Nitrogen-containing 5,6-condensed compound, intermediate thereof, preparation method and use

Abstract

The present invention discloses a nitrogen-containing 5,6-condensed compound, an intermediate thereof, a preparation method and uses. The present invention provides a compound represented by Formula I, a pharmaceutically acceptable salt or an isotope compound thereof. The compounds of the present invention have relatively good PARG inhibitory activity. Also, the permeability and / or solubility of the compounds of the present invention have been greatly improved as compared with existing inventions. 【Chemical 1】 JPEG2025523576000678.jpg27169

Description

Detailed Description of the Invention

[0001] This application claims the priority of Chinese Patent Application No. 2022107849339 filed on June 29, 2022. This application claims the priority of Chinese Patent Application No. 2022115596106 filed on December 6, 2022. This application claims the priority of Chinese Patent Application No. 2023107306040 filed on June 19, 2023. This application incorporates the entire text of the above-mentioned Chinese patent applications by reference.

[0002] 〔Technical Field〕 The present invention relates to a nitrogen-containing 5,6-condensed compound, an intermediate thereof, a preparation method and uses thereof.

[0003] 〔Background Art〕 PARG is a poly(ADP-ribose) hydrolase that is encoded by a single gene and was first identified (Mirella et al. Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments. Experimental Cell Research, 2004, 297(2):521-532.) and can hydrolyze the O-glycosidic bond between ADP-ribose subunits. PARG consists of four structures, including an N-terminal disordered domain, a linker domain, a C-terminal catalytic domain, and an ADP-ribose binding domain (Meyer B et al. Clustered DNA damage induces pan-nuclear H2AX phosphorylation mediated by ATM and DNA-PK. Nucleic Acids Res, 2003, 41:6109-6118.; O’Sullivan J. et al. Emerging roles of eraser enzymes in the dynamic control of protein ADP-ribosylation. Nature Communication, 2019, 10, 1182.). Among them, the non-conserved disordered domain at the N-terminus is not essential for in vitro activity, and the ADP-ribose binding domain at the C-terminus is highly conserved with other Macro-domains and forms the minimum structure with complete enzyme activity in vitro together with the catalytic domain (Slade D et al. The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase. Nature, 2011, 477:616-620.).

[0004] Poly(ADP-ribosyl)ation (PARylation), as a unique post-translational modification, plays an important role in maintaining genomic stability in various signaling pathways, especially in DNA damage repair. Poly(ADP-ribose), abbreviated as PAR, consists of adenosine diphosphate-ribose units, uses NAD + as a donor, is formed by the catalysis of poly(ADP-ribose) polymerases (PARPs), and can be rapidly degraded by polyribosyl hydrolase. After DNA damage, many DNA damage response factors recognize PARylation and are mobilized in the vicinity of the DNA damage site through PARylation. However, PARylation needs to be rapidly digested so that DNA damage response factors can directly recognize DNA damage and perform repair functions. Otherwise, DNA repair factors will be trapped in the vicinity of DNA damage by PARylation and cannot perform their repair functions normally. Therefore, dePARylation, as a direct downstream procedure of PARylation in DNA repair, can affect PARylation-dependent DNA damage repair by inhibiting this process and selectively kill tumor cells with DNA repair defects.

[0005] As the most major poly(ADP-ribose) hydrolase, PARG functions on approximately 90% of PAR in cells (Laetitia Detal. Poly(ADP-ribose) glycohydrolase (PARG) and its therapeutic potential. Front Biosci, 2009, 14(5): 1619-1626.), and is involved in various cellular processes such as DNA damage repair, DNA replication, chromatin control, transcription, and apoptosis. The imbalance of intracellular PAR levels caused by PARG dysfunction is thought to affect the transformation and invasion of cancer cells. (Rack J Detal. Macrodomain: structure, function, evolution, and catalytic activities. Annu Rev Biochem. 2016, 85: 431-454; Marques M et al. Oncogenic activity of poly(ADP-ribose) glycohydrolase. Oncogene, 2019, 38: 2177-2191).

[0006] PARG has been shown to be associated with various diseases, and data suggest that elevated PARG is associated with poor prognosis in HER2+ patients (Maud Metal, Oncogenic activity of poly(ADP-ribose) glycohydrolase. Oncogene, 2019, 38: 2177-2191.). PARG and HER2 synergistically promote the proliferation of breast cancer cells, and PARG inhibition significantly affects the proliferation and migration of breast cancer. Also, according to (Mincheng Ye et al. PARG inhibition limits HCC progression and potentiates the efficacy of immune checkpoint therapy. Hepatic and Biliary Cancer, 2022, S0168-8278(22)00072-1.), high expression of PARG is closely related to poor prognosis of liver cancer, and specific PARG dysfunction in hepatocytes affects tumorigenesis. Therefore, PARG inhibitors are attracting increasing attention as potential therapeutic means. At present, there are many PARG inhibitors in development, but all are in the preclinical research stage. For this reason, it is of great research significance to develop small molecule drugs that can provide patients with safer and more effective PARG inhibitors that target and inhibit the activity of PARG, and to provide patients with safer and more effective PARG inhibitors.

[0007] 〔Summary of the Invention〕 The technical problem to be solved by the present invention is that the structure of the compound having a PARG inhibitor in the prior art is relatively single. Therefore, the present invention provides a nitrogen-containing 5,6-condensed compound, an intermediate thereof, a preparation method and uses. The compound of the present invention has relatively good PARG inhibitory activity. Also, the permeability and / or solubility of the compound of the present invention have been greatly improved compared to existing inventions.

[0008] The present invention provides a compound represented by formula I, a pharmaceutically acceptable salt or isotope compound thereof, wherein,

[0009]

Chemical formula

[0010] and R A is hydrogen or a C1-C6 alkyl group, ring B is an unsubstituted or 5,6-fused heteroaromatic ring substituted by one or two Rs B or an unsubstituted or 5,5-fused heteroaromatic ring substituted by one or two Rs B wherein the heteroatom of the 5,6-fused heteroaromatic ring is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5,5-fused heteroaromatic ring is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and R B is each independently oxa, a hydroxy group, a halogen, or a C1-C6 alkyl group, or two Rs B together with the atom to which it is attached form a 3-6 membered cycloalkyl group, R 1 is a hydroxy group, a C1-C6 alkyl group unsubstituted or substituted by one or more Rs 1-1 a C3-C6 cycloalkyl group unsubstituted or substituted by one or more Rs 1-2 a 3-6 membered heterocycloalkyl group unsubstituted or substituted by one or more Rs 1-3 or an amino group unsubstituted or substituted by one or two Rs

[0011]

Chemical formula

[0012] or an amino group unsubstituted or substituted by one or two Rs 1-5 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, each R 1-1each independently being deuterium, a hydroxy group, a cyano group, a halogen, a 3- to 6-membered heterocycloalkyl group, a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-1-1 a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-1-2 a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, and each R 1-1-1 is each independently deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-2 is each independently deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-3 is each independently deuterium, a hydroxy group, a cyano group or a halogen, each R 1-2 is each independently deuterium, a hydroxy group, a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-2-1 a C2-C6 alkynyl group which is unsubstituted or substituted by one or more R 1-2-2 a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3 a C2-C6 alkenyl group which is unsubstituted or substituted by one or two R 1-2-4 an amino group which is unsubstituted or substituted by one or two R 1-2-5 or

[0013]

Chemical formula

[0014] and each R 1-2-1 is each independently deuterium, a halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-1-1 and each R 1-2-1-1is independently a halogen, each R 1-2-2 is independently a halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-2-1 each R 1-2-2-1 is independently a halogen, each R 1-2-3 is independently a halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3-1 each R 1-2-3-1 is independently a halogen, each R 1-2-4 is independently a halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-4-1 each R 1-2-4-1 is independently a halogen, each R 1-2-6 is independently an amino group, each R 1-2-5 is independently

[0015]

Chemical formula

[0016] each R 1-2-5-1 is independently a C1-C6 alkyl group, each R 1-3 is independently a cyano group, deuterium, a hydroxy group, an amino group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-3-1 a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-3-2 or a C2-C6 alkynyl group, each R 1-3-1 is independently a halogen, each R 1-3-2 is independently a halogen R 1-4 is a C1-C6 alkyl group each R 1-5 is independently a C1-C6 alkyl group

[0017] [Chemical formula]

[0018] or a C3-C6 cycloalkyl group, R 1-5-1 is a C1-C6 alkyl group or an amino group, or the atoms in R 1 and the atoms in A are linked to form a 5-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 0 wherein the heteroatoms of the 5-10 membered heterocycloalkyl group are selected from one or more of N, O, P and S, the number of heteroatoms is 3, 4 or 5, and each R 0 is independently a C1-C6 alkyl group or oxa, R 2 is hydrogen, a 6-10 membered aryl group which is unsubstituted or substituted by one or more R 2-1 a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more R 2-2 a 4-12 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3 ,

