Nitrogen-containing tricondensed ring PRMT5 inhibitor, method for producing the same, and pharmaceutical uses

Abstract

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

Description

Detailed description of the invention 【0001】 [Technical field] This invention belongs to the field of drug synthesis and, more specifically, relates to nitrogen-containing tricondensed ring PRMT5 inhibitors, methods for producing the same, and pharmaceutical uses. 【0002】 [Background technology] Epigenetic gene regulation is a crucial biological regulatory mechanism for protein synthesis and cell differentiation, and plays a vital role in many human diseases. 【0003】 Epigenetic regulation involves controlling inheritable genetic material without altering its nucleic acid sequence. Generally, epigenetic regulation involves controlling the transition between transcriptionally active and inactive states in chromatin conformations through selective and reversible modifications (e.g., methylation) of DNA and proteins (e.g., histones). These covalent modifications can be controlled by enzymes such as methyltransferases (e.g., PRMT5), many of which are associated with specific genetic alterations in many human pathogenic genes. PRMT5 plays a crucial role in many diseases, including tumors, metabolic disorders, and hematological disorders. 【0004】 Homozygous deletions of tumor suppressor genes are drivers of tumors and often result in deletions of passenger genes near the suppressor gene. These passenger gene deletions lead to a lack of tumor cell specificity and can be targeted by targeted therapies. Homozygous deletions at chromosome 9p21 include the prominent tumor suppressor gene CDKN2A and occur in 15% of tumors, and also often include deletions of the passenger gene MTAP. MTAP is a key enzyme in the methionine and adenine recycling pathway. MTAP deletion results in the accumulation of its substrate, MTA. MTA and S-adenosylmethionine (SAM) are structurally similar, while the latter is a methyl substrate donor for type II methyltransferase PRMT5. Elevated MTA levels due to MTAP deletion selectively compete for binding to SAM and PRMT5, rendering the methyltransferase dysfunctional and making it more susceptible to PRMT5 inhibition. ShRNA screening across numerous different genomic ranges using a wide range of tumor cell lines has shown a correlation between MTAP deletion and cell line dependence on PRMT5, drawing attention to the influence of this metabolic sensitivity. However, as PRMT5 is a critical gene for cells, both conditional knockout of PRMT5 and siRNA knockout studies have suggested that inhibition of PRMT5 in normal tissues has significant side effects (e.g., cytopenia, infertility, skeletal muscle loss, myocardial hypertrophy). Therefore, a new strategy is needed to apply and explore this metabolic sensitivity, selectively targeting PRMT5 in MTAP-deficient tumors while avoiding its effects in normal tissues (MTAP wild-type). 【0005】 Small molecule inhibitors that target PRMT5, which acts in conjunction with MTA, can selectively target only PRMT5 bound to MTA. However, such PRMT5 is enriched only in MTAP-deficient tumor cells. Therefore, in normal cells with intact MTAP, PRMT5 is not targeted when MTA levels are very low, thus providing a better therapeutic window. 【0006】 [Overview of the prefecture] The object of the present invention is to provide nitrogen-containing tricondensed ring PRMT5 inhibitors, methods for producing the same, and pharmaceutical uses. The series of compounds of the present invention exhibit very strong inhibitory effects against PRMT5. It has the potential to be widely used in the manufacture of drugs that have an effect and treat and / or prevent diseases mediated by PRMT5, thereby leading to expectations for the development of a new generation of PRMT5 inhibitors. 【0007】 A first aspect of the present invention provides a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof: 【0008】 [ka] 【0009】 (Here, 【0010】 [ka] " is a double bond or a single bond, 【0011】 X1 is either C or N, and X2 is either C or N, with the condition that at least one of X1 and X2 is N. X3 is CR5 or N, X4 is CR6 or N, and X5 is CR7 or N. X6 is CR8 or N, X7 is CR9 or N, and X8 is CR 10 or N, R1 is -(CR 11 R 12 ) m -R, or R1 and R2 together with a nitrogen atom directly linked to them form a ring B, wherein ring B is a 4-10 member nitrogen-containing heterocyclic group or a 5-10 member nitrogen-containing heteroaryl group, wherein ring B may optionally further contain R, deuterium, halogen, cyano group, nitro group, azide group, C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C2-10 An alkynyl group, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-O-S(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-O-R 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-S-C(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-O-C(O)R 15 , -C 0-8 Alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C<​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​These are, independently, hydrogen, deuterium, halogen, cyano group, nitro group, azide group, and C 1-10 Alkyl 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, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Selected from, or if n≧2, two R in the same carbon a These groups form C(O) together with carbon atoms directly bonded to them, and these groups can independently and optionally further include deuterium, halogen, cyano group, nitro group, azide group, and C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12A cycloalkyl group, a 3- to 12-member heterocyclic group, C 6-10 An aryl group, a 5- to 10-member heteroaryl group, =O, =S, -C 0-8 An alkyl-SF5, -C 0-8 An alkyl-O-S(O)2R 13 、-C 0-8 An alkyl-S(O) r R 13 、-C 0-8 An alkyl-O-R 14 、-C 0-8 An alkyl-C(O)OR 14 、-C 0-8 An alkyl-C(O)SR 14 、-C 0-8 An alkyl-S-C(O)R 15 、-C 0-8 An alkyl-C(O)R 15 、-C 0-8 An alkyl-O-C(O)R 15 、-C 0-8 An alkyl-P(O)(R 15 )2、-C 0-8 An alkyl-NR 16 R 17 、-C 0-8 An alkyl-C(O)NR 16 R 17 And -C<00001​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​Condensed with an aryl group or a 5-10 membered heteroaryl group, the C 6-10 The aryl group or 5-10 membered heteroaryl group may optionally be further C 3-12 It is condensed to a cycloalkyl group or a 4-10 membered heterocyclic group, and the group can be independently and optionally further condensed to a deuterium, halogen, cyano group, nitro group, azide group, C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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, halogen-substituted C 3-6 Cycloalkyl groups, halogen-substituted 3-6 membered heterocyclic groups, halogen-substituted C 6-8 Aryl group, halogen-substituted 5-8 membered heteroaryl group, C 1-4 Alkyl-substituted C 3-6 Cycloalkyl groups, C 1-4 Alkyl-substituted 3-6 membered heterocyclic group, C 1-4 Alkyl-substituted C 6-8 Aryl group, C 1-4 Alkyl-substituted 5-8 member heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, R3 and R4 are independently hydrogen, deuterium, a hydroxyl group, and C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12 Selected from cycloalkyl groups and 3-12 membered heterocyclic groups, or R3 and R4, together with a nitrogen atom directly linked to them, form a single 4-10 membered nitrogen-containing heterocyclic group or a 5-10 membered nitrogen-containing heteroaryl group, wherein the groups may independently and optionally further consist of deuterium, halogen, cyano group, hydroxyl group, =O, =S, C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, heavy water elementary substitution C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 1-10 Alkoxy group, C 3-12 Cycloalkyl groups, C 3-12 Cycloalkoxy groups, 3-12 membered heterocyclic groups, 3-12 membered heterocyclic oxy groups, and -NR 16 R 17 Substituted by one or more substituents selected from, R5, R6, and R7 are independently hydrogen, deuterium, halogen, cyano group, nitro group, azide group, and C 1-10 Alkyl 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, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-OS(O)2R 13 , -C 0-8 Alkyl-S(O)r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Selected from, the group can independently and optionally be further deuterium, halogen, cyano group, nitro group, azide group, C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, R8, R9 and R 10 These are, independently, hydrogen, deuterium, halogen, cyano group, nitro group, azide group, and C 1-10 Alkyl 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, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C0-8 Alkyl-N(R 16 )-C(O)R 15 Selected from, the group can independently and optionally be further deuterium, halogen, cyano group, nitro group, azide group, C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Each R 11 and R 12 These are, independently, hydrogen, deuterium, halogen, cyano group, nitro group, azide group, and C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C2-10 Alkynyl group, C 3-12 Cycloalkyl group, 3-12 membered heterocyclic group, C 6-10 Aryl group, 5-10 membered heteroaryl group, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-OS(O)2 R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Selected from, or R 11 and R 12 It has one C along with the carbon atom that is directly bonded to it. 3-12 Cycloalkyl group, 4-10 membered heterocyclic group, C 6-10 It forms an aryl group or a 5-10 membered heteroaryl group, and the group can independently optionally further contain deuterium, halogen, cyano group, nitro group, azide group, C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12 Cycloalkyl group, 3-12 membered heterocyclic group, C 6-10Aryl group, 5-10 membered heteroaryl group, =O, =S, -C 0-8 Alkyl-SF5, -C 0-8 Alkyl-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Each R 13 These independently consist of hydrogen, deuterium, a hydroxyl group, and C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 3-12 Cycloalkyl group, 3-12 membered heterocyclic group, C 6-10 Aryl groups, 5-10 membered heteroaryl groups, and -NR 16 R 17 Selected from, the group can independently and optionally further consist of deuterium, halogen, hydroxyl group, =O, C 1-10 Alkyl alkyl group, C 1-10 Alkoxy group, C 3-12 Cycloalkyl groups, C 3-12 Cycloalkoxy group, 3-12 membered heterocyclic group, 3-12 membered heterocyclic oxy group, C 6-10 Aryl group, C 6-10Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryloxy group and -NR 16 R 17 Substituted by one or more substituents selected from, Each R 14 These are hydrogen, deuterium, and C, independently. 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 3-12 Cycloalkyl group, 3-12 membered heterocyclic group, C 6-10 Selected from aryl groups and 5-10 membered heteroaryl groups, the group can be independently and optionally further comprising deuterium, halogen, hydroxyl, =O, cyano, and C. 1-10 Alkyl alkyl group, C 1-10 Alkoxy group, C 3-12 Cycloalkyl groups, C 3-12 Cycloalkoxy group, 3-12 membered heterocyclic group, 3-12 membered heterocyclic oxy group, C 6-10 Aryl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryloxy group and -NR 16 R 17 Substituted by one or more substituents selected from, Each R 15 These independently consist of hydrogen, deuterium, a hydroxyl group, and C 1-10 Alkyl alkyl group, C 1-10 Alkoxy group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12 Cycloalkyl groups, C 3-12 Cycloalkoxy group, 3-12 membered heterocyclic group, 3-12 membered heterocyclic oxy group, C 6-10 Aryl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryloxy group and -NR 16 R 17 Selected from, the group can independently and optionally further consist of deuterium, halogen, hydroxyl group, =O, cyano group, C 1-10 Alkyl alkyl group, C 1-10 Alkoxy group, C 3-12 Cycloalkyl groups, C 3-12 Cycloalkoxy group, 3-12 membered heterocyclic group, 3-12 membered heterocyclic oxy group, C6-10 Aryl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryloxy group and -NR 16 R 17 Substituted by one or more substituents selected from, Each R 16 and R 17 These are, independently, hydrogen, deuterium, a hydroxyl group, and C 1-10 Alkyl 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, sulfinyl group, sulfonyl group, methylsulfonyl group, isopropylsulfonyl group, cyclopropyl toluenesulfonyl group, p-toluenesulfonyl group, aminosulfonyl group, dimethylaminosulfonyl group and C 1-10 Selected from alkanoyl groups, the group can independently and optionally further consist of deuterium, halogen, hydroxyl, =O, and C. 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl alkyl group, C 1-10 Alkoxy group, C 3-12 Cycloalkyl groups, C 3-12 Cycloalkoxy group, 3-12 membered heterocyclic group, 3-12 membered heterocyclic oxy group, C 6-10 Aryl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryloxy group, amino group, C 1-10 Alkyl monosubstituted amino group, C 1-10 Alkyl double-substituted amino group and C 1-10 Substituted by one or more substituents selected from the alkanoyl group, R 16 and R 17These, together with a nitrogen atom directly linked to them, form a 4-10 membered heterocyclic group or a 5-10 membered heteroaryl group, and the 4-10 membered heterocyclic group or 5-10 membered heteroaryl group may optionally further contain deuterium, halogen, hydroxyl group, =O, C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl alkyl group, C 1-10 Alkoxy group, C 3-12 Cycloalkyl groups, C 3-12 Cycloalkoxy group, 3-12 membered heterocyclic group, 3-12 membered heterocyclic oxy group, C 6-10 Aryl group, C 6-10 Aryloxy group, 5-10 membered heteroaryl group, 5-10 membered heteroaryloxy group, amino group, C 1-10 Alkyl monosubstituted amino group, C 1-10 Alkyl double-substituted amino group and C 1-10 Substituted with one or more substituents selected from the alkanoyl group, m is 0, 1, or 2. n is 0, 1, 2, 3, 4, 5, or 6. (Each r is independently 0, 1, or 2). 【0012】 In a more preferred form, in the compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, R3 and R4 are independently hydrogen, deuterium, a hydroxyl group, and C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Selected from cycloalkyl groups and 3-6 membered heterocyclic groups, the group can be independently and optionally further composed of deuterium, halogen, cyano group, hydroxyl group, =O, =S, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 1-4 Alkoxy group, C 3-6Cycloalkyl groups, C 3-6 Cycloalkoxy groups, 3-6 membered heterocyclic groups, 3-6 membered heterocyclic oxy groups, and -NR 16 R 17 They may be substituted with one or more substituents selected from, Here, R 16 and R 17 This is as described in the compound represented by formula (I). 【0013】 In a more preferred form, in the compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, R3 and R4 are, independently, hydrogen, deuterium, a hydroxyl group, and C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Selected from cycloalkyl groups and 3-6 membered heterocyclic groups. 【0014】 In a more preferred embodiment, in the compound represented by formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof, R5, R6, and R7 are each independently hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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-OS(O)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-OR 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4 Alkyl-SC(O)R 15 , -C0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-OC(O)R 15 , -C 0-4 alkyl-P(O)(R 15 )2, -C 0- 4-alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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-OS(O)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-OR 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4 Alkyl-SC(O)R 15 , -C 0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-OC(O)R 15 , -C 0-4 alkyl-P(O)(R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Here, R 13 , R 14 , R 15 , R 16 , R 17 And r are as described in the compound represented by formula (I). 【0015】 In a more preferred form, in the compound represented by formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof, R5, R6, and R7 are each independently hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8Aryl group, 5-8 membered heteroaryl group, =O, =S, -SF5, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Here, R 13 , R 14 , R 15 , R 16 , R 17 And r are as described in the compound represented by formula (I). 