PRMT5 Inhibitor, Method for Producing the Same, and Application in Pharmacy

Abstract

The present invention relates to a PRMT5 inhibitor, a method for producing the same, and its application in pharmacy. In particular, the present invention relates to a PRMT5 inhibitor having the structure of formula (I), a method for producing the same, a pharmaceutical composition containing the same, its use as a PRMT5 inhibitor, and its use in the treatment and / or prevention of diseases mediated by PRMT5. The definition of each substituent in formula (I) is the same as the definition in the specification. 【Chemical 1】 TIFF2025520530000195.tif46170

Description

Detailed Description of the Invention

[0001] [Technical Field] The present invention belongs to the field of drug synthesis, and specifically relates to a PRMT5 inhibitor, a method for producing the same, and an application in pharmacy.

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

[0003] Epigenetic control involves regulating heritable genetic material without changing the nucleic acid sequence. Usually, epigenetic control controls the conversion between the transcriptionally active state and the inactive state 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 of the methyltransferases are associated with specific genetic changes in many human disease-causing 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 driving factor for tumors and often causes deletion of passenger genes near the suppressor genes. Deletion of these passenger genes results in specific vulnerabilities of tumor cells and can be targeted by targeted therapies. Homozygous deletion of the chromosomal 9p21 site containing the well-known tumor suppressor gene CDKN2A occurs in 15% of tumors and often includes deletion of the passenger gene MTAP. MTAP is an important enzyme in the recycling pathway of methionine and adenine. Deletion of MTAP causes accumulation of its substrate MTA. MTA is structurally similar to S-adenosylmethionine (SAM), which is the methyl group donor substrate for type II methyltransferase PRMT5. An increase in MTA levels due to deletion of MTAP may selectively compete with SAM in the binding of PRMT5, rendering the methyltransferase ineffective and more susceptible to inhibition by PRMT5. A number of different genome-wide siRNA screenings applied to a wide range of tumor cell lines have shown a correlation between deletion of MTAP and PRMT5-dependence of the cell line, so this metabolic susceptibility effect has come to the spotlight. However, PRMT5 is a very important gene for cells, and all studies on conditional knockout or siRNA knockout of PRMT5 suggest that inhibition of PRMT5 in normal tissues causes serious side effects. (For example, decrease in blood cells, infertility, decrease in skeletal muscle, cardiac hypertrophy, etc.). Therefore, there is a need for a new strategy to apply and explore metabolic susceptibility by selectively targeting PRMT5 in MTAP-deleted tumors while avoiding the action on PRMT5 in normal tissues (MTAP wild type).

[0005] Small molecule inhibitors targeting PRMT5 that work with MTA can selectively target only PRMT5, which is enriched only in MTAP-deleted tumor cells in a bound state with MTA. Therefore, when MTAP is complete and MTA levels are very low in normal cells, PRMT5 is not targeted, thereby providing a better therapeutic window.

[0006] [Summary of the Invention] The object of the present invention is to provide a PRMT5 inhibitor, a method for producing the same, and an application in pharmacy. A series of compounds of the present invention have a strong inhibitory effect on PRMT5 and can be widely applied to the production of drugs for treating and / or preventing diseases mediated by PRMT5, and the development of a new generation of PRMT5 inhibitors can be expected.

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

[0008]

Chemical formula

[0009] wherein X1 is CR6 or N, X2 is CR7 or N, X3 is CR8 or N, Ring A is a C 3-10 cycloalkyl group, a 4- to 10-membered heterocyclic group, a C 6-10 aryl group or a 5- to 10-membered heteroaryl group, and the C 3-10 cycloalkyl group or 4- to 10-membered heterocyclic group is further condensed with a C 6-10 aryl group or a 5- to 10-membered heteroaryl group, and the C 6-10 aryl group or a 5- to 10-membered heteroaryl group is further condensed with a C 3-10 cycloalkyl group or a 4- to 10-membered heterocyclic group, Ring B is a C 4-12 cycloalkyl group, a 4- to 12-membered heterocyclic group, a C 6-10 aryl group or a 5- to 10-membered heteroaryl group, Each R1 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, a 3- to 12-membered heterocyclic group, C 6-10 aryl group, a 5- to 10-membered heteroaryl group, -C 0-8 alkyl-SF5, -C 0-8 alkyl-O-S(O)2R9, -C 0-8Alkyl-S(O) r R9, -C 0-8 Alkyl-O-R 10 , -C 0-8 Alkyl-C(O)OR 10 , -C 0-8 Alkyl-C(O)SR 10 , -C 0-8 Alkyl-S-C(O)R 11 , -C 0-8 Alkyl-C(O)R 11 , -C 0-8 Alkyl-O-C(O)R 11 , -C 0-8 Alkyl-P(O)(R 11 )2, -C 0-8 Alkyl-NR 12 R 13 , -C 0-8 Alkyl-C(O)NR 12 R 13 and -C 0-8 Alkyl-N(R 12 )-C(O)R 11 selected from, and said groups are independently optionally 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-SF5, -C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 , -C 0-8 alkyl-C(O)OR 10 , -C 0-8 alkyl-C(O)SR 10 , -C 0-8 alkyl-S-C(O)R 11 , -C 0-8 alkyl-C(O)R 11 , -C 0-8Alkyl-O-C(O)R 11 , -C 0-8 Alkyl-P(O)(R 11 )2, -C 0-8 Alkyl-NR 12 R 13 , -C 0-8 Alkyl-C(O)NR 12 R 13 and -C 0-8 Alkyl-N(R 12 )-C(O)R 11 further substituted by one or more substituents selected from R2 is hydrogen, deuterium, 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, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 and -C(O)NR 12 R 13 and the groups are independently optionally 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-SF5, -C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 , -C 0-8 alkyl-C(O)OR 10 , -C 0-8 alkyl-C(O)SR 10 , -C 0-8 alkyl-S-C(O)R 11, -C 0-8 alkyl-C(O)R 11 , -C 0-8 alkyl-O-C(O)R 11 , -C 0-8 alkyl-P(O)(R 11 )2, -C 0-8 alkyl-NR 12 R 13 , -C 0-8 alkyl-C(O)NR 12 R 13 and -C 0-8 alkyl-N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R3 and R4 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 3-12 membered heterocyclic group, or R3 and R4 together with the nitrogen atom to which they are directly attached form a 4-10 membered heterocyclic group or a 5-10 membered heteroaryl group, said groups being independently optionally deuterium, halogen, cyano, hydroxy, =O, =S, C 1-10 alkyl group, halogen-substituted C 1-10 alkyl group, deuterium-substituted C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, a C 1-10 alkoxy group, a C 3-12 cycloalkyl group, a C 3-12 cycloalkoxy group, a 3-12 membered heterocyclic group, a 3-12 membered heterocyclic oxy group and -NR 12 R 13 and is further substituted by one or more substituents selected from Each R5 is independently hydrogen, deuterium, halogen, cyano, nitro, azide, C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, a C 3-12 cycloalkyl group, a 3-12 membered heterocyclic group, C 6-10An aryl group, a 5- to 10-membered heteroaryl group, -C 0-8 alkyl-SF5, -C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 , -C 0-8 alkyl-C(O)OR 10 , -C 0-8 alkyl-C(O)SR 10 , -C 0-8 alkyl-S-C(O)R 11 , -C 0-8 alkyl-C(O)R 11 , -C 0-8 alkyl-O-C(O)R 11 , -C 0-8 alkyl-P(O)(R 11 )2, -C 0-8 alkyl-NR 12 R 13 , -C 0-8 alkyl-C(O)NR 12 R 13 and -C 0-8 alkyl-N(R 12 )-C(O)R 11 selected from, and said groups are independently optionally 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-SF5, -C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 , -C 0-8 alkyl-C(O)OR 10 , -C 0-8 alkyl-C(O)SR 10 , -C0-8 Alkyl-SC(O)R 11 , -C 0-8 Alkyl-C(O)R 11 , -C 0-8 Alkyl-OC(O)R 11 , -C 0-8 Alkyl-P(O)(R 11 )2, -C 0-8 Alkyl-NR 12 R 13 , -C 0-8 Alkyl-C(O)NR 12 R 13 and -C 0-8 Alkyl-N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R6, R7 and R8 are each independently hydrogen, deuterium, a halogen, a cyano group, a nitro group, an azide group, or 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, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-OS(O)2R9, -C 0-8 Alkyl-S(O) r R9, -C 0-8 Alkyl-OR 10 , -C 0-8 Alkyl-C(O)OR 10 , -C 0-8 Alkyl-C(O)SR 10 , -C 0-8 Alkyl-SC(O)R 11 , -C 0-8 Alkyl-C(O)R 11 , -C 0-8 Alkyl-OC(O)R 11 , -C 0-8 Alkyl-P(O)(R 11 )2, -C 0-8 Alkyl-NR 12 R13 , -C 0-8 alkyl - C(O)NR 12 R 13 and -C 0-8 alkyl - N(R 12 ) - C(O)R 11 selected from, each R9 is independently hydrogen, deuterium, a hydroxy group, C 1-10 alkyl group, C 2-10 alkenyl group, C 3-12 cycloalkyl group, a 3 - 12 membered heterocyclic group, C 6-10 aryl group, a 5 - 10 membered heteroaryl group and -NR 12 R 13 selected from, and the groups are independently optionally 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 - 12 membered heterocyclic group, a 3 - 12 membered heterocyclic oxy group, C 6-10 aryl group, C 6-10 aryloxy group, a 5 - 10 membered heteroaryl group, a 5 - 10 membered heteroaryloxy group and -NR 12 R 13 substituted further by one or more substituents selected from, each R 10 is independently hydrogen, deuterium, C 1-10 alkyl group, C 2-10 alkenyl group, C 3-12 cycloalkyl group, a 3 - 12 membered heterocyclic group, C 6-10 aryl group and a 5 - 10 membered heteroaryl group selected from, and the groups are independently optionally deuterium, halogen, hydroxy group, =O, cyano group, C 1-10 alkyl group, C 1-10 alkoxy group, C 3-12 cycloalkyl group, C 3-12 cycloalkoxy group, a 3 - 12 membered heterocyclic group, a 3 - 12 membered heterocyclic oxy group, C 6-10 aryl group, C 6-10 aryloxy group, a 5 - 10 membered heteroaryl group, a 5 - 10 membered heteroaryloxy group and -NR 12 R 13further substituted by one or more substituents selected from each R 11 is independently hydrogen, deuterium, a hydroxy 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, 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 12 R 13 is selected from, and the groups are independently optionally deuterium, halogen, hydroxy group, =O, cyano group, 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 12 R 13 and is further substituted by one or more substituents selected from each R 12 and R 13 are each independently hydrogen, deuterium, hydroxy group, C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl 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, sulfinyl group, sulfonyl group, methylsulfonyl group, isopropylsulfonyl group, cyclopropylsulfonyl group, p-toluenesulfonyl group, aminosulfonyl group, dimethylaminosulfonyl group, and C 1-10 alkanoyl group, and the groups are independently optionally deuterium, halogen, hydroxy group, =O, C 1-10 alkyl group, C 2-10An alkenyl group, C 2-10 An alkynyl group, a halogen-substituted C 1-10 An alkyl group, a deuterium-substituted 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, an amino group, C 1-10 An alkyl-monosubstituted amino group, C 1-10 An alkyl-disubstituted amino group and C 1-10 Is further substituted by one or more substituents selected from an alkanoyl group, or R 12 And R 13 Together with the nitrogen atom to which they are directly attached, form a 4- to 10-membered heterocyclic group or a 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocyclic group or 5- to 10-membered heteroaryl group is optionally deuterium, halogen, hydroxy group, =O, C 1-10 An alkyl group, C 2-10 An alkenyl group, C 2-10 An alkynyl group, a halogen-substituted C 1-10 An alkyl group, a deuterium-substituted 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, an amino group, C 1-10 An alkyl-monosubstituted amino group, C 1-10 An alkyl-disubstituted amino group and C 1-10 Is further substituted by one or more substituents selected from an alkanoyl group, Each r is independently 0, 1 or 2, m is selected from 0, 1, 2, 3, 4, 5 or 6, and n is selected from 0, 1, 2, 3, 4 or 5.

[0010] In a preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, ring A is C 3-8 a cycloalkyl group, a 4- to 8-membered heterocyclic group, C 6-8 an aryl group or a 5- to 8-membered heteroaryl group, and said C 3-8 cycloalkyl group or 4- to 8-membered heterocyclic group is further condensed with C 6-8 an aryl group or a 5- to 8-membered heteroaryl group, said C 6-8 aryl group or 5- to 8-membered heteroaryl group is further condensed with C 3-8 a cycloalkyl group or a 4- to 8-membered heterocyclic group, ring B is C 4-6 a cycloalkyl group, a 4- to 6-membered heterocyclic group, C 6-8 an aryl group or a 5- to 8-membered heteroaryl group, each R1 is independently hydrogen, deuterium, halogen, cyano group, 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- to 6-membered heterocyclic group, C 6-8 an aryl group, a 5- to 8-membered heteroaryl group, -C 0-4 alkyl-SF5, -C 0-4 alkyl-O-S(O)2R9, -C 0-4 alkyl-S(O) r R9, -C 0-4 alkyl-O-R 10 、-C 0-4 alkyl-C(O)OR 10 、-C 0-4 alkyl-C(O)SR 10 、-C 0-4 alkyl-S-C(O)R 11 、-C 0-4 alkyl-C(O)R 11 、-C 0-4 alkyl-O-C(O)R 11 、-C 0-4 alkyl-P(O)(R 11 )2、-C 0-4 alkyl-NR 12 R 13 、-C0-4 alkyl-C(O)NR 12 R 13 and -C 0-4 alkyl-N(R 12 )-C(O)R 11 selected from, said groups are independently optionally 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-SF5, -C 0-4 alkyl-O-S(O)2R9, -C 0-4 alkyl-S(O) r R9, -C 0-4 alkyl-O-R 10 , -C 0-4 alkyl-C(O)OR 10 , -C 0-4 alkyl-C(O)SR 10 , -C 0-4 alkyl-S-C(O)R 11 , -C 0-4 alkyl-C(O)R 11 , -C 0-4 alkyl-O-C(O)R 11 , -C 0-4 alkyl-P(O)(R 11 )2, -C 0-4 alkyl-NR 12 R 13 , -C 0-4 alkyl-C(O)NR 12 R 13 and -C 0-4 alkyl-N(R 12 )-C(O)R 11 further substituted by one or more substituents selected from, R2 is hydrogen, deuterium, C 1-10 alkyl group, C 2-10 alkenyl group, C 2-10 alkynyl group, C 3-12Cycloalkyl group, 3- to 12-membered heterocyclic group, C 6-10 Aryl group, 5- to 10-membered heteroaryl group, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 And -C(O)NR 12 R 13 Selected from, and said groups are independently optionally 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, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-O-S(O)2R9, -C 0-4 Alkyl-S(O) r R9, -C 0-4 Alkyl-O-R 10 , -C 0-4 Alkyl-C(O)OR 10 , -C 0-4 Alkyl-C(O)SR 10 , -C 0-4 Alkyl-S-C(O)R 11 , -C 0-4 Alkyl-C(O)R 11 , -C 0-4 Alkyl-O-C(O)R 11 , -C 0-4 Alkyl-P(O)(R 11 )2, -C 0-4 Alkyl-NR 12 R 13 , -C 0-4 Alkyl-C(O)NR 12 R 13 And -C 0-4 Alkyl-N(R 12 )-C(O)R 11 Further substituted by one or more substituents selected from, R3 and R4 are each independently hydrogen, deuterium, hydroxy group, C 1-4An 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, or R3 and R4, together with the nitrogen atom to which they are directly attached, form a 4- to 6-membered heterocyclic group or a 5- to 8-membered heteroaryl group, and the group is independently optionally deuterium, halogen, cyano group, hydroxy group, =O, =S, C 1-4 An alkyl group, halogen-substituted C 1-4 An alkyl group, 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 12 R 13 Further substituted by one or more substituents selected from Each R5 is independently hydrogen, deuterium, halogen, cyano group, 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- to 6-membered heterocyclic group, C 6-8 An aryl group, a 5- to 8-membered heteroaryl group, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-O-S(O)2R9, -C 0-4 Alkyl-S(O) r R9, -C 0-4 Alkyl-O-R 10 , -C 0-4 Alkyl-C(O)OR 10 , -C 0-4 Alkyl-C(O)SR 10 , -C 0-4 Alkyl-S-C(O)R 11 , -C 0-4 Alkyl-C(O)R 11 , -C 0-4 Alkyl-O-C(O)R 11 , -C 0-4 Alkyl-P(O)(R 11 )2, -C0-4 Alkyl-NR 12 R 13 、 -C 0-4 Alkyl-C(O)NR 12 R 13 and -C 0-4 Alkyl-N(R 12 )-C(O)R 11 selected from, and said groups are independently optionally 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, -C 0-4 alkyl-SF5, -C 0-4 alkyl-O-S(O)2R9, -C 0-4 alkyl-S(O) r R9, -C 0-4 alkyl-O-R 10 、 -C 0-4 alkyl-C(O)OR 10 、 -C 0-4 alkyl-C(O)SR 10 、 -C 0-4 alkyl-S-C(O)R 11 、 -C 0-4 alkyl-C(O)R 11 、 -C 0-4 alkyl-O-C(O)R 11 、 -C 0-4 alkyl-P(O)(R 11 )2, -C 0-4 alkyl-NR 12 R 13 、 -C 0-4 alkyl-C(O)NR 12 R 13 and -C 0-4 alkyl-N(R 12 )-C(O)R 11 further substituted by one or more substituents selected from, R6, R7 and R8 are each independently hydrogen, deuterium, halogen, cyano group, C 1-4Alkyl 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, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-O-S(O)2R9, -C 0-4 Alkyl-S(O) r R9, -C 0-4 Alkyl-O-R 10 , -C 0-4 Alkyl-C(O)OR 10 , -C 0-4 Alkyl-C(O)SR 10 , -C 0-4 Alkyl-S-C(O)R 11 , -C 0-4 Alkyl-C(O)R 11 , -C 0-4 Alkyl-O-C(O)R 11 , -C 0-4 Alkyl-P(O)(R 11 )2, -C 0-4 Alkyl-NR 12 R 13 , -C 0-4 Alkyl-C(O)NR 12 R 13 and -C 0-4 Alkyl-N(R 12 )-C(O)R 11 selected from, wherein, R9, R 10 , R 11 , R 12 , R 13 and R are as defined in the compound of formula (I).

