Compounds containing five-membered heteroaryl ring structures, pharmaceutical compositions and uses thereof

Abstract

The present invention discloses a compound containing a five-membered heteroaryl ring structure, its pharmaceutical composition and use. The present invention provides a compound containing a five-membered heteroaryl ring structure represented by formula I, its pharma- ceutically acceptable salt, its stereoisomer, its tautomer or its isotope. The compound containing a five-membered heteroaryl ring structure is expected to be used for the treatment and / or prevention of several diseases associated with poly(ADP-ribose) glycohydrolase (PARG). [Formula 1] TIFF2025509180000268.tif30163

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the priority of Chinese Patent Application No. 202210214607.4, filed on March 4, 2022, the priority of Chinese Patent Application No. 202210831127.2, filed on July 15, 2022, and the priority of Chinese Patent Application No. 202211288698.2, filed on October 20, 2022. The entire contents of the above Chinese patent applications are incorporated herein by reference.

[0002] The present invention relates to compounds containing five-membered heteroaryl ring structures, pharmaceutical compositions and uses thereof. [Background technology]

[0003] The division and proliferation of cancer cells is often uncontrolled, leading to a higher incidence of DNA damage and defective DNA repair, making them more dependent on DNA damage repair mechanisms than normal cells.

[0004] Poly(ADP-ribose) polymerase (PARP), poly(ADP-ribose) glycohydrolase (PARG), and several other proteins play important roles in DNA repair and are important targets for anticancer drug research and development. PARP binds to breaks in single-stranded DNA and promotes the production of poly(ADP-ribose) (PARG) chains, thereby initiating the repair process. PARG's role is to degrade PAR on PARP and promote the completion of the entire repair cycle. Inhibition of either PARP or PARG affects the entire repair process.

[0005] Currently, the research and development of PARP inhibitors has achieved great success, with several drugs already approved and on the market, demonstrating the feasibility of targeting DNA repair proteins. However, PARP inhibitors are not effective in all patients and have issues such as drug resistance. Research on PARG inhibitors is still in the exploratory stage, and no compounds have yet entered clinical trials. There is ample room for research in this targeting direction, and it is expected that they will fulfill unmet clinical needs. Summary of the Invention [Problem to be solved by the invention]

[0006] The technical problem that the present invention aims to solve is that the prior art lacks effective pharmaceuticals for use in clinical treatment as PARG inhibitors. Therefore, the present invention provides a five-membered heteroaryl ring structure-containing compound, pharmaceutical composition thereof and use thereof, and the five-membered heteroaryl ring structure-containing compound is expected to be used in the treatment and / or prevention of several types of diseases associated with PARG. [Means for solving the problem]

[0007] The present invention solves the above technical problems by the following technical solutions.

[0008] The present invention provides a five-membered heteroaryl ring structure-containing compound represented by formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof, [ka] however," [ka] " represents a single or double bond, [ka] The two cyclos in the ring are both aromatic. R a1, R a2 and R a3 are independently hydrogen, halogen, cyano group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, OR a-1 , C(=O)R a-2 , -NR a-31 R a-32 , -C(=O)OR a-4 , -C(=O)NR a-51 R a-52 , or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen, a hydroxy group or -OC 1-6 is an alkyl group, Or R a2 and R a3 is the connected carbon atom and C 3-7 Cycloalkane, one or more R a2-1 C replaced with 3-7 Cycloalkane, "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R a2-2 and when there are a plurality of substituents, they may be the same or different, and R a2-1 and R a2-2 are independently halogen, oxo, hydroxyl group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, R a-1 , R a-2 , R a-31 , R a-32 , R a-4 , R a-51 and R a-52 are independently H, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, X is *-NH-S(O) y -or*-S(O) y -NH-, where y is 1 or 2, and * indicates that one end marked with * is [ka] and A1 is N or CR 1 and R 1 is hydrogen, cyano group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 alkyl group, one or more R 1-1 C replaced with 1-6 Alkyl group, halogen, hydroxy group, -OC 1-6 alkyl group, one or more R 1-2 -OC substituted with 1-6 Alkyl group, -C(=O)R 1a , -NR 1b1 R 1b2 , -C(=O)OR 1c , -C(=O)NR 1d1 R 1d2 , C 3-10 cycloalkyl group, one or more R 1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-4 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-7 C replaced with 5-7a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-8 "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-9 C replaced with 2-6 an alkynyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1 , R 1-2 , R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 and R 1-9 are independently an azide group, a halogen, a hydroxy group, a cyano group, an oxo group, or C 1-6 alkyl group, one or more R 1-1-1 C replaced with 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OC 1-6 alkyl group, one or more R 1-1-2 -OC substituted with 1-6 Alkyl group, -C(=O)R 11a , -NR 11b1 R 11b2 , -C(=O)OR 11c , -C(=O)NR 11d1 R 11d2 , -S(O)NR 11e1 R 11e2 , -S(O)2R 11f , C 3-10 cycloalkyl group, one or more R 1-1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-1-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-1-5 C replaced with 6-20an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-1-8 and when there are a plurality of substituents, they may be the same or different, R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 and R 1-1-8 are independently halogen, oxo, -C(=O)R 11g , hydroxy group, C 1-6 an alkyl group or one or more R 1-1-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1-1-1 is a halogen, hydroxy group, -OC 1-6 Alkyl group or -NR a R b and R a and R b are independently hydrogen or C 1-6 is an alkyl group, R 1a , R 1b1 , R 1b2 , R 1c , R 1d1 , R 1d2 , R 11a , R 11b1 , R 11b2 , R 11c , R 11d1 , R 11d2 , R 11e1 , R11e2 , R 11f and R 11g are independently hydrogen, C 1-6 alkyl group, one or more R 1-2-1 C replaced with 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 1-2-2 -OC substituted with 1-6 Alkyl group, C 3-10 cycloalkyl group, one or more R 1-2-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-2-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-2-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-2-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-2-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-2-8 "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with -C(=O)R 11h and R 11h is C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1 , R 1-2-2 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 and R 1-2-8are independently a halogen, a hydroxy group, or -NR 12c R 12d , Oxo, C 1-6 an alkyl group or one or more R 1-2-1-1 C replaced with 1-6 is an alkyl group, and R 12c and R 12d are independently hydrogen or C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1-1 are independently a halogen, a hydroxy group, or -OC 1-6 Alkyl group or -NR c R d and R c and R d are independently hydrogen or C 1-6 is an alkyl group, Or R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 , R 1-1-8 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 , and R 1-2-8 If the number of is greater than 1, then two optional R 1-3 , two optional R 1-4 , two optional R 1-5 , two optional R 1-6 , two optional R 1-7 , two optional R 1-8 , two optional R 1-1-3 , two optional R 1-1-4 , two optional R 1-1-5 , two optional R 1-1-6 , two optional R 1-1-7 , two optional R 1-1-8 , two optional R 1-2-3 , two optional R 1-2-4, two optional R 1-2-5 , two optional R 1-2-6 , two optional R 1-2-7 , or optionally two R 1-2-8 are connected to each other and independently form a 3- to 8-membered carbocyclic ring together with the atoms connected thereto, one or more R 1-3-1 a 3- to 8-membered carbocyclic ring substituted with one or more R 1-3-2 "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 Aromatic ring, one or more R 1-3-3 C replaced with 6-20 an aromatic ring, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-3-4 "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with C 5-7 Cycloolefin, one or more R 1-3-5 C replaced with 5-7 Cycloolefin, "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-3-6 and when there are a plurality of substituents, they may be the same or different, to form a "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with R 1-3-1 , R 1-3-2 , R 1-3-3 , R 1-3-4 , R 1-3-5 and R 1-3-6 are independently oxo, hydroxyl, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; Or R a-31 and R a-32 , Ra-51 and R a-52 , R 1b1 and R 1b2 , R 1d1 and R 1d2 , R 11b1 and R 11b2 , R 11d1 and R 11d2 , R 11e1 and R 11e2 , R a and R b , R c and R d , R 12c and R 12d are each independently, together with the N to which they are linked, a "3- to 8-membered heterocycle in which one is N and the others are independently selected from O, S, and N and contain 1 to 3 heteroatoms," or one or more R 1-4-1 and forming a "3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-4-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; A2 and A3 are independently N or CR 2 and R 2 is hydrogen or halogen, When a, b, and c are single bonds, A4 is NR 4a and A5 is N or CR 5b and When b is a single bond and a and c are double bonds, A4 is N or CR 4d and A5 is O, S or NR 5d and R 6 means "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R 6-1and a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R 6-1 is a halogen, hydroxy group, cyano group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, one or more -OC 1-6 Alkyl-substituted C 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 4a and R 4d are independently hydrogen, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 alkyl group or one or more R 4-1 C replaced with 1-6 is an alkyl group, and R 4-1 is a hydroxy group or -OC 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 5b and R 5d is independent, [ka] and L1 is a connecting bond, C 1-6 an alkylene group or —C(═O)—; Q1 is hydrogen, halogen, cyano group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, hydroxy group, -C(=O)R 52a , -NR 52b1 R 52b2 , -C(=O)OR 52c , -C(=O)NR 52d1 R 52d2 , C substituted with one or more halogens 1-6 alkyl groups, C substituted with one or more hydroxy groups 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R5-1-1 -OC substituted with 1-6 Alkyl group, C 6-20 an aryl group, one or more R 5-1-2 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 5-1-3 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 3-12 cycloalkyl group, one or more R 5-1-4 C replaced with 3-12 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 5-1-5 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 5-7 Cycloalkenyl group, one or more R 5-1-6 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 5-1-7 and when there are a plurality of substituents, they may be the same or different, Or R 1 and R 5d are linked to each other and together with the atoms linked thereto form a "5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N," R 5-1-1 , R 5-1-2 , R 5-1-3 , R 5-1-4 , R 5-1-5 , R 5-1-6 and R 5-1-7 are independently a halogen, a hydroxy group, an oxo group, a cyano group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, C 2-6 Alkenyl group, C2-6 Alkynyl group, -OC 1-6 Alkyl groups, -OC substituted with one or more halogens 1-6 Alkyl group, -C(=O)R 51a , -NR 51b1 R 51b2 , -C(=O)OR 51c , or -C(=O)NR 51d1 R 51d2 and when there is more than one substituent, they may be the same or different; R 52a , R 52b1 , R 52b2 , R 52c , R 52d1 , R 52d2 , R 51a , R 51b1 , R 51b2 , R 51c , R 51d1 and R 51d2 are independently hydrogen, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, Or R 52b1 and R 52b2 , R 52d1 and R 52d2 , R 51b1 and R 51b2 , R 51d1 and R 51d2 are each independently, together with the N to which they are linked, a "3- to 8-membered heterocycle in which one is N and the others are independently selected from O, S, and N and contain 1 to 3 heteroatoms," or one or more R 1-5-1 and forming a "3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-5-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 In the case of an alkyl group, when there are a plurality of substituents, they may be the same or different.

[0009] In one embodiment, in the five-membered heteroaryl ring structure-containing compound represented by formula I, its pharmaceutically acceptable salt, its stereoisomer, its tautomer, or its isotope, the five-membered heteroaryl ring structure-containing compound represented by formula I has the following structure: [ka] however," [ka] " represents a single or double bond, [ka] The two cyclos in the ring are both aromatic. R a1 , R a2 and R a3 are independently hydrogen, halogen, cyano group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, OR a-1 , C(=O)R a-2 , -NR a-31 R a-32 , -C(=O)OR a-4 , -C(=O)NR a-51 R a-52 , or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen, a hydroxy group or -OC 1-6 is an alkyl group, Or R a2 and R a3 is the connected carbon atom and C 3-7 Cycloalkane, one or more R a2-1 C replaced with 3-7 Cycloalkane, "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R a2-2and when there are a plurality of substituents, they may be the same or different, and R a2-1 and R a2-2 are independently halogen, oxo, hydroxyl group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, R a-1 , R a-2 , R a-31 , R a-32 , R a-4 , R a-51 and R a-52 are independently H, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, A1 is N or CR 1 and R 1 is hydrogen, cyano group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 alkyl group, one or more R 1-1 C replaced with 1-6 Alkyl group, halogen, hydroxy group, -OC 1-6 alkyl group, one or more R 1-2 -OC substituted with 1-6 Alkyl group, -C(=O)R 1a , -NR 1b1 R 1b2 , -C(=O)OR 1c , -C(=O)NR 1d1 R 1d2 , C 3-10 cycloalkyl group, one or more R 1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-4"4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-8 "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-9 C replaced with 2-6 an alkynyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1 , R 1-2 , R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 and R 1-9 are independently an azide group, a halogen, a hydroxy group, a cyano group, an oxo group, or C 1-6 alkyl group, one or more R 1-1-1 C replaced with 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OC 1-6 alkyl group, one or more R 1-1-2 -OC substituted with 1-6 Alkyl group, -C(=O)R 11a , -NR 11b1 R 11b2 , -C(=O)OR 11c , -C(=O)NR 11d1 R 11d2 , -S(O)NR 11e1R 11e2 , -S(O)2R 11f , C 3-10 cycloalkyl group, one or more R 1-1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-1-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-1-8 and when there are a plurality of substituents, they may be the same or different, R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 and R 1-1-8 are independently halogen, oxo, -C(=O)R 11g , hydroxy group, C 1-6 an alkyl group or one or more R 1-1-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1-1-1 is a halogen, hydroxy group, -OC 1-6 Alkyl group or -NR a Rb and R a and R b are independently hydrogen or C 1-6 is an alkyl group, R 1a , R 1b1 , R 1b2 , R 1c , R 1d1 , R 1d2 , R 11a , R 11b1 , R 11b2 , R 11c , R 11d1 , R 11d2 , R 11e1 , R 11e2 , R 11f and R 11g are independently hydrogen, C 1-6 alkyl group, one or more R 1-2-1 C replaced with 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 1-2-2 -OC substituted with 1-6 Alkyl group, C 3-10 cycloalkyl group, one or more R 1-2-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-2-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-2-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-2-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-2-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-2-8"5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with -C(=O)R 11h and R 11h is C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1 , R 1-2-2 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 and R 1-2-8 are independently a halogen, a hydroxy group, or -NR 12c R 12d , Oxo, C 1-6 an alkyl group or one or more R 1-2-1-1 C replaced with 1-6 is an alkyl group, and R 12c and R 12d are independently hydrogen or C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1-1 are independently a halogen, a hydroxy group, or -OC 1-6 Alkyl group or -NR c R d and R c and R d are independently hydrogen or C 1-6 is an alkyl group, Or R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 , R 1-1-8 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 , and R 1-2-8 If the number of is greater than 1, then two optional R 1-3 , two optional R 1-4, two optional R 1-5 , two optional R 1-6 , two optional R 1-7 , two optional R 1-8 , two optional R 1-1-3 , two optional R 1-1-4 , two optional R 1-1-5 , two optional R 1-1-6 , two optional R 1-1-7 , two optional R 1-1-8 , two optional R 1-2-3 , two optional R 1-2-4 , two optional R 1-2-5 , two optional R 1-2-6 , two optional R 1-2-7 , or optionally two R 1-2-8 are connected to each other and independently form a 3- to 8-membered carbocyclic ring together with the atoms connected thereto, one or more R 1-3-1 a 3- to 8-membered carbocyclic ring substituted with one or more R 1-3-2 "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 Aromatic ring, one or more R 1-3-3 C replaced with 6-20 an aromatic ring, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-3-4 "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with C 5-7 Cycloolefin, one or more R 1-3-5 C replaced with 5-7 Cycloolefin, "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-3-6 and when there are a plurality of substituents, they may be the same or different, to form a "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with R 1-3-1 , R 1-3-2, R 1-3-3 , R 1-3-4 , R 1-3-5 and R 1-3-6 are independently oxo, hydroxyl, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; Or R a-31 and R a-32 , R a-51 and R a-52 , R 1b1 and R 1b2 , R 1d1 and R 1d2 , R 11b1 and R 11b2 , R 11d1 and R 11d2 , R 11e1 and R 11e2 , R a and R b , R c and R d , R 12c and R 12d are each independently, together with the N to which they are linked, a "3- to 8-membered heterocycle in which one is N and the others are independently selected from O, S, and N and contain 1 to 3 heteroatoms," or one or more R 1-4-1 and forming a "3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-4-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; A2 and A3 are independently N or CR 2 and R 2 is hydrogen or halogen, When a, b, and c are single bonds, A4 is NR 4a and A5 is N or CR 5b and When b is a single bond and a and c are double bonds, A4 is N or CR 4d and A5 is O, S or NR 5d and R 6 means "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R 6-1 and a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R 6-1 is a halogen, hydroxy group, cyano group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, one or more -OC 1-6 Alkyl-substituted C 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 4a and R 4d are independently hydrogen, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 alkyl group or one or more R 4-1 C replaced with 1-6 is an alkyl group, and R 4-1 is a hydroxy group or -OC 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 5b and R 5d is independent, [ka] and L1 is a connecting bond, C 1-6 an alkylene group or —C(═O)—; Q1 is hydrogen, halogen, cyano group, C 2-6Alkenyl group, C 2-6 Alkynyl group, hydroxy group, -C(=O)R 52a , -NR 52b1 R 52b2 , -C(=O)OR 52c , -C(=O)NR 52d1 R 52d2 , C substituted with one or more halogens 1-6 alkyl groups, C substituted with one or more hydroxy groups 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 5-1-1 -OC substituted with 1-6 Alkyl group, C 6-20 an aryl group, one or more R 5-1-2 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 5-1-3 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 3-12 cycloalkyl group, one or more R 5-1-4 C replaced with 3-12 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 5-1-5 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 5-7 Cycloalkenyl group, one or more R 5-1-6 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 5-1-7 and when there are a plurality of substituents, they may be the same or different, Or R 1 and R 5dare linked to each other and together with the atoms linked thereto form a "5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N," R 5-1-1 , R 5-1-2 , R 5-1-3 , R 5-1-4 , R 5-1-5 , R 5-1-6 and R 5-1-7 are independently a halogen, a hydroxy group, an oxo group, a cyano group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OC 1-6 Alkyl groups, -OC substituted with one or more halogens 1-6 Alkyl group, -C(=O)R 51a , -NR 51b1 R 51b2 , -C(=O)OR 51c , or -C(=O)NR 51d1 R 51d2 and when there is more than one substituent, they may be the same or different; R 52a , R 52b1 , R 52b2 , R 52c , R 52d1 , R 52d2 , R 51a , R 51b1 , R 51b2 , R 51c , R 51d1 and R 51d2 are independently hydrogen, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, Or R 52b1 and R 52b2 , R 52d1 and R 52d2 , R 51b1 and R 51b2 , R 51d1 and R 51d2are independently, respectively, and together with the N to which they are linked, "a 3- to 8-membered heterocycle in which one is N and the others are independently selected from O, S, and N and contain 1 to 3 heteroatoms," or one or more R 1-5-1 and forming a "3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-5-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 In the case of an alkyl group, when there are a plurality of substituents, they may be the same or different.

[0010] In one embodiment, in the five-membered heteroaryl ring structure-containing compound represented by formula I, its pharmaceutically acceptable salt, its stereoisomer, its tautomer, or its isotope, some groups have the following definitions, and the definitions of groups not mentioned are as described in any of the embodiments of the present invention (hereinafter, the content of this paragraph is abbreviated as "in one embodiment"). In the five-membered heteroaryl ring structure-containing compound represented by formula I, R a1 is a cyano group, C 1-6 an alkyl group or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen, R a2 and R a3 independently, C 1-6 is an alkyl group, or R a2 and R a3 is the bonded carbon atom and C 3-7 forming a cycloalkane, X is *-NH-S(O) y -, where y is 1 or 2, and * indicates that one end marked with * [ka] and A1 is N or CR 1 and R 1 is hydrogen, one or more R 1-1 C replaced with 1-6 alkyl group, halogen, "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-3 C replaced with 3-10 cycloalkyl group, one or more R 1-4 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-8 "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-9 C replaced with 2-6 an alkynyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1 , R 1-3 , R 1-4 , R 1-5 , R 1-7 , R 1-8 and R 1-9 are independently an azide group, a halogen, a hydroxy group, C 1-6 alkyl group, one or more R 1-1-1 C replaced with 1-6 Alkyl group, C 6-20 Aryl group, -C(=O)R 11a , -NR 11b1 R 11b2 , -C(=O)NR 11d1 R 11d2 , -S(O)2R 11f"4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R 1-1-4 and when there are a plurality of substituents, they may be the same or different, R 1-1-1 and R 1-1-4 are independently -C(=O)R 11g , oxo, hydroxy group or one or more R 1-1-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1-1-1 are independently a hydroxy group, R 11a , R 11b1 , R 11b2 , R 11d1 , R 11d2 , R 11f and R 11g are independently hydrogen, C 1-6 alkyl group, one or more R 1-2-1 C replaced with 1-6 Alkyl group, C 3-10 cycloalkyl group, one or more R 1-2-3 C replaced with 3-10 cycloalkyl group, one or more R 1-2-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," or -C(=O)R 11h and R 11h is C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1 , R 1-2-3 and R 1-2-4 are independently a halogen, a hydroxy group, or -NR 12c R12d , or C 1-6 is an alkyl group, and R 12c and R 12d are independently hydrogen or C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; Or R 1-4 and R 1-8 If the number of is greater than 1, then two optional R 1-4 or two optional R's 1-8 are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms independently selected from O, S, and N" or a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," Or R 11d1 and R 11d2 are independently, respectively, taken together with the N to which they are linked, to form "a 3- to 8-membered heterocycloalkane, one of which is N and the others are independently 1 to 3 heteroatoms selected from O, S, and N," or one or more R 1-4-1 and forming a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-4-1 is halogen or oxo, A2 and A3 are independently N or CR 2 and R 2 is hydrogen or halogen, When a, b, and c are single bonds, A4 is NR 4a and A5 is N, When b is a single bond and a and c are double bonds, A4 is N or CR 4d and A5 is S or NR 5d and R 4a and R 4d are independently hydrogen, halogen, or one or more R 4-1 C replaced with 1-6 When the alkyl group has a plurality of substituents, the substituents may be the same or different. 4-1is a halogen, a hydroxy group or -OC 1-6 is an alkyl group, R 5d teeth, [ka] and L1 is a connecting bond or C 1-6 is an alkylene group, Q1 is hydrogen, cyano group, hydroxy group, C substituted with one or more halogens 1-6 alkyl groups, C substituted with one or more hydroxy groups 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 5-1-2 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 5-1-3 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 3-12 a cycloalkyl group, and when there are a plurality of substituents, they may be the same or different; Or R 1 and R 5d each form, together with the atom to which it is linked, a 5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N; R 5-1-2 and R 5-1-3 are independently halogen or C 1-6 is an alkyl group, R 6 is one or more R 6-1 and a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R 6-1 is C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 an alkyl group or one or more -OC 1-6 Alkyl-substituted C 1-6 In the case of an alkyl group, when there are a plurality of substituents, they may be the same or different.

[0011] In one embodiment, in the five-membered heteroaryl ring structure-containing compound of formula I, R a1 is a cyano group, C 1-6 an alkyl group or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen, R a2 and R a3 independently, C 1-6 is an alkyl group, or R a2 and R a3 is the bonded carbon atom and C 3-7 forming a cycloalkane, X is *-NH-S(O) y -, where y is 2 and * is the end marked with *. [ka] and A1 is N or CR 1 and R 1 is hydrogen, one or more R 1-1 C replaced with 1-6 alkyl group, halogen, "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-3 C replaced with 3-10 cycloalkyl group, one or more R 1-4 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R1-8 "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-9 C replaced with 2-6 an alkynyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1 , R 1-3 , R 1-4 , R 1-5 , R 1-7 , R 1-8 and R 1-9 are independently an azide group, a halogen, a hydroxy group, C 1-6 alkyl group, one or more R 1-1-1 C replaced with 1-6 Alkyl group, C 6-20 Aryl group, -C(=O)R 11a , -NR 11b1 R 11b2 , -C(=O)NR 11d1 R 11d2 , -S(O)2R 11f "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R 1-1-4 and when there are a plurality of substituents, they may be the same or different, R 1-1-1 and R 1-1-4 are independently -C(=O)R 11g , oxo, hydroxy group or one or more R 1-1-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1-1-1 are independently a hydroxy group, R 11a , R 11b1 , R 11b2 , R 11d1 , R 11d2 , R 11f and R 11gare independently hydrogen, C 1-6 alkyl group, one or more R 1-2-1 C replaced with 1-6 Alkyl group, C 3-10 cycloalkyl group, one or more R 1-2-3 C replaced with 3-10 cycloalkyl group, one or more R 1-2-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," or -C(=O)R 11h and R 11h is C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1 , R 1-2-3 and R 1-2-4 are independently a halogen, a hydroxy group, or -NR 12c R 12d , or C 1-6 is an alkyl group, and R 12c and R 12d are independently hydrogen or C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; Or R 1-4 and R 1-8 If the number of is greater than 1, then two optional R 1-4 or two optional R's 1-8 are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms independently selected from O, S, and N" or a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," Or R 11d1 and R 11d2 are independently, respectively, taken together with the N to which they are linked, to form "a 3- to 8-membered heterocycloalkane, one of which is N and the others are independently 1 to 3 heteroatoms selected from O, S, and N," or one or more R 1-4-1and forming a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-4-1 is a halogen or =O, A2 and A3 are independently N or CR 2 and R 2 is hydrogen or halogen, When a, b, and c are single bonds, A4 is NR 4a and A5 is N, When b is a single bond and a and c are double bonds, A4 is N or CR 4d and A5 is S or NR 5d and R 4a and R 4d are independently hydrogen, halogen, or one or more R 4-1 C replaced with 1-6 When the alkyl group has a plurality of substituents, the substituents may be the same or different. 4-1 is a halogen, a hydroxy group or -OC 1-6 is an alkyl group, R 5d teeth, [ka] and L1 is a connecting bond or C 1-6 is an alkylene group, Q1 is hydrogen, cyano group, hydroxy group, C substituted with one or more halogens 1-6 alkyl groups, C substituted with one or more hydroxy groups 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 5-1-2 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 5-1-3 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 3-12a cycloalkyl group, and when there are a plurality of substituents, they may be the same or different; Or R 1 and R 5d each form, together with the atom to which it is linked, a 5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N; R 5-1-2 and R 5-1-3 are independently halogen or C 1-6 is an alkyl group, R 6 is one or more R 6-1 and a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R 6-1 is C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 an alkyl group or one or more -OC 1-6 Alkyl-substituted C 1-6 In the case of an alkyl group, when there are a plurality of substituents, they may be the same or different.

[0012] In one embodiment, in the five-membered heteroaryl ring structure-containing compound represented by Formula I, its pharmaceutically acceptable salt, its stereoisomer, its tautomer, or its isotopic compound, some groups have the following definitions, and definitions that are not mentioned are as described in any embodiment of the present invention.

[0013] In one embodiment, R a1 , R a2 and R a3 independently, C 1-6 It is an alkyl group.

[0014] In one embodiment, R a1 is a cyano group, C 1-6 an alkyl group or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen.

[0015] In one embodiment, R a2 and R a3 is the bonded carbon atom and C 3-7 Form a cycloalkane, R a1 is a cyano group, C 1-6 an alkyl group or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen.

[0016] In one embodiment, X is -NH-S(O) y -, where y is 1 or 2, and * indicates that one end marked with * [ka] It indicates that it is connected to

[0017] In one embodiment, A1 is N.

[0018] In one embodiment, A1 is CR 1 is.

[0019] In one embodiment, R 1 is hydrogen, one or more R 1-1 C replaced with 1-6 Alkyl groups, halogens, one or more R 1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-4 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-7 C replaced with 5-7a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-8 "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-9 C replaced with 2-6 In the case of an alkynyl group, when there are multiple substituents, they may be the same or different.

[0020] In one embodiment, R 1-1 are independently halogen or one or more R 1-1-4 and a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with

[0021] In one embodiment, R 1-1 In R 1-1-4 may independently be one or more R 1-1-1-1 C replaced with 1-6 Alkyl group or -C(=O)R 11g and R 1-1-1-1 are independently hydroxy groups, and R 11g is C 1-6 It is an alkyl group.

[0022] In one embodiment, R 1-3 are independently -C(=O)NR 11d1 R 11d2 and R 11d1 and R 11d2 forms, together with the N atom to which it is linked, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N."

[0023] In one embodiment, R 1-4 are independently an azide group, a hydroxy group, or —C(═O)R 11a , C 1-6 alkyl group, one or more R 1-1-1 C replaced with 1-6 Alkyl group, C 6-20Aryl group, -C(=O)NR 11d1 R 11d2 , -S(O)2R 11f "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R 1-1-4 and when there are a plurality of substituents, they may be the same or different, or ... 1-4 If the number of is greater than 1, then two optional R 1-4 are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms independently selected from O, S, and N," and R 1-4 If the number of is greater than 1, then two optional R 1-4 are linked to each other and independently form, together with the atoms linked thereto, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N."

[0024] In one embodiment, R 1-4 In R 1-1-1 is a hydroxy group.

[0025] In one embodiment, R 1-4 In R 11a is C 1-6 Alkyl group, C 3-10 cycloalkyl group, one or more R 1-2-1 C replaced with 1-6 alkyl group, one or more R 1-2-3 C replaced with 3-10 Cycloalkyl groups, C 6-20 an aryl group or a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; R 1-2-1 is a halogen, a hydroxy group or -NR 12c R 12d and R 12c and R12d are independently hydrogen, and R 1-2-3 is C 1-6 It is an alkyl group.

[0026] In one embodiment, R 1-4 In R 11d1 and R 11d2 independently, C 1-6 alkyl group, one or more R 1-2-1 C replaced with 1-6 is an alkyl group, and R 1-2-1 Ha-NR 12c R 12d and R 12c and R 12d independently, C 1-6 is an alkyl group, or R 11d1 and R 11d2 means, together with the linked N atom, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," or one or more R 1-4-1 and R 1-4-1 is a halogen.

[0027] In one embodiment, R 1-4 In R 11f is C 1-6 It is an alkyl group.

[0028] In one embodiment, R 1-4 In R 1-1-4 is oxo.

[0029] In one embodiment, R 1-5 is -C(=O)NR 11d1 R 11d2 and R 11d1 and R 11d2 independently C 1-6 is an alkyl group, or R 11d1 and R 11d2forms, together with the N atom to which it is linked, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N."

[0030] In one embodiment, R 1-7 are independently C(=O)NR 11d1 R 11d2 or R 1-7 If the number of is greater than 1, then two optional R 1-7 are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 4 heteroatoms independently selected from O, S, and N."

[0031] In one embodiment, R 1-7 In R 11d1 and R 11d2 forms, together with the N atom to which it is linked, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N."

[0032] In one embodiment, R 1-8 is -C(=O)R 11a , -S(O)2R 11f , -C(=O)NR 11d1 R 11d2 or R 1-8 If the number of is greater than 1, then two optional R 1-8 are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms independently selected from O, S, and N."

[0033] In one embodiment, R 1-8 In R 11a is C 1-6 Alkyl group, C 3-10 A cycloalkyl group or one or more R 1-2-1 C replaced with 1-6 is an alkyl group, and R 1-2-1 is a hydroxy group or NR 12c R12d and R 12c and R 12d are independently hydrogen.

[0034] In one embodiment, R 1-8 In R 11f is C 1-6 It is an alkyl group.

[0035] In one embodiment, R 1-8 In R 11d1 and R 11d2 forms, together with the N atom to which it is linked, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N."

[0036] In one embodiment, R 1-9 Ha-NR 11b1 R 11b2 and R 11b1 and R 11b2 are independently hydrogen or —C(═O)R 11h and R 11h is C 1-6 It is an alkyl group.

[0037] In one embodiment, R 1-9 In R 11b1 is hydrogen and R 11b2 is -C(=O)R 11h and R 11h is C 1-6 It is an alkyl group.

[0038] In one embodiment, when a and b are single bonds, A4 is NR 4a and A5 is N.

[0039] In one embodiment, when b is a single bond and a is a double bond, A4 is N or CR 4d and A5 is S or NR 5d and R 4d is hydrogen or halogen.

[0040] In one embodiment, when b is a single bond and a is a double bond, A4 is N and A5 is NR 5d is.

[0041] In one embodiment, R 4a is one or more R 4-1 C replaced with 1-6 is an alkyl group, and R 4-1 is a hydroxy group or -OC 1-6 It is an alkyl group.

[0042] In one embodiment, L1 is a linking bond or C 1-6 is an alkylene group, and Q1 is hydrogen, C 3-12 Cycloalkyl groups, C substituted with one or more halogens 1-6 Alkyl, cyano, hydroxy, C substituted with one or more hydroxy groups 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 5-1-2 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 5-1-3 and a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with

[0043] In one embodiment, L1 is a connecting bond and Q1 is hydrogen, C 3-12 Cycloalkyl group or C substituted with one or more halogens 1-6 It is an alkyl group.

[0044] In one embodiment, L1 is C 1-6 an alkylene group, and Q1 is hydrogen, a cyano group, a hydroxy group, or a C substituted with one or more hydroxy groups. 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 5-1-2 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R5-1-3 "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with C 3-12 It is a cycloalkyl group.

[0045] In one embodiment, R 5-1-2 is a halogen.

[0046] In one embodiment, R 5-1-3 is C 1-6 It is an alkyl group.

[0047] In one embodiment, A1 is N or CR 1 and R 1 is hydrogen, halogen, or one or more R 1-1 C replaced with 1-6 When the alkyl group has a plurality of substituents, the substituents may be the same or different. 1-1 is a halogen, A5 is NR 5d and R 5d teeth [ka] and L1 is a connecting bond or C 1-6 is an alkylene group, Q1 is one or more R 5-1-2 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," or one or more R 5-1-3 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 3-12 is a cycloalkyl group, and R 5-1-2 and R 5-1-3 The definition is the same as above.

[0048] In one embodiment, in the five-membered heteroaryl ring structure-containing compound of formula I, A1 is CR 1and A5 is NR 5d or S and R 1 is one or more R 1-1 C replaced with 1-6 an alkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-3 C replaced with 3-10 cycloalkyl group, one or more R 1-4 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-8 "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-9 C replaced with 2-6 is an alkynyl group, R 5d teeth, [ka] and L1 is a connecting bond or C 1-6 is an alkylene group, and Q1 is hydrogen, a cyano group, a hydroxy group, or -OC 1-6 Alkyl groups, C substituted with one or more halogens 1-6 alkyl groups, C substituted with one or more hydroxy groups 1-6 alkyl group, one or more R 5-1-3 "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with C 3-12 It is a cycloalkyl group.

[0049] In one aspect, R a1 、R a2 、R a3 、R a1-1 、R a2-1 、R a2-2 、R a-1 、R a-2 、R a-31 、R a-32 、R a-4 、R a-51 、R a-52 、R 1 、R 1-1 、R 1-2 、R 1-3 、R 1-4 、R 1-5 、R 1-6 、R 1-7 、R 1-8 、R 1-9 、R 1-1-1 、R 1-1-2 、R 1-1-3 、R 1-1-4 、R 1-1-5 、R 1-1-6 、R 1-1-7 、R 1-1-8 、R 1-1-1-1 、R 1-2-1 、R 1-2-2 、R 1-2-3 、R 1-2-4 、R 1-2-5 、R 1-2-6 、R 1-2-7 、R 1-2-8 、R 1-2-1-1 、R 1-3-1 、R 1-3-2 、R 1-3-3 、R 1-3-4 、R 1-3-5 、R 1-3-6 、R 1-4-1 、A2, A3, R 6-1 、R 4a 、R 4d 、Q1, R 5-1-1 、R 5-1-2 、R 5-1-3 、R 5-1-4 、R 5-1-5 、R 5-1-6 、R 5-1-7 、R 52a 、R 52b1 、R 52b2 、R 52c 、R 52d1 、R 52d2 、R 51a 、R51b1 , R 51b2 , R 51c , R 51d1 , R 51d2 and R 1-5-1 When a halogen is mentioned in the definition of , said halogen is fluorine, chlorine, bromine or iodine.

[0050] In one embodiment, R a1 , R a2 , R a3 , R a1-1 , R a2-1 , R a2-2 , R a-1 , R a-2 , R a-31 , R a-32 , R a-4 , R a-51 , R a-52 , R 1 , R 1-1 , R 1-2 , R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 , R 1-9 , R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 , R 1-1-8 , R 1-1-1-1 , R 1a , R 1b1 , R 1b2 , R 1c , R 1d1 , R 1d2 , R 11a , R 11b1 , R 11b2 , R 11c , R 11d1 , R 11d2 , R 11e1 , R 11e2 , R 11f and R 11g , R 1-2-1 , R 1-2-2 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R1-2-7 , R 1-2-8 , R 1-2-1-1 , R 1-3-1 , R 1-3-2 , R 1-3-3 , R 1-3-4 , R 1-3-5 , R 1-3-6 , R 1-4-1 , R 6-1 , R 4a , R 4d , Q1, R 5-1-1 , R 5-1-2 , R 5-1-3 , R 5-1-4 , R 5-1-5 , R 5-1-6 , R 5-1-7 , R 52a , R 52b1 , R 52b2 , R 52c , R 52d1 , R 52d2 , R 51a , R 51b1 , R 51b2 , R 51c , R 51d1 , R 51d2 and R 1-5-1 C in the definition 1-6 When an alkyl group is mentioned, the C 1-6 The alkyl group is C 1-4 Alkyl groups include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl groups.

[0051] In one embodiment, R 1 , R 1-1 , R 1-2 , R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 , R 1-9 , R 1a , R 1b1 , R 1b2 , R 1c , R 1d1 , R 1d2 , R 11a , R 11b1 , R 11b2 , R 11c , R 11d1 , R11d2 , R 11e1 , R 11e2 , R 11f and R 11g C in the definition 3-10 When a cycloalkyl group is mentioned, the C 3-10 The cycloalkyl group is a C3-C6 cycloalkyl group, for example, a cyclopropyl group, a cyclobutyl group, or a cyclopentyl group.

[0052] In one embodiment, R 1 , R 1-1 , R 1-2 , R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 , R 1-9 , R 1a , R 1b1 , R 1b2 , R 1c , R 1d1 , R 1d2 , R 11a , R 11b1 , R 11b2 , R 11c , R 11d1 , R 11d2 , R 11e1 , R 11e2 , R 11f , R 11g and C in the definition of Q1 6-20 When an aryl group is mentioned, the C 6-20 The aryl group is C 6-10 An aryl group is, for example, a phenyl group or a naphthyl group, also for example, a phenyl group.

