substituted pyridyl group, pyrimidinyl group, methoxy group, ethoxy group and cyclopropoxy group.

[0053] More preferably, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, each R 2 is independently selected from hydrogen, deuterium, methyl group, ethyl group, trifluoromethyl group, trifluoroethyl group, trideuteriomethyl group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, cyclobutyl group or the structure of the substituent represented by the following:

[0054]

Chemical formula

[0055] Even more preferably, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound represented by the formula (I) is the following formula (V 1-1-1 ) or formula (V1-1-2 ) having the structure of the compound represented by

[0056] [Chemical Formula]

[0057] (where each Y 7 is independently CH or N, and each Z is independently O or CH 2 and each R a is independently hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF 5 selected from, each R 7 is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group, each R 8 is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group, where R 2 is as described in the compound represented by formula (I)).

[0058] Even more preferably, in the compound represented by formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound represented by formula (I) has the structure of the compound represented by the following formula (V 1-2-1 ) or formula (V 1-2-2 ),

[0059] [Chemical Formula]

[0060] (where each Y 6 and each Y 7 is independently CH or N, and Ra is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF 5 and is selected from R 7 is selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group, R 8 is selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group).

[0061] More preferably, in the compound represented by the formula (I), its stereoisomer, or its pharmaceutically acceptable salt, the compound represented by the formula (I) has the structure of the compound represented by the following formula (V 2-1-1 ) or formula (V 2-1-2 ),

[0062]

Chemical formula

[0063] (where each R a is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF 5 and is selected from each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group, each R 7 is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group, each R 8(each independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group).

[0064] Even more preferably, in the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound represented by the formula (I) has the structure of the following formula (V 2-2-1 ) or the formula (V 2-2-2 ) and has the structure of the compound represented by

[0065]

Chemical formula

[0066] (wherein each R a is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, methyl-substituted piperidinyl group, dimethylaminoethyl group and -SF 5 selected from, each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group, each R 7 is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group, each R 8 is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group).

[0067] Most preferably, the compound represented by the formula (I), its stereoisomer or its pharmaceutically acceptable salt includes, but is not limited to, the following compounds:

[0068]

Chem.

[0069] The second aspect of the present invention provides a pharmaceutical composition comprising a compound represented by formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The third aspect of the present invention provides the use of a compound represented by formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating MATP-related tumors.

[0070] More preferably, the tumor is selected from the group consisting of carcinoma, lymphoma, leukemia, osteoma, malignant teratoma, intraepithelial carcinoma, adenoma, fibroma, melanoma, fallopian tube cancer, bladder cancer, teratoma, fetal cancer, choriocarcinoma, lipoma, liver cancer, cholangiocarcinoma, lung cancer, gastric cancer, hemangioma, gallbladder cancer, cancer of the dilated portion, malignant melanoma, nevus, dysplastic nevus, myeloproliferative disease, Hodgkin's disease, chordoma, myxoma, rhabdomyoma, leiomyoma, error tumor, mesothelioma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, viper tumor, granuloma, xanthoma, Paget's disease, schwannoma, congenital tumor, meningioma, glioma, skin cancer, head and neck cancer, and sarcoma.

[0071] As a more preferred form, the cell tumor is selected from granulosa-theca cell tumor, Sertoli cell tumor, germ cell tumor, nephroblastoma, seminoma, hepatoblastoma, malignant fibrous histiocytoma, chondroblastoma, giant cell tumor, astrocytoma, medulloblastoma, glioblastoma multiforme, anaplastic glioma, retinoblastoma, squamous cell carcinoma, clear cell carcinoma, transitional cell carcinoma, interstitial cell carcinoma, and basal cell carcinoma, The lymphoma is selected from malignant lymphoma and non-Hodgkin lymphoma, The leukemia is selected from acute and chronic myeloid leukemia, acute lymphocytic leukemia, and chronic lymphocytic leukemia, The bone tumor is selected from osteochondroma, benign chondroma, osteoid osteoma, chondromatous pseudotumor, multiple myeloma, and skull tumor, The adenoma is selected from fibroadenoma, adenomatoid tumor, hepatocellular adenoma, bronchial adenoma, tubular adenoma, villous adenoma, breast cancer, pancreatic cancer, endometrial adenocarcinoma, prostate cancer, ductal adenocarcinoma, and colorectal adenocarcinoma, The fibroma is selected from fibroma, chondromyxofibroma, neurofibroma, and spinal neurofibroma, The myeloproliferative disease is selected from multiple myeloma and myelodysplastic syndrome, The lung cancer is selected from bronchogenic carcinoma and alveolar carcinoma, The sarcoma is selected from fibrosarcoma, sarcoma botryoides, angiosarcoma, Kaposi sarcoma, osteosarcoma, chondrosarcoma, Ewing sarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, and meningioma.

[0072] The present invention further relates to the compound represented by the formula (I), its stereoisomer, or its pharmaceutically acceptable salt, which is used as a PRMT5 inhibitor drug. The present invention further relates to the use of the compound represented by the formula (I), its stereoisomer, or its pharmaceutically acceptable salt in the manufacture of a drug for treating and / or preventing diseases mediated by PRMT5.

[0073] The present invention further relates to a method for treating and / or preventing a disease mediated by PRMT5, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound represented by the above formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0074] [Specific Embodiments] As a result of extensive and in-depth research, the inventors of the present application have for the first time developed a PRMT5 inhibitor having a structure represented by the following formula (I). A series of compounds of the present invention can be widely used in the manufacture of drugs for treating and / or preventing diseases mediated by PRMT5, and the development of a new generation of PRMT5 inhibitors is expected. Based on this, the present invention has been completed.

[0075] Special Note: Unless otherwise stated or specifically explained, the following terms used in the specification and claims have the following meanings. "Alkyl group" refers to a saturated aliphatic hydrocarbon group containing a straight-chain or branched-chain, preferably a straight-chain alkyl group and a branched-chain alkyl group containing 1 to 10 or 1 to 6 or 1 to 4 carbon atoms, including a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, an s-butyl group, an n-pentyl group, a 1,1-dimethylpropyl group, a 1,2-dimethylpropyl group, a 2,2-dimethylpropyl group, a 1-ethylpropyl group, a 2-methylbutyl group, a 3-methylbutyl group, an n-hexyl group, a 1-ethyl-2-methylpropyl group, a 1,1,2-trimethylpropyl group, a 1,1-dimethylbutyl group, a 1,2-dimethylbutyl group, a 2,2-dimethylbutyl group, a 1,3-dimethylbutyl group, a 2-ethylbutyl group, a 2-methylpentyl group, a 3-methylpentyl group, a 4-methylpentyl group, a 2,3-dimethylbutyl group, an n-heptyl group, a 2-methylhexyl group, a 3-methylhexyl group, a 4-methylhexyl group, a 5-methylhexyl group, a 2,3-dimethylpentyl group, a 2,4-dimethylpentyl group, a 2,2-dimethylpentyl group, a 3,3-dimethylpentyl group, a 2-ethylpentyl group, a 3-ethylpentyl group, an n-octyl group, a 2,3-dimethylhexyl group, a 2,4-dimethylhexyl group, a 2,5-dimethylhexyl group, a 2,2-dimethylhexyl group, a 3,3-dimethylhexyl group, a 4,4-dimethylhexyl group, a 2-ethylhexyl group, a 3-ethylhexyl group, a 4-ethylhexyl group, a 2-methyl-2-ethylpentyl group, a 2-methyl-3-ethylpentyl group or various branched-chain isomers thereof, etc., but not limited thereto. "C 1-10 alkyl group" is a straight-chain alkyl group and a branched-chain alkyl group containing 1 to 10 carbon atoms, "C 1-4 alkyl group" is a straight-chain alkyl group and a branched-chain alkyl group containing 1 to 4 carbon atoms, "C 0-8 alkyl group" is a straight-chain alkyl group and a branched-chain alkyl group containing 0 to 8 carbon atoms, "C 0-4 alkyl group" is a straight-chain alkyl group and a branched-chain alkyl group containing 0 to 4 carbon atoms.

[0076] The alkyl group may be optionally substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cyc loalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 , -C 0-8 alkyl-O-S(O) 2 R 13 , -C 0-8 alkyl-S(O) r R 13 , -C 0-8 alkyl-O-R 14 , -C 0-8 alkyl-C(O)OR 14 , -C 0-8 alkyl-C(O)SR 14 , -C 0-8 alkyl-S-C(O)R 15 , -C 0-8 alkyl-C(O)R 15 , -C 0-8 alkyl-O-C(O)R 15 , -C 0-8 alkyl-P(O)(R 15 ) 2 , -C 0-8 alkyl-NR 16 R 17 , -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 selected from one or more (preferably one, two, three or four) groups.

[0077] "Cycloalkyl group" or "carbocyclic ring" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, and the partially unsaturated cyclic hydrocarbon means that the cyclic hydrocarbon may contain one or more (preferably one, two or three) double bonds, but does not have a completely conjugated π-electron system. The cycloalkyl group is divided into a monocyclic cycloalkyl group and a polycyclic cycloalkyl group, and is preferably a cycloalkyl group containing 3 to 12 or 3 to 8 or 3 to 6 carbon atoms. For example, " 3-12 Cycloalkyl group" refers to a cycloalkyl group containing 3 to 12 carbon atoms, " 4-8 Cycloalkyl group" refers to a cycloalkyl group containing 4 to 8 carbon atoms, " 3-8 Cycloalkyl group" refers to a cycloalkyl group containing 3 to 8 carbon atoms, " 3-6 Cycloalkyl group" refers to a cycloalkyl group containing 3 to 6 carbon atoms. Here, The monocyclic cycloalkyl group includes, but is not limited to, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclopentenyl group, a cyclohexyl group, a cyclohexenyl group, a cyclohexadienyl group, a cycloheptyl group, a cycloheptatrienyl group, a cyclooctyl group, etc.

[0078] The polycyclic cycloalkyl group includes spiro ring, fused ring and bridged ring cycloalkyl groups. "Spirocycloalkyl group" refers to a polycyclic group that shares one carbon atom (referred to as a spiro atom) between monocyclic rings. These groups may contain one or more (preferably one, two or three) double bonds, but do not have a completely conjugated π-electron system. According to the number of spiro atoms shared between rings, the spirocycloalkyl group is divided into a monospirocycloalkyl group, a bisspirocycloalkyl group or a polyspirocycloalkyl group. The spirocycloalkyl group includes, but is not limited to, the following:

[0079]

Chemical formula

[0080] "Condensed cycloalkyl group" refers to a fully carbon polycyclic group in which each ring in the system shares a pair of carbon atoms adjacent to another ring in the system, and one or more (preferably one, two or three) of the rings therein may contain one or more double bonds, but there is no ring having a fully conjugated π - electron system. It may be divided into bicyclic, tricyclic, tetracyclic or polycyclic condensed cycloalkyl groups according to the number of constituent rings, and the condensed cycloalkyl group includes, but is not limited to, the following:

[0081]

Chem.

[0082] "Bridged cycloalkyl group" refers to a fully carbon polycyclic group in which two carbon atoms that are not directly connected to each other in any two rings are shared, and these groups may contain one or more (preferably one, two or three) double bonds, but there is no ring having a fully conjugated π - electron system. It may be divided into bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyl groups according to the number of constituent rings, and the bridged cycloalkyl group includes, but is not limited to, the following:

[0083]

Chem.

[0084] The ring of the cycloalkyl group may be condensed with the ring of an aryl group, a heteroaryl group or a heterocycloalkyl group. Here, the ring connected to the parent structure is a cycloalkyl group, including, but not limited to, an indanyl group, a tetrahydronaphthyl group, a benzocycloheptyl group, etc.

[0085] The "cycloalkyl group" or "carbocyclic ring" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen - substituted C 1-10 alkyl group, deuterium - substituted C1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 , -C 0-8 alkyl-O-S(O) 2 R 13 , -C 0-8 alkyl-S(O) r R 13 , -C 0-8 alkyl-O-R 14 , -C 0-8 alkyl-C(O)OR 14 , -C 0-8 alkyl-C(O)SR 14 , -C 0-8 alkyl-S-C(O)R 15 , -C 0-8 alkyl-C(O)R 15 , -C 0-8 alkyl-O-C(O)R 15 , -C 0-8 alkyl-P(O)(R 15 ) 2 , -C 0-8 alkyl-NR 16 R 17 , -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 is one or more (preferably one, two, three, or four) groups selected from

[0086] "Heterocyclic group" or "heterocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, and the partially unsaturated cyclic hydrocarbon may contain one or more (preferably one, two, or three) double bonds, but does not have a completely conjugated π electron system, and one or more (preferably one, two, three, or four) ring atoms in the heterocyclic group are N, O, N·O, or S(O)r (Here, r is an integer of 0, 1, or 2), and it is selected from heteroatoms, does not contain a ring moiety of -O-O-, -O-S- or -S-S-, and the remaining ring atoms are carbon. Preferably, it contains 3 to 12 or also a heterocyclic group containing 3 to 8 or 3 to 6 ring atoms. For example, "3-6 membered heterocyclic group" refers to a heterocyclic group containing 3 to 6 ring atoms, "3-8 membered heterocyclic group" refers to a heterocyclic group containing 3 to 8 ring atoms, "4-8 membered heterocyclic group" refers to a heterocyclic group containing 4 to 8 ring atoms, "4-10 membered heterocyclic group" refers to a heterocyclic group containing 4 to 10 ring atoms, "5-8 membered heterocyclic group" refers to a heterocyclic group containing 5 to 8 ring atoms, and "3-12 membered heterocyclic group" refers to a heterocyclic group containing 3 to 12 ring atoms.

[0087] Monocyclic heterocyclic groups include, but are not limited to, pyrrolidinyl group, piperidinyl group, piperazinyl group, morpholinyl group, thiomorpholinyl group, homopiperazinyl group, oxetanyl group, tetrahydrofuranyl group, etc.