[0019] [Chemical formula]

[0020] a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-6 ,

[0021] [Chemical formula]

[0022] a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-9 and a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-10a C3-C6 cycloalkenyl group replaced by

[0023]

Chemical formula

[0024] wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. each R 2-1 is independently a cyano group, a halogen, a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 2-1-1 or an alkoxy group of C1-C6 which is unsubstituted or substituted by one or more R

[0025]

Chemical formula

[0026] or an alkoxy group of C1-C6 which is unsubstituted or substituted by one or more R 2-1-4 wherein each R is independently a cyano group or a halogen, R 2-1-1 is hydrogen or a C1-C6 alkyl group, each R 2-1-2 is independently hydrogen or a C1-C6 alkyl group, each R 2-1-3 is independently hydrogen or a C1-C6 alkyl group, each R 2-1-4 is independently a halogen. each R 2-2 is independently a cyano group, a halogen, a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 2-2-1 or an alkoxy group of C1-C6 which is unsubstituted or substituted by one or more R

[0027]

Chemical formula

[0028] and Each R 2-2-1 is, independently of one another, a cyano group or a halogen, and R 2-2-2 is hydrogen or a C1-C6 alkyl group, and each R 2-2-3 is, independently of one another, hydrogen or a C1-C6 alkyl group, and each R 2-2-4 is, independently of one another, a C1-C6 alkyl group or a C3-C6 cycloalkyl group, Each R 2-3 is, independently of one another, a cyano group, oxa, a hydroxy group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-1 groups,

[0029]

Chemical formula

[0030] a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3-4 groups, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-5 groups, a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-6 groups, an amino group which is unsubstituted or substituted by one or more R 2-3-7 groups,

[0031]

Chemical formula

[0032] a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-3-9 groups, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-3-1is, independently of one another, a hydroxy group, a cyano group, a halogen, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-1-1 a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-1-2 an amino group which is unsubstituted or substituted by one or more R 2-3-1-3 wherein, R 2-3-2 is hydrogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-2-1 a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-2-2 wherein,

[0033]

Chemical formula

[0034] a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-2-4 a 3-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3-2-5 a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more R 2-3-2-6 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-3-3 is, independently of one another, hydrogen or a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-3-1 wherein, each R 2-3-4 is, independently of one another, a C1-C6 alkyl group or oxa, each R 2-3-5 is, independently of one another, a halogen or deuterium, each R 2-3-6is, independently of each other, a C1-C6 alkyl group, each R 2-3-7 is, independently of each other, a C1-C6 alkyl group, each R 2-3-8 is, independently of each other, a C1-C6 alkyl group, or a C3-C6 cycloalkyl group, each R 2-3-9 is, independently of each other, a C1-C6 alkyl group, each R 2-3-1-1 is, independently of each other, a halogen, each R 2-3-1-2 is, independently of each other, a C1-C6 alkoxy group, each R 2-3-1-3 is, independently of each other, a C1-C6 alkyl group, each R 2-3-2-1 is, independently of each other, a halogen, carboxyl group, hydroxy group, oxa, C1-C6 alkoxy group,

[0035]

Chemical formula

[0036] an amino group which is unsubstituted or substituted by one or more Rs 2-3-2-1-2 a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more Rs 2-3-2-1-3 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-3-2-1-1 is, independently of each other, a C1-C6 alkyl group or a 6-10 membered aryl group, each R 2-3-2-1-2 is, independently of each other, a C1-C6 alkyl group, each R 2-3-2-1-3 is, independently of each other, a C1-C6 alkyl group, each R 2-3-2-2 is, independently of each other, a halogen, hydroxy group, an unsubstituted or one or more Rs 2-3-2-2-1a C1-C6 alkyl group substituted by, unsubstituted or one or more Rs 2-3-2-2-2 a C1-C6 alkoxy group substituted by, unsubstituted or one or more Rs 2-3-2-2-3 is an amino group substituted by, each R 2-3-2-2-1 is independently a halogen or a hydroxy group, each R 2-3-2-2-2 is independently a carboxyl group, a halogen, deuterium, oxa or a hydroxy group, each R 2-3-2-2-3 is independently a C1-C6 alkyl group, each R 2-3-2-3 is independently hydrogen or

[0037]

Chemical formula

[0038] and each R 2-3-2-3-1 is independently an unsubstituted or a 6-10 membered aryl group substituted by one or more Rs 2-3-2-3-1-1 each R 2-3-2-3-1-1 is independently a C1-C6 alkoxy group, each R 2-3-2-4 is independently a halogen, each R 2-3-2-5 is independently a halogen, a hydroxy group, oxa, a C1-C6 alkoxy group, an unsubstituted or a C1-C6 alkyl group substituted by one or more Rs 2-3-2-5-1 each R 2-3-2-5-1 is independently a halogen, each R 2-3-2-6 is independently a C1-C6 alkyl group, each R 2-3-3-1 is independently an unsubstituted or an amino group substituted by one or more Rs 2-3-3-1-1 each R 2-3-3-1-1 is independently a C1-C6 alkyl group, each R 2-4is an unsubstituted or 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-4-1 is an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 2-4-2 is an unsubstituted or 6- to 10-membered aryl group substituted by one or more R 2-4-3 is a C3-C6 cycloalkyl group substituted by one or more R 2-4-4 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-4-1 is independently a hydroxy group, a halogen, a C1-C6 alkyl group,

[0039]

Chemical formula

[0040] and each R 2-4-2 is independently a hydroxy group, a halogen, or a C1-C6 alkyl group, each R 2-4-3 is independently a hydroxy group, a halogen, or a C1-C6 alkyl group, each R 2-4-4 is independently a hydroxy group, a halogen, or a C1-C6 alkyl group, R 2-4-1-1 is a C1-C6 alkyl group, each R 2-4-1-2 is a C1-C6 alkyl group, each R 2-5 is independently hydrogen, an unsubstituted or 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-5-1 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R

[0041]

Chemical formula

[0042] unsubstituted or a 6-10 membered aryl group or a C1-C6 alkyl group substituted by one or more R 2-5-3 wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-5-1 is, independently of one another,

[0043]

Chemical formula

[0044] and R 2-5-1-1 is hydrogen or a C1-C6 alkyl group, each R 2-5-1-2 is, independently of one another, hydrogen or a C1-C6 alkyl group, R 2-5-2 is independently a C1-C6 alkyl group, each R 2-5-3 is, independently of one another, a C1-C6 alkoxy group, each R 2-6 is, independently of one another, halogen, a C1-C6 alkyl group, unsubstituted or a 4-10 membered heterocycloalkyl group substituted by one or more R 2-6-1 or a 5-10 membered heteroaryl group substituted by one or more R 2-6-2 wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, and the heteroatom of the 5-10 membered heteroaryl group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-6-1 is, independently of one another, halogen, a C1-C6 alkyl group or

[0045]

Chemical formula

[0046] and R 2-6-1-1 is a C1-C6 alkyl group, each R 2-6-2 is independently a halogen or a C1-C6 alkyl group, each R 2-7 is independently a C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-7-1 with a 4-10 membered heterocycloalkyl group, or unsubstituted or substituted by one or more R 2-7-2 with a 5-10 membered heteroaryl group, wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-7-1 is independently a halogen, a C1-C6 alkyl group,

[0047]

Chemical formula

[0048] and R 2-7-1-1 is a C1-C6 alkyl group, R 2-7-1-2 is a C1-C6 alkyl group, each R 2-7-2 is independently a halogen or a C1-C6 alkyl group, each R 2-8 is independently a C1-C6 alkyl group, or two Rs 2-8 together with the atom to which it is attached form a 4-10 membered heterocycloalkyl group, unsubstituted or substituted by one or more R 2-8-1 wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-8-1are each independently

[0049] [Chemical formula]

[0050] and R 2-8-1-1 is hydrogen or a C1-C6 alkyl group, each R 2-9 is each independently an unsubstituted or a 5-10 membered heteroaryl group substituted by one or more R 2-9-1 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-9-1 is each independently a C1-C6 alkyl group, each R 2-10 is each independently an unsubstituted or a 5-10 membered heteroaryl group substituted by one or more R 2-10-1 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-10-1 is each independently a C1-C6 alkyl group, each R 2-11 is each independently an unsubstituted or a 5-10 membered heteroaryl group substituted by one or more R 2-11-1 and an unsubstituted or a 5-10 membered heterocycloalkyl group substituted by one or more R 2-11-2 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, and the heteroatom of the 5-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-11-1 is each independently a C1-C6 alkyl group, each R 2-11-2is, independently of each other, a C1-C6 alkyl group, R 3 is unsubstituted or a 5-10 membered heteroaryl group substituted by one or more R 3-1 or an unsubstituted or 3-10 membered heterocycloalkyl group substituted by one or more R 3-2 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 3-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 3-1 is, independently of each other, a hydroxy group, a halogen, a C1-C6 alkyl group unsubstituted or substituted by one or more R 3-1-1 or