[0053] In one embodiment, R a1 C substituted with one or more halogens 1-6 When the alkyl group is an alkyl group, the C substituted with one or more halogens is 1-6 The alkyl group is a C substituted with one halogen. 1-2 An alkyl group, for example, —CH2F.

[0054] In one embodiment, R a2 and R a3is connected to the carbon atom and C 3-7 When forming a cycloalkane, 3-7 The cycloalkane is a C3-C6 cycloalkane, such as cyclopropane, cyclobutane or cyclopentane.

[0055] In one embodiment, R 1 One or more R 1-1 C replaced with 1-6 In the case of alkyl groups, the plurality is two or three.

[0056] In one embodiment, R 1 One or more R 1-1 C replaced with 1-6 is an alkyl group, and R 1-1 are independently halogen, then said one or more R 1-1 C replaced with 1-6 The alkyl group is a C substituted with two or three halogens. 1-2 An alkyl group, for example a trifluoromethyl group.

[0057] In one embodiment, R 1-1 independently, one or more R 1-1-4 When the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is substituted with , the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is a monocyclic or bridged ring heteroalkyl group. When the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" has a monocyclic structure, the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" can be substituted with a "5- to 6-membered heterocycloalkyl group containing 1 to 2 heteroatoms independently selected from N", for example. [ka] When the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is a bridged cyclic alkyl group, the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" can be replaced with an "8- to 10-membered heterocycloalkyl group containing 1 to 2 heteroatoms independently selected from N", for example [ka] is.

[0058] In one embodiment, R 1 is "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" or one or more R 1-4 When the "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is substituted with R 1-4 Among the "4- to 12-membered heterocycloalkyl groups containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, the "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is a monocyclic heteroalkyl group, a spirocyclic heteroalkyl group, a fused-ring heteroalkyl group, or a bridged-ring alkyl group. The monocyclic heteroalkyl group is a "4- to 6-membered heterocycloalkyl group containing 1 to 2 heteroatoms independently selected from O and N", and examples thereof include: [ka] The spirocyclic heteroalkyl group may be an "8- to 11-membered heterocycloalkyl group containing 1 to 2 heteroatoms independently selected from O and N", for example, [ka] The fused ring heteroalkyl group may be an "8- to 11-membered heterocycloalkyl group containing 1 to 2 heteroatoms independently selected from O and N", for example, [ka] The bridged cyclic heteroalkyl group may be an "8- to 11-membered heterocycloalkyl group containing 1 to 2 heteroatoms independently selected from O and N", for example, [ka] It could be.

[0059] In one embodiment, R 1 One or more R 1-4 When the "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is substituted with one or more of the R 1-4 The "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-4 and may be a "6-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-4 "6-membered heterocycloalkyl group containing two heteroatoms independently selected from N and O" substituted with [ka] , and for example [ka] ), or one or more R 1-4 "6-membered heterocycloalkyl groups containing one heteroatom selected from N" substituted with [ka] ) can be.

[0060] In one embodiment, R1 One or more R 1-4 When the "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is substituted with one or more of the R 1-4 The "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-4 It may be a "6-membered heterocycloalkyl group containing one heteroatom selected from N" substituted with

[0061] In one embodiment, R 1-3 In R 11d1 and R 11d2 When these form "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N," together with the N atom to which they are linked, the "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N" is not considered to be a "3- to 6-membered heterocycloalkane containing one N heteroatom (for example, [ka] ), or a 3- to 6-membered heterocycloalkane containing two heteroatoms, N and O, respectively.

[0062] In one embodiment, R 1-4 One or more R 1-1-4 In the case where the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" is substituted with a , the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" is a "4- to 6-membered heterocycloalkyl group containing 1 N."

[0063] In one embodiment, R 1-5 In R 11d1 and R 11d2form "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N," together with the N atom to which it is linked, the "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N" is "a 3- to 6-membered heterocycloalkane containing one N heteroatom, or a 3- to 6-membered heterocycloalkane containing two heteroatoms independently selected from N and O."

[0064] In one embodiment, R 1 is "a 5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R 1-6 In the case where the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" is a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with one or more R 1-6 The "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" in the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with is a "5- to 9-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from O, S, and N", for example [ka] It could be.

[0065] In one embodiment, R 1-4 If the number of is greater than 1, then two optional R 1-4 are linked to form, together with the atoms linked thereto, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," when the two R 1-4 is two R on two adjacent atoms 1-4 is.

[0066] In one embodiment, two R on two adjacent atoms1-4 form a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N", the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" can be replaced with a "5- to 6-membered heteroaryl group containing 1 to 2 heteroatoms independently selected from O, S, and N", for example. [ka] and said one or more R 1-4 The "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with [ka] is.

[0067] In one embodiment, R 1-4 In R 11a is one or more R 1-2-1 C replaced with 1-6 In the case of alkyl groups, the plurality is two or three.

[0068] In one embodiment, R 1-4 In R 11a One or more R 1-2-1 C replaced with 1-6 is an alkyl group, and R 1-2-1 is halogen, 11a is a halogen-substituted C 1-2 An alkyl group, for example a trifluoromethyl group or a trifluoroethyl group.

[0069] In one embodiment, R 1-4 In R 11ais a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" is a "5- to 6-membered heteroaryl group containing 1 to 2 heteroatoms independently selected from O, S, and N," for example, a pyridyl group.

[0070] In one embodiment, R 1-4 In R 11d1 and R 11d2 together with the N atom to which it is linked, is a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," or one or more R 1-4-1 When forming a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," the "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N" is a "4- to 6-membered heterocycloalkane containing one N." For example, the -C(=O)NR 11d1 R 11d2 teeth, [ka] is.

[0071] In one embodiment, R 1-7 In R 11d1 and R 11d2 form "a 3- to 8-membered heterocycloalkane containing one N and 1 to 3 heteroatoms the others of which are independently selected from O, S, and N" together with the N atom to which it is linked, the "3- to 8-membered heterocycle containing one N and 1 to 3 heteroatoms the others of which are independently selected from O, S, and N" is a "4- to 6-membered heterocycloalkane containing one N."

[0072] In one embodiment, R 1is "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-8 In the case of a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with , the "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is a monocyclic or bridged cyclic heterocycloalkenyl group. The monocyclic group is a "5- to 7-membered heterocycloalkenyl group containing one N." The bridged cyclic group is a "5- to 10-membered heterocycloalkenyl group containing 1 to 2 heteroatoms independently selected from O and N."

[0073] In one embodiment, R 1 One or more R 1-9 C replaced with 2-6 When the C is an alkynyl group, 2-6 The alkynyl group is C 2-3 Alkynyl groups, for example ethynyl, propynyl or propargyl groups.

[0074] In one embodiment, Q1 is C substituted with one or more halogens. 1-6 When Q1 is an alkyl group, Q1 is C substituted with 2 to 3 halogen atoms. 1-2 C alkyl group, preferably C substituted with 2 to 3 fluorines 1-2 An alkyl group is, for example, a trifluoroethyl group or a difluoromethyl group.

[0075] In one embodiment, Q is C substituted with one or more hydroxy groups. 1-6 When Q1 is an alkyl group, Q1 is a C substituted with 1 to 3 hydroxy groups. 1-2 It is an alkyl group.

[0076] In one embodiment, Q1 is a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," or one or more R 5-1-3and containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with , the "5 to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" is a "5 to 9-membered heteroaryl group containing 1 to 2 heteroatoms independently selected from S and N."

[0077] In one embodiment, Q1 is C 3-12 When the C is a cycloalkyl group, 3-12 The cycloalkyl group is C 3-6 Cycloalkyl groups are, for example, cyclopropyl, cyclobutyl or cyclopentyl groups.

[0078] In one embodiment, R 1 and R 5d When each of these forms a "5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" together with the atom to which it is linked, the "5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" is a "5- to 7-membered heterocycloolefin containing 1 to 2 heteroatoms independently selected from O and N", for example, a "5- to 7-membered heterocycloolefin containing 2 N atoms", and for example [ka] is.

[0079] In one embodiment, L1 is C 1-6 When C is an alkylene group, 1-6 The alkylene group can be -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH(CH3)CH2-, -CH2CH2CH2CH2-, -CH(CH3)CH2CH2-, -CH2CH(CH3)CH2CH2-, or -C(CH3)2CH2-.

[0080] In one embodiment, [ka] teeth, [ka] and, [ka] For example, [ka] is.

[0081] In one embodiment, A2 is CH or CF.

[0082] In one embodiment, A3 is N, CH or CF.

[0083] In one embodiment, A1 is CR 1 and R 1 is hydrogen, -F, -CF3, [ka] TIFF2025509180000038.tif254166, In one embodiment, A1 is CR 1 wherein A2 is CH and A3 is CH or CF.

[0084] In one embodiment, A1 is N, A2 is CH, and A3 is CH.

[0085] In one embodiment, A4 is N or CR 4d and In one embodiment, R 4d is hydrogen or chlorine.

[0086] In one embodiment, when a and b are single bonds, A4 is NR 4a and A5 is N.

[0087] In one embodiment, A5 is S or NR 5d and R 5dis H, -CH3, [ka] is.

[0088] In one embodiment, R 6 teeth, [ka] is.

[0089] In one embodiment, the five-membered heteroaryl ring structure-containing compound represented by Formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof is embodiment 1, embodiment 2, or embodiment 3.

[0090] Aspect 1: A five-membered heteroaryl ring structure-containing compound represented by formula IV, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof, [ka] , but R a1 is hydrogen, halogen, cyano group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OR a-1 , -C(=O)R a-2 , -NR a-31 R a-32 , -C(=O)OR a-4 , -C(=O)NR a-51 R a-52 , or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen, a hydroxy group or -OC 1-6 is an alkyl group, A1 is N or CR 1 and R 1 is hydrogen, one or more R 1-1 C replaced with 1-6 Alkyl groups, halogens, C 3-10cycloalkyl group, one or more R 1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-4 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-8 and when there are a plurality of substituents, they may be the same or different, R 1-1 , R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 and R 1-8 are independently a halogen, a hydroxy group, a cyano group, an oxo group, C 1-6 alkyl group, one or more R 1-1-1 C replaced with 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OC 1-6 alkyl group, one or more R 1-1-2 -OC substituted with 1-6 Alkyl group, -C(=O)R 11a , -NR 11b1 R 11b2 , -C(=O)OR 11c , -C(=O)NR11d1 R 11d2 , -S(O)NR 11e1 R 11e2 , -S(O)2R 11f , C 3-10 cycloalkyl group, one or more R 1-1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-1-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-1-8 and when there are a plurality of substituents, they may be the same or different, R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 and R 1-1-8 are independently halogen, hydroxyl, oxo, C 1-6 an alkyl group or one or more R 1-1-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1-1-1 is a halogen, hydroxy group, -OC 1-6Alkyl group or -NR a R b and R a and R b are independently hydrogen or C 1-6 is an alkyl group, R 11a , R 11b1 , R 11b2 , R 11c , R 11d1 , R 11d2 , R 11e1 , R 11e2 and R 11f are independently hydrogen, C 1-6 alkyl group, one or more R 1-2-1 C replaced with 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 1-2-2 -OC substituted with 1-6 Alkyl group, C 3-10 cycloalkyl group, one or more R 1-2-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-2-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-2-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-2-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-2-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-2-8and when there are a plurality of substituents, they may be the same or different, R 1-2-1 , R 1-2-2 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 and R 1-2-8 are independently halogen, oxo, C 1-6 an alkyl group or one or more R 1-2-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1-1 are independently a halogen, a hydroxy group, or -OC 1-6 Alkyl group or -NR c R d and R c and R d are independently hydrogen or C 1-6 is an alkyl group, Or R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 , R 1-1-8 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 , and R 1-2-8 If the number of is greater than 1, then two optional R 1-3 , two optional R 1-4 , two optional R 1-5 , two optional R 1-6 , two optional R 1-7 , two optional R 1-8 , two optional R 1-1-3 , two optional R 1-1-4 , two optional R 1-1-5, two optional R 1-1-6 , two optional R 1-1-7 , two optional R 1-1-8 , two optional R 1-2-3 , two optional R 1-2-4 , two optional R 1-2-5 , two optional R 1-2-6 , two optional R 1-2-7 , or optionally two R 1-2-8 are connected to each other and independently form a 3- to 8-membered carbocyclic ring together with the atoms connected thereto, one or more R 1-3-1 a 3- to 8-membered carbocyclic ring substituted with one or more R 1-3-2 "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-3-3 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-3-4 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-3-5 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-3-6 and forming a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with R 1-3-1 , R 1-3-2 , R 1-3-3 , R 1-3-4 , R 1-3-5 and R 1-3-6 are independently oxo, hydroxyl, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6-OC substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, Or R a-31 and R a-32 , R a-51 and R a-52 , R 11b1 and R 11b2 , R 11d1 and R 11d2 , R 11e1 and R 11e2 , R a and R b , R c and R d are independently, respectively, and together with the N to which they are linked, "a 3- to 8-membered heterocycle in which one is N and the others are independently selected from O, S, and N and contain 1 to 3 heteroatoms," or one or more R 1-4-1 and R 1-4-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, A2 and A3 are independently N or CR 2 and R 2 is hydrogen or halogen, A4 is N or CR 4d and R 4d is hydrogen, halogen, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, R 5d teeth, [ka] and L1 is a connecting bond or C 1-6 is an alkylene group, Q1 is hydrogen, halogen, cyano group, C 2-6 Alkenyl group, C2-6 Alkynyl group, hydroxy group, -C(=O)R 52a , -NR 52b1 R 52b2 , -C(=O)OR 52c , -C(=O)NR 52d1 R 52d2 , C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 an alkyl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 5-1-3 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 3-12 cycloalkyl group, one or more R 5-1-4 C replaced with 3-12 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 5-1-5 and when there are a plurality of substituents, they may be the same or different, R 5-1-3 , R 5-1-4 and R 5-1-5 are independently a halogen, a hydroxy group, an oxo group, a cyano group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 Alkyl groups, -OC substituted with one or more halogens 1-6 Alkyl group, -C(=O)R 51a , -NR 51b1 R 51b2 , -C(=O)OR 51c , or -C(=O)NR 51d1 R 51d2 and when there is more than one substituent, they may be the same or different; R 52a , R 52b1 , R 52b2 , R 52c , R 52d1 , R 52d2 , R 51a , R51b1 , R 51b2 , R 51c , R 51d1 and R 51d2 are independently hydrogen, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, Or R 52b1 and R 52b2 , R 52d1 and R 52d2 , R 51b1 and R 51b2 , R 51d1 and R 51d2 are independently, respectively, and together with the N to which they are linked, a "3- to 8-membered heterocycle in which one is N and the others are independently 1 to 3 heteroatoms selected from O, S, and N", or one or more R 1-5-1 and forming a "3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-5-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 6 means "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R 6-1 and a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R 6-1 is C 1-6 C substituted with alkyl groups or one or more halogens 1-6 It is an alkyl group.

[0091] Aspect 2: A five-membered heteroaryl ring structure-containing compound represented by formula IV', a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof, [ka] ,however, R a1 is hydrogen, halogen, cyano group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OR a-1 , -C(=O)R a-2 , -NR a-31 R a-32 , -C(=O)OR a-4 , -C(=O)NR a-51 R a-52 , or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen, a hydroxy group or -OC 1-6 is an alkyl group, A1 is N or CR 1 and R 1 is hydrogen, C 1-6 alkyl group, one or more R 1-1 C replaced with 1-6 Alkyl groups, halogens, C 3-10 cycloalkyl group, one or more R 1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-4 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-7 C replaced with 5-7a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-8 and when there are a plurality of substituents, they may be the same or different, R 1-1 , R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 and R 1-8 are independently an azide group, a halogen, a hydroxy group, a cyano group, an oxo group, C 1-6 alkyl group, one or more R 1-1-1 C replaced with 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OC 1-6 alkyl group, one or more R 1-1-2 -OC substituted with 1-6 Alkyl group, -C(=O)R 11a , -NR 11b1 R 11b2 , -C(=O)OR 11c , -C(=O)NR 11d1 R 11d2 , -S(O)NR 11e1 R 11e2 , -S(O)2R 11f , C 3-10 cycloalkyl group, one or more R 1-1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-1-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-1-6"5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-1-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-1-8 and when there are a plurality of substituents, they may be the same or different, R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 and R 1-1-8 are independently halogen, hydroxyl, oxo, C 1-6 an alkyl group or one or more R 1-1-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1-1-1 is a halogen, hydroxy group, -OC 1-6 Alkyl group or -NR a R b and R a and R b are independently hydrogen or C 1-6 is an alkyl group, R 11a , R 11b1 , R 11b2 , R 11c , R 11d1 , R 11d2 , R 11e1 , R 11e2 and R 11f are independently hydrogen, C 1-6 alkyl group, one or more R 1-2-1 C replaced with 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 1-2-2 -OC substituted with 1-6 Alkyl group, C 3-10cycloalkyl group, one or more R 1-2-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-2-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-2-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-2-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-2-7 C replaced with 5-7 a cycloalkenyl group, a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-2-8 and when there are a plurality of substituents, they may be the same or different, R 1-2-1 , R 1-2-2 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 and R 1-2-8 are independently a halogen, a hydroxy group, or -NR 12c R 12d , Oxo, C 1-6 an alkyl group or one or more R 1-2-1-1 C replaced with 1-6 is an alkyl group, and R 12c and R 12d are independently hydrogen or C 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1-1 are independently a halogen, a hydroxy group, or -OC 1-6Alkyl group or -NR c R d and R c and R d are independently hydrogen or C 1-6 is an alkyl group, Or R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 , R 1-1-8 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 , and R 1-2-8 If the number of is greater than 1, then two optional R 1-3 , two optional R 1-4 , two optional R 1-5 , two optional R 1-6 , two optional R 1-7 , two optional R 1-8 , two optional R 1-1-3 , two optional R 1-1-4 , two optional R 1-1-5 , two optional R 1-1-6 , two optional R 1-1-7 , two optional R 1-1-8 , two optional R 1-2-3 , two optional R 1-2-4 , two optional R 1-2-5 , two optional R 1-2-6 , two optional R 1-2-7 , or optionally two R 1-2-8 are connected to each other and independently form a 3- to 8-membered carbocyclic ring together with the atoms connected thereto, one or more R 1-3-1 a 3- to 8-membered carbocyclic ring substituted with one or more R 1-3-2 "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C6-20 Aromatic ring, one or more R 1-3-3 C replaced with 6-20 an aromatic ring, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-3-4 "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with C 5-7 Cycloolefin, one or more R 1-3-5 C replaced with 5-7 Cycloolefin, "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 1-3-6 and forming a "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with R 1-3-1 , R 1-3-2 , R 1-3-3 , R 1-3-4 , R 1-3-5 and R 1-3-6 are independently oxo, hydroxyl, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, Or R a-31 and R a-32 , R a-51 and R a-52 , R 11b1 and R 11b2 , R 11d1 and R 11d2 , R 11e1 and R 11e2 , R a and R b , R c and R d are independently, respectively, and together with the N to which they are linked, a "3- to 8-membered heterocycle in which one is N and the others are independently 1 to 3 heteroatoms selected from O, S, and N", or one or more R 1-4-1and R 1-4-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, A2 and A3 are independently N or CR 2 and R 2 is hydrogen or halogen, A4 is N or CR 4d and R 4d is hydrogen, halogen, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, A5 is S or NR 5d and R 5d teeth, [ka] and L1 is a connecting bond or C 1-6 is an alkylene group, Q1 is hydrogen, halogen, cyano group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, hydroxy group, -C(=O)R 52a , -NR 52b1 R 52b2 , -C(=O)OR 52c , -C(=O)NR 52d1 R 52d2 , C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 Alkyl group, C 6-20 an aryl group, one or more R 5-1-2 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 5-1-3"5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 3-12 cycloalkyl group, one or more R 5-1-4 C replaced with 3-12 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 5-1-5 and when there are a plurality of substituents, they may be the same or different, R 5-1-2 , R 5-1-3 , R 5-1-4 and R 5-1-5 are independently a halogen, a hydroxy group, an oxo group, a cyano group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 Alkyl groups, -OC substituted with one or more halogens 1-6 Alkyl group, -C(=O)R 51a , -NR 51b1 R 51b2 , -C(=O)OR 51c , or -C(=O)NR 51d1 R 51d2 and when there is more than one substituent, they may be the same or different; R 52a , R 52b1 , R 52b2 , R 52c , R 52d1 , R 52d2 , R 51a , R 51b1 , R 51b2 , R 51c , R 51d1 and R 51d2 are independently hydrogen, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, Or R 52b1 and R 52b2 , R 52d1 and R 52d2 , R 51b1 and R51b2 , R 51d1 and R 51d2 are independently, respectively, and together with the N to which they are linked, a "3- to 8-membered heterocycle in which one is N and the others are independently 1 to 3 heteroatoms selected from O, S, and N", or one or more R 1-5-1 and forming a "3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-5-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 6 means "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R 6-1 and a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R 6-1 is C 1-6 C substituted with alkyl groups or one or more halogens 1-6 It is an alkyl group.

[0092] Aspect 3: A five-membered heteroaryl ring structure-containing compound represented by formula IV″, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof, [ka] however, R a1 is hydrogen, halogen, cyano group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OR a-1 , -C(=O)R a-2 , -NR a-31 R a-32 , -C(=O)ORa-4 , -C(=O)NR a-51 R a-52 , or one or more R a1-1 C replaced with 1-6 is an alkyl group, and R a1-1 is a halogen, a hydroxy group or -OC 1-6 is an alkyl group, R 1 is C 3-10 cycloalkyl group, one or more R 1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-4 "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-7 C replaced with 5-7 Cycloalkenyl group, "C containing 1 to 3 heteroatoms independently selected from O, S and N" 5-7 heterocycloalkenyl group" or one or more R 1-8 "C containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with 5-7 heterocycloalkenyl group" and when there are multiple substituents, they may be the same or different, R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 and R 1-8 are independently a halogen, a hydroxy group, a cyano group, an oxo group, C 1-6 alkyl group, one or more R 1-1-1 C replaced with 1-6Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, -OC 1-6 alkyl group, one or more R 1-1-2 -OC substituted with 1-6 Alkyl group, -C(=O)R 11a , -NR 11b1 R 11b2 , -C(=O)OR 11c , -C(=O)NR 11d1 R 11d2 , -S(O)NR 11e1 R 11e2 , C 3-10 cycloalkyl group, one or more R 1-1-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-1-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-1-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-1-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-1-7 C replaced with 5-7 Cycloalkenyl group, "C containing 1 to 3 heteroatoms independently selected from O, S and N" 5-7 heterocycloalkenyl group" or one or more R 1-1-8 "C containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with 5-7 heterocycloalkenyl group" and when there are multiple substituents, they may be the same or different, R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R1-1-7 and R 1-1-8 are independently halogen, oxo, C 1-6 an alkyl group or one or more R 1-1-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-1-1-1 is a halogen, hydroxy group, -OC 1-6 Alkyl group or -NR a R b and R a and R b are independently hydrogen or C 1-6 is an alkyl group, R 11a , R 11b1 , R 11b2 , R 11c , R 11d1 , R 11d2 , R 11e1 and R 11e2 are independently hydrogen, C 1-6 alkyl group, one or more R 1-2-1 C replaced with 1-6 Alkyl group, -OC 1-6 alkyl group, one or more R 1-2-2 -OC substituted with 1-6 Alkyl group, C 3-10 cycloalkyl group, one or more R 1-2-3 C replaced with 3-10 a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R 1-2-4 "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-2-5 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-2-6 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-2-7C replaced with 5-7 Cycloalkenyl group, "C containing 1 to 3 heteroatoms independently selected from O, S and N" 5-7 heterocycloalkenyl group" or one or more R 1-2-8 "C containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with 5-7 heterocycloalkenyl group" and when there are multiple substituents, they may be the same or different, R 1-2-1 , R 1-2-2 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 and R 1-2-8 are independently halogen, oxo, C 1-6 an alkyl group or one or more R 1-2-1-1 C replaced with 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 1-2-1-1 are independently a halogen, a hydroxy group, or -OC 1-6 Alkyl group or -NR c R d and R c and R d are independently hydrogen or C 1-6 is an alkyl group, Or R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 , R 1-8 , R 1-1-3 , R 1-1-4 , R 1-1-5 , R 1-1-6 , R 1-1-7 , R 1-1-8 , R 1-2-3 , R 1-2-4 , R 1-2-5 , R 1-2-6 , R 1-2-7 , and R 1-2-8 If the number of is greater than 1, then two optional R 1-3 , two optional R 1-4 , two optional R 1-5 , two optional R1-6 , two optional R 1-7 , two optional R 1-8 , two optional R 1-1-3 , two optional R 1-1-4 , two optional R 1-1-5 , two optional R 1-1-6 , two optional R 1-1-7 , two optional R 1-1-8 , two optional R 1-2-3 , two optional R 1-2-4 , two optional R 1-2-5 , two optional R 1-2-6 , two optional R 1-2-7 , or optionally two R 1-2-8 are connected to each other and independently form a 3- to 8-membered carbocyclic ring together with the atoms connected thereto, one or more R 1-3-1 a 3- to 8-membered carbocyclic ring substituted with one or more R 1-3-2 "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with C 6-20 an aryl group, one or more R 1-3-3 C replaced with 6-20 an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R 1-3-4 "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C 5-7 Cycloalkenyl group, one or more R 1-3-5 C replaced with 5-7 Cycloalkenyl group, "C containing 1 to 3 heteroatoms independently selected from O, S and N" 5-7 heterocycloalkenyl group" or one or more R 1-3-6 "C containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with 5-7 forming a "heterocycloalkenyl group" R 1-3-1 , R 1-3-2 , R 1-3-3 , R 1-3-4 , R1-3-5 and R 1-3-6 are independently oxo, hydroxyl, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, Or R a-31 and R a-32 , R a-51 and R a-52 , R 11b1 and R 11b2 , R 11d1 and R 11d2 , R 11e1 and R 11e2 , R a and R b , R c and R d are independently, respectively, and together with the N to which they are linked, a "3- to 8-membered heterocycle in which one is N and the others are independently 1 to 3 heteroatoms selected from O, S, and N", or one or more R 1-4-1 and R 1-4-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, A2 and A3 are independently N or CR 2 and R 2 is hydrogen or halogen, A4 is N or CR 4d and R 4d is hydrogen, halogen, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, R 5d teeth, [ka] and L1 is a connecting bond or C 1-6 is an alkylene group, Q1 is hydrogen, halogen, cyano group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, hydroxy group, -C(=O)R 52a , -NR 52b1 R 52b2 , -C(=O)OR 52c , -C(=O)NR 52d1 R 52d2 , C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 Alkyl group, C 3-12 cycloalkyl group, one or more R 5-1-4 C replaced with 3-12 a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R 5-1-5 and when there are a plurality of substituents, they may be the same or different, R 5-1-4 and R 5-1-5 are independently a halogen, a hydroxy group, an oxo group, a cyano group, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 Alkyl groups, -OC substituted with one or more halogens 1-6 Alkyl group, -C(=O)R 51a , -NR 51b1 R 51b2 , -C(=O)OR 51c , or -C(=O)NR 51d1 R 51d2 and when there is more than one substituent, they may be the same or different; R 52a , R 52b1 , R 52b2 , R 52c , R 52d1 , R 52d2 , R 51a , R51b1 , R 51b2 , R 51c , R 51d1 and R 51d2 are independently hydrogen, C 1-6 C substituted with alkyl groups or one or more halogens 1-6 is an alkyl group, Or R 52b1 and R 52b2 , R 52d1 and R 52d2 , R 51b1 and R 51b2 , R 51d1 and R 51d2 are independently, respectively, and together with the N to which they are linked, a "3- to 8-membered heterocycle in which one is N and the others are independently 1 to 3 heteroatoms selected from O, S, and N", or one or more R 1-5-1 and forming a "3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N," substituted with R 1-5-1 is an oxo, hydroxy group, halogen, C 1-6 Alkyl groups, C substituted with one or more halogens 1-6 Alkyl group, -OC 1-6 -OC substituted with alkyl groups or one or more halogens 1-6 alkyl group, and when there are a plurality of substituents, they may be the same or different; R 6 means "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R 6-1 and a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R 6-1 is C 1-6 C substituted with alkyl groups or one or more halogens 1-6 It is an alkyl group.

[0093] In one embodiment, the five-membered heteroaryl ring structure-containing compound represented by formula I may have any one of the following structures:

[0094] [ka] TIFF2025509180000048.tif229162TIFF2025509180000049.tif250163TIFF20255091800 00050.tif232161TIFF2025509180000051.tif246162TIFF2025509180000052.tif253163 TIFF2025509180000053.tif194163TIFF2025509180000054.tif191163TIFF2025509180000055.tif194165.

[0095] The present invention further provides a method for preparing the five-membered heteroaryl ring structure-containing compound represented by the above formula I, which is any one of Routes 1 to 9.

[0096] Route 1, [ka] However, R a1 , R a2 , R a3 , R 5d , R 6 The definitions of A1, A2, and A3 are as described above, and MET represents a metal group, for example, [ka] , BF3K, B(OH)2, PG is a protecting group, such as Boc or THP, and the steps of Route 1 are as follows: introducing a protecting group into Compound A1 to obtain Compound A2, converting A2 into a metal compound A3, coupling A3 to generate Compound A4, converting A4 into a benzylthio group compound A5, deprotecting A5 to generate Compound A6, converting A6 into Compound A7 by a reaction such as nucleophilic substitution, and further converting A7 to obtain Compound I1.

[0097] Route 2: [ka] However, R a1 , R a2 , R a3 , R 5d , R 6 The definitions of A1, A2, and A3 are as described above. ALK is C 1-6 The alkyl group, such as a methyl group or an ethyl group, can be selected from the group consisting of ester group B1, hydrazine group, acyl group, and cyclohexane. The steps of Route 2 are as follows: ester group B1 is converted into compound B2 under the action of a hydrazine compound, acyl group is introduced into B2, ring formation is performed to generate compound B3, B3 is converted into compound B4 by a reaction such as nucleophilic substitution, B4 is converted into benzylthio group B5, and B5 is further converted to obtain compound I2.

[0098] Route 3: [ka] However, R a1 , R a2 , R a3 , R 5d , R 6 , A2, A3, R 1 are all defined as above, and MET is a metal group, for example [ka] , BF3K, B(OH)2, PG is a protecting group, such as Boc or THP. The steps of Route 3 are as follows: converting compound C1 to benzylthio group compound C2, introducing a protecting group to C2 to obtain compound C3, converting C3 to metal compound C4, coupling C4 to generate compound C5, deprotecting C5 to generate compound C6, converting C6 to compound C7 by nucleophilic substitution or other reaction, further converting C7 to obtain compound C8, and converting C8 by nucleophilic substitution, coupling or other reaction to obtain compound I3.

[0099] Route 4: [ka] However, R a1 , R a2 , R a3 , R 5d , R 6 , A2, A3, R 1 are all defined as above, and MET is a metal group, for example [ka] , BF3K, B(OH)2, PG is a protecting group, for example, Boc, THP, ALK is C 1-6 The alkyl group is, for example, a methyl group or an ethyl group, and the steps of Route 4 are as follows: introducing a protecting group into Compound C1 to obtain Compound D1, converting D1 to a metal compound D2, coupling D2 to generate Compound D3, converting D3 to Compound D4, deprotecting D4 to generate Compound D5, converting D5 to Compound D6 by a reaction such as nucleophilic substitution, oxidizing D6 to Compound D7, further converting D7 to obtain Compound C8, and converting C8 by a reaction such as nucleophilic substitution or coupling to obtain Compound I3.

[0100] Route 5: [ka] However, R a1 , R a2 , R a3 , X, R 5d , R 6 , A2, A3, R 1 The definitions of are as above, and ALK is C 1-6 The alkyl group is, for example, a methyl group or an ethyl group, and the steps of Route 5 are as follows: Compound D6 is converted to Compound E1 by a reaction such as nucleophilic substitution or coupling, E1 is oxidized to give Compound E2, and E2 is further converted to give Compound I3.

[0101] Route 6: [ka] However, R a1, R a2 , R a3 , R 5d , R 6 , R 1 The definitions of are as above, and ALK is C 1-6 The alkyl group is, for example, a methyl group or an ethyl group, and the steps of Route 6 are as follows: Compound F1 is chlorosulfonated to obtain Compound F2, F2 is converted into Compound F3 by bromination, F3 is further converted into Compound F4, F4 is converted into Compound F5 under the action of a hydrazine compound, an acyl group is introduced into F5, and Compound F6 is generated by ring formation, and F6 is converted into Compound I4 by nucleophilic substitution, coupling, or other reactions.

[0102] Route 7: [ka] However, R a1 , R a2 , R a3 , R 6 , R 1 The definitions of are as above, and ALK is C 1-6 The alkyl group is, for example, a methyl group or an ethyl group, and the steps of Route 7 are as follows: Compound G1 is oxidized to obtain Compound G2, G2 is further converted to obtain Compound G3, G3 is converted to Compound G4 under the action of a hydrazine compound, an acyl group is introduced into G4, and Compound G5 is generated by ring formation, and G5 is converted to Compound I5 by nucleophilic substitution, coupling, or other reactions.

[0103] Route 8, [ka] However, R a1 , R a2 , R a3 , R 5d , R 6 , R 1 The definitions of A, A2, and A3 are as described above. ALK is C 1-6The alkyl group, such as a methyl group or an ethyl group, can be selected from the group consisting of ester group H1, methyl group, ethyl group ...

[0104] Route 9, [ka] However, R a1 , R a2 , R a3 , R 5d , R 6 The definitions of A1, A2, and A3 are as described above. ALK is C 1-6 The alkyl group is, for example, a methyl group or an ethyl group, and the steps of Route 9 are as follows: Compound K1 is converted into compound K2 by coupling and oxidation, K2 is converted into compound K3 by a reaction such as nucleophilic substitution, and K3 is further converted to compound I1.

[0105] The present invention further provides a pharmaceutical composition comprising a substance A and a pharmaceutical excipient, wherein the substance A is a therapeutically effective amount of a five-membered heteroaryl ring structure-containing compound represented by the above formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof.

[0106] The present invention further provides a use of substance A in preparing a PARG inhibitor, wherein substance A is a five-membered heteroaryl ring structure-containing compound represented by the above formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof or an isotope thereof.

[0107] The present invention further provides a method for using substance A to inhibit PARG, comprising administering to a subject an effective amount of substance A. The substance A is a five-membered heteroaryl ring structure-containing compound represented by the above formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof.

[0108] The present invention further provides a use of substance A in preparing a medicine, the medicine being used for treating or preventing a PARG-mediated disease, wherein substance A is a five-membered heteroaryl ring structure-containing compound represented by the above formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof or an isotope thereof.

[0109] The present invention further provides a method for treating or preventing a PARG-mediated disease with substance A, comprising administering to a subject an effective amount of substance A. The substance A is a five-membered heteroaryl ring structure-containing compound represented by the above formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof.

[0110] The present invention further provides use of substance A in preparing a medicament for treating or preventing cancer, wherein substance A is a five-membered heteroaryl ring structure-containing compound represented by the above formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof, such as one or more of colon cancer, appendix cancer, pancreatic cancer, MYH-associated polyposis, blood cancer, breast cancer, endometrial cancer, gallbladder cancer, biliary tract cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, testicular cancer, kidney cancer, head and neck cancer, bone cancer, skin cancer, rectal cancer, liver cancer, esophageal cancer, gastric cancer, thyroid cancer, bladder cancer, lymphoma, leukemia, and melanoma.

[0111] The present invention further provides a method for treating or preventing cancer with substance A, which comprises administering to a subject an effective amount of substance A. The substance A is a five-membered heteroaryl ring structure-containing compound represented by the above formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof. The cancer is, for example, one or more of colon cancer, appendix cancer, pancreatic cancer, MYH-associated polyposis, blood cancer, breast cancer, endometrial cancer, gallbladder cancer, biliary tract cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, testicular cancer, kidney cancer, head and neck cancer, bone cancer, skin cancer, rectal cancer, liver cancer, esophageal cancer, stomach cancer, thyroid cancer, bladder cancer, lymphoma, leukemia, and melanoma.

[0112] The term "pharmaceutically acceptable salt" refers to a salt obtained by preparing a compound of the present invention with a relatively non-toxic, pharmaceutically acceptable acid or base. When a compound of the present invention contains a relatively acidic functional group, a base addition salt can be obtained by contacting the neutral form of such a compound with a sufficient amount of a pharmaceutically acceptable base in pure solution or in a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, lithium, sodium, potassium, calcium, aluminum, magnesium, zinc, bismuth, ammonium, and diethanolamine salts. When a compound of the present invention contains a relatively basic functional group, an acid addition salt can be obtained by contacting the neutral form of such a compound with a sufficient amount of a pharmaceutically acceptable acid in pure solution or in a suitable inert solvent. Such pharmaceutically acceptable acids include inorganic acids, including, but not limited to, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, phosphoric acid, phosphorous acid, sulfuric acid, and the like. The pharmaceutically acceptable acids include organic acids, including, but not limited to, acetic acid, propionic acid, oxalic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, salicylic acid, tartaric acid, methanesulfonic acid, isonicotinic acid, acidic citric acid, oleic acid, tannic acid, pantothenic acid, bitartrate, ascorbic acid, gentisic acid, fumaric acid, gluconic acid, saccharic acid, formic acid, ethanesulfonic acid, pamoic acid (i.e., 4,4'-methylene-bis(3-hydroxy-2-naphthoic acid)), amino acids (e.g., glutamic acid, arginine), etc. When the compounds of the present invention contain relatively acidic and relatively basic functional groups, they can be converted into base or acid addition salts.Specifically, reference can be made to Berge et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science 66:1-19 (1977), or Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl and Camille G. Wermuth, ed., Wiley-VCH, 2002).

[0113] In the present invention, when there are a plurality of substituents, they may be the same or different.

[0114] The term "stereoisomer" refers to isomers that arise from the same interconnection sequence of atoms or atomic groups in a molecule but different spatial arrangements, such as cis-trans isomers, optical isomers, or atropisomers. These stereoisomers can be separated, purified, and enriched by asymmetric synthesis or chiral separation techniques (including, but not limited to, thin layer chromatography, rotary chromatography, column chromatography, gas chromatography, high pressure liquid chromatography, etc.), or can be obtained by chiral resolution via bonding (e.g., chemical bonding) or salt formation (e.g., physical bonding) with other chiral compounds.