[0088] Polycyclic heterocyclic groups include spiro ring, fused ring and bridged ring heterocyclic groups. "Spiro heterocyclic group" refers to a polycyclic heterocyclic group that shares one atom (called a spiro atom) between monocyclic rings, and one or more (preferably 1, 2, 3 or 4) of the ring atoms therein are N, O, N·O or S(O) r (Here, r is an integer of 0, 1, or 2), selected from heteroatoms, and the remaining ring atoms are carbon. These groups may contain one or more double bonds (preferably 1, 2 or 3), but there is no ring having a completely conjugated π electron system. Depending on the number of spiro atoms shared between rings, spiro heterocyclic groups are divided into monospiro heterocyclic groups, bisspiro heterocyclic groups or polysspiro heterocyclic groups. Spiro heterocyclic groups include, but are not limited to, the following:

[0089]

Chemical formula

[0090] "Condensed heterocyclic group" refers to a polycyclic heterocyclic group in which each ring in the system shares a pair of atoms adjacent to another ring in the system. One or more (preferably one, two, three or four) rings may contain one or more (preferably one, two or three) double bonds, but there is no ring having a completely conjugated π - electron system, and one or more (preferably one, two, three or four) ring atoms therein are selected from heteroatoms of N, O, N·O or S(O) r (where r is an integer of 0, 1, 2), and the remaining ring atoms are carbon. It may be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused heterocycloalkyl groups according to the number of constituent rings. The condensed heterocyclic group includes, but is not limited to, the following:

[0091]

Chemical formula

[0092] "Bridged heterocyclic group" refers to a polycyclic heterocyclic group in which two non - directly - connected rings share two atoms. These groups may contain one or more (preferably one, two or three) double bonds, but there is no ring having a completely conjugated π - electron system, and one or more (preferably one, two, three or four) ring atoms therein are selected from heteroatoms of N, O, N·O or S(O) r (where r is an integer of 0, 1, 2), and the remaining ring atoms are carbon. It may be divided into bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocyclic groups according to the number of constituent rings. The bridged heterocyclic group includes, but is not limited to, the following:

[0093]

Chemical formula

[0094] The rings of the heterocyclic group may be condensed with the rings of an aryl group, a heteroaryl group or a cycloalkyl group. Here, the ring connected to the parent structure is a heterocyclic group, including, but not limited to, the following:

[0095] [Chemistry]

[0096] The "heterocyclic ring group" or "heterocyclic ring" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic ring group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 , -C 0-8 alkyl -O-S(O) 2 R 13 , -C 0-8 alkyl-S(O) r R 13 , -C 0-8 alkyl-O-R 14 , -C 0-8 alkyl-C(O)OR 14 , -C 0-8 alkyl-C(O)SR 14 , -C 0-8 alkyl-S-C(O)R 15 , -C 0-8 alkyl-C(O)R 15 , -C 0-8 alkyl-O-C(O)R 15 , -C 0-8 alkyl-P(O)(R 15 ) 2 , -C 0-8 alkyl-NR 16 R 17 , -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15One or more (preferably one, two, three or four) groups selected from

[0097] An "aryl group" or an "aromatic ring" is a group of all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent carbon atom pairs) groups, and refers to a polycyclic (i.e., a ring having adjacent carbon atom pairs) group having a conjugated π electron system, preferably an all-carbon aryl group containing 6 to 10 or 6 to 8 carbon atoms. For example, "C 6-10 An "aryl group" refers to an all-carbon aryl group containing 6 to 10 carbon atoms, including, but not limited to, a phenyl group and a naphthyl group. "C 6-8 An "aryl group" refers to an all-carbon aryl group containing 6 to 8 carbon atoms. The ring of the aryl group may be fused to the ring of a heteroaryl group, a heterocyclic group or a cycloalkyl group. Here, the ring linked to the parent structure is the ring of the aryl group, including, but not limited to, the following:

[0098]

Chemical formula

[0099] An "aryl group" or an "aromatic ring" may be substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 、-C 0-8 alkyl-O-S(O) 2 R 13 、-C 0-8 alkyl-S(O) r R 13 、-C 0-8Alkyl-O-R 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-S-C(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-O-C(O)R 15 , -C 0-8 Alkyl-P(O)(R 15 ) 2 , -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 And -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Is one or more (preferably one, two, three or four) groups selected from

[0100] The "heteroaryl group" or "heteroaryl ring" refers to a heteroaromatic system containing one or more (preferably one, two, three or four) heteroatoms, and the heteroatoms are N, O, N·O and S(O) r (where r is an integer of 0, 1, 2), and is preferably a heteroaromatic system containing 5 to 10 or 5 to 8 or 5 to 6 ring atoms. For example, the "5-8 membered heteroaryl group" refers to a heteroaromatic System, the "5-10 membered heteroaryl group" refers to a heteroaromatic system containing 5 to 10 ring atoms, and includes, but is not limited to, a furyl group, a thienyl group, a pyridyl group, a pyrrolyl group, an N-alkylpyrrolyl group, a pyrimidinyl group, a pyrazinyl group, an imidazolyl group, a tetrazolyl group, etc. The ring of the heteroaryl group may be condensed with the ring of an aryl group, a heterocyclic group or a cycloalkyl group. Here, the ring connected to the parent structure is the ring of the heteroaryl group, and includes, but is not limited to, the following:

[0101] [Chemistry]

[0102] The "heteroaryl group" or "heteroaryl ring" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 , -C 0-8 alkyl-O-S(O) 2 R 13 , -C 0-8 alkyl-S(O) r R 13 , -C 0-8 alkyl-O-R 14 , -C 0-8 alkyl-C(O)OR 14 , -C 0-8 alkyl-C(O)SR 14 , -C 0-8 alkyl-S-C(O)R 15 , -C 0-8 alkyl-C(O)R 15 , -C 0-8 alkyl-O-C(O)R 15 , -C 0-8 alkyl-P(O)(R 15 ) 2 , -C 0-8 alkyl-NR 16 R 17 , -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15One or more (preferably one, two, three or four) groups selected from

[0103] "Alkenyl group" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon double bond, preferably a linear or branched alkenyl group containing 2 to 10 or 2 to 4 carbon atoms. For example, "C 2-10 Alkenyl group" is a linear or branched alkenyl group containing 2 to 10 carbon atoms, and "C 2-4 Alkenyl group" is a linear or branched alkenyl group containing 2 to 4 carbon atoms. It includes, but is not limited to, vinyl group, 1-propenyl group, 2-propenyl group, 1-butenyl group, 2-butenyl group or 3-butenyl group, etc.

[0104] "Alkenyl group" may be substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 Alkyl group, halogen-substituted C 1-10 Alkyl group, deuterium-substituted C 1-10 Alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12 Cycloalkyl group, 3-12 membered heterocyclic group, C 6-10 Aryl group, 5-10 membered heteroaryl group, =O, =S, -C 0-8 Alkyl-SF 5 、-C 0-8 Alkyl-O-S(O) 2 R 13 、-C 0-8 Alkyl-S(O) r R 13 、-C 0-8 Alkyl-O-R 14 、-C 0-8 Alkyl-C(O)OR 14 、-C 0-8 Alkyl-C(O)SR 14 、-C 0-8 Alkyl-S-C(O)R 15 、-C 0-8alkyl-C(O)R 15 , -C 0-8 alkyl-O-C(O)R 15 , -C 0-8 alkyl-P(O)(R 15 ) 2 , -C 0-8 alkyl-NR 16 R 17 , -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0 -8 alkyl-N(R 16 )-C(O)R 15 is one or more (preferably one, two, three or four) groups selected from.

[0105] The "alkynyl group" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon triple bond, preferably a linear or branched alkynyl group containing 2 to 10 or 2 to 4 carbon atoms. For example, the "C 2-10 alkynyl group" is a linear or branched alkynyl group containing 2 to 10 carbon atoms, and the "C 2-4 alkynyl group" is a linear or branched alkynyl group containing 2 to 4 carbon atoms. It includes, but is not limited to, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group or 3-butynyl group, etc.

[0106] The "alkynyl group" may be substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C0-8 Alkyl-SF 5 , -C 0-8 Alkyl-O-S(O) 2 R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-O-R 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-S-C(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-O-C(O)R 15 , -C 0-8 Alkyl-P(O)(R 15 ) 2 , -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 is one or more (preferably one, two, three or four) groups selected from

[0107] "Alkoxy group" refers to an -O-alkyl group, where the definition of the alkyl group is as described above. For example, "C 1-10 alkoxy group" refers to an alkyloxy group containing 1 to 10 carbon atoms, "C 1-4 alkoxy group" refers to an alkyloxy group containing 1 to 4 carbon atoms, "C 1-2 alkoxy group" refers to an alkyloxy group containing 1 to 2 carbon atoms, and includes, but is not limited to, methoxy group, ethoxy group, propoxy group, butoxy group, etc.

[0108] The "alkoxy group" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 、-C 0-8 alkyl-O-S(O) 2 R 13 、-C 0-8 alkyl-S(O) r R 13 、-C 0-8 alkyl-O-R 14 、-C 0-8 alkyl-C(O)OR 14 、-C 0-8 alkyl-C(O)SR 14 、-C 0-8 alkyl-S-C(O)R 15 、-C 0-8 alkyl-C(O)R 15 、-C 0-8 alkyl-O-C(O)R 15 、-C 0-8 alkyl-P(O)(R 15 ) 2 、-C 0-8 alkyl-NR 16 R 17 、-C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 selected from one or more (preferably one, two, three or four) groups.

[0109] The "cycloalkoxy group" or "cycloalkyloxy group" refers to an -O-cycloalkyl group, where the definition of the cycloalkyl group is as described above. For example, "C 3-12 cycloalkoxy group" refers to a cycloalkyloxy group containing 3 to 12 carbon atoms, and "C 3-6 cycloalkoxy group" refers to a cycloalkyloxy group containing 3 to 6 carbon atoms and includes, but is not limited to, cyclopropoxy group, cyclobutoxy group, cyclopentoxy group, cyclohexyloxy group, etc.

[0110] The "cycloalkoxy group" or "cycloalkyloxy group" may be either optionally substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 、-C 0-8 alkyl-O-S(O) 2 R 13 、-C 0-8 alkyl-S(O) r R 13 、-C 0-8 alkyl-O-R 14 、-C 0-8 alkyl-C(O)OR 14 、-C 0-8 alkyl-C(O)SR 14 、-C 0-8 alkyl-S-C(O)R 15 、-C 0-8 alkyl-C(O)R 15 、-C 0-8 alkyl-O-C(O)R 15 、-C 0-8 alkyl-P(O)(R 15) 2 、 -C 0-8 alkyl-NR 16 R 17 、 -C 0-8 alkyl-C(O)NR 16 R 17 and -C 0-8 alkyl-N(R 16 )-C(O)R 15 is one or more (preferably one, two, three, or four) groups selected from.

[0111] The "heterocyclyloxy group" or "heterocyclic oxy group" refers to -O-heterocyclic group, where the definition of the heterocyclic group is as described above, and includes, but is not limited to, azetidinyl oxy group, oxetanyl oxy group, azacyclopentyl oxy group, azacyclohexyl oxy group, oxacyclohexyl oxy group, etc.

[0112] The "heterocyclyloxy group" or "heterocyclic oxy group" may be optionally substituted or unsubstituted. When substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12 cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 aryl group, 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 alkyl-SF 5 、 -C 0-8 alkyl-O-S(O) 2 R 13 、 -C 0-8 alkyl-S(O) r R 13 、 -C 0-8 alkyl-O-R 14 、 -C 0-8 alkyl-C(O)OR 14 、 -C 0-8 alkyl-C(O)SR 14 、 -C 0-8Alkyl-S-C(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-O-C(O)R 15 , -C 0-8 Alkyl-P(O)(R 15 ) 2 , -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 is one or more (preferably one, two, three or four) groups selected from.

[0113] "C 1-10 alkanoyl group" refers to a monovalent atomic group remaining after removing a hydroxy group from C 1-10 alkanoic acid, and is usually also represented as "C 0-9 alkyl-C(O)-". For example, "C 1 alkyl-C(O)-" refers to an acetyl group, "C 2 alkyl-C(O)-" refers to a propionyl group, and "C 3 alkyl-C(O)-" refers to a butyryl group or an isobutyryl group.

[0114] "-C 0-8 alkyl-O-S(O) 2 R 13 " refers to a group in which the oxygen atom in -O-S(O) 2 R 13 is linked to a C 0-8 alkyl group, where the definition of the C 0-8 alkyl group is as described above.

[0115] "-C 0-8 alkyl-S(O) r R 13 " refers to a group in which the sulfur atom in -S(O) r R 13 is linked to a C 0-8Refers to those linked to an alkyl group, where C 0-8 The definition of the alkyl group is as described above.

[0116] 「-C 0-8 alkyl - O - R 14 」 means that the oxygen atom in -O - R 14 is linked to a C 0-8 alkyl group, where C 0-8 The definition of the alkyl group is as described above. 「-C 0-8 alkyl - C(O)OR 14 」 means that the carbonyl group in -C(O)OR 14 is linked to a C 0-8 alkyl group, where C 0-8 The definition of the alkyl group is as described above.

[0117] 「-C 0-8 alkyl - C(O)SR 14 」 means that the carbonyl group in -C(O)SR 14 is linked to a C 0-8 alkyl group, where C 0-8 The definition of the alkyl group is as described above.

[0118] 「-C 0-8 alkyl - S - C(O)R 15 」 means that the sulfur atom in -S - C(O)R 15 is linked to a C 0-8 alkyl group, where C 0-8 The definition of the alkyl group is as described above.

[0119] 「-C 0-8 alkyl - C(O)R 15 」 means that the carbonyl group in -C(O)R 15 is linked to a C 0-8 alkyl group, where C 0-8 The definition of the alkyl group is as described above.

[0120] 「-C 0-8 alkyl - O - C(O)R 15 」 means -O - C(O)R15 in which the oxygen atom is bonded to a C 0-8 alkyl group, where the definition of the C 0-8 alkyl group is as described above.

[0121] 「-C 0-8 alkyl-P(O)(R 15 ) 2 」 means that the phosphorus atom in -P(O)(R 15 ) 2 is bonded to a C 0-8 alkyl group, where the definition of the C 0-8 alkyl group is as described above.

[0122] 「-C 0-8 alkyl-NR 16 R 17 」 means that the nitrogen atom in -NR 16 R 17 is bonded to a C 0-8 alkyl group, where the definition of the C 0-8 alkyl group is as described above.

[0123] 「-C 0-8 alkyl-C(O)NR 16 R 17 」 means that the carbonyl group in -C(O)NR 16 R 17 is bonded to a C 0-8 alkyl group, where the definition of the C 0-8 alkyl group is as described above.

[0124] 「-C 0-8 alkyl-N(R 16 )-C(O)R 15 」 means that the nitrogen atom in -N(R 16 )-C(O)R 15 is bonded to a C 0-8 alkyl group, where the definition of the C 0-8 alkyl group is as described above.

[0125] 「Halogen-substituted C 1-10"Alkyl group" refers to an alkyl group having 1 to 10 carbon atoms in which a hydrogen atom in the alkyl group is arbitrarily substituted with an atom of fluorine, chlorine, bromine, or iodine, including, but not limited to, a difluoromethyl group, a dichloromethyl group, a dibromomethyl group, a trifluoromethyl group, a trichloromethyl group, a tribromomethyl group, etc.

[0126] "Halogen-substituted C 1-10 "Alkoxy group" refers to an alkoxy group having 1 to 10 carbon atoms in which a hydrogen atom in the alkyl group is arbitrarily substituted with a fluorine, chlorine, bromine, or iodine atom. It includes, but is not limited to, a difluoromethoxy group, a dichloromethoxy group, a dibromomethoxy group, a trifluoromethoxy group, a trichloromethoxy group, a tribromomethoxy group, etc.

[0127] "Deuterium-substituted C 1-10 "Alkyl group" refers to an alkyl group having 1 to 10 carbon atoms in which a hydrogen atom in the alkyl group is arbitrarily substituted with a deuterium atom. It includes, but is not limited to, a monodeuteromethyl group, a dideuteromethyl group, a trideuteromethyl group, etc.

[0128] "Halogen" refers to fluorine, chlorine, bromine, or iodine, "EA" refers to ethanol, "PE" refers to petroleum ether, "EtOAc" refers to ethyl acetate, "DCM" refers to dichloromethane, "DMSO" refers to dimethyl sulfoxide, "Cs 2 CO 3 " refers to cesium carbonate, "ACN" refers to acetonitrile, "Pd(OH) 2 " refers to palladium hydroxide on carbon, "MeOH" refers to methanol, "rt" refers to room temperature, "1,2-dichlorobenzene" refers to 1,2-dichlorobenzene, "N,N-dimethylaniline" refers to N,N-dimethylaniline, "POCl 3"PCl₃" refers to phosphorus oxychloride, "DIPEA" refers to N,N - diisopropylethylamine, "NMP" refers to N - methylpyrrolidone, "TFA" refers to trifluoroacetic acid, "LiOH" refers to lithium hydroxide, "THF" refers to tetrahydrofuran, "PyBrOP" refers to bromotripyrrolidinophosphonium hexafluorophosphate, and "DMA" refers to N,N - dimethylacetamide.

[0129] "Optional" or "optionally" means that the event or situation described thereafter may or may not occur, and this description includes both the case where the event or situation occurs and the case where it does not occur, that is, both the case where substitution occurs and the case where substitution does not occur. For example, "a heterocyclic group optionally substituted with an alkyl group" means that an alkyl group may or may not be present, and this description includes the case where the heterocyclic group is substituted with an alkyl group and the case where the heterocyclic group is not substituted with an alkyl group.

[0130] "Substituted" means that one or more "hydrogen atoms" in a group are independently substituted by an appropriate number of substituents. Of course, the substituents are only at their chemically possible positions and are consistent with the chemical valence bond theory, and those skilled in the art can confirm whether substitution is possible or not without much effort (by experiment or theory). For example, an amino group or a hydroxy group having free hydrogen may be unstable when bonded to a carbon atom having an unsaturated bond (such as an olefin).