[0051]

Chemical formula

[0052] and each R 3-1-1 is, independently of each other, a halogen or a hydroxy group, R 3-1-2 is a C1-C6 alkyl group or a C2-C6 alkenyl group, each R 3-2 is, independently of each other, a hydroxy group, a halogen, a C1-C6 alkyl group unsubstituted or substituted by one or more R 3-2-1 or

[0053]

Chemical formula

[0054] and each R 3-2-1 is, independently of each other, a halogen, R 3-2-2 is a C1-C6 alkyl group or a C2-C4 alkenyl group, R4 is hydrogen, deuterium, a halogen, a cyano group, a 5- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 or a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 4-2 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 4-1 is independently

[0055]

Chemical formula

[0056] and each R 4-2 is independently a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 4-2-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, R 4-1-1 is a C1-C6 alkyl group, each R 4-1-2 is independently a C1-C6 alkyl group, each R 4-2-1 is independently a C1-C6 alkyl group, when ring B is

[0057]

Chemical formula

[0058] then R 2 is

[0059]

Chemical formula

[0060] and

[0061] The present invention provides a compound represented by formula I, a pharmaceutically acceptable salt or isotope compound thereof, wherein,

[0062]

Chemical formula

[0063] is, R A is hydrogen or a C1-C6 alkyl group, ring B is an unsubstituted, 5,6-fused heteroaromatic ring substituted by one or two R B or an unsubstituted, 5,5-fused heteroaromatic ring substituted by one or two R B wherein the heteroatom of the 5,6-fused heteroaromatic ring is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5,5-fused heteroaromatic ring is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and R B are each independently oxa, a hydroxy group, a halogen, or a C1-C6 alkyl group, or two R B together with the atom to which they are attached form a 3-6 membered cycloalkyl group, R 1 is a hydroxy group, a C1-C6 alkyl group unsubstituted or substituted by one or more R 1-1 , a C3-C6 cycloalkyl group unsubstituted or substituted by one or more R 1-2 , a 3-6 membered heterocycloalkyl group unsubstituted or substituted by one or more R 1-3 ,

[0064]

Chemical formula

[0065] or an unsubstituted or one or two R 1-5is an amino group substituted by, wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 1-1 is independently deuterium, a hydroxy group, a cyano group, a halogen, a 3-6 membered heterocycloalkyl group, a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-1-1 a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-1-2 or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-1-3 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, and each R 1-1-1 is independently deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-2 is independently deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-3 is independently deuterium, a hydroxy group, a cyano group or a halogen, each R 1-2 is independently deuterium, a hydroxy group, a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-2-1 a C2-C6 alkynyl group which is unsubstituted or substituted by one or more R 1-2-2 a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3 a C2-C6 alkenyl group which is unsubstituted or substituted by one or more R 1-2-4 or an amino group which is unsubstituted or substituted by one or two R 1-2-5 wherein each R 1-2-1 is independently a halogen, a hydroxy group, or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-1-1 wherein each R 1-2-1-1 is independently a halogen, and each R 1-2-2is, independently of one another, halogen, a hydroxy group, or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-2-1 where each R 1-2-2-1 is, independently of one another, halogen, and each R 1-2-3 is, independently of one another, halogen, a hydroxy group, or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3-1 where each R 1-2-3-1 is, independently of one another, halogen, and each R 1-2-4 is, independently of one another, halogen, a hydroxy group, or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-4-1 where each R 1-2-4-1 is, independently of one another, halogen, each R 1-3 is, independently of one another, a cyano group, deuterium, a hydroxy group, an amino group, halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-3-1 or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-3-2 where each R 1-3-1 is, independently of one another, halogen, and each R 1-3-2 is, independently of one another, halogen, R 1-4 is a C1-C6 alkyl group, each R 1-5 is, independently of one another, a C1-C6 alkyl group,

[0066]

Chemical formula

[0067] or a C3-C6 cycloalkyl group, R 1-5-1 is a C1-C6 alkyl group or an amino group, or, the atoms in R 1 and the atoms in A are linked to form a group which is unsubstituted or substituted by one or more R 0forms a 5- to 10-membered heterocycloalkyl group replaced by, wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, P, and S, the number of heteroatoms is 3, 4, or 5, and each R 0 is, independently of one another, a C1-C6 alkyl group or oxa, each R 2 is hydrogen, an unsubstituted 6- to 10-membered aryl group substituted by one or more R 2-1 , an unsubstituted 5- to 10-membered heteroaryl group substituted by one or more R 2-2 , an unsubstituted 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-3 ,

[0068]

Chemical formula

[0069] an unsubstituted C1-C6 alkyl group substituted by one or more R 2-6 ,

[0070]

Chemical formula

[0071] and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-1 is, independently of one another, a cyano group, a halogen, an unsubstituted C1-C6 alkyl group substituted by one or more R 2-1-1 ,

[0072]

Chemical formula

[0073] or unsubstituted or a C1-C6 alkoxy group substituted by one or more Rs 2-1-4 wherein each R is, independently, a cyano group or a halogen, R is hydrogen or a C1-C6 alkyl group, each R is, independently, hydrogen or a C1-C6 alkyl group, and each R is, independently, a halogen each R 2-1-1 is, independently, a cyano group or a halogen, R is hydrogen or a C1-C6 alkyl group, and each R is, independently, hydrogen or a C1-C6 alkyl group 2-1-2 is hydrogen or a C1-C6 alkyl group, and each R is, independently, hydrogen or a C1-C6 alkyl group 2-1-3 is, independently, hydrogen or a C1-C6 alkyl group, and each R is, independently, hydrogen or a C1-C6 alkyl group 2-1-4 is, independently, a halogen each R 2-2 is, independently, a cyano group, a halogen, an unsubstituted or a C1-C6 alkyl group substituted by one or more Rs 2-2-1 wherein each R is, independently, a cyano group or a halogen, R is hydrogen or a C1-C6 alkyl group, each R is, independently, hydrogen or a C1-C6 alkyl group, and each R is, independently, a halogen

[0074]

Chemical formula

[0075] and each R is, independently, a cyano group or a halogen, R is hydrogen or a C1-C6 alkyl group, each R is, independently, hydrogen or a C1-C6 alkyl group 2-2-1 is, independently, a cyano group or a halogen, R is hydrogen or a C1-C6 alkyl group, and each R is, independently, hydrogen or a C1-C6 alkyl group 2-2-2 is hydrogen or a C1-C6 alkyl group, and each R is, independently, hydrogen or a C1-C6 alkyl group 2-2-3 is, independently, hydrogen or a C1-C6 alkyl group, and each R is, independently, hydrogen or a C1-C6 alkyl group each R 2-3 is, independently, a cyano group, an oxa, a hydroxy group, a halogen, an unsubstituted or a C1-C6 alkyl group substituted by one or more Rs 2-3-1 wherein each R is, independently, a cyano group or a halogen, R is hydrogen or a C1-C6 alkyl group, each R is, independently, hydrogen or a C1-C6 alkyl group, and each R is, independently, a halogen

[0076]

Chemical formula

[0077] an unsubstituted or a 3-6 membered heterocycloalkyl group substituted by one or more Rs 2-3-4 is, independently, a cyano group, a halogen, an unsubstituted or a C1-C6 alkyl group substituted by one or more Rs 2-3-5is a C1-C6 alkoxy group replaced by, wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-3-1 is, independently of one another, a cyano group, a halogen, an unsubstituted or C1-C6 alkyl group substituted by one or more R 2-3-1-1 groups, R 2-3-2 is hydrogen or an unsubstituted or C1-C6 alkyl group substituted by one or more R 2-3-2-1 groups, each R 2-3-3 is, independently of one another, hydrogen or a C1-C6 alkyl group, each R 2-3-4 is, independently of one another, a C1-C6 alkyl group, each R 2-3-5 is, independently of one another, a halogen, each R 2-3-1-1 is, independently of one another, a halogen, each R 2-3-2-1 is, independently of one another, a halogen, each R 2-4 is an unsubstituted or 4-10 membered heterocycloalkyl group substituted by one or more R 2-4-1 groups, an unsubstituted or 5-10 membered heteroaryl group substituted by one or more R 2-4-2 groups, an unsubstituted or 6-10 membered aryl group substituted by one or more R 2-4-3 groups, or an unsubstituted or C3-C6 cycloalkyl group substituted by one or more R 2-4-4 groups, wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, and the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-4-1 is, independently of one another, a hydroxy group, a halogen, a C1-C6 alkyl group,

[0078]

Chem.