[0011] In a preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, each R9 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 6-8An aryl group, a 5- to 8-membered heteroaryl group, and -NR 12 R 13 selected from, and said group is independently optionally 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- 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 12 R 13 selected from one or more substituents and further substituted by, each R 10 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 selected from, and said group is independently optionally 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 12 R 13 selected from one or more substituents and further substituted by, each R 11 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 6-8An aryloxy group, a 5-8 membered heteroaryl group, a 5-8 membered heteroaryloxy group and -NR 12 R 13 selected from, said groups being independently optionally 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, 3-6 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 12 R 13 selected from, and further substituted by one or more substituents selected from, each R 12 and R 13 being independently hydrogen, deuterium, 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 selected from, said groups being independently optionally 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, C1-4 an alkyl disubstituted amino group and C 1-4 is further substituted by one or more substituents selected from an alkanoyl group, or R 12 and R 13 together with the nitrogen atom to which they are directly attached form a 4- to 6-membered heterocyclic group or a 5- to 8-membered heteroaryl group, and the 4- to 6-membered heterocyclic group or 5- to 8-membered heteroaryl group is optionally 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- 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, amino group, C 1-4 alkylmonosubstituted amino group, C 1-4 alkyl disubstituted amino group and C 1-4 is further substituted by one or more substituents selected from an alkanoyl group.

[0012] In a preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound of formula (I) has the structure of the compound of the following formula (II),

[0013]

Chemical formula

[0014] wherein X1 is CR6 or N, X2 is CR7 or N, X3 is CR8 or N, Y1 is CR 1a or N, Y2 is CR 1b or N, Y3 is CR 1c or N, Y4 is CR 1dor N, Z is -C(R 1e R 1f )-, -C(R 1e R 1f )O-, -N(R 1g )-, -O- or -S-, Ring B is a C 4-6 cycloalkyl group, a 4- to 6-membered heterocyclic group, a C 6-8 aryl group or a 5- to 8-membered heteroaryl group, R 1a , R 1b , R 1c , R 1d 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, a 3- to 6-membered heterocyclic group, C 6-8 aryl group, a 5- to 8-membered heteroaryl group, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R 11 , -C(O)R 11 , -O-C(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 selected from, and the groups are independently optionally 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, a 3- to 6-membered heterocyclic group, C 6-8 aryl group, a 5- to 8-membered heteroaryl group, =O, =S, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR10 , -C(O)SR 10 , -SC(O)R 11 , -C(O)R 11 , -OC(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R 1e , R 1f are 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 groups, 3-6 membered heterocyclic groups, C 6-8 Aryl groups, 5-8 membered heteroaryl groups, -SF5, -OS(O)2R9, -S(O) r R9, -OR 10 , -C(O)OR 10 , -C(O)SR 10 , -SC(O)R 11 , -C(O)R 11 , -OC(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 or R 1e and R 1f Together with the carbon atom to which they are directly attached, they form one C 3-6 A cycloalkyl group or a 4-6 membered heterocyclic group, said groups being independently optionally selected from 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 3-6A cycloalkyl group, a 3- to 6-membered heterocyclic group, C 6-8 An aryl group, a 5- to 8-membered heteroaryl group, =O, =S, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R 11 , -C(O)R 11 , -O-C(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R 1g is hydrogen, deuterium, 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, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -C(O)R 11 and -C(O)NR 12 R 13 and the said groups are independently optionally 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, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R11 , -C(O)R 11 , -OC(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from Each R 1h are 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 groups, 3-6 membered heterocyclic groups, C 6-8 Aryl groups, 5-8 membered heteroaryl groups, -SF5, -OS(O)2R9, -S(O) r R9, -OR 10 , -C(O)OR 10 , -C(O)SR 10 , -SC(O)R 11 , -C(O)R 11 , -OC(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 wherein the groups are independently selected from 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 groups, 3-6 membered heterocyclic groups, C 6-8 Aryl groups, 5-8 membered heteroaryl groups, =O, =S, -SF5, -OS(O)2R9, -S(O) r R9, -OR 10 , -C(O)OR 10 , -C(O)SR 10 , -SC(O)R11 , -C(O)R 11 , -OC(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R2 is hydrogen, deuterium, C 1-4 Alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups, C 6-8 Aryl groups, 5-8 membered heteroaryl groups, -OR 10 and -C(O)R 11 wherein the groups are independently selected from 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 groups, 3-6 membered heterocyclic groups, C 6-8 Aryl groups, 5-8 membered heteroaryl groups, =O, =S, -SF5, -OS(O)2R9, -S(O) r R9, -OR 10 , -C(O)OR 10 , -C(O)SR 10 , -SC(O)R 11 , -C(O)R 11 , -OC(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R3 and R4 are independently hydrogen, deuterium, a hydroxyl group, or C 1-4 Alkyl group, C3-6 selected from a cycloalkyl group and a 3- to 6-membered heterocyclic group, or R3 and R4, together with the nitrogen atom to which they are directly attached, form a 4- to 6-membered heterocyclic group or a 5- to 8-membered heteroaryl group, and the group is independently optionally deuterium, halogen, cyano group, hydroxy group, =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 12 R 13 and is further substituted by one or more substituents selected from Each R5 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- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R 11 , -C(O)R 11 , -O-C(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 and the group is independently optionally 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, C3-6 Cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 Aryl group, 5- to 8-membered heteroaryl group, =O, =S, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R 11 , -C(O)R 11 , -O-C(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R6, R7, and R8 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- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R 11 , -C(O)R 11 , -O-C(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 selected from, o is 0, 1, 2, or 3, m1 is 0, 1, or 2, wherein, R9, R 10 , R11 、 R 12 、 R 13 、 n and R are as defined in the compound of formula (I).

[0015] In a more preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, ring B, together with the moiety to which they are directly attached, forms the following structure:

[0016]

Chemical Structure

[0017] Each R 5a is independently hydrogen, deuterium, halogen, cyano group, 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, -SF5 and -O-R 10 selected from, and the said groups are independently optionally 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, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R 11 , -C(O)R 11 , -O-C(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R11 further substituted by one or more substituents selected from each R 5b is independently hydrogen, deuterium, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, and -O-R 10 selected from, and the groups are independently optionally 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, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R 11 , -C(O)R 11 , -O-C(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 further substituted by one or more substituents selected from each R 5c is independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 aryl group, 5- to 8-membered heteroaryl group, -SF5, and -O-R 10 selected from, and the groups are independently optionally 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, C3-6 Cycloalkyl group, 3- to 6-membered heterocyclic group, C 6-8 Aryl group, 5- to 8-membered heteroaryl group, =O, =S, -SF5, -O-S(O)2R9, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)SR 10 , -S-C(O)R 11 , -C(O)R 11 , -O-C(O)R 11 , -P(O)(R 11 )2, -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from X1 is CR6 or N, and each R6 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 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, -SF5 and -O-R 10 selected from X2 is CR7 or N, and each R7 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 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, -SF5 and -O-R 10 selected from each R8 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 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, -SF5 and -O-R 10 selected from wherein, R9, R 10 , R 11 , R 12 , R13 and R is as defined in the compound of formula (II).

[0018] In a preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound of formula (I) has the structure of the compound of the following formula (III),

[0019]

Chemical formula

[0020] wherein X1 is CR6 or N, X2 is CR7 or N, Y1 is CR 1a or N, Y2 is CR 1b or N, Z is -C(R 1e R 1f )-, -C(R 1e R 1f )O-, -N(R 1g )- or -O-, Ring B, together with the moiety to which they are directly attached, forms the following structure,

[0021]

Chemical formula

[0022] R 1a 、R 1b 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, -SF5 and -O-R 10 selected from, and the said groups are independently optionally deuterium, halogen, cyano group, C 1-4 alkyl group, halogen substituted C 1-4 alkyl group, deuterium substituted C 1-4an alkyl group, C 2-4 an alkenyl group, C 2-4 an alkynyl group, C 3-6 a cycloalkyl group, a 3- to 6-membered heterocyclic group, C 6-8 an aryl group, a 5- to 8-membered heteroaryl group, =O, =S, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R 1e , R 1f 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, -SF5 and -O-R 10 and are independently optionally 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, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11further substituted by one or more substituents selected from R 1g is hydrogen, deuterium, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, hydroxy group, C 1-4 alkoxy group and -C(O)R 11 selected from, and said groups are independently optionally 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, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 further substituted by one or more substituents selected from each R 1h 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, -SF5 and -O-R 10 selected from, and said groups are independently optionally 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, C6-8 An aryl group, a 5- to 8-membered heteroaryl group, =O, =S, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from R2 is hydrogen, deuterium, 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-R 10 and -C(O)R 11 selected from, and the said groups are independently optionally 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, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 is further substituted by one or more substituents selected from Each R 5a is independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C3-6 A cycloalkyl group, a 3- to 6-membered heterocyclic group, -SF5, and -O-R 10 selected from, and said groups are independently optionally 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, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 substituted further by one or more substituents selected from, each R 5b is independently hydrogen, deuterium, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group and -O-R 10 selected from, and said groups are independently optionally 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, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R13 and -N(R 12 )-C(O)R 11 and is further substituted by one or more substituents selected from each R 5c is independently hydrogen, deuterium, halogen, cyano group, 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, -SF5 and -O-R 10 selected from, and said groups are independently optionally 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, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 and is further substituted by one or more substituents selected from R6 is 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, -SF5 and -O-R 10 selected from, R7 is hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, halogen substituted C1-4 An alkyl group, 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- to 6-membered heterocyclic group, C 6-8 An aryl group, a 5- to 8-membered heteroaryl group, -SF5 and -O-R 10 selected from, R8 is hydrogen, deuterium, halogen, cyano group, C 1-4 An alkyl group, halogen-substituted C 1-4 An alkyl group, 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- to 6-membered heterocyclic group, C 6-8 An aryl group, a 5- to 8-membered heteroaryl group, -SF5 and -O-R 10 selected from, o is 1 or 2, m1 is 0, 1 or 2, wherein R9, R 10 , R 11 , R 12 , R 13 , n and R are as defined in the compound of formula (I).

[0023] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, Y1 is CH or N, Y2 is CR 1b , R 1b is hydrogen, deuterium, halogen, cyano group, C 1-4 An alkyl group, C 3-6 A cycloalkyl group, a 3- to 6-membered heterocyclic group, C 6-8 An aryl group, a 5- to 8-membered heteroaryl group, -SF5 and -O-R 10 selected from, and the groups are independently optionally deuterium, halogen, cyano group, C 1-4 An alkyl group, halogen-substituted C 1-4 An alkyl group, deuterium-substituted C 1-4 An alkyl group, C 2-4 An alkenyl group, C 2-4 An alkynyl group, C3-6 A cycloalkyl group, a 3- to 6-membered heterocyclic group, C 6-8 is further substituted by one or more substituents selected from an aryl group, a 5- to 8-membered heteroaryl group, =O, =S and -SF5, wherein R 10 is as defined in the compound of formula (III).

[0024] In a more preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, R 1e , R 1f are each independently hydrogen, deuterium, halogen, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, -SF5 and -O-R 10 selected from, and the groups are independently optionally 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 is further substituted by one or more substituents selected from an aryl group, a 5- to 8-membered heteroaryl group, =O, =S and -SF5, R 1g is hydrogen, deuterium, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, hydroxy group, methoxy group and acetyl group selected from, and the groups are independently optionally 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 is further substituted by one or more substituents selected from an aryl group, a 5- to 8-membered heteroaryl group, =O, =S and -SF5, Each R 1his independently hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, -SF5 and -O-R 10 selected from, and said groups are independently optionally 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 and -SF5, and further substituted by one or more substituents selected from, wherein R 10 is as defined in the compound of formula (III).

[0025] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, each X1 is independently CR6 or N, each X2 is independently CH, each R6 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 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, -SF5 and -O-R 10 selected from, each R8 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 3-6 cycloalkyl group, 3- to 6-membered heterocyclic group, -SF5 and -O-R 10 selected from, wherein R 10 is as defined in the compound of formula (III).

[0026] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, each R 5a is independently selected from hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, -SF5 and -O-R 10 and the groups are independently optionally further substituted by one or more substituents 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 and -SF5, each R 5b is independently selected from hydrogen, deuterium, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group and -O-R 10 and the groups are independently optionally further substituted by one or more substituents 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 and -SF5, each R 5c is independently selected from hydrogen, deuterium, halogen, cyano group, C 1-4 alkyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, -SF5 and -O-R 10 and the groups are independently optionally further substituted by one or more substituents selected from deuterium, halogen, cyano group, C 1-4 alkyl group, halogen substituted C 1-4 alkyl group, deuterium substituted C 1-4an alkyl group, C 2-4 an alkenyl group, C 2-4 an alkynyl group, C 3-6 a cycloalkyl group, a 3- to 6-membered heterocyclic group, C 6-8 an aryl group, a 5- to 8-membered heteroaryl group, and is further substituted by one or more substituents selected from =O, =S, and -SF5, wherein R 10 is as defined for the compound of formula (III).

[0027] In a more preferred form, in the compound of formula (I), its stereoisomer, or its pharmaceutically acceptable salt, R2 is hydrogen, deuterium, C 1-4 an alkyl group, C 3-6 a cycloalkyl group, a 3- to 6-membered heterocyclic group, C 6-8 an aryl group, or a 5- to 8-membered heteroaryl group, and the groups are independently optionally deuterium, halogen, cyano group, C 1-4 an alkyl group, halogen-substituted C 1-4 an alkyl group, 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- to 6-membered heterocyclic group, C 6-8 an aryl group, a 5- to 8-membered heteroaryl group, =O, =S, -SF5, -S(O) r R9, -O-R 10 , -C(O)OR 10 , -C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(O)NR 12 R 13 and -N(R 12 )-C(O)R 11 and is further substituted by one or more substituents selected from wherein R9, R 10 , R 11 , R 12 , R 13 are as defined for the compound of formula (III).

[0028] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, R2 is selected from 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, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group and pyrimidyl group, and the said groups are independently optionally 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, bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyrimidyl group, =O, =S, -SF5, sulfinyl group, sulfonyl group, methylsulfonyl group, isopropylsulfonyl group, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group, formyl group, acetyl group, n-propionyl group, isopropionyl group, formyloxy group, acetoxy group, n-propionyloxy group, isopropionyloxy group, amino group, mono-C 1-4 alkylamino group and bis-C 1-4 alkylamino group, and is further substituted by one or more substituents selected therefrom.

[0029] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, "

[0030]

Chemical formula

[0031] [Chemical formula] selected from

[0032] each R 1b is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, trifluoromethoxy group, difluoromethoxy group, trideuteromethoxy group, dideuteromethoxy group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF5, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group, cyclobutoxy group, phenyl group, and pyrazolyl group substituted by a methyl group.

[0033] In a more preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, "

[0034] [Chemical formula] " has the following structure:

[0035] [Chemical formula] selected from

[0036] each R 1b is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, trifluoromethoxy group, difluoromethoxy group, trideuteromethoxy group, dideuteromethoxy group, cyclopropyl group, and pyrazolyl group substituted by a methyl group.

[0037] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound of formula (I) has the structure of the compound of formula (IVa) as follows:

[0038]

Chemical formula

[0039] wherein, "

[0040]

Chemical formula

[0041]

Chemical formula

[0042] Ring B and the moiety "

[0043]

Chemical formula

[0044]

Chemical formula

[0045] each X1 is independently CR6 or N, Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF5, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, Each R 5a is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF5, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, and the group is further substituted by one or more substituents independently and optionally selected from deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF5, Each R 5cis independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF5, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, and the group is further optionally substituted by one or more substituents independently selected from 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, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF5, R2 is selected from methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group and pyrimidyl group, and the group is further optionally substituted by one or more substituents independently selected from 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, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyrimidyl group, =O, =S, -SF5, hydroxyl group and methoxy group, provided that when R2 is selected from methyl groups, "

[0046]

Chemical formula

[0047] [Chemistry] is not.