[0131] "Stereoisomer" has the English name "stereoisomer" and refers to isomers formed by differences in the spatial arrangement of atoms in a molecule. It may be divided into two types: cis-trans isomers and enantiomers, or it may also be divided into two types: enantiomers and diastereomers. Stereoisomers formed by the rotation of single bonds are called conformational stereo-isomers and may also be called rotamers. Stereoisomers formed due to bond length, bond angle, the presence of double bonds or rings in the molecule, etc. are called configuration stereo-isomers, and configuration stereo-isomers are further divided into two types. Here, isomers formed by the inability of double bonds or single bonds of ring-constituting carbon atoms to rotate freely are geometric isomers, also called cis-trans isomers, and are divided into two types of configurations: Z and E. For example, cis-2-butene and trans-2-butene are a pair of geometric isomers, and stereoisomers with different optical activity properties formed by the absence of an axis of symmetry in the molecule are called optical isomers and are divided into R and S configurations. The "stereoisomer" described in the present invention may be understood to include one or more of the above-mentioned enantiomers, configuration stereo-isomers, and conformational stereo-isomers unless otherwise specified.

[0132] "Pharmaceutically acceptable salts" refer to pharmaceutically acceptable acid addition salts in the present invention and include inorganic acid salts and organic acid salts, and these salts can be produced by known methods in this field.

[0133] "Drug composition" refers to a mixture of one or more compounds described in this specification or their physiologically / pharmaceutically acceptable salts or prodrugs and other chemical components, and other components, such as physiologically / pharmaceutically acceptable carriers and excipients. The drug composition is for promoting administration to a living body, contributing to the absorption of the active ingredient, and further exerting biological activity.

[0134] The present invention will be described in more detail and comprehensively in conjunction with the following examples, but it is by no means intended to limit the present invention, nor is the present invention limited only to the content of the examples. The structure of the compounds of the present invention is confirmed by nuclear magnetic resonance (NMR) and / or liquid chromatography mass spectrometry (LC-MS). The chemical shift (δ) of NMR is shown in parts per million (ppm). The NMR measurement uses a Bruker AVANCE-400 / 500 nuclear magnetic resonance apparatus, and the solvent for the measurement is deuterated dimethyl sulfoxide (DMSO-d 6 ), deuterated methanol (MeOH-d 4 ), and deuterated chloroform (CDCl 3 ), and the internal standard is tetramethylsilane (TMS).

[0135] The measurement of liquid chromatography mass spectrometry LC-MS uses an Agilent 6120 mass spectrometer. The HPLC measurement uses an Agilent 1200DAD high-pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high-pressure liquid chromatograph (Gimini C18 150×4.6 mm column).

[0136] The silica gel plate for thin layer chromatography uses a silica gel plate of Yantai Huanghai HSGF254 or Qingdao GF254. The specification used for TLC is 0.15 mm to 0.20 mm, and the specification used for the separation and purification of products by thin layer chromatography is 0.4 mm to 0.5 mm. Column chromatography generally uses silica gel of 200-300 mesh of Yantai Huanghai silica gel as the carrier.

[0137] The starting materials in the examples of the present invention are known and can be purchased from the market, or can be synthesized by methods known in this field or according thereto. Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in an atmosphere of dry nitrogen gas or argon gas, the solvent is a dry solvent, and the unit of reaction temperature is degrees Celsius (°C).

[0138] I. Preparation of Intermediate Preparation of Intermediate 1, 4-Amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic Acid

[0139]

Chemical formula

[0140] First Step: Synthesis of Methyl 3-(2-Methyl-1H-imidazol-1-yl)-4-nitrobenzoate

[0141]

Chemical formula

[0142] Methyl 3-Fluoro-4-nitrobenzoate (1.5 g, 7.54 mmol) and 2-Methyl-1H-imidazole (0.74 g, 9.05 mmol) were dissolved in acetonitrile (20 mL), cesium carbonate (3.69 g, 11.31 mmol) was added, and the mixture was stirred at 80 °C overnight. After completion of the reaction, water was added to quench the reaction, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain methyl 3-(2-methyl-1H-imidazol-1-yl)-4-nitrobenzoate (1.97 g, 100%), which was used directly in the next step. MS m / z (ESI): 262 [M+H] + 。

[0143] Second Step: Synthesis of Methyl 4-Amino-3-(2-methyl-1H-imidazol-1-yl)benzoate

[0144]

Chemical formula

[0145] Methyl 3-(2-methyl-1H-imidazol-1-yl)-4-nitrobenzoate (1.97 g, 7.54 mmol) was dissolved in methanol (30 mL), palladium hydroxide (0.4 g, 20% w / w) was added, and the mixture was stirred overnight at room temperature. After completion of the reaction, it was filtered and concentrated, and separated by silica gel column chromatography [5% methanol-dichloromethane system] to obtain methyl 4-amino-3-(2-methyl-1H-imidazol-1-yl)benzoate (800 mg, 46%). MS m / z (ESI): 232 [M+H] + 。

[0146] Third step: Synthesis of methyl 1-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate

[0147]

Chemical formula

[0148] Methyl 4-amino-3-(2-methyl-1H-imidazol-1-yl)benzoate (800 mg, 3.46 mmol) and di(1H-imidazol-1-yl)methanone (729 mg, 4.50 mmol) were placed in 1,2-dichlorobenzene (30 mL), heated to 160-170 °C, and stirred at this temperature for 3 hours. After cooling, it was concentrated to remove the solvent, slurried in methanol for 10 minutes, filtered and dried to obtain methyl 1-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate (680 mg, 76%). MS m / z (ESI): 258 [M+H] + 。

[0149] Fourth step: Synthesis of methyl 4-chloro-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate

[0150] [Chemistry]

[0151] Methyl 1-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate (680 mg, 2.64 mmol) was placed in phosphorus oxychloride (50 mL), N,N-dimethylaniline (115.9 mg, 0.53 mmol) was added, heated to 120 °C, stirred overnight. Since the reaction of some raw materials was not complete, after cooling, it was concentrated, quenched with ice water in an ice-water bath, extracted three times with dichloromethane. The organic phases were combined, washed with saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and then separated by silica gel column chromatography [40 - 60% ethyl acetate - petroleum ether system] to obtain methyl 4-chloro-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (460 mg, 63%). MS m / z (ESI): 276 [M+H] + .

[0152] Step 5: Synthesis of methyl 4-((2,4-dimethoxybenzyl)amino)-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate

[0153] [Chemistry]

[0154] Methyl 4-chloro-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (460 mg, 1.67 mmol) was dissolved in N-methylpyrrolidone (8 mL), (2,4-dimethoxybenzyl)amino (646 mg, 5.01 mmol) was added, and the mixture was heated to 110 °C and stirred for 3 hours. When the reaction was completed, water was added to quench it, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography [9% methanol-dichloromethane system] to obtain methyl 4-((2,4-dimethoxybenzyl)amino)-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (6 05 mg, 89%). MS m / z (ESI): 407 [M+H] + .

[0155] Sixth step: Synthesis of methyl 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate

[0156] [Chemical formula]

[0157] Methyl 4-((2,4-dimethoxybenzyl)amino)-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (330 mg, 0.81 mmol) was dissolved in trifluoroacetic acid (10 mL), stirred at 60 °C for 6 hours, concentrated after the reaction was completed, an appropriate amount of water was added, and the pH was adjusted to about 6 with an aqueous sodium hydrogen carbonate solution. After filtration, it was dried to obtain methyl 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (370 mg of crude product). MS m / z (ESI): 257 [M+H] + .

[0158] Seventh step: Synthesis of 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid

[0159] [Chemical]

[0160] Methyl 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (370 mg, 0.81 mmol) was dissolved in methanol (10 mL) and tetrahydrofuran (10 mL), lithium hydroxide monohydrate (102 mg, 2.43 mmol) was added, and the mixture was stirred at 50 °C overnight. After completion of the reaction, it was concentrated, an appropriate amount of water was added, and the pH was adjusted to about 6 with dilute hydrochloric acid. It was filtered, and the filter cake was washed several times with water and dried to obtain 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid (150 mg, 76%). MS m / z (ESI): 243 [M+H] + .

[0161] Intermediates 2 to 7 were prepared by selecting the corresponding raw materials with reference to all or part of the synthesis methods of Intermediate 1.

[0162] [Table 1]

[0163] Preparation of Intermediate 8, 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylic acid

[0164] [Chemical]

[0165] First step: Synthesis of methyl 5-(2-cyano-1H-pyrrol-1-yl)-2-fluoro-4-nitrobenzoate

[0166] [Chemical]

[0167] Methyl 2,5-difluoro-4-nitrobenzoate (2.0 g, 9.21 mmol) was dissolved in acetonitrile (20 mL), and 1H-pyrrole-2-carbonitrile (0.78 mL, 9.21 mmol) and cesium fluoride (1.40 g, 9.21 mmol) were added, and the reaction was carried out with stirring at 20 °C for 16 hours. The reaction solution was concentrated by rotary evaporation, and the crude product was separated by a normal-phase column to obtain methyl 5-(2-cyano-1H-pyrrol-1-yl)-2-fluoro-4-nitrobenzoate (500 mg, 19%).

[0168] 1 H NMR (400 MHz, CDCl 3 ) δ 8.15 (d, J = 6.4 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.04 (dd, J = 4.0, 1.6 Hz, 1H), 6.93 (dd, J = 2.8, 1.6 Hz, 1H), 6.43 (dd, J = 4.0, 2.8 Hz, 1H), 4.01 (s, 3H).

[0169] Second step: Synthesis of methyl 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylate

[0170]

Chemical formula

[0171] Methyl 5-(2-cyano-1H-pyrrol-1-yl)-2-fluoro-4-nitrobenzoate (1.5 g, 5.19 mmol) was dissolved in tetrahydrofuran (20 mL), and iron powder (2.90 g, 51.86 mmol) and glacial acetic acid (20 mL) were added. The mixture was reacted with stirring at 20 °C for 16 hours. The reaction solution was dried by rotary evaporation. The crude product was separated by a normal-phase column to obtain methyl 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylate (650 mg, 48%).

[0172] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.47 (d, J = 7.2 Hz, 1H), 8.36 (s, 1H), 7.52 (s, 2H), 7.25-7.06 (m, 2H), 6.75 (m, 1H), 3.88 (s, 3H).

[0173] Step 3: Synthesis of 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylic acid

[0174]

Chemical Structure

[0175] Methyl 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylate (600 mg, 2.31 mmol) was dissolved in tetrahydrofuran (10 mL) and water (3 mL), lithium hydroxide monohydrate (583 mg, 13.89 mmol) was added, and the mixture was reacted at 50 °C for 16 hours. After evaporating the organic solvent under reduced pressure, water (5 mL) was added thereto. The pH was adjusted to 3-4 with 1 M hydrochloric acid, filtered, the filter cake was washed with water (20 mL) and acetonitrile (20 mL), and after drying the filter cake, 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylic acid (341 mg, 60%) was obtained. MS m / z (ESI): 246 [M+H] + .

[0176] 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.99 (s, 1H), 9.15 (s, 1H), 8.83-8.53 (m, 2H), 7.79 (d, J = 3.6 Hz, 1H), 7.57 (d, J = 10.8 Hz, 1H), 6.94 (d, J = 3.6 Hz, 1H). Production of Intermediate 9, 1-Cyclopropyl-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)methanamine

[0177]

Chem.

[0178] First Step: Synthesis of 1-Cyclopropyl-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)methanamine

[0179]

Chem.

[0180] 5-(Trifluoromethyl)picolinaldehyde (350 mg, 2.0 mmol) was dissolved in dichloromethane (10 mL), cyclopropylmethanamine (156 mg, 2.2 mmol) and acetic acid (132 mg, 2.2 mmol) were added, and the reaction was carried out with stirring at room temperature for half an hour. Sodium triacetoxyborohydride (355 mg, 1.68 mmol) was added, and the mixture was stirred at room temperature for one hour. The reaction solution was diluted with dichloromethane and saturated sodium bicarbonate solution, separated, and the organic phase was concentrated by rotary evaporation. The crude product was separated by column chromatography (methanol / dichloromethane = 1 / 19) to obtain 1-cyclopropyl-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)methanamine (400 mg, 84%). MS m / z (ESI): 231 [M+H] + .

[0181] Intermediates 10 - 19 were prepared by selecting the corresponding raw materials with reference to all or part of the synthesis methods of Intermediate 9.

[0182]

Table 2

[0183] Production of Intermediate 20, 6-(Trifluoromethyl)benzofuran-3(2H)-one

[0184]

Chemical formula

[0185] First Step: Synthesis of Methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate

[0186]

Chemical formula

[0187] Methyl 2-hydroxy-4-(trifluoromethyl)benzoate (15.0 g, 68.1 mmol) was dissolved in acetone (200 mL), potassium carbonate (12.24 g, 88.6 mmol) was added, then methyl bromoacetate (8.42 mL, 88.6 mmol) was added dropwise to the reaction solution, and then the temperature was raised to 55 °C and reacted for 18 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove the solid, and the filter cake was washed with ethyl acetate. The filtrate was washed with saturated brine, dried and concentrated to obtain methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate (22.0 g, 94%). MS m / z (ESI): 293 [M+H] + 。

[0188] Second Step: Synthesis of 2-(Carboxymethoxy)-4-(trifluoromethyl)benzoic acid

[0189]

Chemical formula

[0190] Methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate (74.0 g, 253.2 mmol) was dissolved in a mixed solvent of methanol (500 mL) and water (250 mL), lithium hydroxide monohydrate (31.91 g, 759.7 mmol) was added, and the reaction was carried out at room temperature for 18 hours. The reaction solution was acidified with 1 N hydrochloric acid to pH = 2, the reaction solution was concentrated to remove methanol, the aqueous phase was filtered, and the solid was washed with water. The filter cake was dried to obtain 2-(carboxymethoxy)-4-(trifluoromethyl)benzoic acid (61.0 g, 91%). MS m / z (ESI): 265 [M+H] + 。

[0191] Step 3: Synthesis of 6-(trifluoromethyl)benzofuran-3(2H)-one

[0192]

Chemical formula

[0193] A mixture of 2-(carboxymethoxy)-4-(trifluoromethyl)benzoic acid (61 g, 230.9 mmol), acetic anhydride (377 mL, 4.02 mol), sodium acetate (28.41 g, 346.4 mmol), and acetic acid (110 mL) was heated to 150 °C and reacted for 18 hours. After completion of the reaction, the reaction solution was cooled to room temperature, diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous sodium sulfate, and then concentrated. After concentration, it was separated by silica gel column chromatography to obtain an intermediate (42 g). The intermediate was dissolved in methanol (300 mL), 1 N hydrochloric acid (300 mL) was added, the temperature was raised to 100 °C and reacted for 6 hours. The reaction solution was cooled to room temperature, water was added, and it was extracted with ethyl acetate. The extracted organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated. After concentration, it was slurried with methyl tert-butyl ether to obtain 6-(trifluoromethyl)benzofuran-3(2H)-one (17.0 g, 36%).

[0194] 1 H NMR (400 MHz, CDCl 3 ) δ 7.80 (d, J = 8.0 Hz, 1H), 7.43 (s, 1H), 7.35 (dd, J = 8.1, 1.4 Hz, 1H), 4.72 (s, 2H). Production of Intermediate 21, 2-(Trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-one

[0195]

Chemical Structure

[0196] First Step: Synthesis of Methyl 2-bromo-6-(trifluoromethyl)nicotinate

[0197]

Chemical Structure

[0198] 2-Oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylic acid (5.0 g, 24.14 mmol) and pyridine (1.95 mL, 24.14 mmol) were dissolved in chlorobenzene (50 mL). Phosphorus oxychloride (4.91 mL, 48.28 mmol) was gradually added in several portions at room temperature, and the temperature was raised to 120 °C and the reaction was carried out with stirring for 16 hours. After completion of the reaction, the reaction solution was concentrated in vacuo. The concentrate was cooled to 0 °C in an ice bath, and then dry methanol (20 mL) previously cooled with dry ice was gradually added dropwise, and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated in vacuo to obtain a brown oil. The oil was diluted with water, and the pH of the solution was adjusted to 8 with saturated sodium bicarbonate solution, and then extracted three times with ethyl acetate (50 mL × 3). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was separated by silica gel column chromatography to obtain methyl 2-bromo-6-(trifluoromethyl)nicotinate (5.7 g, 83%). MS m / z (ESI): 284, 286 [M+H] + 。

[0199] 1 H NMR (400 MHz, CDCl 3 ) δ 8.21 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 4.00 (s, 3H).