【0016】 A more preferred embodiment is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R8, R9, and R 10 These are, independently, hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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-OS(O)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-OR 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4Alkyl-SC(O)R 15 , -C 0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-OC(O)R 15 , -C 0-4 alkyl-P(O)(R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-OR 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4 Alkyl-SC(O)R 15 , -C 0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-OC(O)R 15 , -C 0-4 alkyl-P(O)(R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Here, R 13 , R 14 , R 15 , R 16 , R 17 And r are as described in the compound represented by formula (I). 【0017】 A more preferred form is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R8, R9, and R 10 These are, independently, hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Aryl group, 5-8 membered heteroaryl group, =O, =S, -SF5, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Here, R 13 , R 14 , R 15 , R 16 , R 17 And r are as described in the compound represented by formula (I). 【0018】 A more preferred embodiment is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, in which each R 11 and R 12 These are, independently, hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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-OS(O)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-OR 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4Alkyl-C(O)SR 14 , -C 0-4 Alkyl-SC(O)R 15 , -C 0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-OC(O)R 15 , -C 0-4 alkyl-P(O)(R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Selected from, or R 11 and R 12 It has one C along with the carbon atom that is directly bonded to it. 3-6 Cycloalkyl group, 4-8 membered heterocyclic group, C 6-8 It forms an aryl group or a 5-8 membered heteroaryl group, and the group can independently and optionally further consist of deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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-OS(O)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-OR 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4 Alkyl-SC(O)R 15 , -C 0-4Alkyl-C(O)R 15 , -C 0-4 Alkyl-OC(O)R 15 , -C 0-4 Alkyl-P(O) (R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Here, R 13 , R 14 , R 15 , R 16 , R 17 And r are as described in the compound represented by formula (I). 【0019】 A more preferred form is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, in which each R 11 and R 12 These are, independently, hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16)-C(O)R 15 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Here, R 13 , R 14 , R 15 , R 16 , R 17 And r are as described in the compound represented by formula (I). 【0020】 A more preferred embodiment is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, in which R1 is -(CR 11 R 12 ) m -R, or R1 and R2 together with a nitrogen atom directly linked to them form a ring B, wherein ring B is a 4-10 member nitrogen-containing heterocyclic group or a 5-10 member nitrogen-containing heteroaryl group, and ring B optionally further contains R, deuterium, halogen, cyano group, C 1-4 Alkyl alkyl group, C 2-4An alkenyl group, C 2-4 An alkynyl group, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-O-S(O)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-O-R 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4 Alkyl-S-C(O)R 15 , -C 0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-O-C(O)R 15 , -C 0-4 Alkyl-P(O)(R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16 R 17 And -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from R is -ring A-(R a ) n where ring A is selected from a C 3-6 cycloalkyl group, a 4- to 8-membered heterocyclic group, a C 6-8 aryl group or a 5- to 8-membered heteroaryl group, and the C 3-6 cycloalkyl group or 4- to 8-membered heterocyclic group is optionally further fused to a C 6-8 aryl group or a 5- to 8-membered heteroaryl group, and the C 6-8 aryl group or a 5- to 8-membered heteroaryl group is optionally fused to a 5- to 8-membered heteroaryl group, a C 3-6 cycloalkyl group or a 4- to 8-membered heterocyclic group, Each R a is independently hydrogen, deuterium, halogen, cyano group, C 1-4Alkyl 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)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-O-R 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4 Alkyl-S-C(O)R 15 , -C 0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-O-C(O)R 15 , -C 0-4 Alkyl-P(O)(R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 selected from, and said groups are independently optionally further deuterium, halogen, cyano group, C 1-4 alkyl group, halogen-substituted C 1-4 alkyl group, deuterium-substituted C 1-4 alkyl group, C 2-4 alkenyl group, C 2-4 alkynyl group, C 3-6 cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 aryl group, 5-8 membered heteroaryl group, =O, =S, -C 0-4 alkyl-SF5, -C 0-4 alkyl-O-S(O)2R 13 , -C 0-4 alkyl-S(O)r R 13 , -C 0-4 Alkyl-OR 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4 Alkyl-SC(O)R 15 , -C 0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-OC(O)R 15 , -C 0-4 alkyl-P(O)(R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, R2 is hydrogen, deuterium, C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Aryl group, 5-8 membered heteroaryl group, -S(O) r R 13 , -OR 14 , -C(O)OR 14 , -C(O)R 15 and -C(O)NR 16 R 17 Selected from, the group can be independently and optionally further, deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Aryl group, 5-8 membered heteroaryl group, halogen-substituted C3-6 Cycloalkyl groups, halogen-substituted 3-6 membered heterocyclic groups, halogen-substituted C 6-8 Aryl group, halogen-substituted 5-8 membered heteroaryl group, C 1-4 Alkyl-substituted C 3-6 Cycloalkyl groups, C 1-4 Alkyl-substituted 3-6 membered heterocyclic group, C 1-4 Alkyl-substituted C 6-8 Aryl group, C 1-4 Alkyl-substituted 5-8 member heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, =O, =S, -C 0-4 Alkyl-SF5, -C 0-4 Alkyl-OS(O)2R 13 , -C 0-4 Alkyl-S(O) r R 13 , -C 0-4 Alkyl-OR 14 , -C 0-4 Alkyl-C(O)OR 14 , -C 0-4 Alkyl-C(O)SR 14 , -C 0-4 Alkyl-SC(O)R 15 , -C 0-4 Alkyl-C(O)R 15 , -C 0-4 Alkyl-OC(O)R 15 , -C 0-4 alkyl-P(O)(R 15 )2, -C 0-4 Alkyl-NR 16 R 17 , -C 0-4 Alkyl-C(O)NR 16 R 17 and -C 0-4 Alkyl-N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Here, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 m, n, and r are as described in the compound represented by formula (I). 【0021】 A more preferred embodiment is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, in which each R 13 These independently consist of hydrogen, deuterium, a hydroxyl group, and C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Aryl groups, 5-8 membered heteroaryl groups, and -NR 16 R 17 Selected from, the group can independently and optionally further consist of deuterium, halogen, hydroxyl group, =O, C 1-4 Alkyl alkyl group, C 1-4 Alkoxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkoxy group, 3-6 membered heterocyclic group, 3-6 membered heterocyclic oxy group, C 6-8 Aryl group, C 6-8 Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group and -NR 16 R 17 Substituted by one or more substituents selected from, Each R 14 These are hydrogen, deuterium, and C, independently. 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Selected from aryl groups and 5-8 membered heteroaryl groups, the group can be independently and optionally further composed of deuterium, halogen, hydroxyl, =O, cyano, and C. 1-4 Alkyl alkyl group, C 1-4 Alkoxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkoxy group, 3-6 membered heterocyclic group, 3-6 membered heterocyclic oxy group, C 6- 8 aryl group, C 6-8 Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group and -NR 16 R 17 Substituted by one or more substituents selected from, Each R15 These independently consist of hydrogen, deuterium, a hydroxyl group, and C 1-4 Alkyl alkyl group, C 1-4 Alkoxy group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkoxy group, 3-6 membered heterocyclic group, 3-6 membered heterocyclic oxy group, C 6-8 Aryl group, C 6-8 Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group and -NR 16 R 17 Selected from, the group can independently and optionally further consist of deuterium, halogen, hydroxyl group, =O, cyano group, C 1-4 Alkyl alkyl group, C 1-4 Alkoxy group, C 3-6 Cycloalkyl groups, C 3-6 Cycloalkoxy group, 3-6 membered heterocyclic group, 3-6 membered heterocyclic oxy group, C 6-8 Aryl group, C 6-8 Aryloxy group, 5-8 membered heteroaryl group, 5-8 membered heteroaryloxy group and -NR 16 R 17 Substituted by one or more substituents selected from, Each R 16 and R 17 These are, independently, hydrogen, deuterium, a hydroxyl group, and C 1-4 Alkyl 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 Selected from alkanoyl groups, the group can independently and optionally further consist of deuterium, halogen, hydroxyl, =O, and C. 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, halogen-substituted C 1-4Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 1-4 Alkoxy group, C 3-6 Cycloalkyl groups, 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 monosubstituted amino group, C 1-4 Alkyl double-substituted amino group and C 1-4 Substituted with one or more substituents selected from the alkanoyl group, R 16 and R 17 These atoms, together with a nitrogen atom directly bonded to them, form a single 4-8 membered heterocyclic group or a 5-8 membered heteroaryl group, and the 4-8 membered heterocyclic group or 5-8 membered heteroaryl group may optionally further contain deuterium, halogen, hydroxyl group, =O, C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 1-4 Alkoxy group, C 3-6 Cycloalkyl groups, 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 monosubstituted amino group, C 1-4 Alkyl double-substituted amino group and C 1-4 It is substituted with one or more substituents selected from the alkanoyl group. 【0022】 A more preferred embodiment is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (I) has the structure of the compound represented by the following formula (II): 【0023】 [ka] 【0024】 (Here, X3 is CR5 or N, X4 is CR6 or N, X5 is CR7 or N, X6 is CR8 or N, X7 is CR9 or N, R1 is -(CR 11 R 12 ) m -R, or R1 and R2 together with a nitrogen atom directly linked to them form a ring B, wherein ring B is a 4-10 member nitrogen-containing heterocyclic group or a 5-10 member nitrogen-containing heteroaryl group, and ring B optionally further contains R, deuterium, halogen, cyano group, C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, =O, =S, -SF5, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, R has the following structure: 【0025】 [ka] And, 【0026】 Here, Y1, Y2, Y4, Y5, Y6, Y7, Y8, Y9, Y 10 , Y 11 , Y12 , Y 13 Each of them independently performs CR a or N, and Y3 is -O-, -S-, or -NR a3 - and Z is -O-, -S-, -CR a1 R a2 -, -CR a1 R a2 -O- or -NR a3 - and p is 0, 1, 2 or 3, Each R a These are, independently, hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14, -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,- P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Each R a1 and R a2 These are, independently, hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8Aryl group, 5-8 membered heteroaryl group, =O, =S, -SF5, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Each R a3 These are hydrogen, deuterium, and C, respectively, independently. 1-4 Alkyl alkyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Aryl group, 5-8 membered heteroaryl group, -SF5, -C(O)OR 14 -C(O)SR 14 , -C(O)R 15 and -C(O)NR 16 R 17 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, Each R2 independently contains hydrogen, deuterium, and C 1-4 Alkyl alkyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Selected from aryl groups and 5-8 membered heteroaryl groups, the group can be independently and optionally further comprising deuterium, halogen, cyano group, or C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Aryl group, 5-8 membered heteroaryl group, halogen-substituted C 3-6 Cycloalkyl groups, halogen-substituted 3-6 membered heterocyclic groups, halogen-substituted C 6-8 Aryl group, halogen-substituted 5-8 membered heteroaryl group, C 1-4 Alkyl-substituted C 3-6 Cycloalkyl groups, C 1-4 Alkyl-substituted 3-6 membered heterocyclic group, C 1-4 Alkyl-substituted C 6-8 Aryl group, C 1-4 Alkyl-substituted 5-8 member heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, =O, =S, -SF5, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR16 R 17 and -N(R 16 )-C(O)R 15 Substituted by one or more substituents selected from, R5, R6, and R7 are independently hydrogen, deuterium, halogen, cyano group, and C, respectively. 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R1 Selected from 5, R8 and R9 are independently hydrogen, deuterium, halogen, cyano group, and C, respectively. 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15, -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Selected from, Each R 11 and R 12 These are, independently, hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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, -OS(O)2R 13 , -S(O) r R 13 , -OR 14 , -C(O)OR 14 -C(O)SR 14 ,-SC(O)R 15 , -C(O)R 15 -OC(O)R 15 ,-P(O)(R 15 )2, -NR 16 R 17 -C(O)NR 16 R 17 and -N(R 16 )-C(O)R 15 Selected from, Here, R 13 , R 14 , R 15 , R 16 , R 17 (where r and m are as described in the compound represented by formula (I)). 【0027】 A more preferred embodiment is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (I) has the structure of the compound represented by the following formula (III1) or formula (III2): 【0028】 [ka] 【0029】 (Here, each X3 is independently CR5 or N, each X4 is independently CR6 or N, each X5 is independently CR7 or N, and each X6 is independently CR8 or N, In the structure of the compound represented by formula (III2), ring B is a 4-10 member nitrogen-containing heterocyclic group, and the 4-10 member nitrogen-containing heterocyclic group may optionally further contain hydrogen, deuterium, halogen, cyano group, hydroxyl group, carboxyl group, or C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 1-4 Alkoxy group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic groups, -SF5 and -NR 16 R 17 Substituted by one or more substituents selected from, Each R independently has the following structure: 【0030】 [ka] And, 【0031】 Here, Y1, Y2, Y6, Y7, Y8, Y9, Y 10 and Y 11 Each of them independently performs CR a or N, Y3 is -O- or -S-, Z is -O-, -S-, -CH2- or -CH2-O-, and p is 0, 1, 2 or 3, Each R a These are, independently, hydrogen, deuterium, halogen, cyano group, and C 1-4 Alkyl 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, -OR 14 , -C(O)OR 14 -C(O)SR 14 , -C(O)R 15 -OC(O)R 15 and -NR 16 R 17 Selected from, the group can independently and optionally further include deuterium, halogen, cyano group, C 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl 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, -OR 14 , -C(O)OR 14 , -C(O)R 15 -OC(O)R 15 and -NR 16 R 17 Substituted by one or more substituents selected from, R2 is hydrogen, deuterium, C 1-4 Alkyl alkyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8 Selected from aryl groups and 5-8 membered heteroaryl groups, the group can be independently and optionally further divided into deuterium, halogen, cyano, and C. 1-4 Alkyl, halogen-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl alkyl group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl group, 3-6 membered heterocyclic group, C 6-8Aryl group, 5-8 membered heteroaryl group, halogen-substituted C 3-6 Cycloalkyl groups, halogen-substituted 3-6 membered heterocyclic groups, halogen-substituted C 6-8 Aryl group, halogen-substituted 5-8 membered heteroaryl group, C 1-4 Alkyl-substituted C 3-6 Cycloalkyl groups, C 1-4 Alkyl-substituted 3-6 membered heterocyclic group, C 1-4 Alkyl-substituted C 6-8 Aryl group, C 1-4 Alkyl-substituted 5-8 member heteroaryl group, (2-(trimethylsilyl)ethoxy)methyl group, =O, =S, -SF5, -OR 14 , -C(O)OR 14 , -C(O)R 15 -OC(O)R 15 and -NR 16 R 17 They may be substituted with one or more substituents selected from, Each of R5, R6, and R7 independently consists of hydrogen, deuterium, halogen, cyano group, hydroxyl group, carboxyl group, and C. 1-4 Alkyl alkyl group, C 1-4 alkoxy group, halogen-substituted C 1-4 Alkyl, halogen-substituted C 1-4 Alkoxy group, deuterium-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkoxy group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl groups, 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, -SF5 and -NR 16 R 17 Selected from, Each R8 independently consists of hydrogen, deuterium, halogen, cyano group, hydroxyl group, carboxyl group, and C 1-4 Alkyl alkyl group, C 1-4 alkoxy group, halogen-substituted C 1-4 Alkyl, halogen-substituted C1-4 Alkoxy group, deuterium-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkoxy group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl groups, 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, -SF5 and -NR 16 R 17 Selected from, Each R 11 and R 12 These are, independently, hydrogen, deuterium, halogen, cyano group, hydroxyl group, carboxyl group, and C 1-4 Alkyl alkyl group, C 1-4 alkoxy group, halogen-substituted C 1-4 Alkyl, halogen-substituted C 1-4 Alkoxy group, deuterium-substituted C 1-4 Alkyl, heavy water elementary substitution C 1-4 Alkoxy group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl groups, 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, -SF5 and -NR 16 R 17 Selected from, Here, R 14 , R 15 , R 16 and R 17 (This is as described in the compound represented by formula (I).) 