[0115] The term "tautomer" refers to a functional isomer resulting from the rapid migration of an atom between two positions within a molecule. For example, acetone and 1-propen-2-ol are converted into each other by the rapid migration of a hydrogen atom on the oxygen and on the α-carbon.

[0116] The term "isotopic compound" refers to a compound in which one or more atoms have been replaced with one or more atoms having a specific atomic mass or mass number. Illustrative isotopes that can be incorporated into the compounds of the invention include, but are not limited to, isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, sulfur, and chlorine (e.g., H, C, C, N, O, O, F, S, and Cl). Isotopic compounds of the invention can generally be prepared by replacing a non-isotopically labeled reagent with an isotopically labeled reagent according to the methods described herein.

[0117] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0118] The term "alkyl group" refers to a straight or branched chain alkyl group having the specified number of carbon atoms. Illustrative examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like.

[0119] The term "alkylene group" refers to a linking group between two other classes, which may be straight or branched chain, and examples include, but are not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2CH(CH3)-, -CH2CH(CH2CH3)CH2-.

[0120] The terms "cycloalkyl group" and "carbocycle" refer to a saturated cyclic group consisting solely of carbon atoms, which may be monocyclic, bridged, or spirocyclic, having a specified number of carbon atoms (e.g., C3-C6). Cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

[0121] The term "aryl group" refers to an aromatic group of carbon atoms in which each ring is aromatic, such as a phenyl group or a naphthyl group.

[0122] The term "heteroaryl group" refers to a cyclic group having a specified number of ring atoms (e.g., 5-12 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatom (one or more of N, O, and S), which may be monocyclic or polycyclic, and in which at least one ring is aromatic (meets Hückel's rule). Heteroaryl groups are connected to other segments within the molecule through rings that may or may not be aromatic. Heteroaryl groups include, but are not limited to, furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, and the like.

[0123] The terms "heterocyclic group," "heterocycle," or "heterocycloalkyl group" refer to a cyclic group having a specified number of ring atoms (e.g., 3 to 8 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatom (one or more of N, O, and S), which may be monocyclic, bridged, or spirocyclic, and in which each ring is saturated. Heterocycloalkyl groups include, but are not limited to, azetidinyl, tetrahydropyrrolyl, tetrahydrofuranyl, morpholino, piperidinyl, and the like.

[0124] The term "hydroxy" refers to an -OH group.

[0125] The term "cyano" refers to the group -CN.

[0126] The term "oxo" refers to the group =O.

[0127] The term "a 3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N" refers to "a 3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms, one of which is N, and further, if there are other heteroatoms, the other heteroatoms are independently selected from O, S, and N."

[0128] "C x1 -C y1 " alkyl group, "C x1 -C y1 " cycloalkyl group, "C x1 -C y1 "Cycloalkenyl group, "C x1 -C y1 " alkoxy group, "C x1 -C y1 " alkenyl group, "C x1 -C y1 "Alkynyl group, "C x1 -C y1 " aryl group, "C x1 -C y1 " heteroaryl group or "C x1 -C y1 " heterocyclic group, such as the carbon number range determined above "C x1 -C y1 " (x1 and y1 are integers) each represent the number of carbon atoms not including the substituent, for example, a C1-C6 alkyl group represents a C1-C6 alkyl group not including the substituent.

[0129] As long as it does not go against common knowledge in the art, the above-mentioned preferable conditions can be arbitrarily combined to obtain each preferred embodiment of the present invention.

[0130] All of the reagents and raw materials used in the present invention are commercially available. [Effects of the Invention]

[0131] The positive effects of the present invention are as follows: The present invention provides a five-membered heteroaryl ring structure-containing compound, a pharmaceutical composition thereof, and use thereof, and the five-membered heteroaryl ring-containing compound has a favorable inhibitory effect on any of multiple types of disease cells in which PARG is involved, and is expected to be used in the treatment and / or prevention of multiple types of diseases in which PARG is involved. DETAILED DESCRIPTION OF THE INVENTION

[0132] The present invention will be further described below by way of examples, but the present invention is not limited to the scope of the examples. In the following examples, experimental methods for which specific conditions are not specified are selected according to conventional methods and conditions or according to product instructions.

[0133] In the present invention, room temperature refers to ambient temperature, which is 10° C. to 35° C. Overnight refers to 8 to 15 hours. Reflux refers to the temperature at which the solvent refluxes under normal pressure.

[0134] Below is a list of abbreviations used in the examples.

[0135] DCM dichloromethane DMF N,N-dimethylformamide EA Ethyl acetate DMSO dimethyl sulfoxide MTBE Methyl tert-butyl ether DMAP 4-dimethylaminopyridine DIPEA Diisopropylethylamine Pd2(dba)3 tris(dibenzylideneacetone)dipalladium(0) m-CPBA m-chloroperoxybenzoic acid Xantphos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene RuPhos 2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl DMF-DMA N,N-dimethylformamide dimethyl acetal THF tetrahydrofuran THP 2-Tetrahydropyran TFA trifluoroacetic acid Ms Methylsulfonyl Tf Trifluoromethanesulfonyl CDI Carbonyldiimidazole EDCI 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride HOBT 1-Hydroxybenzotriazole PMBCl p-Methoxybenzyl chloride DBDMH Dibromohydantoin SEMCl 2-(trimethylsilyl)ethoxymethyl chloride DHP 3,4-dihydro-2H-pyran RuPhos Pd G3 Methanesulfonato(2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) NMM N-methylmorpholine [Ir(COD)OMe]2(1,5-cyclooctadiene)(methoxy)iridium(I) dimer SelectFluor II 1-Fluoro-4-methyl-1,4-diazabicyclo[2.2.2]octane Tetrafluoroborate Synthesis of intermediate 1-f [ka] Synthesis of compound 1-g Thiosemicarbazide (3 g, 32.9 mmol) was added in four portions to difluoroacetic anhydride (8.6 g, 49.4 mol) in an ice bath. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at 85 °C for 36 h. The reaction mixture was cooled to room temperature and the pH was adjusted to 7-8 with saturated sodium bicarbonate solution in an ice bath. After a portion of the solid precipitated, it was filtered, washed with water (5 mL), added with acetonitrile (10 mL), and dried under reduced pressure by spin drying to obtain the product. The filtrate was extracted eight times with DCM:MeOH = 10:1 (100 mL). The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (SiO2, DCM:MeOH = 10:1) to obtain the product. In total, solid compound 1-g (1.6 g, 32%) was obtained. LC-MS (ESI): m / z 152.1 (M+H). + ; 1 H NMR(400MHz,DMSO-d6):δ 7.77(s,2H),7.24(t,J=56.0Hz,1H). Preparation of compound 1-f Compound 1-g (400 mg, 2.65 mmol) was dissolved in anhydrous acetonitrile (20 mL) and copper bromide (620.1 mg, 2.78 mmol) was added. The mixture was cooled to 0 °C, and then isoamyl nitrite (1.183 g, 5.3 mmol) dissolved in 1 mL of acetonitrile was added dropwise. After the addition was complete, the reaction mixture was stirred at room temperature for 20 min and then at 63 °C for 12 h. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth, and the filtrate was rotary evaporated under reduced pressure to obtain a concentrate. The concentrate was purified by column chromatography (SiO, petroleum ether:ethyl acetate = 10:1) to obtain compound 1-f (370 mg, 65%) as a yellow liquid. 1 H NMR(400MHz,DMSO-d6):δ 7.59(t,J=52.0Hz,1H). Example 1: Synthesis of Compound 1 [ka] Synthesis of compound 1-e While cooling in an ice bath, 5-bromoindazole (1.5 g, 7.61 mmol), acetonitrile (20 mL), di-tert-butyl dicarbonate (2.50 g, 11.40 mmol), triethylamine (770 mg, 7.61 mmol), and DMAP (93 mg, 7.60 mmol) were added to the reaction flask. The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate 100 / 0 to 80 / 20) to give compound 1-e (2.0 g, 88%). LC-MS (ESI): m / z 297.0 (M+H). + . Synthesis of compound 1-d Under an argon atmosphere, [Ir(COD)OMe]2 (153 mg, 0.23 mmol), 4,4'-di-tert-butyl-2,2'-bipyridine (125 mg, 0.47 mmol), bis(pinacolato)diboron (829 mg, 3.26 mmol), and anhydrous methyl tert-butyl ether (10 mL) were added to a reaction flask. The reaction mixture was stirred at room temperature for 5 minutes, and then a solution of 1-e (1.85 g, 6.22 mmol) in anhydrous methyl tert-butyl ether (10 mL) was added. After the addition was complete, the reaction mixture was stirred at 25 °C under an argon atmosphere for 1 hour, and then at 80 °C under an argon atmosphere for 1 hour. The reaction mixture was concentrated to give compound 1-d (2.9 g crude). LC-MS (ESI): m / z 341.1 (M+H). + . Synthesis of compound 1-c A reaction flask was charged with 1-d (1.9 g crude, 4.00 mmol), 1-f (540 mg, 2.52 mmol), palladium acetate (32 mg, 0.13 mmol), XantPhos (73 mg, 0.13 mmol), toluene (20 mL), and purified water (10 mL). Cesium carbonate (2.46 g, 7.56 mmol) was added while cooling in an ice bath. After the addition was complete, the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated NaCl, dried over anhydrous Na2SO4, filtered, concentrated, and purified by column chromatography (mobile phase: petroleum ether, dichloromethane (4:1) / ethyl acetate 100 / 0 to 80 / 20) to give compound 1-c (550 mg, 50%). LC-MS (ESI): m / z 431.0 (M+H). + . Synthesis of compound 1-b To a reaction flask, 1-c (525 mg, 1.22 mmol), benzyl mercaptan (460 mg, 3.65 mmol), tris(dibenzylideneacetone)dipalladium (112 mg, 0.12 mmol), XantPhos (140 mg, 0.24 mmol), DIPEA (630 mg, 4.87 mmol), and 1,4-dioxane (20 mL) were added. After the addition was complete, the reaction mixture was stirred at 110 °C for 20 h. The reaction mixture was concentrated and purified by column chromatography (mobile phase: petroleum ether, dichloromethane (4:1) / ethyl acetate 100 / 0 to 70 / 30) to give compound 1-b (340 mg, 74%). LC-MS (ESI): m / z 375.0 (M+H). + . Synthesis of compound 1-a To a reaction flask were added 1-b (190 mg, 0.51 mmol), 5-(chloromethyl)-2,4-dimethyl-1,3-thiazole (164 mg, 1.01 mmol), and DMF (5 mL). While cooling in an ice bath, cesium carbonate (496 mg, 1.52 mmol) was added. After the addition was complete, the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated NaCl, dried over anhydrous Na2SO4, filtered, concentrated, and purified by column chromatography (mobile phase: petroleum ether, dichloromethane (4:1) / ethyl acetate 100 / 0 to 70 / 30) to give compound 1-a (200 mg, 78%). LC-MS (ESI): m / z 500.0 (M+H). + ; 1 H NMR(400MHz,CDCl3):δ 8.24(1H,d,J=1.6Hz),7.90(1H,d,J=9.0Hz),7.67(1H,t,J=53.2Hz),7.61(1H,dd,J=8.8,1.7Hz),7.40-7.33 (2H,m),7.27(2H,dd,J=8.2,6.5Hz),7.23-7.18(1H,m),5.94(2H,s),4.31(2H,s),2.50(3H,s),2.46(3H,s). Synthesis of Compound 1 A reaction flask was charged with 1-a (30 mg, 0.06 mmol), acetonitrile (2 mL), acetic acid (50 mg), and water (50 mg), and dichlorohydantoin (18 mg, 0.09 mmol) was added in an ice-salt bath (approximately -18 °C). The reaction mixture was stirred at -18 to -10 °C for 1.5 h. Dichlorohydantoin (12 mg, 0.06 mmol) was added in an ice-salt bath (approximately -18 to -10 °C). The reaction mixture was continued to stir at -18 to -10 °C for 1 h. Dichlorohydantoin (12 mg, 0.06 mmol) was added in an ice-salt bath (approximately -18 to -10 °C). The reaction mixture was continued to stir at -18 to -10 °C for 1 h. The reaction mixture was evaporated to dryness, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous Na2SO4, filtered, and evaporated to dryness to give the crude intermediate. 1-Methylcyclopropylamine hydrochloride (13 mg, 0.12 mmol) was added to the crude intermediate, and anhydrous dichloromethane (3 mL) and DIPEA (30 mg, 0.23 mmol) were added under ice bath conditions. The reaction mixture was stirred at 25 °C for 2 h. The reaction mixture was evaporated to dryness and purified by column chromatography (mobile phase: dichloromethane / methanol 100 / 0 to 90 / 10, dichloromethane / (dichloromethane / methanol / 7M ammonia / methanol (20:1:1)) 100 / 0 to 20 / 80) to obtain the crude product. This was separated on a C8 column (mobile phase: 10 mM aqueous ammonium bicarbonate / acetonitrile 95 / 5 to 5 / 95) to obtain compound 1 (6 mg, 19%) as a white solid. LC-MS (ESI): m / z 511.0 (M+H). + . Example 2: Synthesis of Compound 2 [ka] Synthesis of compound 2-d 5-Bromo-2-methyl-1,3,4-thiadiazole (100 mg, 0.56 mmol) was dissolved in 10 mL of toluene at room temperature, and 5 mL of water, 1-d (381 mg, approximately 0.67 mmol in terms of purity), palladium acetate (25 mg, 0.11 mmol), Xantphos (129 mg, 0.22 mmol), and N-methylmorpholine (0.12 mL, 1.12 mmol) were added sequentially. After the addition was complete, the reaction mixture was stirred at room temperature under a nitrogen atmosphere for 16 h. 20 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (50 mL * 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified using a high-performance column (PE / EA = 1:2) to obtain compound 2-d (108 mg, 48%) as a white solid. LC-MS(ESI): m / z=395.0[M+1] + . Synthesis of compound 2-c Compound 2-d (108 mg, 0.27 mmol) was dissolved in 10 mL of 1,4-dioxane at room temperature. Pd2(dba)3 (25 mg, 0.027 mmol), XantPhos (32 mg, 0.055 mmol), DIPEA (135 μL, 0.82 mmol), and benzyl mercaptan (35 μL, 0.30 mmol) were added sequentially. The reaction mixture was stirred at 110 °C under a nitrogen atmosphere for 16 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and purified using a high-performance separation column (PE / EA = 1:1) to give compound 2-c (115 mg) as a yellow oil. The crude product was used directly in the next reaction. LC-MS (ESI): m / z = 439.1 [M+1] + . Synthesis of compound 2-b At room temperature, 2-c (115 mg) was dissolved in 9 mL of DCM and cooled to 0 °C. 3 mL of TFA was added, and the reaction mixture was warmed to room temperature and stirred for 3 h. The mixture was concentrated under reduced pressure, and 50 mL of ethyl acetate was added to the residue. The mixture was washed with 50 mL of saturated sodium bicarbonate solution, and the aqueous phase was extracted with ethyl acetate (50 mL x 2). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified using a high-performance column (DCM / MeOH = 10:1) to give compound 2-b (40 mg, 44% yield for the two steps) as a yellow solid. LC-MS (ESI): m / z = 339.0 [M+1]+ . Synthesis of compound 2-a 2-b (58 mg, 0.17 mmol) was dissolved in 5 mL of DMF at room temperature, and cesium carbonate (111 mg, 0.34 mmol) was added. The mixture was stirred at room temperature for 10 minutes. 5-(Chloromethyl)-2,4-dimethyl-1,3-thiazole (41 mg, 0.25 mmol) was added, and the mixture was stirred at room temperature for 2 hours. 20 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (50 mL × 2). The organic phase was washed with saturated brine (100 mL × 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified using a high-performance separation column (PE / EA = 1:1 to EA) to obtain compound 2-a (45 mg, 57%) as a yellow solid. LC-MS (ESI): m / z = 464.1 [M+1] + . Synthesis of compound 2 2-a (45 mg, 0.097 mmol) was dissolved in 5 mL of acetonitrile at 0 °C, and acetic acid (22 μL, 0.39 mmol), water (18 μL, 1.0 mmol), and dichlorohydantoin (38 mg, 0.19 mmol) were added sequentially. The mixture was stirred at 0 °C for 2 hours. The reaction mixture was concentrated under reduced pressure and dried in vacuo for 30 minutes to obtain the crude intermediate. The intermediate was dissolved in 5 mL of DCM at 0 °C, and 1-methylcyclopropanamine hydrochloride (31 mg, 0.29 mmol) and triethylamine (108 μL, 0.78 mmol) were added sequentially. The reaction mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was concentrated under reduced pressure, and the crude product was purified by high-performance column chromatography (DCM / MeOH=20:1) and preparative TLC (DCM / MeOH=20:1) to give compound 2 (22 mg, 48%) as a white solid. LC-MS (ESI): m / z=475.0 [M+1] + ; 1 H NMR(CDCl3,400MHz):δ 9.11(1H,s),7.97(1H,d,J=8.4Hz),7.51(1H,d,J=8.8Hz),7.37-7.27(1H,m),5.70(2H,s), 2.87(3H,s),2.62(3H,s),2.56(3H,s),1.22(3H,s),0.81-0.78(2H,m),0.49-0.46(2H,m). Example 3: Synthesis of Compound 3 [ka] Synthesis of compound 3-g A three-necked flask was charged with 5-bromo-7-chloroindazole (2.0 g, 8.64 mmol), Xantphos (0.50 g, 0.85 mmol), 1,4-dioxane (60 mL), DIPEA (4.5 mL, 25.06 mmol), and benzyl mercaptan (3 mL, 24.79 mmol) and flushed with nitrogen twice. Pd(dba) (0.40 g, 0.42 mmol) was added and flushed with nitrogen three times. The reaction mixture was heated to reflux at 100 °C for 5 h. The reaction mixture was cooled to room temperature, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 3-g (2.3 g, 97%) as a light brown viscous liquid.

[0136] Synthesis of compound 3-f To a reaction flask were added 3-g (2.3 g, 8.37 mmol), 3,4-dihydro-2H-pyran (30 mL), and trifluoroacetic acid (0.12 mL, 1.57 mmol). After the addition was complete, the reaction mixture was stirred at 90 °C for 3 h. The reaction mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate solution, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 3-f (2.10 g, 70%) as a brown viscous liquid. LC-MS (ESI): m / z 359.1 (M+H). + . Synthesis of compound 3-e A microwave tube was charged with (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (0.175 g, 0.27 mmol), 4,4'-di-tert-butyl-2,2'-dipyridine (0.144 g, 0.54 mmol), bis(pinacolato)diboron (1.38 g, 5.43 mmol), and methyl tert-butyl ether (6 mL). The mixture was purged with nitrogen twice and stirred at room temperature for 5 minutes. A solution of 3-f (0.65 g, 1.81 mmol) in methyl tert-butyl ether (6 mL) was added, purged with nitrogen three times, and stirred at 80 °C for 3.5 hours. The reaction mixture was evaporated to dryness to give compound 3-e (870 mg, 99%) as a brown viscous liquid.

[0137] Synthesis of compound 3-d A reaction flask was charged with 3-e (870 mg, 1.79 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (374 mg, 1.74 mmol), palladium acetate (44 mg, 0.20 mmol), Xantphos (224 mg, 0.39 mmol), toluene (20 mL), and water (10 mL). The mixture was purged with nitrogen twice, and N-methylmorpholine (0.64 mL, 5.80 mmol) was added. The reaction mixture was stirred at 25 °C for 18 h. The reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 3-d (200 mg, 23%) as a light brown solid. LC-MS (ESI): m / z 493.2 (M+H). + . Synthesis of compound 3-c A reaction flask was charged with 3-d (180 mg, 0.37 mmol), acetonitrile (3 mL), acetic acid (0.014 mL, 0.25 mmol), and water (0.015 mL, 0.832 mmol), and dichlorohydantoin (144 mg, 0.73 mmol) was added in an ice bath. The reaction mixture was stirred in an ice bath for 1.5 hours. The reaction mixture was spin-dried at room temperature and dried on an oil pump for 10 minutes. 1-Methylcyclopropylamine hydrochloride (79 mg, 0.73 mmol) and dichloromethane (5 mL) were added to the crude intermediate, and triethylamine (0.25 mL, 1.8 mmol) was added in an ice bath. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was evaporated to dryness and purified by column chromatography (mobile phase: (petroleum ether / dichloromethane 4:1) / ethyl acetate, 100 / 0 to 70 / 30) to give compound 3-c (70 mg, 46%) as a light brown solid. LC-MS (ESI): m / z 420.2 (M+H). + . Synthesis of compound 3-b A reaction flask was charged with 3-c (70 mg, 0.17 mmol) and DMF (2.5 mL), and sodium hydride (27 mg, 0.67 mmol) was added under ice bath conditions. The reaction mixture was stirred for 5 minutes under ice bath conditions, and then SEMCl (83 mg, 0.50 mmol) was added. After the addition was complete, stirring was continued for 1 hour. The reaction mixture was quenched with saturated ammonium chloride, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 90 / 10) to give compound 3-b (40 mg, 35%) as a light brown solid.

[0138] Synthesis of compound 3-a A microwave tube was charged with 3-b (30 mg, 0.044 mmol), 2-methyl-1-(piperazin-1-yl)propyl-1-one (28 mg, 0.18 mmol), RuPhos (4.1 mg, 0.009 mmol), RuPhos Pd G3 (3.7 mg, 0.004 mmol), cesium carbonate (43 mg, 0.13 mmol), and 1,4-dioxane (3 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 100 °C for 2 h. After cooling to room temperature, the 1,4-dioxane was spun off, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give compound 3-a (35 mg, 99%) as a brown solid. LC-MS (ESI): m / z 822.4 (M+Na). + . Synthesis of compound 3 A reaction flask was charged with 3-a (35 mg, 0.044 mmol), dichloromethane (2 mL), and anisole (0.2 mL). Trifluoroacetic acid (0.5 mL) was added dropwise at room temperature. The reaction mixture was allowed to react at room temperature for 5 hours. The solvent was spun off at room temperature, diluted with ethyl acetate, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: dichloromethane / (dichloromethane / methanol / ammonia methanol (7M) = 20:1:1), 100 / 0 to 75 / 25) to give compound 3 (3.1 mg, 13%) as an off-white solid. LC-MS (ESI): m / z 540.2 (M+H). + ; 1 H NMR(DMSO-d6,400MHz):δ 14.54(1H,s),8.49(1H,d,J=1.3Hz),8.11(1H,s),7.70(1H,t,J=53.2Hz),7.29(1H,s),3.85-3.73(4H,m),3.24-3. 08(4H,m),2.98(1H,hept,J=6.7Hz),1.05(6H,d,J=6.7Hz),1.02(3H,s),0.62(2H,t,J=5.3Hz),0.38-0.34(2H,m). Example 4: Synthesis of Compound 4 [ka] Synthesis of compound 4 Compound 1-a (43 mg, 0.086 mmol) was dissolved in dichloromethane (5 mL), and acetic acid (26 mg, 0.43 mmol) and water (8 mg, 0.43 mmol) were added. The reaction mixture was cooled to 0 °C, and then sulfonyl chloride (58 mg, 0.43 mmol) dissolved in dichloromethane (0.1 mL) was added. After the addition was complete, the reaction mixture was stirred at 0 °C for 1 h. Saturated brine (20 mL) was added to the reaction mixture, and the mixture was stirred for 20 s. The organic phase was separated and concentrated under reduced pressure to obtain a crude product. Acetonitrile (10 mL) was added to the crude product, and the mixture was rotary evaporated under reduced pressure to obtain a crude product. The crude product was dissolved in N,N-dimethylformamide (5 mL) and 1-(fluoromethyl)cyclopropanamine hydrochloride (22 mg, 0.17 mmol), 4-dimethylaminopyridine (11 mg, 0.086 mmol), and diisopropylethylamine (67 mg, 0.52 mmol) were added. After the addition was complete, the reaction mixture was stirred at 50 °C for 1 h under a nitrogen atmosphere. Water (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL). The organic phase was washed with saturated brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by preparative HPLC (basic conditions) to obtain compound 4 (13 mg, 28%). LC-MS (ESI): m / z 529.0 (M+H). + ; 1 H NMR(400MHz,DMSO-d6):δ 8.82(s,1H),8.60(s,1H),8.19(d,J=12.0Hz,1H),7.96(d,J=8.0Hz,1H),7.70(t,J=52.0Hz ,1H),6.03(s,1H),4.25(s,1H),4.13(s,1H),2.50(s,3H),2.48(s,3H),0.74-0.65(m,4H). Example 5: Synthesis of Compound 5 [ka] Synthesis of compound 5-e A reaction flask was charged with 3-d (160 mg, 0.32 mmol) and dichloromethane (4 mL). Trifluoroacetic acid (1.5 mL) was added dropwise with stirring at room temperature. After the addition was complete, the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, diluted with ethyl acetate, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give compound 5-e (132 mg, 99%) as a white solid. LC-MS (ESI): m / z 409.0 (M+H). + . Synthesis of compound 5-d A reaction flask was charged with 5-e (132 mg, 0.32 mmol), DMF (3 mL), and cesium carbonate (480 mg, 1.47 mmol). Methyl iodide (0.069 mL, 0.84 mmol) was added dropwise with stirring at room temperature. After the addition was complete, the reaction mixture was reacted at room temperature for 3 hours. A small amount of methanol and ethyl acetate were added to the reaction mixture, and the mixture was rotary evaporated in room temperature water for 5 minutes. The residue was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate 100 / 0 to 50 / 50) to give compound 5-d (100 mg, 73%) as a solid.

[0139] Synthesis of compound 5-c A reaction flask was charged with 5-d (100 mg, 0.24 mmol), acetonitrile (4 mL), acetic acid (0.014 mL, 0.25 mmol), and water (0.015 mL, 0.83 mmol), and dichlorohydantoin (93 mg, 0.47 mmol) was added in an ice bath. The reaction mixture was stirred in an ice bath for 1.5 hours. The reaction mixture was spin-dried at low temperature and dried on an oil pump for 10 minutes. 1-Methylcyclopropylamine hydrochloride (51 mg, 0.47 mmol) and dichloromethane (5 mL) were added to the crude intermediate, and triethylamine (0.18 mL, 1.29 mmol) was added in an ice bath. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was evaporated to dryness and purified by column chromatography (mobile phase: (petroleum ether / dichloromethane 4:1) / ethyl acetate, 100 / 0 to 70 / 30) to give compound 5-c (102 mg, 99%) as a light brown solid. LC-MS (ESI): m / z 434.0 (M+H). + . Synthesis of compound 5-b A reaction flask was charged with 5-c (102 mg, 0.24 mmol) and DMF (2.8 mL), and sodium hydride (28 mg, 0.70 mmol) was added under ice bath conditions. After the addition was complete, the reaction mixture was stirred under ice bath conditions for 5 minutes, and then SEMCl (60 mg, 0.36 mmol) was added and the mixture was stirred for 1 hour. The reaction mixture was quenched with saturated ammonium chloride, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 5-b (120 mg, 90%) as a white solid. LC-MS (ESI): m / z 581.2 (M+NH4). + . Synthesis of compound 5-a A microwave tube was charged with 5-b (51 mg, 0.090 mmol), 2-methyl-1-(piperazin-1-yl)propyl-1-one (42 mg, 0.27 mmol), RuPhos (7.5 mg, 0.016 mmol), RuPhos Pd G3 (7.5 mg, 0.009 mmol), cesium carbonate (88 mg, 0.27 mmol), and 1,4-dioxane (3.5 mL). The reaction mixture was purged with nitrogen three times. The mixture was stirred at 80 °C for 7 h. The reaction mixture was cooled to room temperature, and the 1,4-dioxane was spun off. The mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: dichloromethane / methanol, 100 / 0 to 98 / 2) to give compound 5-a (55 mg, 89%) as a light brown solid. LC-MS(ESI):m / z701.3(M+NH4) + . Synthesis of compound 5 A reaction flask was charged with 5-a (55 mg, 0.080 mmol), dichloromethane (2.8 mL), and anisole (0.3 mL). Trifluoroacetic acid (0.7 mL) was added dropwise at room temperature. After the addition was complete, the reaction mixture was allowed to react at room temperature for 5 hours. The reaction mixture was spin-dried at low temperature, and the residue was diluted with ethyl acetate, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: dichloromethane / (dichloromethane / methanol / ammoniacal methanol = 20:1:1), 100 / 0 to 75 / 25). The resulting sample was purified again by column chromatography (mobile phase: 10 mM ammonium bicarbonate / acetonitrile, 95 / 5 to 48 / 52) to give compound 5 (13.8 mg, 31%) as a white solid. LC-MS (ESI): m / z 554.2 (M+H). + ; 1H NMR(DMSO-d6,400MHz):δ 8.59(1H,d,J=1.5Hz),7.63(1H,t,J=53.1Hz),7.56(1H,d,J=1.5Hz),4.55(1H,bs),4.50(3H,s),4.10(1H,bs),3.55-3.40(2H, m),3.30-2.65(4H,m),2.97(1H,hept,J=6.6Hz),1.06(6H,d,J=6.6Hz),1.02(3H,s),0.62(2H,q,J=4.5Hz),0.40-0.35(2H,m). (Example 6) Synthesis of Compound 6 [ka] Synthesis of compound 6-f Compound 5-bromoindazole (2 g, 10.15 mmol) was dissolved in dichloromethane (20 mL), p-toluenesulfonic acid monohydrate (0.17 g, 0.89 mmol), and 3,4-dihydropyran (0.85 g, 10.15 mmol) were added, and the reaction mixture was stirred at room temperature for 12 hours. Saturated sodium bicarbonate solution (10 mL) and water (50 mL) were added, followed by extraction with dichloromethane (100 mL), washing with saturated brine (50 mL), drying over sodium sulfate, filtering the desiccant, and spin-drying under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1) to obtain compound 6-f (1.20 g, 42%).

[0140] Synthesis of compound 6-e Bis(pinacolato)diboron (361.29 mg, 1.42 mmol), 2,2'-bis(4-tert-butylpyridine) (38.19 mg, 0.14 mmol), and (1,5-cyclooctadiene)(methoxy)iridium(I) (dimer) (47.15 mg, 0.07 mmol) were mixed in a microwave tube, and methyl tert-butyl ether (4 mL) was added under a nitrogen atmosphere. The mixture was then stirred at room temperature for 10 minutes. A solution of 6-f (200 mg, 0.71 mmol) in methyl tert-butyl ether (4 mL) was added under a nitrogen atmosphere. After purging with nitrogen for 60 seconds, the mixture was sealed and stirred at 85 °C for 3 hours. The reaction mixture was cooled to room temperature and rotary evaporated under reduced pressure to give crude 6-e (650 mg, crude). LC-MS (ESI): m / z 325.0 (M+H). + . Synthesis of compound 6-d Compound 2-bromo-5-difluoromethyl-1,3,4-thiadiazole (229.27 mg, 1.07 mmol), palladium acetate (15.96 mg, 0.07 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (82.26 mg, 0.14 mmol), 6-e (231 mg, 0.71 mmol), toluene (10 mL), and water (5 mL) were added to a reaction flask, and cesium carbonate (463.21 mg, 1.42 mmol) was added thereto. The reaction mixture was purged with nitrogen three times and stirred in an oil bath at 26 ° C. for 16 hours. Water (100 mL) was added to the reaction mixture, which was then extracted with ethyl acetate (100 mL), washed with saturated brine (50 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 10 / 1) to obtain compound 6-d (154 mg, 47%). LC-MS (ESI): m / z 415.0 (M+H) + . Synthesis of compound 6-c Compound 6-d (179 mg, 0.43 mmol), benzyl mercaptan (160.61 mg, 1.29 mmol), tris(dibenzylideneacetone)dipalladium (39.47 mg, 0.04 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (49.88 mg, 0.09 mmol), and diisopropylethylamine (222.86 mg, 1.72 mmol) were added to 1,4-dioxane (20 mL). The reaction mixture was purged with nitrogen three times and then stirred in a 120 °C oil bath for 12 hours. The reaction mixture was then rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 10 / 1) to obtain compound 6-c (189 mg, 96%). LC-MS (ESI): m / z 459.2 (M+H). + . Synthesis of compound 6-b Compound 6-c (189 mg, 0.41 mmol) was dissolved in dichloromethane (15 mL), trifluoroacetic acid (4 mL) was added, and the reaction mixture was stirred at room temperature for 12 hours. The pH of the reaction mixture was then adjusted to 8 with saturated sodium bicarbonate solution, extracted with dichloromethane (100 mL), washed with saturated brine (50 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, DCM / EA = 10 / 1) to obtain compound 6-b (115 mg, 75%). LC-MS (ESI): m / z 375.0 (M+H) + . Synthesis of compound 6-a Compound 6-b (115 mg, 0.31 mmol) was dissolved in N,N-dimethylformamide (6 mL), cesium carbonate (300.21 mg, 0.92 mmol), and bromomethylcyclopropane (62.19 mg, 0.46 mmol) were added, and the reaction mixture was stirred in an oil bath at 50 °C for 1 h. Water (50 mL) was added, and the mixture was extracted twice with ethyl acetate (100 mL), washed with saturated brine (100 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 10 / 1) to obtain compound 6-a (120 mg, 91%). LC-MS (ESI): m / z 429.0 (M+H). +. Synthesis of compound 6 Compound 6-a (35 mg, 0.08 mmol) was dissolved in dichloromethane (5 mL), and acetic acid (24.52 mg, 0.41 mmol) and water (7.36 mg, 0.41 mmol) were added thereto. The reaction solution was cooled to 0°C, and then sulfonyl chloride (55.12 mg, 0.41 mmol) dissolved in dichloromethane (0.1 mL) was added dropwise thereto. After the addition was complete, the reaction mixture was stirred at 0 °C for 1 h. Saturated brine (20 mL) was added to the reaction mixture, and after stirring for 10 s, the organic phase was separated, dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. N,N-dimethylformamide (5 mL) was added to dissolve the product. 1-(fluoromethyl)cyclopropanamine hydrochloride (14.61 mg, 0.12 mol), dimethylaminopyridine (9.98 mg, 0.08 mmol), and diisopropylethylamine (52.99 mg, 0.41 mmol) were added, and the reaction mixture was stirred in an oil bath at 50 °C for 1 h. Water (50 mL) was added to the mixture, and the mixture was extracted with ethyl acetate (100 mL), washed with saturated brine (50 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 10 / 1) to obtain compound 6 (10 mg, 25%). LC-MS(ESI):m / z442.0(M+H) + ; 1 H NMR(400MHz,DMSO-d6):δ 8.69(s,1H),8.08(d,J=12.0Hz,1H),7.84~7.56(m,2H),7.35(s,1H),4.56~4.42(m,2H),4.41~4.31(m ,1H),1.41~1.33(m,1H),1.13~1.05(m,1H),0.96~0.89(m,1H),0.88~0.81(m,2H),0.60~0.44(m,4H). Example 7: Synthesis of Compound 7 [ka] Synthesis of compound 7-e Methyl 5-bromo-1H-indole-3-carboxylate (1.0 g, 3.94 mmol) and 20 mL of ethanol were mixed at room temperature, followed by the addition of hydrazine hydrate (1.9 mL, 33 mmol). The mixture was stirred at 80°C under nitrogen gas for 16 hours. The reaction mixture was cooled to room temperature, filtered, and the solid collected and washed with ethanol (10 mL). The solid was dried under vacuum for 2 hours to give crude compound 7-e (468 mg) as a pale yellow solid. The crude product was used directly in the next reaction without further purification. LC-MS (ESI): m / z = 253.9 [M+1] + . Synthesis of compound 7-d Compound 7-e (368 mg, 1.45 mmol) was dissolved in 10 mL of THF at room temperature, and DCM (10 mL) and TEA (604 μL, 4.35 mmol) were added. The mixture was cooled to 0°C, and then difluoroacetic anhydride (216 μL, 1.74 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was concentrated under reduced pressure, and the crude product was purified using a high-performance separation column (DCM / MeOH = 10:1) to obtain compound 7-d (120 mg, 25%) as a white solid. LC-MS (ESI): m / z = 332.0 [M+1] + . Synthesis of compound 7-c Compound 7-d (120 mg, 0.36 mmol) was dissolved in 15 mL of 1,4-dioxane at room temperature, Lawesson's reagent (219 mg, 0.54 mmol) was added, and the reaction mixture was stirred at 80 °C under a nitrogen atmosphere for 3 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The crude product was purified using a high-performance separation column (PE / EA = 1:1) to obtain compound 7-c (105 mg, 88%) as a white solid. LC-MS (ESI): m / z = 329.9 [M+1] + . Synthesis of compound 7-b Compound 7-c (105 mg, 0.32 mmol) was dissolved in 5 mL of DMF at 0 °C. 5-Chloromethyl-2,4-dimethyl-1,3-thiazole hydrochloride (95 mg, 0.48 mmol) and cesium carbonate (311 mg, 0.95 mmol) were added. The mixture was stirred at room temperature under a nitrogen atmosphere for 16 h. The reaction was quenched by adding 10 mL of water, extracted with ethyl acetate (80 mL × 2). The organic phase was washed with saturated brine (100 mL × 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified using a high-performance separation column (PE / EA = 1:2) to give compound 7-b (103 mg, 71%) as a white solid. LC-MS (ESI): m / z = 454.9 [M+1] + . Synthesis of compound 7-a Compound 7-b (103 mg, 0.23 mmol) was dissolved in 10 mL of anhydrous 1,4-dioxane at room temperature. Pd2(dba)3 (21 mg, 0.023 mmol), Xantphos (26 mg, 0.045 mmol), DIPEA (112 μL, 0.68 mmol), and benzyl mercaptan (29 μL, 0.25 mmol) were added. The reaction mixture was stirred at 105 °C for 16 h under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and the crude product was purified using a high-performance column (PE / EA = 1:1 to EA) to obtain compound 7-a (103 mg, 91%) as a pale yellow solid. LC-MS (ESI): m / z = 499.2 [M+1] + . Synthesis of compound 7 Compound 7-a (50 mg, 0.10 mmol) was dissolved in 5 mL of anhydrous acetonitrile under room temperature and nitrogen gas conditions. The mixture was cooled to 0 °C, and acetic acid (23 µL, 0.40 mmol), water (9.0 µL, 0.50 mmol), and dichlorohydantoin (40 mg, 0.2 mmol) were added. After the addition was complete, the reaction mixture was stirred at 0 °C under a nitrogen atmosphere for 2 hours, concentrated under reduced pressure at room temperature, and the resulting intermediate was dried under vacuum for 30 minutes. 10 mL of dichloromethane was then added, cooled to 0 °C, and 1-methyl-cyclopropylamine hydrochloride (32 mg, 0.30 mmol) and triethylamine (360 µL, 2.59 mmol) were added. The reaction mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was concentrated under reduced pressure to obtain a crude product. The crude product was purified by prep-HPLC (base method) to obtain compound 7 (6 mg, 11%) as a white solid. LC-MS(ESI):m / z=543.8[M+1] + ; 1 H NMR(CDCl3,400MHz):δ9.20(1H,d,J=1.6Hz),7.93(1H,dd,J 1= 1.6Hz,J 2= 8.4Hz),7.46(1H,d,J=8.8Hz),7.12(1H,t,J=53.6Hz),5.58(2H,s),4.96 (1H,s),2.56(6H,s),1.21(3H,s),0.89-0.79(2H,m),0.51-0.45(2H,m). (Example 8) Synthesis of Compound 8 [ka] Synthesis of compound 8 Compound 7-a (50 mg, 0.10 mmol) was dissolved in 5 mL of dichloromethane at room temperature under nitrogen gas conditions, and the solution was cooled to 0°C. Acetic acid (23 μL, 0.40 mmol), water (7.4 μL, 0.41 mmol), and sulfone chloride (33 μL, 0.41 mmol) were added. After the addition was complete, the reaction mixture was stirred at 0°C under a nitrogen atmosphere for 1 hour, concentrated under reduced pressure at room temperature, and the resulting intermediate was dried in vacuo for 30 minutes. 3 mL of DMF was then added, the mixture was cooled to 0°C, and 1-methyl-cyclopropylamine hydrochloride (32 mg, 0.30 mmol), DMAP (25 mg, 0.2 mmol), and DIPEA (66 μL, 0.40 mmol) were added. The reaction mixture was warmed to room temperature and stirred for 30 minutes. The reaction was quenched by adding 10 mL of water, extracted with ethyl acetate (50 mL * 2), and the organic phase was washed with saturated brine (100 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified using a high-performance separation column (DCM / MeOH = 10:1) to obtain compound 8 (50 mg, 98%) as a white solid. LC-MS (ESI): m / z = 510.0 [M+1] + ; 1 H NMR(DMSO-d6,400MHz):δ8.77(1H,s),8.64(1H,s),8.05(1H,s),7.86(1H,d,J=9.2Hz),7.80-7.70(1H,m),7.6 4(1H,t,J=52.8Hz),5.74(2H,s),3.33(3H,s),2.46(3H,s),1.03(3H,s),0.65-0.55(2H,m),0.37-0.30(2H,m). Example 9: Synthesis of Compound 9 [ka] Synthesis of compound 9-f To a solution of 5-bromo-1H-pyrazolo[3,4-b]pyridine (0.5 g, 2.53 mmol) in dichloromethane (10 mL) were added 3,4-dihydro-2H-pyran (0.69 mL, 8.08 mmol) and p-toluenesulfonic acid monohydrate (48 mg, 0.25 mmol). After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, the reaction mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. Purification using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 50%) yielded compound 9-f (0.5 g, 70%) as a colorless oil. LC-MS (ESI): m / z = 282.0 [M+H] + . Synthesis of compound 9-e A microwave tube was charged with (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (139 mg, 0.21 mmol), 4,4'-di-tert-butyl-2,2'-dipyridine (114 mg, 0.43 mmol), bis(pinacolato)diboron (675 mg, 2.66 mmol), and methyl tert-butyl ether (6 mL). The mixture was purged with nitrogen twice and stirred at room temperature for 5 minutes. A solution of 9-f (0.3 g, 1.06 mmol) in methyl tert-butyl ether (6 mL) was added, purged with nitrogen three times, and stirred at 85 °C for 3.5 hours. The reaction mixture was evaporated to dryness to give compound 9-e (430 mg, 99%) as a brown viscous liquid.