[0200] Step 2: Synthesis of Methyl (E)-2-(3-methoxy-3-oxoprop-1-en-1-yl)-6-(trifluoromethyl)nicotinate

[0201]

Chem.

[0202] To a solution of methyl 2-bromo-6-(trifluoromethyl)nicotinate (5.7 g, 20.07 mmol) and methyl acrylate (4.52 mL, 50.17 mmol) in toluene (100 mL) and N,N-dimethylformamide (15 mL) were added allylpalladium(II) chloride dimer (0.37 g, 1.00 mmol), tris(o-methylphenyl)phosphine (0.61 g, 2.01 mmol), and sodium carbonate (6.38 g, 60.20 mmol). The mixture was then stirred at 120 °C for 16 h under a nitrogen gas atmosphere. The reaction solution was filtered, and the filter cake was washed three times with ethyl acetate (3 × 30 mL). The organic phases were combined and concentrated in vacuo. The concentrate was separated by silica gel column chromatography to give methyl (E)-2-(3-methoxy-3-oxoprop-1-en-1-yl)-6-(trifluoromethyl)nicotinate (5.1 g, 88%). MS m / z (ESI): 290 [M+H] + .

[0203] 1 H NMR (400 MHz, CDCl 3) δ 8.46 (d, J = 15.2 Hz, 1H), 8.40 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 2.8 Hz, 1H), 4.01 (s, 3H), 3.84 (s, 3H).

[0204] Step 3: Synthesis of methyl 2-(3-methoxy-3-oxopropyl)-6-(trifluoromethyl)nicotinate

[0205]

Chemical Structure

[0206] A solution of methyl (E)-2-(3-methoxy-3-oxoprop-1-en-1-yl)-6-(trifluoromethyl)nicotinate (5.1 g, 17.63 mmol) and rhodium(III) chloride triphenylphosphine (1.31 g, 1.41 mmol) in ethanol (50 mL) was stirred at room temperature for 48 h under a hydrogen gas atmosphere (15 atm). The reaction mixture was filtered, and the filtrate was concentrated in vacuo. The crude product was separated by silica gel column chromatography to give methyl 2-(3-methoxy-3-oxopropyl)-6-(trifluoromethyl)nicotinate (4.9 g, 95%). MS m / z (ESI): 292 [M+H] + 。

[0207] 1 H NMR (400 MHz, CDCl 3 ) δ 8.34 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 3.96 (s, 3H), 3.67 (s, 3H), 3.57 (t, J = 7.2 Hz, 2H), 2.85 (t, J = 7.2 Hz, 2H). Step 4: Synthesis of 2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-one

[0208] [Chemical]

[0209] To a solution of methyl 2-(3-methoxy-3-oxopropyl)-6-(trifluoromethyl)nicotinate (4.9 g, 16.82 mmol) in methanol (60 mL), sodium methoxide (1.36 g, 25.23 mmol) was added in several portions, and the reaction mixture was stirred at 80 °C overnight. After completion of the reaction, the reaction mixture was cooled to room temperature and then concentrated to obtain a brown solid. The brown solid was dispersed in concentrated hydrochloric acid (60 mL) and stirred at 80 °C for 3 hours. The reaction mixture was cooled to room temperature, adjusted to pH = 6 with 1 M sodium hydroxide solution, and extracted with dichloromethane (2 × 100 mL). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a brown solid. The brown solid was separated by silica gel column chromatography to obtain 2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-one (2.07 g, 43%). MS m / z (ESI): 202 [M+H] + 。

[0210] 1 H NMR (400 MHz, CDCl 3 ) δ 8.21 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 3.42 - 3.36 (m, 2H), 2.92 - 2.85 (m, 2H). Production of Intermediate 22, 6-(Trifluoromethyl)furo[2,3-b]pyridin-3(2H)-one

[0211] [Chemical]

[0212] First Step: Synthesis of Ethyl 2-Chloro-6-(Trifluoromethyl)nicotinate

[0213] [Chemical]

[0214] At room temperature, dichlorosulfoxide (3.62 mL, 49.9 mmol) was added dropwise to a solution of 2-chloro-6-(trifluoromethyl)nicotinic acid (7.5 g, 33.25 mmol) in ethanol (150 mL) protected with nitrogen gas. Subsequently, the reaction solution was heated to 70 °C and reacted with stirring for 14 hours. After the reaction was completed, the reaction solution was concentrated to remove ethanol, the residue was dissolved in ethyl acetate (200 mL), the organic phase was washed with water (100 mL×3), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated product was separated by column chromatography [85% ethyl acetate - petroleum ether system], and ethyl 2-chloro-6-(trifluoromethyl)nicotinate (7 .72 g, 92%) was obtained. MS m / z (ESI): 254 [M+H] + .

[0215] 1 H NMR (400 MHz, CDCl 3 ) δ 8.30 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H), 4.46 (d, J = 7.2 Hz, 2H), 1.43 (d, J = 7.2 Hz, 3H).

[0216] Second step: Synthesis of ethyl 3-hydroxy-6-(trifluoromethyl)furo[2,3-b]pyridine-2-carboxylate

[0217]

Chemical formula

[0218] At 0 °C, sodium hydride (15.22 g, 380.5 mmol, 60% purity) was added in several portions to a solution of ethyl glycolate (36.7 mL, 380.5 mmol) in ethylene glycol dimethyl ether (530 mL). The reaction mixture was warmed to room temperature and stirred for 30 minutes. Subsequently, ethyl 2-chloro-6-(trifluoromethyl)nicotinate (38.6 g, 152.2 mmol) was dissolved in ethylene glycol dimethyl ether (530 mL) and added dropwise to the reaction mixture, and the reaction was carried out at 35 °C for 2 hours. After completion of the reaction, the reaction mixture was diluted with ethyl acetate and quenched with saturated sodium hydrogen carbonate solution. The organic phase was extracted, washed with saturated brine, dried over anhydrous sodium sulfate and then concentrated. After concentration, it was slurried with acetonitrile (300 mL) to obtain ethyl 3-hydroxy-6-(trifluoromethyl)furo[2,3-b]pyridine-2-carboxylate (29.5 g, 70%).

[0219] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.24 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 4.17 (q, J = 7.2 Hz,2H), 1.26 (t, J = 7.2 Hz, 3H).

[0220] Third step: Synthesis of 6-(trifluoromethyl)furo[2,3-b]pyridin-3(2H)-one

[0221]

Chemical formula

[0222] Ethyl 3-hydroxy-6-(trifluoromethyl)furo[2,3-b]pyridine-2-carboxylate (2.83 g, 10.28 mmol) was dissolved in a mixed solvent of tetrahydrofuran (32.0 mL) and water (8.0 mL), and lithium hydroxide monohydrate (1.73 g, 41.1 mmol) was added. The temperature was raised to 40 °C and the reaction was carried out for 2 days The reaction was completed. The reaction solution was cooled to room temperature, filtered, and the filter cake was washed with tetrahydrofuran. Subsequently, the filter cake was dissolved in a mixed solvent of ethyl acetate and water, and the system was acidified with 1 M hydrochloric acid in an ice-water bath to a pH of 6 - 7. Liquid separation was performed, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by rotary evaporation to obtain 6-(trifluoromethyl)furo[2,3-b]pyridin-3(2H)-one (1.43 g, 68%). MS m / z (ESI): 204 [M+H] + 。

[0223] 1 H NMR (400 MHz, CDCl 3 ) δ 8.23 (d, J = 7.6 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 4.85 (s, 2H). Production of Intermediate 23, 7-(trifluoromethyl)isochroman-4-one

[0224]

Chemical Structure

[0225] First Step: Synthesis of 2-((allyloxy)methyl)-1-bromo-4-(trifluoromethyl)benzene

[0226]

Chemical Structure

[0227] (2-Bromo-5-(trifluoromethyl)phenyl)methanol (7.39 g, 29.0 mmol) was dissolved in tetrahydrofuran (100 mL), sodium hydride (1.74 g, 43.5 mmol) was added at 0 °C, and the mixture was reacted at 0 °C for 0.5 h. Then, 3-bromoprop-1-ene (2.52 mL, 29.0 mmol) was added to the reaction mixture, and the mixture was reacted at 25 °C for 2 h. Water (50 mL) was added to the reaction mixture, and the mixture was extracted three times with ethyl acetate (30 mL). The organic phases were combined and concentrated. The crude product was separated by normal-phase column chromatography to obtain 2-((allyloxy)methyl)-1-bromo-4-(trifluoromethyl)benzene (8.1 g, 95%).

[0228] 1 H NMR (400 MHz, CDCl 3 ) δ 7.98-7.73 (m, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.40 (dd, J = 8.4, 2.4 Hz, 1H), 6.13-5.90 (m, 1H), 5.49-5.33 (m, 1H), 5.33-5.18 (m, 1H), 4.59 (s, 2H), 4.15 (dt, J = 5.6, 1.6 Hz, 2H).

[0229] Second step: Synthesis of 4-methylene-7-(trifluoromethyl)isochroman

[0230]

Chemical formula

[0231] 2-((allyloxy)methyl)-1-bromo-4-(trifluoromethyl)benzene (8.1 g, 27.4 mmol) was dissolved in N,N-dimethylformamide (160 mL), cesium carbonate (10.73 g, 32.9 mmol), triphenylphosphine (3.24 g, 12.4 mmol) and palladium acetate (0.92 g, 4.1 mmol) were added, and the reaction was carried out at 90 °C for 16 hours. The reaction solution was concentrated, and the crude product was separated by a normal-phase column to obtain 4-methylene-7-(trifluoromethyl)isochroman (3.8 g, 65%).

[0232] 1 H NMR (400 MHz, CDCl 3 ) δ 7.78 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.4, 2.0 Hz, 1H), 7.30 (s, 1H), 5.72 (s, 1H), 5.15 (t, J = 1.2 Hz, 1H), 4.84 (s, 2H), 4.47 (t, J = 1.2 Hz, 2H).

[0233] Step 3: Synthesis of 4-(hydroxymethyl)-7-(trifluoromethyl)isochroman-4-ol

[0234]

Chemical formula

[0235] 4-Methylene-7-(trifluoromethyl)isochroman (3.8 g, 17.74 mmol) was dissolved in water (10 mL) and acetone (40 mL), potassium osmate dihydrate (0.65 g, 1.77 mmol) was added, and the mixture was reacted at 25 °C for 5 minutes. Then N-methylmorpholine N-oxide (7.27 g, 62.1 mmol) was added, and the reaction was continued at 25 °C for 16 hours. A saturated sodium thiosulfate solution (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL). The organic phase was rotary evaporated, and the crude product was separated by normal phase column chromatography to obtain 4-(hydroxymethyl)-7-(trifluoromethyl)isochroman-4-ol (3.57 g, 81%).

[0236] 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 8.4 Hz, 1H), 7.60-7.51 (m, 1H), 7.28 (s, 1H), 4.83 (s, 2H), 4.16 (d, J = 11.2 Hz, 1H), 3.90 (dd, J = 11.2, 6.4 Hz, 1H), 3.70 (ddd, J = 11.2, 4.8, 1.2 Hz, 1H), 3.63 (dd, J = 11.2, 1.2 Hz, 1H), 2.87 (s, 1H).

[0237] Fourth step: Synthesis of 7-(trifluoromethyl)isochroman-4-one

[0238]

Chem.

[0239] 4-(Hydroxymethyl)-7-(trifluoromethyl)isochroman-4-ol (3.57 g, 14.38 mmol) was dissolved in tetrahydrofuran (50 mL) and water (5 mL), and then sodium periodate (10.46 g, 48.90 mmol) was added, and the reaction was carried out at 25 °C for 16 hours. A saturated solution of sodium thiosulfate (40 mL) was added to the reaction solution, and the mixture was extracted three times with ethyl acetate (40 mL). The organic phase was rotary dried, and the crude product was separated by normal phase column to obtain 7-(trifluoromethyl)isochroman-4-one (2.88 g, 93%).

[0240] 1 H NMR (400 MHz, CDCl 3 ) δ 8.16 (d, J = 8.4 Hz, 1H), 7.68 (dd, J = 8.4, 1.6 Hz, 1H), 7.52 (d, J = 2.0 Hz, 1H), 4.95 (s, 2H), 4.42 (s, 2H). Production of Intermediate 24, 6-(1-methyl-1H-pyrazol-4-yl)benzofuran-3(2H)-one

[0241]

Chemical formula

[0242] 6-Bromobenzofuran-3(2H)-one (1.00 g, 4.69 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.17 g, 5.63 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (343 Mg (0.114 g, 0.469 mmol), potassium carbonate (1.94 g, 14.07 mmol) were dissolved in dioxane (15 mL) and water (5 mL), heated to 85 °C under nitrogen gas protection, stirred overnight. When the reaction was completed, water was added to quench, and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and filtered. The obtained crude product was separated by silica gel column chromatography to obtain 6-(1-methyl-1H-pyrazol-4-yl)benzofuran-3(2H)-one (0.8 g, 80%). MS m / z (ESI): 215 [M+H] + 。

[0243] Preparation of Intermediate 25, (S)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-amine

[0244]

Chemical Structure

[0245] First Step: Synthesis of (R)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-ol

[0246]

Chemical Structure

[0247] (R)-2-Methyl-CBS-oxazaborolidine (5.94 g, 21.4 mmol) was dissolved in tetrahydrofuran (1100 mL), and the temperature was lowered to 0 °C. Subsequently, borane dimethyl sulfide complex (53.5 mL, 107.1 mmol, 2 M in THF) was added to the solution and stirred for 1 hour. The reaction system was cooled to -70 °C, 6-(trifluoromethyl)furo[2,3-b]pyridin-3(2H)-one (14.5 g, 71.4 mmol) was dissolved in tetrahydrofuran (140 mL), added dropwise to the reaction system, kept warm and stirred for 1 hour, and then the temperature was raised to -10 °C and stirring was continued for 2 hours. When the completion of the reaction was detected, it was quenched with methanol and stirred at room temperature for 30 minutes. 70 mL of aqueous ammonia was added, stirred, and then the supernatant was discarded, concentrated, and the residue was separated by silica gel column chromatography (dichloromethane / ethyl acetate = 10 / 1) to obtain (R)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-ol (12.0 g, 82%). MS m / z (ESI): 206 [M+H] + 。

[0248] Second step: Synthesis of (S)-3-azido-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridine

[0249]

Chemical formula

[0250] (R)-6-(Trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-ol (12.0 g, 58.5 mmol) was dissolved in tetrahydrofuran (100 mL), the temperature was lowered to 0 °C, diphenylphosphoric acid azide (15.2 mL, 70.2 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (10.5 (mL, 70.2 mmol) was added. The temperature was raised to room temperature and the reaction was carried out for 18 hours. After completion of the reaction, water was added to the reaction solution for dilution, and the mixture was extracted with ethyl acetate. The organic phase was dried and then concentrated, and subsequently separated by silica gel column chromatography to obtain (S)-3-azido-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridine (12.5 g, 93%). MS m / z (ESI): 231 [M+H] + 。

[0251] Step 3: Synthesis of (S)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-amine hydrochloride

[0252]

Chemical formula

[0253] (S)-3-azido-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridine (12.5 g, 54.3 mmol) was dissolved in tetrahydrofuran (200 mL) and water (6 mL), triphenylphosphine (42.74 g, 162.9 mmol) was added, and the temperature was raised to 50 °C and the reaction was carried out for 18 hours. 0.5 M hydrochloric acid was added, and the mixture was extracted 3 times with ethyl acetate. The aqueous phase obtained by liquid separation was concentrated to obtain (S)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-amine hydrochloride (11.0 g, 84%). MS m / z (ESI): 205 [M+H] + 。

[0254] Intermediates 26 - 32 were prepared by selecting the corresponding raw materials with reference to all or part of the synthesis method of Intermediate 25.