【0032】 A more preferred form is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the structure contains " 【0033】 [ka] The structure is as follows: 【0034】 [ka] 【0035】 Selected from, Each X6 is independently either CR8 or N. Each of R5, R6, and R7 independently consists of hydrogen, deuterium, halogen, cyano group, hydroxyl group, carboxyl group, and C. 1-4 Alkyl alkyl group, C 1-4 alkoxy group, halogen-substituted C 1-4 Alkyl, halogen-substituted C 1-4 Alkoxy group, deuterium-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkoxy group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl groups, 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, -SF5, amino group, monoC 1-4 Alkyl-substituted amino groups and bisC 1-4 Selected from alkyl-substituted amino groups, Each R8 independently consists of hydrogen, deuterium, halogen, cyano group, hydroxyl group, carboxyl group, and C 1-4 Alkyl alkyl group, C 1-4 alkoxy group, halogen-substituted C 1-4 Alkyl, halogen-substituted C 1-4 Alkoxy group, deuterium-substituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkoxy group, C 2-4 Alkenyl group, C 2-4 Alkynyl group, C 3-6 Cycloalkyl groups, C 3-6Cycloalkoxy 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, -SF5, amino group, monoC 1-4 Alkyl-substituted amino groups and bisC 1-4 Selected from alkyl-substituted amino groups. 【0036】 A more preferred embodiment is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (I) is the following (IV 1-1 ), (IV 1-2 ), (IV 2-1 ) or (IV 2-2 The compound has the structure represented by ), 【0037】 [ka] 【0038】 (Here, each X4 is independently CR6 or N, and each X5 is independently CR7 or N, Each Y6 and each Y7 is independently CH or N, Z is O or CH2, and p is 1 or 2. Formula (IV 2-1 ) or (IV 2-2 In the structure of the compound represented by ), ring B, together with the substituent on it, has the following structure: 【0039】 [ka] q is selected from 0, 1 or 2, 【0040】 Each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, trifluoromethyl group, trideuteromethyl group, methoxy group, ethoxy group, cyclopropyl group, and -SF5. Each R'' is independently selected from hydrogen, deuterium, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R2 independently consists of hydrogen, deuterium, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azetidinyl group, tetrahydrofuranyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyridyl group, pyridadinyl group, pyrimidinyl group, and Selected from riadinyl groups, the group can be independently and optionally further 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, diduteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azacyclopentyl group, tetrahydrof Substituted by one or more substituents selected from lanyl group, phenyl group, pyrazolyl group, 2-(trimethylsilyl)ethoxy group, methyl-substituted pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyridyl group, fluorine-substituted pyridyl group, pyridadinyl group, pyrimidinyl group, triazinyl group, =O, =S, -SF5, hydroxyl group, methoxy group, ethoxy group, cyclopropoxy group, cyclobutoxy group, amino group, methylamino group and dimethylamino group, Each R aEach of these groups 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, methoxy group, ethoxy group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, diduteromethyl group, trifluoromethoxy group, trideuteromethoxy group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, methyl-substituted cyclopropyl group, methyl-substituted cyclobutyl group, cyclopropoxy group, cyclobutoxy group, oxetanyl group, azetidinyl group, tetrahydropyrrolyl group, piperidinyl group, methyl-substituted piperidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyrimidinyl group, methyl-substituted pyrazolyl group, -SF5, hydroxyl group, amino group, methylamino group, dimethylamino group, dimethylaminomethyl group, and dimethylaminoethyl group. Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, trideuteromethyl group, trideuteromethoxy group, and cyclopropyl group. Each R7 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, trideuteromethyl group, trideuteromethoxy group, and cyclopropyl group. Each R8 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, triduomethyl group, triduomethoxy group, and cyclopropyl group. R 11 and R 12 (Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group). 【0041】 A more preferred form is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the structure contains 【0042】 [ka] The structure is as follows: 【0043】 [ka] Selected from, 【0044】 R7 is selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group. R8 is selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. 【0045】 A more preferred embodiment is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein formula (IV 1-2 ) and (IV 2-1 The structure of the compound represented by ) contains " 【0046】 [ka] The structure is as follows: 【0047】 [ka] Selected from, 【0048】 Formula (IV 1-1 The structure of the compound represented by ) contains " 【0049】 [ka] The structure is as follows: 【0050】 [ka] Selected from, 【0051】 Each R a Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, isopropyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF5. 【0052】 A more preferred embodiment is the compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, in which each R2 is independently selected from hydrogen, deuterium, methyl group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azetidinyl group, tetrahydrofuranyl group, pyrazolyl group, imidazolyl group, thiazolyl group, pyridyl group, and pyrimidinyl group, and the group is independently and optionally further selected from deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl Substituted by one or more substituents selected from the following groups: 1, 2, 3, 4 【0053】 A more preferred embodiment is the compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, in which each R2 is independently hydrogen, deuterium, methyl group, ethyl group, trifluoromethyl group, trifluoroethyl group, trideuteromethyl group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, cyclobutyl group, or a substituent represented as follows: 【0054】 [ka] They are selected from among them. 【0055】 A more preferred form is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (I) is the following (V 1-1-1 ) or formula (V 1-1-2 The compound has the structure represented by ), 【0056】 [ka] 【0057】 (Here, each Y7 is independently CH or N, each Z is independently O or CH2, and each R a Each is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF5. Each R7 is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R8 is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Here, R2 is as described in the compound represented by formula (I). 【0058】 A more preferred form is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (I) is the following (V 1-2-1 ) or formula (V 1-2-2 The compound has the structure represented by ), 【0059】 [ka] 【0060】 (Here, each Y6 and each Y7 is independently CH or N, and R a These are selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF5. R7 is selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group. R8 is selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. 【0061】 A more preferred form is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (I) is the following (V 2-1-1 ) or formula (V 2-1-2 The compound has the structure represented by ), 【0062】 [ka] 【0063】 (Here, each R aEach is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF5. Each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R7 is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R8 is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. 【0064】 A more preferred form is a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (I) is the following (V 2-2-1 ) or formula (V 2-2-2 The compound has the structure represented by ), 【0065】 [ka] 【0066】 (Here, each R a Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, methyl-substituted piperidinyl group, dimethylaminoethyl group, and -SF5. Each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R7 is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R8 is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. 【0067】 In its most preferred form, the compound represented by formula (I), its stereoisomers, or pharmaceutically acceptable salts include, but are not limited to, the following compounds: 【0068】 [ka] TIFF0007873890000023.tif206169TIFF0007873890000024.tif203168TIFF0007873890000025.tif242168TIFF00078738900 00026.tif234168TIFF0007873890000027.tif253168TIFF0007873890000028.tif220168TIFF0007873890000029.tif228168 TIFF0007873890000030.tif239168TIFF0007873890000031.tif236168TIFF0007873890000032.tif230170TIFF00078738900 00033.tif224169TIFF0007873890000034.tif227169TIFF0007873890000035.tif236170TIFF0007873890000036.tif111170 【0069】 A second aspect of the present invention provides a drug composition comprising a compound represented by formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. A third aspect of the present invention provides the use of a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating MATP-associated tumors. 【0070】 A more preferred form of tumor is selected from cell tumors, lymphomas, leukemias, osteomas, malignant teratomas, carcinomas in situ, adenomas, fibromas, melanomas, fallopian tube cancers, bladder cancers, teratomas, fetal carcinomas, choriocarcinomas, lipomas, liver cancers, bile duct cancers, lung cancers, gastric cancers, hemangiomas, gallbladder cancers, ampulla cancers, malignant melanomas, nevi, dysplastic nevi, myeloproliferative disorders, Hodgkin's disease, chordomas, myxomas, rhabdomyomas, leiomyomas, hamartomas, mesotheliomas, insulinomas, glucagonomas, gastrinomas, carcinoid tumors, snake venomous tumors, granulomas, xanthomas, osteoosteitis, ependymomas, schwannomas, congenital tumors, meningiomas, gliomas, skin cancers, head and neck cancers, and sarcomas. 【0071】 A more preferred form of the cell tumor is selected from granuloflorous cell tumor, Sertoli cell tumor, germ cell tumor, nephroblastoma, seminomas, hepatoblastoma, malignant fibrous histiocytoma, chondroblastoma, giant cell tumor, astrocytoma, medulloblastoma, glioblastoma multiforme, oligodendroglioma, retinoblastoma, squamous cell carcinoma, clear cell carcinoma, transitional cell carcinoma, stromal cell carcinoma, and basal cell carcinoma. The aforementioned lymphomas are selected from malignant lymphomas and non-Hodgkin lymphomas. The aforementioned leukemia is selected from acute chronic myeloid leukemia, acute lymphoblastic leukemia, and chronic lymphoblastic leukemia. The aforementioned osteomas are selected from osteochondroma, benign chondroma, osteoid osteoma, chondromatoid hamartoma, multiple myeloma, and cranial osteoma. The adenoma is selected from fibroadenoma, adenomatous tumor, hepatocellular adenoma, bronchial adenoma, tubular adenoma, chorioadenoma, breast cancer, pancreatic cancer, endometrial adenocarcinoma, prostate cancer, ductal adenocarcinoma, and colorectal adenocarcinoma. The fibroma is selected from fibroma, chondromyxofibroma, neurofibroma, and spinal neurofibroma. The aforementioned myeloproliferative disorders are selected from multiple myeloma and myelodysplastic syndromes. The lung cancers mentioned above are selected from bronchopulmonary cancer and alveolar cancer. The aforementioned sarcomas are selected from fibrosarcoma, staphyloid sarcoma, angiosarcoma, Kaposi's sarcoma, osteosarcoma, chondrosarcoma, Ewing's sarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, and meningiosarcoma. 【0072】 The present invention further relates to a compound represented by formula (I), its stereoisomers, or pharmaceutically acceptable salts thereof, used as a PRMT5 inhibitory drug. The present invention further relates to the use of a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating and / or preventing a PRMT5-mediated disease. 【0073】 The present invention further relates to a method for treating and / or preventing a PRMT5-mediated disease, comprising administering a therapeutically effective amount of a compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof to a patient in need. 【0074】 [Specific implementation details] The inventors of this invention, through extensive and in-depth research, have developed for the first time a PRMT5 inhibitor having the structure represented by the following formula (I). The series of compounds of the present invention can be widely used in the manufacture of drugs that treat and / or prevent PRMT5-mediated diseases, and the development of a new generation of PRMT5 inhibitors is anticipated. Based on this, the present invention has been completed. 【0075】 Note: Unless otherwise stated or specifically explained, the following terms used in the specification and claims have the meanings set forth below. "Alkyl group" refers to a saturated aliphatic hydrocarbon group containing a linear or branched chain, preferably a linear alkyl group containing 1 to 10 or 1 to 6 carbon atoms or 1 to 4 carbon atoms, and a branched alkyl group containing a linear or branched chain, including methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, s-butyl group, n-pentyl group, 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, 2,2-dimethylpropyl group, 1-ethylpropyl group, 2-methylbutyl group, 3-methylbutyl group, n-hexyl group, 1-ethyl-2-methylpropyl group, 1,1,2-trimethylpropyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2-ethylbutyl group, 2-methylpentyl group, 3-methyl This includes, but is not limited to, pentyl groups, 4-methylpentyl groups, 2,3-dimethylbutyl groups, n-heptyl groups, 2-methylhexyl groups, 3-methylhexyl groups, 4-methylhexyl groups, 5-methylhexyl groups, 2,3-dimethylpentyl groups, 2,4-dimethylpentyl groups, 2,2-dimethylpentyl groups, 3,3-dimethylpentyl groups, 2-ethylpentyl groups, 3-ethylpentyl groups, n-octyl groups, 2,3-dimethylhexyl groups, 2,4-dimethylhexyl groups, 2,5-dimethylhexyl groups, 2,2-dimethylhexyl groups, 3,3-dimethylhexyl groups, 4,4-dimethylhexyl groups, 2-ethylhexyl groups, 3-ethylhexyl groups, 4-ethylhexyl groups, 2-methyl-2-ethylpentyl groups, 2-methyl-3-ethylpentyl groups, or various branched isomers thereof. 1-10 "Alkyl alkyl groups" are linear alkyl groups containing 1 to 10 carbon atoms and branched alkyl groups containing C 1-4 "Alkyl alkyl groups" are linear alkyl groups containing 1 to 4 carbon atoms and branched alkyl groups containing C 0-8 "Alkyl alkyl groups" are linear alkyl groups containing 0 to 8 carbon atoms and branched alkyl groups containing C 0-4 "Alkyl alkyl groups" include linear alkyl groups containing 0 to 4 carbon atoms and branched alkyl groups containing branched chains. 