[0141] Synthesis of compound 9-d A reaction flask was charged with 9-e (430 mg, 1.04 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (446 mg, 2.08 mmol), palladium acetate (23 mg, 0.10 mmol), Xantphos (120 mg, 0.21 mmol), toluene (20 mL), and water (10 mL). The mixture was purged with nitrogen twice, and cesium carbonate (1.01 g, 3.10 mmol) was added. The reaction mixture was stirred at 25 °C for 18 h. The reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 9-d (120 mg, 28%) as an ochre solid. LC-MS (ESI): m / z = 416.0 [M+H] + . Synthesis of compound 9-c A three-neck flask was charged with 9-d (120 mg, 0.29 mmol), Xantphos (34 mg, 0.058 mmol), 1,4-dioxane (10 mL), DIPEA (0.15 mL, 0.87 mmol), and benzyl mercaptan (0.051 mL, 0.43 mmol). The mixture was purged with nitrogen twice. Pd2(dba)3 (27 mg, 0.029 mmol) was added and the mixture was purged with nitrogen three times. The reaction mixture was heated to reflux at 100 °C for 5 h. The reaction mixture was cooled to room temperature, evaporated to dryness, and purified on a column (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 9-c (110 mg, 83%) as a light brown viscous liquid. LC-MS (ESI): m / z = 460.1 [M+H] + . Synthesis of compound 9-b TFA (5 mL) was added to a solution of 9-c (110 mg, 0.24 mmol) in dichloromethane (10 mL) at room temperature. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, the solvent was removed by rotary evaporation at room temperature, diluted with ethyl acetate, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified using a high-speed separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to obtain compound 9-b (80 mg, 89%) as an ochre solid. LC-MS (ESI): m / z = 376.0 [M+H] + . Synthesis of compound 9-a Cesium carbonate (139 mg, 0.43 mmol) and 5-(chloromethyl)-2,4-dimethyl-1,3-thiazole hydrochloride (63 mg, 0.32 mmol) were added to a solution of 9-b (1 g, 2.83 mmol) in DMF (5 mL) at room temperature. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. Purification using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) afforded compound 9-a (70 mg, 66%) as an amber oil. LC-MS (ESI): m / z = 501.2 [M+H] + . Synthesis of compound 9 To a solution of 9-a (70 mg, 0.14 mmol) in acetonitrile (5 mL) was added acetic acid (34 mg, 0.56 mmol) and HO (10 mg, 0.57 mmol). The mixture was cooled to -15 °C, and dichlorohydantoin (55 mg, 0.28 mmol) was added under ice bath conditions. After the addition was complete, the reaction mixture was stirred at low temperature for 1 h. The reaction mixture was spin-dried at room temperature and dried under oil pump for 10 min. 1-Methylcyclopropylamine hydrochloride (30 mg, 0.28 mmol) and dichloromethane (5 mL) were added to the crude intermediate, and triethylamine (0.078 mL, 0.56 mol) was added under ice bath conditions. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was evaporated to dryness to give the crude product. Purification by prep-HPLC gave 9 (5 mg, 7%) as a white solid. LC-MS (ESI): m / z = 512.1 [M+H] + ; 1 H NMR(DMSO-d6,400MHz):δ 9.11(1H,d,J=2.0Hz),9.09(1H,d,J=2.0Hz),8.23(1H,bs),7.71(1H,t,J=52.8Hz),5.9 9(2H,s),2.52(3H,s),2.48(3H,s),1.09(3H,s),0.60-0.64(2H,m),0.42-0.46(2H,m). Example 10: Synthesis of Compound 10 [ka] Synthesis of compound 10-f 5-Bromo-7-(trifluoromethyl)-1H-indazole (500 mg, 1.89 mmol) was suspended in 5 mL of 3,4-dihydro-2H-pyran (DHP) at room temperature, trifluoroacetic acid (20 μL, 0.26 mmol) was added, and the mixture was stirred at 95 °C under nitrogen gas for 3 h. The reaction mixture was cooled to room temperature, and 100 mL of DCM was added. The mixture was washed sequentially with saturated sodium bicarbonate (100 mL) and saturated brine (100 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was purified using a high-performance separation column (PE / EA = 2:1) to obtain compound 10-f (577 mg, 88%) as a yellow oil. LC-MS (ESI): m / z = 349.0 [M+1]+ . Synthesis of compound 10-e Bis(pinacolato)diboron (164 mg, 0.65 mmol) was dissolved in 3 mL of MTBE at room temperature under a nitrogen atmosphere. (1,5-Cyclooctadiene)(methoxy)iridium(I) (dimer) (29 mg, 0.043 mmol) and 4,4'-di-tert-butyl-2,2'-dipyridine (23 mg, 0.086 mmol) were added, and the mixture was stirred at room temperature under a nitrogen atmosphere for 10 minutes. Next, a solution of compound 10-f (151 mg, 0.43 mmol) in MTBE (3 mL) was added, and the reaction mixture was stirred at 85 °C under a nitrogen atmosphere for 16 hours. The reaction mixture was concentrated under reduced pressure to give crude compound 10-e (265 mg) as a brown oil. The crude product was used directly in the next reaction.

[0142] Synthesis of compound 10-d 5-Bromo-2-(difluoromethyl)-1,3,4-thiadiazole (100 mg, 0.47 mmol) was dissolved in 10 mL of toluene at room temperature. Water (5 mL), compound 10-e (265 mg, estimated to be approximately 0.56 mmol), palladium acetate (21 mg, 0.093 mmol), Xantphos (108 mg, 0.19 mmol), and NMM (0.15 mL, 1.40 mmol) were added sequentially. The reaction mixture was stirred at 50 °C under a nitrogen atmosphere for 18 h. The reaction mixture was cooled to room temperature, 20 mL of water was added, and the mixture was extracted with ethyl acetate (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified using a high-performance column (PE / EA = 1:1) to give compound 10-d (150 mg, 67%) as a white solid. LC-MS(ESI):m / z=483.0[M+1] + . Synthesis of compound 10-c Compound 10-d (150 mg, 0.31 mmol) was dissolved in 10 mL of anhydrous 1,4-dioxane at room temperature. Pd2(dba)3 (28 mg, 0.031 mmol), Xantphos (36 mg, 0.062 mmol), DIPEA (154 μL, 0.93 mmol), and benzyl mercaptan (40 μL, 0.34 mmol) were added. The reaction mixture was stirred at 110 °C for 16 h under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The crude product was purified using a high-performance separation column (PE / EA = 3:1) to give crude compound 10-c (186 mg) as a pale yellow oil. LC-MS (ESI): m / z = 527.1 [M+1] + . Synthesis of compound 10-b Compound 10-c (186 mg, 0.35 mmol) was dissolved in 10 mL of DCM at 0 °C, and TFA (6 mL) was added. The reaction mixture was warmed to room temperature and stirred for 5 hours. The reaction mixture was concentrated under reduced pressure, and the crude product was suspended in saturated sodium bicarbonate solution (50 mL) and extracted with DCM (50 mL * 2). The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and the crude product was purified using a high-performance separation column (PE / EA = 2:1) to obtain compound 10-b (118 mg, 75%) as a pale yellow solid. LC-MS (ESI): m / z = 443.0 [M+1] + . Synthesis of compound 10-a Compound 10-b (118 mg, 0.27 mmol) was dissolved in 5 mL of DMF at 0 °C, and 5-chloromethyl-2,4-dimethyl-1,3-thiazole hydrochloride (79 mg, 0.40 mmol) and cesium carbonate (261 mg, 0.80 mmol) were added. The mixture was stirred at room temperature under a nitrogen atmosphere for 16 h. The reaction was quenched by adding 20 mL of water, extracted with ethyl acetate (80 mL × 2). The organic phase was washed with saturated brine (100 mL × 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified using a high-performance separation column (PE / EA = 1:1) to obtain compound 10-a (110 mg, 73%) as a white solid. LC-MS (ESI): m / z = 568.2 [M+1] + . Synthesis of compound 10 Compound 10-a (50 mg, 0.088 mmol) was dissolved in 5 mL of dichloromethane at room temperature under nitrogen gas conditions. The solution was cooled to 0°C, and acetic acid (20 μL, 0.35 mmol), water (6.5 μL, 0.36 mmol), and sulfone chloride (29 μL, 0.36 mmol) were added. After the addition was complete, the reaction mixture was stirred at 0°C under a nitrogen atmosphere for 1 hour, concentrated under reduced pressure at room temperature, and the resulting intermediate was dried in vacuo for 30 minutes. 3 mL of DMF was then added, cooled to 0°C, and 1-methyl-cyclopropylamine hydrochloride (28 mg, 0.26 mmol), DMAP (22 mg, 0.18 mmol), and DIPEA (73 μL, 0.44 mmol) were added. The reaction mixture was warmed to room temperature and stirred for 30 minutes. The reaction was quenched by adding 10 mL of water, extracted with ethyl acetate (50 mL * 2), and the organic phase was washed with saturated brine (100 mL * 3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was separated and purified using a high-performance separation column (DCM / MeOH = 20:1) and Prep-HPLC (base method) to obtain compound 10 (30 mg, 59%) as a white solid. LC-MS (ESI): m / z = 579.1 [M+1] + ; 1 H NMR(DMSO-d6,400MHz):δ9.18(1H,s),8.50(1H,brs),8.35(1H,s),7.70(1H,t,J=53.2Hz), 5.91(2H,s),2.51(3H,s),2.43(3H,s),1.05(3H,s),0.65-0.55(2H,m),0.50-0.40(2H,m). Example 11: Synthesis of Compound 11 [ka] Synthesis of compound 11-f To a solution of 5-bromo-1H-pyrazolo[4,3-b]pyridine (0.5 g, 2.53 mmol) in dichloromethane (10 mL) were added 3,4-dihydro-2H-pyran (0.69 mL, 8.08 mmol) and p-toluenesulfonic acid monohydrate (48 mg, 0.25 mmol). After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, the reaction mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. Purification using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 50%) yielded compound 11-f (0.5 g, 70%) as a colorless oil. LC-MS (ESI): m / z = 282.0 [M+H] + . Synthesis of compound 11-e A microwave tube was charged with (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (93 mg, 0.14 mmol), 4,4'-di-tert-butyl-2,2'-dipyridine (76 mg, 0.28 mmol), bis(pinacolato)diboron (765 mg, 3.01 mmol), and methyl tert-butyl ether (6 mL). The mixture was purged with nitrogen twice and stirred at room temperature for 5 minutes. A solution of 11-f (0.5 g, 1.77 mmol) in methyl tert-butyl ether (6 mL) was added, purged with nitrogen three times, and stirred at 85 °C for 3.5 hours. The reaction mixture was evaporated to dryness to give compound 11-e (720 mg, 99%) as a brown viscous liquid.

[0143] Synthesis of compound 11-d A reaction flask was charged with 11-e (720 mg, 1.76 mmol), 2-bromo-5-(difluoromethyl)-1,3,4-thiadiazole (680 mg, 3.16 mmol), palladium acetate (36 mg, 0.16 mmol), Xantphos (183 mg, 0.32 mmol), toluene (20 mL), and water (10 mL). The mixture was purged with nitrogen twice, and cesium carbonate (1.03 g, 3.16 mmol) was added. The reaction mixture was stirred at 25 °C for 18 h. The reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 11-d (120 mg, 18%) as an ochre solid. LC-MS (ESI): m / z = 416.0 [M+H] + . Synthesis of compound 11-c A three-neck flask was charged with 11-d (120 mg, 0.29 mmol), Xantphos (34 mg, 0.058 mmol), 1,4-dioxane (10 mL), DIPEA (0.15 mL, 0.87 mmol), and benzyl mercaptan (0.051 mL, 0.43 mmol). The mixture was purged with nitrogen twice. Pd2(dba)3 (27 mg, 0.029 mmol) was added and the mixture was purged with nitrogen three times. The reaction mixture was heated to reflux at 100 °C for 6 h. The reaction mixture was cooled to room temperature, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 11-c (100 mg, 75%) as an ochre solid. LC-MS (ESI): m / z = 460.5 [M+H] + . Synthesis of compound 11-b TFA (5 mL) was added to a solution of 11-c (100 mg, 0.22 mmol) in dichloromethane (10 mL) at room temperature. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, the solvent was removed by rotary evaporation at room temperature, diluted with ethyl acetate, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified using a high-speed separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 11-b (60 mg, 73%) as an ochre solid. LC-MS (ESI): m / z = 376.0 [M+H] + . Synthesis of compound 11-a To a solution of 11-b (60 mg, 0.16 mmol) in DMF (5 mL) at room temperature, cesium carbonate (104 mg, 0.32 mmol) and 5-(chloromethyl)-2,4-dimethyl-1,3-thiazole hydrochloride (48 mg, 0.24 mmol) were added. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. Purification using a high-performance column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) afforded compound 11-a (40 mg, 50%) as an amber oil. LC-MS (ESI): m / z = 501.2 [M+H] + . Synthesis of compound 11 To a solution of 11-a (19 mg, 0.08 mmol) in DCM (10 mL) were added acetic acid (19 mg, 0.32 mmol) and HO (6 mg, 0.33 mmol). The mixture was cooled to 0 °C, and sulfonyl chloride (44 mg, 0.33 mmol) was carefully added dropwise. After the addition was complete, the reaction mixture was stirred at 0 °C for 1 h. After the reaction was complete, the mixture was concentrated under reduced pressure at room temperature and dried on an oil pump for 10 min to obtain the crude sulfonyl chloride compound. This crude product was dissolved in DMF (5 mL), cooled to 0 °C, and 1-methylcyclopropylamine hydrochloride (13 mg, 0.12 mmol), N,N-diisopropylethylamine (0.042 mL, 0.24 mmol), and DMAP (10 mg, 0.08 mmol) were added. The reaction mixture was stirred at room temperature for 30 min. After the reaction was complete, the mixture was diluted with ethyl acetate and water. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with water, saturated aqueous sodium chloride, dried over anhydrous Na2SO4, filtered, and evaporated to dryness to give the crude product, which was purified by Prep-HPLC to give 11 (12 mg, 29%) as a white solid. LC-MS (ESI): m / z = 511.9 [M+H] + ; 1 H NMR(DMSO-d6,400MHz):δ 8.72(1H,d,J=9.2Hz),8.57(1H,bs),8.18(1H,d,J=9.2Hz),7.72(1H,t,J=53.2Hz),6.0 9(2H,s),2.52(3H,s),2.47(3H,s),1.14(3H,s),0.68-0.76(2H,m),0.38-0.45(2H,m). Example 12: Synthesis of Compound 12 [ka] Synthesis of compound 12 Compound 6 (31 mg, 0.07 mmol) was dissolved in dichloromethane (6 mL), and the reaction mixture was cooled to 0 °C. m-Chloroperoxybenzoic acid (21 mg, 0.11 mmol) was added to the solution. After the addition was complete, the reaction mixture was stirred at room temperature for 2 hours. Saturated sodium bicarbonate solution (10 mL) was added to the solution, and the mixture was extracted with dichloromethane (50 mL), washed with saturated brine (50 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1 to 1 / 1) and then by preparative HPLC (ammonium bicarbonate conditions) to obtain 12 (6 mg, 19%). LC-MS (ESI): m / z 458.1 (M+H). + ; 1 H NMR(400MHz,DMSO-d6):δ 8.83(s,1H),8.60(s,1H),8.17(d,J=12.0H,1H),7.95~7.85(m,1H),7.70(t,J=56.0Hz,1H),4.53( d,J=4.0Hz,2H),4.20(d,J=48.0Hz,2H),1.46~1.33(m,1H),0.78~0.62(m,1H),0.60~0.45(m,4H). (Example 13) Synthesis of Compound 13 [ka] Synthesis of compound 13-f A reaction flask was charged with 5-bromo-6-fluoroindazole (300 mg, 1.40 mmol), DMAP (20 mg, 0.16 mmol), and dichloromethane (15 mL). Di-tert-butyl dicarbonate (470 mg, 2.15 mmol) was added. The reaction was stirred at room temperature for 2 h. The solvent was spun off, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 13-f (439 mg, 99%) as a brown liquid, which hardened upon standing. LC-MS (ESI): m / z 315.0 (M+H). + . Synthesis of compound 13-e Under an argon atmosphere, a microwave tube was charged with (1,5-cyclooctadiene)(methoxy)iridium(I) (dimer) (45 mg, 0.069 mmol), 4,4'-di-tert-butyl-2,2'-dipyridine (37 mg, 0.14 mmol), bis(pinacolato)diboron (354 mg, 1.39 mmol), and methyl tert-butyl ether (4 mL). The mixture was purged with nitrogen twice and stirred at room temperature for 5 minutes. A solution of 13-f (439 mg, 1.39 mmol) in methyl tert-butyl ether (4 mL) was added, the mixture was purged with nitrogen twice, and the mixture was stirred at 80 °C for 2 hours. The mixture was evaporated to dryness to give compound 13-e (499 mg, 99%) as a brown solid. LC-MS (ESI): m / z 359.0 (M+H). + . Synthesis of compound 13-d A reaction flask was charged with 13-e (499 mg, 1.39 mmol), 1-f (452 ​​mg, 2.10 mmol), palladium acetate (27 mg, 0.12 mmol), XANT PHOS (152 mg, 0.26 mmol), toluene (10 mL), and water (5 mL). The mixture was purged with nitrogen twice, and cesium carbonate (860 mg, 2.64 mmol) was added. The reaction mixture was stirred at 20 °C for 18 h. Cesium carbonate (420 mg, 1.29 mmol) was added. The reaction mixture was stirred at 20 °C for 4 h. The reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 88 / 12) to give compound 13-d (200 mg, 32%) as a pale yellow solid. LC-MS(ESI):m / z449.1(M+H) + . Synthesis of compound 13-c A reaction flask was charged with 13-d (200 mg, 0.45 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), XANT PHOS (25 mg, 0.043 mmol), 1,4-dioxane (10 mL), DIPEA (180 mg, 1.39 mmol), and benzyl mercaptan (180 mg, 1.45 mmol), and the atmosphere was purged with nitrogen three times. The reaction mixture was heated to reflux at 100 °C for 2 h. The mixture was then cooled to room temperature. The reaction mixture was evaporated to dryness to give compound 13-c (219 mg, 99%) as a dark green viscous liquid. LC-MS (ESI): m / z 493.1 (M+H). + . Synthesis of compound 13-b A reaction flask was charged with 13-c (219 mg, 0.44 mmol), dichloromethane (3 mL), and anisole (0.3 mL). Trifluoroacetic acid (0.7 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 3 hours. The solvent was spun off at room temperature and purified by column chromatography (mobile phase: (petroleum ether: dichloromethane = 4:1) / ethyl acetate, 100 / 0 to 90 / 10) to give 13-b (115 mg, 66%) as a white solid. LC-MS (ESI): m / z 393.1 (M+H). + . Synthesis of compound 13-a A reaction flask was charged with 13-b (80 mg, 0.20 mmol), 5-(chloromethyl)-2,4-dimethyl-1,3-thiazole hydrochloride (80 mg, 0.40 mmol), tetrahydrofuran (3 mL), and DMF (1 mL). The atmosphere was flushed with nitrogen twice. While cooling in an ice bath, sodium hydride (40 mg, 1.00 mmol) was added. The reaction mixture was stirred in an ice bath for 20 minutes and then at room temperature for 2 hours. The reaction was monitored by rapid sampling with an uncapped capillary. The color darkened. The reaction mixture was stirred at room temperature for 2 hours. The color changed to deep red. The reaction mixture was quenched with dry ice, diluted with ethyl acetate, and saturated aqueous ammonium chloride was added. The layers were separated, and the organic phase was evaporated to dryness. The mixture was purified by column chromatography (mobile phase: dichloromethane / ethyl acetate, 100 / 0 to 90 / 10) to give 13-a (30 mg, 28%) as a colorless solid. LC-MS(ESI):m / z518.1(M+H) + . Synthesis of compound 13 A reaction flask was charged with 13-a (38 mg, 0.073 mmol), acetonitrile (2 mL), acetic acid (0.005 mL, 0.083 mmol), and water (0.005 mL, 0.28 mmol), and dichlorohydantoin (36 mg, 0.18 mmol) was added in an ice bath. The reaction mixture was stirred in an ice bath for 1 h. The reaction mixture was spin-dried at room temperature and dried on an oil pump for 10 min. 1-Methylcyclopropylamine hydrochloride (32 mg, 0.30 mmol) and dichloromethane (2.5 mL) were added to the crude product, and triethylamine (0.11 mL, 0.79 mmol) was added in an ice bath. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was spin-dried at low temperature and purified by column chromatography (mobile phase: dichloromethane / ethyl acetate, 100 / 0 to 69 / 31) to give 13 (10 mg, 27%) as a white solid. LC-MS(ESI):m / z529.0(M+H) + ; 1 H NMR(DMSO-d6,400MHz)δ 8.82(1H,d,J=6.8Hz),8.54(1H,s),8.21(1H,d,J=10.4Hz),7.70(1H,t,J=53.0Hz),5.9 7(2H,s),2.52(3H,s),2.47(3H,s),1.13(3H,s),0.68-0.62(2H,m),0.46-0.39(2H,m). (Example 14) Synthesis of Compound 14 [ka] Synthesis of compound 14-f 5-Bromo-7-fluoroindazole (645 mg, 3.00 mmol) and 3,4-dihydro-2H-pyran (6.4 mL) were added to a reaction flask, and trifluoroacetic acid (0.012 mL, 0.16 mmol) was added while stirring. The reaction mixture was stirred at 90 °C for 2 hours, diluted with dichloromethane, washed with saturated sodium bicarbonate solution, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 88 / 12) to give compound 14-f (680 mg, 76%) as a colorless viscous liquid. LC-MS (ESI): m / z 299.0 M+H+ . Synthesis of compound 14-e A microwave tube was charged with (1,5-cyclooctadiene)(methoxy)iridium(I) (dimer) (57 mg, 0.087 mmol), 4,4'-di-tert-butyl-2,2'-dipyridine (57 mg, 0.21 mmol), bis(pinacolato)diboron (308 mg, 1.21 mmol), and methyl tert-butyl ether (4 mL). The mixture was purged with nitrogen twice and stirred at room temperature for 5 min. A solution of 14-f (350 mg, 1.17 mmol) in methyl tert-butyl ether (4 mL) was added, purged with nitrogen twice, and stirred at 80 °C for 2 h. The mixture was evaporated to dryness to give compound 14-e (497 mg, 99%) as a brown viscous liquid.

[0144] Synthesis of compound 14-d A reaction flask was charged with 14-e (497 mg, 1.17 mmol), 1-f (377 mg, 1.75 mmol), palladium acetate (26 mg, 0.12 mmol), XANT PHOS (123 mg, 0.21 mmol), toluene (10 mL), and water (5 mL). The mixture was purged with nitrogen twice, and cesium carbonate (760 mg, 2.33 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours, diluted with ethyl acetate, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 88 / 12) to give compound 14-d (370 mg, 73%) as a white solid. LC-MS (ESI): m / z 433.1 (M+H). + . Synthesis of compound 14-c A reaction flask was charged with 14-d (370 mg, 0.85 mmol), XANT PHOS (49 mg, 0.085 mmol), Pd(dba) (39 mg, 0.043 mmol), 1,4-dioxane (10 mL), DIPEA (330 mg, 2.55 mmol), and benzyl mercaptan (320 mg, 2.58 mmol). The mixture was purged with nitrogen three times and heated to reflux at 100 °C for 3 h. The mixture was cooled to room temperature, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 88 / 12) to give compound 14-c (280 mg, 68%) as a yellow solid. LC-MS (ESI): m / z 477.1 (M+H). + . Synthesis of compound 14-b To a reaction flask were added 14-c (280 mg, 0.59 mmol) and dichloromethane (3 mL), followed by dropwise addition of trifluoroacetic acid (0.6 mL). The reaction mixture was allowed to react at room temperature for 3 hours. HCl / 1,4-dioxane (0.7 mL) was added. The reaction mixture was allowed to react at room temperature for 2 hours. The solvent was spun off at room temperature. The mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. To a reaction flask were added dichloromethane (3 mL), and HCl / methanol (1 mL) was added dropwise in an ice bath. The reaction mixture was allowed to react at room temperature for 1 hour. Trifluoroacetic acid (0.6 mL) was added dropwise. The reaction mixture was allowed to react at room temperature for 1 hour. The solvent was spun off at room temperature. The mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: (petroleum ether: dichloromethane = 4:1) / ethyl acetate, 100 / 0 to 85 / 15) to give 14-b (90 mg, 39%) as a white solid. LC-MS (ESI): m / z 393.0 (M+H). + . Synthesis of compound 14-a A reaction flask was charged with 14-b (85 mg, 0.22 mmol), 5-(chloromethyl)-2,4-dimethyl-1,3-thiazole hydrochloride (65 mg, 0.33 mmol), cesium carbonate (260 mg, 0.80 mmol), and DMF (2.5 mL). The reaction mixture was stirred at room temperature for 1 h and rapidly sampled with an uncapped capillary tube to detect the reaction. The reaction mixture was stirred at room temperature for 1.5 h, at which point the color changed to light brown. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous ammonium chloride, water, and saturated brine, and dried over anhydrous sodium sulfate. The organic phase was evaporated to dryness and purified by column chromatography (mobile phase: dichloromethane / ethyl acetate, 100 / 0 to 90 / 10) to give solid 14-a (90 mg, 80%). LC-MS (ESI): m / z 518.1 (M+H). + . Synthesis of compound 14 A reaction flask was charged with 14-a (90 mg, 0.17 mmol), acetonitrile (3 mL), acetic acid (0.014 mL, 0.25 mmol), and water (0.015 mL, 0.83 mmol). Dichlorohydantoin (137 mg, 0.70 mmol) was added in three portions (1 hour intervals) in an ice bath. The reaction mixture was stirred in an ice bath for 3 hours. The reaction mixture was spin-dried at low temperature and dried on an oil pump for 10 minutes to obtain the crude product. A second reaction flask was charged with 1-methylcyclopropylamine hydrochloride (75 mg, 0.70 mmol), dichloromethane (4 mL), and triethylamine (0.234 mL, 1.68 mmol). After stirring at room temperature for 5 minutes, the resulting solution was added to the crude reaction flask in an ice bath. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was spin-dried at room temperature and purified by column chromatography (mobile phase: dichloromethane / ethyl acetate, 100 / 0 to 69 / 31) to give compound 14 (58.0 mg, 63%) as a light brown solid. LC-MS (ESI): m / z 529.0 (M+H). + ; 1H NMR(DMSO-d6,400MHz):δ 8.67(1H,d,J=1.2Hz),8.34(1H,s),7.77(1H,dd,J=11.2,1.2Hz),7.71(1H,t,J=53.0Hz), 6.00(2H,s),2.52(3H,s),2.45(3H,s),1.08(3H,s),0.66-0.58(2H,m),0.45-0.39(2H,m). Example 15: Synthesis of Compound 15 [ka] Synthesis of compound 15-d Compound 5-e (100 mg, 0.24 mol) was dissolved in N,N-dimethylformamide (10 mL) and bromomethylcyclopropane (66 g, 0.49 mmol) and cesium carbonate (239 mg, 0.73 mmol) were added. The reaction mixture was stirred at 40 °C for 12 hours, after which water (50 mL) was added to the reaction mixture, extracted twice with ethyl acetate (100 mL), washed with saturated brine (100 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 10 / 1) to give compound 15-d (110 mg, 97%). LC-MS (ESI): m / z 463.2 (M+H). + . Synthesis of compound 15-c Compound 15-d (155 mg, 0.33 mmol) was dissolved in acetonitrile (10 mL), acetic acid (98 mg, 1.63 mmol), and water (29 mg, 1.61 mmol) were added, and the reaction mixture was cooled to 0 °C. Dichlorohydantoin (129 mg, 0.65 mmol) was added in three portions, and the reaction mixture was stirred at 0 °C for 1 h. The reaction mixture was rotary evaporated under reduced pressure at room temperature to obtain the crude product. Simultaneously, diisopropylethylamine (50 μL) was added to a solution of 1-methylcyclopropylamine hydrochloride (70 mg, 0.65 mmol) in dichloromethane (2 mL). The mixture was stirred at room temperature for 20 min, and then the crude product was added to a dichloromethane (10 mL) solution. Diisopropylethylamine (211 mg, 1.65 mmol) was added, and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was rotary evaporated under reduced pressure to give a crude product, which was purified by column chromatography (mobile phase, PE / EA=3 / 1) to give compound 15-c (93 mg, 59%). LC-MS (ESI): m / z 474.2 (M+H). + . Synthesis of compound 15-b Compound 15-c (93 mg, 0.20 mmol) was dissolved in tetrahydrofuran (6 mL), purged with nitrogen, and the mixture was cooled to 0 °C. Sodium hydride (24 mg, 0.60 mmol) was added under a nitrogen atmosphere. The reaction mixture was then stirred at 0 °C for 30 minutes, followed by the addition of 2-(trimethylsilyl)ethoxymethyl chloride (49 mg, 0.29 mmol). After the addition was complete, the mixture was stirred at 0 °C for 3 hours, and then stirred at 0 °C for 20 minutes while adding 5 g of dry ice in several portions. The reaction mixture was rotary evaporated under reduced pressure to obtain a crude product, which was purified by column chromatography (mobile phase, PE / EA = 10 / 1) to obtain compound 15-b (108 mg, 91%). LC-MS (ESI): m / z 604.3 (M+H). + . Synthesis of compound 15-a Compound 15-b (108 mg, 0.18 mmol), 1-(2-methylacetonyl)-piperazine (56 mg, 0.36 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (17 mg, 0.04 mmol), (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (15 mg, 0.03 mmol), and cesium carbonate (174 mg, 0.53 mmol) were added to a microwave tube containing 1,4-dioxane (6 mL). The tube was purged with nitrogen three times, and then heated and stirred at 80°C for 12 hours in a sealed container. The reaction mixture was cooled to room temperature and rotary evaporated under reduced pressure to obtain a crude product, which was purified by column chromatography (mobile phase, PE / EA = 3 / 1 to 1 / 1) to obtain compound 15-a (67 mg, 52%). LC-MS (ESI): m / z 724.5 (M+H). + . Synthesis of compound 15 Compound 15-a (67 mg, 0.09 mmol) was dissolved in dichloromethane (7 mL), trifluoroacetic acid (3 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (100 mL), washed with saturated brine (50 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by preparative HPLC (basic conditions) to obtain compound 15 (15 mg, 27%). LC-MS (ESI): m / z 594.2 (M+H). + ; 1 HNMR((400MHz,DMSO-d6):δ 8.64(s,1H),8.14(s,1H),7.85-7,56(m,2H),4.74-4.65(m,2H),4.6-4.5(m,1H),4.19-4.08(m,1H),3.45-3.34(m,1H) ),3.30-3.20(m,2H),3.02-2.80(m,3H),2.77-2.64(m,1H),1.47-1.34(m,1H),1.14-0.97(m,7H),0.68-0.32(m,7H). (Example 16) Synthesis route of compound 16 [ka] Synthesis of compound 16-d Cesium carbonate (191 mg, 0.59 mmol) and 2-iodopropane (0.073 mL, 0.73 mmol) were added to a solution of 5-e (200 mg, 0.49 mmol) in DMF (5 mL) at room temperature. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. Compound 16-d (175 mg, 79%) was obtained by separation and purification using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 50%). LC-MS (ESI): m / z = 451.1 [M+H] + . Synthesis of compound 16-c To a solution of 16-d (175 mg, 0.39 mmol) in acetonitrile (5 mL) were added acetic acid (0.089 mL, 1.55 mmol) and HO (0.029 mL, 1.59 mmol). The mixture was cooled to 0 °C, and dichlorohydantoin (153 mg, 0.78 mmol) was carefully added. After the addition was complete, the reaction mixture was stirred at 0 °C for 1 h. After the reaction was complete, the mixture was concentrated under reduced pressure at room temperature and dried on an oil pump for 30 min to obtain the crude sulfonyl chloride compound. This crude product was dissolved in DCM (10 mL), cooled to 0 °C, and 1-methylcyclopropylamine hydrochloride (63 mg, 0.58 mmol) and triethylamine (0.27 mL, 1.94 mmol) were added. The reaction mixture was warmed to room temperature and stirred for 30 min. After the reaction was complete, the mixture was diluted with dichloromethane and water. The organic phase was separated, and the aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with water, washed with saturated aqueous sodium chloride, dried over anhydrous Na2SO4, filtered, and evaporated to dryness to obtain the crude product, which was purified by high-speed separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to obtain 16-c (80 mg, 45%). LC-MS (ESI): m / z = 462.1 [M+H] + . Synthesis of compound 16-b A reaction flask was charged with 16-c (80 mg, 0.17 mmol) and THF (10 mL), and sodium hydride (60% in oil, 21 mg, 0.52 mmol) was added under ice bath conditions. The reaction mixture was stirred for 10 minutes under ice bath conditions, and then SEMCl (43 mg, 0.26 mmol) was added. After the addition was complete, stirring was continued for 1 hour. The reaction mixture was carefully quenched with dry ice powder, stirred for 30 minutes, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 16-b (60 mg, 59%). LC-MS (ESI): m / z = 592.1 [M+H] + . Synthesis of compound 16-a A microwave tube was charged with 16-b (40 mg, 0.068 mmol), 2-methyl-1-(piperazin-1-yl)propyl-1-one (21 mg, 0.14 mmol), Xantphos (7.82 mg, 0.014 mmol), Pd2dba3 (6.89 mg, 0.007 mmol), cesium carbonate (66 mg, 0.20 mmol), and 1,4-dioxane (3 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 90 °C for 6 h. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 16-a (20 mg, 42%). LC-MS(ESI): m / z 729.3 (M+NH4 + ) + . Synthesis of compound 16 A reaction flask was charged with 16-a (20 mg, 0.028 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 5 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Purification by prep-HPLC yielded compound 16 (2.5 mg, 15%). LC-MS (ESI): m / z 582.2 (M+H). + . (Example 17) Synthesis route of compound 17 [ka] Synthesis of compound 17-i To a solution of 5-bromo-7-chloro-1H-indazole (5 g, 21.6 mmol) in 3,4-dihydro-2H-pyran (74 mL, 864.01 mmol), trifluoroacetic acid (0.17 mL, 2.16 mmol) was added. After the addition was complete, the reaction mixture was heated to 90 °C and stirred for 3 hours. After the reaction was complete, the reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. Purification using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 10%) yielded compound 17-i (5.7 g, 84%). LC-MS (ESI): m / z = 315.0 [M+H] + . Synthesis of compound 17-h A sealed tube was charged with bis(pinacolato)diboron (1.21 g, 4.75 mmol), 4,4'-di-tert-butyl-2,2'-dipyridine (208 mg, 0.32 mmol), and methyl tert-butyl ether (10 mL). Under a nitrogen atmosphere, (1,5-cyclooctadiene)(methoxy)iridium(I) (dimer) (170 mg, 0.63 mmol) was added. The mixture was purged with nitrogen gas twice and stirred at room temperature for 10 minutes. A solution of 17-i (1.0 g, 3.17 mmol) in methyl tert-butyl ether (10 mL) was added. The mixture was purged with nitrogen gas three times and stirred at 85 °C for 3.5 hours. The reaction mixture was concentrated to give the crude borate ester.