[0255]

Table 3

[0256] Production of Intermediate 33, (S)-N-(1-Methyl-1H-pyrazol-4-yl)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-amine

[0257] [Chemical formula]

[0258] (S)-6-(Trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-amine hydrochloride (5.5 g, 22.9 mmol) was dissolved in dioxane (500 mL), and 4-bromo-1-methyl-1H-pyrazole (4.23 g, 26.3 mmol), methanesulfonic acid (2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (5.45 g, 6.86 mmol) and sodium t ert-butoxide (6.59 g, 68.58 mmol) were added. After replacing with nitrogen gas three times, the temperature was raised to 95 °C and reacted for 2 hours. After cooling to room temperature, water was added and extracted with ethyl acetate. The organic phase obtained by liquid separation was dried and concentrated, and then subjected to silica gel column chromatography (PE / EA = 1 / 10) and C18 reverse phase column (Water (10 mM NH 4 HCO 3 )-ACN: 21% - 51%) for separation to obtain (S)-N-(1-methyl-1H-pyrazol-4-yl)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-amine (2.40 g, 37%). MS m / z (ESI): 285 [M+H] + .

[0259] 1 H NMR (400 MHz, DMSO-d 6 ) δ 7.88 (d, J = 7.4 Hz, 1H), 7.41 (d, J = 7.4 Hz, 1H), 7.22 (d, J = 1.0 Hz, 1H), 7.02 (d, J = 1.0 Hz, 1H), 5.19 (d, J = 8.9 Hz, 1H), 5.02 (td, J = 8.5, 4.5 Hz, 1H), 4.84 (dd, J = 9.6, 8.1 Hz, 1H), 4.38 (dd, J = 9.6, 4.6 Hz, 1H), 3.71 (s, 3H). Intermediates 34 to 38 were prepared by selecting corresponding raw materials with reference to all or part of the synthesis methods of Intermediate 33.

[0260]

Table 4

[0261] Preparation of Intermediate 39, (R)-N-(Cyclopropylmethyl)-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amine

[0262]

Chemical formula

[0263] (R)-5-(Trifluoromethyl)-2,3-dihydro-1H-inden-1-amine hydrochloride (200 mg, 0.84 mmol) was dissolved in a mixed solution of dichloromethane (3 mL) and ethanol (3 mL), and potassium acetate (82 mg, 0.84 mmol), cyclopropanecarboxaldehyde (59 mg, 0.84 mmol), acetic acid (5 mg, 0.084 mmol) and sodium triacetoxyborohydride (355 mg, 1.68 mmol) were added. The mixture was stirred at room temperature overnight. The reaction solution was diluted with dichloromethane and saturated sodium bicarbonate solution, separated, and the organic phase was concentrated by rotary evaporation. The crude product was separated by column chromatography (methanol / dichloromethane = 1 / 19) to obtain (R)-N-(cyclopropylmethyl)-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amine (108 mg, 48%). MS m / z (ESI): 256 [M+H] + 。

[0264] Intermediates 40 to 43 were prepared by selecting the corresponding raw materials with reference to all or part of the synthesis methods of Intermediate 39.

[0265]

Table 5

[0266] Intermediate 44, N-Methyl-6-(trifluoromethyl)-2,3-dihydrobenzofur an-3-amine production

[0267]

Chemical formula

[0268] 6-(Trifluoromethyl)-2,3-dihydrobenzofuran-3-amine (600 mg, 2.95 mmol) was dissolved in hexafluoroisopropanol (5 mL), methyl trifluoromethanesulfonate (727 mg, 4.43 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with ethyl acetate and saturated sodium bicarbonate solution, separated, and the organic phase was concentrated by rotary evaporation. The crude product was separated by column chromatography to obtain N-methyl-6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-amine (450 mg, 70%). MS m / z (ESI): 218 [M+H] + 。

[0269] Intermediates 45 to 47 were prepared by selecting the corresponding raw materials with reference to all or part of the synthetic methods of Intermediate 44.

[0270]

Table 6

[0271] Intermediate 48: Preparation of 5-((2R,5S)-5-methylpiperidin-2-yl)benzo[d]thiazole

[0272]

Chemical formula

[0273] First step: Synthesis of methyl 4-methyl-5-oxopentanoate

[0274]

Chemical formula

[0275] In an ice bath, propionaldehyde (5.0 g, 86.09 mmol) was added to hexahydropyridine (14.66 g, 172.2 mmol) and potassium carbonate (4.76 g, 34.43 mmol), and the mixture was vigorously stirred at room temperature for 18 h. It was filtered, the mother liquor was dried over anhydrous sodium sulfate, further filtered, and the filtrate was concentrated and then dissolved in acetonitrile (50 mL). Methyl acrylate (14.82 g, 172.2 mmol) was gradually added dropwise. The reaction solution was heated to reflux for 24 h. Glacial acetic acid (10.34 g, 172.2 mmol) and water (50 mL) were added, and it was refluxed for another 24 h. After adding water to dilute the reaction solution, it was extracted with tert-butyl methyl ether. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The crude product was separated by a normal phase column to obtain methyl 4-methyl-5-oxopentanoate (6.22 g, 48%).

[0276] 1 H NMR (400 MHz, CDCl 3 ) δ 9.63 (d, J = 1.6 Hz, 1H), 3.68 (s, 3H), 2.48-2.40 (m, 1H), 2.41-2.35 (m, 2H), 2.10-2.02 (m, 1H), 1.71 (dq, J = 14.3, 7.3 Hz, 1H), 1.14 (d, J = 7.2 Hz, 3H).

[0277] Second step: Synthesis of (3R,8S)-8-methyl-3-phenylhexahydro-5H-oxazolo[3,2-a]pyridin-5-one

[0278]

Chemical formula

[0279] Methyl 4-methyl-5-oxopentanoate (6.222 g, 43.16 mmol) was added to toluene (100 mL), and (R)-2-amino-2-phenylethan-1-ol (5.92 g, 43.16 mmol) was added thereto. The mixture was heated under reflux for 24 hours, and water was removed using a water separator. The reaction solution was concentrated, and the crude product was separated by a normal-phase column to obtain (3R,8S)-8-methyl-3-phenylhexahydro-5H-oxazolo[3,2-a]pyridin-5-one (4.866 g, 46%). MS m / z (ESI): 232 [M+H] + .

[0280] 1 H NMR (400 MHz, CDCl 3 ) δ 7.33-7.20 (m, 5H), 4.93 (dd, J = 6.8, 1.3 Hz, 1H), 4.44 (d, J = 8.8 Hz, 1H), 4.17-4.08 (m, 2H), 4.01 (dd, J = 9.0, 1.3 Hz, 1H), 2.46-2.28 (m, 2H), 2.02-1.87 (m, 2H), 1.60-1.45 (m, 1H), 1.21 (d, J = 6.4 Hz, 3H).

[0281] Third step: Synthesis of (S)-1-((R)-2-hydroxy-1-phenylethyl)-5-methylpiperidin-2-one

[0282] [Chemical formula]

[0283] (3R,8S)-8-Methyl-3-phenylhexahydro-5H-oxazolo[3,2-a]pyridin-5-one (4.866 g, 21.04 mmol) was added to a dichloromethane anhydrous solution (200 mL), and triethylsilane (7.34 g, 63.12 mmol) and titanium tetrachloride (17.96 g, 94.68 mmol) were added thereto. The mixture was reacted at 50 °C for 24 hours. Further, triethylsilane (7.34 g, 63.12 mmol) and titanium tetrachloride (17.96 g, 94.68 mmol) were added, and the reaction was continued at 50 °C for 24 hours. The reaction solution was gradually poured into saturated sodium bicarbonate solution (500 mL), and after filtering the aqueous phase, it was extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was separated by normal-phase column chromatography to obtain (S)-1-((R)-2-hydroxy-1-phenylethyl)-5-methylpiperidin-2-one (1.54 g, 31%). MS m / z (ESI): 234 [M+H] + 。

[0284] Fourth step: Synthesis of (S)-5-methyl-1-(1-phenylvinyl)piperidin-2-one

[0285]

Chemical formula

[0286] (S)-1-((R)-2-hydroxy-1-phenylethyl)-5-methylpiperidin-2-one (10.3 g, 44.15 mmol) in dimethyl sulfoxide (150 mL) was added with lithium hydroxide monohydrate (37.05 g, 882.9 mmol). The mixture was reacted at 135 °C for 4 days. It was poured into water, extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain (S)-5-methyl-1-(1-phenylvinyl)piperidin-2-one (7.383 g, 66%). MS m / z (ESI): 216 [M+H] + 。

[0287] Fifth step: Synthesis of (S)-5-methylpiperidin-2-one

[0288]

Chemical formula

[0289] (S)-5-Methyl-1-(1-phenylvinyl)piperidin-2-one (7.28 g, 33.81 mmol) in dichloromethane (30 mL) was added to TFA (30 mL) and water (3 mL). The reaction was carried out overnight at 40 °C. After concentration, it was separated by a reverse-phase column to obtain a crude product. After lyophilization, aqueous ammonia (3 mL) was added, and it was further concentrated and dried. It was slurried with ethyl acetate and filtered to obtain (S)-5-methylpiperidin-2-one (2.52 g, 63%). MS m / z (ESI): 114 [M+H] + 。

[0290] 1 H NMR (400 MHz, MeOH-d 4 ) δ 3.30 - 3.24 (m, 1H), 2.86 (dd, J = 12.2, 10.1 Hz, 1H), 2.39 - 2.26 (m, 2H), 1.96 - 1.80 (m, 2H), 1.54 - 1.40 (m, 1H), 1.01 (d, J = 6.5 Hz, 3H).

[0291] Sixth step: Synthesis of tert-butyl (S)-5-methyl-2-oxopiperidine-1-carboxylate

[0292]

Chemical formula

[0293] (S)-5-Methylpiperidin-2-one (2.02 g, 17.85 mmol) in tetrahydrofuran (25 mL) was added to 4-dimethylaminopyridine (327 mg, 2.68 mmol) and di-tert-butyl dicarbonate (6.22 g, 26.78 mmol). The reaction was carried out with stirring overnight at 25 °C. After concentrating the reaction solution, it was diluted with dichloromethane and washed with a 5% potassium bisulfate solution. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain tert-butyl (S)-5-methyl-2-oxopiperidine-1-carboxylate (3.48 g, 70%). MS m / z (ESI): 214 [M+H]+ .

[0294] 1 H NMR (400 MHz, CDCl 3 ) δ 3.83 - 3.75 (m, 1H), 3.11 (dd, J = 12.7, 10.4 Hz, 1H), 2.63 - 2.53 (m, 1H), 2.53 - 2.41 (m, 1H), 2.01 - 1.93 (m, 1H), 1.92 - 1.83 (m, 1H), 1.53 (s, 9H), 1.46 - 1.40 (m, 1H), 1.04 (d, J = 6.6 Hz, 3H).

[0295] Seventh Step: Synthesis of tert - butyl (S)-3 - methyl - 6 -(((trifluoromethyl)sulfonyl)oxy)-3,4 - dihydropyridine - 1(2H)-carboxylate

[0296] [Chemical Structure Diagram]

[0297] Under the condition of - 78 °C, sodium bis(trimethylsilyl)amide (3.52 mL, 7.03 mmol) was added to a solution of tert - butyl (S)-5 - methyl - 2 - oxopiperidine - 1 - carboxylate (1.00 g, 4.69 mmol) in anhydrous tetrahydrofuran (25 mL). The reaction mixture was reacted at this temperature for 1 hour. Next, N - phenylbis(trifluoromethanesulfonimide) (2.18 g, 6.10 mmol) was added. The reaction mixture was gradually warmed to room temperature and stirred for 3.5 hours. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was separated by a normal - phase column to obtain tert - butyl (S)-3 - methyl - 6 -(((trifluoromethyl)sulfonyl)oxy)-3,4 - dihydropyridine - 1(2H)-carboxylate (1.05 g, 62%). MS m / z (ESI): 290 [M + H - 56] + .

[0298] 1 H NMR (400 MHz, CDCl 3 ) δ 5.25 (t, J = 3.8 Hz, 1H), 3.87 (dd, J = 12.8, 3.3 Hz, 1H), 3.00 (dd, J = 12.7, 9.1 Hz, 1H), 2.44 - 2.34 (m, 1H), 1.98 - 1.88 (m, 1H), 1.88 - 1.78 (m, 1H), 1.49 (s, 9H), 0.99 (d, J = 6.6 Hz, 3H).

[0299] Step 8: Synthesis of tert - butyl (S) - 6 - (benzo[d]thiazol - 5 - yl) - 3 - methyl - 3,4 - dihydropyridine - 1(2H) - carboxylate

[0300]

Chem.

[0301] (S)-tert-Butyl 3-methyl-6-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydropyridine-1(2H)-carboxylate (1.39 g, 4.02 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (1.00 g, 3.83 mmol), sodium carbonate (1.01 g, 9.57 mmol) and 1,1'-bis(diphenylphosphino)ferrocene dichloropalladium (140 mg, 0.191 mmol) were added to 1,4-dioxane (30 mL) and water (10 mL), and the mixture was reacted at 90 °C for 18 h under nitrogen gas protection. The reaction solution was diluted with ethyl acetate, washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was separated by normal phase column chromatography to obtain (S)-tert-butyl 6-(benzo[d]thiazol-5-yl)-3-methyl-3,4-dihydropyridine-1(2H)-carboxylate (1.01 g, 75%). MS m / z (ESI): 331 [M+H] + .

[0302] Step 9: Synthesis of (S)-5-(5-methyl-3,4,5,6-tetrahydropyridin-2-yl)benzo[d]thiazole

[0303] [Chemical formula]

[0304] To a solution of (S)-tert-butyl 6-(benzo[d]thiazol-5-yl)-3-methyl-3,4-dihydropyridine-1(2H)-carboxylate (1.01 g, 3.05 mmol) in dichloromethane (9 mL) was added trifluoroacetic acid (3 mL, 2.68 (0.70 g, 92%) of (S)-5-(5-methyl-3,4,5,6-tetrahydropyridin-2-yl)benzo[d]thiazole was obtained. MS m / z (ESI): 231 [M+H] was added. The reaction was carried out overnight at 25 °C. After concentrating the reaction solution, water was added for dilution, and the pH was adjusted to 8 with aqueous ammonia, followed by extraction with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. + 。

[0305] Step 10: Synthesis of 5-((2R,5S)-5-methylpiperidin-2-yl)benzo[d]thiazole

[0306]

Chemical Structure

[0307] In an ice-water bath, sodium borohydride (308 mg, 9.12 mmol) was added to a solution of (S)-5-(5-methyl-3,4,5,6-tetrahydropyridin-2-yl)benzo[d]thiazole (0.70 g, 3.04 mmol) in methanol (5 mL). The reaction solution was stirred at room temperature for 45 minutes. After concentrating the reaction solution, water was added for dilution, and the pH was adjusted to 8 with aqueous ammonia, followed by extraction with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain 5-((2R,5S)-5-methylpiperidin-2-yl)benzo[d]thiazole (0.69 g, 98%). MS m / z (ESI): 233 [M+H] + 。

[0308] 1 H NMR (400 MHz, CDCl 3 ) δ 8.98 (s, 1H), 8.15 (d, J = 1.7 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.56 (dd, J = 8.3, 1.7 Hz, 1H), 3.78 (dd, J = 11.4, 2.6 Hz, 1H), 3.22 - 3.13 (m, 1H), 2.48 (t, J = 11.4 Hz, 1H), 1.97 - 1.87 (m, 2H), 1.86 - 1.68 (m, 2H), 1.30 - 1.19 (m, 1H), 0.92 (d, J = 6.6 Hz, 3H). Intermediate 49 was prepared by selecting the corresponding raw materials with reference to all or part of the synthesis methods of Intermediate 48.