[0048] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, each R 1b is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, and a pyrazolyl group substituted by a methyl group; R6 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF5, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group, and cyclobutoxy group; R2 is selected from a methyl group substituted by a cyclopropyl group, a methyl group substituted by a cyclobutyl group, a methyl group substituted by a thiazolyl group, a methyl group substituted by a pyrimidyl group, ethyl group, an ethyl group substituted by a cyclopropyl group, an ethyl group substituted by a cyclobutyl group, 2,2,2-trifluoroethyl group, methoxyethyl group, an ethyl group substituted by a thiazolyl group, an ethyl group substituted by a pyrimidyl group, an isopropyl group substituted by a methoxy group, cyclopropyl group, a pyrazolyl group substituted by a methyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, and pyrimidyl group.

[0049] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound of formula (I) has the structure of the compound of formula (Va) below,

[0050] [Chemistry]

[0051] Here, "

[0052] [Chemical formula] " has the following structure:

[0053] [Chemical formula] is selected from, and each R 1b is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, and cyclopropyl group,

[0054] R6 is selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. In a more preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound of formula (I) has the structure of the compound of the following formula (IVb),

[0055] [Chemical formula]

[0056] Here, "

[0057] [Chemical formula] " has the following structure

[0058] [Chemical formula] is selected from, and each R 1bis independently selected from a pyrazolyl group substituted by hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group and methyl group,

[0059] Ring B and the part "

[0060]

Chem.

[0061]

Chem.

[0062] each X1 is independently CR6 or N, each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF5, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, each R 5ais independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF5, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, and said group is independently optionally further substituted by one or more substituents selected from 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, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF5, Each R 5b is independently selected from hydrogen, deuterium, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group and hydroxyl group, and said group is independently optionally further substituted by one or more substituents selected from 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, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF5, Each R 5cis independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF5, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, and said group is independently optionally further substituted by one or more substituents selected from deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF5, wherein R2 is as defined in the compound of formula (III).

[0063] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, ring B and the moiety directly connecting thereto "

[0064]

Chemical formula

[0065]

Chemical formula

[0066] each X1 is independently CR6, and each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group, each R 5a is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group, each R 5bare each independently selected from hydrogen, deuterium, a methyl group, a trifluoromethyl group, a trideuteriomethyl group, and a cyclopropyl group, each R 5c is each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteriomethyl group, and a cyclopropyl group.

[0067] In a more preferred form, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, R2 is selected from a substituted methyl group, a substituted ethyl group, a substituted or unsubstituted n-propyl group, a substituted isopropyl group, a bicyclo[1.1.1]pentyl group, an oxetanyl group, an azetidinyl group, a phenyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazolyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group, and a pyrimidyl group, the substituents of the substituted methyl group, substituted ethyl group, substituted n-propyl group, and substituted isopropyl group are each independently one or more selected from fluorine, chlorine, bromine, a cyclobutyl group, a bicyclo[1.1.1]pentyl group, an oxetanyl group, an azetidinyl group, a phenyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazolyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group, a pyrimidyl group, -SF5, a hydroxyl group, and a methoxy group, The bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, and pyrimidyl group are each 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, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteriomethyl group, dideuteriomethyl group, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyrimidyl group, =O, =S, -SF5, hydroxyl group, and methoxy group.

[0068] More preferably, in the compound of formula (I), its stereoisomer, or its pharmaceutically acceptable salt, R2 is selected from a substituted methyl group, a substituted ethyl group, a substituted or unsubstituted n-propyl group, a substituted isopropyl group, a phenyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazolyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group, and a pyrimidyl group. The substituents of the substituted methyl group, substituted ethyl group, substituted n-propyl group, and substituted isopropyl group are each independently one or more selected from fluorine, chlorine, bromine, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyrimidyl group, and methoxy group. The phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, and pyrimidyl group are each independently optionally further substituted by one or more substituents selected from deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, trifluoromethyl group, difluoromethyl group, trideuteriomethyl group, dideuteriomethyl group, cyclopropyl group, -SF5, hydroxyl group, and methoxy group.

[0069] More preferably, in the compound of formula (I), its stereoisomer, or its pharmaceutically acceptable salt, R2 is a trifluoromethyl group, a methyl group substituted by a pyrazolyl group, a methyl group substituted by an imidazolyl group, a methyl group substituted by a triazolyl group, a methyl group substituted by an oxazolyl group, a methyl group substituted by a thiazolyl group, a methyl group substituted by an isothiazolyl group, a methyl group substituted by a thiadiazolyl group, a methyl group substituted by a pyrimidyl group, a fluorine-substituted ethyl group, a methoxyethyl group, an ethyl group substituted by a pyrazolyl group, an ethyl group substituted by an imidazolyl group, an ethyl group substituted by a triazolyl group, an ethyl group substituted by an oxazolyl group, an ethyl group substituted by a thiazolyl group, an ethyl group substituted by an isothiazolyl group, an ethyl group substituted by a thiadiazolyl group, an ethyl group substituted by a pyrimidyl group, an isopropyl group substituted by a methoxy group, a pyrazolyl group, a pyrazolyl group substituted by a methyl group, an imidazolyl group, an imidazolyl group substituted by a methyl group, a triazolyl group, a triazolyl group substituted by a methyl group, an oxazolyl group, an oxazolyl group substituted by a methyl group, a thiazolyl group, a thiazolyl group substituted by a methyl group, an isothiazolyl group, an isothiazolyl group substituted by a methyl group, a thiadiazolyl group, a thiadiazolyl group substituted by a methyl group, a pyrimidyl group, and a pyrimidyl group substituted by a methyl group.

[0070] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, R2 is a methyl group substituted by a thiazolyl group, a methyl group substituted by a pyrimidyl group, a 2,2,2-trifluoroethyl group, a methoxyethyl group, an ethyl group substituted by a thiazolyl group, an ethyl group substituted by a pyrimidyl group, an isopropyl group substituted by a methoxy group, a pyrazolyl group substituted by a methyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group and a pyrimidyl group.

[0071] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, R2 has the following structure:

[0072]

Chemical formula

[0073] More preferably, in the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, the compound of formula (I) has the structures of the following compound of formula (Vb1), compound of formula (Vb2), compound of formula (Vb3), and compound of formula (Vb4),

[0074]

Chemical formula

[0075] Each R 1b Is independently selected from hydrogen, deuterium, a methyl group, a trifluoromethyl group, a trideuteromethyl group, a trifluoromethoxy group, a trideuteromethoxy group and a cyclopropyl group, Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, a cyano group and a methyl group, Each R 5b Is independently selected from hydrogen, deuterium, a methyl group, a trifluoromethyl group, a trideuteromethyl group and a cyclopropyl group.

[0076] In the most preferred form, the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt includes, but is not limited to, the following compounds.

[0077]

Chemical formula

[0078] The second aspect of the present invention provides a method for producing a compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt, and the production method includes the following steps,

[0079]

Chemical formula

[0080] Here, X is a fluorine, chlorine, bromine or hydroxy group, and ring A, ring B, X1, X2, X3, R1, R2, R3, R4, R5, m and n are as in the compound of formula (I). The third aspect of the present invention provides a pharmaceutical composition comprising a compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

[0081] A fourth aspect of the present invention provides the use of a compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating MATP-related cancer or tumor. In a preferred form, the tumor or cancer is selected from endometrial adenocarcinoma, granulosa theca cell tumor, testicular sertoli cell tumor, germ cell tumor, malignant teratoma, squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma, clear cell carcinoma, squamous cell carcinoma, sarcoma botryoides, fallopian tube carcinoma, adenocarcinoma, nephroblastoma, lymphoma, leukemia, bladder carcinoma, squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma, prostate carcinoma, seminoma, teratoma, fetal carcinoma, teratoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumor, lipoma, liver carcinoma, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma, gallbladder carcinoma, ampullary carcinoma, cholangiocarcinoma, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, nevus, dysplastic nevus, lipoma, hemangioma, acute and chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes, Hodgkin's disease, non-Hodgkin lymphoma, osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma, multiple myeloma, malignant giant cell tumor, chordoma, osteochondroma, benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma, giant cell tumor, angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma, myxoma, rhabdomyoma, fibroma, lipoma and teratoma, bronchogenic lung carcinoma, alveolar carcinoma, bronchial adenoma, sarcoma, lymphoma, chondroid hamartoma, mesothelioma, squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma, gastric carcinoma, lymphoma, leiomyosarcoma, ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, viper tumor, adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma, colorectal adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma, cranial tumor, hemangioma, granuloma, xanthoma, Paget's disease, meningioma, meningiosarcoma, gliosis, astrocytoma, medulloblastoma, glioma, ependymomas, germ cell tumor, glioblastoma multiforms, oligodendroglioma, schwannomas, retinoblastoma, congenital tumor, spinal neurofibroma, meningioma, glioma or sarcoma.

[0082] In a more preferred form, the cancer or tumor is selected from breast cancer, pancreatic cancer, skin cancer, bladder cancer, liver cancer or head and neck cancer. The present invention also relates to the compound of formula (I) used as a PRMT5 inhibitor drug, its stereoisomer or its pharmaceutically acceptable salt.

[0083] The present invention also relates to the use of the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt in the manufacture of a drug for treating and / or preventing a disease mediated by PRMT5.

[0084] The present invention also relates to a method for treating and / or preventing a disease mediated by PRMT5, which comprises administering to a patient in need a therapeutically effective amount of the compound of formula (I), its stereoisomer or its pharmaceutically acceptable salt.

Mode for Carrying Out the Invention

[0085] The inventor of the present application has conducted extensive and in-depth research and, for the first time, developed a PRMT5 inhibitor having the structure of the following formula (I). A series of compounds of the present invention can be widely applied to the manufacture of drugs for treating and / or preventing diseases mediated by PRMT5 and are expected to be developed as a new generation of PRMT5 inhibitors. Based on this, the present invention has been completed.

[0086] Detailed Explanation: Unless otherwise stated or otherwise explained, the following terms used in the specification and claims have the following meanings. The term "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, 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 t-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 is not limited thereto. "C 1-10 The "alkyl group" refers to a straight-chain alkyl group and a branched-chain alkyl group containing 1 to 10 carbon atoms, and "C 1-4 The "alkyl group" refers to a straight-chain alkyl group and a branched-chain alkyl group containing 1 to 4 carbon atoms, and "C 0-8 The "alkyl group" refers to a straight-chain alkyl group and a branched-chain alkyl group containing 0 to 8 carbon atoms, and "C 0-4 The "alkyl group" refers to a straight-chain alkyl group and a branched-chain alkyl group containing 0 to 4 carbon atoms.

[0087] The alkyl group may be optionally substituted or unsubstituted. In the case of a substituted alkyl group, the substituents are 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-SF5, C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 , -C 0-8 alkyl-C(O)OR 10 , -C 0-8 alkyl-C(O)SR 10 , -C 0-8 alkyl-S-C(O)R 11 , -C 0-8 alkyl-C(O)R 11 , -C 0-8 alkyl-O-C(O)R 11 , -C 0-8 alkyl-P(O)(R 11 )2, -C 0-8 alkyl-NR 12 R 13 , -C 0-8 alkyl-C(O)NR 12 R 13 and -C 0-8 alkyl-N(R 12 )-C(O)R 11 It is preferably one or more (preferably 1, 2, 3 or 4) groups selected from the above.

[0088] The "cycloalkyl group" or "carbocyclic ring" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent. The partially unsaturated cyclic hydrocarbon means that the cyclic hydrocarbon may contain one or more (preferably 1, 2 or 3) double bonds, but none of the rings has a completely conjugated π - electron system. The cycloalkyl group is divided into a monocyclic cycloalkyl group and a polycyclic cycloalkyl group, and preferably is a cycloalkyl group containing 3 to 12 or 3 to 8 or 3 to 6 carbon atoms. For example, " 3-12 The "cycloalkyl group" refers to a cycloalkyl group containing 3 to 12 carbon atoms, " 4-8 The "cycloalkyl group" refers to a cycloalkyl group containing 4 to 8 carbon atoms, " 3-8 The "cycloalkyl group" refers to a cycloalkyl group containing 3 to 8 carbon atoms, " 3-6 The "cycloalkyl group" refers to a cycloalkyl group containing 3 to 6 carbon atoms. Among them, 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.

[0089] The polycyclic cycloalkyl group includes spiro - ring, fused - ring and bridged - ring cycloalkyl groups. The "spirocycloalkyl group" refers to a polycyclic group that shares one carbon atom (called a spiro atom) between monocyclic rings. These groups may contain one or more (preferably 1, 2 or 3) double bonds, but there is no ring having a completely conjugated π - electron system. Depending on the number of spiro atoms shared between rings, the spirocycloalkyl group is divided into a monospirocycloalkyl group, a dispirocycloalkyl group or a polyspirocycloalkyl group. The spirocycloalkyl group includes the following, but is not limited to these.

[0090] [Chemical formula]

[0091] The term "fused 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 of its rings may contain one or more (preferably 1, 2, or 3) double bonds, but there is no ring having a fully conjugated π - electron system. It can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused cycloalkyl groups according to the number of constituent rings, and the fused cycloalkyl groups include, but are not limited to, the following.

[0092]

Chem.

[0093] The term "bridged cycloalkyl group" refers to a fully carbon polycyclic group in which two carbon atoms that are not directly linked to any two rings are shared, and these groups may contain one or more (preferably 1, 2, or 3) double bonds, but there is no ring having a fully conjugated π - electron system. It can be divided into bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyl groups according to the number of constituent rings, and the bridged cycloalkyl groups include, but are not limited to, the following.

[0094]

Chem.

[0095] The ring of the cycloalkyl group may be fused to an aryl group, a heteroaryl group or a heterocycloalkyl ring. Here, the ring linked to the parent structure is a cycloalkyl group, including, but not limited to, indanyl group, tetrahydronaphthyl group, benzocycloheptyl group, etc.

[0096] The "cycloalkyl group" or "carbocyclic ring" may be optionally substituted or unsubstituted. In the case of being substituted, the substituents are 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, C2-10 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, =O, =S, -C 0-8 An alkyl-SF5, C 0-8 An alkyl-O-S(O)2R9, -C 0-8 An alkyl-S(O) r R9, -C 0-8 An alkyl-O-R 10 , -C 0-8 An alkyl-C(O)OR 10 , -C 0-8 An alkyl-C(O)SR 10 , -C 0-8 An alkyl-S-C(O)R 11 , -C 0-8 An alkyl-C(O)R 11 , -C 0-8 An alkyl-O-C(O)R 11 , -C 0-8 An alkyl-P(O)(R 11 )2, -C 0-8 An alkyl-NR 12 R 13 , -C 0-8 An alkyl-C(O)NR 12 R 13 and -C 0-8 An alkyl-N(R 12 )-C(O)R 11 It is preferably one or more (preferably 1, 2, 3, or 4) groups selected from

[0097] The "heterocyclic group" or "heterocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent. The partially unsaturated cyclic hydrocarbon means that the cyclic hydrocarbon may contain one or more (preferably 1, 2, or 3) double bonds, but none of the rings has a completely conjugated π-electron system. One or more (preferably 1, 2, 3, or 4) ring atoms of the heterocyclic group are N, O, N·O, or S(O) rIt is a heteroatom selected from (where r is an integer 0, 1, 2), does not contain a ring moiety of -O-O-, -O-S- or -S-S-, and the remaining ring atoms are carbon. Preferably, it is a heterocyclic group containing 3 to 12 or 3 to 8 or 3 to 6 ring atoms. For example, a "3-6 membered heterocyclic group" refers to a heterocyclic group containing 3 to 6 ring atoms, a "3-8 membered heterocyclic group" refers to a heterocyclic group containing 3 to 8 ring atoms, a "4-8 membered heterocyclic group" refers to a heterocyclic group containing 4 to 8 ring atoms, a "4-10 membered heterocyclic group" refers to a heterocyclic group containing 4 to 10 ring atoms, a "5-8 membered heterocyclic group" refers to a heterocyclic group containing 5 to 8 ring atoms, and a "3-12 membered heterocyclic group" refers to a heterocyclic group containing 3 to 12 ring atoms.

[0098] The monocyclic heterocyclic group includes, but is not limited to, a pyrrolidyl group, a piperidyl group, a piperazinyl group, a morpholyl group, a thiomorpholyl group, a homopiperazinyl group, an oxetane group, a tetrahydrofuran group, etc.

[0099] The polycyclic heterocycle includes a spiro ring, a fused ring and a bridged ring heterocyclic group. A "spiro heterocyclic group" is 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 its ring atoms are N, O, N·O or S(O) r It refers to a group that is a heteroatom selected from (where r is an integer 0, 1, 2) 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, the spiro heterocyclic group is divided into a monospiro heterocyclic group, a dispiro heterocyclic group or a polyspiro heterocyclic group. The spiro heterocyclic group includes, but is not limited to, the following.

[0100]

Chemical formula

[0101] The term "fused 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 1, 2, 3, or 4) rings may contain one or more (preferably 1, 2, or 3) double bonds, but there is no ring having a completely conjugated π - electron system, and one or more (preferably 1, 2, 3, or 4) of its ring atoms are N, O, N·O, or S(O) r (where r is an integer 0, 1, 2), and the remaining ring atoms are carbon. It can be divided into bicyclic, tricyclic, tetracyclic, or polycyclic fused heterocyclic groups according to the number of constituent rings. The fused heterocyclic groups include, but are not limited to, the following.