【0076】 The alkyl group may be optionally substituted or unsubstituted. If substituted, the substituents are preferably independently deuterium, halogen, cyano group, nitro group, azide group, and C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12 Shik R-alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0077】 "Cycloalkyl group" or "carbocyclic group" refers to saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituents, where the partially unsaturated cyclic hydrocarbon may contain one or more (preferably one, two, or three) double bonds, but does not contain any rings having a fully conjugated π-electron system, and cycloalkyl groups are divided into monocyclic cycloalkyl groups and polycyclic cycloalkyl groups, preferably cycloalkyl groups containing 3 to 12, 3 to 8, or 3 to 6 carbon atoms, for example, "C 3-12 A "cycloalkyl group" refers to a cycloalkyl group containing 3 to 12 carbon atoms, and is called "C 4-8 A "cycloalkyl group" refers to a cycloalkyl group containing 4 to 8 carbon atoms, and is called "C 3-8 A "cycloalkyl group" refers to a cycloalkyl group containing 3 to 8 carbon atoms, and "C 3-6 A "cycloalkyl group" refers to a cycloalkyl group containing 3 to 6 carbon atoms, and here, Monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, and cyclooctyl groups. 【0078】 Polycyclic cycloalkyl groups include cycloalkyl groups of spiro rings, fused rings, and crosslinked rings. “Spirocycloalkyl groups” refer to polycyclic groups that share one carbon atom (called a spiro atom) between monocyclic rings. These groups may contain one or more (preferably one, two, or three) double bonds, but none of the rings have a fully conjugated π-electron system. Depending on the number of spiro atoms shared between the rings, spirocycloalkyl groups are classified as monospirocycloalkyl groups, bisspirocycloalkyl groups, or polyspirocycloalkyl groups. Spirocycloalkyl groups include, but are not limited to, the following: 【0079】 [ka] 【0080】 A "condensed cycloalkyl group" refers to a total-carbon polycyclic group in which each ring in the system shares a pair of adjacent carbon atoms with the other rings in the system, and one or more of these rings may contain one or more (preferably one, two, or three) double bonds, but none of the rings have a fully conjugated π-electron system. Depending on the number of constituent rings, condensed cycloalkyl groups may be classified as bicyclic, tricyclic, tetracyclic, or polycyclic, and condensed cycloalkyl groups include, but are not limited to, the following: 【0081】 [ka] 【0082】 A "crosslinked cycloalkyl group" refers to a whole-carbon polycyclic group in which any two rings share two carbon atoms that are not directly linked. These groups may contain one or more (preferably one, two, or three) double bonds, but none of the rings have a fully conjugated π-electron system. Depending on the number of constituent rings, crosslinked cycloalkyl groups may be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Crosslinked cycloalkyl groups include, but are not limited to, the following: 【0083】 [ka] 【0084】 The cycloalkyl ring may be condensed with an aryl group, a heteroaryl group, or a heterocycloalkyl ring, where the ring linked to the parent structure is a cycloalkyl group, including, but not limited to, an indanyl group, a tetrahydronaphthyl group, a benzocycloheptyl group, etc. 【0085】 The "cycloalkyl group" or "carbon ring" may be optionally substituted or unsubstituted. If substituted, the substituents are preferably independently deuterium, halogen, cyano group, nitro group, azide group, and C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0086】 "Heterocyclic group" or "heterocyclic" refers to saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituents, wherein the partially unsaturated cyclic hydrocarbon may contain one or more (preferably one, two, or three) double bonds, but does not contain any rings having a fully conjugated π-electron system, and the one or more (preferably one, two, three, or four) ring atoms in the heterocyclic group are N, O, N·O, or S(O). r(where r is an integer 0, 1, or 2) selected from heteroatoms, but without the ring portion of -OO-, -OS-, or -SS-, and the remaining ring atoms are carbon. Preferably 3 to 12 or A heterocyclic group is a group containing 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. 【0087】 Monocyclic heterocyclic groups include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, oxetanyl, and tetrahydrofuranyl groups. 【0088】 Polycyclic heterocyclic groups include spiro rings, fused rings, and bridging rings. A "spiro heterocyclic group" refers to a polycyclic heterocyclic group that shares one atom (called a spiro atom) between monocyclic rings, and one or more (preferably one, two, three, or four) of these ring atoms are N, O, N·O, or S(O). r The heteroatoms are selected from (where r is an integer 0, 1, or 2), and the remaining ring atoms are carbon. These groups may contain one or more double bonds (preferably one, two, or three), but none of the rings have a fully conjugated π-electron system. Depending on the number of spiroatoms shared between the rings, spiroheterocyclic groups are classified as monospiroheterocyclic groups, bisspiroheterocyclic groups, or polyspiroheterocyclic groups. Spiroheterocyclic groups include, but are not limited to, the following: 【0089】 [ka] 【0090】 A "condensed heterocyclic group" refers to a polycyclic heterocyclic group in which each ring in the system shares a pair of adjacent atoms with other rings in the system, and one or more (preferably one, two, three, or four) rings may contain one or more (preferably one, two, or three) double bonds, but none of the rings have a fully conjugated π-electron system, and one or more (preferably one, two, three, or four) of the ring atoms are N, O, N·O, or S(O). r (where r is an integer 0, 1, or 2) a heteroatom is selected, and the remaining ring atom is carbon. Depending on the number of constituent rings, the fused heterocycloalkyl groups may be classified as bicyclic, tricyclic, tetracyclic, or polycyclic, and the fused heterocyclic groups include, but are not limited to, the following: 【0091】 [ka] 【0092】 A "bridged heterocyclic group" refers to a polycyclic heterocyclic group in which any two rings share two atoms that are not directly linked. These groups may contain one or more (preferably one, two, or three) double bonds, but none of the rings have a fully conjugated π-electron system, and one or more (preferably one, two, three, or four) of the ring atoms are N, O, N·O, or S(O). r (where r is an integer 0, 1, or 2) a heteroatom is selected, and the remaining ring atom is carbon. Depending on the number of constituent rings, the bridging heterocyclic group may be classified as bicyclic, tricyclic, tetracyclic, or polycyclic, and the bridging heterocyclic group includes, but is not limited to, the following: 【0093】 [ka] 【0094】 The ring of the heterocyclic group may be fused to an aryl group, a heteroaryl group, or a cycloalkyl group, where the ring linked to the parent structure is a heterocyclic group and includes, but is not limited to, the following: 【0095】 [ka] 【0096】 The "heterocyclic group" or "heterocyclic ring" may be optionally substituted or unsubstituted. If substituted, the substituents are preferably independently deuterium, halogen, cyano group, nitro group, azide group, and C. 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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 -OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0097】 An "aryl group" or "aromatic ring" is a monocyclic or fused polycyclic group (i.e., a ring sharing adjacent pairs of carbon atoms) consisting of all carbon atoms, and refers to a polycyclic group (i.e., a ring having adjacent pairs of carbon atoms) having a conjugated π-electron system, preferably an all-carbon aryl group containing 6 to 10 or 6 to 8 carbon atoms, for example, "C 6-10 The term "aryl group" refers to an aryl group containing 6 to 10 carbon atoms, including phenyl and naphthyl groups, but is not limited to these. 6-8 An "aryl group" refers to an all-carbon aryl group containing 6 to 8 carbon atoms. The aryl group ring may be fused to a heteroaryl group, a heterocyclic group, or a cycloalkyl group, where the ring linked to the parent structure is an aryl group ring, and includes, but is not limited to, the following: 【0098】 [ka] 【0099】 The "aryl group" or "aromatic ring" may be substituted or unsubstituted. If substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, and C. 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0100】 A "heteroaryl group" or "heteroaryl ring" refers to a heteroaromatic system containing one or more (preferably one, two, three, or four) heteroatoms, wherein the heteroatoms are N, O, N·O, and S(O). r A heteroaromatic system containing a heteroatom (where r is an integer 0, 1, or 2), preferably containing 5 to 10, 5 to 8, or 5 to 6 ring atoms, for example, a "5-8 membered heteroaryl group" is a heteroaromatic system containing 5 to 8 ring atoms. The term refers to a system, and "5-10 membered heteroaryl group" refers to a heteroaromatic system containing 5 to 10 ring atoms, including, but not limited to, furyl, thienyl, pyridyl, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, imidazolyl, and tetrazolyl groups. The ring of the heteroaryl group may be fused to an aryl group, a heterocyclic group, or a cycloalkyl group, where the ring linked to the parent structure is a heteroaryl ring, and includes, but is not limited to, the following: 【0101】 [ka] 【0102】 The "heteroaryl group" or "heteroaryl ring" may be optionally substituted or unsubstituted. If substituted, the substituents are preferably independently deuterium, halogen, cyano group, nitro group, azide group, and C. 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0103】 "Alkenyl group" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon double bond, preferably a linear or branched alkenyl group containing 2 to 10 or 2 to 4 carbon atoms, for example, "C 2-10 An "alkenyl group" is a linear or branched alkenyl group containing 2 to 10 carbon atoms. 2-4 An "alkenyl group" is a linear or branched alkenyl group containing 2 to 4 carbon atoms. This includes, but is not limited to, vinyl groups, 1-propenyl groups, 2-propenyl groups, 1-butenyl groups, 2-butenyl groups, or 3-butenyl groups. 【0104】 The "alkenyl group" may be substituted or unsubstituted. If substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, and C. 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15)2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C0 -8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0105】 "Alkynyl group" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon triple bond, preferably a linear or branched alkynyl group containing 2 to 10 or 2 to 4 carbon atoms, for example, "C 2-10 An "alkynyl group" is a linear or branched alkynyl group containing 2 to 10 carbon atoms. 2-4 An "alkynyl group" is a linear or branched alkynyl group containing 2 to 4 carbon atoms. This includes, but is not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, or 3-butynyl groups. 【0106】 The "alkynyl group" may be substituted or unsubstituted. If substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, and C. 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0107】 "Alkoxy group" refers to an -O-alkyl group, where the definition of an alkyl group is as described above, for example, "C 1-10 An "alkoxy group" refers to an alkyloxy group containing 1 to 10 carbon atoms, and "C 1-4 An "alkoxy group" refers to an alkyloxy group containing 1 to 4 carbon atoms, and "C 1-2 An "alkoxy group" refers to an alkyloxy group containing one or two carbon atoms, and includes, but is not limited to, methoxy, ethoxy, propoxy, and butoxy groups. 【0108】 The "alkoxy group" may be optionally substituted or unsubstituted. If substituted, the substituents are preferably independently deuterium, halogen, cyano group, nitro group, azide group, and C. 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl alkyl group, C 2-10 Alkenyl group, C 2-10 Alkynyl group, C 3-12Cycloalkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0109】 "Cycloalkoxy group" or "cycloalkyloxy group" refers to -O-cycloalkyl groups, where the definition of a cycloalkyl group is as described above, for example, "C 3-12 A "cycloalkoxy group" refers to a cycloalkyloxy group containing 3 to 12 carbon atoms, and "C 3-6 A "cycloalkoxy group" refers to a cycloalkyloxy group containing 3 to 6 carbon atoms. This includes, but is not limited to, cyclopropoxy groups, cyclobutoxy groups, cyclopentoxy groups, and cyclohexyloxy groups. 【0110】 The "cycloalkoxy group" or "cycloalkyloxy group" may be optionally substituted or unsubstituted. If substituted, the substituents are preferably, independently, deuterium, halogen, cyano group, nitro group, azide group, and C 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R 16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0111】 "Heterocyclyloxy group" or "heterocyclic oxy group" refers to an -O-heterocyclic group, where the definition of a heterocyclic group is as described above, and includes, but is not limited to, azetidinyloxy group, oxetanyloxy group, azacyclopentyloxy group, azacyclohexyloxy group, and oxacyclohexyloxy group. 【0112】 The "heterocyclyloxy group" or "heterocyclic oxy group" may be optionally substituted or unsubstituted. If substituted, the substituents are preferably independently deuterium, halogen, cyano group, nitro group, azide group, and C. 1-10 Alkyl, halogen-substituted C 1-10 Alkyl, deuterium-substituted C 1-10 Alkyl 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-OS(O)2R 13 , -C 0-8 Alkyl-S(O) r R 13 , -C 0-8 Alkyl-OR 14 , -C 0-8 Alkyl-C(O)OR 14 , -C 0-8 Alkyl-C(O)SR 14 , -C 0-8 Alkyl-SC(O)R 15 , -C 0-8 Alkyl-C(O)R 15 , -C 0-8 Alkyl-OC(O)R 15 , -C 0-8 alkyl-P(O)(R 15 )2, -C 0-8 Alkyl-NR 16 R 17 , -C 0-8 Alkyl-C(O)NR 16 R 17 and -C 0-8 Alkyl-N(R16 )-C(O)R 15 One or more (preferably one, two, three, or four) bases selected from the above. 【0113】 "C 1-10 The "alkanoyl group" is C 1-10 This refers to the monovalent group of atoms remaining after removing the hydroxyl group from an alkyl acid, and is usually "C 0-9 It is also written as "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 isobutyryl group. 【0114】 "-C 0-8 Alkyl-OS(O)2R 13 " is -OS(O)2R 13 The oxygen atom in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0115】 "-C 0-8 Alkyl-S(O) r R 13 " is -S(O) r R 13 The sulfur atom in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0116】 "-C 0-8 Alkyl-OR 14 " is -OR 14 The oxygen atom in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. "-C 0-8 Alkyl-C(O)OR 14 " is -C(O)OR 14 The carbonyl group in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8The definition of alkyl groups is as stated above. 【0117】 "-C 0-8 Alkyl-C(O)SR 14 " is -C(O)SR 14 The carbonyl group in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0118】 "-C 0-8 Alkyl-SC(O)R 15 " is -SC(O)R 15 The sulfur atom in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0119】 "-C 0-8 Alkyl-C(O)R 15 " is -C(O)R 15 The carbonyl group in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0120】 "-C 0-8 Alkyl-OC(O)R 15 " is -OC(O)R 15 The oxygen atom in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0121】 "-C 0-8 alkyl-P(O)(R 15 )2" is -P(O)(R 15 The phosphorus atom in )2 is C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0122】 "-C 0-8 Alkyl-NR 16 R 17" is -NR 16 R 17 The nitrogen atom in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0123】 "-C 0-8 Alkyl-C(O)NR 16 R 17 " is -C(O)NR 16 R 17 The carbonyl group in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0124】 "-C 0-8 Alkyl-N(R 16 )-C(O)R 15 " is -N(R 16 )-C(O)R 15 The nitrogen atom in C 0-8 This refers to a molecule linked to an alkyl group, where C 0-8 The definition of alkyl groups is as stated above. 【0125】 "Halogen substitution C" 1-10 An alkyl group is an alkyl group consisting of 1 to 10 carbon atoms in which the hydrogen atoms in the alkyl group are optionally substituted with fluorine, chlorine, bromine, or iodine atoms. This includes, but is not limited to, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, and tribromomethyl groups. 【0126】 "Halogen substitution C" 1-10 An "alkoxy group" refers to an alkoxy group consisting of 1 to 10 carbon atoms in which a hydrogen atom in the alkyl group is optionally substituted with a fluorine, chlorine, bromine, or iodine atom. This includes, but is not limited to, difluoromethoxy, dichloromethoxy, dibromomethoxy, trifluoromethoxy, trichloromethoxy, and tribromomethoxy groups. 【0127】 Deuterium-substituted C 1-10An "alkyl group" refers to an alkyl group consisting of 1 to 10 carbon atoms in which a hydrogen atom is optionally replaced by a deuterium atom. This includes, but is not limited to, monodeuteromethyl, diduteromethyl, and trideuteromethyl groups. 