[0145] The resulting crude borate ester was dissolved in toluene (20 mL) and water (10 mL), and 1-f (886 mg, 4.12 mmol), palladium acetate (71 mg, 0.32 mmol), Xantphos (367 mg, 0.63 mmol), and 1-methylmorpholine (1.05 mL, 9.51 mmol) were added. The atmosphere was purged with nitrogen gas twice. The reaction mixture was stirred at 40 °C for 18 h. After completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography (mobile phase: ethyl acetate / petroleum ether, 0% to 50%) to give compound 17-h (1.0 g, 70%). LC-MS (ESI): m / z = 449.0 (M+H). + . Synthesis of compound 17-g A reaction flask was charged with 17-h (200 mg, 0.44 mmol), XANT PHOS (16 mg, 0.028 mmol), Pd2(dba)3 (11 mg, 0.01 mmol), 1,4-dioxane (4 mL), DIPEA (180 mg, 1.39 mmol), and methyl 3-mercaptopropionate (57 mg, 0.47 mmol). The atmosphere was flushed with nitrogen three times. The reaction mixture was heated to reflux at 85 °C for 2 h. The mixture was then cooled to room temperature. The reaction mixture was evaporated to dryness, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give compound 17-g (217 mg, 100%). LC-MS (ESI): m / z 489.0 (M+H). + . Synthesis of compound 17-f A reaction flask was charged with 17-g (217 mg, 0.44 mmol) and dichloromethane (4.5 mL). Trifluoroacetic acid (1.5 mL) was added dropwise in an ice bath. The reaction mixture was stirred at room temperature for 2 hours. The solvent was spun off, diluted with ethyl acetate, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 17-f (179 mg, 100%). LC-MS (ESI): m / z 405.0 (M+H). + . Synthesis of compound 17-e A reaction flask was charged with 17-f (171 mg, 0.42 mmol), DMF (4.2 mL), and cesium carbonate (360 mg, 1.10 mmol). Methyl iodide (0.042 mL, 0.68 mmol) was added dropwise under ice bath conditions. The reaction mixture was allowed to react at room temperature for 2 hours. A small amount of methanol and ethyl acetate were added. Rotary evaporation was carried out at room temperature for 5 minutes. The reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, evaporated to dryness, and purified by column chromatography (mobile phase: dichloromethane / methanol 100 / 0 to 96 / 4) to give 17-e (140 mg, 79%). LC-MS (ESI): m / z 419.0 (M+H). + . Synthesis of compound 17-d A reaction flask was charged with 17-e (110 mg, 0.26 mmol) and DCM (12 mL). m-CPBA (136 mg, 0.79 mmol) was added under ice bath conditions. The reaction mixture was stirred under ice bath conditions for 1 hour. The mixture was diluted with ethyl acetate, washed with aqueous sodium bicarbonate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: (petroleum ether / dichloromethane 4:1) / ethyl acetate, 100 / 0 to 50 / 50, dichloromethane / methanol, 100 / 0 to 96 / 4) to give compound 17-d (110 mg, 93%). LC-MS (ESI): m / z 451.0 (M+H). + . Synthesis of compound 17-c A reaction flask was charged with 17-d (110 mg, 0.24 mmol) and methanol (3 mL). While cooling in an ice bath, sodium methanolate (40 mg, 0.74 mmol) was added. The reaction mixture was allowed to react in the ice bath for 30 minutes, after which dichloromethane (2 mL) was added and the mixture was allowed to react at room temperature for 30 minutes. TLC showed the reaction was complete. In an ice bath, 1-amino-1-cyclopropanecarbonitrile hydrochloride (116 mg, 0.98 mmol) was added and stirred until the solid dissolved. The solvent was spun off at room temperature and dried on an oil pump for 15 minutes. A small amount of dry 3A molecular sieves and DMF (3 mL) were added. In an ice bath, triethylamine (0.034 mL, 0.25 mmol) and NCS (98 mg, 0.73 mmol) were added. The reaction mixture was stirred in the ice bath for 2 hours. The reaction mixture was diluted with ethyl acetate, washed once with dilute sodium bisulfite solution, washed once with water, and back-extracted once with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 17-c (108 mg, 100%). LC-MS (ESI): m / z 444.9 (M+H). + . Synthesis of compound 17-b A reaction flask was charged with 17-c (108 mg, 0.24 mmol) and triethylamine (0.14 mL, 0.97 mmol). SEMCl (81 mg, 0.49 mmol) was added dropwise under ice bath. The reaction mixture was allowed to react at room temperature for 1 hour. Methanol (0.25 mL) was added dropwise under ice bath. The reaction mixture was stirred at room temperature for 10 minutes. The solvent was spun off at room temperature. The crude product was purified by column chromatography (mobile phase: (petroleum ether, dichloromethane 4:1) / ethyl acetate, 100 / 0 to 60 / 40) to give 17-b (115 mg, 82%). LC-MS (ESI): m / z 575.0 (M+H). + . Synthesis of compound 17-a A microwave tube was charged with 17-b (90 mg, 0.16 mmol), 2-methyl-1-(piperazin-1-yl)propan-1-one (98 mg, 0.63 mmol), RuPhos (7 mg, 0.015 mmol), RuPhos Pd G3 (7 mg, 0.008 mmol), cesium carbonate (158 mg, 0.48 mmol), and 1,4-dioxane (2.5 mL). The atmosphere was purged with nitrogen gas three times. The reaction mixture was heated at 75-80 °C for 2 h. The mixture was transferred to a large microwave tube and charged with 2-methyl-1-(piperazin-1-yl)propan-1-one (86 mg, 0.54 mmol), RuPhos (28 mg, 0.060 mmol), RuPhos Pd G3 (27 mg, 0.032 mmol), cesium carbonate (102 mg, 0.31 mmol), and 1,4-dioxane (6 mL). The reaction was heated to 85°C under argon for 1.5 hours and then cooled to room temperature. The 1,4-dioxane was spun off, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column (mobile phase: (petroleum ether / dichloromethane 4:1) / ethyl acetate, 100 / 0 to 60 / 40, dichloromethane / methanol, 100 / 0 to 95 / 5) to give compound 17-a (90 mg, 83%). LC-MS (ESI): m / z 695.3 (M+H). + . Synthesis of compound 17 A reaction flask was charged with 17-a (90 mg, 0.13 mmol) and dichloromethane (3 mL). Trifluoroacetic acid (1 mL) was added dropwise in an ice bath. The reaction mixture was allowed to react at room temperature for 2.5 hours. The solvent was spun off at room temperature, diluted with ethyl acetate, washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: 10 mM aqueous ammonium bicarbonate, acetonitrile) to give 17 (15.5 mg, 21%). LC-MS (ESI): m / z 565.2 (M+H). + ; 1H NMR(DMSO-d6,400MHz)δ 9.19(1H,s),8.65(1H,d,J=1.6Hz),7.77(1H,t,J=53.2Hz),7.57(1H,d,J=1.6Hz),4.51(4H,s),4.11(1H ,s),3.51-3.48(2H,m),3.11-2.69(5H,m),1.49-1.41(2H,m),1.36-1.29(2H,m),1.06(6H,d,J=6.4Hz). (Example 18) Synthesis route of compound 18 [ka] Synthesis of compound 18-c A microwave tube was charged with 17-g (120 mg, 0.24 mmol), 2-methyl-1-(piperazin-1-yl)propan-1-one (153 mg, 0.98 mmol), RuPhos (23 mg, 0.049 mmol), RuPhos Pd G3 (21 mg, 0.025 mmol), cesium carbonate (245 mg, 0.75 mmol), and 1,4-dioxane (8 mL). The atmosphere was flushed with argon three times. The reaction was heated at 80°C under an argon atmosphere for 3 hours. The reaction was continued to be heated at 80°C under an argon atmosphere for 2 hours. The reaction was cooled to room temperature. The dioxane was spun off, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: (petroleum ether / dichloromethane 4:1) / ethyl acetate, 100 / 0 to 0 / 100) to give compound 18-c (100 mg, 67%). LC-MS (ESI): m / z 609.3 (M+H). + . Synthesis of compound 18-b A reaction flask was charged with 18-c (100 mg, 0.16 mmol) and acetonitrile (5 mL). A solution of Oxone (302 mg, 0.49 mmol) in water (8 mL) was added dropwise under ice bath conditions. The reaction mixture was allowed to react under ice bath conditions for 2 hours. Oxone (40 mg, 0.065 mmol) was then added. The reaction mixture was allowed to react under ice bath conditions for 1 hour, after which ethyl acetate was added to dilute the mixture, and a small amount of solid sodium bisulfite was added. The mixture was stirred under ice bath conditions for 5 minutes. The layers were separated, and the aqueous phase was extracted once with ethyl acetate. The organic phases were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give compound 18-b (97 mg, 92%). LC-MS (ESI): m / z 663.2 (M+Na). + . Synthesis of compound 18-a A reaction flask was charged with 18-b (97 mg, 0.15 mmol) and methanol (5 mL). While cooling in an ice bath, sodium methanol (28 mg, 0.52 mmol) was added. The reaction mixture was allowed to react in the ice bath for 30 minutes, then at room temperature for 30 minutes, at which point TLC showed the reaction was complete. 1-Amino-1-cyclopropanecarbonitrile hydrochloride (90 mg, 0.76 mmol) was added in an ice bath and stirred until the solid dissolved. The solvent was spun off at room temperature and dried on an oil pump for 15 minutes. A small amount of dry 3A molecular sieves and DMF (3 mL) were added. Triethylamine (0.022 mL, 0.16 mmol) and NCS (61 mg, 0.46 mmol) were added in an ice bath. The reaction mixture was stirred in an ice bath for 1 hour. The reaction mixture was diluted with ethyl acetate and washed once with dilute sodium bisulfite solution and once with water. The washings were back-extracted once with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 18-a (90 mg, 94%). LC-MS (ESI): m / z 635.3 (M+H). + . Synthesis of compound 18 A reaction flask was charged with 18-a (90 mg, 0.14 mmol) and dichloromethane (3 mL). While cooling in an ice bath, trifluoroacetic acid (1 mL) was added dropwise. The reaction mixture was allowed to react in an ice bath under a nitrogen atmosphere for 1 hour. The solvent was spun off at room temperature, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and spun dry. The crude product was purified on a column (mobile phase: dichloromethane / methanol, 100 / 0 to 96 / 4) and further purified on a column (C8 column, mobile phase: 10 mM aqueous ammonium bicarbonate / acetonitrile) to give 18 (24.4 mg, 31%). LC-MS (ESI): m / z 551.2 (M+H). + ; 1 H NMR(DMSO-d6,400MHz)δ 9.07(1H,bs),8.53(1H,d,J=1.6Hz),7.69(1H,t,J=53.2Hz),7.26(1H,s),3.84-3.74(4H,m),3. 28-3.16(4H,m),3.05-2.90(1H,m),1.44-1.37(2H,m),1.33-1.28(2H,m),1.05(6H,d,J=6.7Hz). Example 19: Synthesis of Compound 19 [ka] Synthesis of compound 19-d Compound 5-e (100 mg, 0.24 mol) was dissolved in N,N-dimethylformamide (8 mL), and cesium carbonate (239 mg, 0.73 mmol) and 5-chloromethyl-2,4-dimethyl-1,3-thiazole hydrochloride (73 mg, 0.37 mmol) were added. The reaction mixture was stirred at room temperature for 4 hours. Water (100 mL) was added to the reaction mixture, and the mixture was washed with ethyl acetate (100 mL) and saturated brine (50 mL). The mixture was dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 1 / 1) to obtain compound 19-d (78 mg, 59%). LC-MS (ESI): m / z 543.0 (M+H). + . Synthesis of compound 19-c Compound 19-d (78 mg, 0.14 mmol) was dissolved in acetonitrile (8 mL), acetic acid (44 mg, 0.73 mmol), and water (13 mg, 0.73 mmol) were added, and the reaction mixture was cooled to 0 °C. Dichlorohydantoin (72 mg, 0.40 mmol) was added in three portions, and the reaction mixture was stirred at 0 °C for 1 h. The reaction mixture was rotary evaporated under reduced pressure at room temperature to give a crude product. The crude product and 1-methylcyclopropylamine hydrochloride (31 mg, 0.29 mmol) were dissolved in dichloromethane (8 mL), and diisopropylethylamine (94 mg, 0.73 mmol) was added. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 h. The reaction mixture was rotary evaporated under reduced pressure to give a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 1 / 1) to give compound 19-c (40 mg, 50%). LC-MS(ESI):m / z545.0(M+H) + . Synthesis of compound 19-b Compound 19-c (40 mg, 0.07 mmol) was dissolved in tetrahydrofuran (5 mL), purged with nitrogen, and the mixture was cooled to 0 °C. Sodium hydride (15 mg, 0.37 mmol) was added under a nitrogen atmosphere, followed by the addition of 2-(trimethylsilyl)ethoxymethyl chloride (18 mg, 0.11 mmol) at 0 °C. After the addition was complete, the mixture was stirred at 0 °C for 30 min. 5 g of dry ice was then added in several portions to the reaction mixture at 0 °C, followed by stirring for 10 min. The reaction mixture was rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1) to obtain compound 19-b (40 mg, 80%). LC-MS (ESI): m / z 675.3 (M+H). + . Synthesis of compound 19-a Compound 19-b (40 mg, 0.06 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (8 mg, 0.02 mmol), (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (7 mg, 0.01 mmol), cesium carbonate (19 mg, 0.06 mmol), and 1-(2-methylacetonyl)-piperazine (14 mg, 0.09 mmol) were added to 1,4-dioxane (3 mL), purged with nitrogen for 2 min, and then the mixture was sealed and heated and stirred at 85°C for 10 h. The reaction mixture was cooled to room temperature and rotary evaporated under reduced pressure to obtain a crude product, which was purified by column chromatography (mobile phase: PE / EA = 1 / 1 to DCM / EA = 1 / 1) to obtain compound 19-a (10 mg, 21%). LC-MS (ESI): m / z 795.7 (M+H). + . Synthesis of compound 19 Compound 19-a (45 mg, 0.06 mmol) was dissolved in dichloromethane (7 mL), trifluoroacetic acid (2.5 mL) was added, and the reaction was stirred at room temperature for 2 hours. The reaction mixture was rotary evaporated to remove dichloromethane, the pH was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (100 mL) and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by TLC (eluent: DCM / MeOH, 10 / 1) to obtain a crude product, which was then purified by preparative HPLC (basic conditions) to obtain compound 19 (8 mg, 21%). LC-MS (ESI): m / z 665.3 (M+H). + . Example 20: Synthesis of Compound 20 [ka] Compound 20 was synthesized by following the synthesis method of compound 5, using 5-b as the starting reactant and 5,6,7,8-tetrahydroimidazo-1,5-pyrazine instead of 2-methyl-1-(piperazin-1-yl)propyl-1-one. LC-MS (ESI): m / z 521.1 (M+H). + . (Example 21) Synthesis route of compound 21 [ka] Synthesis of compound 21-d Compound 5-e (250 mg, 0.61 mmol), cyclopropylboronic acid (131 mg, 1.53 mmol), copper acetate (122 mg, 0.61 mmol), 2,2'-bipyridine (96 mg, 0.61 mmol), and sodium carbonate (130 mg, 1.22 mmol) were dissolved in 1,2-dichloroethane (15 mL). The reaction mixture was stirred in air at 70 °C for 2 h. The mixture was then cooled to room temperature, filtered through diatomaceous earth, and rotary evaporated under reduced pressure to give a crude product. The crude product was added with saturated ammonium chloride solution (10 mL) and water (100 mL), extracted with ethyl acetate (150 mL), washed with saturated brine (100 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to give a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1) to give compound 21-d (200 mg, 73%). LC-MS(ESI):m / z449.0(M+H) + . Synthesis of compound 21-c Compound 21-d (230 mg, 0.51 mmol) was dissolved in acetonitrile (20 mL), and acetic acid (92 mg, 1.54 mmol) and water (28 mg, 1.54 mmol) were added. The reaction mixture was cooled to 0 °C, and dichlorohydantoin (202 mg, 1.03 mmol) was added in three portions. The reaction mixture was stirred at 0 °C for 1 h. The reaction mixture was then rotary evaporated under reduced pressure to give a crude product. The crude product and 1-methylcyclopropylamine hydrochloride (110 mg, 1.03 mmol) were dissolved in dichloromethane (20 mL), and diisopropylethylamine (529 mg, 4.10 mmol) was added. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 h. The reaction mixture was then rotary evaporated under reduced pressure to give a crude product. The crude product was purified by column chromatography (mobile phase, DCM / EA = 10 / 1) to give compound 21-c (180 mg, 76%). LC-MS(ESI):m / z460.0(M+H) + . Synthesis of compound 21-b Compound 21-c (180 mg, 0.39 mmol) was dissolved in N,N-dimethylformamide (6 mL) and tetrahydrofuran (6 mL). The mixture was cooled to 0 °C, and then sodium hydride (63 mg, 1.57 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (131 mg, 0.78 mmol) were added under a nitrogen atmosphere. After the addition, the reaction mixture was stirred at 0 °C for 30 min. Then, 5 g of dry ice was added to the reaction mixture in several portions at 0 °C, and the mixture was stirred for 10 min. The mixture was then rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1) to obtain compound 21-b (220 mg, 95%). LC-MS (ESI): m / z 590.1 (M+H). + . Synthesis of compound 21-a Compound 21-b (100 mg, 0.17 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (32 mg, 0.07 mmol), (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (29 mg, 0.03 mmol), and cesium carbonate (166 mg, 0.51 mmol) were added to 1,4-dioxane (10 mL), followed by addition of 1-(2-methylacetonyl)-piperazine (53 mg, 0.34 mmol). The mixture was purged with nitrogen 10 times, sealed, and heated and stirred at 78°C for 2 hours. The reaction mixture was cooled to room temperature and rotary evaporated under reduced pressure to obtain a crude product, which was purified by column chromatography (mobile phase: PE / EA = 3 / 1 to DCM / EA = 10 / 1) to obtain compound 21-a (75 mg, 62%). LC-MS (ESI): m / z 710.3 (M+H). + . Synthesis of compound 21 Compound 21-a (90 mg, 0.13 mmol) was dissolved in dichloromethane (4 mL) and trifluoroacetic acid (2 mL) was added at 0 °C. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was rotary evaporated to remove dichloromethane, the pH was adjusted to 8 with saturated sodium bicarbonate solution, extracted with ethyl acetate (100 mL), and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by TLC (eluent: DCM / MeOH, 10 / 1) to obtain a crude product, which was then purified by HPLC (basic conditions) to obtain compound 21 (23 mg, 31%). LC-MS (ESI): m / z 580.2 (M+H). + ; 1 H NMR(400MHz,DMSO-d6):δ 8.57(s,1H),8.16(s,1H),7.69(t,J=56.0Hz,1H),7.55(s,1H),4.85-4.76(m,1H),4.65-4.40(m,1H),4.19-3.94(m,1H),3.56-3.46(m,2) H),3.02-2.93(m,2H),2.87-2.64(m,2H),1.45-1.38(m,2H),1.28-1.21(m,3H),1.08-1.02(m,9H),0.65-0.61(m,2H),0.41-0.36(m,2H). (Example 22) Synthetic route of compound 22 [ka] Synthesis of compound 22-d Compound 5-e (141 mg, 0.34 mmol) was dissolved in N,N-dimethylformamide (4 mL) and iodoethane (0.055 mL, 0.69 mmol) and Cs2CO3 (338 mg, 1.04 mmol) were added. The reaction mixture was stirred overnight at 40 °C, water (30 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (60 mL x 6), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to give a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 20 / 1) to give compound 22-d (85 mg, 56%). LC-MS (ESI): m / z = 437.1 (M+H). + . Synthesis of compound 22-c Compound 22-d (85 mg, 0.20 mmol) was dissolved in acetonitrile (5 mL). The reaction mixture was cooled to 0 °C, and then acetic acid (0.056 mL, 0.97 mmol) and water (0.018 mL, 0.97 mmol) were added. Dichlorohydantoin (77 mg, 0.40 mmol) was added in three portions, and the reaction mixture was stirred at 0 °C for 1 h. The reaction mixture was then rotary evaporated under reduced pressure at room temperature to obtain the crude product. The crude product was dissolved in DCM (5 mL), cooled to 0 °C, and a solution of 1-methylcyclopropylamine hydrochloride (43 mg, 0.40 mmol) and diisopropylethylamine (50 μL) in dichloromethane (1 mL) was slowly added. Finally, diisopropylethylamine (0.14 mL, 0.76 mmol) was added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was rotary evaporated under reduced pressure to give a crude product, which was then purified by column chromatography (mobile phase, PE / EA=3 / 1) to give compound 22-c (54 mg, 62%). LC-MS (ESI): m / z=448.0 (M+H). + . Synthesis of compound 22-b A reaction flask was charged with 22-c (162 mg, 0.36 mmol) and DMF (4.5 mL), and cesium carbonate (295 mg, 0.90 mmol) was added under ice bath conditions. The reaction mixture was stirred under ice bath conditions for 5 minutes, and then SEMCl (79 mg, 0.47 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour. Cesium carbonate (118 mg, 0.36 mmol) and SEMCl (39 mg, 0.24 mmol) were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give compound 22-b (180 mg, 86%). LC-MS (ESI): m / z 595.0 (M+NH4). + . Synthesis of compound 22-a A microwave tube was charged with RuPhos (19 mg, 0.041 mmol), RuPhos Pd G3 (17 mg, 0.020 mmol), and cesium carbonate (135 mg, 0.41 mmol). A solution of 22-b (80 mg, 0.14 mmol) in 1,4-dioxane (4 mL) was added to a syringe. The atmosphere was purged with nitrogen gas twice. A solution of 2-methyl-1-(piperazin-1-yl)propan-1-one (64 mg, 0.41 mmol) in 1,4-dioxane (4 mL) was added to a syringe. The atmosphere was purged with nitrogen gas twice. The reaction mixture was heated at 70-75 °C for 4 hours and then cooled to room temperature. In a separate microwave tube, RuPhos (19 mg, 0.041 mmol), RuPhos Pd G3 (17 mg, 0.020 mmol), and cesium carbonate (135 mg, 0.41 mmol) were added. A solution of 22-b (80 mg, 0.14 mmol) in 1,4-dioxane (4 mL) was added via syringe. The atmosphere was purged with nitrogen gas twice. A solution of 2-methyl-1-(piperazin-1-yl)propan-1-one (64 mg, 0.41 mmol) in dioxane (4 mL) was added via syringe. The atmosphere was purged with nitrogen gas twice. The reaction mixture was heated at 60 °C for 4 hours and then cooled to room temperature. The two reaction mixtures were combined, the solvent was spun off, diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified on a silica gel column (mobile phase (petroleum ether / dichloromethane (4:1)) / ethyl acetate, 0% to 70%) to give 22-a (64 mg, 33%). LC-MS (ESI): m / z 715.4 (M+NH4). + . Synthesis of compound 22 22-a (64 mg, 0.092 mmol) was added to a reaction flask, and while cooling in an ice bath, dichloromethane (1.5 mL) and trifluoroacetic acid (0.5 mL) were added. The reaction mixture was reacted in an ice bath for 10 minutes, then at room temperature for 2 hours. The solvent was spun off, diluted with ethyl acetate, washed once with saturated sodium bicarbonate solution, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by column (C8 column, mobile phase: 10 mM ammonium bicarbonate aqueous solution, acetonitrile) to give 22 (20 mg, 38%). LC-MS (ESI): m / z 568.2 (M+H).+ . 1 H NMR (DMSO-d6, 400 MHz): δ 8.62(1H,d,J=1.6Hz),8.15(1H,s),7.86-7.55(2H,m),4.95-4.79(2H,m),4.5 5(1H,d,J=12.8Hz),4.14(1H,d,J=13.2Hz),3.52-3.41(1H,m),3.33-3.25(2H ,m),3.04-2.91(2H,m),2.91-2.81(1H,m),2.79-2.67(1H,m),1.53(3H,t,J=7 .2Hz),1.11-1.03(6H,m),1.03(3H,s),0.66-0.60(2H,m),0.45-0.35(2H,m). (Example 23) Synthesis route of compound 23 [ka] Synthesis of compound 23-d To a solution of 5-e (200 mg, 0.49 mmol) in DMF (5 mL) at room temperature, potassium carbonate (101 mg, 0.73 mmol) and trifluoromethanesulfonic acid 2,2,2-trifluoroethyl ester (0.14 mL, 0.98 mmol) were added. After the addition was complete, the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. Compound 23-d (200 mg, 83%) was obtained by separation and purification using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 50%). LC-MS (ESI): m / z = 491.0 [M+H] + . Synthesis of compound 23-c To a solution of 23-d (200 mg, 0.41 mmol) in acetonitrile (5 mL) were added acetic acid (0.093 mL, 1.63 mmol) and HO (0.030 mL, 1.67 mmol). The mixture was cooled to 0 °C, and dichlorohydantoin (161 mg, 0.82 mmol) was carefully added. After the addition was complete, the reaction mixture was stirred at 0 °C for 1 h. After the reaction was complete, the mixture was concentrated under reduced pressure at room temperature and dried on an oil pump for 30 min to obtain the crude sulfonyl chloride compound. This crude product was dissolved in DCM (10 mL), cooled to 0 °C, and 1-methylcyclopropylamine hydrochloride (66 mg, 0.61 mmol) and triethylamine (0.28 mL, 2.04 mmol) were added. The reaction mixture was warmed to room temperature and stirred for 30 min. After the reaction was complete, the mixture was diluted with dichloromethane and water. The organic phase was separated, and the aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with water, washed with saturated aqueous sodium chloride, dried over anhydrous Na2SO4, filtered, and evaporated to dryness to obtain the crude product, which was purified by high-speed separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to obtain 23-c (150 mg, 73%). LC-MS (ESI): m / z = 502.0 [M+H] + . Synthesis of compound 23-b Compound 23-c (150 mg, 0.3 mmol) was dissolved in N,N-dimethylformamide (5 mL) and tetrahydrofuran (5 mL). The mixture was cooled to 0 °C, and then sodium hydride (48 mg, 1.20 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (100 mg, 0.60 mmol) were added under a nitrogen atmosphere. After the addition, the reaction mixture was stirred at 0 °C for 30 min. Then, 5 g of dry ice was added to the reaction mixture at 0 °C in several portions and stirred for 10 min. The mixture was then rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 10 / 1) to obtain compound 23-b (148 mg, 78%).

[0146] Synthesis of compound 23-a Compound 23-b (112 mg, 0.18 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (33 mg, 0.07 mmol), (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (30 mg, 0.04 mmol), and cesium carbonate (173 mg, 0.53 mmol) were added to 1,4-dioxane (12 mL), followed by addition of 1-(2-methylacetonyl)-piperazine (55 mg, 0.35 mmol). The mixture was purged with nitrogen gas 10 times, sealed, and heated and stirred at 67°C for 8 hours. The reaction mixture was cooled to room temperature and rotary evaporated under reduced pressure to obtain a crude product, which was purified by column chromatography (mobile phase, PE / EA = 3 / 1 to 1 / 1) to obtain compound 23-a (31 mg, 24%). LC-MS (ESI): m / z 752.1 (M+H). + . Synthesis of compound 23 Compound 23-a (40 mg, 0.05 mmol) was dissolved in dichloromethane (3 mL) and trifluoroacetic acid (1 mL) was added at 0° C. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was rotary evaporated to remove dichloromethane, the pH was adjusted to 8 with saturated sodium bicarbonate solution, extracted with ethyl acetate (100 mL), washed with saturated brine (50 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by preparative HPLC (basic conditions) to obtain compound 23 (15 mg, 45%). LC-MS (ESI): m / z 622.1 (M+H). + ; 1 HNMR(400MHz,DMSO-d6):δ 8.72(s,1H),8.18(s,1H),7.91(s,1H),7.72(t,J=56.0Hz,1H),5.87-5.76(m,2H),4.57(d,J=12.0Hz,1H),4.16(d,J=12.0Hz) ,1H),3.45-3.35(m,1H),3.17(d,J=8.0Hz,2H),2.99-2.75(m,4H),1.10-0.99(m,9H),0.69-0.60(m,2H),0.42-0.37(m,2H). Example 24: Synthesis of Compound 24 [ka] Synthesis of compound 24-a Compound 17-b (100 mg, 0.17 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (32 mg, 0.07 mmol), (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (29 mg, 0.04 mmol), and cesium carbonate (170 mg, 0.52 mmol) were added to 1,4-dioxane (10 mL) and stirred at room temperature for 5 minutes. 1-(cyclopropylcarbonyl)piperazine (54 mg, 0.35 mmol) was then added, and the mixture was purged with nitrogen gas 12 times. The mixture was then sealed and heated at 62°C for 12 hours with stirring. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth, and the filtrate was rotary evaporated under reduced pressure to give a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1 to DCM / EA = 3 / 1) to give compound 24-a (105 mg, 87%). LC-MS (ESI): m / z 1385.6 (2M+H). + . Synthesis of compound 24 Compound 24-a (145 mg, 0.21 mmol) was dissolved in dichloromethane (4.5 mL) at 0 °C, and trifluoroacetic acid (1.5 mL) was added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was rotary evaporated to remove dichloromethane, and the pH was adjusted to 7-8 with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate (100 mL), washed with saturated brine (100 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by HPLC (basic conditions) to obtain compound 24 (35 mg, 30%). LC-MS (ESI): m / z 563.1 (M+H). + ; 1H NMR(400MHz,DMSO-d6):δ 9.18(s,1H),8.65(s,1H),7.71(t,J=52.0Hz,1H),7.58(s,1H),4.52(s,3H),4.45-4.35(m,1H), 3.62-3.47(m,2H),3.09-2.68(m,3H),2.58-2.50(m,2H),1.46-1.22(m,5H),0.80-0.74(m,4H). Example 25: Synthesis of Compound 25 [ka] Synthesis of compound 25-a A microwave tube was charged with 5-b (30 mg, 0.053 mmol), morpholine (14 mg, 0.088 mmol), Xantphos (6.13 mg, 0.011 mmol), Pd2dba3 (4.85 mg, 0.005 mmol), cesium carbonate (52 mg, 0.16 mmol), and 1,4-dioxane (3 mL). The atmosphere was purged with nitrogen gas three times. The reaction mixture was heated at 85 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. This crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to obtain compound 25-a (25 mg, 76%). LC-MS (ESI): m / z 1251.6 (2M+Na + ) + . Synthesis of compound 25 A reaction flask was charged with 25-a (25 mg, 0.041 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 5 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Purification by prep-HPLC yielded compound 25 (8 mg, 41%). LC-MS (ESI): m / z 485.0 (M+H). + ; 1H NMR(DMSO-d6,400MHz):δ 8.58(1H,d,J=1.6Hz),7.70(1H,t,J=52.8Hz),7.55(1H,d,J=1.2Hz),4.49(3H,s),3.7 5-4.11(4H,m),2.80-3.29(4H,m),1.03(3H,s),0.58-0.66(2H,m),0.34-0.41(2H,m). (Example 26) Synthesis route of compound 26 [ka] Synthesis of compound 26-f A reaction flask was charged with 17-f (160 mg, 0.40 mmol) and DMF (3 mL). Under ice bath conditions, cesium carbonate (385 mg, 1.18 mmol) was added and stirred for 5 minutes. Iodoethane (120 mg, 0.77 mmol) was added dropwise. The reaction mixture was allowed to react at room temperature for 2 hours. The mixture was rotary evaporated at room temperature for 5 minutes, diluted with ethyl acetate, washed twice with water, and the aqueous phase was back-extracted once with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 26-f (171 mg, 100%). LC-MS (ESI): m / z 432.9 (M+H). + . Synthesis of compound 26-e A reaction flask was charged with 26-f (171 mg, 0.40 mmol) and acetonitrile (7 mL). A solution of oxone (729 mg, 1.19 mmol) in water (7 mL) was added dropwise in an ice bath. The reaction mixture was allowed to react in an ice bath for 1 hour. The mixture was extracted twice with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 26-e (177 mg, 99%).

[0147] Synthesis of compound 26-d To a solution of 26-e (200 mg, 0.45 mmol) in dichloromethane (10 mL) was added m-CPBA (231 mg, 1.34 mmol) in an ice bath. After the addition was complete, the reaction mixture was warmed to 0 °C and stirred for 1 h. After the reaction was complete, rotary evaporation at room temperature gave 26-d (150 mg, 72%). LC-MS (ESI): m / z = 929.0 [2M+H] + . Synthesis of compound 26-c A reaction flask was charged with 26-d (150 mg, 0.32 mmol), methanol (10 mL), and dichloromethane (10 mL). The reaction mixture was cooled to 0 °C in an ice bath, sodium chloride (52 mg, 0.97 mmol) was added, and the reaction mixture was allowed to react for 1 h while maintaining the ice bath. 1-Amino-1-cyclopropanecarbonitrile hydrochloride (153 mg, 1.29 mmol) was added, and the mixture was concentrated at room temperature to remove the solvent and then vacuum dried for 20 min. DMF (8 mL) and a small amount of 3A molecular sieves were added. After stirring for 3 min in an ice bath, triethylamine (0.09 mL, 0.65 mmol) and 1-amino-1-cyclopropanecarbonitrile hydrochloride (38 mg, 0.32 mmol) were added. NCS (86 mg, 0.65 mmol) was then added in an ice bath. The reaction mixture was stirred for 1 h in an ice bath. The mixture was diluted with ethyl acetate, washed with sodium bisulfite solution, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 26-c (100 mg, 68%). LC-MS (ESI): m / z = 459.0 [M+H] + . Synthesis of compound 26-b A reaction flask was charged with 26-c (100 mg, 0.22 mmol) and DCM (10 mL). Triethylamine (0.12 mL, 0.87 mmol) and SEMCl (0.077 mL, 0.44 mmol) were added under ice bath conditions. After the addition was complete, the mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was quenched under ice bath conditions with methanol (0.25 mL) and stirred for 10 min. After completion, the mixture was concentrated at low temperature to remove the solvent. The crude product was purified by column chromatography (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 26-b (110 mg, 86%). LC-MS (ESI): m / z = 589.0 [M+H] + . Synthesis of compound 26-a A microwave tube was charged with 26-b (110 mg, 0.19 mmol), 1-(2-methylacetonyl)-piperazine (58 mg, 0.37 mmol), Ruphos (35 mg, 0.075 mmol), Ruphos Pd G3 (31 mg, 0.037 mmol), cesium carbonate (183 mg, 0.56 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / (petroleum ether / dichloromethane 4:1), 0% to 100%) to give compound 26-a (110 mg, 83%). LC-MS(ESI):m / z1417.4[2M+H] + . Synthesis of compound 26 A reaction flask was charged with 26-a (110 mg, 0.16 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Purification by prep-HPLC yielded compound 26 (10 mg, 11%). LC-MS (ESI): m / z 579.1 [M+H] + . (Example 27) Synthetic route of compound 27 [ka] Synthesis of compound 27-a A microwave tube was charged with 5-b (80 mg, 0.14 mmol), cyclopropyl-piperazin-1-yl-methyl ketone (44 mg, 0.28 mmol), Xantphos (16 mg, 0.028 mmol), Pd2dba3 (13 mg, 0.014 mmol), cesium carbonate (139 mg, 0.44 mmol), and 1,4-dioxane (3 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 85 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 27-a (70 mg, 72%). LC-MS(ESI):m / z704.0[M+Na] + . Synthesis of compound 27 A reaction flask was charged with 27-a (70 mg, 0.10 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Compound 27 (15 mg, 26%) was obtained by separation and purification using a high-performance separation column (mobile phase: methanol / dichloromethane, 0% to 10%). LC-MS (ESI): m / z 552.1 [M+H] + ; 1 H NMR(DMSO-d6,400MHz):δ 8.59(1H,s),8.14(1H,s),7.70(1H,t,J=53.2Hz),7.57(1H,s),4.51(3H,s),4.15-4.58(2H,m),3.40-3.80(2H, m),2.60-3.23(4H,m),2.02-2.13(1H,m),1.03(3H,s),0.71-0.91(4H,m),0.58-0.68(2H,m),0.34-0.45(2H,m). (Example 28) Synthesis route of compound 28 [ka] Synthesis of compound 28-h Chlorosulfonic acid (30 mL) was added to the reaction flask, and 1-methyl-3-methoxycarbonylindazole (10 g, 52.58 mmol) was added in portions over 10 minutes in an ice bath. The reaction was allowed to proceed at room temperature for 5 minutes. The reaction mixture was stirred at 65 °C for 18 hours (with a tail gas dryer / absorber). The reaction mixture was cooled to room temperature, added dropwise to 300 g of ice, extracted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 28-h (13.5 g, 89%).

[0148] Synthesis of compound 28-g A reaction flask was charged with 28-h (13.5 g, 46.76 mmol) and dichloromethane (135 mL). Dibromohydantoin (13.37 g, 46.76 mmol) was added in an ice bath. Trifluoromethanesulfonic acid (5 mL) was added dropwise to the suspension. The reaction mixture was stirred in an ice bath for 10 minutes and then at room temperature for 1.5 hours. Trifluoromethanesulfonic acid (5 mL) was added dropwise to the suspension. Dichloromethane (60 mL) was added. The reaction mixture was stirred at room temperature for 1.5 hours. Ice water was added to the reaction mixture, which was then extracted twice with ethyl acetate, washed twice with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified using a column (mobile phase: petroleum ether / ethyl acetate, 100:0 to 60:40) to obtain product 28-g (10.1 g, 59%).