[0102]

Chemical formula

[0103] The term "bridged heterocyclic group" refers to a polycyclic heterocyclic group in which two rings that are not directly connected share two atoms. These rings may contain one or more (preferably 1, 2, or 3) double bonds, but there is no ring having a completely conjugated π - electron system, and one or more (preferably 1, 2, 3, or 4) of its ring atoms are N, O, N·O, or S(O) r (where r is an integer 0, 1, 2), and the remaining ring atoms are carbon. It can be divided into bicyclic, tricyclic, tetracyclic, or polycyclic bridged heterocyclic groups according to the number of constituent rings. The bridged heterocyclic groups include, but are not limited to, the following.

[0104]

Chemical formula

[0105] The ring of the heterocyclic group may be condensed with the ring 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.

[0106]

Chemical formula

[0107] The "heterocyclic group" or "heterocycle" may be optionally substituted or unsubstituted. In the case of being substituted, the substituents are 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-SF5, C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 , -C 0-8 alkyl-C(O)OR 10 , -C 0-8 alkyl-C(O)SR 10 , -C 0-8 alkyl-S-C(O)R 11 , -C 0-8 alkyl-C(O)R 11 , -C 0-8 alkyl-O-C(O)R 11 , -C 0-8 alkyl-P(O)(R 11 )2, -C 0-8 alkyl-NR 12 R 13 , -C 0-8 alkyl-C(O)NR 12 R 13 and -C 0-8 alkyl-N(R 12 )-C(O)R 11 and is preferably one or more (preferably 1, 2, 3 or 4) groups selected from

[0108] The "aryl group" or "aromatic ring" refers to a group of a monocyclic or condensed polycyclic ring composed entirely of carbon (i.e., a ring sharing adjacent carbon atom pairs), and a group of a polycyclic ring (i.e., a ring having adjacent carbon atom pairs) having a conjugated π electron system, preferably a fully carbon aryl group containing 6-10 or 6-8 carbon atoms. For example, "C 6-10 aryl group" refers to a fully carbon aryl group containing 6-10 carbon atoms, including but not limited to phenyl group and naphthyl group. "C 6-8 aryl group" refers to a fully carbon aryl group containing 6-8 carbon atoms. The ring of the aryl group may be condensed with a heteroaryl group, a heterocyclic group or a cycloalkyl ring. Here, the ring connected to the parent structure is an aryl ring, including but not limited to the following.

[0109]

Chemical formula

[0110] The "aryl group" or "aromatic ring" may be substituted or unsubstituted. In the case of being substituted, the substituents are 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-SF5, C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 、-C 0-8 alkyl-C(O)OR 10 、-C 0-8 alkyl-C(O)SR 10 、-C 0-8 alkyl-S-C(O)R 11 、-C 0-8Alkyl-C(O)R 11 , -C 0-8 Alkyl-O-C(O)R 11 , -C 0-8 Alkyl-P(O)(R 11 )2, -C 0-8 Alkyl-NR 12 R 13 , -C 0-8 Alkyl-C(O)NR 12 R 13 and -C 0-8 Alkyl-N(R 12 )-C(O)R 11 It is preferably one or more (preferably 1, 2, 3 or 4) groups selected from the following.

[0111] The "heteroaryl group" or "heteroaromatic ring" is a heteroaromatic system containing one or more (preferably 1, 2, 3 or 4) heteroatoms, and the heteroatoms are N, O, N·O and S(O)r (where r is an integer of 0, 1, 2), preferably a heteroaromatic system containing 5-10 or 5-8 or 5-6 ring atoms. For example, the "5-8 membered heteroaryl group" refers to a heteroaromatic system containing 5-8 ring atoms, the "5-10 membered heteroaryl group" refers to a heteroaromatic system containing 5-10 ring atoms, and includes, but is not limited to, furyl group, thienyl group, pyridyl group, pyrrolyl group, N-alkylpyrrolyl group, pyrimidinyl group, pyrazinyl group, imidazolyl group, tetrazolyl group, etc. The ring of the heteroaryl group may be condensed with an aryl group, a heterocyclic group or a cycloalkyl ring. Here, the ring connected to the parent structure is a heteroaryl ring, and includes, but is not limited to, the following.

[0112]

Chemical formula

[0113] The "heteroaryl group" or "heteroaromatic ring" may be optionally substituted or unsubstituted. In the case of being substituted, the substituents are independently deuterium, halogen, cyano group, nitro group, azide group, C1-10 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-SF5, C 0-8 Alkyl-O-S(O)2R9, -C 0-8 Alkyl-S(O) r R9, -C 0-8 Alkyl-O-R 10 , -C 0-8 Alkyl-C(O)OR 10 , -C 0-8 Alkyl-C(O)SR 10 , -C 0-8 Alkyl-S-C(O)R 11 , -C 0-8 Alkyl-C(O)R 11 , -C 0-8 Alkyl-O-C(O)R 11 , -C 0-8 Alkyl-P(O)(R 11 )2, -C 0-8 Alkyl-NR 12 R 13 , -C 0-8 Alkyl-C(O)NR 12 R 13 and -C 0-8 Alkyl-N(R 12 )-C(O)R 11 It is preferably one or more (preferably 1, 2, 3, or 4) groups selected from the above.

[0114] The "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, and is preferably a linear or branched alkenyl group containing 2-10 or 2-4 carbons. For example, the "C 2-10 alkenyl group" refers to a linear or branched alkenyl group containing 2-10 carbons, and the "C 2-4The "alkenyl group" refers to a linear or branched alkenyl group containing 2 to 4 carbons. It includes, but is not limited to, vinyl group, 1-propenyl group, 2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, etc.

[0115] The "alkenyl group" may be substituted or unsubstituted. In the case of being substituted, the substituents are 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-SF5, C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 , -C 0-8 alkyl-C(O)OR 10 , -C 0-8 alkyl-C(O)SR 10 , -C 0-8 alkyl-S-C(O)R 11 , -C 0-8 alkyl-C(O)R 11 , -C 0-8 alkyl-O-C(O)R 11 , -C 0-8 alkyl-P(O)(R 11 )2, -C 0-8 alkyl-NR 12 R 13 , -C 0-8 alkyl-C(O)NR 12 R 13 and -C 0-8 alkyl-N(R 12 )-C(O)R 11 and is preferably one or more (preferably 1, 2, 3, or 4) groups selected from the following.

[0116] The term "alkynyl group" refers to an alkyl group as defined above, which consists of at least two carbon atoms and at least one carbon-carbon triple bond, and is preferably a linear or branched alkynyl group containing 2-10 or 2-4 carbon atoms. For example, "C 2-10 alkynyl group" refers to a linear or branched alkynyl group containing 2-10 carbon atoms, and "C 2-4 alkynyl group" refers to a linear or branched alkynyl group containing 2-4 carbon atoms. It includes, but is not limited to, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, etc.

[0117] The "alkynyl group" may be substituted or unsubstituted. In the case of a substituted one, the substituents are 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-SF5, C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 , -C 0-8 alkyl-C(O)OR 10 , -C 0-8 alkyl-C(O)SR 10 , -C 0-8 alkyl-S-C(O)R 11 , -C 0-8 alkyl-C(O)R 11 , -C 0-8 alkyl-O-C(O)R 11 , -C 0-8 alkyl-P(O)(R 11 )2, -C 0-8Alkyl-NR 12 R 13 、 -C 0-8 Alkyl-C(O)NR 12 R 13 And -C 0-8 Alkyl-N(R 12 )-C(O)R 11 It is preferably one or more (preferably 1, 2, 3, or 4) groups selected from the above.

[0118] The "alkoxy group" refers to an -O-alkyl group, and the definition of the alkyl group is as described above. For example, the "C 1-10 alkoxy group" refers to an alkoxy group containing 1 - 10 carbons, the "C 1-4 alkoxy group" refers to an alkoxy group containing 1 - 4 carbons, the "C 1-2 alkoxy group" refers to an alkoxy group containing 1 - 2 carbons, and includes, but is not limited to, methoxy group, ethoxy group, propoxy group, butoxy group, etc.

[0119] The "alkoxy group" may be optionally substituted or unsubstituted. In the case of being substituted, the substituents are 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-SF5, C 0-8 alkyl-O-S(O)2R9, -C 0-8 alkyl-S(O) r R9, -C 0-8 alkyl-O-R 10 、 -C 0-8 alkyl-C(O)OR 10 、 -C 0-8 alkyl-C(O)SR 10 、 -C 0-8 alkyl-S-C(O)R11 , -C 0-8 alkyl-C(O)R 11 , -C 0-8 alkyl-O-C(O)R 11 , -C 0-8 alkyl-P(O)(R 11 )2, -C 0-8 alkyl-NR 12 R 13 , -C 0-8 alkyl-C(O)NR 12 R 13 and -C 0-8 alkyl-N(R 12 )-C(O)R 11 It is preferred to be one or more (preferably 1, 2, 3 or 4) groups selected from

[0120] The "cycloalkoxy group" or "cycloalkyloxy group" refers to an -O-cycloalkyl group, and the definition of the cycloalkyl group is as described above. For example, the "C 3-12 cycloalkoxy group" refers to a cycloalkyloxy group containing 3 - 12 carbons, and the "C 3-6 cycloalkoxy group" refers to a cycloalkyloxy group containing 3 - 6 carbons, including but not limited to cyclopropoxy group, cyclobutoxy group, cyclopentyloxy group, cyclohexyloxy group, etc.

[0121] The "cycloalkoxy group" or "cycloalkyloxy group" may be optionally substituted or unsubstituted. In the case of being substituted, the substituents are 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-SF5, C 0-8 alkyl-O-S(O)2R9, -C0-8 Alkyl-S(O) r R9, -C 0-8 Alkyl-O-R 10 , -C 0-8 Alkyl-C(O)OR 10 , -C 0-8 Alkyl-C(O)SR 10 , -C 0-8 Alkyl-S-C(O)R 11 , -C 0-8 Alkyl-C(O)R 11 , -C 0-8 Alkyl-O-C(O)R 11 , -C 0-8 Alkyl-P(O)(R 11 )2, -C 0-8 Alkyl-NR 12 R 13 , -C 0-8 Alkyl-C(O)NR 12 R 13 and -C 0-8 Alkyl-N(R 12 )-C(O)R 11 is preferably one or more (preferably 1, 2, 3, or 4) groups selected from the following:

[0122] The "heterocyclic oxy group" or "heterocyclyloxy group" refers to -O-heterocyclic group, and the definition of the heterocyclic group is as described above, including, but not limited to, azetidinyl oxy group, oxetanyl oxy group, azacyclopentaoxy group, nitrogen, oxanyl oxy group, etc.

[0123] The "heterocyclic oxy group" or "heterocyclyloxy group" may be optionally substituted or unsubstituted. In the case of being substituted, the substituents are 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 6-10An aryl group, a 5- to 10-membered heteroaryl group, =O, =S, -C 0-8 Alkyl-SF5, C 0-8 Alkyl-O-S(O)2R9, -C 0-8 Alkyl-S(O) r R9, -C 0-8 Alkyl-O-R 10 , -C 0-8 Alkyl-C(O)OR 10 , -C 0-8 Alkyl-C(O)SR 10 , -C 0-8 Alkyl-S-C(O)R 11 , -C 0-8 Alkyl-C(O)R 11 , -C 0-8 Alkyl-O-C(O)R 11 , -C 0-8 Alkyl-P(O)(R 11 )2, -C 0-8 Alkyl-NR 12 R 13 , -C 0-8 Alkyl-C(O)NR 12 R 13 And -C 0-8 Alkyl-N(R 12 )-C(O)R 11 It is preferably one or more (preferably 1, 2, 3, or 4) groups selected from the following.

[0124] "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, "C1 alkyl-C(O)-" refers to an acetyl group, "C2 alkyl-C(O)-" refers to a propionyl group, and "C3 alkyl-C(O)-" refers to a butyryl group or an isobutyryl group.

[0125] "-C 0-8 Alkyl-O-S(O)2R9" refers to a group in which the oxygen atom in -O-S(O)2R9 is linked to a C 0-8 Alkyl group, and the definition of the C 0-8 Alkyl group is as described above.

[0126] 「-C 0-8 alkyl-S(O) r R9」 means -S(O) r wherein the sulfur atom in R9 is C 0-8 linked to an alkyl group, and the C 0-8 definition of the alkyl group is as described above. 「-C 0-8 alkyl-O-R 10 」 means -O-R 10 wherein the oxygen atom in is C 0-8 linked to an alkyl group, and the C 0-8 definition of the alkyl group is as described above.

[0127] 「-C 0-8 alkyl-C(O)OR 10 」 means -C(O)OR 10 wherein the carbonyl group in is C 0-8 linked to an alkyl group, and the C 0-8 definition of the alkyl group is as described above.

[0128] 「-C 0-8 alkyl-C(O)SR 10 」 means -C(O)SR 10 wherein the carbonyl group in is C 0-8 linked to an alkyl group, and the C 0-8 definition of the alkyl group is as described above.

[0129] 「-C 0-8 alkyl-S-C(O)R 11 」 means -S-C(O)R 11 wherein the sulfur atom in is C 0-8 linked to an alkyl group, and the C 0-8 definition of the alkyl group is as described above.

[0130] 「-C 0-8 alkyl-C(O)R 11 」 means -C(O)R 11 wherein the carbonyl group in is C 0-8 linked to an alkyl group, and the C0-8 The definition of the alkyl group is as described above.

[0131] 「-C 0-8 alkyl-O-C(O)R 11 」 means that the oxygen atom in -O-C(O)R 11 is linked to the C 0-8 alkyl group, and the definition of the C 0-8 alkyl group is as described above.

[0132] 「-C 0-8 alkyl-P(O)(R 11 )2」 means that the phosphorus atom in -P(O)(R 11 )2 is linked to the C 0-8 alkyl group, and the definition of the C 0-8 alkyl group is as described above.

[0133] 「-C 0-8 alkyl-NR 12 R 13 」 means that the nitrogen atom in -NR 12 R 13 is linked to the C 0-8 alkyl group, and the definition of the C 0-8 alkyl group is as described above. 「-C 0-8 alkyl-C(O)NR 12 R 13 」 means that the carbonyl group in -C(O)NR 12 R 13 is linked to the C 0-8 alkyl group, and the definition of the C 0-8 alkyl group is as described above.

[0134] 「-C 0-8 alkyl-N(R 12 )-C(O)R 11 」 means that the nitrogen atom in -N(R 12 )-C(O)R 11 is linked to the C 0-8 alkyl group, and the definition of the C 0-8 alkyl group is as described above.

[0135] "Halogen-substituted C 1-10 "alkyl group" means a 1-10 carbon alkyl group in which the hydrogen in the alkyl group is arbitrarily substituted with an atom of fluorine, chlorine, bromine, or iodine, including, but not limited to, difluoromethyl group, dichloromethyl group, dibromomethyl group, trifluoromethyl group, trichloromethyl group, tribromomethyl group, etc.

[0136] "Halogen-substituted C 1-10 "alkoxy group" means a 1-10 carbon alkoxy group in which the hydrogen in the alkyl group is arbitrarily substituted with an atom of fluorine, chlorine, bromine, or iodine. It includes, but is not limited to, difluoromethoxy group, dichloromethoxy group, dibromomethoxy group, trifluoromethoxy group, trichloromethoxy group, tribromomethoxy group, etc.

[0137] "Deuterium-substituted C 1-10 "alkyl group" means a 1-10 carbon alkyl group in which the hydrogen in the alkyl group is arbitrarily substituted with a deuterium atom. It includes, but is not limited to, deuteromethyl group, dideuteromethyl group, trideuteromethyl group, etc.

[0138] "Halogen" means fluorine, chlorine, bromine or iodine; "EA" means ethanol; "PE" means petroleum ether; "EtOAc" means ethyl acetate; "MeOH" means methanol; "DCM" means dichloromethane; "DMSO" means dimethyl sulfoxide.

[0139] "Optional" or "optionally" means possible depending on the matters or circumstances described below but not necessarily occurring. The description includes the cases where the matters or circumstances occur or do not occur, that is, it includes both the substituted and unsubstituted cases. For example, "a heterocyclic group optionally substituted by an alkyl group" means that the alkyl group may or may not be present, and the description includes the cases where the heterocyclic group is substituted by an alkyl group and the cases where the heterocyclic group is not substituted by an alkyl group.

[0140] "Substitution" means that one or more "hydrogen atoms" in the base are independently substituted by an appropriate number of substituents. Of course, the substituents are only at positions where they are chemically possible, conform to the theory of chemical valence bonds, and those skilled in the art can confirm whether substitution is possible or not without special efforts (experimentally or theoretically). 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).

[0141] "Stereoisomer" refers to stereoisomer in English and refers to isomers caused by differences in the spatial arrangement of atoms within a molecule, which can be divided into two types: cis-trans isomers and enantiomers, and can also be divided into two types: enantiomers and diastereoisomers. Stereoisomers caused by the rotation of single bonds are called conformational stereo-isomers and also called rotamers. Stereoisomers caused by bond length, bond angle, double bonds within the molecule, the presence of rings, etc. are called configuration stereo-isomers, and the configuration stereo-isomers are divided into two types. Among them, isomers caused by the inability of double bonds or single bonds of ring-forming carbon atoms to rotate freely are geometric isomers and also called cis-trans isomers, which are divided into two structures: Z and E. For example, cis-2-butene and trans-2-butene are a pair of geometric isomers, and stereoisomers with different optical properties caused by the lack of anti-axis symmetry within the molecule are called optical isomers, which are divided into structures R and S. In the present invention, the "stereoisomer" may be understood to include one or more of the enantiomers, configuration stereo-isomers, and conformational stereo-isomers unless otherwise specified.