[0079] and each R 2-4-2 is, independently of one another, a hydroxy group, a halogen or a C1-C6 alkyl group, and each R 2-4-3 is, independently of one another, a hydroxy group, a halogen or a C1-C6 alkyl group, and each R 2-4-4 is, independently of one another, a hydroxy group, a halogen or a C1-C6 alkyl group, R 2-4-1-1 is a C1-C6 alkyl group, and each R 2-4-1-2 is a C1-C6 alkyl group, each R 2-5 is, independently of one another, hydrogen, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-5-1 groups,

[0080]

Chem.

[0081] and the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-5-1 is, independently of one another,

[0082]

Chem.

[0083] and R 2-5-1-1 is hydrogen or a C1-C6 alkyl group, each R 2-5-1-2 is, independently of one another, hydrogen or a C1-C6 alkyl group, R 2-5-2 is, independently, a C1-C6 alkyl group, each R2-6 is, independently of each other, halogen, a C1-C6 alkyl group, a 4-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more Rs 2-6-1 or a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more Rs 2-6-2 wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-6-1 is, independently of each other, halogen, a C1-C6 alkyl group or

[0084]

Chemical formula

[0085] and R 2-6-1-1 is a C1-C6 alkyl group, each R 2-6-2 is, independently of each other, halogen or a C1-C6 alkyl group, each R 2-7 is, independently of each other, a C1-C6 alkyl group, a 4-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more Rs 2-7-1 or a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more Rs 2-7-2 wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-7-1 is, independently of each other, halogen, a C1-C6 alkyl group,

[0086]

Chemical formula

[0087] and R 2-7-1-1 is a C1-C6 alkyl group, and R 2-7-1-2 is a C1-C6 alkyl group, each R 2-7-2 is independently a halogen or a C1-C6 alkyl group, each R 2-8 is independently a C1-C6 alkyl group, or two Rs 2-8 together with the atom to which it is attached form an unsubstituted or one or more Rs 2-8-1 substituted 4- to 10-membered heterocycloalkyl group, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-8-1 is independently

[0088]

Chemical formula

[0089] and R 2-8-1-1 is hydrogen or a C1-C6 alkyl group, R 3 is an unsubstituted or one or more Rs 3-1 substituted 5- to 10-membered heteroaryl group, or an unsubstituted or one or more Rs 3-2 substituted 3- to 10-membered heterocycloalkyl group, wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, and the heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 3-1 is independently a hydroxy group, a halogen, an unsubstituted or one or more Rs 3-1-1a C1-C6 alkyl group replaced by

[0090] [Chemical formula]

[0091] and each R 3-1-1 is, independently of one another, halogen, and R 3-1-2 is a C1-C6 alkyl group or a C2-C6 alkenyl group, each R 3-2 is, independently of one another, a hydroxy group, halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 3-2-1 or

[0092] [Chemical formula]

[0093] and each R 3-2-1 is, independently of one another, halogen, and R 3-2-2 is a C1-C6 alkyl group or a C2-C4 alkenyl group, R 4 is hydrogen, halogen, a 5-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 or a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 4-2 wherein the heteroatom of the 5-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 4-1 is, independently of one another,

[0094] [Chemical formula]

[0095] and each R4-2 is, independently of each other, a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 4-2-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, R 4-1-1 is a C1-C6 alkyl group, and each R 4-1-2 is, independently of each other, a C1-C6 alkyl group, and each R 4-2-1 is, independently of each other, a C1-C6 alkyl group, when ring B is

[0096]

Chemical formula

[0097] then R 2 is

[0098]

Chemical formula

[0099] is as follows.

[0100] In a preferred embodiment, in the compound represented by the formula II, its pharmaceutically acceptable salt or isotopic compound, a specific group may be defined as described below, and other groups may be defined as described in any of the above embodiments (hereinafter referred to as "in a preferred embodiment").

[0101] In a preferred embodiment, R 1 is a hydroxy group, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-1 a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-2 a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 1-3 wherein,

[0102] [Chemical formula]

[0103] or an amino group which is unsubstituted or substituted by one or two Rs 1-5 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, each R 1-1 is independently deuterium, a hydroxy group, a cyano group, a halogen, a 3- to 6-membered heterocycloalkyl group, a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more Rs 1-1-1 a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 1-1-2 or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs 1-1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and each R 1-1-1 is independently deuterium, a hydroxy group, a cyano group, or a halogen, and each R 1-1-2 is independently deuterium, a hydroxy group, a cyano group, or a halogen, and each R 1-1-3 is independently deuterium, a hydroxy group, a cyano group, or a halogen, each R 1-2 is independently deuterium, a hydroxy group, a halogen, a C2-C6 alkynyl group which is unsubstituted or substituted by one or more Rs 1-2-2 a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs 1-2-3 a C2-C6 alkenyl group which is unsubstituted or substituted by one or more Rs 1-2-4 an amino group which is unsubstituted or substituted by one or two Rs or 1-2-5

[0104] [Chemical formula]​

[0105] and each R 1-2-2-1 is independently halogen, and each R 1-2-3 is independently halogen, a hydroxy group, or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3-1 ; and each R 1-2-3-1 is independently halogen, and each R 1-2-4 is independently halogen, a hydroxy group, or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-4-1 ; and each R 1-2-4-1 is independently halogen, and each R 1-2-6 is independently an amino group, and each R 1-2-5 is independently

[0106]

Chemical formula

[0107] and each R 1-2-5-1 is independently a C1-C6 alkyl group, and each R 1-3 is independently a cyano group, deuterium, a hydroxy group, an amino group, halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-3-1 ; a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-3-2 ; or a C2-C6 alkynyl group, and each R 1-3-1 is independently halogen, and each R 1-3-2 is independently halogen, R 1-4 is a C1-C6 alkyl group, each R 1-5 is independently a C1-C6 alkyl group,

[0108]

Chemical formula

[0109] or a C3-C6 cycloalkyl group, R 1-5-1 is a C1-C6 alkyl group or an amino group, or, R 1 the atoms in R and the atoms in A are linked to form a 5-10 membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 0 wherein the heteroatoms of the 5-10 membered heterocycloalkyl group are selected from one or more of N, O, P, and S, the number of heteroatoms is 3, 4, or 5, and each R 0 is independently a C1-C6 alkyl group or oxa.

[0110] In a preferred embodiment, R 2 is hydrogen, a 6-10 membered aryl group that is unsubstituted or substituted by one or more R 2-1 a 5-10 membered heteroaryl group that is unsubstituted or substituted by one or more R 2-2 a 4-12 membered heterocycloalkyl group that is substituted by one or more R 2-3

[0111]

Chemical Formula

[0112] a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 2-6

[0113]

Chemical Formula

[0114] a C3-C6 cycloalkyl group that is unsubstituted or substituted by one or more R 2-9 2-10 ​​​a C3-C6 cycloalkenyl group replaced by

[0115]

Chemical formula

[0116] and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. each R 2-1 is independently a cyano group, a halogen, a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 2-1-1 or an unsubstituted or C1-C6 alkoxy group substituted by one or more R

[0117]

Chemical formula

[0118] or an unsubstituted or C1-C6 alkoxy group substituted by one or more R 2-1-4 ; each R 2-1-1 is independently a cyano group or a halogen, R 2-1-2 is hydrogen or a C1-C6 alkyl group, each R 2-1-3 is independently hydrogen or a C1-C6 alkyl group, each R 2-1-4 is independently a halogen, each R 2-2 is independently a cyano group, a halogen, a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 2-2-1 ;

[0119]

Chemical formula

[0120] a C1-C6 alkoxy group or

[0121]

Chemical formula

[0122] and each R 2-2-1 is, independently of one another, a cyano group or a halogen, R 2-2-2 is hydrogen or a C1-C6 alkyl group, each R 2-2-3 is, independently of one another, hydrogen or a C1-C6 alkyl group, each R 2-2-4 is, independently of one another, a C1-C6 alkyl group or a C3-C6 cycloalkyl group, each R 2-3 is, independently of one another, a C1-C6 alkyl group substituted by one or more R 2-3-1 a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R

[0123]

Chemical formula

[0124] is unsubstituted or a 3- to 6-membered heterocycloalkyl group substituted by one or more R 2-3-4 an amino group which is unsubstituted or substituted by one or more R 2-3-7 a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-3-9 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-3-1 is, independently of one another, a cyano group, a C3-C6 cycloalkyl group which is unsubstituted or substituted by three or more R 2-3-1-2 and R 2-3-2 is hydrogen or a group which is unsubstituted or substituted by one or more R2-3-2-1 a C1-C6 alkyl group substituted by 2-3-2-2 a C3-C6 cycloalkyl group substituted by

[0125]