[0149] Synthesis of compound 28-f A reaction flask was charged with 1-amino-1-cyclopropanecarbonitrile hydrochloride (7.05 g, 59.46 mmol), pyridine (35 mL), and a small amount of 3A molecular sieves. The mixture was stirred in an ice bath for 5 minutes. A solution of 28-f (10.1 g, 27.48 mmol) in dichloromethane (70 mL) containing dry molecular sieves was added dropwise over 5 minutes in an ice bath. After 10 minutes in the ice bath, the mixture was allowed to react at room temperature for 2 hours. The solvent was then spun off. Ice water and solid sodium hydrogen sulfate were added until the pH reached 6-7. Petroleum ether was added, filtered, and the filter cake was washed with aqueous sodium hydrogen sulfate, water, and petroleum ether. The aqueous phase was extracted with ethyl acetate, the extract was washed with water, evaporated to dryness, triturated with ethyl acetate and petroleum ether, and the solids were combined and dried under vacuum to give 28-f (11.3 g, 100%). LC-MS(ESI):m / z412.9(M+H) + . Synthesis of compound 28-e A reaction flask was charged with 28-f (11.3 g, 27.34 mmol) and dichloromethane (150 mL). Triethylamine (12.5 mL, 89.93 mmol) was added in an ice bath and stirred for 10 minutes. SEMCl (8.0 mL, 45.20 mmol) was added dropwise in an ice bath and stirred for 10 minutes. The mixture was stirred in a room temperature water bath for 1.5 hours. The solvent was spun off at room temperature, water and ethyl acetate were added, and the mixture was thoroughly stirred and filtered. The filtrate was separated, and the aqueous phase was extracted once with ethyl acetate. The organic phases were combined, washed with water, washed with saturated brine, and evaporated to dryness to give 28-e (14.8 g, 100%). LC-MS (ESI): m / z 560.1 (M+NH4). + . Synthesis of compound 28-d A reaction flask was charged with 28-e (14.8 g, 27.23 mmol), absolute ethanol (150 mL), and hydrazine hydrate (10 mL, 206.15 mmol). The reaction mixture was heated and stirred at 52 °C for 7 h. The reaction mixture was then cooled to room temperature. The solvent was spun off at room temperature, ice water was added, and the mixture was extracted twice with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 28-d (14.5 g, 98%). LC-MS (ESI): m / z 1084.8 (2M+H).+ . Synthesis of compound 28-c A reaction flask was charged with 28-d (14.5 g, 26.68 mmol) and dichloromethane (150 mL). Triethylamine (5.19 mL, 37.35 mmol) was added dropwise in an ice bath. The mixture was stirred for 5 minutes in an ice bath. Difluoroacetic anhydride (3.25 mL, 28.01 mmol) was added dropwise in an ice bath. The reaction mixture was stirred for 1 hour in an ice bath. Methanol (2.5 mL) was added, and the mixture was warmed from the ice bath to room temperature and stirred for 20 minutes. The solvent was spun off at room temperature. Water and ethyl acetate were added to the reaction flask, and the mixture was separated. The aqueous phase was extracted once, and the organic phases were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 60 / 40) to give 28-c (13.2 g, 80%). LC-MS(ESI):m / z638.0(M+NH4) + . Synthesis of compound 28-b A reaction flask was charged with 28-c (11.3 g, 18.18 mmol), Lawesson's reagent (17.75 g, 43.89 mmol), and THF (200 mL). The reaction mixture was heated and stirred at 80 °C under an argon atmosphere for 10 h. The mixture was cooled to room temperature, and the solvent was spun off. The crude product was diluted with an ethyl acetate / petroleum ether mixture, washed three times with aqueous sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give a crude product. Ammonia in methanol / methanol / dichloromethane (1:1:20) (200 mL) was added and the mixture was stirred at room temperature for 2 h. The mixture was evaporated to dryness and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 70 / 30) to give 28-b (5.8 g, 51%). LC-MS (ESI): m / z 619.0 (M+H). + . Synthesis of compound 28-a Compound 28-b (30 mg, 0.048 mmol), phenylboronic acid (18 mg, 0.15 mmol), tetrakis(triphenylphosphine)palladium (6 mg, 0.0050 mmol), and Cs2CO3 (31 mg, 0.096 mmol) were added to a mixture of 1,4-dioxane (5 mL) and water (1 mL) at room temperature. The reaction mixture was stirred overnight at 100 °C under nitrogen. After cooling to room temperature, saturated brine (50 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (50 mL x 3). The organic phase was washed with saturated brine (60 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified using a high-performance separation column (PE / EA = 10:1) to give compound 28-a (20 mg, 67%). LC-MS (ESI): m / z = 617.1 [M+1] + . Synthesis of compound 28 Compound 28-a (20 mg, 0.032 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetic acid (1 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (60 mL x 3), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain the crude product. The crude product was purified by prep-TLC (DCM:MeOH = 20:1) to obtain compound 28 (5 mg, 32%). LC-MS (ESI): m / z = 487.0 [M+1] + . (Example 29) Synthesis route of compound 29 [ka] Synthesis of compound 29-a A microwave tube was charged with 28-b (90 mg, 0.15 mmol), morpholine (25 mg, 0.29 mmol), Ruphos (27 mg, 0.058 mmol), Ruphos Pd G3 (24 mg, 0.029 mmol), cesium carbonate (142 mg, 0.44 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. This crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / (petroleum ether / dichloromethane 4:1), 0% to 100%) to give compound 29-a (70 mg, 77%). LC-MS(ESI):m / z1251.2[2M+H] + . Synthesis of compound 29 A reaction flask was charged with 29-a (70 mg, 0.11 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Compound 29 (20 mg, 36%) was obtained by separation and purification using a high-performance separation column (mobile phase: ethyl acetate / (petroleum ether / dichloromethane 4:1), 0% to 100%). LC-MS (ESI): m / z 496.0 [M+H] + ; 1 H NMR(DMSO-d6,400MHz):δ 9.22(1H,s),8.64(1H,s),7.01(1H,t,J=53.2Hz),7.56(1H,s),4.50(3H,s), 3.70-3.99(4H,m),2.85-3.26(4H,m),1.39-1.49(2H,m),1.25-1.36(2H,m). (Example 30) Synthesis route of compound 30 [ka] Synthesis of compound 30-e Compound 17-f (880 mg, 2.17 mmol) and potassium carbonate (601 mg, 4.35 mmol) were added to N,N-dimethylformamide (20 mL), and trifluoromethanesulfonic acid 2,2,2-trifluoroethyl ester (757 mg, 3.26 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 2 hours. Water (100 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL). The mixture was washed with water (100 mL) and saturated brine (100 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 10 / 1) to obtain compound 30-e (263 mg, 25%). LC-MS (ESI): m / z 486.8 (M+H). + . Synthesis of compound 30-d Compound 30-e (163 mg, 0.34 mmol) was dissolved in dichloromethane (10 mL) and m-chloroperoxybenzoic acid (204 mg, 1.00 mmol) was added in portions at 0 °C. The reaction mixture was stirred at 0 °C for 1 hour, followed by the addition of saturated sodium bicarbonate solution (50 mL) and water (50 mL). The mixture was extracted with dichloromethane (100 mL), washed with water (100 mL), washed with saturated brine (100 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1 to PE:DCM (4:1) / EA = 3 / 1) to obtain compound 30-d (153 mg, 88%), which was used directly in the next reaction. LC-MS (ESI): m / z 518.8 (M+H). + . Synthesis of compound 30-c Compound 30-d (153 mg, 0.30 mmol) was dissolved in dichloromethane (4 mL) and methanol (4 mL), and sodium methanolate (48 mg, 0.89 mmol) was added thereto at 0°C. The reaction mixture was stirred at 0°C for 1 hour, and then 1-amino-cyclopropanecarbonitrile hydrochloride (140 mg, 1.18 mmol) was added thereto. The mixture was stirred at room temperature for 10 minutes, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was dried in vacuum with an oil pump for 1.5 hours, and then dissolved in N,N-dimethylformamide. The resulting mixture was dissolved in 30-c (15 mL) of methyl amine and added with triethylamine (33 mg, 0.32 mmol) and N-chlorosuccinimide (118 mg, 0.89 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 2 h, added with water (100 mL), extracted with ethyl acetate (200 mL), washed with water (50 mL) and saturated brine (100 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to give crude 30-c (190 mg), which was used directly in the next reaction. LC-MS (ESI): m / z 512.6 (M+H). + . Synthesis of compound 30-b Compound 30-c (190 mg, 0.37 mmol) was dissolved in dichloromethane (20 mL), triethylamine (112 mg, 1.11 mmol) was added, and 2-(trimethylsilyl)ethoxymethyl chloride (124 mg, 0.74 mmol) was added dropwise. After the addition, the reaction mixture was stirred at room temperature for 2 h. Methanol (0.5 mL) was added to the reaction mixture, and the mixture was stirred for 10 min. The mixture was rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1) to obtain compound 30-b (110 mg, 46%). LC-MS (ESI): m / z 642.9 (M+H). + . Synthesis of compound 30-a Compound 30-b (43 mg, 0.07 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (12 mg, 0.03 mmol), (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (11 mg, 0.01 mmol), and cesium carbonate (65 mg, 0.20 mmol) were added to 1,4-dioxane (5 mL) and stirred at room temperature for 10 minutes. 1-(2-methylacetonyl)-piperazine (21 mg, 0.13 mmol) was then added, and the mixture was purged with nitrogen 10 times. The mixture was then sealed and heated and stirred at 72°C for 16 hours. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth, and the filtrate was rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1 to 1 / 1) to obtain compound 30-a (10 mg, 20%). LC-MS (ESI): m / z 763.1 (M+H). + . Synthesis of compound 30 Compound 30-a (53 mg, 0.07 mmol) was dissolved in dichloromethane (3 mL) at 0 °C, and trifluoroacetic acid (1 mL) was added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was rotary evaporated to remove dichloromethane, and the pH was adjusted to 7-8 with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate (100 mL), washed with saturated brine (100 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by HPLC (basic conditions) to obtain compound 30 (9 mg, 20%). LC-MS (ESI): m / z 633.1 (M+H). + . (Example 31) Synthesis route of compound 31 [ka] Synthesis of compound 31-a Compound 28-b (50 mg, 0.081 mmol), 4-(tri-n-butylstannyl)pyrimidine (45 mg, 0.12 mmol), tetrakis(triphenylphosphine)palladium (9 mg, 0.0080 mmol), and LiCl (0.1 mg, 0.0020 mmol) were added to toluene (5 mL) at room temperature, and the reaction mixture was stirred overnight under nitrogen gas at 110 °C. The mixture was cooled to room temperature and concentrated under reduced pressure to obtain a crude product. The crude product was purified using a high-performance separation column (PE / EA = 10:1) to obtain compound 31-a (25 mg, 50%). LC-MS (ESI): m / z = 619.2 [M+H] + . Synthesis of compound 31 Compound 31-a (25 mg, 0.040 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetic acid (1 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (60 mL x 3), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain the crude product. The crude product was purified by pre-TLC (DCM:MeOH = 20:1) to obtain compound 31 (5 mg, 25%). LC-MS (ESI): m / z = 489.0 [M+1] + . (Example 32) Synthesis route of compound 32 [ka] Synthesis of compound 32-a Compound 17-b (145 mg, 0.25 mmol), 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl (47 mg, 0.10 mmol), (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate (42 mg, 0.05 mmol), and cesium carbonate (246 mg, 0.76 mmol) were added to 1,4-dioxane (13 mL) and stirred at room temperature for 5 minutes. 1-acetylpiperazine (32 mg, 0.25 mmol) was then added, and the mixture was purged with nitrogen gas 12 times. The mixture was then sealed and heated and stirred at 62°C for 12 hours. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth, and the filtrate was rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 10 / 1 to 1 / 1) to obtain compound 32-a (100 mg, 59%). LC-MS (ESI): m / z 667.0 (M+H). + . Synthesis of compound 32 Compound 32-a (100 mg, 0.15 mmol) was dissolved in dichloromethane (4 mL) and trifluoroacetic acid (1.5 mL) was added at 0°C. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was rotary evaporated to remove dichloromethane, the pH was adjusted to 7-8 with saturated sodium bicarbonate solution, extracted with ethyl acetate (100 mL), washed with saturated brine (100 mL), and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by HPLC (basic conditions) to obtain compound 32 (32 mg, 40%). LC-MS (ESI): m / z 537.1 (M+H). + ; 1 H NMR((400MHz,DMSO-d6):δ 9.19(s,1H),8.65(s,1H),7.71(t,J=52.0Hz,1H),7.56(s,1H),4.51(s,3H),4.48-4.36(m,1 H),4.02-3.90(m,1H),3.56-3.38(m,2H),3.16-2.58(m,4H),2.09(s,3H),1.46-1.29(m,4H). (Example 33) Synthesis route of compound 33 [ka] Synthesis of compound 33-a A microwave tube was charged with 28-b (80 mg, 0.13 mmol), piperazine-1-carboxylic acid dimethylamide (41 mg, 0.26 mmol), Ruphos (24 mg, 0.052 mmol), Ruphos Pd G3 (22 mg, 0.026 mmol), cesium carbonate (126 mg, 0.39 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. This crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / (petroleum ether / dichloromethane 4:1), 0% to 100%) to give compound 33-a (70 mg, 77%). LC-MS(ESI):m / z696.2[M+H] + . Synthesis of compound 33 A reaction flask was charged with 33-a (70 mg, 0.10 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Prep-TLC (PE:EA=1:2) yielded compound 33 (20 mg, 35%). LC-MS (ESI): m / z 566.1 [M+H] + . (Example 34) Synthesis route of compound 34 [ka] Synthesis of compound 34-a A microwave tube was charged with 28-b (30 mg, 0.048 mmol), 1-methylsulfonylpiperazine (16 mg, 0.096 mmol), Ruphos (9 mg, 0.019 mmol), Ruphos Pd G3 (8 mg, 0.010 mmol), cesium carbonate (47 mg, 0.15 mmol), and 1,4-dioxane (3 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. This crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / (petroleum ether / dichloromethane 4:1), 0% to 100%) to give compound 34-a (25 mg, 73%). LC-MS(ESI):m / z703.1[M+H] + . Synthesis of compound 34 A reaction flask was charged with 34-a (25 mg, 0.036 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Prep-TLC (PE:EA=1:2) yielded compound 34 (10 mg, 49%). LC-MS (ESI): m / z 573.0 [M+H] + . (Example 35) Synthesis route of compound 35 [ka] Synthesis of compound 35-a A reaction flask was charged with 28-b (80 mg, 0.13 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Compound 35-a (50 mg, 79%) was obtained by separation and purification using a high-performance separation column (mobile phase: ethyl acetate / (petroleum ether / dichloromethane 4:1), 0% to 100%). LC-MS (ESI): m / z 488.9 [M+H] + . Synthesis of compound 35 A microwave tube was charged with 35-a (30 mg, 0.061 mmol), (S)-2-methylmorpholine (12 mg, 0.12 mmol), Ruphos (12 mg, 0.025 mmol), Ruphos Pd G3 (10 mg, 0.012 mmol), cesium carbonate (60 mg, 0.18 mmol), and 1,4-dioxane (3 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. The next day, the reaction mixture was heated to 90 °C and stirred for 4 h. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove 1,4-dioxane. The mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give the crude product, which was identified by prep-TLC (PE:EA = 1:1) to give compound 35 (8 mg, 26%). LC-MS(ESI):m / z510.1[M+H] + . (Example 36) Synthesis route of compound 36 [ka] Synthesis of compound 36-a A microwave tube was charged with 28-b (30 mg, 0.048 mmol), 1-benzoylpiperazine (18 mg, 0.096 mmol), Ruphos (9 mg, 0.019 mmol), Ruphos Pd G3 (8 mg, 0.010 mmol), cesium carbonate (47 mg, 0.15 mmol), and 1,4-dioxane (3 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. This crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / (petroleum ether / dichloromethane 4:1), 0% to 100%) to give compound 36-a (25 mg, 71%). LC-MS(ESI):m / z729.1[M+H] + . Synthesis of compound 36 A reaction flask was charged with 36-a (25 mg, 0.034 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Prep-TLC (PE:EA=1:2) yielded compound 36 (15 mg, 73%). LC-MS (ESI): m / z 599.1 [M+H] + . (Example 37) Synthesis route of compound 37 [ka] Synthesis of compound 37-a A microwave tube was charged with 28-b (50 mg, 0.081 mmol), (R)-2-methylmorpholine chloride (22 mg, 0.16 mmol), Ruphos (15 mg, 0.032 mmol), Ruphos Pd G3 (14 mg, 0.016 mmol), cesium carbonate (132 mg, 0.40 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give the crude product. The crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 37-a (40 mg, 77%). LC-MS(ESI):m / z640.1[M+H] + . Synthesis of compound 37 A reaction flask was charged with 37-a (40 mg, 0.063 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Prep-TLC (PE:EA=1:1) yielded compound 37 (15 mg, 47%). LC-MS (ESI): m / z 510.0 [M+H] + . (Example 38) Synthesis route of compound 38 [ka] Synthesis of compound 38-c N-Boc-piperazine (500 mg, 2.68 mmol), dichloromethane (5 mL), and triethylamine (1.12 mL, 8.05 mmol) were added to a reaction flask, and then 1-methyl-cyclopropanecarbonyl chloride (477 mg, 4.02 mmol) was added dropwise under ice bath conditions. The mixture was stirred overnight at room temperature. The next day, the reaction was quenched with water, extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, spin-dried, and purified by column chromatography (mobile phase: methanol / dichloromethane: 0% to 10%) to give compound 38-c (700 mg, 97%). LC-MS (ESI): m / z = 269.1 [M+H] + . Synthesis of compound 38-b A reaction flask was charged with 38-c (700 mg, 2.61 mmol) and 1,4-dioxane (10 mL). A solution of hydrochloric acid in dioxane (4 M, 4.66 mL, 18.63 mmol) was added dropwise in an ice bath, and the reaction mixture was stirred overnight at room temperature. The next day, the reaction mixture was filtered, and the resulting white filter cake was washed with a small amount of 1,4-dioxane and dried under vacuum to give compound 38-b (400 mg, 75%). LC-MS (ESI): m / z 169.0 [M+H] + . Synthesis of compound 38-a A microwave tube was charged with 28-b (45 mg, 0.073 mmol), 38-b (30 mg, 0.15 mmol), Ruphos (14 mg, 0.029 mmol), Ruphos Pd G3 (12 mg, 0.015 mmol), cesium carbonate (118 mg, 0.36 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen gas three times. The reaction mixture was heated at 60 °C overnight. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove 1,4-dioxane. The mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. This crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 38-a (40 mg, 78%). LC-MS (ESI): m / z 707.1 [M+H] + . Synthesis of compound 38 A reaction flask was charged with 38-a (40 mg, 0.057 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Compound 38 (15 mg, 46%) was obtained by prep-HPLC. LC-MS (ESI): m / z 577.0 [M+H] + ; 1 H NMR(DMSO-d6,400MHz):δ 9.12(1H,bs),8.65(1H,d,J=1.6Hz),7.70(1H,t,J=53.2Hz),7.58(1H,d,J=1.6Hz),4.52(3H,s),4.18-4.49(2H,m),3.04- 3.43(4H,m),2.70-3.02(2H,m),1.38-1.51(2H,m),1.30-1.35(2H,m),1.29(3H,s),0.83-0.89(2H,m),0.55-0.62(2H,m). Example 39: Synthesis of Compound 39 [ka] Compound 39 was synthesized by following the synthesis method of compound 30, using 30-b as the starting reactant and 38-b instead of 1-(2-methylacetonyl)-piperazine. LC-MS (ESI): m / z 645.0 (M+H). + . Example 40: Synthesis of Compound 40 [ka] Synthesis of compound 40-b Compound 1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (100 mg, 0.48 mmol) was dissolved in dichloromethane (5 mL), diisopropylethylamine (185 mg, 1.43 mmol) was added, and the system was cooled to 0 ° C., and isobutyric acid chloride (61 mg, 0.57 mmol) was added dropwise. After the addition was complete, the reaction mixture was stirred at room temperature for 2 hours. Saturated sodium bicarbonate solution (10 mL) was added to the reaction mixture, and the mixture was extracted twice with dichloromethane (50 mL), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 1 / 1 to 1 / 5) to obtain compound 40-b (75 mg, 56%). LC-MS (ESI): m / z 280.2 (M+H). + . Synthesis of compound 40-a Compound 28-b (55 mg, 0.09 mmol), 40-b (37 mg, 0.13 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13 mg, 0.02 mmol), and potassium carbonate (37 mg, 0.27 mmol) were added to 1,4-dioxane (5 mL) and water (0.5 mL). The reaction mixture was purged with nitrogen gas 10 times, then sealed and heated at 100 °C with stirring for 6 h. The reaction mixture was cooled to room temperature and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (mobile phase, PE / EA = 3 / 1 to 1 / 1) to obtain compound 40-a (60 mg, 98%). LC-MS (ESI): m / z 692.1 (M+H). + . Synthesis of compound 40 Compound 40-a (70 mg, 0.10 mmol) was dissolved in dichloromethane (4.5 mL) at 0 °C, and trifluoroacetic acid (1.5 mL) was added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was rotary evaporated to remove dichloromethane, and the pH was adjusted to 7-8 with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate (100 mL), washed with saturated brine (100 mL), and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by HPLC (basic conditions) to obtain compound 40 (30 mg, 53%). LC-MS (ESI): m / z 562.2 (M+H). + . (Example 41) Synthesis route of compound 41 [ka] Synthesis of compound 41-a 28-b (100 mg, 0.16 mmol), 1-(6-pyridazinyl)piperazine (53 mg, 0.32 mmol), RuPhos Pd G3 (27 mg, 0.032 mmol), RuPhos (30 mg, 0.065 mmol), Cs2CO3 (105 mg, 0.32 mmol), and 1,4-dioxane (6 mL) were added to a 25 mL sealed tube at room temperature. The reaction mixture was stirred overnight at 90 °C under nitrogen. After cooling to room temperature, saturated brine (60 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (50 mL x 3). The organic phase was washed with saturated brine (40 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified using a high-performance separation column (PE / EA = 3:1) to give compound 41-a (65 mg, 57%). LC-MS(ESI): m / z=703.1[M+H] + . Synthesis of compound 41 Compound 41-a (65 mg, 0.092 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetic acid (1 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (60 mL x 3), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain the crude product. The crude product was purified by prep-TLC (DCM / MeOH = 20 / 1) to obtain compound 41 (9 mg, 17%). LC-MS (ESI): m / z = 573.0 [M+H] + . (Example 42) Synthesis route of compound 42 [ka] Synthesis of compound 42-a Compound 28-b (50 mg, 0.081 mmol), 4-hydroxypiperidine (16 mg, 0.16 mmol), RuPhos Pd G3 (14 mg, 0.016 mmol), RuPhos (15 mg, 0.032 mmol), CsCO3 (79 mg, 0.24 mmol), and 1,4-dioxane (5 mL) were added to a 25 mL sealed tube at room temperature. The reaction mixture was stirred overnight at 90 °C under nitrogen atmosphere. After cooling to room temperature, saturated brine (60 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (50 mL x 3). The organic phase was washed with saturated brine (60 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude compound. The crude compound was purified using a high-performance separation column (PE / EA = 3:1) to give compound 42-a (13 mg, 25%). LC-MS(ESI): m / z=640.2[M+H] + . Synthesis of compound 42 Compound 42-a (13 mg, 0.020 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetic acid (1 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (60 mL x 3), dried over anhydrous sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by pre-HPLC (TFA method) to obtain compound 42 (2 mg, 19%). LC-MS (ESI): m / z = 510.1 [M+H] + . (Example 43) Synthesis route of compound 43 [ka] Synthesis of compound 43-a 28-b (50 mg, 0.081 mmol), 1-(pyridin-2-ylcarbonyl)piperazine (31 mg, 0.16 mmol), RuPhos Pd G3 (13.50 mg, 0.016 mmol), RuPhos (15 mg, 0.032 mmol), Cs2CO3 (79 mg, 0.24 mmol), and 1,4-dioxane (5 mL) were added to a 25 mL sealed tube at room temperature. The reaction mixture was stirred overnight at 90 °C under nitrogen. After cooling to room temperature, saturated brine (60 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (50 mL x 3). The organic phase was washed with saturated brine (40 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified using a high-performance separation column (PE / EA = 3:1) to give compound 43-a (40 mg, 68%). LC-MS(ESI): m / z=730.1[M+H] + . Synthesis of compound 43 Compound 43-a (40 mg, 0.055 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetic acid (1 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (60 mL x 3), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by pre-HPLC (TFA method) to obtain compound 43 (2 mg, 6.1%). LC-MS (ESI): m / z = 600.2 [M+H] + . (Example 44) Synthesis route of compound 44 [ka] Synthesis of compound 44-a 28-b (100 mg, 0.16 mmol), 4-piperidinemethanol (37 mg, 0.32 mmol), RuPhos Pd G3 (27 mg, 0.032 mmol), RuPhos (30 mg, 0.065 mmol), CsCO3 (105 mg, 0.32 mmol), and 1,4-dioxane (6 mL) were added to a 25 mL sealed tube at room temperature. The reaction mixture was stirred overnight at 90 °C under nitrogen atmosphere. After cooling to room temperature, saturated brine (60 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (50 mL x 3). The organic phase was washed with saturated brine (40 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified using a high-performance separation column (PE / EA = 3:1) to give compound 44-a (85 mg, 81%). LC-MS(ESI): m / z=654.1[M+H] + . Synthesis of compound 44 Compound 44-a (85 mg, 0.13 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetic acid (1 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (60 mL x 3), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain a crude product. The crude product was purified by prep-HPLC (NH4HCO3 method) to obtain compound 44 (2 mg, 2.9%). LC-MS (ESI): m / z = 524.0 [M+H] + . Example 45: Synthesis of Compound 45 [ka] Synthesis of compound 45-a A microwave tube was charged with 28-b (50 mg, 0.081 mmol), 1-(piperazin-1-yl)propan-1-one (23 mg, 0.16 mmol), Ruphos (15 mg, 0.032 mmol), Ruphos Pd G3 (14 mg, 0.016 mmol), cesium carbonate (79 mg, 0.24 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove 1,4-dioxane. The mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give the crude product, which was purified using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 45-a (40 mg, 73%). LC-MS(ESI):m / z681.1[M+H] + . Synthesis of compound 45 A reaction flask was charged with 45-a (40 mg, 0.059 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Prep-TLC (PE:EA=1:2) yielded compound 45 (20 mg, 62%). LC-MS (ESI): m / z 551.1 [M+H] + . (Example 46) Synthesis route of compound 46 [ka] Synthesis of compound 46-a A microwave tube was charged with 28-b (50 mg, 0.081 mmol), 2-oxa-7-azaspiro[3.5]nonane (21 mg, 0.16 mmol), Ruphos (15 mg, 0.032 mmol), Ruphos Pd G3 (14 mg, 0.016 mmol), cesium carbonate (79 mg, 0.24 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove 1,4-dioxane. The mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give the crude product, which was purified using a high-performance column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 46-a (40 mg, 74%). LC-MS(ESI):m / z666.1[M+H] + . Synthesis of compound 46 A reaction flask was charged with 46-a (40 mg, 0.060 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Prep-TLC (PE:EA=1:2) yielded compound 46 (15 mg, 47%). LC-MS (ESI): m / z 536.0 [M+H] + . (Example 47) Synthesis route of compound 47 [ka] Synthesis of compound 47-a 28-b (100 mg, 0.16 mmol), trifluoroacetylpiperazine (59 mg, 0.32 mmol), RuPhos Pd G3 (27 mg, 0.032 mmol), RuPhos (30 mg, 0.065 mmol), CsCO3 (105 mg, 0.32 mmol), and 1,4-dioxane (6 mL) were added to a 25 mL sealed tube at room temperature. The reaction mixture was stirred overnight at 90 °C under nitrogen atmosphere. After cooling to room temperature, saturated brine (60 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (50 mL x 3). The organic phase was washed with saturated brine (40 mL x 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified using a high-performance separation column (PE / EA = 3:1) to give compound 47-a (77 mg, 66%). LC-MS(ESI): m / z=721.1[M+H] + . Synthesis of compound 47 Compound 47-a (77 mg, 0.11 mmol) was dissolved in dichloromethane (4 mL), trifluoroacetic acid (1 mL) was added, and the reaction mixture was stirred at room temperature for 2 hours. The pH of the reaction mixture was adjusted to 8 with saturated sodium bicarbonate solution, water (30 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 3), washed with saturated brine (60 mL x 3), dried over sodium sulfate, filtered, and rotary evaporated under reduced pressure to obtain the crude product. The crude product was purified by prep-TLC (DCM / MeOH = 20 / 1) to obtain compound 47 (35 mg, 55%). LC-MS (ESI): m / z = 591.0 [M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 9.20(1H,s),8.67(1H,d,J=1.2Hz),7.70(1H,d,J=53.2Hz),7.61(1H,d,J=1.2Hz),4.52(3H,s),4.49-4.2 9(1H,m),4.08-3.63(2H,m),3.62-3.35(3H,m),3.20-2.72(2H,m),1.46-1.39(2H,m),1.35-1.27(2H,m). (Example 48) Synthesis of Compound 48 [ka] Compound 48 was synthesized by following the synthesis method of compound 29, using 28-b as the starting reactant and 1-(isopropylsulfonyl)piperazine instead of morpholine. LC-MS (ESI): m / z 601.1 [M+H] + . Example 49: Synthesis of Compound 49 [ka] Compound 49 was synthesized by following the synthesis method of compound 29, using 28-b as the starting reactant and N-isobutylpiperazine instead of morpholine. LC-MS (ESI): m / z 551.1 [M+H] + ; 1 H NMR(DMSO-d6,400MHz):δ 9.18(1H,s),8.62(1H,s),7.70(1H,t,J=53.2Hz),7.56(1H,s),4.48(3H,s),2.72-3.30(6H,m),2.23-2.45(2 H,m),2.17(2H,d,J=7.2Hz),1.77-1.89(1H,m),1.39-1.49(2H,m),1.29-1.35(2H,m),0.96(6H,d,J=6.4Hz). Example 50: Synthesis of Compound 50 [ka] Synthesis of compound 50-c N-Boc-piperazine (500 mg, 2.68 mmol), dichloromethane (10 mL), DMAP (618 mg, 3.22 mmol), and EDCI (618 mg, 3.22 mmol) were added to a reaction flask, followed by 2-methylbutanoic acid (0.35 mL, 3.22 mmol). The mixture was stirred overnight at room temperature. The next day, the reaction was quenched with water, extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, spun dry, and purified by column chromatography (mobile phase: ethyl acetate / petroleum ether: 0% to 50%) to give compound 50-c (700 mg, 96%). LC-MS (ESI): m / z = 271.2 [M+H] + . Synthesis of compound 50-b A reaction flask was charged with 50-c (700 mg, 2.59 mmol) and 1,4-dioxane (10 mL). A solution of 1,4-dioxane in hydrochloric acid (4 M, 3.24 mL, 12.96 mmol) was added dropwise in an ice bath, and the reaction mixture was stirred overnight at room temperature. The next day, the reaction mixture was filtered, and the resulting white filter cake was washed with a small amount of 1,4-dioxane and dried under vacuum to give compound 50-b (400 mg, 75%). LC-MS (ESI): m / z 171.2 [M+H] + . Synthesis of compound 50 Compound 50 was synthesized by following the synthesis method of compound 29, using 28-b as the starting reactant and 50-b instead of morpholine. LC-MS (ESI): m / z 579.1 [M+H] + . (Example 51) Synthesis route of compound 51 [ka] Synthesis of compound 51-c N-Boc-piperazine (500 mg, 2.68 mmol), dichloromethane (5 mL), and triethylamine (1.12 mL, 8.05 mmol) were added to a reaction flask, and then 1-pyrrolidinecarboxylic acid chloride (0.59 mL, 5.37 mmol) was added dropwise under ice bath conditions. The mixture was stirred overnight at room temperature. The next day, the reaction was quenched with water, extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, spin-dried, and purified by column chromatography (mobile phase: methanol / dichloromethane: 0% to 10%) to give compound 51-c (700 mg, 92%). LC-MS (ESI): m / z = 284.2 [M+H] + . Synthesis of compound 51-b A reaction flask was charged with 51-c (700 mg, 2.47 mmol) and 1,4-dioxane (10 mL). A solution of 1,4-dioxane in hydrochloric acid (4 M, 3.09 mL, 12.35 mmol) was added dropwise in an ice bath, and the reaction mixture was stirred overnight at room temperature. The next day, the reaction mixture was filtered, and the resulting white filter cake was washed with a small amount of 1,4-dioxane and dried under vacuum to give compound 51-b (400 mg, 74%). LC-MS (ESI): m / z 184.2 [M+H]+ . Synthesis of compound 51 Compound 51 was synthesized by following the synthesis method of compound 29, using 28-b as the starting reactant and 51-b instead of morpholine. LC-MS (ESI): m / z 592.1 [M+H] + . (Example 52) Synthesis of Compound 52 [ka] Compound 52 was synthesized by following the synthesis method of compound 29, using 28-b as the starting reactant and 3,3,3-trifluoro-1-(piperazin-1-yl)propan-1-one instead of morpholine. LC-MS (ESI): m / z = 605.1 [M+H] + . (Example 53) Synthesis of Compound 53 [ka] Compound 53 was synthesized by following the synthesis method of compound 29, using 28-b as the starting reactant and N-phenylpiperazine instead of morpholine. LC-MS (ESI): m / z = 571.0 [M+H] + . (Example 54) Synthesis of Compound 54 [ka] Compound 54 was synthesized by following the synthesis method of compound 17, using 17-b as the starting reactant and 1-isopropylpiperazine instead of 2-methyl-1-(piperazin-1-yl)propan-1-one. LC-MS (ESI): m / z 537.1 (M+H). + . Example 55: Synthesis of Compound 55 [ka] Synthesis of compound 55-e To a solution of 17-f (400 mg, 0.99 mmol) in acetonitrile (10 mL) at room temperature, potassium fluoride (115 mg, 1.98 mmol) and bromodifluoromethyl diethylphosphonate (0.35 mL, 1.98 mmol) were added. After the addition was complete, the reaction mixture was warmed to 35 °C and stirred overnight. After the reaction was complete, the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. Compound 55-e (120 mg, 27%) was obtained by separation and purification using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 50%). LC-MS (ESI): m / z = 454.9 [M+H] + . Synthesis of compound 55-d To a solution of 55-e (120 mg, 0.26 mmol) in dichloromethane (10 mL) was added m-CPBA (137 mg, 0.79 mmol) in an ice bath. After the addition, the reaction mixture was stirred at 0 °C for 1 h. After the reaction was completed, the solvent was removed by rotary evaporation at room temperature, diluted with ethyl acetate, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 55-d (100 mg, 78%). LC-MS (ESI): m / z = 487.0 [M+H] + . Synthesis of compound 55-c A reaction flask was charged with 55-d (100 mg, 0.21 mmol), methanol (10 mL), and dichloromethane (10 mL). The reaction mixture was cooled to 0 °C in an ice bath, sodium methanol (33 mg, 0.62 mmol) was added, and the reaction mixture was allowed to react for 1 h while maintaining the ice bath. 1-Amino-1-cyclopropanecarbonitrile hydrochloride (97 mg, 0.82 mmol) was added, and the mixture was concentrated at room temperature to remove the solvent and then vacuum dried for 20 min. DMF (8 mL) and a small amount of 3A molecular sieves were added. After stirring for 3 min in an ice bath, triethylamine (0.06 mL, 0.41 mmol) and 1-amino-1-cyclopropanecarbonitrile hydrochloride (24 mg, 0.21 mmol) were added. NCS (55 mg, 0.41 mmol) was then added in an ice bath. The reaction mixture was stirred in an ice bath for 1 h. The mixture was diluted with ethyl acetate, washed with sodium bisulfite solution, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give 55-c (80 mg, 81%). LC-MS (ESI): m / z = 480.9 [M+H] + . Synthesis of compound 55-b A reaction flask was charged with 55-c (80 mg, 0.17 mmol) and DCM (10 mL). Triethylamine (0.093 mL, 0.67 mmol) and SEMCl (0.059 mL, 0.33 mmol) were added under ice bath conditions. After the addition was complete, the mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was quenched under ice bath conditions with methanol (0.25 mL) and stirred for 10 min. After completion, the mixture was concentrated at low temperature to remove the solvent. The crude product was purified by column chromatography (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 55-b (85 mg, 84%). LC-MS (ESI): m / z = 611.0 [M+H] + . Synthesis of compound 55-a A microwave tube was charged with 55-b (60 mg, 0.098 mmol), 1-(2-methylacetonyl)-piperazine (31 mg, 0.20 mmol), Ruphos (18 mg, 0.039 mmol), Ruphos Pd G3 (16 mg, 0.020 mmol), cesium carbonate (96 mg, 0.30 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After the reaction was completed, the mixture was cooled to room temperature, the 1,4-dioxane was spun off, and the mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. This crude product was purified using a high-performance column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 55-a (40 mg, 56%). LC-MS(ESI):m / z731.1[M+H] + . Synthesis of compound 55 A reaction flask was charged with 55-a (40 mg, 0.055 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Purification by prep-HPLC yielded compound 55 (10 mg, 30%). LC-MS (ESI): m / z 601.0 [M+H] + ; 1 H NMR(DMSO-d6,400MHz):δ 9.08(1H,bs),8.60(1H,t,J=57.2Hz),7.92(1H,s),7.79(1H,t,J=52.8Hz),6.96(1H,s),3.35 -3.88(8H,m),2.91-3.03(1H,m),1.39-1.49(2H,m),1.27-1.35(2H,m),1.05(6H,d,J=6.4Hz). (Example 56) Synthesis route of compound 56 [ka] Synthesis of compound 56-c A reaction flask was charged with 28-d (0.48 g, 0.88 mmol) and dichloromethane (10 mL). Triethylamine (0.18 mL, 1.33 mmol) was added dropwise in an ice bath. The mixture was stirred for 5 minutes in an ice bath. Acetic anhydride (0.087 mL, 0.93 mmol) was added dropwise in an ice bath. The reaction mixture was stirred for 1 hour in an ice bath. Methanol (2.5 mL) was added, and the mixture was warmed from the ice bath to room temperature and stirred for 20 minutes. The solvent was spun off at room temperature. Water and ethyl acetate were added to the reaction flask, and the mixture was separated. The aqueous phase was extracted once, and the organic phases were combined, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 60 / 40) to give 56-c (0.45 g, 87%). LC-MS(ESI):m / z585.0[M+H] + . Synthesis of compound 56-b A reaction flask was charged with 56-c (0.45 g, 0.77 mmol), Lawesson's reagent (0.78 g, 1.92 mmol), and THF (20 mL). The reaction mixture was heated and stirred at 80 °C under a nitrogen atmosphere for 10 h. The mixture was cooled to room temperature, and the solvent was spun off. The crude product was diluted with an ethyl acetate / petroleum ether mixture, washed three times with aqueous sodium bicarbonate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give a crude product. Ammonia in methanol / methanol / dichloromethane (1:1:20) (20 mL) was added and the mixture was stirred at room temperature for 2 h. The mixture was evaporated to dryness and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 70 / 30) to give 56-b (0.2 g, 45%). LC-MS (ESI): m / z 583.0 [M+H] + . Synthesis of compound 56-a A microwave tube was charged with 56-b (80 mg, 0.14 mmol), 1-(2-methylacetonyl)-piperazine (43 mg, 0.27 mmol), Ruphos (26 mg, 0.055 mmol), Ruphos Pd G3 (23 mg, 0.027 mmol), cesium carbonate (134 mg, 0.41 mmol), and 1,4-dioxane (8 mL). The atmosphere was purged with nitrogen three times. The reaction mixture was heated at 60 °C overnight. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove 1,4-dioxane. The mixture was diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give the crude product, which was purified using a high-performance separation column (mobile phase: ethyl acetate / petroleum ether, 0% to 100%) to give compound 56-a (60 mg, 66%). LC-MS(ESI):m / z659.4[M+H] + . Synthesis of compound 56 A reaction flask was charged with 56-a (60 mg, 0.091 mmol) and dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added dropwise at room temperature. The reaction mixture was reacted at room temperature for 4 hours and then concentrated at room temperature to remove the solvent. The mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain a crude product. Purification by prep-TLC (PE:EA = 1:2) gave compound 56 (25 mg, 52%). LC-MS (ESI): m / z 529.2 [M+H] + . (Example 57) Synthesis route of compound 57 [ka] Synthesis of compound 57-f A reaction flask was charged with methyl 5-bromo-1H-indazole-3-carboxylate (2.55 g, 9.997 mmol), DMF (12.5 mL), and ethanol (12.5 mL). Hydrazine hydrate (2.5 mL, 51.538 mmol) was added dropwise at room temperature. The reaction mixture was heated and stirred at 55°C for 6 hours. The ethanol was spun off, poured into ice water, filtered, and dried to give 57-f (2.40 g, 94%). LC-MS (ESI): m / z 255.0 (M+H).+ . Synthesis of compound 57-e A reaction flask was charged with 57-f (2.40 g, 9.41 mmol), dichloromethane (20 mL), and DMF (10 mL). Triethylamine (1.962 mL, 14.114 mmol) was added under ice bath conditions. Difluoroacetic anhydride (1.97 g, 11.291 mmol) was added dropwise in six portions (one every 5 minutes) under ice bath conditions. After the addition was complete, the reaction mixture was stirred under ice bath conditions for 30 minutes. The dichloromethane was spun off. The remaining suspension was added to ice water, filtered, and dried to give 57-e (2.9 g, 93%). LC-MS (ESI): m / z 332.9 (M+H). + . Synthesis of compound 57-d A reaction flask was charged with 57-e (2.9 g, 8.706 mmol), Lawesson's reagent (4.6 g, 11.373 mmol), and tetrahydrofuran (40 mL). The reaction mixture was heated to reflux under a nitrogen atmosphere for 3 hours. The mixture was cooled to room temperature, and the solvent was spun off. The mixture was diluted with ethyl acetate, dichloromethane, and petroleum ether, washed twice with saturated sodium bicarbonate solution, washed once with saturated brine, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, from 100 / 0 to 80 / 20, with ethyl acetate mixed; the product was very poorly soluble and tailing) to give compound 57-d (2.5 g, 87%). LC-MS (ESI): m / z 330.8 (M+H). + . Synthesis of compound 57-c A reaction flask was charged with 57-d (500 mg, 1.510 mmol), Pd2(dba)3 (69.13 mg, 0.075 mmol), XANT PHOS (87.37 mg, 0.151 mmol), 1,4-dioxane (6 mL), DIPEA (586 mg, 4.534 mmol), and methyl 3-mercaptopropionate (362.90 mg, 3.020 mmol), sequentially. The atmosphere was purged with nitrogen three times. The reaction mixture was heated and stirred at 110 °C for 3 h, at which point a large amount of solid precipitated. After cooling to room temperature, the solvent was spun off, diluted with ethyl acetate, washed twice with water, and the suspension was spun dry to give 57-c (559 mg, 100%). LC-MS (ESI): m / z 371.0 (M+H). + . Synthesis of compound 57-b A reaction flask was charged with 57-c (559 mg, 1.51 mmol) and dichloromethane (20 mL). m-CPBA (651 mg, 3.773 mmol) was added under ice bath conditions. The reaction mixture was stirred under ice bath conditions for 1 hour. m-CPBA (469 mg, 2.72 mmol) was added. The reaction mixture was stirred under ice bath conditions for 1 hour. The solvent was spun off at room temperature, diluted with ethyl acetate, washed five times with 5% aqueous sodium bicarbonate solution, evaporated to dryness, and purified by column chromatography (mobile phase: petroleum ether / ethyl acetate, 100 / 0 to 80 / 20) to give compound 57-b (450 mg, 74%). LC-MS (ESI): m / z 403.0 (M+H). + . Synthesis of compound 57-a To a solution of 57-b (100 mg, 0.25 mmol) in DMF (5 mL) at room temperature, potassium carbonate (69 mg, 0.50 mmol) and 4-fluorobenzyl bromide (71 mg, 0.37 mmol) were added. Aft...