[0142] In the present invention, "pharmaceutically acceptable salt" refers to a pharmaceutically acceptable acid addition salt, including inorganic acid salts and organic acid salts, and these salts can be produced by methods known in the art.

[0143] The "pharmaceutical 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 purpose of the pharmaceutical composition is to facilitate administration to an organism and exert biological activity by contributing to the absorption of the active ingredient.

[0144] Hereinafter, the present invention will be described in more detail and comprehensively with reference to examples, which do not limit the present invention, and the present invention is not limited only to the content of the examples. The structure of the compound of the present invention was confirmed by nuclear magnetic resonance (NMR) or / and liquid chromatography-mass spectrometry (LC-MS). The chemical shift (?) of NMR is shown in units of parts per million (ppm). The NMR measurement was performed using a Bruker AVANCE-400 / 500 nuclear magnetic resonance apparatus, and the solvents for the measurement were deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), and deuterated chloroform (CDCl3), and the internal standard was tetramethylsilane (TMS).

[0145] The measurement of liquid chromatography-mass spectrometry LC-MS was performed using an Agilent 6120 mass spectrometer. The HPLC measurement was performed using an Agilent 1200DAD high-pressure liquid chromatograph (Sunfire C18 150 × 4.6 mm chromatographic column) and a Waters 2695-2996 high-pressure liquid chromatograph (Gimini C18 150 × 4.6 mm chromatographic column).

[0146] For thin layer chromatography, silica gel plates of Yantai Huanghai HSGF254 or Qingdao GF254 were used. The specifications used for TLC were 0.15 mm to 0.20 mm, and the specifications used for the separation of products by thin layer chromatography were 0.4 mm to 0.5 mm. For column chromatography, silica gel of 200 to 300 mesh of Yantai Huanghai silica gel was usually used as the carrier.

[0147] The starting materials in the examples of the present invention are known commercially available products or those that can be synthesized by methods known in the art. Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in an atmosphere of dry nitrogen or argon, the solvent is a dry solvent, and the unit of the reaction temperature is degrees Celsius (°C).

[0148] Manufacture of an intermediate Manufacture of Intermediate 1, 4-Amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid

[0149]

Chemical formula

[0150] First step: Synthesis of methyl 4-amino-5-bromo-2-fluorobenzoate

[0151]

Chemical formula

[0152] Methyl 4-amino-2-fluorobenzoate (20.8 g, 123.0 mmol) was dissolved in chloroform (500 mL), and N-bromobutanimide (21.89 g, 123.0 mmol) was added at 0 °C, followed by stirring and reacting 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 4-amino-5-bromo-2-fluorobenzoate (27.9 g, 112.5 mmol, 91%). MS m / z (ESI): 247.9, 250.0 [M+H] + 。

[0153] 1 H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.2 Hz, 1H), 6.46 (d, J = 12.2 Hz, 1H), 4.62 (s, 2H), 3.88 (s, 3H).

[0154] Second Step: Synthesis of Methyl 4-Amino-2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate

[0155]

Chem.

[0156] Methyl 4-amino-5-bromo-2-fluorobenzoate (27.9 g, 112.5 mmol) and bis(pinacolato)diboron (35 mL, 135 mmol) were dissolved in dioxane (300 mL), and potassium acetate (33.12 g, 337.4 mmol) and 1,1'-bis(diphenylphosphino)ferrocenedichloropalladium(II) (8.23 g, 11.2 mmol) were added. The mixture was stirred and reacted at 100 °C for 18 hours. The reaction solution was filtered and then rotary dried. The crude product was diluted with water, extracted three times with ethyl acetate, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was rotary evaporated to concentrate. The crude product was separated by normal phase column to obtain methyl 4-amino-2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (25.2 g, 85.4 mmol, 76%). MS m / z (ESI): 296.2 [M+H] + 。

[0157] 1 H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 9.2 Hz,1H), 6.24 (d, J =13.2 Hz,1H), 5.29 (s, 2H), 3.86 (s, 3H),1.34 (s,12H).

[0158] Third Step: Synthesis of Methyl 4-Amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carboxylate

[0159]

Chem.

[0160] 5-Bromo-1-methyl-1H-pyrazole-4-carbonitrile (9.1 g, 48.9 mmol), methyl 4-amino-2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (14.4 g, 48.9 mmol), potassium carbonate (27.04 g, 195.7 mmol) and tetrakis(triphenylphosphine)palladium (7.35 g, 6.4 mmol) were added to 1,4-dioxane (100 mL) and water (100 mL), and the reaction was carried out at 100 °C for 16 h under the protection of nitrogen gas. The organic solvent was evaporated under reduced pressure, filtered, the filter cake was washed with ethanol (50 mL), and the filter cake was dried to obtain methyl 4-amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carboxylate (13.28 g, 48.4 mmol, 99%). MS m / z (ESI): 275.1 [M+H] + 。

[0161] Fourth step: Synthesis of 4-amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid

[0162]

Chemical formula

[0163] Methyl 4-amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carboxylate (13.28 g, 48.4 mmol) was added to tetrahydrofuran (100 mL) and water (100 mL), and then lithium hydroxide monohydrate (4.06 g, 96.8 mmol) was added and the mixture was heated to 50 oThe reaction was carried out for 16 hours under the conditions of C. After the reaction was completed, the organic phase was rotary dried, diluted by adding water, and extracted with ethyl acetate (200 mL * 6). The aqueous phase was adjusted to pH = 2 with saturated potassium bisulfate, and a large amount of solid precipitated. It was filtered, and the filter cake was washed with water (100 mL) and acetonitrile (100 mL), and the filter cake was dried to obtain 4-amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid (6.7 g, 25.7 mmol, 53%). MS m / z (ESI): 261.1 [M+H] + 。

[0164] 1 1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J = 8.0 Hz, 1H), 8.27 (s, 1H), 7.54 (s, 2H), 7.27 (d, J = 13.2 Hz, 1H), 4.38 (s, 3H). Intermediates 2 to 5 can be prepared by referring to all or part of the synthesis method of Intermediate 1 and selecting the corresponding raw materials.

[0165]

Table 1

[0166] Preparation of Intermediate 6, 6-(Trifluoromethyl)benzofuran-3(2H)-one

[0167]

Chemical formula

[0168] The first step: Synthesis of methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate

[0169]

Chemical formula

[0170] 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, and then methyl bromoacetate (8.42 mL, 88.6 mmol) was added dropwise to the reaction solution. Subsequently, the temperature was raised to 55 °C and the reaction was carried out for 18 hours. After the reaction was complete, the reaction solution was cooled to room temperature, the solid was removed by filtration, and the filter cake was washed with ethyl acetate. The filtrate was washed with saturated brine, dried, and then concentrated to obtain methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate (22.0 g, 64.0 mmol, 94%). MS m / z (ESI): 293.1 [M+H] + 。

[0171] Second step: Synthesis of 2-(carboxylmethoxy)-4-(trifluoromethyl)benzoic acid

[0172]

Chemical formula

[0173] 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. After it was detected by TLC that the reaction was complete, the reaction solution was acidified to pH = 2 with 1 N hydrochloric acid, 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-(carboxylmethoxy)-4-(trifluoromethyl)benzoic acid (61 g, 230.9 mmol, 91%). MS m / z (ESI): 265.0 [M+H] + 。

[0174] Third step: Synthesis of 6-(trifluoromethyl)benzofuran-3(2H)-one

[0175] [Chemical formula]

[0176] A mixture of 2-(carboxylmethoxy)-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 the reaction was completed, 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. It was detected by LCMS that the reaction was completed. The reaction solution was cooled to room temperature, water was added, and it was extracted with ethyl acetate. The organic phase was extracted, washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated. After concentration, it was triturated with methyl tert-butyl ether (MTBE) to obtain 6-(trifluoromethyl)benzofuran-3(2H)-one (17.0 g, 84.1 mmol, 36%).

[0177] 1 H NMR (400 MHz, CDCl3) 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).

[0178] Production of Intermediate 7, 2-(Trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-one

[0179] [Chemical formula]

[0180] First step: Synthesis of methyl 2-bromo-6-(trifluoromethyl)nicotinate

[0181]

Chem.

[0182] 2-Oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylic acid (5.0 g, 24.14 mmol), pyridine (1.95 mL, 24.14 mmol) were dissolved in chlorobenzene (50 mL), and phosphoryl bromide (4.91 mL, 48.28 mmol) was slowly added in several portions at room temperature. The temperature was raised to 120 °C and the mixture was stirred and reacted for 16 hours. After the reaction was completed, the reaction solution was concentrated in vacuo. The concentrate was cooled to 0 °C in an ice bath, and then dry methanol (20 mL) pre-cooled with dry ice was slowly 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 solution was adjusted to pH 8 with saturated sodium bicarbonate solution, 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): 283.9, 285.9 [M+H] + 。

[0183] 1 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 4.00 (s, 3H).

[0184] Second step: Synthesis of methyl (E)-2-(3-methoxy-3-oxopropyl-1-en-1-yl)-6-(trifluoromethyl)nicotinate

[0185]

Chem.

[0186] A solution of methyl 2-bromo-6-(trifluoromethyl)nicotinate (5.7 g, 20.07 mmol), methyl acrylate (4.52 mL, 50.17 mmol) in toluene (100 mL) and N,N-dimethylformamide (15 mL) was added with allylpalladium(II) chloride dimer (0.37 g, 1.00 mmol), tris(2-methylphenyl)phosphine (0.61 g, 2.01 mmol) and sodium carbonate (6.38 g, 60.20 mmol), and then stirred at 120 °C for 16 h under an atmosphere of nitrogen gas. The reaction mixture was filtered, and the filter cake was washed three times with ethyl acetate (30 mL * 3). The organic phases were combined and concentrated in vacuo, and the concentrate was separated by silica gel column chromatography to obtain methyl (E)-2-(3-methoxy-3-oxopropyl-1-en-1-yl)-6-(trifluoromethyl)nicotinate (5.1 g, 88%). MS m / z (ESI): 290.0 [M+H] + 。

[0187] 1 H NMR (400 MHz, CDCl3) 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).

[0188] Third step: Synthesis of methyl 2-(3-methoxy-3-oxopropyl)-6-(trifluoromethyl)nicotinate

[0189]

Chemical formula

[0190] A solution of methyl (E)-2-(3-methoxy-3-oxopropyl-1-en-1-yl)-6-(trifluoromethyl)nicotinate (5.1 g, 17.63 mmol) and Wilkinson's catalyst (1.31 g, 1.41 mmol) in ethanol (50 mL) was stirred at room temperature for 48 h under an atmosphere of hydrogen gas (15 Psi). 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): 292.1 [M+H] + .

[0191] 1 H NMR (400 MHz, CDCl3) 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).

[0192] Fourth step: Synthesis of 2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-one

[0193]

Chemical formula

[0194] A solution of methyl 2-(3-methoxy-3-oxopropyl)-6-(trifluoromethyl)nicotinate (4.9 g, 16.82 mmol) in methanol (60 mL) was added sodium methoxide (1.36 g, 25.23 mmol) in several portions, and the reaction mixture was stirred at 80 °C overnight. After the reaction was completed, the reaction mixture was cooled to room temperature and concentrated to obtain a brown solid. The brown solid was dispersed in 12 M 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 (100 mL * 2). 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): 201.9 [M+H] + 。

[0195] 1 H NMR (400 MHz, CDCl3) 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).

[0196] Production of Intermediate 8, 6-(Trifluoromethyl)furo[2,3-b]pyridin-3(2H)-one

[0197]

Chemical formula

[0198] First step: Synthesis of ethyl 2-chloro-6-(trifluoromethyl)nicotinate

[0199]

Chemical formula

[0200] At room temperature, thionyl chloride (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 by nitrogen gas. Subsequently, the reaction solution was heated to 70 °C and stirred for 14 hours for reaction. 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] to obtain ethyl 2-chloro-6-(trifluoromethyl)nicotinate (7.72 g, 30.44 mmol, 92%). MS m / z (ESI): 254.0 [M+H] + . 1 H NMR (400 MHz, CDCl3) 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).

[0201] Second step: Synthesis of ethyl 3-hydroxy-6-(trifluoromethyl)furo[2,3-b]pyridine-2-carboxylate

[0202]

Chemical formula

[0203] 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 bicarbonate solution. The organic phase was extracted, washed with saturated brine, dried over anhydrous sodium sulfate and then concentrated. After concentration, it was triturated with acetonitrile (300 mL) to obtain ethyl 3-hydroxy-6-(trifluoromethyl)furo[2,3-b]pyridine-2-carboxylate (29.5 g, 107.2 mmol, 70%).

[0204] 1 H NMR (400 MHz, DMSO-d6) 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).

[0205] Third step: Synthesis of 6-(trifluoromethyl)furo[2,3-b]pyridin-3(2H)-one

[0206]

Chemical formula

[0207] 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 to pH 6 - 7 with 1 M hydrochloric acid in an ice-water bath. After liquid separation, 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, 7.04 mmol, 68%). MS m / z (ESI): 204.0 [M+H] + 。

[0208] 1 H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 7.6 Hz,1H), 7.52 (d, J = 7.6 Hz,1H), 4.85 (s, 2H).

[0209] Production of Intermediate 9, (S)-N-(1-methyl-1H-pyrazol-4-yl)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-amine

[0210]

Chemical formula

[0211] First step: Synthesis of (R)-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridin-3-ol

[0212]

Chemical formula

[0213] (R)-Me-CBS (5.94 g, 21.416 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, and 6-(trifluoromethyl)furo[2,3-b]pyridin-3(2H)-one (14.5 g, 71.4 mmol) was dissolved in tetrahydrofuran (140 mL) and added dropwise to the reaction system, followed by stirring for 1 hour while maintaining the temperature, and then the temperature was raised to -10 °C and stirring was continued for 2 hours. It was detected that the reaction was completed, quenched with methanol, and stirred at room temperature for 30 minutes. 70 mL of aqueous ammonia was added, stirred, and then the supernatant was poured out, 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, 58.5 mmol, 82%). MS m / z (ESI): 205.9 [M+H] + .

[0214] Second step: Synthesis of (S)-3-azido-6-(trifluoromethyl)-2,3-dihydrofuro[2,3-b]pyridine

[0215] [Chemical formula]

[0216] (R)-6-(Trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-ol (12 g, 58.5 mmol) was dissolved in tetrahydrofuran (100 mL), cooled to 0 °C, and diphenylphosphoryl azide (15.2 mL, 70.2 mmol) and DBU (10.5 mL, 70.2 mmol) were 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 extraction 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-dihydrofuran[2,3-b]pyridine (12.5 g, 54.3 mmol, 93%). MS m / z (ESI): 231.0 [M+H] + 。

[0217] Step 3: Synthesis of (S)-6-(Trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-amine hydrochloride

[0218]

Chemical formula

[0219] (S)-3-Azido-6-(trifluoromethyl)-2,3-dihydrofuran[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. After it was detected by LCMS that the reaction had ended, 0.5 M hydrochloric acid was added and extraction was carried out 3 times with ethyl acetate. The aqueous phase obtained by liquid separation was concentrated to obtain (S)-6-(trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-amine hydrochloride (11.0 g, 45.7 mmol, 84%). MS m / z (ESI): 205.1 [M+H] + 。

[0220] Fourth Project: Synthesis of (S)-N-(1-methyl-1H-pyrazol-4-yl)-6-(trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-amine

[0221] [Chemical formula]

[0222] (S)-6-(Trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-amine hydrochloride (5.5 g, 22.9 mmol) was dissolved in dioxane (500 mL), 4-bromo-1-methyl-1H-pyrazole (4.23 g, 26.3 mmol), methanesulfonic acid (2-di-t-butylphosphinyl-2’,4’,6’-triisopropyl-1,1’-biphenyl)(2’-amino-1,1’-biphenyl-2-yl)palladium(II) (5.45 g, 6.86 mmol) and sodium tert-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 the mixture was extracted with ethyl acetate. The organic phase obtained by liquid separation was dried and concentrated, and then separated by silica gel column chromatography (PE / EA = 1 / 10) and C18 reverse phase column (Water (10 mM NH4HCO3)-ACN: 21%-51%) to obtain (S)-N-(1-methyl-1H-pyrazol-4-yl)-6-(trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-amine (2.4 g, 8.44 mmol, 37%). MS m / z (ESI): 285.1 [M+H] + .

[0223] 11H NMR (400 MHz, DMSO-d6) 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 10 to 19 can be produced by referring to all or part of the synthesis method of Intermediate 9 and selecting the corresponding raw materials.

[0224] [Table 2] TIFF2025520530000079.tif125170

[0225] Production of Intermediate 20, (R)-N-(cyclopropylmethyl)-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amine

[0226] [Chemical formula]

[0227] First step: Synthesis of (R)-N-(cyclopropylmethyl)-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amine

[0228] [Chemical formula]

[0229] (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): 256.1 [M+H] + 。

[0230] Intermediates 21 to 22 can be prepared by referring to all or part of the synthetic method of Intermediate 20 and selecting the corresponding raw materials.