Chemical formula

[0126] a 5-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more 2-3-2-5 a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more 2-3-2-6 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each 2-3-4 R is independently a C1-C6 alkyl group, each 2-3-7 R is independently a C1-C6 alkyl group, each 2-3-9 R is independently oxa or a C1-C6 alkyl group, each 2-3-1-2 R is independently a C1-C6 alkoxy group, each 2-3-2-1 R is independently a hydroxy group, oxa,

[0127]

Chemical formula

[0128] a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more 2-3-2-1-3 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each 2-3-2-1-1is, independently of one another, a C1-C6 alkyl group or a 6-10 membered aryl group, each R 2-3-2-1-2 is, independently of one another, a C1-C6 alkyl group, each R 2-3-2-1-3 is, independently of one another, a C1-C6 alkyl group, each R 2-3-2-2 is, independently of one another, halogen, a hydroxy group, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-2-2-1 , a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-2-2-2 , or an amino group which is unsubstituted or substituted by one or more R 2-3-2-2-3 , each R 2-3-2-2-1 is, independently of one another, halogen or a hydroxy group, each R 2-3-2-2-2 is, independently of one another, halogen, deuterium, oxa or a hydroxy group, each R 2-3-2-2-3 is, independently of one another, a C1-C6 alkyl group, each R 2-3-2-3 is, independently of one another, hydrogen or

[0129]

Chemical formula

[0130] and each R 2-3-2-3-1 is, independently of one another, a 6-10 membered aryl group which is unsubstituted or substituted by one or more R 2-3-2-3-1-1 , each R 2-3-2-3-1-1 is, independently of one another, a C1-C6 alkoxy group, each R 2-3-2-4 is, independently of one another, halogen, each R 2-3-2-5 is, independently of one another, halogen, a hydroxy group, oxa, a C1-C6 alkoxy group, a C1-C6 alkyl group substituted by one or more R 2-3-2-5-1 , each R 2-3-2-5-1 is, independently of one another, halogen, each R2-3-2-6 is, independently of each other, a C1-C6 alkyl group, each R 2-4 is unsubstituted or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-4-1 is unsubstituted or a 5- to 10-membered heteroaryl group substituted by one or more R 2-4-2 is unsubstituted or a 6- to 10-membered aryl group substituted by one or more R 2-4-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-4-1 is, independently of each other, a hydroxy group, a halogen, a C1-C6 alkyl group,

[0131]

Chemical formula

[0132] and each R 2-4-2 is, independently of each other, a hydroxy group, a halogen, or a C1-C6 alkyl group, each R 2-4-3 is, independently of each other, a hydroxy group, a halogen, or a C1-C6 alkyl group, each R 2-5 is, independently of each other, hydrogen, a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-5-1 is unsubstituted or a 4- to 10-membered heterocycloalkyl group substituted by one or more R

[0133]

Chemical formula

[0134] is unsubstituted or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-5-3is a 6- to 10-membered aryl group or a C1-C6 alkyl group replaced thereby, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-5-1 is, independently of one another,

[0135]

Chemical formula

[0136] and R 2-5-1-1 is hydrogen or a C1-C6 alkyl group, Each R 2-5-1-2 is, independently of one another, hydrogen or a C1-C6 alkyl group, R 2-5-2 is independently a C1-C6 alkyl group, Each R 2-5-3 is, independently of one another, a C1-C6 alkoxy group, Each R 2-6 is, independently of one another, halogen, a C1-C6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-6-1 or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-6-2 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-6-1 is, independently of one another, halogen, a C1-C6 alkyl group or

[0137]

Chemical formula

[0138] and R2-6-1-1 is a C1-C6 alkyl group, each R 2-6-2 is independently a halogen or a C1-C6 alkyl group, each R 2-7 is independently a C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-7-1 to form a 4- to 10-membered heterocycloalkyl group, or unsubstituted or substituted by one or more R 2-7-2 to form a 5- to 10-membered heteroaryl group, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-7-1 is independently a halogen, a C1-C6 alkyl group,

[0139]

Chemical formula

[0140] and R 2-7-1-1 is a C1-C6 alkyl group, R 2-7-1-2 is a C1-C6 alkyl group, each R 2-7-2 is independently a halogen or a C1-C6 alkyl group, each R 2-8 is independently a C1-C6 alkyl group, or a 4- to 10-membered heterocycloalkyl group formed by two R 2-8 together with the atom to which it is attached, unsubstituted or substituted by one or more R 2-8-1 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-8-1 is independently

[0141]

Chem.

[0142] and R 2-8-1-1 is hydrogen or a C1-C6 alkyl group, each R 2-9 is independently either unsubstituted or a 5-10 membered heteroaryl group substituted by one or more R 2-9-1 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-9-1 is independently a C1-C6 alkyl group, each R 2-10 is independently either unsubstituted or a 5-10 membered heteroaryl group substituted by one or more R 2-10-1 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-10-1 is independently a C1-C6 alkyl group, each R 2-11 is independently either unsubstituted or a 5-10 membered heteroaryl group substituted by one or more R 2-11-1 or a 5-10 membered heterocycloalkyl group substituted by one or more R 2-11-2 wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, and the heteroatom of the 5-10 membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-11-1 is independently a C1-C6 alkyl group, and each R 2-11-2 is independently a C1-C6 alkyl group.

[0143] In a preferred embodiment, R 3 is a 5- to 10-membered heteroaryl group that is unsubstituted or substituted by one or more R 3-1 , or a 3- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 3-2 . The heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. The heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 3-1 is independently a hydroxy group, a halogen, a C1-C6 alkyl group substituted by one or more R 3-1-1 or

[0144]

Chemical formula

[0145] and each R 3-1-1 is independently a hydroxy group, and R 3-1-2 is a C1-C6 alkyl group or a C2-C6 alkenyl group. Each R 3-2 is independently a hydroxy group, a halogen, a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 3-2-1 or

[0146]

Chemical formula

[0147] and each R 3-2-1 is independently a halogen, and R 3-2-2 is a C1-C6 alkyl group or a C2-C4 alkenyl group.

[0148] In a preferred embodiment, R 4is deuterium, a cyano group, a 5- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 4-1 or a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 4-2 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 4-1 is independently,

[0149]

Chemical formula

[0150] and, each R 4-2 is independently a 5- to 10-membered heteroaryl group that is unsubstituted or substituted by one or more R 4-2-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, R 4-1-1 is a C1-C6 alkyl group, each R 4-1-2 is independently a C1-C6 alkyl group, and each R 4-2-1 is independently a C1-C6 alkyl group.

[0151] In a preferred embodiment, R 1 is a hydroxy group, a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 1-1 a C3-C6 cycloalkyl group that is unsubstituted or substituted by one or more R 1-2 a 3- to 6-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 1-3

[0152]

Chemical formula

[0153] or an amino group which is unsubstituted or substituted by one or two Rs 1-5 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, each R 1-1 is independently deuterium, a hydroxy group, a cyano group, a halogen, a 3- to 6-membered heterocycloalkyl group, a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more Rs 1-1-1 a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 1-1-2 or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, and each R 1-1-3 is independently deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-1 is independently deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-2 is independently deuterium, a hydroxy group, a cyano group or a halogen, 1-1-3 and each R each R 1-2 is independently deuterium, a hydroxy group, a halogen, a C2-C6 alkynyl group which is unsubstituted or substituted by one or more Rs 1-2-2 a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs 1-2-3 a C2-C6 alkenyl group which is unsubstituted or substituted by one or more Rs or an amino group which is unsubstituted or substituted by one or two Rs, and each R 1-2-4 is independently a halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs, and each R 1-2-5 is independently a halogen, and each R 1-2-2 is independently a halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs, and each R 1-2-2-1 is independently a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs, and each R 1-2-2-1 is independently a halogen, and each R 1-2-3is, independently of each other, halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3-1 where each R 1-2-3-1 is, independently of each other, halogen, and each R 1-2-4 is, independently of each other, halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-4-1 where each R 1-2-4-1 is, independently of each other, halogen, each R 1-3 is, independently of each other, cyano, deuterium, a hydroxy group, an amino group, halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-3-1 or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-3-2 where each R 1-3-1 is, independently of each other, halogen, and each R 1-3-2 is, independently of each other, halogen, R 1-4 is a C1-C6 alkyl group, each R 1-5 is, independently of each other, a C1-C6 alkyl group,

[0154]

Chemical formula

[0155] or a C3-C6 cycloalkyl group, R 1-5-1 is a C1-C6 alkyl group or an amino group, or the atoms in R 1 and the atoms in A are linked to form a 5-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 0 where the hetero atoms of the 5-10 membered heterocycloalkyl group are selected from any one or more of N, O, P and S, the number of hetero atoms is 3, 4 or 5, and each R 0are each independently a C1-C6 alkyl group or oxa.