[0309] [Table 7]

[0310] Preparation of Intermediate 50, (3R,5S)-3-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)morpholine

[0311] [Chemical formula]

[0312] First step: Synthesis of (R)-1-((tributylstannyl)methoxy)propan-2-amine

[0313] [Chemical formula]

[0314] Sodium hydride (204 mg, 5.10 mmol, in 60% kerosene) was dissolved in N,N-dimethylformamide (20 mL), cooled in an ice-water bath, and (R)-2-aminopropan-1-ol (0.36 mL, 4.64 mmol) was slowly added dropwise. After the addition was complete, the mixture was stirred at room temperature for one hour. The reaction mixture was cooled in an ice-water bath, and a solution of tributyl(iodomethyl)stannane (2.00 g, 4.64 mmol) in N,N-dimethylformamide (20 mL) was slowly added dropwise, and the mixture was stirred at room temperature overnight. The reaction mixture was cooled in an ice bath, saturated ammonium chloride solution was slowly added to quench the reaction, and the layers were separated. The organic layer was washed with saturated brine. The organic layer was concentrated by rotary evaporation, and the crude product was separated by column chromatography to obtain (R)-1-((tributylstannyl)methoxy)propan-2-amine (1.30 g, 71%). MS m / z (ESI): 380 [M+H] + 。

[0315] Second step: Synthesis of (R,E)-N-(1-((tributylstannyl)methoxy)propan-2-yl)-1-(5-(trifluoromethyl)pyridin-2-yl)methanimine

[0316]

Chemical Structure

[0317] (R)-1-((tributylstannyl)methoxy)propan-2-amine (800 mg, 2.11 mmol) was dissolved in dichloromethane (20 mL), 5-(trifluoromethyl)pyridine-2-carbaldehyde (370 mg, 2.11 mmol) and molecular sieves (1.50 g, 3.41 mmol) were added, and the mixture was stirred at room temperature overnight. The reaction mixture was filtered, washed with dichloromethane, and the filtrate was concentrated by rotary evaporation to obtain (R,E)-N-(1-((tributylstannyl)methoxy)propan-2-yl)-1-(5-(trifluoromethyl)pyridin-2-yl)methanimine (1100 mg, 97%).

[0318] 11H NMR (400 MHz, CDCl 3 ) δ 8.90 (dt, J = 1.9, 0.9 Hz, 1H), 8.40 (s, 1H), 8.14 (dt, J = 8.3, 0.9 Hz, 1H), 7.95 (dd, J = 8.3, 2.3 Hz, 1H), 3.79 - 3.63 (m, 3H), 3.43 (d, J = 6.2 Hz, 2H), 1.48 - 1.36 (m, 6H), 1.28 - 1.18 (m, 9H), 0.95 - 0.81 (m, 15H).

[0319] Step 3: Synthesis of (3R,5S)-3-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)morpholine

[0320]

Chemical Structure

[0321] (S,S)-2,2'-Isopropylidenebis(4-phenyl-2-oxazoline) (70 mg, 0.21 mmol) was dissolved in hexafluoroisopropanol (10 mL), and copper trifluoromethanesulfonate (151 mg, 0.42 mmol) was added. The mixture was stirred at room temperature overnight. A solution of (R,E)-N-(1-((tributylstannyl)methoxy)propan-2-yl)-1-(5-(trifluoromethyl)pyridin-2-yl)methanimine (1113 mg, 2.08 mmol) in hexafluoroisopropanol (5 mL) was added to the reaction solution by syringe, and the mixture was stirred at room temperature for 24 hours. The reaction solution was diluted with dichloromethane and aqueous ammonia solution, separated, and the organic phase was concentrated by rotary evaporation. The crude product was separated by reverse-phase column chromatography to obtain (3R,5S)-3-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)morpholine (195 mg, 37%). MS m / z (ESI): 247 [M+H] + 。

[0322] II. Preparation of Examples Example 1: (R)-4-Amino-1-methyl-N-(1-(pyrimidin-2-yl)ethyl)-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)imidazo [1,5-a]quinoxaline-8-carboxamide production

[0323]

Chemical Structure

[0324] 4-Amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid (30.0 mg, 0.12 mmol) and 2-methoxy-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)ethan-1-amine (34.9 mmol, 0.12 mmol) were dissolved in N,N-dimethylacetamide (3 mL), bromotripyrrolidinophosphonium hexafluorophosphate (75.1 mmol, 0.16 mmol) and N,N-diisopropylethylamine (48.0 mg, 0.37 mmol) were added, and the mixture was stirred overnight at room temperature. After completion of the reaction, water was added to quench it, and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography [9% methanol-dichloromethane system] to obtain a crude product. Further separation was carried out by a reverse phase column [50% acetonitrile-10 nM ammonium bicarbonate aqueous solution system], and after lyophilization, (R)-4-amino-1-methyl-N-(1-(pyrimidin-2-yl)ethyl)-N-((5-(trifluoromethyl)pyridin-2-yl)methyl)imidazo[1,5-a]quinoxaline-8-carboxamide (18 mg, 28%) was obtained. MS m / z (ESI): 507 [M+H] + .

[0325] 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.88-8.76 (m, 3H), 8.29 (s, 1H), 8.11 (dd, J = 8.5, (2.4 Hz, 1H), 7.80 (singlet, 1H), 7.61 - 7.47 (multiplet, 3H), 7.41 (triplet, J = 4.9 Hz, 1H), 7.30 (singlet, 2H), 5.56 (singlet, 1H), 5.00 - 4.47 (multiplet, 2H), 2.89 (singlet, 3H), 1.60 (doublet, J = 7.0 Hz, 3H).

[0326] Example 2: Preparation of (S)-4-Amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazol-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)imidazo[1,5-a]quinoxaline-8-carboxamide

[0327]

Chemical Structure

[0328] First Step: Synthesis of 4-Amino-7-fluoro-1-methylimidazo[1,5-a]quinoxaline-8-carbonyl Chloride Hydrochloride

[0329]

Chemical Structure

[0330] 4-Amino-7-fluoro-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid (100 mg, 0.38 mmol) was placed in dichloromethane (10 mL), and 1,4-dioxane solution of hydrochloric acid (0.5 mL, 2.0 mmol, 4 mol / L) was added. The mixture was stirred at room temperature for half an hour, and the reaction solution was evaporated under reduced pressure by rotary evaporation and concentrated until dry. Thionyl chloride (1.0 mL, 13.79 mmol) was added to the residue, and the reaction was carried out with stirring at 65 °C overnight. The reaction solution was evaporated under reduced pressure by rotary evaporation and concentrated. Dry dichloromethane (5 mL) was added to the residue, and after rotary evaporation and concentration, 4-amino-7-fluoro-1-methylimidazo[1,5-a]quinoxaline-8-carbonyl chloride hydrochloride (118 mg, 99%) was obtained. MS m / z (ESI): 275 [M+H] + .

[0331] Second step: Synthesis of (S)-4-amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazol-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)imidazo[1,5-a]quinoxaline-8-carboxamide

[0332] [Chemical formula]

[0333] 4-Amino-7-fluoro-1-methylimidazo[1,5-a]quinoxaline-8-carbonyl chloride hydrochloride (77 mg, 0.24 mmol) was placed in dichloroethane (6 mL), pyridine (0.10 mL, 1.22 mmol) and (S)-1-methyl-N-(6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)-1H-pyrazole-4-amine (69 mg, 0.24 mmol) were added, and the reaction was carried out with stirring at 60 °C for 5 h. After completion of the reaction, the reaction solution was concentrated by rotary evaporation, and the crude product was separated by reverse-phase column chromatography to obtain ((S)-4-amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazol-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)imidazo[1,5-a]quinoxaline-8-carboxamide (32 mg, 25%). MS m / z (ESI): 526 [M+H] + .

[0334] 1 H NMR (400 MHz, DMSO-d 6 ) δ 7.96 (d, J = 6.2 Hz, 1H), 7.80 (s, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.46 (s, 2H), 7.41 (s, 1H), 7.33 (d, J = 7.9 Hz, 1H), 7.11 (s, 1H), 6.99 (d, J = 10.6 Hz, 1H), 6.87 (s, 1H), 6.61 (s, 1H), 4.88 (t, J = 10.0 Hz, 1H), 4.67 (dd, J = 10.6, 4.0 Hz, 1H), 3.50 (s, 3H), 2.93 (s, 3H). Examples 3 to 233 were prepared by selecting the corresponding raw materials with reference to all or part of the synthesis methods of Example 1 or Example 2.

[0335]

Table 8

[0336] The nuclear magnetic data of the compounds obtained by manufacturing in the above examples are as follows.

[0337]

Table 9

[0338] Biological measurement and evaluation I. Human colon cancer HCT116 cell proliferation inhibition test 1. Seed HCT116 MTAP knockout and MTAP wild-type cells in a 96-well flat-bottom plate, and use McCoy's 5A medium containing 10% fetal bovine serum + 1% penicillin-streptomycin to culture overnight at 37°C and 5% CO 2 under the condition.

[0339] 2. The next day, the compound was dissolved in DMSO, sequentially diluted with DMSO and medium, transferred to a cell plate, serially diluted 4-fold to a final concentration of 10 μM of the compound, and DMSO controls were added at 9 concentration gradients.

[0340] 3. Cells not treated with the compound were taken out, the cell viability was detected using the CellTiter-Glo Luminescent Cell Viability Assay (Promega) with reference to the reagent kit instructions, and then the cell plate was placed on an EnVision Multilabel Reader to detect the luminescence signal.

[0341] 4. At the same time, the cell plate treated with the addition of the compound was cultured continuously for 6 days at 37 °C and 5% CO 2 conditions. 5. Next, the cell viability was similarly detected with CellTiter-Glo.

[0342] 6. Finally, a dose-response curve was plotted using the four-parameter dose-response curve module of GraphPad Prism v 9.2.0 software, and the growth inhibition IC 50 (unit: nM) was calculated. The test results are as follows.

[0343]

Table 10

[0344] According to the biological activity data of the compounds of the specific examples, a series of compounds of the present invention have a very strong inhibitory effect on the proliferation of human colon cancer HCT116 MTAP knockout cells at the cell level and have very high selectivity for wild-type cells.

[0345] All documents cited in this application are cited as references in this application, each document being cited separately as a reference. Further, after reading the above disclosure of the present invention, those skilled in the art can make various changes and modifications to the present invention, and it should be understood that those equivalent forms are also included in the scope of the claims attached to this application.

Claims

1. A compound represented by formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, 【Chemistry 1】 Here, " 【Chemistry 2】 " is a double bond or a single bond, X １ is C or N, and X ２ is C or N, and as a condition, X １ , X ２ is N; X ３ is CR ５ or N, and X ４ is CR ６ or N, and X ５ is CR ７ or N, X ６ is CR ８ or N, and X ７ is CR ９ or N, and X ８ is CR １０ or N, R １ is -(CR １１ R １２ ) ｍ -R, or R １ and R ２ form one ring B together with the nitrogen atom directly bonded thereto, and the ring B is a 4-10 membered nitrogen-containing heterocyclic group or a 5-10 membered nitrogen-containing heteroaryl group, and the ring B optionally further comprises R, deuterium, halogen, cyano group, nitro group, azide group, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl groups, ═O, ═S, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from R is -ring A-(R ａ ) ｎ and Ring A is C ３－１２ Cycloalkyl group, 4-10 membered heterocyclic group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ３－１２ The cycloalkyl group or the 4- to 10-membered heterocyclic group may optionally further comprise C ６－１０ fused to an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl group or 5-10 membered heteroaryl group may optionally further comprise a 5-10 membered heteroaryl group, C ３－１２ fused to a cycloalkyl group or a 4- to 10-membered heterocyclic group; Each R ａ are each independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ an aryl group, a 5- to 10-membered heteroaryl group, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ or, when n≧2, two R ａ together with the carbon atom directly attached thereto form C(O), and said groups may independently optionally further comprise deuterium, halogen, cyano group, nitro group, azide group, C １－１０ Alkyl group, halogen-substituted C １－１０ Alkyl group, deuterium-substituted C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ Aryl group, 5-10 membered heteroaryl group, ═O, ═S, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from R ２ is hydrogen, deuterium, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ Aryl group, 5-10 membered heteroaryl group, —S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)R １５ and —C(O)NR １６ R １７ and C ３－１２ The cycloalkyl group or the 3- to 12-membered heterocyclic group may optionally further comprise C ６－１０ fused to an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl group or 5-10 membered heteroaryl group may optionally further comprise C ３－１２ fused to a cycloalkyl group or a 4-10 membered heterocyclic group, which groups independently optionally further contain deuterium, halogen, cyano, nitro, azido, C １－１０ Alkyl group, halogen-substituted C １－１０ Alkyl group, deuterium-substituted C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ Aryl group, 5-10 membered heteroaryl group, halogen-substituted C ３－６ Cycloalkyl group, halogen-substituted 3-6 membered heterocyclic group, halogen-substituted C ６－８ Aryl group, halogen-substituted 5-8 membered heteroaryl group, C １－４ Alkyl-substituted C ３－６ Cycloalkyl group, C １－４ Alkyl-substituted 3-6 membered heterocyclic group, C １－４ Alkyl-substituted C ６－８ Aryl group, C １－４ Alkyl-substituted 5-8 membered heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, ═O, ═S, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from R ３ and R ４ are each independently hydrogen, deuterium, a hydroxyl group, or C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ cycloalkyl groups and 3- to 12-membered heterocyclic groups, or R ３ and R ４ together with the nitrogen atom directly linked thereto form a 4-10 membered nitrogen-containing heterocyclic group or a 5-10 membered nitrogen-containing heteroaryl group, which independently and optionally further contain deuterium, halogen, cyano group, hydroxy group, ═O, ═S, C １－１０ Alkyl group, halogen-substituted C １－１０ Alkyl group, deuterium-substituted C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C １－１０ Alkoxy group, C ３－１２ Cycloalkyl group, C ３－１２ Cycloalkoxy group, 3- to 12-membered heterocyclic group, 3- to 12-membered heterocyclic oxy group, and —NR １６ R １７ may be substituted by one or more substituents selected from R ５ , R ６ and R ７ are each independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ an aryl group, a 5- to 10-membered heteroaryl group, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ wherein the groups are independently optionally further selected from deuterium, halogen, cyano, nitro, azido, C １－１０ Alkyl group, halogen-substituted C １－１０ Alkyl group, deuterium-substituted C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ Aryl group, 5-10 membered heteroaryl group, ═O, ═S, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from R ８ , R ９ and R １０ are each independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ an aryl group, a 5- to 10-membered heteroaryl group, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ wherein the groups are independently optionally further selected from deuterium, halogen, cyano, nitro, azido, C １－１０ Alkyl group, halogen-substituted C １－１０ Alkyl group, deuterium-substituted C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ Aryl group, 5-10 membered heteroaryl group, ═O, ═S, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Each R １１ and R １２ are each independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ an aryl group, a 5- to 10-membered heteroaryl group, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ or R １１ and R １２ are one C together with the carbon atom directly connected to them. ３－１２ Cycloalkyl group, 4-10 membered heterocyclic group, C ６－１０ aryl or 5-10 membered heteroaryl groups, which may independently optionally further comprise deuterium, halogen, cyano, nitro, azido, C １－１０ Alkyl group, halogen-substituted C １－１０ Alkyl group, deuterium-substituted C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ Aryl group, 5-10 membered heteroaryl group, ═O, ═S, —C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O—S(O) ２ R １３ , -C ０－８ Alkyl-S(O) ｒ R １３ , -C ０－８ Alkyl-O-R １４ , -C ０－８ Alkyl-C(O)OR １４ , -C ０－８ Alkyl-C(O)SR １４ , -C ０－８ Alkyl-S—C(O)R １５ , -C ０－８ Alkyl-C(O)R １５ , -C ０－８ Alkyl-O—C(O)R １５ , -C ０－８ Alkyl-P(O)(R １５ ) ２ , -C ０－８ Alkyl-NR １６ R １７ , -C ０－８ Alkyl-C(O)NR １６ R １７ and -C ０－８ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Each R １３ are independently hydrogen, deuterium, a hydroxyl group, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ Aryl groups, 5- to 10-membered heteroaryl groups, and —NR １６ R １７ wherein said groups are independently optionally further selected from deuterium, halogen, hydroxyl group, ═O, C １－１０ Alkyl group, C １－１０ Alkoxy group, C ３－１２ Cycloalkyl group, C ３－１２ cycloalkoxy group, 3- to 12-membered heterocyclic group, 3- to 12-membered heterocyclic oxy group, C ６－１０ Aryl group, C ６－１０ Aryloxy group, 5- to 10-membered heteroaryl group, 5- to 10-membered heteroaryloxy group and —NR １６ R １７ and is substituted by one or more substituents selected from Each R １４ are independently hydrogen, deuterium, and C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ aryl groups and 5-10 membered heteroaryl groups, said groups independently optionally further comprising deuterium, halogen, hydroxyl groups, ═O, cyano groups, C １－１０ Alkyl group, C １－１０ Alkoxy group, C ３－１２ Cycloalkyl group, C ３－１２ cycloalkoxy group, 3- to 12-membered heterocyclic group, 3- to 12-membered heterocyclic oxy group, C ６－１０ Aryl group, C ６－１０ Aryloxy group, 5- to 10-membered heteroaryl group, 5- to 10-membered heteroaryloxy group and —NR １６ R １７ and is substituted by one or more substituents selected from Each R １５ are independently hydrogen, deuterium, a hydroxyl group, C １－１０ Alkyl group, C １－１０ Alkoxy group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl group, C ３－１２ cycloalkoxy group, 3- to 12-membered heterocyclic group, 3- to 12-membered heterocyclic oxy group, C ６－１０ Aryl group, C ６－１０ Aryloxy group, 5- to 10-membered heteroaryl group, 5- to 10-membered heteroaryloxy group and —NR １６ R １７ wherein said groups independently optionally further comprise deuterium, halogen, hydroxyl, ═O, cyano, C １－１０ Alkyl group, C １－１０ Alkoxy group, C ３－１２ Cycloalkyl group, C ３－１２ cycloalkoxy group, 3- to 12-membered heterocyclic group, 3- to 12-membered heterocyclic oxy group, C ６－１０ Aryl group, C ６－１０ Aryloxy group, 5- to 10-membered heteroaryl group, 5- to 10-membered heteroaryloxy group and —NR １６ R １７ and is substituted by one or more substituents selected from Each R １６ and R １７ are each independently hydrogen, deuterium, a hydroxyl group, or C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, C ３－１２ Cycloalkyl groups, 3-12 membered heterocyclic groups, C ６－１０ Aryl group, 5- to 10-membered heteroaryl group, sulfinyl group, sulfonyl group, methylsulfonyl group, isopropylsulfonyl group, cyclopropylsulfonyl group, p-toluenesulfonyl group, aminosulfonyl group, dimethylaminosulfonyl group, and C １－１０ alkanoyl groups, said groups independently optionally further containing deuterium, halogen, hydroxyl group, ═O, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, halogen-substituted C １－１０ Alkyl group, deuterium-substituted C １－１０ Alkyl group, C １－１０ Alkoxy group, C ３－１２ Cycloalkyl group, C ３－１２ cycloalkoxy group, 3- to 12-membered heterocyclic group, 3- to 12-membered heterocyclic oxy group, C ６－１０ Aryl group, C ６－１０ an aryloxy group, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryloxy group, an amino group, C １－１０ Alkyl-single-substituted amino group, C １－１０ Alkyl doubly substituted amino groups and C １－１０ substituted by one or more substituents selected from alkanoyl groups, R １６ and R １７ form a 4-10 membered heterocyclic group or a 5-10 membered heteroaryl group together with the nitrogen atom directly linked thereto, and the 4-10 membered heterocyclic group or the 5-10 membered heteroaryl group may optionally further contain deuterium, halogen, a hydroxy group, ═O, C １－１０ Alkyl group, C ２－１０ Alkenyl group, C ２－１０ Alkynyl group, halogen-substituted C １－１０ Alkyl group, deuterium-substituted C １－１０ Alkyl group, C １－１０ Alkoxy group, C ３－１２ Cycloalkyl group, C ３－１２ cycloalkoxy group, 3- to 12-membered heterocyclic group, 3- to 12-membered heterocyclic oxy group, C ６－１０ Aryl group, C ６－１０ an aryloxy group, a 5- to 10-membered heteroaryl group, a 5- to 10-membered heteroaryloxy group, an amino group, C １－１０ Alkyl-single-substituted amino group, C １－１０ Alkyl doubly substituted amino groups and C １－１０ substituted by one or more substituents selected from alkanoyl groups, m is 0, 1 or 2; n is 0, 1, 2, 3, 4, 5, or 6; A compound represented by formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, characterized in that each r is independently 0, 1 or 2.