[0231]

Table 3

[0232] Preparation of Intermediates 23, 24, 25, N-(Cyclopropylmethyl)-2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-amine

[0233]

Chemical formula

[0234] 2-(Trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-one (1.35 g, 6.71 mmol) was dissolved in ethanol (20 mL), and a mixture of aminomethylcyclopropane (1.75 mL, 20.13 mmol) and acetic acid (0.24 mL, 1.34 mmol) was added. The mixture was stirred at 40 °C overnight. The reaction mixture was cooled in an ice bath, sodium borohydride (0.45 g, 13.42 mmol) was added, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture to quench it, and the mixture was extracted with ethyl acetate. The organic phase was concentrated by rotary evaporation, and the crude product was separated by column chromatography (methanol / dichloromethane = 1 / 10) to obtain (N-(cyclopropylmethyl)-2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-amine (850 mg, 49%). MS m / z (ESI): 257.1 [M+H] + 。

[0235] 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.8 Hz,1H), 7.50 (d, J = 7.8 Hz,1H), 4.35 (t, J = 7.0 Hz,1H), 3.21-3.13 (m,1H), 3.04-2.95 (m,1H), 2.70-2.50 (m, 3H),1.94-1.87 (m,1H),1.07-0.95 (m,1H), 0.55-0.47 (m, 2H), 0.22-0.10 (m, 2H). (N-(Cyclopropylmethyl)-2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-amine (700 mg, 2.73 mmol) was separated by a chiral preparative column to obtain (S)-N-(cyclopropylmethyl)-2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-amine (24) (310 mg, 44%) and (R)-N-(cyclopropylmethyl)-2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-amine (25) (305 mg, 43%).

[0236] Intermediates 26 to 38 can be produced by referring to all or part of the synthesis methods of Intermediates 23, 24, and 25 and selecting the corresponding raw materials.

[0237] [Table 4] TIFF2025520530000085.tif230170TIFF2025520530000086.tif37170

[0238] I. Production of Examples Example 1: Production of (S)-5-Amino-N-(cyclopropylmethyl)-N-(2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-yl)benzo[c][2,6]diazonaphthalene-9-carboxamide

[0239] [Chemical formula]

[0240] First Step: Synthesis of N-Ethyl-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amine

[0241] [Chemical formula]

[0242] 5-Aminobenzo[c][2,6]diazonaphthalene-9-carboxylic acid (67 mg, 0.28 mmol) was dissolved in N,N-dimethylacetamide (3 mL), 2-chloro-1-methylpyridinium iodide (72 mg, 0.28 mmol) and N,N-diisopropylethylamine (121 mg, 0.94 mmol) were added, and the mixture was stirred at 40 °C for 1 hour. (S)-N-(Cyclopropylmethyl)-2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-amine (60 mg, 0.23 mmol) was added to the reaction solution, and the stirring reaction was continued at 40 °C overnight. The reaction solution was directly subjected to reverse phase separation (40% acetonitrile - 10 mM ammonium bicarbonate aqueous solution system), and after lyophilization, (S)-5-amino-N-(cyclopropylmethyl)-N-(2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-5-yl)benzo[c][2,6]diazonaphthalene-9-formamide (37 mg, yield: 33%) was obtained. MS m / z (ESI): 478.2 [M+H] + 。

[0243] 1 H NMR (400 MHz, MeOH-d4) δ10.00 (s,1H), 8.80 (d, J = 5.6 Hz,1H), 8.71 (s,1H), 8.17 (d, J = 5.6 Hz,1H), 8.09 (d, J = 7.9 Hz,1H), 7.70-7.67 (m, 3H), 5.63-5.56 (m,1H), 3.54-3.35 (m, 2H), 2.87-2.52 (m, 4H),1.16-1.01 (m,1H), 0.55-0.45 (m, 2H), 0.14-0.01 (m, 2H).

[0244] Example 2: Preparation of (S)-4-Amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazol-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-yl)-1H-pyrazolo[4,3-c]quinoline-8-formamide

[0245] [Chemical formula]

[0246] Step 1: Synthesis of 4-amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carbonyl chloride hydrochloride

[0247] [Chemical formula]

[0248] 4-Amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid (100 mg, 0.38 mmol) was placed in dichloromethane (10 mL), 1,4-dioxane solution of hydrochloric acid (0.5 mL, 2.0 mmol, 4 mol / L) was added, and the mixture was stirred at room temperature for half an hour. The reaction solution was concentrated by rotary evaporation under reduced pressure until dry. The residue was added to thionyl chloride (1.0 mL, 13.79 mmol), and the mixture was stirred and reacted at 70 °C overnight. The reaction solution was concentrated by rotary evaporation under reduced pressure, and the residue was added to dry dichloromethane (5 mL). After rotary evaporation and concentration, 4-amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carbonyl chloride hydrochloride (118 mg, yield: 99%) was obtained. MS m / z (ESI): 275.2 [M+H] + .

[0249] Step 2: Synthesis of (S)-4-amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazol-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-yl)-1H-pyrazolo[4,3-c]quinoline-8-formamide

[0250] [Chemical formula]

[0251] 4-Amino-7-fluoro-1-methyl-1H-pyrazolo[4,3-c]quinoline-8-carbonyl chloride hydrochloride (119 mg, 0.38 mmol) was placed in dichloroethane (6 mL), pyridine (0.26 mL, 3.20 mmol) and (S)-N-(1-methyl-1H-pyrazol-4-yl)-6-(trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-amine (96 mg, 0.34 mmol) were added, and the mixture was stirred and reacted at 70 °C for 4 hours. After the reaction was completed, saturated sodium bicarbonate solution and dichloromethane were added. After filtration, the layers were separated. The aqueous phase was extracted with dichloromethane. The organic phase was concentrated by rotary evaporation. The crude product was separated by silica gel column chromatography [5% methanol-dichloromethane system] to obtain (S)-4-amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazol-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrofuran[2,3-b]pyridin-3-yl)-1H-pyrazolo[4,3-c]quinoline-8-formamide (140 mg, yield: 82%). MS m / z (ESI): 527.2 [M+H] + 。

[0252] 1 H NMR (400 MHz, MeOH-d4) δ 8.26 (d, J = 7.1 Hz,1H), 8.18 (s,1H), 8.14 (d, J = 7.5 Hz,1H), 7.48-7.42 (m, 2H), 7.15-7.05 (m, 2H), 6.67 (d, J = 8.3 Hz,1H), 4.99 (t, J = 9.7 Hz,1H), 4.85 (dd, J =10.8, 3.8 Hz,1H), 4.41 (s, 3H), 3.57 (s, 3H). Examples 6 to 238 can be produced by referring to all or part of the synthesis methods of Example 1 or Example 2 and selecting the corresponding raw materials.

[0253]

Table 5

[0254] The nuclear magnetic data of the compounds produced in the above examples are as follows.

[0255]

Table 6

[0256] Biological measurement and evaluation I. Human colorectal cancer HCT116 cell growth inhibition test 1. Seed HCT 116 MTAP knockout cells and MTAP wild-type cells in a 96-well flat-bottom plate and culture them overnight at 37°C and 5% CO2 in McCoy's 5A medium containing 10% fetal bovine serum + 1% penicillin-streptomycin.

[0257] 2. The next day, dissolve the compound in DMSO, dilute the compound in DMSO and medium in sequence and transfer it to the cell plate. The final concentrations of the compound are 10 μM, 4-fold dilution, nine concentration gradients and a DMSO control.

[0258] 3. Take out the cells not treated with the compound, detect the cell viability with CellTiter-Glo Luminescent Cell Viability Assay (Promega). The operation refers to the kit instruction manual. Then, place the cell plate in an EnVision Multilabel Reader to detect the luminescence signal.

[0259] 4. At the same time, continuously culture the cell plate treated with the compound at 37°C and 5% CO2 for 6 days. 5. Then, detect the cell viability with CellTiter-Glo in the same way.

[0260] 6. Finally, draw a dose-response curve using the four-parameter dose-response curve module of GraphPad Prism v 9.2.0 software and calculate the growth inhibition IC 50 (unit: nM). The test results are as follows.

[0261]

Table 7

[0262] From the biological activity data of the compounds of the specific examples, a series of compounds of the present invention have a strong inhibitory effect on the growth of human colorectal cancer HCT116 MTAP knockout cells at the cellular level, and some of the compounds have a weak inhibitory effect on MTAP wild-type HCT116 cells and have high selectivity.

[0263] II. Measurement of mouse pharmacokinetics 1. Purpose of the study The purpose of this test is to study the pharmacokinetic behavior of some compounds of the present invention. The administration methods are single oral administration (PO) to ICR mice, respectively, and the administration dose is 10 mg / kg.

[0264] 2. Test protocol 2.1 Test drug The compounds used in this test are derived from the compounds of the specific examples of the present invention.

[0265] 2.2 Test animals ICR male mice N = 3 Source: Shanghai Xipu'er-Bikai Experimental Animal Co., Ltd. 2.3 Preparation and administration of drugs The compounds were weighed and dissolved in a solvent of 20% PG + 10% Solutol HS15 + 70% pH3 citrate buffer, respectively, and shaken and sonicated to form a colorless and transparent solution. After fasting 9 mice overnight, they were orally administered. The administration dose is 10 mg / kg.

[0266] 2.4 Sample collection 1) About 90 μL of blood was collected from the submandibular vein at each time point, anticoagulated with sodium heparin, placed on ice after collection, and centrifuged within 1 hour to separate plasma (centrifugation conditions: 8000 revolutions / min, 6 minutes, 2 - 8 degrees). 2) The blood collection time points were the 1st, 4th, and 24th hours. The samples were stored in a refrigerator at -20 degrees. 3) 40 μL of plasma samples were added to 160 μL of ice-cold acetonitrile containing an internal standard, vortexed for 3 minutes, and centrifuged at 11000 revolutions / min for 5 minutes. 4) 100 μL of the supernatant was added to 100 μL of water, and 5 μL thereof was injected into LC / MS / MS for analysis.

[0267] 3. Blood-brain barrier permeability analysis Calculate Kp from the AUC or concentration in the brain or plasma measured by the above method. Kp refers to the relationship between the drug concentrations in the brain and blood and is used to evaluate the blood-brain barrier permeability ability of the drug. The Kp after administration is calculated by the following formula.

[0268] Kp = [AUC (brain) / AUC (plasma)], or Kp = [drug concentration (brain) / drug concentration (plasma)]

[0269]

Table 8

[0270] As can be seen from the above data, a plurality of compounds of the present invention have a significantly higher Kp than Comparative Compound 2 and have superior blood-brain barrier permeability characteristics than the comparative compounds of the prior art. All documents related to the present invention are cited herein for reference as each document is cited independently. Also, after reading the above content 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 included in the scope of the claims of the present invention.

Claims

1. A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein: 【Chemical 1】 Here, X １ is CR ６ or N, and X ２ is CR ７ or N, and X ３ is CR ８ or N, and Ring A is C ３－１０ a cycloalkyl group, a 4- to 10-membered heterocyclic group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, and the C ３－１０ cycloalkyl group or 4- to 10-membered heterocyclic group is further condensed with a C ６－１０ aryl group or a 5- to 10-membered heteroaryl group, and the C ６－１０ aryl group or a 5- to 10-membered heteroaryl group is further condensed with a C ３－１０ cycloalkyl group or a 4- to 10-membered heterocyclic group, Ring B is C ４－１２ a cycloalkyl group, a 4- to 12-membered heterocyclic group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, Each R １ 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 ９ -, -C ０－８ alkyl-S(O) ｒ R ９ -, -C ０－８ alkyl-O-R １０ -, -C ０－８ alkyl-C(O)OR １０ -, -C ０－８ alkyl-C(O)SR １０ -, -C ０－８ alkyl-S-C(O)R １１ -, -C ０－８ alkyl-C(O)R １１ -, -C ０－８ alkyl-O-C(O)R １１ -, -C ０－８ alkyl-P(O)(R １１ ) ２ -, -C ０－８ alkyl-NR １２ R １３ -, -C ０－８ alkyl-C(O)NR １２ R １３ and -C ０－８ alkyl-N(R １２ )-C(O)R １１ selected from, and the groups are independently optionally 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 groups, 5-10 membered heteroaryl groups, ═O, ═S, -C ０－８ Alkyl-SF ５ , -C ０－８ Alkyl-O-S(O) ２ R ９ , -C ０－８ Alkyl-S(O) ｒ R ９ , -C ０－８ Alkyl-O-R １０ , -C ０－８ Alkyl-C(O)OR １０ , -C ０－８ Alkyl-C(O)SR １０ , -C ０－８ Alkyl-S-C(O)R １１ , -C ０－８ Alkyl-C(O)R １１ , -C ０－８ Alkyl-O-C(O)R １１ , -C ０－８ Alkyl-P(O)(R １１ ) ２ , -C ０－８ Alkyl-NR １２ R １３ , -C ０－８ Alkyl-C(O)NR １２ R １３ and -C ０－８ Alkyl-N(R １２ )-C(O)R １１ is further 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 group, 3- to 12-membered heterocyclic group, C ６－１０ aryl group, 5- to 10-membered heteroaryl group, -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ and -C(O)NR １２ R １３ selected from, and said groups are independently optionally 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 ９ , -C ０－８ alkyl-S(O) ｒ R ９ , -C ０－８ alkyl-O-R １０ , -C ０－８ alkyl-C(O)OR １０ , -C ０－８ alkyl-C(O)SR １０ , -C ０－８ alkyl-S-C(O)R １１ , -C ０－８ alkyl-C(O)R １１ , -C ０－８ alkyl-O-C(O)R １１ , -C ０－８ alkyl-P(O)(R １１ ) ２ , -C ０－８ alkyl-NR １２ R １３ , -C ０－８ alkyl-C(O)NR １２ R １３ and -C ０－８ alkyl-N(R １２ )-C(O)R １１ further substituted by one or more substituents selected from R ３ and R ４ are each independently hydrogen, deuterium, a hydroxy group, C １－１０ alkyl group, C ２－１０ alkenyl group, C ２－１０ alkynyl group, 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 heterocyclic group or a 5- to 10-membered heteroaryl group, and the groups are each independently optionally 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 １２ R １３ and are further substituted by one or more substituents selected from, Each R ５ 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 ９ 、-C ０－８ alkyl-S(O) ｒ R ９ 、-C ０－８ alkyl-O-R １０ 、-C ０－８ alkyl-C(O)OR １０ 、-C ０－８ alkyl-C(O)SR １０ 、-C ０－８ alkyl-S-C(O)R １１ 、-C ０－８ alkyl-C(O)R １１ 、-C ０－８ alkyl-O-C(O)R １１ 、-C ０－８ alkyl-P(O)(R １１ ) ２ 、-C ０－８ alkyl-NR １２ R １３ 、-C ０－８ alkyl-C(O)NR １２ R １３ and -C ０－８ alkyl-N(R １２ )-C(O)R １１ selected from, and said groups are independently optionally 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 An aryl group, a 5- to 10-membered heteroaryl group, =O, =S, -C ０－８ Alkyl-SF ５ 、-C ０－８ Alkyl-O-S(O) ２ R ９ 、-C ０－８ Alkyl-S(O) ｒ R ９ 、-C ０－８ Alkyl-O-R １０ 、-C ０－８ Alkyl-C(O)OR １０ 、-C ０－８ Alkyl-C(O)SR １０ 、-C ０－８ Alkyl-S-C(O)R １１ 、-C ０－８ Alkyl-C(O)R １１ 、-C ０－８ Alkyl-O-C(O)R １１ 、-C ０－８ Alkyl-P(O)(R １１ ) ２ 、-C ０－８ Alkyl-NR １２ R １３ 、-C ０－８ Alkyl-C(O)NR １２ R １３ And -C ０－８ Alkyl-N(R １２ )-C(O)R １１ Further substituted by one or more substituents selected from R ６ 、 R ７ and R ８ are each independently hydrogen, 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, -C ０－８ alkyl-SF ５ 、 -C ０－８ alkyl-O-S(O) ２ R ９ 、 -C ０－８ alkyl-S(O) ｒ R ９ 、 -C ０－８ alkyl-O-R １０ 、 -C ０－８ alkyl-C(O)OR １０ 、 -C ０－８ alkyl-C(O)SR １０ 、 -C ０－８ alkyl-S-C(O)R １１ 、 -C ０－８ alkyl-C(O)R １１ 、 -C ０－８ alkyl-O-C(O)R １１ 、 -C ０－８ alkyl-P(O)(R １１ ) ２ 、 -C ０－８ alkyl-NR １２ R １３ 、 -C ０－８ alkyl-C(O)NR １２ R １３ and -C ０－８ alkyl-N(R １２ ) -C(O)R １１ selected from, Each R ９ 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 １２ R １３ selected from, and the group is independently optionally 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 １２ R １３ further substituted by one or more substituents selected from, Each R １０ is independently selected from hydrogen, deuterium, C １－１０ alkyl group, C ２－１０ alkenyl group, C ３－１２ cycloalkyl group, 3- to 12-membered heterocyclic group, C ６－１０ aryl group and 5- to 10-membered heteroaryl group, and the said groups are independently optionally further substituted by one or more substituents selected from deuterium, halogen, hydroxy group, =O, cyano group, 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 １２ R １３ and is further substituted by one or more substituents selected therefrom, Each R １１ is independently hydrogen, deuterium, a hydroxy 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, 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 １２ R １３ selected from, and the above groups are independently optionally deuterium, halogen, hydroxy group, =O, cyano group, 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 １２ R １３ further substituted by one or more substituents selected from, Each R １２ and R １３ are each independently hydrogen, deuterium, a hydroxy 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, sulfinyl group, sulfonyl group, methylsulfonyl group, isopropylsulfonyl group, cyclopropylsulfonyl group, p-toluenesulfonyl group, aminosulfonyl group, dimethylaminosulfonyl group, and C １－１０ alkanoyl group, and the groups are each independently optionally further substituted by one or more substituents selected from deuterium, halogen, 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 aryloxy group, 5- to 10-membered heteroaryl group, 5- to 10-membered heteroaryloxy group, amino group, C １－１０ alkylmonosubstituted amino group, C １－１０ alkyldisubstituted amino group, and C １－１０ alkanoyl group, or R １２ and R １３ together with the nitrogen atom to which they are directly attached form a 4- to 10-membered heterocyclic group or a 5- to 10-membered heteroaryl group, and the 4- to 10-membered heterocyclic group or 5- to 10-membered heteroaryl group is optionally deuterium, halogen, 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 aryloxy group, 5- to 10-membered heteroaryl group, 5- to 10-membered heteroaryloxy group, amino group, C １－１０ alkylmonosubstituted amino group, C １－１０ alkyldisubstituted amino group and C １－１０ alkanoyl group, and is further substituted by one or more substituents selected from each r is independently 0, 1 or 2; m is selected from 0, 1, 2, 3, 4, 5 or 6; and n is selected from 0, 1, 2, 3, 4 or 5,