[0156] In a preferred embodiment, each R 2 is hydrogen, a 6-10 membered aryl group which is unsubstituted or substituted by one or more R 2-1 , a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more R 2-2 , a 4-10 membered heterocycloalkyl group substituted by one or more R 2-3 ,

[0157]

Chemical formula

[0158] a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-6 ,

[0159]

Chemical formula

[0160] and the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 4-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. Each R 2-1 is each independently a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-1-1 ,

[0161]

Chemical formula

[0162] or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-1-4 . Each R 2-1-1 is, independently of one another, a cyano group or a halogen, and R 2-1-2 is hydrogen or a C1-C6 alkyl group, and each R 2-1-3 is, independently of one another, hydrogen or a C1-C6 alkyl group, and each R 2-1-4 is, independently of one another, a halogen, Each R 2-2 is, independently of one another, a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-2-1 s,

[0163]

Chemical formula

[0164] and Each R 2-2-1 is, independently of one another, a cyano group or a halogen, and R 2-2-2 is hydrogen or a C1-C6 alkyl group, and each R 2-2-3 is, independently of one another, hydrogen or a C1-C6 alkyl group, Each R 2-3 is, independently of one another, a C1-C6 alkyl group substituted by one or more R 2-3-1 s,

[0165]

Chemical formula

[0166] is an unsubstituted or 3- to 6-membered heterocycloalkyl group substituted by one or more R 2-3-4 s, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-3-1 is, independently of one another, a cyano group, R 2-3-2 is hydrogen, and each R 2-3-4 is, independently of one another, a C1-C6 alkyl group, Each R 2-4 is either unsubstituted or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-4-1 is either unsubstituted or a 5- to 10-membered heteroaryl group substituted by one or more R 2-4-2 is either unsubstituted or a 6- to 10-membered aryl group substituted by one or more R 2-4-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Each R 2-4-1 is independently a hydroxy group, a halogen, a C1-C6 alkyl group,

[0167]

Chemical formula

[0168] and each R 2-4-2 is independently a hydroxy group, a halogen, or a C1-C6 alkyl group, and each R 2-4-3 is independently a hydroxy group, a halogen, or a C1-C6 alkyl group. Each R 2-5 is independently hydrogen, a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-5-1 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3;

[0169]

Chemical formula

[0170] and each R is independently 2-5-1 and

[0171] [Chemical formula]

[0172] and R 2-5-1-1 is hydrogen or a C1-C6 alkyl group, each R 2-5-1-2 is independently hydrogen or a C1-C6 alkyl group, R 2-5-2 is independently a C1-C6 alkyl group, each R 2-6 is independently halogen, a C1-C6 alkyl group, a 4-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-6-1 or a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more R 2-6-2 ; the heteroatom of the 4-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. each R 2-6-1 is independently halogen, a C1-C6 alkyl group or

[0173] [Chemical formula]

[0174] and R 2-6-1-1 is a C1-C6 alkyl group, each R 2-6-2 is independently halogen or a C1-C6 alkyl group, each R 2-7 is independently a C1-C6 alkyl group, a 4-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-7-1 or a 5-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-7-2is a 5- to 10-membered heteroaryl group substituted thereby, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-7-1 is, independently of one another, halogen, a C1-C6 alkyl group,

[0175]

Chemical formula

[0176] and R 2-7-1-1 is a C1-C6 alkyl group, and R 2-7-1-2 is a C1-C6 alkyl group. Each R 2-7-2 is, independently of one another, halogen or a C1-C6 alkyl group. Each R 2-8 is, independently of one another, a C1-C6 alkyl group, or a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-8 and is formed together with the atom to which it is attached, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. 2-8-1 is a 4- to 10-membered heterocycloalkyl group substituted thereby, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-8-1 is, independently of one another,

[0177]

Chemical formula

[0178] and R 2-8-1-1 is hydrogen or a C1-C6 alkyl group.

[0179] In a preferred embodiment, R 3 is unsubstituted or one or more R3-1 a 5- to 10-membered heteroaryl group substituted by 3-2 a 3- to 10-membered heterocycloalkyl group substituted by each R 3-1 is independently a hydroxy group, a halogen or

[0180]

Chemical formula

[0181] and R 3-1-2 is a C1-C6 alkyl group or a C2-C6 alkenyl group, each R 3-2 is independently a hydroxy group, a halogen, a C1-C6 alkyl group substituted by 3-2-1 one or more R

[0182]

Chemical formula

[0183] and each R 3-2-1 is independently a halogen, and R 3-2-2 is a C1-C6 alkyl group or a C2-C4 alkenyl group.

[0184] In a preferred embodiment, R 4 is a 5- to 10-membered heterocycloalkyl group substituted by 4-1 one or more R 4-2is a C1-C6 alkyl group substituted by, the heteroatom of the 5-10 membered heterocycloalkyl group being selected from any one or more of N, O and S, the number of heteroatoms being 1, 2 or 3, each R 4-1 is, independently of one another,

[0185]

Chemical formula

[0186] and each R 4-2 is, independently of one another, unsubstituted or a 5-10 membered heteroaryl group substituted by one or more R 4-2-1 the heteroatom of the 5-10 membered heteroaryl group being selected from any one or more of N, O and S, the number of heteroatoms being 1, 2 or 3, R 4-1-1 is a C1-C6 alkyl group, each R 4-1-2 is, independently of one another, a C1-C6 alkyl group, each R 4-2-1 is, independently of one another, a C1-C6 alkyl group.

[0187] In a preferred embodiment, in the compound represented by formula II, its pharmaceutically acceptable salt or isotopic compound, a specific group may be defined as described below, and other groups may be defined as described in any of the above embodiments (hereinafter referred to as "in a preferred embodiment"): the compound represented by formula I is a compound represented by formula I-a,

[0188]

Chemical formula

[0189] Y is C or N, X is C or N, W is N, CH, O, NR 4 or CR 4 and Z is CH, O or N, T1 is C or N, T2 is C or N, A, R 1 , R 2 , R 3 and R 4 are defined as described above.

[0190] In a preferred embodiment, at least one of T1, T2, X and Y is N, or Y, W and Z contain only one heteroatom.

[0191] In a preferred embodiment, the compound represented by Formula I-a is a compound represented by Formula I-A, Formula I-B or Formula I-C

[0192]

Chemical formula

[0193] is.

[0194] In a preferred embodiment, the compound represented by Formula I-a can be a compound represented by Formula IV,

[0195]

Chemical formula

[0196] Ring D is a 3- to 6-membered heterocycloalkyl group, and the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, (the meaning of the 3- to 6-membered heterocycloalkyl group in Ring D is the same as that in R 1 is the same as that in) Ring C is a 4- to 12-membered heterocycloalkyl group, and the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, (the meaning of the 4- to 12-membered heterocycloalkyl group in Ring C is the same as that in R 2 is the same as that in) Ring A is a 5- to 10-membered heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, (the meaning of the 5- to 10-membered heteroaryl group in Ring A is the same as that in R 3 as defined above). n is 0, 1, or 2, m is 0, 1, or 2, k is 0, 1, or 2, R 1-3’ is hydrogen or R 1-3 as defined above, R 1-3 、R 2-3 and R 3-1 are defined as described above.

[0197] In a preferred embodiment, the compound represented by Formula I-a can be a compound represented by Formula V,

[0198]

Chemical formula

[0199] M is N, O, or S, i is 0, 1, or 2, j is 0, 1, or 2, and is 0 when i and j are different, Ring C, Ring A, R 1-3’ 、R 1-3 、R 2-3 、R 3-1 、n, m, and k are defined as described above.

[0200] In a preferred embodiment, the compound represented by Formula I-a can be a compound represented by Formula VI,

[0201]

Chemical formula

[0202] Ring C, Ring A, R 1-3’ 、R 1-3 、R 2-3 、R 3-1The definitions of n, m, k, i, and j are as described above.

[0203] In a preferred embodiment, the compound represented by Formula I-a can be a compound represented by Formula VII,

[0204]

Chemical formula

[0205] V 1 is CH, N, or O, and V 2 is CH, N, or O, and V 1 and V 2 are different, it is CH, R 3-1’ is hydrogen or R 3-1 and R V 1 is hydrogen or R 2-3 and R V 2 is hydrogen or R 2-3 and R 1-3’ 、R 1-3 、R 2-3 、R 3-1 The definitions of n, m, i, and j are as described above.

[0206] In a preferred embodiment, the compound represented by Formula I-a can be a compound represented by Formula VIII,

[0207]

Chemical formula

[0208] R V 1 、R V 2 、R 1-3’ 、R 1-3 、R 2-3 、R 3-1’ The definitions of n, m, i, and j are as described above.