Claims

1. A compound having a five-membered heteroaryl ring structure represented by formula I, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof. 【Chemistry 1】 (Here, " 【Chemistry 2】 " represents a single bond or a double bond, 【Chemistry 3】 The two cycloalkyls in the ring are both aromatic. R ａ１ , R ａ２ and R ａ３ are independently hydrogen, halogen, cyano group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, OR ａ－１ , C(=O)R ａ－２ , -NR ａ－３１ R ａ－３２ , -C(=O)OR ａ－４ , -C(=O)NR ａ－５１ R ａ－５２ , or one or more R ａ１－１ C substituted with １－６ is an alkyl group, R ａ１－１ is a halogen, a hydroxyl group or -OC １－６ is an alkyl group, Or, R ａ２ and R ａ３ is a connected carbon atom and C ３－７ Cycloalkane, one or more R ａ２－１ C substituted with ３－７ Cycloalkane, "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R ａ２－２ and forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with R ａ２－１ and R ａ２－２ are independently a halogen, an oxo, a hydroxyl group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ is an alkyl group, R ａ－１ , R ａ－２ , R ａ－３１ , R ａ－３２ , R ａ－４ , R ａ－５１ and R ａ－５２ are independently H, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, X is *-NH-S(O) ｙ - or *-S(O) ｙ -NH-, where y is 1 or 2, and * indicates that the end marked with * is 【Chemistry 4】 is connected to A １ is N or CR １ and R １ is hydrogen, a cyano group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ an alkyl group, one or more R １－１ C substituted with １－６ Alkyl group, halogen, hydroxyl group, -OC １－６ an alkyl group, one or more R １－２ -OC substituted with １－６ Alkyl group, -C(=O)R １ａ , -NR １ｂ１ R １ｂ２ , -C(=O)OR １ｃ , -C(=O)NR １ｄ１ R １ｄ２ , C ３－１０ Cycloalkyl group, one or more R １－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－４ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－７ C substituted with ５－７ Cycloalkenyl group, "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－８ or one or more R １－９ C substituted with ２－６ In the case of an alkynyl group, when the substituents are plural, they may be the same or different, R １－１ , R １－２ , R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ and R １－９ are independently an azide group, a halogen, a hydroxyl group, a cyano group, an oxo group, １－６ an alkyl group, one or more R １－１－１ C substituted with １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OC １－６ an alkyl group, one or more R １－１－２ -OC substituted with １－６ Alkyl group, -C(=O)R １１ａ , -NR １１ｂ１ R １１ｂ２ , -C(=O)OR １１ｃ , -C(=O)NR １１ｄ１ R １１ｄ２ , -S(O) ２ N.R. １１ｅ１ R １１ｅ２ , -S(O) ２ R １１ｆ , C ３－１０ Cycloalkyl group, one or more R １－１－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－１－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－１－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－１－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－１－７ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－１－８ and when the substituents are multiple, they may be the same or different, R １－１－１ , R １－１－２ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ and R １－１－８ are independently halogen, oxo, -C(=O)R １１ｇ , a hydroxy group, C １－６ An alkyl group or one or more R １－１－１－１ C substituted with １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－１－１－１ is a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ａ R ｂ and R ａ and R ｂ are independently hydrogen or C １－６ is an alkyl group, R １ａ , R １ｂ１ , R １ｂ２ , R １ｃ , R １ｄ１ , R １ｄ２ , R １１ａ , R １１ｂ１ , R １１ｂ２ , R １１ｃ , R １１ｄ１ , R １１ｄ２ , R １１ｅ１ , R １１ｅ２ , R １１ｆ and R １１ｇ are independently hydrogen, C １－６ an alkyl group, one or more R １－２－１ C substituted with １－６ Alkyl group, -OC １－６ an alkyl group, one or more R １－２－２ -OC substituted with １－６ Alkyl group, C ３－１０ Cycloalkyl group, one or more R １－２－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－２－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－２－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－２－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－２－７ C substituted with ５－７ Cycloalkenyl group, "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－２－８ "5-7 membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with -C(=O)R １１ｈ and R １１ｈ is C １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－２－１ , R １－２－２ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ and R １－２－８ are independently a halogen, a hydroxyl group, or -NR １２ｃ R １２ｄ , Oxo, C １－６ An alkyl group or one or more R １－２－１－１ C substituted with １－６ is an alkyl group, R １２ｃ and R １２ｄ are independently hydrogen or C １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－２－１－１ are independently a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ｃ R ｄ and R ｃ and R ｄ are independently hydrogen or C １－６ is an alkyl group, Or, R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ , R １－１－８ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ , and R １－２－８ If the number of R is greater than 1, then two optional R １－３ , two optional R １－４ , two optional R １－５ , two optional R １－６ , two optional R １－７ , two optional R １－８ , two optional R １－１－３ , two optional R １－１－４ , two optional R １－１－５ , two optional R １－１－６ , two optional R １－１－７ , two optional R １－１－８ , two optional R １－２－３ , two optional R １－２－４ , two optional R １－２－５ , two optional R １－２－６ , two optional R １－２－７ , or optionally two R １－２－８ are connected to each other and independently, together with the atoms connected thereto, form a 3- to 8-membered carbocyclic ring, one or more R １－３－１ a 3- to 8-membered carbocyclic ring substituted with "a 3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S, and N"; １－３－２ "3-8 membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ Aromatic ring, one or more R １－３－３ C substituted with ６－２０ an aromatic ring, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R １－３－４ "5-12 membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloolefin, one or more R １－３－５ C substituted with ５－７ Cycloolefin, "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－３－６ and forming a "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, R １－３－１ , R １－３－２ , R １－３－３ , R １－３－４ , R １－３－５ and R １－３－６ are independently oxo, a hydroxy group, a halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; Or, R ａ－３１ and R ａ－３２ , R ａ－５１ and R ａ－５２ , R １ｂ１ and R １ｂ２ , R １ｄ１ and R １ｄ２ , R １１ｂ１ and R １１ｂ２ , R １１ｄ１ and R １１ｄ２ , R １１ｅ１ and R １１ｅ２ , R ａ and R ｂ , R ｃ and R ｄ , R １２ｃ and R １２ｄ Each independently represents, together with the N to which it is linked, "a 3- to 8-membered heterocycle in which one is N and the others are independently selected from O, S, and N and each of the R １－４－１ forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S and N" substituted with R １－４－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; A ２ and A ３ are independently N or CR ２ and R ２ is hydrogen or halogen, When a, b and c are single bonds, A ４ is NR ４ａ And A ５ is N or CR ５ｂ and When b is a single bond and a and c are double bonds, A ４ is N or CR ４ｄ And A ５ is O, S or NR ５ｄ and R ６ is a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R ６－１ "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with R ６－１ is a halogen, a hydroxyl group, a cyano group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, one or more -OC １－６ C substituted with alkyl group １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; R ４ａ and R ４ｄ are independently hydrogen, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ An alkyl group or one or more R ４－１ C substituted with １－６ is an alkyl group, R ４－１ is a hydroxy group or -OC １－６ alkyl group, and when the substituents are plural, they may be the same or different; R ５ｂ and R ５ｄ is, independently, 【Chemistry 5】 and L １ is a connecting bond, C １－６ an alkylene group or -C(=O)-, Q １ is hydrogen, halogen, cyano group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, hydroxy group, -C(=O)R ５２ａ , -NR ５２ｂ１ R ５２ｂ２ , -C(=O)OR ５２ｃ , -C(=O)NR ５２ｄ１ R ５２ｄ２ , C substituted with one or more halogens １－６ Alkyl group, C substituted with one or more hydroxy groups １－６ Alkyl group, -OC １－６ an alkyl group, one or more R ５－１－１ -OC substituted with １－６ Alkyl group, C ６－２０ an aryl group, one or more R ５－１－２ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; ５－１－３ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ３－１２ Cycloalkyl group, one or more R ５－１－４ C substituted with ３－１２ a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R ５－１－５ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R ５－１－６ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R ５－１－７ and when the substituents are multiple, they may be the same or different, Or, R １ and R ５ｄ are linked to each other and each together with the atom linked thereto forms a "5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N"; R ５－１－１ , R ５－１－２ , R ５－１－３ , R ５－１－４ , R ５－１－５ , R ５－１－６ and R ５－１－７ are independently a halogen, a hydroxyl group, an oxo group, a cyano group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OC １－６ Alkyl group, —OC substituted with one or more halogens １－６ Alkyl group, -C(=O)R ５１ａ , -NR ５１ｂ１ R ５１ｂ２ , -C(=O)OR ５１ｃ or -C(=O)NR ５１ｄ１ R ５１ｄ２ and when there is more than one substituent, they may be the same or different, R ５２ａ , R ５２ｂ１ , R ５２ｂ２ , R ５２ｃ , R ５２ｄ１ , R ５２ｄ２ , R ５１ａ , R ５１ｂ１ , R ５１ｂ２ , R ５１ｃ , R ５１ｄ１ and R ５１ｄ２ are independently hydrogen, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, Or, R ５２ｂ１ and R ５２ｂ２ , R ５２ｄ１ and R ５２ｄ２ , R ５１ｂ１ and R ５１ｂ２ , R ５１ｄ１ and R ５１ｄ２ Each independently represents, together with the N to which it is linked, "a 3- to 8-membered heterocycle in which one is N and the others are independently selected from O, S, and N and each of the R １－５－１ forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S and N" substituted with R １－５－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ When the alkyl group has a plurality of substituents, the substituents may be the same or different.

2. The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, characterized in that the compound has a structure as shown in formula II. The compound having a five-membered heteroaryl ring structure represented by formula I, its pharma- ceutically acceptable salt, its stereoisomer, its tautomer or its isotope compound. 【Chemistry 6】 (Here, " 【Chemistry 7】 " represents a single bond or a double bond, 【Chemistry 8】 The two cycloalkyls in the ring are both aromatic. R ａ１ , R ａ２ and R ａ３ are independently hydrogen, halogen, cyano group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, OR ａ－１ , C(=O)R ａ－２ , -NR ａ－３１ R ａ－３２ , -C(=O)OR ａ－４ , -C(=O)NR ａ－５１ R ａ－５２ , or one or more R ａ１－１ C substituted with １－６ is an alkyl group, R ａ１－１ is a halogen, a hydroxyl group or -OC １－６ is an alkyl group, Or, R ａ２ and R ａ３ is a connected carbon atom and C ３－７ Cycloalkane, one or more R ａ２－１ C substituted with ３－７ Cycloalkane, "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R ａ２－２ and forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with R ａ２－１ and R ａ２－２ are independently a halogen, an oxo, a hydroxyl group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ is an alkyl group, R ａ－１ , R ａ－２ , R ａ－３１ , R ａ－３２ , R ａ－４ , R ａ－５１ and R ａ－５２ are independently H, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, A １ is N or CR １ and R １ is hydrogen, a cyano group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C １－６ an alkyl group, one or more R １－１ C substituted with １－６ Alkyl group, halogen, hydroxyl group, -OC １－６ an alkyl group, one or more R １－２ -OC substituted with １－６ Alkyl group, -C(=O)R １ａ , -NR １ｂ１ R １ｂ２ , -C(=O)OR １ｃ , -C(=O)NR １ｄ１ R １ｄ２ , C ３－１０ Cycloalkyl group, one or more R １－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－４ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－７ C substituted with ５－７ Cycloalkenyl group, "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－８ or one or more R １－９ C substituted with ２－６ In the case of an alkynyl group, when the substituents are plural, they may be the same or different, R １－１ , R １－２ , R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ and R １－９ are independently an azide group, a halogen, a hydroxyl group, a cyano group, an oxo group, １－６ an alkyl group, one or more R １－１－１ C substituted with １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OC １－６ an alkyl group, one or more R １－１－２ -OC substituted with １－６ Alkyl group, -C(=O)R １１ａ , -NR １１ｂ１ R １１ｂ２ , -C(=O)OR １１ｃ , -C(=O)NR １１ｄ１ R １１ｄ２ , -S(O) ２ N.R. １１ｅ１ R １１ｅ２ , -S(O) ２ R １１ｆ , C ３－１０ Cycloalkyl group, one or more R １－１－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－１－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－１－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－１－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－１－７ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－１－８ and when the substituents are multiple, they may be the same or different, R １－１－１ , R １－１－２ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ and R １－１－８ are independently halogen, oxo, -C(=O)R １１ｇ , a hydroxy group, C １－６ An alkyl group or one or more R １－１－１－１ C substituted with １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－１－１－１ is a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ａ R ｂ and R ａ and R ｂ are independently hydrogen or C １－６ is an alkyl group, R １ａ , R １ｂ１ , R １ｂ２ , R １ｃ , R １ｄ１ , R １ｄ２ , R １１ａ , R １１ｂ１ , R １１ｂ２ , R １１ｃ , R １１ｄ１ , R １１ｄ２ , R １１ｅ１ , R １１ｅ２ , R １１ｆ and R １１ｇ are independently hydrogen, C １－６ an alkyl group, one or more R １－２－１ C substituted with １－６ Alkyl group, -OC １－６ an alkyl group, one or more R １－２－２ -OC substituted with １－６ Alkyl group, C ３－１０ Cycloalkyl group, one or more R １－２－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－２－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－２－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－２－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－２－７ C substituted with ５－７ Cycloalkenyl group, "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－２－８ "5-7 membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with -C(=O)R １１ｈ and R １１ｈ is C １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－２－１ , R １－２－２ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ and R １－２－８ are independently a halogen, a hydroxyl group, or -NR １２ｃ R １２ｄ , Oxo, C １－６ An alkyl group or one or more R １－２－１－１ C substituted with １－６ is an alkyl group, R １２ｃ and R １２ｄ are independently hydrogen or C １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－２－１－１ are independently a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ｃ R ｄ and R ｃ and R ｄ are independently hydrogen or C １－６ is an alkyl group, Or, R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ , R １－１－８ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ , and R １－２－８ If the number of R is greater than 1, then two optional R １－３ , two optional R １－４ , two optional R １－５ , two optional R １－６ , two optional R １－７ , two optional R １－８ , two optional R １－１－３ , two optional R １－１－４ , two optional R １－１－５ , two optional R １－１－６ , two optional R １－１－７ , two optional R １－１－８ , two optional R １－２－３ , two optional R １－２－４ , two optional R １－２－５ , two optional R １－２－６ , two optional R １－２－７ , or optionally two R １－２－８ are connected to each other and independently, together with the atoms connected thereto, form a 3- to 8-membered carbocyclic ring, one or more R １－３－１ a 3- to 8-membered carbocyclic ring substituted with "a 3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S, and N"; １－３－２ "3-8 membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ Aromatic ring, one or more R １－３－３ C substituted with ６－２０ an aromatic ring, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R １－３－４ "5-12 membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloolefin, one or more R １－３－５ C substituted with ５－７ Cycloolefin, "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－３－６ and forming a "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, R １－３－１ , R １－３－２ , R １－３－３ , R １－３－４ , R １－３－５ and R １－３－６ are independently oxo, a hydroxy group, a halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; Or, R ａ－３１ and R ａ－３２ , R ａ－５１ and R ａ－５２ , R １ｂ１ and R １ｂ２ , R １ｄ１ and R １ｄ２ , R １１ｂ１ and R １１ｂ２ , R １１ｄ１ and R １１ｄ２ , R １１ｅ１ and R １１ｅ２ , R ａ and R ｂ , R ｃ and R ｄ , R １２ｃ and R １２ｄ Each independently represents, together with the N to which it is linked, "a 3- to 8-membered heterocycle in which one is N and the others are independently selected from O, S, and N and each of the R １－４－１ forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S and N" substituted with R １－４－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; A ２ and A ３ are independently N or CR ２ and R ２ is hydrogen or halogen, When a, b and c are single bonds, A ４ is NR ４ａ And A ５ is N or CR ５ｂ and When b is a single bond and a and c are double bonds, A ４ is N or CR ４ｄ And A ５ is O, S or NR ５ｄ and R ６ is a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R ６－１ "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with R ６－１ is a halogen, a hydroxyl group, a cyano group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, one or more -OC １－６ C substituted with alkyl group １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; R ４ａ and R ４ｄ are independently hydrogen, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ An alkyl group or one or more R ４－１ C substituted with １－６ is an alkyl group, R ４－１ is a hydroxy group or -OC １－６ alkyl group, and when the substituents are plural, they may be the same or different; R ５ｂ and R ５ｄ is independent, 【Chemistry 9】 and L １ is a connecting bond, C １－６ an alkylene group or -C(=O)-, Q １ is hydrogen, halogen, cyano group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, hydroxy group, -C(=O)R ５２ａ , -NR ５２ｂ１ R ５２ｂ２ , -C(=O)OR ５２ｃ , -C(=O)NR ５２ｄ１ R ５２ｄ２ , C substituted with one or more halogens １－６ Alkyl group, C substituted with one or more hydroxy groups １－６ Alkyl group, -OC １－６ an alkyl group, one or more R ５－１－１ -OC substituted with １－６ Alkyl group, C ６－２０ Aryl groups, one or more Ｒ５－１－２ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; ５－１－３ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ３－１２ Cycloalkyl group, one or more R ５－１－４ C substituted with ３－１２ a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R ５－１－５ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R ５－１－６ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R ５－１－７ and when the substituents are multiple, they may be the same or different, Or, R １ and R ５ｄ are linked to each other and each together with the atom linked thereto forms a "5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N"; R ５－１－１ , R ５－１－２ , R ５－１－３ , R ５－１－４ , R ５－１－５ , R ５－１－６ and R ５－１－７ are independently a halogen, a hydroxyl group, an oxo group, a cyano group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OC １－６ Alkyl group, —OC substituted with one or more halogens １－６ Alkyl group, -C(=O)R ５１ａ , -NR ５１ｂ１ R ５１ｂ２ , -C(=O)OR ５１ｃ or -C(=O)NR ５１ｄ１ R ５１ｄ２ and when there is more than one substituent, they may be the same or different, R ５２ａ , R ５２ｂ１ , R ５２ｂ２ , R ５２ｃ , R ５２ｄ１ , R ５２ｄ２ , R ５１ａ , R ５１ｂ１ , R ５１ｂ２ , R ５１ｃ , R ５１ｄ１ and R ５１ｄ２ are independently hydrogen, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, Or, R ５２ｂ１ and R ５２ｂ２ , R ５２ｄ１ and R ５２ｄ２ , R ５１ｂ１ and R ５１ｂ２ , R ５１ｄ１ and R ５１ｄ２ Each independently represents, together with the N to which it is linked, a "3- to 8-membered heterocycle, one of which is N and the others each independently contain 1 to 3 heteroatoms selected from O, S, and N," or one or more R １－５－１ forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S and N" substituted with R １－５－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ When the alkyl group has a plurality of substituents, the substituents may be the same or different.

3. In the five-membered heteroaryl ring structure-containing compound of formula I, R ａ１ is a cyano group, C １－６ An alkyl group or one or more R ａ１－１ C substituted with １－６ is an alkyl group, R ａ１－１ is a halogen, R ａ２ and R ａ３ is independently １－６ is an alkyl group, or R ａ２ and R ａ３ is the bonded carbon atom and C ３－７ Forming a cycloalkane, X is *-NH-S(O) ｙ -, where y is 1 or 2, and * indicates that the end marked with * is 【Chemistry 10】 is connected to A １ is N or CR １ and R １ is hydrogen, one or more R １－１ C substituted with １－６ an alkyl group, a halogen, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－３ C substituted with ３－１０ Cycloalkyl group, one or more R １－４ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－７ C substituted with ５－７ Cycloalkenyl group, "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－８ or one or more R １－９ C substituted with ２－６ In the case of an alkynyl group, when the substituents are plural, they may be the same or different, R １－１ , R １－３ , R １－４ , R １－５ , R １－７ , R １－８ and R １－９ are independently an azide group, a halogen, a hydroxyl group, C １－６ an alkyl group, one or more R １－１－１ C substituted with １－６ Alkyl group, C ６－２０ Aryl group, -C(=O)R １１ａ , -NR １１ｂ１ R １１ｂ２ , -C(=O)NR １１ｄ１ R １１ｄ２ , -S(O) ２ R １１ｆ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－１－４ and when there are a plurality of substituents, they are the same or different, R １－１－１ and R １－１－４ are independently -C(=O)R １１ｇ , oxo, hydroxyl group, or one or more R １－１－１－１ C substituted with １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－１－１－１ are independently a hydroxy group; R １１ａ , R １１ｂ１ , R １１ｂ２ , R １１ｄ１ , R １１ｄ２ , R １１ｆ and R １１ｇ are independently hydrogen, C １－６ an alkyl group, one or more R １－２－１ C substituted with １－６ Alkyl group, C ３－１０ Cycloalkyl group, one or more R １－２－３ C substituted with ３－１０ Cycloalkyl group, one or more R １－２－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, "a 5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or -C(=O)R １１ｈ and R １１ｈ is C １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－２－１ , R １－２－３ and R １－２－４ are independently a halogen, a hydroxyl group, or -NR １２ｃ R １２ｄ , or C １－６ is an alkyl group, R １２ｃ and R １２ｄ are independently hydrogen or C １－６ alkyl group, and when the substituents are plural, they may be the same or different; Or, R １－４ and R １－８ If the number of R is greater than 1, then two optional R １－４ or optionally two R １－８ are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms independently selected from O, S, and N" or a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N"; Or, R １１ｄ１ and R １１ｄ２ Each independently represents, together with the linked N, "a 3- to 8-membered heterocycloalkane, one of which is N and the others each independently contain 1 to 3 heteroatoms selected from O, S, and N," or one or more R １－４－１ and forming a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S and N," substituted with R １－４－１ is halogen or oxo, A ２ and A ３ are independently N or CR ２ and R ２ is hydrogen or halogen, When a, b and c are single bonds, A ４ is NR ４ａ And A ５ is N, When b is a single bond and a and c are double bonds, A ４ is N or CR ４ｄ And A ５ is S or NR ５ｄ and R ４ａ and R ４ｄ are independently hydrogen, halogen, or one or more R ４－１ C substituted with １－６ R is an alkyl group, and when the substituents are plural, they may be the same or different. ４－１ is a halogen, a hydroxyl group or -OC １－６ is an alkyl group, R ５ｄ teeth, 【Chemistry 11】 and L １ is a connecting bond or C １－６ is an alkylene group, Q １ is a C substituted with hydrogen, a cyano group, a hydroxyl group, or one or more halogens. １－６ Alkyl group, C substituted with one or more hydroxy groups １－６ Alkyl group, -OC １－６ an alkyl group, one or more R ５－１－２ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; ５－１－３ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with ３－１２ cycloalkyl group, the substituents, if any, are the same or different; Or, R １ and R ５ｄ each form, together with the atom to which it is linked, a 5-12 membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S and N; R ５－１－２ and R ５－１－３ are independently halogen or C １－６ is an alkyl group, R ６ is one or more R ６－１ "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with R ６－１ is C １－６ Alkyl group, C substituted with one or more halogens １－６ An alkyl group or one or more -OC １－６ C substituted with alkyl group １－６ The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, characterized in that the substituents are alkyl groups, and when there are multiple substituents, they are the same or different. ...

4. R ａ１ is a cyano group, C １－６ An alkyl group or one or more R ａ１－１ C substituted with １－６ is an alkyl group, R ａ１－１ is a halogen, And / or R ａ２ and R ａ３ is the bonded carbon atom and C ３－７ Forming a cycloalkane, And / or X is *-NH-S(O) ｙ -, where y is 1 or 2, and * indicates that the end marked with * is 【Chemistry 12】 is connected to And / or A １ is N or CR １ and And / or R １ is hydrogen, one or more R １－１ C substituted with １－６ Alkyl group, halogen, one or more R １－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－４ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－７ C substituted with ５－７ Cycloalkenyl group, "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－８ or one or more R １－９ C substituted with ２－６ In the case of an alkynyl group, when the substituents are plural, they may be the same or different, And / or R １－１ are independently halogen or one or more R １－１－４ "a 4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with And / or R １－１ In the above, R １－１－４ independently represents one or more R １－１－１－１ C substituted with １－６ Alkyl group or -C(=O)R １１ｇ and R １－１－１－１ are independently a hydroxy group; R １１ｇ is C １－６ is an alkyl group, And / or R １－３ are independently -C(=O)NR １１ｄ１ R １１ｄ２ and R １１ｄ１ and R １１ｄ２ forms, together with the linked N atom, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S and N"; And / or R １－４ are independently an azide group, a hydroxyl group, or -C(=O)R １１ａ , C １－６ an alkyl group, one or more R １－１－１ C substituted with １－６ Alkyl group, C ６－２０ Aryl group, -C(=O)NR １１ｄ１ R １１ｄ２ , -S(O) ２ R １１ｆ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－１－４ or a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R １－４ If the number of R is greater than 1, then two optional R １－４ are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms independently selected from O, S, and N"; R １－４ If the number of R is greater than 1, then two optional R １－４ are linked to each other and independently form, together with the atoms linked thereto, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N"; And / or R １－４ In the above, R １－１－１ is a hydroxy group, And / or R １－４ In the above, R １１ａ is C １－６ Alkyl group, C ３－１０ Cycloalkyl group, one or more R １－２－１ C substituted with １－６ an alkyl group, one or more R １－２－３ C substituted with ３－１０ Cycloalkyl group, C ６－２０ an aryl group or a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; R １－２－１ is a halogen, a hydroxyl group or -NR １１ｂ１ R １１ｂ２ and R １１ｂ１ and R １１ｂ２ are independently hydrogen; R １－２－３ is C １－６ is an alkyl group, And / or R １－４ In the above, R １１ｄ１ and R １１ｄ２ is independently １－６ an alkyl group, one or more R １－２－１ C substituted with １－６ is an alkyl group, R １－２－１ is -NR １２ｃ R １２ｄ and R １２ｃ and R １２ｄ is independently １－６ an alkyl group, or R １１ｄ１ and R １１ｄ２ means, together with the N atom to which it is linked, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N" or one or more R １－４－１ and R １－４－１ is a halogen, And / or R １－４ In the above, R １１ｆ is C １－６ is an alkyl group, And / or R １－４ In the above, R １－１－４ is oxo, And / or R １－５ is -C(=O)NR １１ｄ１ R １１ｄ２ and R １１ｄ１ and R １１ｄ２ is independently C １－６ an alkyl group, or R １１ｄ１ and R １１ｄ２ forms, together with the linked N atom, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S and N"; And / or R １－７ are independently -C(=O)NR １１ｄ１ R １１ｄ２ Or R １－７ If the number of R is greater than 1, then two optional R １－７ are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 4 heteroatoms independently selected from O, S, and N"; And / or R １－７ In the above, R １１ｄ１ and R １１ｄ２ forms, together with the linked N atom, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N"; And / or R １－８ is -C(=O)R １１ａ , -S(O) ２ R １１ｆ , -C(=O)NR １１ｄ１ R １１ｄ２ Or R １－８ If the number of R is greater than 1, then two optional R １－８ are linked to each other and independently form, together with the atoms linked thereto, a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms independently selected from O, S, and N"; And / or R １－８ In the above, R １１ａ is C １－６ Alkyl group, C ３－１０ A cycloalkyl group or one or more R １－２－１ C substituted with １－６ is an alkyl group, R １－２－１ is a hydroxy group or NR １２ｃ R １２ｄ and R １２ｃ and R １２ｄ are independently hydrogen; And / or R １－８ In the above, R １１ｆ is C １－６ is an alkyl group, And / or R １－８ In the above, R １１ｄ１ and R １１ｄ２ forms, together with the linked N atom, "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N"; And / or R １－９ Ha-NR １１ｂ１ R １１ｂ２ and R １１ｂ１ and R １１ｂ２ are independently hydrogen or -C(=O)R １１ｈ and R １１ｈ is C １－６ is an alkyl group, And / or, when a and b are single bonds, A ４ is NR ４ａ And A ５ is N, And / or, when b is a single bond and a is a double bond, A ４ is N or CR ４ｄ And A ５ is S or NR ５ｄ and R ４ｄ is hydrogen or halogen, And / or R ４ａ is one or more R ４－１ C substituted with １－６ is an alkyl group, R ４－１ is a hydroxy group or -OC １－６ is an alkyl group, And / or L １ is a connecting bond or C １－６ is an alkylene group, and Q １ is hydrogen, C ３－１２ Cycloalkyl groups, C substituted with one or more halogens １－６ Alkyl group, cyano group, hydroxy group, C substituted with one or more hydroxy groups １－６ Alkyl group, -OC １－６ an alkyl group, one or more R ５－１－２ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; ５－１－３ "a 5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with And / or R ５－１－２ is a halogen, And / or R ５－１－３ is C １－６ is an alkyl group, 2. The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, its pharma- ceutically acceptable salt, its stereoisomer, its tautomer or its isotope.

5. R ａ１ , R ａ２ and R ａ３ is independent, C １－６ is an alkyl group, And / or L １ is a connecting bond, and Q １ is hydrogen, C ３－１２ Cycloalkyl group or C substituted with one or more halogens １－６ is an alkyl group, or L １ is C １－６ is an alkylene group, and Q １ is a hydrogen atom, a cyano group, a hydroxyl group, or a C substituted with one or more hydroxyl groups. １－６ Alkyl group, -OC １－６ an alkyl group, one or more R ５－１－２ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; ５－１－３ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ３－１２ is a cycloalkyl group, 2. The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, its pharma- ceutically acceptable salt, its stereoisomer, its tautomer or its isotope.

6. A １ is N or CR １ and R １ is hydrogen, halogen, or one or more R １－１ C substituted with １－６ R is an alkyl group, and when the substituents are plural, they may be the same or different. １－１ is a halogen, A ５ is NR ５ｄ and R ５ｄ teeth 【Chemistry 13】 and L １ is a connecting bond or C １－６ is an alkylene group, Q １ is one or more R ５－１－２ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," or one or more R ５－１－３ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ３－１２ is a cycloalkyl group, Or, A １ is CR １ And A ５ is N.R. ５ｄ or S, R １ is one or more R １－１ C substituted with １－６ an alkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－３ C substituted with ３－１０ Cycloalkyl group, one or more R １－４ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－７ C substituted with ５－７ Cycloalkenyl group, "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N"; one or more R １－８ or one or more R １－９ C substituted with ２－６ is an alkynyl group, R ５ｄ teeth 【Chemistry 14】 and L １ is a connecting bond or C １－６ is an alkylene group, and Q １ is a hydrogen atom, a cyano group, a hydroxyl group, -OC １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, C substituted with one or more hydroxy groups １－６ an alkyl group, one or more R ５－１－３ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ３－１２ is a cycloalkyl group, 2. The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, its pharma- ceutically acceptable salt, its stereoisomer, its tautomer or its isotope.