2. R ３ and R ４ are each independently hydrogen, deuterium, a hydroxyl group, or C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ cycloalkyl groups and 3-6 membered heterocyclic groups, said groups independently optionally further containing deuterium, halogen, cyano, hydroxy, ═O, ═S, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C １－４ Alkoxy group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, and —NR １６ R １７ and is substituted by one or more substituents selected from Here, R １６ and R １７ is characterized in that it is as defined in claim 1 A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

3. R 3 and R 4 are each independently selected from hydrogen, deuterium, a hydroxy group, a C 1-4 alkyl group, a halogen-substituted C 1-4 alkyl group, a deuterium-substituted C 1-4 alkyl group, a C 2-4 alkenyl group, a C 2-4 alkynyl group, a C 3-6 cycloalkyl group, and a 3- to 6-membered heterocyclic group.

3. A compound represented by formula (I) according to claim 2, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

4. R ５ , R ６ and R ７ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ an aryl group, a 5- to 8-membered heteroaryl group, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ wherein said groups are independently optionally further selected from deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, ═O, ═S, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Here, R １３ , R １４ , R １５ , R １６ , R １７ and r are as defined in claim 1. A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

5. R 5 , R 6 and R 7 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and —N(R 16 )—C(O)R 15 , said groups being independently optionally further selected from deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, ═O, ═S, —SF 5 , —O—S(O) 2 R 13 , —S(O) r R 13 , —O—R 14 , —C(O)OR 14 , —C(O)SR 14 , —S—C(O)R 15 , —C(O)R 15 , —O—C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ; wherein R 13 , R 14 , R 15 , R 16 , R 17 and r are as defined in claim 1.

5. A compound represented by formula (I) according to claim 4, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

6. R ８ , R ９ and R １０ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ an aryl group, a 5- to 8-membered heteroaryl group, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ wherein said groups are independently optionally further selected from deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, ═O, ═S, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Here, R １３ , R １４ , R １５ , R １６ , R １７ and r are as defined in claim 1. A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

7. R 8 , R 9 and R 10 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and —N(R 16 )—C(O)R 15 are independently optionally further selected from deuterium, halogen, cyano, C 1-4 alkyl, halogen-substituted C 1-4 alkyl, deuterium-substituted C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-8 aryl, 5-8 membered heteroaryl, ═O, ═S, —SF 5 , —O—S(O) 2 R 13 , —S(O) r R 13 , —O—R 14 , —C(O)OR 14 , —C(O)SR 14 , —S—C(O)R 15 , —C(O)R 15 , —O—C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ; wherein R 13 , R 14 , R 15 , R 16 , R 17 and r are as defined in claim 1.

7. A compound represented by formula (I) according to claim 6, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

8. Each R １１ and R １２ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ an aryl group, a 5- to 8-membered heteroaryl group, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ or R １１ and R １２ are one C together with the carbon atom directly connected to them. ３－６ Cycloalkyl groups, 4-8 membered heterocyclic groups, C ６－８ aryl or 5-8 membered heteroaryl groups, which may independently optionally further comprise deuterium, halogen, cyano, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, ═O, ═S, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Here, R １３ , R １４ , R １５ , R １６ , R １７ and r are as defined in claim 1. A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

9. Each R 11 and R 12 independently represents hydrogen, deuterium, halogen, cyano, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-8 aryl, 5-8 membered heteroaryl, -SF 5 , -O-S(O) 2 R 13 , -S(O) r R 13 , -O-R 14 , -C(O)OR 14 , -C(O)SR 14 , -S-C(O)R 15 , -C(O)R 15 , -O-C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and —N(R 16 )—C(O)R 15 , said groups being independently optionally further selected from deuterium, halogen, cyano, C 1-4 alkyl, halogen-substituted C 1-4 alkyl, deuterium-substituted C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-8 aryl, 5-8 membered heteroaryl, ═O, ═S, —SF 5 , —O—S(O) 2 R 13 , —S(O) r R 13 , —O—R 14 , —C(O)OR 14 , —C(O)SR 14 , —S—C(O)R 15 , —C(O)R 15 , —O—C(O)R 15 , -P(O)(R 15 ) 2 , -NR 16 R 17 , -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 ; wherein R 13 , R 14 , R 15 , R 16 , R 17 and r are as defined in claim 1.

9. A compound represented by formula (I) according to claim 8, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

10. R １ is -(CR １１ R １２ ) ｍ -R, or R １ and R ２ form one ring B together with the nitrogen atom directly bonded thereto, and the ring B is a 4-10 membered nitrogen-containing heterocyclic group or a 5-10 membered nitrogen-containing heteroaryl group, and the ring B optionally further contains R, deuterium, halogen, a cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl groups, ═O, ═S, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from R is -ring A-(R ａ ) ｎ wherein ring A is C ３－６ Cycloalkyl groups, 4-8 membered heterocyclic groups, C ６－８ an aryl group or a 5- to 8-membered heteroaryl group, ３－６ The cycloalkyl group or the 4- to 8-membered heterocyclic group may optionally further comprise C ６－８ fused to an aryl group or a 5- to 8-membered heteroaryl group, ６－８ The aryl group or 5-8 membered heteroaryl group is optionally a 5-8 membered heteroaryl group, C ３－６ fused to a cycloalkyl group or a 4- to 8-membered heterocyclic group; Each R ａ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ an aryl group, a 5- to 8-membered heteroaryl group, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ wherein said groups are independently optionally further selected from deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, ═O, ═S, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from R ２ is hydrogen, deuterium, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, —S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)R １５ and —C(O)NR １６ R １７ wherein said groups independently optionally further comprise deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, halogen-substituted C ３－６ Cycloalkyl group, halogen-substituted 3-6 membered heterocyclic group, halogen-substituted C ６－８ Aryl group, halogen-substituted 5-8 membered heteroaryl group, C １－４ Alkyl-substituted C ３－６ Cycloalkyl group, C １－４ Alkyl-substituted 3-6 membered heterocyclic group, C １－４ Alkyl-substituted C ６－８ Aryl group, C １－４ Alkyl-substituted 5-8 membered heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, ═O, ═S, —C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O—S(O) ２ R １３ , -C ０－４ Alkyl-S(O) ｒ R １３ , -C ０－４ Alkyl-O-R １４ , -C ０－４ Alkyl-C(O)OR １４ , -C ０－４ Alkyl-C(O)SR １４ , -C ０－４ Alkyl-S—C(O)R １５ , -C ０－４ Alkyl-C(O)R １５ , -C ０－４ Alkyl-O—C(O)R １５ , -C ０－４ Alkyl-P(O)(R １５ ) ２ , -C ０－４ Alkyl-NR １６ R １７ , -C ０－４ Alkyl-C(O)NR １６ R １７ and -C ０－４ Alkyl-N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Here, R １１ , R １２ , R １３ , R １４ , R １５ , R １６ , R １７ , m, n and r are as defined in claim 1. A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

11. Each R １３ are independently hydrogen, deuterium, a hydroxyl group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl groups, 5-8 membered heteroaryl groups and -NR １６ R １７ wherein said groups are independently optionally further selected from deuterium, halogen, hydroxyl group, ═O, C １－４ Alkyl group, C １－４ Alkoxy group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group and —NR １６ R １７ and is substituted by one or more substituents selected from Each R １４ are independently hydrogen, deuterium, and C １－４ Alkyl group, C ２－４ Alkenyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ aryl groups and 5-8 membered heteroaryl groups, said groups independently optionally further comprising deuterium, halogen, hydroxyl groups, ═O, cyano groups, C １－４ Alkyl group, C １－４ Alkoxy group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group and —NR １６ R １７ and is substituted by one or more substituents selected from Each R １５ are independently hydrogen, deuterium, a hydroxyl group, C １－４ Alkyl group, C １－４ Alkoxy group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group and —NR １６ R １７ wherein said groups independently optionally further comprise deuterium, halogen, hydroxyl, ═O, cyano, C １－４ Alkyl group, C １－４ Alkoxy Group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group and —NR １６ R １７ and is substituted by one or more substituents selected from Each R １６ and R １７ are each independently hydrogen, deuterium, a hydroxyl group, or C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ an aryl group, a 5- to 8-membered heteroaryl group, a sulfinyl group, a sulfonyl group, a methylsulfonyl group, an isopropylsulfonyl group, a cyclopropylsulfonyl group, a p-toluenesulfonyl group, an aminosulfonyl group, a dimethylaminosulfonyl group, and C １－４ alkanoyl groups, said groups independently optionally further containing deuterium, halogen, hydroxyl group, ═O, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C １－４ Alkoxy group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group, amino group, C １－４ Alkyl-single-substituted amino group, C １－４ Alkyl doubly substituted amino groups and C １－４ substituted by one or more substituents selected from alkanoyl groups, R １６ and R １７ form a 4-8 membered heterocyclic group or a 5-8 membered heteroaryl group together with the nitrogen atom directly linked thereto, and the 4-8 membered heterocyclic group or the 5-8 membered heteroaryl group may optionally further contain deuterium, halogen, a hydroxy group, ═O, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C １－４ Alkoxy group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group, amino group, C １－４ Alkyl-single-substituted amino group, C １－４ Alkyl doubly substituted amino groups and C １－４ substituted with one or more substituents selected from alkanoyl groups A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

12. The compound of formula (I) has the structure of the compound of formula (II) below: 【Transformation 3】 Here, X ３ is CR ５ or N, and X ４ is CR ６ or N, and X ５ is CR ７ or N, and X ６ is CR ８ or N, and X ７ is CR ９ or N, R １ is -(CR １１ R １２ ) ｍ -R, or R １ and R ２ form one ring B together with the nitrogen atom directly bonded thereto, and the ring B is a 4-10 membered nitrogen-containing heterocyclic group or a 5-10 membered nitrogen-containing heteroaryl group, and the ring B optionally further contains R, deuterium, halogen, a cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, ═O, ═S, —SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , -C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from R is the following structure: 【Chemistry 4】 and Here, Y １ , Y ２ , Y ４ , Y ５ , Y ６ , Y ７ , Y ８ , Y ９ , Y １０ , Y １１ , Y １２ , Y １３ are each independently CR ａ or N, and Y ３ is —O—, —S— or —NR ａ３ -, and Z is -O-, -S-, or -CR ａ１ R ａ２ -, -CR ａ１ R ａ２ —O— or —NR ａ３ -, and p is 0, 1, 2 or 3; Each R ａ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, -SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ wherein said groups are independently optionally further selected from deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, ═O, ═S, —SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Each R ａ１ and R ａ２ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, -SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ wherein said groups are independently optionally further selected from deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, ═O, ═S, —SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Each R ａ３ are independently hydrogen, deuterium, and C １－４ Alkyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, -SF ５ , -C(O)OR １４ , -C(O)SR １４ , -C(O)R １５ and —C(O)NR １６ R １７ wherein said groups are independently optionally further selected from deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, ═O, ═S, —SF ５ , -O-S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from Each R ２ are independently hydrogen, deuterium, and C １－４ Alkyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ aryl groups and 5-8 membered heteroaryl groups, said groups independently optionally further containing deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, halogen-substituted C ３－６ Cycloalkyl group, halogen-substituted 3-6 membered heterocyclic group, halogen-substituted C ６－８ Aryl group, halogen-substituted 5-8 membered heteroaryl group, C １－４ Alkyl-substituted C ３－６ Cycloalkyl group, C １－４ Alkyl-substituted 3-6 membered heterocyclic group, C １－４ Alkyl-substituted C ６－８ Aryl group, C １－４ Alkyl-substituted 5-8 membered heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, ═O, ═S, —SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ and is substituted by one or more substituents selected from R ５ , R ６ and R ７ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, -SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ Selected from R ８ and R ９ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, -SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ Selected from Each R １１ and R １２ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, -SF ５ , —O—S(O) ２ R １３ , -S(O) ｒ R １３ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -S-C(O)R １５ , -C(O)R １５ , —O—C(O)R １５ , -P(O)(R １５ ) ２ , -NR １６ R １７ , —C(O)NR １６ R １７ and -N(R １６ )-C(O)R １５ Selected from Here, R １３ , R １４ , R １５ , R １６ , R １７ , r and m are as defined in claim 1. A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