2. Ring A is C ３－８ a cycloalkyl group, a 4- to 8-membered heterocyclic group, C ６－８ an aryl group or a 5- to 8-membered heteroaryl group, and the C ３－８ cycloalkyl group or 4- to 8-membered heterocyclic group is further condensed with a C ６－８ aryl group or 5- to 8-membered heteroaryl group, and the C ６－８ aryl group or 5- to 8-membered heteroaryl group is further condensed with a C ３－８ cycloalkyl group or 4- to 8-membered heterocyclic group, Ring B is C ４－６ a cycloalkyl group, a 4- to 6-membered heterocyclic group, C ６－８ an aryl group or a 5- to 8-membered heteroaryl group, Each R １ 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- 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 ９ , -C ０－４ alkyl-S(O) ｒ R ９ , -C ０－４ alkyl-O-R １０ , -C ０－４ alkyl-C(O)OR １０ , -C ０－４ alkyl-C(O)SR １０ , -C ０－４ alkyl-S-C(O)R １１ , -C ０－４ alkyl-C(O)R １１ , -C ０－４ alkyl-O-C(O)R １１ , -C ０－４ alkyl-P(O)(R １１ ) ２ , -C ０－４ alkyl-NR １２ R １３ , -C ０－４ alkyl-C(O)NR １２ R １３ and -C ０－４ alkyl-N(R １２ )-C(O)R １１ selected from, and the groups are independently optionally 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, -C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O-S(O) ２ R ９ , -C ０－４ Alkyl-S(O) ｒ R ９ , -C ０－４ Alkyl-O-R １０ , -C ０－４ Alkyl-C(O)OR １０ , -C ０－４ Alkyl-C(O)SR １０ , -C ０－４ Alkyl-S-C(O)R １１ , -C ０－４ Alkyl-C(O)R １１ , -C ０－４ Alkyl-O-C(O)R １１ , -C ０－４ Alkyl-P(O)(R １１ ) ２ , -C ０－４ Alkyl-NR １２ R １３ , -C ０－４ Alkyl-C(O)NR １２ R １３ and -C ０－４ Alkyl-N(R １２ )-C(O)R １１ further 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 group, 3 - 12 membered heterocyclic group, C ６－１０ aryl group, 5 - 10 membered heteroaryl group, -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ and -C(O)NR １２ R １３ selected from, and said groups are independently optionally 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 ９ , -C ０－４ alkyl-S(O) ｒ R ９ , -C ０－４ alkyl-O-R １０ , -C ０－４ alkyl-C(O)OR １０ , -C ０－４ alkyl-C(O)SR １０ , -C ０－４ alkyl-S-C(O)R １１ , -C ０－４ alkyl-C(O)R １１ , -C ０－４ alkyl-O-C(O)R １１ , -C ０－４ alkyl-P(O)(R １１ ) ２ , -C ０－４ alkyl-NR １２ R １３ , -C ０－４ Alkyl-C(O)NR １２ R １３ and -C ０－４ alkyl-N(R １２ )-C(O)R １１ further substituted by one or more substituents selected from R ３ and R ４ are each 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 and a 3-6 membered heterocyclic group, or R ３ and R ４ together with the nitrogen atom to which they are directly attached form a 4-6 membered heterocyclic group or a 5-8 membered heteroaryl group, and the said groups are independently optionally deuterium, halogen, cyano group, hydroxy group, =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, 3-6 membered heterocyclic group, 3-6 membered heterocyclic oxy group and -NR １２ R １３ are further substituted by one or more substituents selected from, Each R ５ 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- 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 ９ 、-C ０－４ alkyl-S(O) ｒ R ９ 、-C ０－４ alkyl-O-R １０ 、-C ０－４ alkyl-C(O)OR １０ 、-C ０－４ alkyl-C(O)SR １０ 、-C ０－４ alkyl-S-C(O)R １１ 、-C ０－４ alkyl-C(O)R １１ 、-C ０－４ alkyl-O-C(O)R １１ 、-C ０－４ alkyl-P(O)(R １１ ) ２ 、-C ０－４ alkyl-NR １２ R １３ 、-C ０－４ alkyl-C(O)NR １２ R １３ and -C ０－４ alkyl-N(R １２ )-C(O)R １１ selected from, and the groups are independently optionally 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, -C ０－４ Alkyl-SF ５ , -C ０－４ Alkyl-O-S(O) ２ R ９ , -C ０－４ Alkyl-S(O) ｒ R ９ , -C ０－４ Alkyl-O-R １０ , -C ０－４ Alkyl-C(O)OR １０ , -C ０－４ Alkyl-C(O)SR １０ , -C ０－４ Alkyl-S-C(O)R １１ , -C ０－４ Alkyl-C(O)R １１ , -C ０－４ Alkyl-O-C(O)R １１ , -C ０－４ Alkyl-P(O)(R １１ ) ２ , -C ０－４ Alkyl-NR １２ R １３ , -C ０－４ Alkyl-C(O)NR １２ R １３ and -C ０－４ Alkyl-N(R １２ )-C(O)R １１ further substituted by one or more substituents selected from R ６ 、 R ７ and R ８ 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- 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 ９ 、 -C ０－４ alkyl-S(O) ｒ R ９ 、 -C ０－４ alkyl-O-R １０ 、 -C ０－４ alkyl-C(O)OR １０ 、 -C ０－４ alkyl-C(O)SR １０ 、 -C ０－４ alkyl-S-C(O)R １１ 、 -C ０－４ alkyl-C(O)R １１ 、 -C ０－４ alkyl-O-C(O)R １１ 、 -C ０－４ alkyl-P(O)(R １１ ) ２ 、 -C ０－４ alkyl-NR １２ R １３ 、 -C ０－４ alkyl-C(O)NR １２ R １３ and -C ０－４ alkyl-N(R １２ ) -C(O)R １１ selected from, Here, R ９ and R １０ and R １１ and R １２ and R １３ and r are as defined in claim 1, characterized in that A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 1.

3. Each R ９ is independently hydrogen, deuterium, a hydroxy group, C １－４ alkyl group, C ２－４ alkenyl group, C ３－６ cycloalkyl group, a 3- to 6-membered heterocyclic group, C ６－８ aryl group, a 5- to 8-membered heteroaryl group, and -NR １２ R １３ selected from, and said group is independently optionally deuterium, halogen, a hydroxy group, =O, C １－４ alkyl group, C １－４ alkoxy group, C ３－６ cycloalkyl group, C ３－６ cycloalkoxy group, a 3- to 6-membered heterocyclic group, a 3- to 6-membered heterocyclic oxy group, C ６－８ aryl group, C ６－８ aryloxy group, a 5- to 8-membered heteroaryl group, a 5- to 8-membered heteroaryloxy group, and -NR １２ R １３ further substituted by one or more substituents selected from, Each R １０ is independently selected from 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 said groups are independently optionally further substituted by one or more substituents selected from 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 １２ R １３ and is further substituted by one or more substituents selected therefrom, Each R １１ is independently hydrogen, deuterium, a 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, a 3- to 6-membered heterocyclic group, a 3- to 6-membered heterocyclic oxy group, C ６－８ aryl group, C ６－８ aryloxy group, a 5- to 8-membered heteroaryl group, a 5- to 8-membered heteroaryloxy group, and -NR １２ R １３ selected from, and said groups are independently optionally 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, a 3- to 6-membered heterocyclic group, a 3- to 6-membered heterocyclic oxy group, C ６－８ aryl group, C ６－８ aryloxy group, a 5- to 8-membered heteroaryl group, a 5- to 8-membered heteroaryloxy group, and -NR １２ R １３ substituted further by one or more substituents selected from, Each R １２ and R １３ are each 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- to 6-membered heterocyclic group, C ６－８ aryl group, 5- to 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 group is further optionally substituted by one or more substituents selected from 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- 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, amino group, C １－４ alkylmonosubstituted amino group, C １－４ alkyldisubstituted amino group and C １－４ alkanoyl group, or R １２ and R １３ together with the nitrogen atom to which they are directly attached form a 4- to 6-membered heterocyclic group or a 5- to 8-membered heteroaryl group, and the 4- to 6-membered heterocyclic group or 5- to 8-membered heteroaryl group is optionally 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- 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, amino group, C １－４ alkylmonosubstituted amino group, C １－４ alkyldisubstituted amino group and C １－４ alkanoyl group, and is further substituted by one or more substituents selected from the group consisting of A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 1.

4. The compound of formula (I) has the structure of a compound of formula (II) below, [Chemical Formula 2] Here, X １ is CR ６ or N, and X ２ is CR ７ or N, and X ３ is CR ８ or N, and Y １ is CR １ａ or N, and Y ２ is CR １ｂ or N, and Y ３ is CR １ｃ or N, and Y ４ is CR １ｄ or N, and Z is -C(R １ｅ R １ｆ ), -C(R １ｅ R １ｆ ), -N(R １ｇ ), -O- or -S- and Ring B is C ４－６ a cycloalkyl group, a 4- to 6-membered heterocyclic group, C ６－８ an aryl group or a 5- to 8-membered heteroaryl group, R １ａ , R １ｂ , R １ｃ , R １ｄ 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , —O—C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ wherein the groups are independently selected from 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, -SF ５ , -O-S(O) ２ R ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , —O—C(O)R １１ , -P(O)(R １１ ), ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ further substituted by one or more substituents selected from R １ｅ 、R １ｆ is independently selected from 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 ９ 、-S(O) ｒ R ９ 、-O-R １０ 、-C(O)OR １０ 、-C(O)SR １０ 、-S-C(O)R １１ 、-C(O)R １１ 、-O-C(O)R １１ 、-P(O)(R １１ ) ２ 、-NR １２ R １３ 、-C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ ; or R １ｅ and R １ｆ together with the carbon atom to which they are directly attached form a C ３－６ cycloalkyl group or a 4- to 6-membered heterocyclic group, and the said groups are independently optionally 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 ９ 、-S(O) ｒ R ９ 、-O-R １０ 、-C(O)OR １０ 、-C(O)SR １０ 、-S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ further substituted by one or more substituents selected from R １ｇ 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 ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -C(O)R １１ and -C(O)NR １２ R １３ selected from, and said groups are independently optionally 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ substituted further by one or more substituents selected from, Each R １ｈ 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ selected from, and the groups are independently optionally 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ further substituted by one or more substituents selected from R ２ is selected from 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, -O-R １０ and -C(O)R １１ and is further substituted by one or more substituents 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ selected therefrom R ３ and R ４ are each independently hydrogen, deuterium, a hydroxy group, C １－４ alkyl group, C ３－６ cycloalkyl group, or a 3- to 6-membered heterocyclic group, or R ３ and R ４ together with the nitrogen atom to which they are directly attached form a 4- to 6-membered heterocyclic group or a 5- to 8-membered heteroaryl group, and the group is independently optionally deuterium, halogen, cyano group, hydroxy group, =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 １２ R １３ and is further substituted by one or more substituents selected from Each R ５ 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ selected from, and the groups are independently optionally 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ 、 -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ is further substituted by one or more substituents selected from R ６ 、R ７ and R ８ 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- to 6-membered heterocyclic group, C ６－８ aryl group, 5- to 8-membered heteroaryl group, -SF ５ 、-O-S(O) ２ R ９ 、-S(O) ｒ R ９ 、-O-R １０ 、-C(O)OR １０ 、-C(O)SR １０ 、-S-C(O)R １１ 、-C(O)R １１ 、-O-C(O)R １１ 、-P(O)(R １１ ) ２ 、-NR １２ R １３ 、-C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ selected from, o is 0, 1, 2 or 3; m1 is 0, 1 or 2; Here, R ９ , R １０ , R １１ , R １２ , R １３ and n and r are as defined in claim 1, and the compound of formula (I) according to claim 1, its stereoisomer or its pharmaceutically acceptable salt, characterized in that.

5. Ring B, together with the moiety to which they are directly attached, forms the following structure: [Chemical Formula 3] 【Chem.】 Each R ５ａ is independently selected from hydrogen, deuterium, halogen, cyano group, C １－４ alkyl 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 and -O-R １０ and is further substituted by one or more substituents independently 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- 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ selected therefrom., Each R ５ｂ is independently hydrogen, deuterium, C １－４ alkyl group, C ３－６ cycloalkyl group, 3- to 6-membered heterocyclic group, and -O-R １０ selected from, and said group is independently optionally 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected from, Each R ５ｃ is independently selected from hydrogen, deuterium, halogen, cyano group, C １－４ alkyl 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 and -O-R １０ and the group is further substituted by one or more substituents independently 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- 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 ９ , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)SR １０ , -S-C(O)R １１ , -C(O)R １１ , -O-C(O)R １１ , -P(O)(R １１ ) ２ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected therefrom, X １ is CR ６ or N, and each R ６ is independently selected from 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 ３－６ cycloalkyl group, 3- to 6-membered heterocyclic group, -SF ５ and -O-R １０ and is selected from X ２ is CR ７ or N, and each R ７ 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 ３－６ cycloalkyl group, 3-6 membered heterocyclic group, -SF ５ and -O-R １０ selected from, Each R ８ is independently selected from 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 ３－６ cycloalkyl group, 3- to 6-membered heterocyclic group, -SF ５ and -O-R １０ and is selected from Here, R ９ R １０ R １１ R １２ R １３ and r are as defined in claim 4, characterized in that A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 4.

6. The compound of formula (I) has the structure of a compound of formula (III) below, 【Chemical Formula 4】 Here, X １ is CR ６ or N, and X ２ is CR ７ or N, and Y １ is CR １ａ or N, and Y ２ is CR １ｂ or N, and Z is -C(R １ｅ R １ｆ ), -C(R １ｅ R １ｆ )O-, -N(R １ｇ )- or -O- and Ring B, together with the moiety to which they are directly attached, forms the following structure: 【Chemical Formula 5】 【Chem.】 R １ａ and R １ｂ 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, -SF ５ and -O-R １０ selected from, and the said groups are independently optionally 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 , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ , -O-C(O)R １１ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected from, R １ｅ and R １ｆ 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 and -O-R １０ selected from, and said groups are independently optionally 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 , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ , -O-C(O)R １１ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and further substituted by one or more substituents selected from, R １ｇ is selected from hydrogen, deuterium, C １－４ alkyl group, C ３－６ cycloalkyl group, 3-6 membered heterocyclic group, hydroxy group, C １－４ alkoxy group and -C(O)R １１ and is further substituted by one or more substituents 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 , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ , -O-C(O)R １１ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected therefrom, Each R １ｈ 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- to 6-membered heterocyclic group, C ６－８ aryl group, 5- to 8-membered heteroaryl group, -SF ５ and -O-R １０ selected from, and said groups are independently optionally 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 , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ , -O-C(O)R １１ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected from, R ２ is selected from hydrogen, deuterium, 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-R １０ and -C(O)R １１ and the groups are independently optionally 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 -, -S(O) ｒ R ９ -, -O-R １０ -, -C(O)OR １０ -, -C(O)R １１ -, -O-C(O)R １１ -, -NR １２ R １３ -, -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected from Each R ５ａ is independently selected from hydrogen, deuterium, halogen, cyano group, C １－４ alkyl group, C ３－６ cycloalkyl group, 3-6 membered heterocyclic group, -SF ５ and -O-R １０ and the group is independently optionally 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 , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ , -O-C(O)R １１ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected from, Each R ５ｂ is independently hydrogen, deuterium, C １－４ alkyl group, C ３－６ cycloalkyl group, 3- to 6-membered heterocyclic group, and -O-R １０ selected from, and said groups are independently optionally 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 , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ , -O-C(O)R １１ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and further substituted by one or more substituents selected from, Each R ５ｃ is independently selected from hydrogen, deuterium, halogen, cyano group, C １－４ alkyl 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 and -O-R １０ and the group is independently optionally 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 , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ , -O-C(O)R １１ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected from R ６ is selected from 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- to 6-membered heterocyclic group, C ６－８ aryl group, 5- to 8-membered heteroaryl group, -SF ５ and -O-R １０ and is selected from R ７ is selected from 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- to 6-membered heterocyclic group, C ６－８ aryl group, 5- to 8-membered heteroaryl group, -SF ５ and -O-R １０ and is selected from R ８ is selected from 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- to 6-membered heterocyclic group, C ６－８ aryl group, 5- to 8-membered heteroaryl group, -SF ５ and -O-R １０ and is selected from: o is 1 or 2; m1 is 0, 1 or 2; Here, R ９ , R １０ , R １１ , R １２ , R １３ , n and r are as defined in claim 1, characterized in that A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 1.