【0128】 "Halogen" refers to fluorine, chlorine, bromine, or iodine; "EA" refers to ethanol; "PE" refers to petroleum ether; "Â" refers to ethyl acetate; "DCM" refers to dichloromethane; "DMSO" refers to dimethyl sulfoxide; "Cs2CO3" refers to cesium carbonate; "ACN" refers to acetonitrile; "Pd(OH)2" refers to palladium carbon hydroxide; "MeOH" refers to methanol; "rt" refers to room temperature; and "1,2-dichlorobenzene" refers to 1,2-dichlorobenzene. "N,N-dimethylaniline" refers to N,N-dimethylaniline, "POCl3" refers to phosphorus oxychloride, "DIPEA" refers to N,N-diisopropylethylamine, "NMP" refers to N-methylpyrrolidone, "TFA" refers to trifluoroacetic acid, "LiOH" refers to lithium hydroxide, "THF" refers to tetrahydrofuran, "PyBrOP" refers to bromotripyrrolidinophosphonium hexafluorophosphate, and "DMA" refers to N,N-dimethylacetamide. 【0129】 "Optional" or "optionally" means that the event or situation described thereafter may or may not occur, and this description includes both cases in which the event or situation occurs and cases in which it does not occur, i.e., both when substituted and when not substituted. For example, "a heterocyclic group optionally substituted with an alkyl group" means that the alkyl group may or may not be present, and this description includes both cases in which the heterocyclic group is substituted with an alkyl group and cases in which the heterocyclic group is not substituted with an alkyl group. 【0130】 "Substitution" refers to the substitution of one or more hydrogen atoms in a group by a corresponding number of substituents that are independent of each other. Of course, substituents are only in their chemically possible positions and are consistent with chemical valence bond theory, and those skilled in the art can determine whether substitution is possible or impossible (experimentally or theoretically) with little effort. For example, an amino group or hydroxyl group with free hydrogen can be unstable when bonded to a carbon atom with an unsaturated bond (e.g., an olefin). 【0131】 "Stereoisomers," whose English name is stereoisomer, refer to isomers formed by differences in the spatial arrangement of atoms in a molecule. They can be divided into two types: cis-trans isomers and enantiomers, or into enantiomers and diastereomers. Stereoiomers formed by the rotation of single bonds are called conformational stereoisomers, and are sometimes called rotamers. Stereoiomers formed by bond length, bond angles, or the presence of double bonds or rings in the molecule are called configurational stereoisomers, and configurational stereoisomers are further divided into two types. Here, isomers formed by the inability of single bonds of double bonds or ring-forming carbon atoms to rotate freely are called geometric isomers, also known as cis-trans isomers, and are divided into two types of configurations: Z and E. For example, cis-2-butene and trans-2-butene are a pair of geometric isomers, and stereoisomers with different optical activity properties formed by the lack of antiaxial symmetry in a molecule are called optical isomers, and are divided into R and S configurations. Unless otherwise specified, the term "stereoisomer" as used in this invention may be understood to include one or more of the enantiomers, configuration isomers, and conformation isomers. 【0132】 "Pharmacologically acceptable salt" refers to a pharmaceutically acceptable acid addition salt in this invention, without This includes organic salts and organic salts, and these salts can be prepared by methods known in the art. 【0133】 "Drug composition" refers to a mixture of one or more compounds described herein or their physiologically / pharmaceutically acceptable salts or prodrugs with other chemical components, and other components, such as physiologically / pharmaceutically acceptable carriers and excipients. Drug compositions are intended to facilitate administration to a living organism and contribute to the absorption of the active ingredient, thereby exerting further biological activity. 【0134】 The present invention will be described in more detail and comprehensively below, along with examples, but this is not intended to limit the present invention, nor is it limited to the contents of the examples. The structure of the compounds of the present invention is confirmed by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). The chemical shift (?) of the NMR is shown in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 / 500 nuclear magnetic resonance spectrometer, with deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (MeOH-d4), and deuterated chloroform (CDCl3) as the solvents, and tetramethylsilane (TMS) as the internal standard. 【0135】 Liquid chromatography-mass spectrometry (LC-MS) measurements were performed using an Agilent 6120 mass spectrometer. HPLC measurements were performed using an Agilent 1200DAD high-pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high-pressure liquid chromatograph (Gimini C18 150×4.6 mm column). 【0136】 For thin-layer chromatography, silica gel plates from Yantai Huanghai HSGF254 or Qingdao GF254 were used. The specifications for TLC were 0.15 mm to 0.20 mm, and the specifications for product separation and purification by thin-layer chromatography were 0.4 mm to 0.5 mm. For column chromatography, 200 to 300 mesh silica gel from Yantai Huanghai silica gel was generally used as the support. 【0137】 The starting materials used in the embodiments of this invention are known and commercially available, or can be synthesized by or in accordance with methods known in the art. Unless otherwise specified, all reactions of the present invention are carried out by continuous magnetic stirring in an atmosphere of dry nitrogen or argon gas, using a dry solvent, and the reaction temperature is measured in degrees Celsius (°C). 【0138】 I. Preparation of Intermediates Preparation of the intermediate 1,4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid 【0139】 [ka] 【0140】 Step 1: Synthesis of methyl 3-(2-methyl-1H-imidazole-1-yl)-4-nitrobenzoate 【0141】 [ka] 【0142】 Methyl 3-fluoro-4-nitrobenzoate (1.5 g, 7.54 mmol) and 2-methyl-1H-imidazole (0.74 g, 9.05 mmol) were dissolved in acetonitrile (20 mL), cesium carbonate (3.69 g, 11.31 mmol) was added, and the mixture was stirred overnight at 80°C. After the reaction was complete, water was added to quench the mixture, and it was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain methyl 3-(2-methyl-1H-imidazole-1-yl)-4-nitrobenzoate (1.97 g, 100%), which was used directly in the next step. MS m / z (ESI): 262 [M+H] + . 【0143】 Step 2: Synthesis of methyl 4-amino-3-(2-methyl-1H-imidazole-1-yl)benzoate 【0144】 [ka] 【0145】 Methyl 3-(2-methyl-1H-imidazole-1-yl)-4-nitrobenzoate (1.97 g, 7.54 mmol) was dissolved in methanol (30 mL), palladium hydroxide (0.4 g, 20% w / w) was added, and the mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was filtered and concentrated, and separated by silica gel column chromatography [5% methanol-dichloromethane system] to obtain methyl 4-amino-3-(2-methyl-1H-imidazole-1-yl)benzoate (800 mg, 46%). MS m / z (ESI): 232 [M+H] + . 【0146】 Step 3: Synthesis of methyl 1-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate 【0147】 [ka] 【0148】 Methyl 4-amino-3-(2-methyl-1H-imidazole-1-yl)benzoate 800 mg, 3.46 mmol of methyl 1H-imidazole-1-yl)methanone (729 mg, 4.50 mmol) and di(1H-imidazole-1-yl)methanone (30 mL) were placed in 1,2-dichlorobenzene (30 mL), heated to 160-170°C, and stirred at that temperature for 3 hours. After cooling, the mixture was concentrated to remove the solvent, slurryed in methanol for 10 minutes, filtered, and dried to obtain methyl 1-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate (680 mg, 76%). MS m / z (ESI): 258 [M+H] + . 【0149】 Step 4: Synthesis of methyl 4-chloro-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate 【0150】 [ka] 【0151】 Methyl 1-methyl-4-oxo-4,5-dihydroimidazo[1,5-a]quinoxaline-8-carboxylate (680 mg, 2.64 mmol) was placed in phosphorus oxychloride (50 mL), N,N-dimethylaniline (115.9 mg, 0.53 mmol) was added, and the mixture was heated to 120°C and stirred overnight. Since the reaction of some of the starting materials was incomplete, the mixture was cooled, concentrated, quenched with ice water in an ice bath, extracted three times with dichloromethane, the organic phases were combined, washed with saturated sodium bicarbonate aqueous solution and saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography [40-60% ethyl acetate-petroleum ether system] to obtain methyl 4-chloro-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (460 mg, 63%). MS m / z (ESI): 276 [M+H] + . 【0152】 Step 5: Synthesis of methyl 4-((2,4-dimethoxybenzyl)amino)-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate 【0153】 [ka] 【0154】 Methyl 4-chloro-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (460 mg, 1.67 mmol) was dissolved in N-methylpyrrolidone (8 mL), 2,4-dimethoxybenzyl)amino (646 mg, 5.01 mmol) was added, and the mixture was heated to 110°C and stirred for 3 hours. After the reaction was complete, water was added to quench the mixture, and it was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated, and separated by silica gel column chromatography [9% methanol-dichloromethane system] to obtain methyl 4-((2,4-dimethoxybenzyl)amino)-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (6 0.5 mg, 89% was obtained. MS m / z (ESI): 407 [M+H] + . 【0155】 Step 6: Synthesis of methyl 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate 【0156】 [ka] 【0157】 Methyl 4-((2,4-dimethoxybenzyl)amino)-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (330 mg, 0.81 mmol) was dissolved in trifluoroacetic acid (10 mL), stirred at 60°C for 6 hours, concentrated after the reaction was complete, an appropriate amount of water was added, and the pH was adjusted to approximately 6 with aqueous sodium bicarbonate solution. After filtration, the mixture was dried to obtain methyl 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (370 mg crude product). MS m / z (ESI): 257 [M+H] + . 【0158】 Step 7: Synthesis of 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid 【0159】 [ka] 【0160】 Methyl 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylate (370 mg, 0.81 mmol) was dissolved in methanol (10 mL) and tetrahydrofuran (10 mL). Lithium hydroxide monohydrate (102 mg, 2.43 mmol) was added, and the mixture was stirred overnight at 50°C. After the reaction was complete, the mixture was concentrated, an appropriate amount of water was added, and the pH was adjusted to approximately 6 with dilute hydrochloric acid. The mixture was filtered, the filter cake was washed several times with water, and after drying, 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid (150 mg, 76%) was obtained. MS m / z (ESI): 243 [M+H] + . 【0161】 Intermediates 2-7 were prepared by selecting the corresponding raw materials by referring to the synthesis method of all or part of intermediate 1. 【0162】 [Table 1] 【0163】 Preparation of the intermediate 8,4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylic acid 【0164】 [ka] 【0165】 Step 1: Synthesis of methyl 5-(2-cyano-1H-pyrrole-1-yl)-2-fluoro-4-nitrobenzoate 【0166】 [ka] 【0167】 Methyl 2,5-difluoro-4-nitrobenzoate (2.0 g, 9.21 mmol) is dissolved in acetonitrile (20 mL), and 1H-pyrrole-2-carbonitrile (0.78 mL, 9.21 mmol) and cesium fluoride (1.40 g, 9.21 mmol) are added. mmol was added, and the mixture was reacted with stirring at 20°C for 16 hours. The reaction mixture was concentrated by rotary evaporation, and the crude product was separated by normal-phase column chromatography to obtain methyl 5-(2-cyano-1H-pyrrole-1-yl)-2-fluoro-4-nitrobenzoate (500 mg, 19%). 【0168】 1 H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 6.4 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.04 (dd, J = 4.0, 1.6 Hz, 1H), 6.93 (dd, J = 2.8, 1.6 Hz, 1H), 6.43 (dd, J = 4.0, 2.8 Hz, 1H), 4.01 (s, 3H). 【0169】 Step 2: Synthesis of methyl 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylate 【0170】 [ka] 【0171】 Methyl 5-(2-cyano-1H-pyrrole-1-yl)-2-fluoro-4-nitrobenzoate (1.5 g, 5.19 mmol) was dissolved in tetrahydrofuran (20 mL), and iron powder (2.90 g, 51.86 mmol) and glacial acetic acid (20 mL) were added. The mixture was reacted at 20°C for 16 hours with stirring. The reaction solution was rotated dry. The crude product was separated by normal-phase column chromatography to obtain methyl 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylate (650 mg, 48%). 【0172】 1 H NMR (400 MHz, DMSO-d6) δ 8.47 (d, J = 7.2 Hz, 1H), 8.36 (s, 1H), 7.52 (s, 2H), 7.25-7.06 (m, 2H), 6.75 (m, 1H), 3.88 (s, 3H). 【0173】 Step 3: Synthesis of 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylic acid 【0174】 [ka] 【0175】 Methyl 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylate (600 mg, 2.31 mmol) was dissolved in tetrahydrofuran (10 mL) and water (3 mL), and lithium hydroxide monohydrate (583 mg, 13.89 mmol) was added. The mixture was reacted at 50°C for 16 hours. After evaporating the organic solvent under reduced pressure, water (5 mL) was added. The pH was adjusted to 3-4 with 1 M hydrochloric acid, the mixture was filtered, and the filter cake was washed with water (20 mL) and acetonitrile (20 mL). After drying the filter cake, 4-amino-7-fluoropyrrolo[1,2-a]quinoxaline-8-carboxylic acid (341 mg, 60%) was obtained. MS m / z (ESI): 246 [M+H] + . 【0176】 1 H NMR (400 MHz, DMSO-d6) δ 9.99 (s, 1H), 9.15 (s, 1H), 8.83-8.53 (m, 2H), 7.79 (d, J = 3.6 Hz, 1H), 7.57 (d, J = 10.8 Hz, 1H), 6.94 (d, J = 3.6 Hz, 1H). Preparation of intermediate 9, 1-cyclopropyl-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)methaneamine 【0177】 [ka] 【0178】 Step 1: Synthesis of 1-cyclopropyl-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)methaneamine 【0179】 [ka] 【0180】 5-(trifluoromethyl)picolinealdehyde (350 mg, 2.0 mmol) was dissolved in dichloromethane (10 mL), and cyclopropylmethaneamine (156 mg, 2.2 mmol) and acetic acid (132 mg, 2.2 mmol) were added. The mixture was reacted at room temperature for half an hour with stirring. Sodium triacetoxyborohydride (355 mg) was added to the reaction mixture. Add (1.68 mmol / mg) and stir at room temperature for 1 hour. Dilute the reaction mixture with dichloromethane and saturated sodium bicarbonate solution, separate the organic phase by liquid-liquid evaporation, concentrate the mixture by rotary evaporation, and separate the crude product by column chromatography (methanol / dichloromethane = 1 / 19) to obtain 1-cyclopropyl-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)methaneamine (400 mg, 84%). MS m / z (ESI): 231 [M+H] + . 【0181】 Intermediates 10-19 were prepared by selecting the corresponding raw materials by referring to the synthesis method of all or part of intermediate 9. 【0182】 [Table 2] TIFF0007873890000062.tif96151 【0183】 Preparation of intermediate 20,6-(trifluoromethyl)benzofuran-3(2H)-one 【0184】 [ka] 【0185】 Step 1: Synthesis of methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate 【0186】 [ka] 【0187】 Methyl 2-hydroxy-4-(trifluoromethyl)benzoate (15.0 g, 68.1 mmol) is dissolved in acetone (200 mL), and potassium carbonate (12.24 mmol) is added. Add (g, 88.6 mmol), then add methyl bromoacetate (8.42 mL, 88.6 mmol of methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate was added dropwise to the reaction solution, and the temperature was raised to 55°C for 18 hours. After the reaction was complete, the reaction solution was cooled to room temperature, filtered to remove the solid, and the filter cake was washed with ethyl acetate. The filtrate was washed with saturated brine, dried, and then concentrated to obtain methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate (22.0 g, 94%). MS m / z (ESI): 293 [M+H] + . 【0188】 Step 2: Synthesis of 2-(carboxymethoxy)-4-(trifluoromethyl)benzoic acid 【0189】 [ka] 【0190】 Methyl 2-(2-methoxy-2-oxoethoxy)-4-(trifluoromethyl)benzoate (74.0 g, 253.2 mmol) was dissolved in a mixed solvent of methanol (500 mL) and water (250 mL), and lithium hydroxide monohydrate (31.91 g, 759.7 mmol) was added. The reaction was allowed to proceed at room temperature for 18 hours. The reaction mixture was acidified with 1 N hydrochloric acid to pH=2, concentrated to remove methanol, filtered the aqueous phase, and washed the solid with water. The filtered cake was dried to obtain 2-(carboxymethoxy)-4-(trifluoromethyl)benzoic acid (61.0 g, 91%). MS m / z (ESI): 265 [M+H] + . 