13. The compound represented by formula (I) is represented by the following formula (III) １ ) or formula (III ２ ) a compound having the structure represented by 【Transformation 5】 Here, each X ３ are each independently CR ５ or N, and each X ４ are each independently CR ６ or N, and each X ５ are each independently CR ７ or N, and each X ６ are each independently CR ８ or N, Formula (III ２ In the structure of the compound represented by the formula (I), ring B is a 4-10 membered nitrogen-containing heterocyclic group, and the 4-10 membered nitrogen-containing heterocyclic group optionally further contains hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C １－４ Alkoxy group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3- to 6-membered heterocyclic group, —SF ５ and -NR １６ R １７ and is substituted by one or more substituents selected from Each R independently represents the following structure: 【Transformation 6】 and Here, Y １ , Y ２ , Y ６ , Y ７ , Y ８ , Y ９ , Y １０ and Y １１ are each independently CR ａ or N, and Y ３ is —O— or —S—, and Z is —O—, —S—, or —CH ２ - or -CH ２ -O-, and p is 0, 1, 2, or 3; Each R ａ are each independently hydrogen, deuterium, halogen, cyano group, C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, -SF ５ , -O-R １４ , -C(O)OR １４ , -C(O)SR １４ , -C(O)R １５ , —O—C(O)R １５ and -NR １６ R １７ wherein said groups are independently optionally further selected from deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, ═O, ═S, —SF ５ , -O-R １４ , -C(O)OR １４ , -C(O)R １５ , —O—C(O)R １５ and -NR １６ R １７ and is substituted by one or more substituents selected from R ２ is hydrogen, deuterium, C １－４ Alkyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ aryl groups and 5-8 membered heteroaryl groups, said groups independently optionally further containing deuterium, halogen, cyano group, C １－４ Alkyl group, halogen-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkyl group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, 3-6 membered heterocyclic group, C ６－８ Aryl group, 5-8 membered heteroaryl group, halogen-substituted C ３－６ Cycloalkyl group, halogen-substituted 3-6 membered heterocyclic group, halogen-substituted C ６－８ Aryl group, halogen-substituted 5-8 membered heteroaryl group, C １－４ Alkyl-substituted C ３－６ Cycloalkyl group, C １－４ Alkyl-substituted 3-6 membered heterocyclic group, C １－４ Alkyl-substituted C ６－８ Aryl group, C １－４ Alkyl-substituted 5-8 membered heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, ═O, ═S, —SF ５ , -O-R １４ , -C(O)OR １４ , -C(O)R １５ , —O—C(O)R １５ and -NR １６ R １７ and is substituted by one or more substituents selected from Each R ５ , R ６ and R ７ are each independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C １－４ Alkyl group, C １－４ Alkoxy group, halogen-substituted C １－４ Alkyl group, halogen-substituted C １－４ Alkoxy group, deuterium-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkoxy group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group, -SF ５ and -NR １６ R １７ Selected from Each R ８ are each independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C １－４ Alkyl group, C １－４ Alkoxy group, halogen-substituted C １－４ Alkyl group, halogen-substituted C １－４ Alkoxy group, deuterium-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkoxy group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group, -SF ５ and -NR １６ R １７ Selected from Each R １１ and R １２ are each independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C １－４ Alkyl group, C １－４ Alkoxy group, halogen-substituted C １－４ Alkyl group, halogen-substituted C １－４ Alkoxy group, deuterium-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkoxy group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group, -SF ５ and -NR １６ R １７ Selected from Here, R １４ , R １５ , R １６ and R １７ is characterized in that it is as defined in claim 1 A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

14. The structure includes 【Transformation 7】 " has the following structure: 【Transformation 8】 Selected from Each X ６ are each independently CR ８ or N, Each R ５ , R ６ and R ７ are each independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C １－４ Alkyl group, C １－４ Alkoxy group, halogen-substituted C １－４ Alkyl group, halogen-substituted C １－４ Alkoxy group, deuterium-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkoxy group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group, -SF ５ , amino group, mono C １－４ Alkyl-substituted amino groups and bisC １－４ alkyl-substituted amino groups; Each R ８ are each independently hydrogen, deuterium, halogen, cyano group, hydroxy group, carboxy group, C １－４ Alkyl group, C １－４ Alkoxy group, halogen-substituted C １－４ Alkyl group, halogen-substituted C １－４ Alkoxy group, deuterium-substituted C １－４ Alkyl group, deuterium-substituted C １－４ Alkoxy group, C ２－４ Alkenyl group, C ２－４ Alkynyl group, C ３－６ Cycloalkyl group, C ３－６ Cycloalkoxy group, 3- to 6-membered heterocyclic group, 3- to 6-membered heterocyclic oxy group, C ６－８ Aryl group, C ６－８ Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group, -SF ５ , amino group, mono C １－４ Alkyl-substituted amino groups and bisC １－４ alkyl-substituted amino groups 14. A compound represented by formula (I) according to claim 13, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

15. The compound represented by formula (I) is represented by the following formula (IV): １－１ ), (IV １－２ ), (IV ２－１ ) or (IV ２－２ ) a compound having the structure represented by 【Chemistry 9】 Here, each X ４ are each independently CR ６ or N, and each X ５ are each independently CR ７ or N, Each Y ６ and each Y ７ are each independently CH or N, and Z is O or CH ２ and p is 1 or 2; Formula (IV ２－１ ) or (IV ２－２ In the structure of the compound represented by the formula (I), ring B, together with the substituents thereon, has the following structure: 【Chemistry 10】 and q is selected from 0, 1 or 2; Each R' is independently hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxy, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, trideuteromethyl, methoxy, ethoxy, cyclopropyl, or -SF ５ Selected from each R″ is independently selected from hydrogen, deuterium, hydroxy, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, trideuteromethyl, and cyclopropyl; Each R ２ are each independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, cyclopropyl, cyclobutyl, bicyclo[1.1.1]pentyl, cyclohexyl, oxetanyl, azetidinyl, tetrahydrofuranyl, phenyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, and triazinyl, which groups may independently and optionally further comprise deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, a methyl group, an isobutyl group, a trifluoromethyl group, a difluoromethyl group, a trideuteromethyl group, a diduteromethyl group, a vinyl group, an ethynyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a bicyclo[1.1.1]pentyl group, a cyclohexyl group, an oxetanyl group, an azacyclopentyl group, a tetrahydrofuranyl group, a phenyl group, a pyrazolyl group, a 2-(trimethylsilyl)ethoxy group, a methyl-substituted pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazolyl group, a thiazolyl group, a pyridyl group, a fluorine-substituted pyridyl group, a pyridazinyl group, a pyrimidinyl group, a triazinyl group, ═O, ═S, or —SF ５ , substituted by one or more substituents selected from a hydroxy group, a methoxy group, an ethoxy group, a cyclopropoxy group, a cyclobutoxy group, an amino group, a methylamino group, and a dimethylamino group; Each R ａ each independently represents hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, trifluoromethyl, difluoromethyl, trideuteromethyl, dideuteromethyl, trifluoromethoxy, trideuteromethoxy, vinyl, ethynyl, cyclopropyl, cyclobutyl, methyl-substituted cyclopropyl, methyl-substituted cyclobutyl, cyclopropoxy, cyclobutoxy, oxetanyl, azetidinyl, tetrahydropyrrolyl, piperidinyl, methyl-substituted piperidinyl, phenyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, pyrimidinyl, methyl-substituted pyrazolyl, -SF ５ , a hydroxy group, an amino group, a methylamino group, a dimethylamino group, a dimethylaminomethyl group, and a dimethylaminoethyl group; Each R ６ are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxy, methyl, ethyl, n-propyl, isopropyl, methoxy, trifluoromethyl, trifluoromethoxy, trideuteromethyl, trideuteromethoxy and cyclopropyl; Each R ７ are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxy, methyl, ethyl, n-propyl, isopropyl, methoxy, trifluoromethyl, trifluoromethoxy, trideuteromethyl, trideuteromethoxy and cyclopropyl; Each R ８ are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano, hydroxy, methyl, ethyl, n-propyl, isopropyl, methoxy, trifluoromethyl, trifluoromethoxy, trideuteromethyl, trideuteromethoxy and cyclopropyl; R １１ and R １２ are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group. A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

16. Included in the structure 【Chemistry 11】 has the following structure: 【Chemistry 12】 Selected from R ７ is selected from hydrogen, deuterium, fluorine, chlorine, methyl, trifluoromethyl, trideuteromethyl and cyclopropyl; R ８ is selected from hydrogen, deuterium, fluorine, chlorine, bromine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group.

16. A compound represented by formula (I) according to claim 15, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

17. Formula (IV １－２ ) and (IV ２－１ ) in the structure of the compound represented by 【Chemistry 13】 " has the following structure: 【Chemistry 14】 Selected from Formula (IV １－１ ) in the structure of the compound represented by 【Chemistry 15】 " has the following structure: 【Chemistry 16】 Selected from Each R ａ each independently represents hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, isopropyl, methoxy, trifluoromethyl, trideuteromethyl, trifluoromethoxy, trideuteromethoxy, cyclopropyl, pyrazolyl, methyl-substituted pyrazolyl, and -SF ５ characterized in that it is selected from 16. A compound represented by formula (I) according to claim 15, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

18. Each R ２ are each independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, bicyclo[1.1.1]pentyl, cyclohexyl, oxetanyl, azetidinyl, tetrahydrofuranyl, pyrazolyl, imidazolyl, thiazolyl, pyridyl, and pyrimidinyl, which groups independently and optionally further include deuterium, fluorine, chlorine, bromine, cyano, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, difluoromethyl, and substituted with one or more substituents selected from a trideuteromethyl group, a diduteromethyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a bicyclo[1.1.1]pentyl group, a cyclohexyl group, an oxetanyl group, an azetidinyl group, a tetrahydrofuranyl group, a pyrazolyl group, a (2-(trimethylsilyl)ethoxy)methyl-substituted pyrazolyl group, an imidazolyl group, a thiazolyl group, a pyridyl group, a fluorine-substituted pyridyl group, a pyrimidinyl group, a methoxy group, an ethoxy group, and a cyclopropoxy group.

16. A compound represented by formula (I) according to claim 15, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

19. Each R ２ each independently represents hydrogen, deuterium, a methyl group, an ethyl group, a trifluoromethyl group, a trifluoroethyl group, a trideuteromethyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, a cyclobutyl group, or the structure of a substituent represented by the following formula: 【Chemistry 17】 characterized in that it is selected from 16. A compound represented by formula (I) according to claim 15, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

20. The compound represented by formula (I) is represented by the following formula (V １－１－１ ) or formula (V １－１－２ ) a compound having the structure represented by [Chemistry 18] Here, each Y ７ are each independently CH or N, and each Z is each independently O or CH ２ and each R ａ each independently represents hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, methoxy, trifluoromethyl, trideuteromethyl, trifluoromethoxy, trideuteromethoxy, cyclopropyl, pyrazolyl, methyl-substituted pyrazolyl, and -SF ５ Selected from Each R ７ are each independently selected from hydrogen, deuterium, fluorine, chlorine, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group; Each R ８ are each independently selected from hydrogen, deuterium, fluorine, chlorine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group; Here, R ２ is characterized in that it is as defined in claim 15 16. A compound represented by formula (I) according to claim 15, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

21. The compound represented by formula (I) is represented by the following formula (V １－２－１ ) or formula (V １－２－２ ) a compound having the structure represented by 【Chemistry 19】 Here, each Y ６ and each Y ７ are each independently CH or N, and R ａ represents hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, methoxy, trifluoromethyl, trideuteromethyl, trifluoromethoxy, trideuteromethoxy, cyclopropyl, pyrazolyl, methyl-substituted pyrazolyl, and -SF ５ Selected from R ７ is selected from hydrogen, deuterium, fluorine, chlorine, methyl, trifluoromethyl, trideuteromethyl and cyclopropyl; R ８ is selected from hydrogen, deuterium, fluorine, chlorine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group.

16. A compound represented by formula (I) according to claim 15, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

22. The compound represented by formula (I) is represented by the following formula (V ２－１－１ ) or formula (V ２－１－２ ) a compound having the structure represented by 【Chemistry 20】 Here, each R ａ each independently represents hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, methoxy, trifluoromethyl, trideuteromethyl, trifluoromethoxy, trideuteromethoxy, cyclopropyl, pyrazolyl, methyl-substituted pyrazolyl, and -SF ５ Selected from each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl, trifluoromethyl, trideuteromethyl, and cyclopropyl; Each R ７ are each independently selected from hydrogen, deuterium, fluorine, chlorine, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group; Each R ８ are each independently selected from hydrogen, deuterium, fluorine, chlorine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group.

16. A compound represented by formula (I) according to claim 15, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

23. The compound represented by formula (I) is represented by the following formula (V ２－２－１ ) or formula (V ２－２－２ ) a compound having the structure represented by 【Chemistry 21】 Here, each R ａ are each independently hydrogen, deuterium, fluorine, chlorine, bromine, cyano, methyl, methoxy, trifluoromethyl, trideuteromethyl, trifluoromethoxy, trideuteromethoxy, cyclopropyl, pyrazolyl, methyl-substituted pyrazolyl, methyl-substituted piperidinyl, dimethylaminoethyl, and -SF ５ Selected from each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl, trifluoromethyl, trideuteromethyl, and cyclopropyl; Each R ７ are each independently selected from hydrogen, deuterium, fluorine, chlorine, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group; Each R ８ are each independently selected from hydrogen, deuterium, fluorine, chlorine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group.

16. A compound represented by formula (I) according to claim 15, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

24. The following compound: 【Chemistry 22】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 characterized in that it is selected from A compound represented by formula (I) according to any one of claims 1 to 23, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

25. 1. A pharmaceutical composition comprising:

10. A pharmaceutical composition comprising the compound of formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

26. 10. Use of the compound of formula (I) according to claim 1, its stereoisomer or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating MATP-associated tumors.

27. The tumor is selected from the group consisting of carcinoma, lymphoma, leukemia, osteoma, malignant teratoma, carcinoma in situ, adenoma, fibroma, melanoma, fallopian tube cancer, bladder cancer, teratoma, embryonal carcinoma, choriocarcinoma, lipoma, liver cancer, bile duct cancer, lung cancer, gastric cancer, hemangioma, gallbladder cancer, ampullary carcinoma, malignant melanoma, nevus, dysplastic nevus, myeloproliferative disorders, Hodgkin's disease, chordoma, myxoma, rhabdomyoma, leiomyoma, hamartoma, mesothelioma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, viperoma, granuloma, xanthomas, osteitis deformans, ependymoma, schwannoma, congenital tumors, meningioma, glioma, skin cancer, head and neck cancer, and sarcoma.

27. The use according to claim 26.

28. the cell tumor is selected from granulosa-thecal cell tumor, Sertoli cell tumor, germ cell tumor, nephroblastoma, seminoma, hepatoblastoma, malignant fibrous histiocytoma, chondroblastoma, giant cell tumor, astrocytoma, medulloblastoma, glioblastoma multiforme, oligodendroglioma, retinoblastoma, squamous cell carcinoma, clear cell carcinoma, transitional cell carcinoma, stromal cell carcinoma, and basal cell carcinoma; the lymphoma is selected from malignant lymphoma and non-Hodgkin's lymphoma; the leukemia is selected from acute chronic myeloid leukemia, acute lymphocytic leukemia, and chronic lymphocytic leukemia; the osteoma is selected from osteochondroma, benign chondroma, osteoid osteoma, chondromatous hamartoma, multiple myeloma, and cranial osteoma; the adenoma is selected from fibroadenoma, adenomatous tumor, hepatocellular adenoma, bronchial adenoma, tubular adenoma, villous adenoma, breast cancer, pancreatic cancer, endometrial adenocarcinoma, prostate cancer, ductal adenocarcinoma, and colorectal adenocarcinoma; the fibroma is selected from fibroma, chondromyxoid fibroma, neurofibroma and spinal neurofibroma; the myeloproliferative disorder is selected from multiple myeloma and myelodysplastic syndrome; the lung cancer is selected from bronchopulmonary carcinoma and alveolar carcinoma; The sarcoma is selected from the group consisting of fibrosarcoma, botryosarcoma, angiosarcoma, Kaposi's sarcoma, osteosarcoma, chondrosarcoma, Ewing's sarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, and meningeal sarcoma.

28. The use according to claim 27.

29. A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, 10. A compound represented by formula (I) according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, which is used as a PRMT5 inhibitor.

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