7. Y １ is CH or N, and Y ２ is CR １ｂ and R １ｂ is selected from hydrogen, deuterium, halogen, cyano group, 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 and -O-R １０ and the groups are independently optionally 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 and -SF ５ and is further substituted by one or more substituents selected from Here, R １０ is as defined in claim 6, characterized in that A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 6.

8. R １ｅ 、R １ｆ each independently represents hydrogen, deuterium, halogen, C １－４ alkyl group, C ３－６ cycloalkyl group, 3- to 6-membered heterocyclic group, -SF ５ and -O-R １０ and is independently selected from 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- to 6-membered heterocyclic group, C ６－８ aryl group, 5- to 8-membered heteroaryl group, =O, =S and -SF ５ and is further substituted by one or more substituents selected from the group consisting of: R １ｇ is selected from hydrogen, deuterium, C １－４ alkyl group, C ３－６ cycloalkyl group, 3-6 membered heterocyclic group, hydroxy group, methoxy group and acetyl group, and the said groups are independently optionally 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 and -SF ５ and is further substituted by one or more substituents selected therefrom, Each R １ｈ is independently selected from hydrogen, deuterium, halogen, cyano group, C １－４ alkyl group, C ３－６ cycloalkyl group, 3-6 membered heterocyclic group, -SF ５ and -O-R １０ and the group is further substituted by one or more substituents independently and optionally 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 and -SF ５ and is further substituted by one or more substituents selected from Here, R １０ is as defined in claim 6, characterized in that A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 6.

9. Each X １ is independently CR ６ or N, and each X ２ is independently CH Each R ６ is independently selected from 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 ３－６ cycloalkyl group, 3- to 6-membered heterocyclic group, -SF ５ and -O-R １０ and is selected from Each R ８ is independently selected from 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 ３－６ cycloalkyl group, 3- to 6-membered heterocyclic group, -SF ５ and -O-R １０ and is selected from Here, R １０ is as defined in claim 6, characterized in that A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 6.

10. Each R ５ａ is independently selected from hydrogen, deuterium, halogen, cyano group, C １－４ alkyl group, C ３－６ cycloalkyl group, 3-6 membered heterocyclic group, -SF ５ and -O-R １０ and the group is independently optionally 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 and -SF ５ and is further substituted by one or more substituents selected from Each R ５ｂ is independently hydrogen, deuterium, C １－４ alkyl group, C ３－６ cycloalkyl group, 3- to 6-membered heterocyclic group and -O-R １０ selected from, and the groups are independently optionally 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 and -SF ５ further substituted by one or more substituents selected from, Each R ５ｃ is independently hydrogen, deuterium, halogen, cyano group, C １－４ alkyl group, C ３－６ cycloalkyl group, 3-6 membered heterocyclic group, -SF ５ and -O-R １０ selected from, and said group is independently optionally 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 and -SF ５ further substituted by one or more substituents selected from, Here, R １０ is as defined in claim 6, characterized in that A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 6.

11. R ２ is selected from 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 the said groups are independently optionally 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 , -S(O) ｒ R ９ , -O-R １０ , -C(O)OR １０ , -C(O)R １１ , -O-C(O)R １１ , -NR １２ R １３ , -C(O)NR １２ R １３ and -N(R １２ )-C(O)R １１ and is further substituted by one or more substituents selected from Preferably, R ２ is selected from 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, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, and pyrimidyl group, and the group is independently optionally 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, bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyrimidyl group, =O, =S, -SF ５ , sulfinyl group, sulfonyl group, methylsulfonyl group, isopropylsulfonyl group, hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group, formyl group, acetyl group, n-propionyl group, isopropionyl group, formyloxy group, acetoxy group, n-propionyloxy group, isopropionyloxy group, amino group, mono-C １－４ alkylamino group, and bis-C １－４ alkylamino group, and is further substituted by one or more substituents selected therefrom A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 6.

12. 「 【Chemical Formula 6】 " is selected from the following structures: 【Chemical Formula 7】 and Each R １ｂ is independently hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, trifluoromethoxy group, difluoromethoxy group, trideuteromethoxy group, dideuteromethoxy group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF ５ , hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group, cyclobutoxy group, phenyl group and a pyrazolyl group substituted by a methyl group, and is characterized by being selected from A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 6.

13. 「 【Chemical Formula 8】 " is selected from the following structures: 【Chemical Formula 9】 and Each R １ｂ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, trifluoromethoxy group, difluoromethoxy group, trideuteromethoxy group, dideuteromethoxy group, cyclopropyl group and a pyrazolyl group substituted by a methyl group, characterized in that A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 6.

14. The compound of formula (I) has the structure of a compound of formula (IVa) below, 【Chemical 10】 wherein " 【Chemical Formula 11】 " is selected from the following structures: 【Chemical 12】 selected from, each R １ｂ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group and a pyrazolyl group substituted by a methyl group, Ring B and the moiety " 【Chemical 13】 " to which they are directly attached is selected from the following structures: 【Chemical Formula 14】 and Each X １ is independently CR ６ or N, and Each R ６ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF ５ , hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, Each R ５ａ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF ５ , hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, and the group is independently optionally deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF ５ and is further substituted by one or more substituents selected from Each R ５ｃ is independently hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF ５ , hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, and the group is independently optionally deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF ５ and is further substituted by one or more substituents selected from R ２ is selected from a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a cyclopropyl group, a cyclobutyl group, a bicyclo[1.1.1]pentyl group, an oxetanyl group, an azetidinyl group, a phenyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazolyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group, and a pyrimidyl group, and the group is independently optionally deuterium, fluorine, chlorine, bromine, a cyano group, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a trifluoromethyl group, a difluoromethyl group, a trideuteromethyl group, a dideuteromethyl group, a cyclopropyl group, a cyclobutyl group, a bicyclo[1.1.1]pentyl group, an oxetanyl group, an azetidinyl group, a phenyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazolyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group, a pyrimidyl group, =O, =S, -SF ５ , a hydroxyl group, and a methoxy group, and is further substituted by one or more substituents selected therefrom, provided that when R ２ is selected from a methyl group, " 【Chemical Formula 15】 is 【Chemical Formula 16】 not A compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof according to claim 6.

15. Each R １ｂ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group and a pyrazolyl group substituted by a methyl group, R ６ is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF ５ , hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, R ２ is selected from a methyl group substituted by a cyclopropyl group, a methyl group substituted by a cyclobutyl group, a methyl group substituted by a thiazolyl group, a methyl group substituted by a pyrimidyl group, an ethyl group, an ethyl group substituted by a cyclopropyl group, an ethyl group substituted by a cyclobutyl group, a 2,2,2-trifluoroethyl group, a methoxyethyl group, an ethyl group substituted by a thiazolyl group, an ethyl group substituted by a pyrimidyl group, an isopropyl group substituted by a methoxy group, a cyclopropyl group, a pyrazolyl group substituted by a methyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group and a pyrimidyl group, characterized in that The compound of formula (I) according to claim 14, its stereoisomer or its pharmaceutically acceptable salt.

16. The compound of formula (I) has the structure of the compound of formula (Va) below, 【Chemical 17】 wherein, " 【Chemical Formula 18】 " is the following structure: 【Chemical Formula 19】 selected from, each R １ｂ is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group and cyclopropyl group, R ６ is characterized by being selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteriomethyl group and cyclopropyl group The compound of formula (I) according to claim 15, its stereoisomer or its pharmaceutically acceptable salt.

17. The compound of formula (I) has the structure of the compound of formula (IVb) below, 【Chemical 20】 wherein, " 【Chemical Formula 21】 " is the following structure: 【Chemical 22】 selected from, each R １ｂ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group and a pyrazolyl group substituted by a methyl group, Ring B and the moiety " 【Chemical 23】 " directly connecting thereto is the following structure: 【Chemical 24】 selected from Each X １ is independently CR ６ or N, and Each R ６ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF ５ , hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, Each R ５ａ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF ５ , hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, and the group is independently optionally deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF ５ and is further substituted by one or more substituents selected from Each R ５ｂ is independently selected from hydrogen, deuterium, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group and hydroxyl group, and the group is independently optionally deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF ５ and is further substituted by one or more substituents selected from Each R ５ｃ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, -SF ５ , hydroxy group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, cyclopropoxy group and cyclobutoxy group, and the group is independently optionally deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, oxetanyl group, azetidinyl group, phenyl group, =O, =S and -SF ５ and is further substituted by one or more substituents selected from Here, R ２ is as defined in claim 6, characterized in that The compound of formula (I) according to claim 6, its stereoisomer or its pharmaceutically acceptable salt.

18. Ring B and the moiety " 【Chemical 25】 " directly connecting thereto is the following structure: 【Chemical Formula 26】 selected from Each X １ is independently CR ６ and each R ６ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group, Each R ５ａ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, a cyano group, a methyl group, a trifluoromethyl group, a trideuteromethyl group, and a cyclopropyl group, Each R ５ｂ is independently selected from hydrogen, deuterium, a methyl group, a trifluoromethyl group, a trideuteriomethyl group, and a cyclopropyl group, Each R ５ｃ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteriomethyl group and cyclopropyl group The compound of formula (I) according to claim 17, its stereoisomer or its pharmaceutically acceptable salt.

19. R ２ is selected from a substituted methyl group, a substituted ethyl group, a substituted or unsubstituted n-propyl group, a substituted isopropyl group, a bicyclo[1.1.1]pentyl group, an oxetanyl group, an azetidinyl group, a phenyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazolyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group, and a pyrimidyl group, The substituents of the replaced methyl group, replaced ethyl group, replaced n-propyl group, and replaced isopropyl group are each independently one or more selected from fluorine, chlorine, bromine, cyclobutyl group, bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyrimidyl group, -SF ５ , hydroxyl group, and methoxy group, and The bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group and pyrimidyl group are each independently optionally further substituted by one or more substituents selected from 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, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, oxetanyl group, azetidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyrimidyl group, =O, =S, -SF ５ , hydroxyl group and methoxy group The compound of formula (I) according to claim 17, its stereoisomer or its pharmaceutically acceptable salt.

20. R ２ is selected from a substituted methyl group, a substituted ethyl group, a substituted or unsubstituted n-propyl group, a substituted isopropyl group, a phenyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazolyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group, and a pyrimidyl group, The substituents of the substituted methyl group, substituted ethyl group, substituted n-propyl group and substituted isopropyl group are each independently one or more selected from fluorine, chlorine, bromine, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, pyrimidyl group and methoxy group, The phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, and pyrimidyl group are each independently optionally further substituted by one or more substituents selected from deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, dideuteromethyl group, cyclopropyl group, -SF ５ , hydroxyl group, and methoxy group The compound of formula (I) according to claim 17, its stereoisomer or its pharmaceutically acceptable salt.

21. R ２ is selected from a trifluoromethyl group; a methyl group substituted with a pyrazolyl group; a methyl group substituted with an imidazolyl group; a methyl group substituted with a triazolyl group; a methyl group substituted with an oxazolyl group; a methyl group substituted with a thiazolyl group; a methyl group substituted with an isothiazolyl group; a methyl group substituted with a thiadiazolyl group; a methyl group substituted with a pyrimidyl group; an ethyl group substituted with fluorine; a methoxyethyl group; an ethyl group substituted with a pyrazolyl group; an ethyl group substituted with an imidazolyl group; an ethyl group substituted with a triazolyl group; an ethyl group substituted with an oxazolyl group; an ethyl group substituted with a thiazolyl group; an ethyl group substituted with an isothiazolyl group; an ethyl group substituted with a thiadiazolyl group; an ethyl group substituted with a pyrimidyl group; an isopropyl group substituted with a methoxy group; a pyrazolyl group; a pyrazolyl group substituted with a methyl group; an imidazolyl group; an imidazolyl group substituted with a methyl group; a triazolyl group; a triazolyl group substituted with a methyl group; an oxazolyl group; an oxazolyl group substituted with a methyl group; a thiazolyl group; a thiazolyl group substituted with a methyl group; an isothiazolyl group; an isothiazolyl group substituted with a methyl group; a thiadiazolyl group; a thiadiazolyl group substituted with a methyl group; a pyrimidyl group; and a pyrimidyl group substituted with a methyl group, characterized in that The compound of formula (I) according to claim 17, its stereoisomer or its pharmaceutically acceptable salt.

22. R ２ is selected from a methyl group substituted by a thiazolyl group, a methyl group substituted by a pyrimidyl group, a 2,2,2-trifluoroethyl group, a methoxyethyl group, an ethyl group substituted by a thiazolyl group, an ethyl group substituted by a pyrimidyl group, an isopropyl group substituted by a methoxy group, a pyrazolyl group substituted by a methyl group, a thiazolyl group, an isothiazolyl group, a thiadiazolyl group and a pyrimidyl group, characterized by The compound of formula (I) according to claim 17, its stereoisomer or its pharmaceutically acceptable salt.

23. R ２ has the following structure: 【Chemical 27】 characterized by being selected from The compound of formula (I) according to claim 17, its stereoisomer or its pharmaceutically acceptable salt.

24. The compound of formula (I) has the structure of the compound of formula (Vb1), formula (Vb2), formula (Vb3), formula (Vb4) below, 【Chemical Formula 28】 Each R １ｂ is independently selected from hydrogen, deuterium, methyl group, trifluoromethyl group, trideuteriomethyl group, trifluoromethoxy group, tri-deuteromethoxy group, and cyclopropyl group, Each R ６ is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, a cyano group, and a methyl group, Each R ５ｂ is independently selected from hydrogen, deuterium, methyl group, trifluoromethyl group, trideuteriomethyl group and cyclopropyl group, respectively. The compound of formula (I) according to claim 1, its stereoisomer or its pharmaceutically acceptable salt.

25. characterized by being selected from the following compounds The compound of formula (I) according to any one of claims 1 to 24, its stereoisomer or its pharmaceutically acceptable salt. 【Chemical 29】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 [Chemical]

26. comprising the following steps, 【Chemical 30】 Here, X is fluorine, chlorine, bromine or a hydroxy group, ring A, ring B, X １ , X ２ , X ３ , R １ , R ２ , R ３ , R ４ , R ５ , m and n are as defined in claim 1 A method for producing the compound of formula (I) according to claim 1, its stereoisomer, or its pharmaceutically acceptable salt.

27. A pharmaceutical composition, The pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 - 25, its stereoisomer or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

28. Use of a compound of formula (I) according to any one of claims 1 to 25, its stereoisomer or its pharmaceutically acceptable salt in the manufacture of a medicament for treating MATP-related cancer or tumor.

29. The tumor or cancer is selected from endometrial adenocarcinoma, granulosa theca cell tumor, testicular sertoli cell tumor, germ cell tumor, malignant teratoma, squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma, clear cell carcinoma, squamous cell carcinoma, sarcoma botryoides, fallopian tube cancer, adenocarcinoma, nephroblastoma, lymphoma, leukemia, bladder cancer, squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma, prostate cancer, seminoma, teratoma, fetal carcinoma, teratoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumor, lipoma, liver cancer, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma, gallbladder cancer, ampullary carcinoma, cholangiocarcinoma, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, nevus, dysplastic nevus, lipoma, hemangioma, acute and chronic myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes, Hodgkin's disease, non-Hodgkin lymphoma, osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma, multiple myeloma, malignant giant cell tumor, chordoma, osteochondroma, benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma, giant cell tumor, angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma, myxoma, rhabdomyoma, fibroma, lipoma and teratoma, bronchogenic lung cancer, alveolar carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma, squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma, gastric cancer, lymphoma, leiomyosarcoma, ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, viper tumor, adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma, colorectal adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma, cranial tumor, hemangioma, granuloma, xanthoma, Paget's disease, meningioma, meningiosarcoma, gliosis, astrocytoma, medulloblastoma, glioma, ependymomas, germ cell tumor, glioblastoma multiforms, oligodendroglioma, schwannomas, retinoblastoma, congenital tumor, spinal neurofibroma, meningioma, glioma or sarcoma, characterized in that The application according to claim 28.

30. The cancer or tumor is characterized by being selected from breast cancer, pancreatic cancer, skin cancer, bladder cancer, liver cancer or head and neck cancer The application according to claim 29.

31. A compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 25, which is used as a PRMT5 inhibitor.

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