[0209] In a preferred embodiment, the compound represented by Formula I-a can be a compound represented by Formula IX,

[0210]

Chemical Formula

[0211] U is CH, N or O, p is 0, 1 or 2, and q is 0, 1 or 2, R 1-3’ 、R 1-3 、R 2-3 、R 3-1’ 、n, m, i and j are defined as described above.

[0212] In a preferred embodiment, the compound represented by Formula I-a can be a compound represented by Formula X,

[0213]

Chemical Formula

[0214] R G is R 2-3-2 or

[0215]

Chemical Formula

[0216] and R 1-3’ 、R 1-3 、R 2-3 、R 3-1’ 、R 2-3-2 、R 2-3-3 、V 1 、V 2 、n, m, i and j are defined as described above.

[0217] In a preferred embodiment, the compound represented by Formula I is a compound represented by Formula I-b, Formula I-c, Formula I-d, Formula I-e, Formula I-f, Formula I-g, Formula I-h, Formula I-i, Formula I-j, Formula I-k, Formula I-L or Formula I-m

[0218]

Chem.

[0219] is as follows.

[0220] In a preferred embodiment, the compound represented by Formula I is a compound represented by Formula I-b, Formula I-c, Formula I-d, Formula I-e, Formula I-f or Formula I-g

[0221]

Chem.

[0222] is as follows.

[0223] In a preferred embodiment, R A wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0224] In a preferred embodiment, in Ring B, the heteroatom of the 5,5-fused heteroaromatic ring may be N, and the number of heteroatoms may be 1, 2 or 3, for example,

[0225]

Chem.

[0226] is as follows.

[0227] In a preferred embodiment, in Ring B, the 3- to 6-membered cycloalkyl group may be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group.

[0228] In a preferred embodiment, in ring B, the heteroatom of the 5,6-fused heteroaromatic ring is N and / or O, and the number of heteroatoms can be 1, 2, or 3. For example,

[0229]

Chemical formula

[0230] is the case.

[0231] In a preferred embodiment, in ring B, the heteroatom of the 5,6-fused heteroaromatic ring can be N and / or O, and the number of heteroatoms can be 1, 2, or 3. For example,

[0232]

Chemical formula

[0233] is the case.

[0234] In a preferred embodiment, for R 1 the C1-C6 alkyl group is a C1-C4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and can also be a methyl group, an ethyl group, an isopropyl group, or a tert-butyl group.

[0235] In a preferred embodiment, for R 1 the C1-C6 alkyl group can be a C1-C4 alkyl group and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and can also be a methyl group, an ethyl group, an isopropyl group, or a tert-butyl group.

[0236] In a preferred embodiment, for R 1In this case, the C3-C6 cycloalkyl group is a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, bicyclopentane or

[0237]

Chemical formula

[0238] and, for example, is a cyclopropyl group, cyclobutane, bicyclopentane or

[0239]

Chemical formula

[0240] is.

[0241] In a preferred embodiment, R 1 In this case, the C3-C6 cycloalkyl group can be a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group or bicyclopentane, and for example, is a cyclopropyl group, cyclobutane or bicyclopentane.

[0242] In a preferred embodiment, R 1 In this case, the heteroatom of the 3-6 membered heterocycloalkyl group is N, O or S, the number of heteroatoms is 1 or 2, the heteroatom of the 3-6 membered heterocycloalkyl group can be O or N, the number of heteroatoms can also be 1, and preferably, it is azetidinyl, oxetanyl, oxolane or azepanyl, and for example,

[0243]

Chemical formula

[0244] is.

[0245] In a preferred embodiment, R 1In this case, the heteroatom of the 3- to 6-membered heterocycloalkyl group can be N, O, or S, the number of heteroatoms can be 1 or 2, the heteroatom of the 3- to 6-membered heterocycloalkyl group can also be O or N, and the number of heteroatoms can also be 1. For example,

[0246]

Chemical formula

[0247] is as follows.

[0248] In a preferred embodiment, R 1-1 In this case, the heteroatom of the 3- to 6-membered heterocycloalkyl group can be N, O, or S, the number of heteroatoms can be 1 or 2, the heteroatom of the 3- to 6-membered heterocycloalkyl group can also be O or N, and the number of heteroatoms can also be 1. For example,

[0249]

Chemical formula

[0250] is as follows.

[0251] In a preferred embodiment, each R 1-1 In this case, the halogen can be fluorine, chlorine, bromine, or iodine, for example, fluorine.

[0252] In a preferred embodiment, each R 1-1 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and can also be a methyl group, an ethyl group, or an isopropyl group.

[0253] In a preferred embodiment, each R 1-1In this case, the C1-C6 alkoxy group may be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group.

[0254] In a preferred embodiment, each R 1-1 In this case, the C3-C6 cycloalkyl group may be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group.

[0255] In a preferred embodiment, each R 1-1-1 In this case, the halogen may be fluorine, chlorine, bromine or iodine, and for example, it may be fluorine.

[0256] In a preferred embodiment, each R 1-1-2 In this case, the halogen may be fluorine, chlorine, bromine or iodine, and for example, it may be fluorine.

[0257] In a preferred embodiment, each R 1-1-3 In this case, the halogen may be fluorine, chlorine, bromine or iodine, and for example, it may be fluorine.

[0258] In a preferred embodiment, each R 1-2 In this case, the halogen may be fluorine, chlorine, bromine or iodine, and for example, it may be fluorine.

[0259] In a preferred embodiment, each R 1-2 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group or an isopropyl group.

[0260] In a preferred embodiment, each R 1-2 In this case, the C2-C6 alkynyl group is

[0261] [Chemical formula]

[0262] is.

[0263] In a preferred embodiment, R 1-2 in which the C1-C6 alkoxy group may be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group.

[0264] In a preferred embodiment, each R 1-2-1 in which the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0265] In a preferred embodiment, each R 1-2-1 in which the C1-C6 alkoxy group may be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and for example, may be a methoxy group or an ethoxy group.

[0266] In a preferred embodiment, each R 1-2-1-1 in which the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0267] In a preferred embodiment, each R 1-2-2 in which the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0268] In a preferred embodiment, each R 1-2-2 in which the C1-C6 alkoxy group may be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and for example, may be a methoxy group or an ethoxy group.

[0269] In a preferred embodiment, each R 1-2-2-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0270] In a preferred embodiment, each R 1-2-3 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0271] In a preferred embodiment, each R 1-2-3 wherein the C1-C6 alkoxy group can be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and can be a methoxy group or an ethoxy group.

[0272] In a preferred embodiment, each R 1-2-3-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0273] In a preferred embodiment, each R 1-2-4 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0274] In a preferred embodiment, each R 1-2-4 wherein the C1-C6 alkoxy group can be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group or an ethoxy group.

[0275] In a preferred embodiment, each R 1-2-4-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0276] In a preferred embodiment, each R 1-2-5In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group or an isopropyl group.

[0277] In a preferred embodiment, each R 1-2-5 In this case, the C3-C6 cycloalkyl group may be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or a bicyclopentane, and for example, may be a cyclopropyl group, a cyclobutane or a bicyclopentane.

[0278] In a preferred embodiment, R 1-2-5-1 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group or an isopropyl group.

[0279] In a preferred embodiment, each R 1-3 In this case, the halogen may be fluorine, chlorine, bromine or iodine, and for example, may be fluorine.

[0280] In a preferred embodiment, each R 1-3 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0281] In a preferred embodiment, each R 1-3 In this case, the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group.

[0282] In a preferred embodiment, each R 1-3 wherein the C2-C6 alkynyl group is

[0283]

Chemical formula

[0284] is as follows.

[0285] In a preferred embodiment, each R 1-3-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0286] In a preferred embodiment, each R 1-3-2 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0287] In a preferred embodiment, R 1-4 wherein the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0288] In a preferred embodiment, each R 1-5 wherein the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0289] In a preferred embodiment, each R 1-5 wherein the C3-C6 cycloalkyl group can be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or a bicyclopentane, for example, a cyclopropyl group, a cyclobutane or a bicyclopentane.

[0290] In a preferred embodiment, R 1-5-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0291] In a preferred embodiment, R 1 when the atom in R and the atom in A are linked to form an unsubstituted or substituted 5- to 10-membered heterocycloalkyl group by one or more R 0 the 5- to 10-membered heterocycloalkyl group may be a 5- to 6-membered heterocycloalkyl group, for example,

[0292]

Chemical formula

[0293] and so on.

[0294] In a preferred embodiment, in each R 0 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0295] In a preferred embodiment, in R 2 the 6- to 10-membered aryl group may be a phenyl group or a naphthalene group, for example, a phenyl group.

[0296] In a preferred embodiment, in R 2 the 5- to 10-membered heteroaryl group is a 5- or 6-membered heteroaryl group or a 5,6-fused heteroaryl group. The heteroatom of the 5- to 10-membered heteroaryl group is selected from one or more of N, O or S, and the number of heteroatoms is 1, 2 or 3.