7. R ａ１ 、R ａ２ 、R ａ３ 、R ａ１－１ 、R ａ２－１ 、R ａ２－２ 、R ａ－１ 、R ａ－２ 、R ａ－３１ 、R ａ－３２ 、R ａ－４ 、R ａ－５１ 、R ａ－５２ 、R １ 、R １－１ 、R １－２ 、R １－３ 、R １－４ 、R １－５ 、R １－６ 、R １－７ 、R １－８ 、R １－９ 、R １－１－１ 、R １－１－２ 、R １－１－３ 、R １－１－４ 、R １－１－５ 、R １－１－６ 、R １－１－７ 、R １－１－８ 、R １－１－１－１ 、R １－２－１ 、R １－２－２ 、R １－２－３ 、R １－２－４ 、R １－２－５ 、R １－２－６ 、R １－２－７ 、R １－２－８ 、R １－２－１－１ 、R １－３－１ 、R １－３－２ 、R １－３－３ 、R １－３－４ 、R １－３－５ 、R １－３－６ 、R １－４－１ 、A ２ 、A ３ 、R ６－１ 、R ４ａ 、R ４ｄ 、Q １ 、R ５－１－１ 、R ５－１－２ 、R ５－１－３ 、R ５－１－４ 、R ５－１－５ 、R ５－１－６ 、R ５－１－７ 、R ５２ａ 、R ５２ｂ１ 、R ５２ｂ２ 、R ５２ｃ 、R ５２ｄ１ 、R ５２ｄ２ , R ５１ａ , R ５１ｂ１ , R ５１ｂ２ , R ５１ｃ , R ５１ｄ１ , R ５１ｄ２ and R １－５－１ When a halogen is mentioned in the definition of the halogen, said halogen is fluorine, chlorine, bromine or iodine; and / or, R ａ１ R ａ２ R ａ３ R ａ１－１ R ａ２－１ R ａ２－２ R ａ－１ R ａ－２ R ａ－３１ R ａ－３２ R ａ－４ R ａ－５１ R ａ－５２ R １ R １－１ R １－２ R １－３ R １－４ R １－５ R １－６ R １－７ R １－８ R １－９ R １－１－１ R １－１－２ R １－１－３ R １－１－４ R １－１－５ R １－１－６ R １－１－７ R １－１－８ R １－１－１－１ R １ａ R １ｂ１ R １ｂ２ R １ｃ R １ｄ１ R １ｄ２ R １１ａ R １１ｂ１ R １１ｂ２ R １１ｃ R １１ｄ１ R １１ｄ２ R １１ｅ１ R １１ｅ２ R １１ｆ and R １１ｇ R １－２－１ R １－２－２ R １－２－３ R １－２－４ R １－２－５ R １－２－６ R １－２－７ R １－２－８ R １－２－１－１ R １－３－１ R １－３－２ R １－３－３ R １－３－４ R １－３－５ R １－３－６ R １－４－１ R ６－１ R ４ａ R ４ｄ , Q １ , R ５－１－１ , R ５－１－２ , R ５－１－３ , R ５－１－４ , R ５－１－５ , R ５－１－６ , R ５－１－７ , R ５２ａ , R ５２ｂ１ , R ５２ｂ２ , R ５２ｃ , R ５２ｄ１ , R ５２ｄ２ , R ５１ａ , R ５１ｂ１ , R ５１ｂ２ , R ５１ｃ , R ５１ｄ１ , R ５１ｄ２ and R １－５－１ In the definition of １－６ When an alkyl group is mentioned, the C １－６ The alkyl group is C １－４ an alkyl group, for example a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, an isobutyl group or a tert-butyl group; And / or R １ , R １－１ , R １－２ , R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ , R １－９ , R １ａ , R １ｂ１ , R １ｂ２ , R １ｃ , R １ｄ１ , R １ｄ２ , R １１ａ , R １１ｂ１ , R １１ｂ２ , R １１ｃ , R １１ｄ１ , R １１ｄ２ , R １１ｅ１ , R １１ｅ２ , R １１ｆ and R １１ｇ In the definition of ３－１０ When a cycloalkyl group is mentioned, the C ３－１０ The cycloalkyl group is C ３ ~C ６ a cycloalkyl group, for example a cyclopropyl group, a cyclobutyl group or a cyclopentyl group; And / or R １ , R １－１ , R １－２ , R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ , R １－９ , R １ａ , R １ｂ１ , R １ｂ２ , R １ｃ , R １ｄ１ , R １ｄ２ , R １１ａ , R １１ｂ１ , R １１ｂ２ , R １１ｃ , R １１ｄ１ , R １１ｄ２ , R １１ｅ１ , R １１ｅ２ , R １１ｆ , R １１ｇ and Q. １ In the definition of ６－２０ When an aryl group is mentioned, the C ６－２０ The aryl group is C ６－１０ an aryl group, such as a phenyl group or a naphthyl group; And / or R ａ１ C substituted with one or more halogens １－６ When it is an alkyl group, it is C substituted with one or more halogens. １－６ The alkyl group is a C substituted with one halogen. １－２ Alkyl groups, such as -CH ２ F. And / or R ａ２ and R ａ３ is connected to the carbon atom C ３－７ When forming a cycloalkane, the C ３－７ Cycloalkanes are C ３ ~C ６ a cycloalkyl group, for example cyclopropane, cyclobutane or cyclopentane; And / or R １ One or more R １－１ C substituted with １－６ is an alkyl group, R １－１ is independently halogen, １－１ C substituted with １－６ The alkyl group is a C substituted with two or three halogens. １－２ is an alkyl group, And / or R １－１ independently represents one or more R １－１－４ In the case of a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is a monocyclic or bridged cyclic heteroalkyl group, And / or R １ is "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" or one or more R １－４ In the case of "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with R １－４ Among the "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, the "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is a monocyclic heteroalkyl group, a spirocyclic heteroalkyl group, a fused ring heteroalkyl group, or a bridged ring alkyl group, And / or R １ One or more R １－４ In the case of a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more of R １－４ The "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with one or more R １－４ and further comprising one or more R １－４ or one or more R １－４ "a 6-membered heterocycloalkyl group containing one heteroatom selected from N" substituted with And / or R １－３ In the above, R １１ｄ１ and R １１ｄ２ forms "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N" together with the N atom to which it is linked, the "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N" is "a 3- to 6-membered heterocycloalkane containing one N heteroatom, or a 3- to 6-membered heterocycloalkane containing two heteroatoms, each of which is N and O", And / or R １－４ One or more R １－１－４ In the case where the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is substituted with, the "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is a "4- to 6-membered heterocycloalkyl group containing one N", And / or R １－５ In the above, R １１ｄ１ and R １１ｄ２ forms "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N," together with the N atom to which it is linked, the "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N" is "a 3- to 6-membered heterocycloalkane containing one N heteroatom, or a 3- to 6-membered heterocycloalkane containing two heteroatoms independently selected from N and O," And / or R １ is "a 5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R １－６ In the case of a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with R １－６ Among the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" substituted with, the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" is a "5- to 9-membered heteroaryl group containing 1 to 3 heteroatoms independently selected from O, S, and N", and / or two R on two adjacent atoms １－４ forms a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N", the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" is a "5- to 6-membered heteroaryl group containing 1 to 2 heteroatoms independently selected from O, S, and N", And / or R １－４ In the above, R １１ａ One or more R １－２－１ C substituted with １－６ is an alkyl group, R １－２－１ is halogen, １１ａ is a halogen-substituted C １－２ an alkyl group, for example a trifluoromethyl group or a trifluoroethyl group; And / or R １－４ In the above, R １１ａ is a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N", the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" is a "5- to 6-membered heteroaryl group containing 1 to 2 heteroatoms independently selected from O, S, and N", And / or R １－４ In the above, R １１ｄ１ and R １１ｄ２ is, together with the N atom to which it is linked, a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N, or one or more R １－４－１ In the case of forming a "3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N", the "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S, and N" is a 4- to 6-membered heterocycloalkane containing one N, And / or R １－７ In the above, R １１ｄ１ and R １１ｄ２ forms "a 3- to 8-membered heterocycloalkane containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N" together with the N atom to which it is linked, the "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others being independently selected from O, S, and N" is a "4- to 6-membered heterocycloalkane containing one N", And / or R １ is a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N", or one or more R １－８ In the case of a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, the "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" is a monocyclic or bridged cyclic heterocycloalkenyl group, And / or R １ One or more R １－９ C substituted with ２－６ When it is an alkynyl group, ２－６ The alkynyl group is ２－３ an alkynyl group, for example an ethynyl group, a propynyl group or a propargyl group; And / or Q １ C substituted with one or more halogens １－６ When Q is an alkyl group, １ is C substituted with 2 to 3 halogens １－２ is an alkyl group, preferably a C １－２ an alkyl group, for example a trifluoroethyl group or a difluoromethyl group; And / or Q １ is substituted with one or more hydroxy groups １－６ When Q is an alkyl group, １ is a C substituted with 1 to 3 hydroxy groups １－２ is an alkyl group, And / or Q １ is a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N", or one or more R ５－１－３ In the case where the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" is substituted with, the "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" is a "5- to 9-membered heteroaryl group containing 1 to 2 heteroatoms independently selected from S and N", And / or Q １ C ３－１２ When it is a cycloalkyl group, ３－１２ The cycloalkyl group is C ３－６ a cycloalkyl group, for example a cyclopropyl group, a cyclobutyl group or a cyclopentyl group; And / or R １ and R ５ｄ each form a "5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" together with the atom to which it is linked, the "5- to 12-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" is a "5- to 7-membered heterocycloolefin containing 1 to 2 heteroatoms independently selected from O and N", And / or L １ C １－６ When it is an alkylene group, １－６ The alkylene group is —CH ２ --, --CH ２ CH ２ --, --CH ２ CH ２ CH ２ -, -CH(CH ３ ) CH ２ --, --CH ２ CH ２ CH ２ CH ２ -, -CH(CH ３ ) CH ２ CH ２ --, --CH ２ CH (CH ３ ) CH ２ - or -C(CH ３ ) ２ CH ２ - is, 2. The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, its pharma- ceutically acceptable salt, its stereoisomer, its tautomer or its isotope.

8. 【Chemical 15】 teeth, 【Chemistry 16】 and, 【Chemistry 17】 and And / or A ２ is CH or CF, And / or A ３ is N, CH or CF, And / or A １ is CR １ and R １ is hydrogen, -F, -CF ３ , 【Chemistry 18】 【change】 and And / or A ４ is N or CR ４ｄ and And / or R ４ｄ is hydrogen or chlorine, And / or, when a and b are single bonds, A ４ is NR ４ａ And A ５ is N, And / or A ５ is S or NR ５ｄ and R ５ｄ is H, -CH ３ , 【Chemistry 19】 and And / or R ６ teeth, 【Chemistry 20】 That is, 2. The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, its pharma- ceutically acceptable salt, its stereoisomer, its tautomer or its isotope.

9. The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, characterized in that it is embodiment 1, embodiment 2 or embodiment 3, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof or an isotope thereof. (Aspect 1: A five-membered heteroaryl ring structure-containing compound represented by formula IV, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof, 【Chemistry 21】 However, R ａ１ is hydrogen, halogen, cyano group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OR ａ－１ , -C(=O)R ａ－２ , -NR ａ－３１ R ａ－３２ , -C(=O)OR ａ－４ , -C(=O)NR ａ－５１ R ａ－５２ , or one or more R ａ１－１ C substituted with １－６ is an alkyl group, R ａ１－１ is a halogen, a hydroxyl group or -OC １－６ is an alkyl group, A １ is N or CR １ and R １ is hydrogen, one or more R １－１ C substituted with １－６ Alkyl group, halogen, C ３－１０ Cycloalkyl group, one or more R １－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－４ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－７ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－８ and when there are a plurality of substituents, they may be the same or different, R １－１ , R １－３ , R １－４ , R １－５ , R １－６ , R １－７ and R １－８ are independently a halogen, a hydroxyl group, a cyano group, an oxo group, １－６ an alkyl group, one or more R １－１－１ C substituted with １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OC １－６ an alkyl group, one or more R １－１－２ -OC substituted with １－６ Alkyl group, -C(=O)R １１ａ , -NR １１ｂ１ R １１ｂ２ , -C(=O)OR １１ｃ , -C(=O)NR １１ｄ１ R １１ｄ２ , -S(O) ２ N.R. １１ｅ１ R １１ｅ２ , -S(O) ２ R １１ｆ , C ３－１０ Cycloalkyl group, one or more R １－１－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－１－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－１－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－１－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－１－７ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－１－８ and when there are a plurality of substituents, they may be the same or different, R １－１－１ , R １－１－２ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ and R １－１－８ are independently a halogen, a hydroxyl group, an oxo group, １－６ An alkyl group or one or more R １－１－１－１ C substituted with １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－１－１－１ is a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ａ R ｂ and R ａ and R ｂ are independently hydrogen or C １－６ is an alkyl group, R １１ａ , R １１ｂ１ , R １１ｂ２ , R １１ｃ , R １１ｄ１ , R １１ｄ２ , R １１ｅ１ , R １１ｅ２ and R １１ｆ are independently hydrogen, C １－６ an alkyl group, one or more R １－２－１ C substituted with １－６ Alkyl group, -OC １－６ an alkyl group, one or more R １－２－２ -OC substituted with １－６ Alkyl group, C ３－１０ Cycloalkyl group, one or more R １－２－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－２－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－２－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－２－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－２－７ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－２－８ and when there are a plurality of substituents, they may be the same or different, R １－２－１ , R １－２－２ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ and R １－２－８ are independently halogen, oxo, C １－６ An alkyl group or one or more R １－２－１－１ C substituted with １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－２－１－１ are independently a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ｃ R ｄ and R ｃ and R ｄ are independently hydrogen or C １－６ is an alkyl group, Or, R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ , R １－１－８ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ , and R １－２－８ If the number of R is greater than 1, then two optional R １－３ , two optional R １－４ , two optional R １－５ , two optional R １－６ , two optional R １－７ , two optional R １－８ , two optional R １－１－３ , two optional R １－１－４ , two optional R １－１－５ , two optional R １－１－６ , two optional R １－１－７ , two optional R １－１－８ , two optional R １－２－３ , two optional R １－２－４ , two optional R １－２－５ , two optional R １－２－６ , two optional R １－２－７ , or optionally two R １－２－８ are connected to each other and independently, together with the atoms connected thereto, form a 3- to 8-membered carbocyclic ring, one or more R １－３－１ a 3- to 8-membered carbocyclic ring substituted with "a 3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S, and N"; １－３－２ "3-8 membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－３－３ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－３－４ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－３－５ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－３－６ forming a "5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with R １－３－１ , R １－３－２ , R １－３－３ , R １－３－４ , R １－３－５ and R １－３－６ are independently oxo, a hydroxy group, a halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ is an alkyl group, Or, R ａ－３１ and R ａ－３２ , R ａ－５１ and R ａ－５２ , R １１ｂ１ and R １１ｂ２ , R １１ｄ１ and R １１ｄ２ , R １１ｅ１ and R １１ｅ２ , R ａ and R ｂ , R ｃ and R ｄ Each independently represents, together with the N to which it is linked, a "3- to 8-membered heterocycle, one of which is N and the others each independently contain 1 to 3 heteroatoms selected from O, S, and N," or one or more R １－４－１ and R １－４－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ is an alkyl group, A ２ and A ３ are independently N or CR ２ and R ２ is hydrogen or halogen, A ４ is N or CR ４ｄ and R ４ｄ is hydrogen, halogen, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, R ５ｄ teeth, 【Chemical 22】 and L １ is a connecting bond or C １－６ is an alkylene group, Q １ is hydrogen, halogen, cyano group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, hydroxy group, -C(=O)R ５２ａ , -NR ５２ｂ１ R ５２ｂ２ , -C(=O)OR ５２ｃ , -C(=O)NR ５２ｄ１ R ５２ｄ２ , C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R ５－１－３ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ３－１２ Cycloalkyl group, one or more R ５－１－４ C substituted with ３－１２ a cycloalkyl group, "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R ５－１－５ "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, and when there are multiple substituents, they may be the same or different, R ５－１－３ , R ５－１－４ and R ５－１－５ are independently a halogen, a hydroxyl group, an oxo group, a cyano group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ Alkyl group, —OC substituted with one or more halogens １－６ Alkyl group, -C(=O)R ５１ａ , -NR ５１ｂ１ R ５１ｂ２ , -C(=O)OR ５１ｃ or -C(=O)NR ５１ｄ１ R ５１ｄ２ and when there is more than one substituent, they may be the same or different, R ５２ａ , R ５２ｂ１ , R ５２ｂ２ , R ５２ｃ , R ５２ｄ１ , R ５２ｄ２ , R ５１ａ , R ５１ｂ１ , R ５１ｂ２ , R ５１ｃ , R ５１ｄ１ and R ５１ｄ２ are independently hydrogen, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, Or, R ５２ｂ１ and R ５２ｂ２ , R ５２ｄ１ and R ５２ｄ２ , R ５１ｂ１ and R ５１ｂ２ , R ５１ｄ１ and R ５１ｄ２ Each independently represents, together with the N to which it is linked, a "3- to 8-membered heterocycle, one of which is N and the others each independently contain 1 to 3 heteroatoms selected from O, S, and N," or one or more R １－５－１ forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S and N" substituted with R １－５－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; R ６ is a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R ６－１ "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with R ６－１ is C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, Aspect 2: A five-membered heteroaryl ring structure-containing compound represented by formula IV′, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof, 【Chemistry 23】 however, R ａ１ is hydrogen, halogen, cyano group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OR ａ－１ , -C(=O)R ａ－２ , -NR ａ－３１ R ａ－３２ , -C(=O)OR ａ－４ , -C(=O)NR ａ－５１ R ａ－５２ , or one or more R ａ１－１ C substituted with １－６ is an alkyl group, R ａ１－１ is a halogen, a hydroxyl group or -OC １－６ is an alkyl group, A １ is N or CR １ and R １ is hydrogen, C １－６ an alkyl group, one or more R １－１ C substituted with １－６ Alkyl group, halogen, C ３－１０ Cycloalkyl group, one or more R １－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－４ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－７ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－８ and when there are a plurality of substituents, they may be the same or different, R １－１ , R １－３ , R １－４ , R １－５ , R １－６ , R １－７ and R １－８ are independently an azide group, a halogen, a hydroxyl group, a cyano group, an oxo group, １－６ an alkyl group, one or more R １－１－１ C substituted with １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OC １－６ an alkyl group, one or more R １－１－２ -OC substituted with １－６ Alkyl group, -C(=O)R １１ａ , -NR １１ｂ１ R １１ｂ２ , -C(=O)OR １１ｃ , -C(=O)NR １１ｄ１ R １１ｄ２ , -S(O) ２ N.R. １１ｅ１ R １１ｅ２ , -S(O) ２ R １１ｆ , C ３－１０ Cycloalkyl group, one or more R １－１－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－１－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－１－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－１－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－１－７ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－１－８ and when there are a plurality of substituents, they may be the same or different, R １－１－１ , R １－１－２ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ and R １－１－８ are independently a halogen, a hydroxyl group, an oxo group, １－６ An alkyl group or one or more R １－１－１－１ C substituted with １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－１－１－１ is a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ａ R ｂ and R ａ and R ｂ are independently hydrogen or C １－６ is an alkyl group, R １１ａ , R １１ｂ１ , R １１ｂ２ , R １１ｃ , R １１ｄ１ , R １１ｄ２ , R １１ｅ１ , R １１ｅ２ and R １１ｆ are independently hydrogen, C １－６ an alkyl group, one or more R １－２－１ C substituted with １－６ Alkyl group, -OC １－６ an alkyl group, one or more R １－２－２ -OC substituted with １－６ Alkyl group, C ３－１０ Cycloalkyl group, one or more R １－２－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－２－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－２－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－２－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－２－７ C substituted with ５－７ a cycloalkenyl group, "a 5- to 7-membered heterocycloalkenyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－２－８ and when there are a plurality of substituents, they may be the same or different, R １－２－１ , R １－２－２ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ and R １－２－８ are independently a halogen, a hydroxyl group, or -NR １２ｃ R １２ｄ , Oxo, C １－６ An alkyl group or one or more R １－２－１－１ C substituted with １－６ is an alkyl group, R １２ｃ and R １２ｄ are independently hydrogen or C １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－２－１－１ are independently a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ｃ R ｄ and R ｃ and R ｄ are independently hydrogen or C １－６ is an alkyl group, Or, R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ , R １－１－８ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ , and R １－２－８ If the number of R is greater than 1, then two optional R １－３ , two optional R １－４ , two optional R １－５ , two optional R １－６ , two optional R １－７ , two optional R １－８ , two optional R １－１－３ , two optional R １－１－４ , two optional R １－１－５ , two optional R １－１－６ , two optional R １－１－７ , two optional R １－１－８ , two optional R １－２－３ , two optional R １－２－４ , two optional R １－２－５ , two optional R １－２－６ , two optional R １－２－７ , or optionally two R １－２－８ are connected to each other and independently, together with the atoms connected thereto, form a 3- to 8-membered carbocyclic ring, one or more R １－３－１ a 3- to 8-membered carbocyclic ring substituted with "a 3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S, and N"; １－３－２ "3-8 membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ Aromatic ring, one or more R １－３－３ C substituted with ６－２０ an aromatic ring, a "5- to 12-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S, and N," one or more R １－３－４ "5-12 membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloolefin, one or more R １－３－５ C substituted with ５－７ Cycloolefin, "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R １－３－６ forming a "5- to 7-membered heterocycloolefin containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with R １－３－１ , R １－３－２ , R １－３－３ , R １－３－４ , R １－３－５ and R １－３－６ are independently oxo, a hydroxy group, a halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ is an alkyl group, Or, R ａ－３１ and R ａ－３２ , R ａ－５１ and R ａ－５２ , R １１ｂ１ and R １１ｂ２ , R １１ｄ１ and R １１ｄ２ , R １１ｅ１ and R １１ｅ２ , R ａ and R ｂ , R ｃ and R ｄ Each independently represents, together with the N to which it is linked, a "3- to 8-membered heterocycle, one of which is N and the others each independently contain 1 to 3 heteroatoms selected from O, S, and N," or one or more R １－４－１ and R １－４－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ is an alkyl group, A ２ and A ３ are independently N or CR ２ and R ２ is hydrogen or halogen, A ４ is N or CR ４ｄ and R ４ｄ is hydrogen, halogen, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, A ５ is S or NR ５ｄ and R ５ｄ teeth, 【Chemistry 24】 and L １ is a connecting bond or C １－６ is an alkylene group, Q １ is hydrogen, halogen, cyano group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, hydroxy group, -C(=O)R ５２ａ , -NR ５２ｂ１ R ５２ｂ２ , -C(=O)OR ５２ｃ , -C(=O)NR ５２ｄ１ R ５２ｄ２ , C substituted with one or more halogens １－６ Alkyl group, -OC １－６ Alkyl group, C ６－２０ an aryl group, one or more R ５－１－２ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; ５－１－３ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ３－１２ Cycloalkyl group, one or more R ５－１－４ C substituted with ３－１２ a cycloalkyl group, "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R ５－１－５ "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, and when there are multiple substituents, they may be the same or different, R ５－１－２ , R ５－１－３ , R ５－１－４ and R ５－１－５ are independently a halogen, a hydroxyl group, an oxo group, a cyano group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ Alkyl group, —OC substituted with one or more halogens １－６ Alkyl group, -C(=O)R ５１ａ , -NR ５１ｂ１ R ５１ｂ２ , -C(=O)OR ５１ｃ or -C(=O)NR ５１ｄ１ R ５１ｄ２ and when there is more than one substituent, they may be the same or different, R ５２ａ , R ５２ｂ１ , R ５２ｂ２ , R ５２ｃ , R ５２ｄ１ , R ５２ｄ２ , R ５１ａ , R ５１ｂ１ , R ５１ｂ２ , R ５１ｃ , R ５１ｄ１ and R ５１ｄ２ are independently hydrogen, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, Or, R ５２ｂ１ and R ５２ｂ２ , R ５２ｄ１ and R ５２ｄ２ , R ５１ｂ１ and R ５１ｂ２ , R ５１ｄ１ and R ５１ｄ２ Each independently represents, together with the N to which it is linked, a "3- to 8-membered heterocycle, one of which is N and the others each independently contain 1 to 3 heteroatoms selected from O, S, and N," or one or more R １－５－１ forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S and N" substituted with R １－５－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; R ６ is a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R ６－１ "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with R ６－１ is C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, Aspect 3: A five-membered heteroaryl ring structure-containing compound represented by formula IV″, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, or an isotope thereof, 【Chemistry 25】 however, R ａ１ is hydrogen, halogen, cyano group, C １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OR ａ－１ , -C(=O)R ａ－２ , -NR ａ－３１ R ａ－３２ , -C(=O)OR ａ－４ , -C(=O)NR ａ－５１ R ａ－５２ , or one or more R ａ１－１ C substituted with １－６ is an alkyl group, R ａ１－１ is a halogen, a hydroxyl group or -OC １－６ is an alkyl group, R １ is C ３－１０ Cycloalkyl group, one or more R １－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－４ "4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－７ C substituted with ５－７ Cycloalkenyl group, "C containing 1 to 3 heteroatoms independently selected from O, S, and N" ５－７ heterocycloalkenyl group" or one or more R １－８ "C containing 1 to 3 heteroatoms independently selected from O, S and N" ５－７ heterocycloalkenyl group, and when the substituents are plural, they may be the same or different, R １－３ , R １－４ , R １－５ , R １－６ , R １－７ and R １－８ are independently a halogen, a hydroxyl group, a cyano group, an oxo group, １－６ an alkyl group, one or more R １－１－１ C substituted with １－６ Alkyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, -OC １－６ an alkyl group, one or more R １－１－２ -OC substituted with １－６ Alkyl group, -C(=O)R １１ａ , -NR １１ｂ１ R １１ｂ２ , -C(=O)OR １１ｃ , -C(=O)NR １１ｄ１ R １１ｄ２ , -S(O) ２ N.R. １１ｅ１ R １１ｅ２ , C ３－１０ Cycloalkyl group, one or more R １－１－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－１－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－１－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－１－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－１－７ C substituted with ５－７ Cycloalkenyl group, "C containing 1 to 3 heteroatoms independently selected from O, S, and N" ５－７ heterocycloalkenyl group" or one or more R １－１－８ "C containing 1 to 3 heteroatoms independently selected from O, S and N" ５－７ heterocycloalkenyl group, and when the substituents are plural, they may be the same or different, R １－１－１ , R １－１－２ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ and R １－１－８ are independently halogen, oxo, C １－６ An alkyl group or one or more R １－１－１－１ C substituted with １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－１－１－１ is a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ａ R ｂ and R ａ and R ｂ are independently hydrogen or C １－６ is an alkyl group, R １１ａ , R １１ｂ１ , R １１ｂ２ , R １１ｃ , R １１ｄ１ , R １１ｄ２ , R １１ｅ１ and R １１ｅ２ are independently hydrogen, C １－６ an alkyl group, one or more R １－２－１ C substituted with １－６ Alkyl group, -OC １－６ an alkyl group, one or more R １－２－２ -OC substituted with １－６ Alkyl group, C ３－１０ Cycloalkyl group, one or more R １－２－３ C substituted with ３－１０ a cycloalkyl group, a "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," one or more R １－２－４ "4- to 10-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－２－５ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－２－６ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－２－７ C substituted with ５－７ Cycloalkenyl group, "C containing 1 to 3 heteroatoms independently selected from O, S, and N" ５－７ heterocycloalkenyl group" or one or more R １－２－８ "C containing 1 to 3 heteroatoms independently selected from O, S and N" ５－７ heterocycloalkenyl group, and when the substituents are plural, they may be the same or different, R １－２－１ , R １－２－２ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ and R １－２－８ are independently halogen, oxo, C １－６ An alkyl group or one or more R １－２－１－１ C substituted with １－６ alkyl group, and when the substituents are plural, they may be the same or different; R １－２－１－１ are independently a halogen, a hydroxyl group, -OC １－６ Alkyl group or -NR ｃ R ｄ and R ｃ and R ｄ are independently hydrogen or C １－６ is an alkyl group, Or, R １－３ , R １－４ , R １－５ , R １－６ , R １－７ , R １－８ , R １－１－３ , R １－１－４ , R １－１－５ , R １－１－６ , R １－１－７ , R １－１－８ , R １－２－３ , R １－２－４ , R １－２－５ , R １－２－６ , R １－２－７ , and R １－２－８ If the number of R is greater than 1, then two optional R １－３ , two optional R １－４ , two optional R １－５ , two optional R １－６ , two optional R １－７ , two optional R １－８ , two optional R １－１－３ , two optional R １－１－４ , two optional R １－１－５ , two optional R １－１－６ , two optional R １－１－７ , two optional R １－１－８ , two optional R １－２－３ , two optional R １－２－４ , two optional R １－２－５ , two optional R １－２－６ , two optional R １－２－７ , or optionally two R １－２－８ are connected to each other and independently, together with the atoms connected thereto, form a 3- to 8-membered carbocyclic ring, one or more R １－３－１ a 3- to 8-membered carbocyclic ring substituted with "a 3- to 8-membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S, and N"; １－３－２ "3-8 membered heterocycle containing 1 to 3 heteroatoms independently selected from O, S and N" substituted with C ６－２０ an aryl group, one or more R １－３－３ C substituted with ６－２０ an aryl group, a "5- to 12-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N"; １－３－４ "5-12 membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with C ５－７ Cycloalkenyl group, one or more R １－３－５ C substituted with ５－７ Cycloalkenyl group, "C containing 1 to 3 heteroatoms independently selected from O, S, and N" ５－７ heterocycloalkenyl group" or one or more R １－３－６ "C containing 1 to 3 heteroatoms independently selected from O, S and N" ５－７ Heterocycloalkenyl group" is formed, R １－３－１ , R １－３－２ , R １－３－３ , R １－３－４ , R １－３－５ and R １－３－６ are independently oxo, a hydroxy group, a halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ is an alkyl group, Or, R ａ－３１ and R ａ－３２ , R ａ－５１ and R ａ－５２ , R １１ｂ１ and R １１ｂ２ , R １１ｄ１ and R １１ｄ２ , R １１ｅ１ and R １１ｅ２ , R ａ and R ｂ , R ｃ and R ｄ Each independently represents, together with the N to which it is linked, a "3- to 8-membered heterocycle, one of which is N and the others each independently contain 1 to 3 heteroatoms selected from O, S, and N," or one or more R １－４－１ and R １－４－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ is an alkyl group, A ２ and A ３ are independently N or CR ２ and R ２ is hydrogen or halogen, A ４ is N or CR ４ｄ and R ４ｄ is hydrogen, halogen, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, R ５ｄ teeth, 【Chemistry 26】 and L １ is a connecting bond or C １－６ is an alkylene group, Q １ is hydrogen, halogen, cyano group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, hydroxy group, -C(=O)R ５２ａ , -NR ５２ｂ１ R ５２ｂ２ , -C(=O)OR ５２ｃ , -C(=O)NR ５２ｄ１ R ５２ｄ２ , C substituted with one or more halogens １－６ Alkyl group, -OC １－６ Alkyl group, C ３－１２ Cycloalkyl group, one or more R ５－１－４ C substituted with ３－１２ a cycloalkyl group, "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N," or one or more R ５－１－５ "a 4- to 12-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from O, S, and N" substituted with, and when there are multiple substituents, they may be the same or different, R ５－１－４ and R ５－１－５ are independently a halogen, a hydroxyl group, an oxo group, a cyano group, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ Alkyl group, —OC substituted with one or more halogens １－６ Alkyl group, -C(=O)R ５１ａ , -NR ５１ｂ１ R ５１ｂ２ , -C(=O)OR ５１ｃ or -C(=O)NR ５１ｄ１ R ５１ｄ２ and when there is more than one substituent, they may be the same or different, R ５２ａ , R ５２ｂ１ , R ５２ｂ２ , R ５２ｃ , R ５２ｄ１ , R ５２ｄ２ , R ５１ａ , R ５１ｂ１ , R ５１ｂ２ , R ５１ｃ , R ５１ｄ１ and R ５１ｄ２ are independently hydrogen, C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group, Or, R ５２ｂ１ and R ５２ｂ２ , R ５２ｄ１ and R ５２ｄ２ , R ５１ｂ１ and R ５１ｂ２ , R ５１ｄ１ and R ５１ｄ２ Each independently represents, together with the N to which it is linked, a "3- to 8-membered heterocycle, one of which is N and the others each independently contain 1 to 3 heteroatoms selected from O, S, and N," or one or more R １－５－１ forming a "3- to 8-membered heterocycle containing 1 to 3 heteroatoms, one of which is N and the others are independently selected from O, S and N" substituted with R １－５－１ is an oxo, hydroxy group, halogen, C １－６ Alkyl group, C substituted with one or more halogens １－６ Alkyl group, -OC １－６ an alkyl group or —OC substituted with one or more halogens; １－６ alkyl group, and when the substituents are plural, they may be the same or different; R ６ is a "five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S, and N" or one or more R ６－１ "a five-membered heteroaryl group containing 1 to 4 heteroatoms independently selected from O, S and N" substituted with R ６－１ is C １－６ C substituted with an alkyl group or one or more halogens １－６ is an alkyl group.

10. The compound having a five-membered heteroaryl ring structure represented by formula I according to claim 1, characterized in that the compound having a five-membered heteroaryl ring structure represented by formula I has any one of the following structures: 【Chemical 27】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 。

11. A process for preparing the compound containing a five-membered heteroaryl ring structure of formula I according to any one of claims 1 to 10, characterized in that it is one of Routes 1 to 9. (Route 1, 【Chemistry 28】 However, R ａ１ , R ａ２ , R ａ３ , R ５ｄ , R ６ , A １ , A ２ , A ３ are defined as in any one of claims 1 to 10, MET is a metal group, PG is a protecting group, and the steps of said pathway 1 are introducing a protecting group into compound A1 to obtain compound A2, converting A2 into metal compound A3, coupling reaction of A3 to produce compound A4, converting A4 into benzylthio group compound A5, deprotecting A5 to produce compound A6, converting A6 into compound A7 by a reaction such as nucleophilic substitution, and further converting A7 to obtain compound I1; Route 2: 【Chemical 29】 However, R ａ１ , R ａ２ , R ａ３ , R ５ｄ , R ６ , A １ , A ２ , A ３ The definitions of are as defined in any one of claims 1 to 10, and ALK is C １－６ the step of said pathway 2 is to convert an ester group compound B1 into a compound B2 under the action of a hydrazine compound, to generate a compound B3 by introducing an acyl group into B2 and forming a ring, to convert B3 into a compound B4 by a reaction such as nucleophilic substitution, to convert B4 into a benzylthio group compound B5, and to further convert B5 to obtain a compound I2; Route 3: 【Chemistry 30】 However, R ａ１ , R ａ２ , R ａ３ , R ５ｄ , R ６ , A ２ , A ３ , R １ are defined as in any one of claims 1 to 10, MET is a metal group, PG is a protecting group, and the steps of route 3 are: converting compound C1 to benzylthio group compound C2, introducing a protecting group to C2 to obtain compound C3, converting C3 to metal compound C4, coupling reaction of C4 to produce compound C5, deprotecting C5 to produce compound C6, converting C6 to compound C7 by a reaction such as nucleophilic substitution, further converting C7 to obtain compound C8, and converting C8 by a reaction such as nucleophilic substitution, coupling, etc. to obtain compound I3; Route 4: 【Chemistry 31】 However, R ａ１ , R ａ２ , R ａ３ , R ５ｄ , R ６ , A ２ , A ３ , R １ are defined as in any one of claims 1 to 10, MET is a metal group, PG is a protecting group, and ALK is C １－６ the alkyl group; the steps of route 4 are to introduce a protecting group into compound C1 to obtain compound D1, convert D1 into metal compound D2, D2 undergoes a coupling reaction to produce compound D3, D3 is converted into compound D4, D4 is deprotected to produce compound D5, D5 is converted into compound D6 through a reaction such as nucleophilic substitution, D6 is oxidized into compound D7, D7 is further converted into compound C8, and C8 is converted into compound I3 through a reaction such as nucleophilic substitution, coupling, etc.; Route 5: 【Chemistry 32】 However, R ａ１ , R ａ２ , R ａ３ , X, R ５ｄ , R ６ , A ２ , A ３ , R １ The definitions of are as defined in any one of claims 1 to 10, and ALK is C １－６ the step of route 5 is to convert compound D6 to compound E1 by a reaction such as nucleophilic substitution, coupling, etc., oxidize E1 to obtain compound E2, and further convert E2 to obtain compound I3; Route 6: 【Chemical Formula 33】 However, R ａ１ , R ａ２ , R ａ３ , R ５ｄ , R ６ , R １ The definitions of are as defined in any one of claims 1 to 10, and ALK is C １－６ the steps of route 6 are: chlorosulfonation of compound F1 to obtain compound F2, conversion of F2 to compound F3 through bromination reaction, further conversion of F3 to compound F4, conversion of F4 to compound F5 under the action of a hydrazine compound, introduction of an acyl group into F5, ring formation to produce compound F6, and conversion of F6 to compound I4 through reactions such as nucleophilic substitution and coupling; Route 7: 【Chemical 34】 However, R ａ１ , R ａ２ , R ａ３ , R ６ , R １ The definitions of are as defined in any one of claims 1 to 10, and ALK is C １－６ the steps of route 7 are: oxidizing compound G1 to obtain compound G2, further converting G2 to obtain compound G3, converting G3 to compound G4 under the action of a hydrazine compound, introducing an acyl group into G4, forming a ring to generate compound G5, and converting G5 to compound I5 through reactions such as nucleophilic substitution and coupling; Route 8, 【Chemistry 35】 However, R ａ１ , R ａ２ , R ａ３ , R ５ｄ , R ６ , R １ , A ２ , A ３ The definitions of are as above, and ALK is C １－６ the alkyl group, for example, methyl group, ethyl group; the steps of said pathway 8 are to convert the ester group compound H1 into compound H2 by a reaction such as nucleophilic substitution, H2 reacts with a hydrazine compound to introduce an acyl group and form a ring to produce compound H3, H3 is converted into H4, H4 is converted into compound H5 by a reaction such as oxidation, substitution, etc., and H5 is further converted to obtain compound I6; Route 9, 【Chemical 36】 However, R ａ１ , R ａ２ , R ａ３ , R ５ｄ , R ６ , A １ , A ２ , A ３ The definitions of are as defined in any one of claims 1 to 10, and ALK is C １－６ The steps of Route 9 are to convert compound K1 to compound K2 through a coupling or oxidation reaction, convert K2 to compound K3 through a reaction such as nucleophilic substitution, and then convert K3 to compound I1.

12. A pharmaceutical composition comprising a substance A and a pharmaceutical excipient, wherein the substance A is a therapeutically effective amount of a five-membered heteroaryl ring structure-containing compound represented by formula I according to any one of claims 1 to 10, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof or an isotope thereof.

13. Use of a substance A in the preparation of a PARG inhibitor, wherein the substance A is a five-membered heteroaryl ring structure-containing compound represented by formula I according to any one of claims 1 to 10, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof or an isotope thereof.

14. 13. Use of a substance A in the preparation of a medicament, wherein the medicament is used for the treatment or prevention of a PARG-mediated disease, and the substance A is a five-membered heteroaryl ring structure-containing compound represented by formula I according to any one of claims 1 to 10, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof or an isotope thereof.

15. 13. Use of a substance A in the preparation of a medicament for the treatment or prevention of cancer, wherein said substance A is a five-membered heteroaryl ring structure-containing compound of formula I according to any one of claims 1 to 10, a pharma- ceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof or an isotope thereof, and said cancer is, for example, one or more of colon cancer, appendix cancer, pancreatic cancer, MYH-associated polyposis, blood cancer, breast cancer, endometrial cancer, gallbladder cancer, biliary tract cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, testicular cancer, kidney cancer, head and neck cancer, bone cancer, skin cancer, rectal cancer, liver cancer, esophageal cancer, gastric cancer, thyroid cancer, bladder cancer, lymphoma, leukemia and melanoma.

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