【0191】 Step 3: Synthesis of 6-(trifluoromethyl)benzofuran-3(2H)-one 【0192】 [ka] 【0193】 A mixture of 2-(carboxymethoxy)-4-(trifluoromethyl)benzoic acid (61 g, 230.9 mmol), anhydride acetic acid (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 complete, the reaction mixture 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, the mixture 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, and the mixture was heated to 100°C and reacted for 6 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extracted organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated. After concentration, the mixture was slurryed with methyl tert-butyl ether to obtain 6-(trifluoromethyl)benzofuran-3(2H)-one (17.0 g, 36%). 【0194】 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). Preparation of intermediate 21,2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-5-one 【0195】 [ka] 【0196】 Step 1: Synthesis of methyl 2-bromo-6-(trifluoromethyl)nicotinate 【0197】 [ka] 【0198】 2-Oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylic acid (5.0 g, 24.14 mmol) and pyridine (1.95 mL, 24.14 mmol) were dissolved in chlorobenzene (50 mL). Phosphorus oxybromide (4.91 mL, 48.28 mmol) was gradually added in several portions at room temperature, and the mixture was heated to 120°C and stirred for 16 hours. After the reaction was complete, the reaction solution was concentrated under vacuum. The concentrate was cooled to 0°C in an ice bath, and then dry methanol (20 mL), which had been previously cooled with dry ice, was gradually added dropwise, and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under vacuum to obtain a brown oily substance. The oily substance was diluted with water, and the pH of the solution was adjusted to 8 with saturated sodium bicarbonate solution. The solution was extracted three times with ethyl acetate (50 mL x 3), the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was separated by silica gel column chromatography to obtain methyl 2-bromo-6-(trifluoromethyl)nicotinate (5.7 g, 83%). MS m / z (ESI): 284, 286 [M+H] + . 【0199】 1 H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 4.00 (s, 3H). 【0200】 Step 2: Synthesis of methyl(E)-2-(3-methoxy-3-oxoprop-1-en-1-yl)-6-(trifluoromethyl)nicotinate 【0201】 [ka] 【0202】 To a solution of methyl 2-bromo-6-(trifluoromethyl)nicotinate (5.7 g, 20.07 mmol) and methyl acrylate (4.52 mL, 50.17 mmol) in toluene (100 mL) and N,N-dimethylformamide (15 mL), allyl palladium(II) chloride dimer (0.37 g, 1.00 mmol), tris(o-methylphenyl)phosphorus (0.61 g, 2.01 mmol), and sodium carbonate (6.38 g, 60.20 mmol) were added, and the mixture was stirred at 120°C for 16 hours under a nitrogen atmosphere. The reaction mixture was filtered, and the filter cake was washed three times with ethyl acetate (3 × 30 mL). The organic phase was combined, concentrated under vacuum, and the concentrate was separated by silica gel column chromatography to obtain methyl(E)-2-(3-methoxy-3-oxoprop-1-en-1-yl)-6-(trifluoromethyl)nicotinate (5.1 g, 88%). MS m / z (ESI): 290 [M+H] + . 【0203】 1 H NMR (400 MHz, 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). 【0204】 Third step: Synthesis of methyl 2-(3-methoxy-3-oxopropyl)-6-(trifluoromethyl)nicotinate. 【0205】 [ka] 【0206】 A solution of methyl(E)-2-(3-methoxy-3-oxopropyl-1-en-1-yl)-6-(trifluoromethyl)nicotinate (5.1 g, 17.63 mmol) and triphenylphosphine rhodium chloride (1.31 g, 1.41 mmol) in ethanol (50 mL) was stirred at room temperature under a hydrogen gas atmosphere (15 atm) for 48 hours. The reaction mixture was filtered, the filtrate was concentrated under vacuum, and the crude product was separated by silica gel column chromatography to obtain methyl 2-(3-methoxy-3-oxopropyl)-6-(trifluoromethyl)nicotinate (4.9 g, 95%). MS m / z (ESI): 292 [M+H] + . 【0207】 1 H NMR (400 MHz, 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). Step 4: Synthesis of 2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-5-one 【0208】 [ka] 【0209】 To a methanol (60 mL) solution of methyl 2-(3-methoxy-3-oxopropyl)-6-(trifluoromethyl)nicotinate (4.9 g, 16.82 mmol), sodium methanol (1.36 g, 25.23 mmol) was added in several portions, and the reaction mixture was stirred overnight at 80°C. After the reaction was complete, the reaction mixture was cooled to room temperature and concentrated to obtain a brown solid. The brown solid was dispersed in concentrated hydrochloric acid (60 mL) and stirred at 80°C for 3 hours. The reaction mixture was cooled to room temperature, the pH was adjusted to 6 with 1 M sodium hydroxide solution, and extracted with dichloromethane (2 × 100 mL). The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a brown solid. The brown solid was separated by silica gel column chromatography to obtain 2-(trifluoromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-5-one (2.07 g, 43%). MS m / z (ESI): 202 [M+H] + . 【0210】 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). Preparation of intermediate 22,6-(trifluoromethyl)fl[2,3-b]pyridine-3(2H)-one 【0211】 [ka] 【0212】 Step 1: Synthesis of ethyl 2-chloro-6-(trifluoromethyl)nicotinate 【0213】 [ka] 【0214】 Dichlorosulfoxide (3.62 mL, 49.9 mmol) at room temperature is treated with nitrogen gas-protected 2-chloro-6-(trifluoromethyl)nicotinic acid (7.5 g, 33.25 mmol). The ethyl 2-chloro-6-(trifluoromethyl)nicotinate (7 mmol) was added dropwise to a 150 mL solution of ethanol. The reaction mixture was then heated to 70°C and stirred for 14 hours. After the reaction was complete, the reaction mixture was concentrated to remove the ethanol, the residue was dissolved in 200 mL of ethyl acetate, the organic phase was washed with water (100 mL x 3), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrated product was separated by column chromatography [85% ethyl acetate-petroleum ether system], and ethyl 2-chloro-6-(trifluoromethyl)nicotinate (7 mmol) was obtained. 0.72 g, 92% was obtained. MS m / z (ESI): 254 [M+H] + . 【0215】 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). 【0216】 Step 2: Synthesis of ethyl 3-hydroxy-6-(trifluoromethyl)fl[2,3-b]pyridine-2-carboxylate 【0217】 [ka] 【0218】 At 0°C, sodium hydride (15.22 g, 380.5 mmol, 60% purity) was added in several portions to a solution of ethyl glycolate (36.7 mL, 380.5 mmol) in ethylene glycol dimethyl ether (530 mL). The reaction mixture was heated 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 the reaction was complete, 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 slurryed with acetonitrile (300 mL) to obtain ethyl 3-hydroxy-6-(trifluoromethyl)fl[2,3-b]pyridine-2-carboxylate (29.5 g, 70%). 【0219】 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). 【0220】 Step 3: Synthesis of 6-(trifluoromethyl)fl[2,3-b]pyridine-3(2H)-one 【0221】 [ka] 【0222】 Ethyl 3-hydroxy-6-(trifluoromethyl)flou[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 mixture was heated to 40°C and reacted for 2 days. The reaction was completed. The reaction mixture was cooled to room temperature, filtered, and the filter cake was washed with tetrahydrofuran. The filter cake was then dissolved in a mixed solvent of ethyl acetate and water, and the system was acidified in an ice bath with 1 M hydrochloric acid to a pH of 6-7. The system was separated, the aqueous phase was extracted with ethyl acetate, the organic phase was combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by rotary evaporation to obtain 6-(trifluoromethyl)fl[2,3-b]pyridine-3(2H)-one (1.43 g, 68%). MS m / z (ESI): 204 [M+H] + . 【0223】 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). Preparation of intermediate 23,7-(trifluoromethyl)isochroman-4-one 【0224】 [ka] 【0225】 Step 1: Synthesis of 2-((allyloxy)methyl)-1-bromo-4-(trifluoromethyl)benzene 【0226】 [ka] 【0227】 (2-bromo-5-(trifluoromethyl)phenyl)methanol (7.39 g, 29.0 mmol) was dissolved in tetrahydrofuran (100 mL), sodium hydride (1.74 g, 43.5 mmol) was added at 0°C, and the mixture was reacted at 0°C for 0.5 hours. Then, 3-bromoprop-1-ene (2.52 mL, 29.0 mmol) was added to the reaction mixture, and the mixture was reacted at 25°C for 2 hours. Water (50 mL) was added to the reaction mixture, and the mixture was extracted three times with ethyl acetate (30 mL). The organic phases were combined and concentrated. The crude product was separated by normal-phase column chromatography to obtain 2-((allyloxy)methyl)-1-bromo-4-(trifluoromethyl)benzene (8.1 g, 95%). 【0228】 1 H NMR (400 MHz, CDCl3) δ 7.98-7.73 (m, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.40 (dd, J = 8.4, 2.4 Hz, 1H), 6.13-5.90 (m, 1H), 5.49-5.33 (m, 1H), 5.33-5.18 (m, 1H), 4.59 (s, 2H), 4.15 (dt, J = 5.6, 1.6 Hz, 2H). 【0229】 Step 2: Synthesis of 4-methylene-7-(trifluoromethyl)isochromane 【0230】 [ka] 【0231】 2-((allyloxy)methyl)-1-bromo-4-(trifluoromethyl)benzene (8.1 g, 27.4 mmol) was dissolved in N,N-dimethylformamide (160 mL), cesium carbonate (10.73 g, 32.9 mmol), triphenylphosphine (3.24 g, 12.4 mmol), and palladium acetate (0.92 g, 4.1 mmol) were added, and the mixture was reacted at 90°C for 16 hours. The reaction mixture was concentrated, and the crude product was separated by normal-phase column chromatography to obtain 4-methylene-7-(trifluoromethyl)isochromane (3.8 g, 65%). 【0232】 1 H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.4, 2.0 Hz, 1H), 7.30 (s, 1H), 5.72 (s, 1H), 5.15 (t, J = 1.2 Hz, 1H), 4.84 (s, 2H), 4.47 (t, J = 1.2 Hz, 2H). 【0233】 Step 3: Synthesis of 4-(hydroxymethyl)-7-(trifluoromethyl)isochroman-4-ol 【0234】 [ka] 【0235】 4-Methylene-7-(trifluoromethyl)isochroman (3.8 g, 17.74 mmol) was dissolved in water (10 mL) and acetone (40 mL), potassium osmate dihydrate (0.65 g, 1.77 mmol) was added, and the mixture was reacted at 25°C for 5 minutes. Then, N-methylmorpholine oxide (7.27 g, 62.1 mmol) was added, and the mixture was reacted at 25°C for 16 hours. A saturated solution of sodium thiosulfate (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL). The organic phase was rotate-dried, and the crude product was separated by normal-phase column chromatography to obtain 4-(hydroxymethyl)-7-(trifluoromethyl)isochroman-4-ol (3.57 g, 81%). 【0236】 1 H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.4 Hz, 1H), 7.60-7.51 (m, 1H), 7.28 (s, 1H), 4.83 (s, 2H), 4.16 (d, J = 11.2 Hz, 1H), 3.90 (dd, J = 11.2, 6.4 Hz, 1H), 3.70 (ddd, J = 11.2, 4.8, 1.2 Hz, 1H), 3.63 (dd, J = 11.2, 1.2 Hz, 1H), 2.87 (s, 1H). 【0237】 Step 4: Synthesis of 7-(trifluoromethyl)isochroman-4-one 【0238】 [ka] 【0239】 4-(hydroxymethyl)-7-(trifluoromethyl)isochroman-4-ol (3.57 g, 14.38 mmol) was dissolved in tetrahydrofuran (50 mL) and water (5 mL), then sodium periodate (10.46 g, 48.90 mmol) was added, and the mixture was reacted at 25°C for 16 hours. Saturated sodium thiosulfate solution (40 mL) was added to the reaction mixture. (mL) was added, and the mixture was extracted three times with ethyl acetate (40 mL). The organic phase was rotate-dried, and the crude product was separated by normal-phase column chromatography to obtain 7-(trifluoromethyl)isochroman-4-one (2.88 g, 93%). 【0240】 1 H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.4 Hz, 1H), 7.68 (dd, J = 8.4, 1.6 Hz, 1H), 7.52 (d, J = 2.0 Hz, 1H), 4.95 (s, 2H), 4.42 (s, 2H). Preparation of intermediate 24,6-(1-methyl-1H-pyrazole-4-yl)benzofuran-3(2H)-one 【0241】 [ka] 【0242】 6-Bromobenzofuran-3(2H)-one (1.00 g, 4.69 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.17 g, 5.63 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (343 mmol) Dissolve 6-(1-methyl-1H-pyrazole-4-yl)benzofuran-3(2H)-one (0.8 g, 80%) in dioxane (15 mL) and water (5 mL). Heat to 85°C under nitrogen gas protection and stir overnight. Once the reaction is complete, add water to quench, extract with ethyl acetate, dry the organic phase over anhydrous sodium sulfate, and filter. Separate the resulting crude product by silica gel column chromatography to obtain 6-(1-methyl-1H-pyrazole-4-yl)benzofuran-3(2H)-one (0.8 g, 80%). MS m / z (ESI): 215 [M+H] + . 【0243】 Preparation of intermediate 25, (S)-6-(trifluoromethyl)-2,3-dihydrofl[2,3-b]pyridine-3-amine 【0244】 [ka] 【0245】 Step 1: Synthesis of (R)-6-(trifluoromethyl)-2,3-dihydrofluoro[2,3-b]pyridine-3-ol 【0246】 [ka] 【0247】 (R)-2-methyl-CBS-oxazaborolidine (5.94 g, 21.4 mmol) was dissolved in tetrahydrofuran (1100 mL) and cooled to 0°C. Subsequently, boranedimethyl sulfide complex (53.5 mL, 107.1 mmol, 2 M in THF) was added to the solution and stirred for 1 hour. The reaction system was cooled to -70°C, 6-(trifluoromethyl)fl[2,3-b]pyridine-3(2H)-one (14.5 g, 71.4 mmol) was dissolved in tetrahydrofuran (140 mL) and added dropwise to the reaction system. The mixture was kept warm and stirred for 1 hour, then the temperature was raised to -10°C and stirring continued for 2 hours. When the end of the reaction was detected, the mixture was quenched with methanol and stirred at room temperature for 30 minutes. 70 mL of aqueous ammonia was added, the mixture was stirred, the supernatant was discarded, and the solution was concentrated. The residue was separated by silica gel column chromatography (dichloromethane / ethyl acetate = 10 / 1) to obtain (R)-6-(trifluoromethyl)-2,3-dihydrofluoro[2,3-b]pyridine-3-ol (12.0 g, 82%). MS m / z (ESI): 206 [M+H] + . 【0248】 Step 2: Synthesis of (S)-3-azido-6-(trifluoromethyl)-2,3-dihydrofl[2,3-b]pyridine 【0249】 [ka] 【0250】 (R)-6-(trifluoromethyl)-2,3-dihydrofl[2,3-b]pyridine-3-ol (12.0 g, 58.5 mmol) is dissolved in tetrahydrofuran (100 mL), cooled to 0°C, and diphenyl phosphate azide (15.2 mL, 70.2 mmol) and 1,8-diazabicyclo[5.4.0]undeca-7-ene (10.5 (mL, 70.2 mmol) was added. The mixture was heated to room temperature and reacted for 18 hours. After the reaction was complete, the reaction solution was diluted with water, extracted with ethyl acetate, and the organic phase was dried and concentrated. Subsequently, it was separated by silica gel column chromatography to obtain (S)-3-azido-6-(trifluoromethyl)-2,3-dihydrofluoro[2,3-b]pyridine (12.5 g, 93%). MS m / z (ESI): 231 [M+H] + . 【0251】 Step 3: Synthesis of (S)-6-(trifluoromethyl)-2,3-dihydrofl[2,3-b]pyridine-3-amine hydrochloride 【0252】 [ka] 【0253】 (S)-3-azido-6-(trifluoromethyl)-2,3-dihydrofl[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 mixture was heated to 50°C and reacted for 18 hours. 0.5 M hydrochloric acid was added, and the mixture was extracted three times with ethyl acetate. After concentration of the aqueous phase obtained by liquid-liquid extraction, (S)-6-(trifluoromethyl)-2,3-dihydrofl[2,3-b]pyridine-3-amine hydrochloride (11.0 g, 84%) was obtained. MS m / z (ESI): 205 [M+H] + . 【0254】 Intermediates 26-32 were prepared by selecting the corresponding raw materials by referring to the synthesis method of all or part of intermediate 25. 【0255】 [Table 3] 【0256】 Preparation of Intermediate 33, (S)-N-(1-methyl-1H-pyrazole-4-yl)-6-(trifluoromethyl)-2,3-dihydrofluoro[2,3-b]pyridine-3-amine 【0257】 [ka] 【0258】 (S)-6-(trifluoromethyl)-2,3-dihydrofluoro[2,3-b]pyridine-3-amine hydrochloride (5.5 g, 22.9 mmol) is dissolved in dioxane (500 mL), and 4-bromo-1-methyl-1H-pyrazole (4.23 g, 26.3 mmol), methanesulfonic acid (2-di-tert-butylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (5.45 g, 6.86 mmol) and sodium t ert-butoxide (6.59 g, 68.58 mmol) was added, and the mixture was purged three times with nitrogen gas. The temperature was then raised to 95°C and the reaction was carried out 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-liquid extraction was dried and concentrated, and then separated by silica gel column chromatography (PE / EA = 1 / 10) and C18 reversed-phase column chromatography (Water (10 mM NH4HCO3)-ACN: 21%~51%) to obtain (S)-N-(1-methyl-1H-pyrazole-4-yl)-6-(trifluoromethyl)-2,3-dihydrofluoro[2,3-b]pyridine-3-amine (2.40 g, 37%). MS m / z (ESI): 285 [M+H] + . 【0259】 1 H 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 34-38 were prepared by selecting the corresponding raw materials by referring to the synthesis method of all or part of intermediate 33. 【0260】 [Table 4] 【0261】 Preparation of Intermediate 39, (R)-N-(cyclopropylmethyl)-5-(trifluoromethyl)-2,3-dihydro-1H-indene-1-amine 【0262】 [ka] 【0263】 (R)-5-(trifluoromethyl)-2,3-dihydro-1H-indene-1-amine hydrochloride (200 mg, 0.84 mmol) was dissolved in a mixed solution of dichloromethane (3 mL) and ethanol (3 mL). Potassium acetate (82 mg, 0.84 mmol), cyclopropanecarboxyaldehyde (59 mg, 0.84 mmol), acetic acid (5 mg, 0.084 mmol), and sodium triacetoxyborohydride (355 mg, 1.68 mmol) were added, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with dichloromethane and saturated sodium bicarbonate solution, separated by liquid-liquid chromatography, 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-indene-1-amine (108 mg, 48%). MS m / z (ESI): 256 [M+H] + . 【0264】 Intermediates 40-43 were prepared by selecting the corresponding raw materials by referring to the synthesis method of all or part of intermediate 39. 【0265】 [Table 5] 【0266】 Intermediate 44, N-methyl-6-(trifluoromethyl)-2,3-dihydrobenzofur Production of n-3-amine 【0267】 [ka] 【0268】 6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-amine (600 mg, 2.95 mmol) was dissolved in hexafluoroisopropanol (5 mL), methyl trifluoromethanesulfonate (727 mg, 4.43 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and saturated sodium bicarbonate solution, separated by liquid-liquid, and the organic phase was concentrated by rotary evaporation. The crude product was separated by column chromatography to obtain N-methyl-6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-amine (450 mg, 70%). MS m / z (ESI): 218 [M+H] + . 【0269】 Intermediates 45-47 were prepared by selecting the corresponding raw materials by referring to the synthesis method of all or part of intermediate 44. 【0270】 [Table 6] 【0271】 Intermediate 48: Preparation of 5-((2R,5S)-5-methylpiperidine-2-yl)benzo[d]thiazole 【0272】 [ka] 【0273】 Step 1: Synthesis of methyl 4-methyl-5-oxopentanoate 【0274】 [ka] 【0275】 In an ice bath, hexahydropyridine (14.66 g, 172.2 mmol), potassium carbonate (4.76 g, 34.43 mmol), and propionaldehyde (5.0 g, 86.09 mmol) were added, and the mixture was vigorously stirred at room temperature for 18 hours. The mixture was filtered, the mother liquor was dried over anhydrous sodium sulfate, filtered again, and the filtrate was concentrated and dissolved in acetonitrile (50 mL). Methyl acrylate (14.82 g, 172.2 mmol) was gradually added dropwise. The reaction mixture was heated under reflux for 24 hours. Glacial acetic acid (10.34 g, 172.2 mmol) and water (50 mL) were added, and the mixture was refluxed for another 24 hours. After diluting the reaction mixture with water, it was extracted with tert-butyl methyl ether, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The crude product was separated by normal-phase column chromatography to obtain methyl 4-methyl-5-oxopentanoate (6.22 g, 48%). 【0276】 1 H NMR (400 MHz, CDCl3) δ 9.63 (d, J = 1.6 Hz, 1H), 3.68 (s, 3H), 2.48-2.40 (m, 1H), 2.41-2.35 (m, 2H), 2.10-2.02 (m, 1H), 1.71 (dq, J = 14.3, 7.3 Hz, 1H), 1.14 (d, J = 7.2 Hz, 3H). 【0277】 Step 2: Synthesis of (3R,8S)-8-methyl-3-phenylhexahydro-5H-oxazolo[3,2-a]pyridine-5-one 【0278】 [ka] 【0279】 Methyl 4-methyl-5-oxopentanoate (6.222 g, 43.16 mmol) was added to toluene (100 mL) with (R)-2-amino-2-phenylethane-1-ol (5.92 g, 43.16 mmol). The mixture was heated under reflux for 24 hours, and water was removed using a water separator. The reaction mixture was concentrated, and the crude product was separated by normal-phase column chromatography to obtain (3R,8S)-8-methyl-3-phenylhexahydro-5H-oxazolo[3,2-a]pyridine-5-one (4.866 g, 46%). MS m / z (ESI): 232 [M+H] + . 【0280】 1 H NMR (400 MHz, CDCl3) δ 7.33-7.20 (m, 5H), 4.93 (dd, J = 6.8, 1.3 Hz, 1H), 4.44 (d, J = 8.8 Hz, 1H), 4.17-4.08 (m, 2H), 4.01 (dd, J = 9.0, 1.3 Hz, 1H), 2.46-2.28 (m, 2H), 2.02-1.87 (m, 2H), 1.60-1.45 (m, 1H), 1.21 (d, J = 6.4 Hz, 3H). 【0281】 Step 3: Synthesis of (S)-1-((R)-2-hydroxy-1-phenylethyl)-5-methylpiperidine-2-one 【0282】 [ka] 【0283】 (3R,8S)-8-methyl-3-phenylhexahydro-5H-oxazolo[3,2-a]pyridine-5-one (4.866 g, 21.04 mmol) was added to a 200 mL solution of anhydrous dichloromethane with triethylsilane (7.34 g, 63.12 mmol) and titanium tetrachloride (17.96 g, 94.68 mmol). The mixture was reacted at 50°C for 24 hours. The reaction was continued for 24 hours at 50°C with the addition of (17.96 g, 94.68 mmol) and titanium tetrachloride (94.68 mmol). The reaction mixture was then mixed with saturated sodium bicarbonate solution (500 ml). The solution was gradually injected into a (mL) volume, and the aqueous phase was filtered and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was separated by normal-phase column chromatography to obtain (S)-1-((R)-2-hydroxy-1-phenylethyl)-5-methylpiperidine-2-one (1.54 g, 31%). MS m / z (ESI): 234 [M+H] + . 【0284】 Step 4: Synthesis of (S)-5-methyl-1-(1-phenylvinyl)piperidine-2-one 【0285】 [ka] 【0286】 (S)-1-((R)-2-hydroxy-1-phenylethyl)-5-methylpiperidine-2-one (10.3 g, 44.15 mmol) dimethyl sulfoxide (150 Lithium hydroxide monohydrate (37.05 g, 882.9 mmol) was added to the solution (mL). The mixture was reacted at 135°C for 4 days. The mixture was injected into water, extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain (S)-5-methyl-1-(1-phenylvinyl)piperidine-2-one (7.383 g, 66%). MS m / z (ESI): 216 [M+H] + . 【0287】 Step 5: Synthesis of (S)-5-methylpiperidine-2-one 【0288】 [ka] 【0289】 (S)-5-methyl-1-(1-phenylvinyl)piperidine-2-one (7.28 g, 33.81 mmol) was dissolved in dichloromethane (30 mL), to which TFA (30 mL) and water (3 mL) were added. The mixture was reacted overnight at 40°C. After concentration, the mixture was separated by reverse-phase column chromatography to obtain the crude product. After lyophilization, aqueous ammonia (3 mL) was added, and the mixture was further concentrated and dried. The mixture was then slurryed with ethyl acetate and filtered to obtain (S)-5-methylpiperidine-2-one (2.52 g, 63%). MS m / z (ESI): 114 [M+H] + . 【0290】 1 H NMR (400 MHz, MeOH-d4) δ 3.30-3.24 (m, 1H), 2.86 (dd, J = 12.2, 10.1 Hz, 1H), 2.39-2.26 (m, 2H), 1.96-1.80 (m, 2H), 1.54-1.40 (m, 1H),1.01 (d, J = 6.5 Hz, 3H). 【0291】 Step 6: Synthesis of tert-butyl(S)-5-methyl-2-oxopiperidine-1-carboxylate 【0292】 [ka] 【0293】 (S)-5-methylpiperidine-2-one (2.02 g, 17.85 mmol) was dissolved in tetrahydrofuran (25 mL), to which 4-dimethylaminopyridine (327 mg, 2.68 mmol) and di-tert-butyl dicarbonate (6.22 g, 26.78 mmol) were added and the mixture was reacted overnight at 25°C with stirring. After concentrating the reaction mixture, it was diluted with dichloromethane and washed with 5% potassium bisulfate solution. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain tert-butyl(S)-5-methyl-2-oxopiperidine-1-carboxylate (3.48 g, 70%). MS m / z (ESI): 214 [M+H] + . 【0294】 1 H NMR (400 MHz, CDCl3) δ 3.83-3.75 (m, 1H), 3.11 (dd, J = 12.7, 10.4 Hz, 1H), 2.63-2.53 (m, 1H), 2.53-2.41 (m, 1H), 2.01-1.93 (m, 1H), 1.92-1.83 (m, 1H), 1.53 (s, 9H), 1.46-1.40 (m, 1H),1.04 (d, J = 6.6 Hz, 3H). 【0295】 Step 7: Synthesis of tert-butyl(S)-3-methyl-6-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydropyridine-1(2H)-carboxylate 【0296】 [ka] 【0297】 Under conditions of -78°C, sodium bis(trimethylsilyl)amide (3.52 mL, 7.03 mmol) was added to a solution of tert-butyl(S)-5-methyl-2-oxopiperidine-1-carboxylate (1.00 g, 4.69 mmol) in anhydrous tetrahydrofuran (25 mL). The reaction mixture was allowed to react at the same temperature for 1 hour. Next, N-phenylbis(trifluoromethanesulfonimide) (2.18 g, 6.10 mmol) was added. The reaction mixture was gradually heated and stirred at room temperature for 3.5 hours. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was separated by normal-phase column to obtain tert-butyl(S)-3-methyl-6-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydropyridine-1(2H)-carboxylate (1.05 g, 62%). MS m / z (ESI): 290 [M+H-56] + . 【0298】 1 H NMR (400 MHz, CDCl3) δ 5.25 (t, J = 3.8 Hz, 1H), 3.87 (dd, J = 12.8, 3.3 Hz, 1H), 3.00 (dd, J = 12.7, 9.1 Hz, 1H), 2.44-2.34 (m, 1H), 1.98-1.88 (m, 1H), 1.88-1.78 (m, 1H), 1.49 (s, 9H), 0.99 (d, J (= 6.6 Hz, 3H). 【0299】 Step 8: Synthesis of tert-butyl(S)-6-(benzo[d]thiazole-5-yl)-3-methyl-3,4-dihydropyridine-1(2H)-carboxylate 【0300】 [ka] 【0301】 tert-butyl(S)-3-methyl-6-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydropyridine-1(2H)-carboxylate (1.39 g, 4.02 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (1.00 g, 3.83 mmol), sodium carbonate (1.01 g, 9.57 mmol), and 1,1'-bisdiphenylphosphinoferocenedichloropalladium (140 mg, 0.191 mmol) were added to 1,4-dioxane (30 mL) and water (10 mL), and the mixture was reacted at 90°C for 18 hours under nitrogen gas protection. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was separated by normal-phase column chromatography to obtain tert-butyl(S)-6-(benzo[d]thiazole-5-yl)-3-methyl-3,4-dihydropyridine-1(2H)-carboxylate (1.01 g, 75%). MS m / z (ESI): 331 [M+H] + . 【0302】 Step 9: Synthesis of (S)-5-(5-methyl-3,4,5,6-tetrahydropyridine-2-yl)benzo[d]thiazole 【0303】 [ka] 【0304】 A solution of tert-butyl(S)-6-(benzo[d]thiazole-5-yl)-3-methyl-3,4-dihydropyridine-1(2H)-carboxylate (1.01 g, 3.05 mmol) in dichloromethane (9 mL) with trifluoroacetic acid (3 mL, 2.68 mmol). mmol) was added. The reaction was carried out overnight at 25°C. After concentrating the reaction mixture, water was added to dilute it, the pH was adjusted to 8 with aqueous ammonia, and the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain (S)-5-(5-methyl-3,4,5,6-tetrahydropyridine-2-yl)benzo[d]thiazole (0.70 g, 92%). MS m / z (ESI): 231 [M+H] + . 【0305】 Step 10: Synthesis of 5-((2R,5S)-5-methylpiperidine-2-yl)benzo[d]thiazole 【0306】 [ka] 【0307】 (S)-5-(5-methyl-3,4,5,6-tetrahydropyridine-2-yl)benzo[d]thiazole (0.70 g, 3.04 mmol) in methanol (5 Sodium borohydride (308 mg, 9.12 mmol) was added to the (mL) solution. The reaction mixture was stirred at room temperature for 45 minutes. After concentrating the reaction mixture, it was diluted with water, the pH was adjusted to 8 with aqueous ammonia, and the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain 5-((2R,5S)-5-methylpiperidine-2-yl)benzo[d]thiazole (0.69 g, 98%). MS m / z (ESI): 233 [M+H] + . 【0308】 1 H NMR (400 MHz, CDCl3) δ 8.98 (s, 1H), 8.15 (d, J = 1.7 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.56 (dd, J = 8.3, 1.7 Hz, 1H), 3.78 (dd, J = 11.4, 2.6 Hz, 1H), 3.22-3.13 (m, 1H), 2.48 (t, J = 11.4 Hz, 1H), 1.97-1.87 (m, 2H), 1.86-1.68 (m, 2H), 1.30-1.19 (m, 1H), 0.92 (d, J = 6.6 Hz, 3H). Intermediate 49 was prepared by selecting the corresponding raw materials by referring to the synthesis method of all or part of intermediate 48. 【0309】 [Table 7] 【0310】 Preparation of intermediate 50, (3R,5S)-3-methyl-5-(5-(trifluoromethyl)pyridine-2-yl)morpholine 【0311】 [ka] 【0312】 Step 1: Synthesis of (R)-1-((tributylstannyl)methoxy)propan-2-amine 【0313】 [ka] 【0314】 Sodium hydride (204 mg, 5.10 mmol, in 60% kerosene) was dissolved in N,N-dimethylformamide (20 mL), cooled in an ice bath, and (R)-2-aminopropan-1-ol (0.36 mL, 4.64 mmol) was gradually added dropwise. After the addition was complete, the mixture was stirred at room temperature for 1 hour. The reaction mixture was cooled in an ice bath, and a solution of tributyl(iodomethyl) stannane (2.00 g, 4.64 mmol) in N,N-dimethylformamide (20 mL) was gradually added dropwise, and the mixture was stirred at room temperature overnight. The reaction mixture was cooled in an ice bath, saturated ammonium chloride solution was gradually added to quench the reaction, and the mixture was separated. The organic phase was washed with saturated brine. The organic phase was concentrated by rotary evaporation, and the crude product was separated by column chromatography to obtain (R)-1-((tributylstannyl)methoxy)propan-2-amine (1.30 g, 71%). MS m / z (ESI): 380 [M+H] + . 【0315】 Step 2: Synthesis of (R,E)-N-(1-((tributylstannyl)methoxy)propan-2-yl)-1-(5-(trifluoromethyl)pyridine-2-yl)methanymine 【0316】 [ka] 【0317】 (R)-1-((tributylstannyl)methoxy)propan-2-amine (800 mg, 2.11 mmol) was dissolved in dichloromethane (20 mL), and 5-(trifluoromethyl)pyridine-2-carbaldehyde (370 mg, 2.11 mmol) and molecular sieves (1.50 g, 3.41 mmol) were added. The mixture was stirred overnight at room temperature. The reaction mixture was filtered, washed with dichloromethane, and the filtrate was concentrated by rotary evaporation to obtain (R,E)-N-(1-((tributylstannyl)methoxy)propan-2-yl)-1-(5-(trifluoromethyl)pyridine-2-yl)methanymine (1100 mg, 97%). 【0318】 1 H NMR (400 MHz, CDCl3) δ 8.90 (dt, J = 1.9, 0.9 Hz, 1H), 8.40 (s, 1H), 8.14 (dt, J = 8.3, 0.9 Hz, 1H), 7.95 (dd, J = 8.3, 2.3 Hz, 1H), 3.79-3.63 (m, 3H), 3.43 (d, J = 6.2 Hz, 2H), 1.48-1.36 (m, 6H), 1.28-1.18 (m, 9H), 0.95-0.81 (m, 15H). 【0319】 Third step: Synthesis of (3R,5S)-3-methyl-5-(5-(trifluoromethyl)pyridine-2-yl)morpholine 【0320】 [ka] 【0321】 (S,S)-2,2'-isopropylidenebis(4-phenyl-2-oxazoline) (70 mg, 0.21 mmol) was dissolved in hexafluoroisopropanol (10 mL), copper trifluoromethanesulfonate (151 mg, 0.42 mmol) was added, and the mixture was stirred overnight at room temperature. A solution of (R,E)-N-(1-((tributylstannyl)methoxy)propan-2-yl)-1-(5-(trifluoromethyl)pyridine-2-yl)methanymine (1113 mg, 2.08 mmol) in hexafluoroisopropanol (5 mL) was added to the reaction mixture using a syringe, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with dichloromethane and aqueous ammonia, separated, and the organic phase was concentrated by rotary evaporation. The crude product was separated by reverse-phase column chromatography to obtain (3R,5S)-3-methyl-5-(5-(trifluoromethyl)pyridine-2-yl)morpholine (195 mg, 37%). MS m / z (ESI): 247 [M+H] + . 【0322】 II. Manufacturing of the Examples Example 1: (R)-4-amino-1-methyl-N-(1-(pyrimidine-2-yl)ethyl)-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)imidazo[ 1,5-a]Quinoxaline-8-carboxamide preparation 【0323】 [ka] 【0324】 4-amino-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid (30.0 mg, 0.12 mmol) and 2-methoxy-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)ethane-1-amine (34.9 mmol, 0.12 mmol) were dissolved in N,N-dimethylacetamide (3 mL). Bromotripyrrolidinophosphonium hexafluorophosphate (75.1 mmol, 0.16 mmol) and N,N-diisopropylethylamine (48.0 mg, 0.37 mmol) were added, and the mixture was stirred overnight at room temperature. After the reaction was complete, water was added to quench the mixture, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The mixture was separated by silica gel column chromatography [9% methanol-dichloromethane system] to obtain the crude product, which was then further filtered by reverse-phase column chromatography [50% acetonitrile-10 The compound was separated using an nM ammonium bicarbonate aqueous solution and freeze-dried to obtain (R)-4-amino-1-methyl-N-(1-(pyrimidine-2-yl)ethyl)-N-((5-(trifluoromethyl)pyridine-2-yl)methyl)imidazo[1,5-a]quinoxaline-8-carboxamide (18 mg, 28%). MS m / z (ESI): 507 [M+H] + . 【0325】 1 H NMR (400 MHz, DMSO-d6) δ 8.88-8.76 (m, 3H), 8.29 (s, 1H), 8.11 (dd, J = 8.5, 2.4 Hz, 1H), 7.80 (s, 1H), 7.61-7.47 (m, 3H), 7.41 (t, J = 4.9 Hz, 1H), 7.30 (s, 2H), 5.56 (s, 1H), 5.00-4.47 (m, 2H), 2.89 (s, 3H), 1.60 (d, J = 7.0 Hz, 3H). 【0326】 Example 2: Preparation of (S)-4-amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazole-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)imidazo[1,5-a]quinoxaline-8-carboxamide 【0327】 [ka] 【0328】 Step 1: Synthesis of 4-amino-7-fluoro-1-methylimidazo[1,5-a]quinoxaline-8-carbonyl chloride hydrochloride 【0329】 [ka] 【0330】 4-amino-7-fluoro-1-methylimidazo[1,5-a]quinoxaline-8-carboxylic acid (100 mg, 0.38 mmol) was placed in dichloromethane (10 mL), and 1,4-dioxane hydrochloride (0.5 mL, 2.0 mmol, 4 mol / L) was added. The mixture was stirred at room temperature for half an hour, and the reaction was concentrated by swift evaporation under reduced pressure until dry. Sulfoxide chloride (1.0 mL, 13.79 mmol) was added to the residue and the mixture was reacted overnight at 65°C with stirring. The reaction was concentrated by swift evaporation under reduced pressure, and dry dichloromethane (5 mL) was added to the residue. After concentration by swift evaporation, 4-amino-7-fluoro-1-methylimidazo[1,5-a]quinoxaline-8-carbonyl chloride hydrochloride (118 mg, 99%) was obtained. MS m / z (ESI): 275 [M+H] + . 【0331】 Step 2: Synthesis of (S)-4-amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazole-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)imidazo[1,5-a]quinoxaline-8-carboxamide 【0332】 [ka] 【0333】 4-amino-7-fluoro-1-methylimidazo[1,5-a]quinoxaline-8-carbonyl chloride hydrochloride (77 mg, 0.24 mmol) was placed in dichloroethane (6 mL), pyridine (0.10 mL, 1.22 mmol) and (S)-1-methyl-N-(6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)-1H-pyrazole-4-amine (69 mg, 0.24 mmol) were added, and the mixture was reacted at 60°C for 5 hours with stirring. After the reaction was complete, the reaction mixture was concentrated by rotary evaporation, and the crude product was separated by reverse-phase column chromatography to obtain ((S)-4-amino-7-fluoro-1-methyl-N-(1-methyl-1H-pyrazole-4-yl)-N-(6-(trifluoromethyl)-2,3-dihydrobenzofuran-3-yl)imidazo[1,5-a]quinoxaline-8-carboxamide (32 mg, 25%). MS m / z (ESI): 526 [M+H] + . 【0334】 1 H NMR (400 MHz, DMSO-d6) δ 7.96 (d, J = 6.2 Hz, 1H), 7.80 (s, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.46 (s, 2H), 7.41 (s, 1H), 7.33 (d, J = 7.9 Hz, 1H), 7.11 (s, 1H), 6.99 (d, J = 10.6 Hz, 1H), 6.87 (s, 1H), 6.61 (s, 1H), 4.88 (t, J = 10.0 Hz, 1H), 4.67 (dd, J = 10.6, 4.0 Hz, 1H), 3.50 (s, 3H), 2.93 (s, 3H). Examples 3 to 233 were prepared by selecting the appropriate raw materials by referring to all or part of the synthesis method of Example 1 or Example 2. 【0335】 Table 8 TIFF0007873890000114.tif198157TIFF0007873890000115.tif189159TIFF0007873890000116.tif212159TIFF0007873890000117.tif226159TIFF0007873890000118.tif229159TIFF0007873890000119.tif232159TIFF0007873890000120.tif235159TIFF0007873890000121.tif200159TIFF0007873890000122.tif208158TIFF0007873890000123.tif236158TIFF0007873890000124.tif225158TIFF0007873890000125.tif226158TIFF0007873890000126.tif237158TIFF0007873890000127.tif232155TIFF0007873890000128.tif208158TIFF0007873890000129.tif236158TIFF0007873890000130.tif230158TIFF0007873890000131.tif210158TIFF0007873890000132.tif235156TIFF0007873890000133.tif211158TIFF0007873890000134.tif237158TIFF0007873890000135.tif210158TIFF0007873890000136.tif210158TIFF0007873890000137.tif211158TIFF0007873890000138.tif215158TIFF0007873890000139.tif219158TIFF0007873890000140.tif225157TIFF0007873890000141.tif220157TIFF0007873890000142.tif221157TIFF0007873890000143.tif227157TIFF0007873890000144.tif232157TIFF0007873890000145.tif236157TIFF0007873890000146.tif209157TIFF0007873890000147.tif222157TIFF0007873890000148.tif231157T IFF0007873890000149.tif221157TIFF0007873890000150.tif212157TIFF0007873 890000151.tif212157TIFF0007873890000152.tif212156TIFF0007873890000153. tif234157TIFF0007873890000154.tif234157TIFF0007873890000155.tif151157. 【0336】 The nuclear magnetic data of the compounds produced in the above examples are as follows. 【0337】 [Table 9] TIFF0007873890000157.tif236156TIFF0007873890000158.tif233156TIFF000 7873890000159.tif236156TIFF0007873890000160.tif231157TIFF0007873890 000161.tif235157TIFF0007873890000162.tif227157TIFF0007873890000163. tif235156TIFF0007873890000164.tif236156TIFF0007873890000165.tif57156 【0338】 Biological measurement and evaluation 1. Human colon cancer HCT116 cell proliferation inhibition test 1. HCT116 MTAP knockout and MTAP wild-type cells were seeded in 96-well flat-bottom plates and cultured overnight at 37°C under 5% CO2 conditions in McCoy's 5A medium containing 10% fetal bovine serum + 1% penicillin-streptomycin. 【0339】 2. The following day, the compound was dissolved in DMSO, and the compound was sequentially diluted with DMSO and culture medium and transferred to a cell plate. The compound was then diluted fourfold to a final concentration of 10 μM, and a DMSO control was added in a 9-concentration gradient. 【0340】 3. Cells that had not been treated with the compound were isolated, and cell activity was detected using the CellTiter-Glo Luminescent Cell Viability Assay (Promega) in accordance with the instructions in the reagent kit. Then, the cell plate was placed on an EnVision Multilabel Reader to detect the luminescence signal. 【0341】 4. Simultaneously, cell plates treated with the compound were cultured continuously for 6 days at 37°C under 5% CO2 conditions. 5. Next, cell activity was similarly detected using CellTiter-Glo. 【0342】 6. Finally, the dose-response curve was plotted using the 4-parameter dose-response curve module of GraphPad Prism v 9.2.0 software, and the growth inhibition IC was observed. 50 The values ​​(in nM) were calculated. The test results are as follows: 【0343】 [Table 10] TIFF0007873890000167.tif186155 【0344】 According to the biological activity data of the compounds in specific examples, the series of compounds of the present invention exhibits very strong inhibitory activity against the proliferation of human colon cancer HCT116 MTAP knockout cells at the cellular level and has very high selectivity for wild-type cells. 【0345】 All documents relating to the present invention are cited herein by reference, so as each document is cited independently. Furthermore, after reading the foregoing disclosure of the present invention, those skilled in the art can make various variations and modifications to the invention, and these equivalent forms should be understood to be included in the claims attached to this application.

Claims

[Claim 1] A compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof, 【Chemistry 1】 Here, the compound represented by formula (I) has the structure of the compound represented by the following formulas (IV 1-1), (IV 1-2), (IV 2-1), or (IV 2-2): 【Chemistry 2】 Here, each X 4 is independently CR 6 or N, and each X 5 is independently CR 7 or N. Each Y6 and each Y7 is independently CH or N, Z is O or CH2, and p is 1 or 2. In the structure of the compound represented by formula (IV 2-1) or (IV 2-2), ring B, together with the substituents on it, has the following structure: 【Transformation 3】 q is selected from 0, 1 or 2, Each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, trifluoromethyl group, trideuteromethyl group, methoxy group, ethoxy group, cyclopropyl group, and -SF5. Each R'' is independently selected from hydrogen, deuterium, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R2 is independently 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, cyclohexyl group, oxetanyl group, azetidinyl group, tetrahydrofuranyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyridyl group, pyridadinyl group, pyrimidinyl group, and triazinyl group, and each of these groups may be independently and optionally further selected from deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group Substituted by one or more substituents selected from the following groups: hydroxyl group, isobutyl group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, diduteromethyl group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azacyclopentyl group, tetrahydrofuranyl group, phenyl group, pyrazolyl group, 2-(trimethylsilyl)ethoxy group, methyl-substituted pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyridyl group, fluorine-substituted pyridyl group, pyridadinyl group, pyrimidinyl group, triazinyl group, =O, =S, -SF5, hydroxyl group, methoxy group, ethoxy group, cyclopropoxy group, cyclobutoxy group, amino group, methylamino group and dimethylamino group, Each R a 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, methoxy group, ethoxy group, trifluoromethyl group, difluoromethyl group, trideuteromethyl group, diduteromethyl group, trifluoromethoxy group, trideuteromethoxy group, vinyl group, ethynyl group, cyclopropyl group, cyclobutyl group, methyl-substituted cyclopropyl group, methyl-substituted cyclobutyl group, cyclopropoxy group, cyclobutoxy group, oxetanyl group, azetidinyl group, tetrahydropyrrolyl group, piperidinyl group, methyl-substituted piperidinyl group, phenyl group, pyrazolyl group, imidazolyl group, triazolyl group, oxazolyl group, thiazolyl group, pyrimidinyl group, methyl-substituted pyrazolyl group, -SF5, hydroxyl group, amino group, methylamino group, dimethylamino group, dimethylaminomethyl group, and dimethylaminoethyl group. Each R6 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, trideuteromethyl group, trideuteromethoxy group, and cyclopropyl group. Each R7 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, triduomethyl group, triduomethoxy group, and cyclopropyl group. Each R8 is independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, hydroxyl group, methyl group, ethyl group, n-propyl group, isopropyl group, methoxy group, trifluoromethyl group, trifluoromethoxy group, trideuteromethyl group, trideuteromethoxy group, and cyclopropyl group. R11 and R12 are each independently selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. A compound represented by formula (I), its stereoisomer, or a pharmaceutically acceptable salt thereof. [Claim 2] Included in the structure 【Chemistry 4】 The structure is as follows: 【Transformation 5】 Selected from, R ７ It is selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group, R ８ It is characterized by being selected from hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 3] Formula (IV １－２ ) and (IV ２－１ The structure of the compound represented by ) 【Transformation 6】 The structure is as follows: 【Transformation 7】 Selected from, Formula (IV １－１ The structure of the compound represented by ) 【Transformation 8】 The structure is as follows: 【Chemistry 9】 Selected from, Each R ａ These are, independently, hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, isopropyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF ５ Characterized by being selected from A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 4] Each R ２ Each of these groups is independently selected from hydrogen, deuterium, methyl group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, cyclobutyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azetidinyl group, tetrahydrofuranyl group, pyrazolyl group, imidazolyl group, thiazolyl group, pyridyl group and pyrimidinyl group, and each of these groups is independently and optionally further selected from deuterium, fluorine, chlorine, bromine, cyano group, methyl group, ethyl group, n-propyl group, isopropyl group, trifluoromethyl group, difluoromethyl group, Characterized by being substituted with one or more substituents selected from trideuteromethyl group, diduteromethyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, bicyclo[1.1.1]pentyl group, cyclohexyl group, oxetanyl group, azetidinyl group, tetrahydrofuranyl group, pyrazolyl group, (2-(trimethylsilyl)ethoxy)methyl-substituted pyrazolyl group, imidazolyl group, thiazolyl group, pyridyl group, fluorine-substituted pyridyl group, pyrimidinyl group, methoxy group, ethoxy group, and cyclopropoxy group. A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 5] Each R ２ is independently hydrogen, deuterium, a methyl group, an ethyl group, a trifluoromethyl group, a trifluoroethyl group, a trideuteromethyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, a cyclobutyl group or a substituent structure represented by the following: 【Chemistry 10】 Characterized by being selected from A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 6] The compound represented by formula (I) is the compound represented by the following formula (V １－１－１ ) or formula (V １－１－２ The compound has the structure represented by ), 【Chemistry 11】 Here, each Y ７ Each is independently CH or N, and each Z is independently O or CH ２ And each R ａ These are, independently, hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF ５ Selected from, Each R ７ Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R ８ Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Here, R ２ The features are as described in claim 1. A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 7] The compound represented by formula (I) is the compound represented by the following formula (V １－２－１ ) or formula (V １－２－２ )in Having the structure of the compound shown, 【Chemistry 12】 Here, each Y ６ and each Y ７ Each is independently CH or N, and R ａ This includes hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group and -SF ５ Selected from, R ７ It is selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group, R ８ (Selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group and cyclopropyl group) A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 8] The compound represented by formula (I) is the compound represented by the following formula (V ２－１－１ ) or formula (V ２－１－２ The compound has the structure represented by ), 【Chemistry 13】 Here, each R ａ These are, independently, hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, and -SF ５ Selected from, Each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R ７ Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R ８ Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 9] The compound represented by formula (I) is the compound represented by the following formula (V ２－２－１ ) or formula (V ２－２－２ The compound has the structure represented by ), 【Chemistry 14】 Here, each R ａ These are, independently, hydrogen, deuterium, fluorine, chlorine, bromine, cyano group, methyl group, methoxy group, trifluoromethyl group, trideuteromethyl group, trifluoromethoxy group, trideuteromethoxy group, cyclopropyl group, pyrazolyl group, methyl-substituted pyrazolyl group, methyl-substituted piperidinyl group, dimethylaminoethyl group, and -SF ５ Selected from, Each R' is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R ７ Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. Each R ８ Each of these is independently selected from hydrogen, deuterium, fluorine, chlorine, cyano group, methyl group, trifluoromethyl group, trideuteromethyl group, and cyclopropyl group. A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 10] The following compounds: 【Chemistry 15】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 Characterized by being selected from A compound represented by formula (I) according to any one of claims 1 to 9, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [Claim 11] A drug composition, The drug composition is characterized by comprising a compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. [Claim 12] Use of a compound represented by formula (I) according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating MTAP-associated tumors. [Claim 13] The tumor is characterized by being selected from cell tumors, lymphomas, leukemias, osteomas, malignant teratomas, carcinomas in situ, adenomas, fibromas, melanomas, fallopian tube cancers, bladder cancers, teratomas, fetal carcinomas, choriocarcinomas, lipomas, liver cancers, bile duct cancers, lung cancers, gastric cancers, hemangiomas, gallbladder cancers, ampulla cancers, malignant melanomas, nevi, dysplastic nevi, myeloproliferative disorders, Hodgkin's disease, chordomas, myxomas, rhabdomyomas, leiomyomas, hamartomas, mesotheliomas, insulinomas, glucagonomas, gastrinomas, carcinoid tumors, snake venomous tumors, granulomas, xanthomas, osteoosteitis, ependymomas, schwannomas, congenital tumors, meningiomas, gliomas, skin cancers, head and neck cancers, and sarcomas. The use described in claim 12. [Claim 14] The aforementioned cell tumors are selected from granular-follicular cell tumors, Sertoli cell tumors, germ cell tumors, nephroblastomas, seminomas, hepatoblastomas, malignant fibrous histiocytomas, chondroblastomas, giant cell tumors, astrocytomas, medulloblastomas, glioblastoma multiforme, oligodendrogliomas, retinoblastomas, squamous cell carcinomas, clear cell carcinomas, transitional cell carcinomas, stromal cell carcinomas, and basal cell carcinomas. The aforementioned lymphomas are selected from malignant lymphomas and non-Hodgkin lymphomas. The aforementioned leukemia is selected from acute chronic myeloid leukemia, acute lymphoblastic leukemia, and chronic lymphoblastic leukemia. The aforementioned osteomas are selected from osteochondroma, benign chondroma, osteoid osteoma, chondromatoid hamartoma, multiple myeloma, and cranial osteoma. The adenoma is selected from fibroadenoma, adenomatous tumor, hepatocellular adenoma, bronchial adenoma, tubular adenoma, chorioadenoma, breast cancer, pancreatic cancer, endometrial adenocarcinoma, prostate cancer, ductal adenocarcinoma, and colorectal adenocarcinoma. The fibroma is selected from fibroma, chondromyxofibroma, neurofibroma, and spinal neurofibroma. The aforementioned myeloproliferative disorders are selected from multiple myeloma and myelodysplastic syndromes. The lung cancers mentioned above are selected from bronchopulmonary cancer and alveolar cancer. The aforementioned sarcoma is characterized by being selected from fibrosarcoma, staphyloid sarcoma, angiosarcoma, Kaposi's sarcoma, osteosarcoma, chondrosarcoma, Ewing's sarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, and meningiosarcoma. The use described in claim 13. [Claim 15] A compound represented by formula (I) as described in claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, A compound represented by formula (I) according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, characterized by being used as a PRMT5 inhibitor.

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