[0297] In a preferred embodiment, R 2 wherein the 5- to 10-membered heteroaryl group may be a 5- or 6-membered heteroaryl group, a 5,5-fused heteroaryl group, or a 5,6-fused heteroaryl group. The heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3.

[0298] The heteroatom of the 5-membered heteroaryl group may be N, the number of heteroatoms is 2, and preferably it is a pyrazole group, for example,

[0299] [Chemical formula]

[0300] and so on.

[0301] The heteroatom of the 6-membered heteroaryl group may be N, the number of heteroatoms is 1, and preferably it is a pyridyl group, for example,

[0302] [Chemical formula]

[0303] and so on.

[0304] The heteroatom of the 5,5-fused heteroaryl group may be N, the number of heteroatoms is 3, and preferably it is a dihydropyrrolopyrazole group, for example,

[0305] [Chemical formula]

[0306] and so on.

[0307] The heteroatom of the 5,6-fused heteroaryl group can be N and / or O, the number of heteroatoms is 1, 2 or 3, preferably benzofuranyl, dihydroimidazopyrazinyl or benzimidazole, for example,

[0308]

Chemical formula

[0309] is.

[0310] In a preferred embodiment, R 2 In, the 5- to 10-membered heteroaryl group is a 5- or 6-membered heteroaryl group or a 5,6-fused heteroaryl group. The heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N and / or S, and the number of heteroatoms is 1 or 2. The heteroatom of the 5-membered heteroaryl group can be selected from N and / or S, and the number of heteroatoms is 2. The heteroatom of the 6-membered heteroaryl group can be N, and the number of heteroatoms is 1 or 2. The heteroatom of the 5,6-fused heteroaryl group can be selected from N and / or O, the number of heteroatoms is 2, and the number of heteroatoms is 1, 2 or 3.

[0311] In a preferred embodiment, R 2 In, the 4- to 12-membered heterocycloalkyl group is any one or more of a monocyclic, bridged ring, fused ring and spiro ring. The monocyclic ring can be a 4- to 6-membered heterocycloalkyl group. The fused ring can be a 5,6-fused heterocycloalkyl group, a 4-membered and 6-membered heterocycloalkyl group or a 5,5-fused heterocycloalkyl group. The spiro ring can be a 4-ring spiro 6-ring, a 4-ring spiro 5-ring, a 4-ring spiro 4-ring, a 5-ring spiro 6-ring or a 3-ring spiro 6-ring. The bridged ring can be bicyclooctane or bicycloheptane. The heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1, 2 or 3.

[0312] The 4- to 12-membered heterocycloalkyl group may be a tricyclic spiro 6,6-fused heterocycloalkyl group, preferably hexahydrospirocyclopropanepyrazinopyrazinyl, for example,

[0313]

Chemical formula

[0314] as follows.

[0315] The bicyclooctane may be bicyclo[2.2.2]octane, for example,

[0316]

Chemical formula

[0317] as follows.

[0318] The bicycloheptane may be bicyclo[3.1.1]heptane, for example,

[0319]

Chemical formula

[0320] as follows.

[0321] The 4- to 6-membered heterocycloalkyl group may be azepanyl, tetrahydropyridyl, piperazinyl, azolanyl or morpholinyl, for example,

[0322]

Chemical formula

[0323] as follows.

[0324] The 5,6-fused heterocycloalkyl group may be tetrahydrofropyridinyl, hexahydropyrrolopyrazinyl, hexahydropyrazinooxazinyl or hexahydroimidazopyrazinyl, for example,

[0325]

Chem.

[0326] is as follows.

[0327] The 5,5-fused heterocycloalkyl group may be tetrahydrofropyrrole, for example,

[0328]

Chem.

[0329] is as follows.

[0330] The 4-ring spiro 6-ring may be oxaazaspirononanil, dioxazaspirononanil or azaspirononanil, for example,

[0331]

Chem.

[0332] is as follows.

[0333] The 3-ring spiro 6-ring may be diazaspirooctyl, for example,

[0334]

Chem.

[0335] is as follows.

[0336] The 5-ring spiro 6-ring may be diazaspirodecanil, for example,

[0337] [Chemical]

[0338] is.

[0339] In a preferred embodiment, R 2 in which the 4- to 12-membered heterocycloalkyl group may be a saturated heterocycloalkyl group or a heterocycloalkyl group containing 1 to 2 double bonds.

[0340] In a preferred embodiment, R 2 in which the 4- to 10-membered heterocycloalkyl group may be a monocyclic, bridged ring, fused ring or spiro ring. The monocyclic ring may be a 4- to 6-membered heterocycloalkyl group. The fused ring may be a 5,6-fused heterocycloalkyl group or a 4,6-fused heterocycloalkyl group. The spiro ring may be a 4-ring spiro 6-ring, 4-ring spiro 5-ring or 4-ring spiro 4-ring. The heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1 or 2.

[0341] In a preferred embodiment, R 2 in which the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0342] In a preferred embodiment, R 2 in which the C3-C6 cycloalkyl group may be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, and for example, may be a cyclopentyl group.

[0343] In a preferred embodiment, R 2 in which the C3-C6 cycloalkenyl group may be a cycloalkenyl group containing one double bond, and may also be a 5-membered cycloalkenyl group, for example,

[0344]

Chem.

[0345] is.

[0346] In a preferred embodiment, each R 2-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0347] In a preferred embodiment, each R 2-1 wherein the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0348] In a preferred embodiment, each R 2-1 wherein the C1-C6 alkoxy group can be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and can also be a methoxy group or an ethoxy group.

[0349] In a preferred embodiment, each R 2-1-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0350] In a preferred embodiment, each R 2-1-2 wherein the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0351] In a preferred embodiment, each R 2-1-3In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0352] In a preferred embodiment, each R 2-1-4 In this case, the halogen may be fluorine, chlorine, bromine or iodine, and for example, it is fluorine.

[0353] In a preferred embodiment, each R 2-2 In this case, the halogen may be fluorine, chlorine, bromine or iodine, and for example, it is fluorine.

[0354] In a preferred embodiment, each R 2-2 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group.

[0355] In a preferred embodiment, each R 2-2 In this case, the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and for example, it is a methoxy group.

[0356] In a preferred embodiment, each R 2-2-1 In this case, the halogen may be fluorine, chlorine, bromine or iodine, and for example, it is fluorine.

[0357] In a preferred embodiment, each R 2-2-2 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0358] In a preferred embodiment, each R 2-2-3 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0359] In a preferred embodiment, each R 2-2-4 wherein the C1-C6 alkyl group is a C1-C4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0360] In a preferred embodiment, each R 2-2-4 wherein the C3-C6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group.

[0361] In a preferred embodiment, each R 2-3 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0362] In a preferred embodiment, each R 2-3 wherein the C1-C6 alkyl group is a C1-C4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group, an isopropyl group or a tert-butyl group.

[0363] In a preferred embodiment, each R 2-3In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0364] In a preferred embodiment, each R 2-3 In this case, the heteroatom of the 3-6 membered heterocycloalkyl group may be N, O or S, the number of heteroatoms may be 1 or 2, the heteroatom of the 3-6 membered heterocycloalkyl group may also be O or N, the number of heteroatoms may also be 1, and preferably, it is oxetanyl, for example,

[0365]

Chemical formula

[0366] is as follows.

[0367] In a preferred embodiment, each R 2-3 In this case, the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and is also a methoxy group, an ethoxy group or an isopropoxy group.

[0368] In a preferred embodiment, each R 2-3 In this case, the C1-C6 alkoxy group may be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and for example, it is a methoxy group or an ethoxy group.

[0369] In a preferred embodiment, each R 2-3 In this case, the C3-C6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, and for example, it is a cyclopropyl group.

[0370] In a preferred embodiment, each R 2-3 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group or a 6-membered heteroaryl group. The heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1, 2, or 3. The heteroatom of the 5-membered heteroaryl group can be N and / or O, the number of heteroatoms can be 2 or 3, and preferably, it is a triazolyl group, an oxadiazolyl group, or an imidazole group, for example,

[0371]

Chemical formula

[0372] and so on. The heteroatom of the 6-membered heteroaryl group can be N, the number of heteroatoms is 1 or 2, and preferably, it is a pyridyl group, for example,

[0373]

Chemical formula

[0374] and so on.

[0375] In a preferred embodiment, each R 2-3-1 wherein the halogen can be fluorine, chlorine, bromine, or iodine, for example, fluorine.

[0376] In a preferred embodiment, each R 2-3-1 wherein the C1-C6 alkoxy group can be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group, or a tert-butoxy group, for example, a methoxy group or an ethoxy group.

[0377] In a preferred embodiment, each R 2-3-1In this case, the C3-C6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group.

[0378] In a preferred embodiment, R 2-3-2 In this case, the C1-C6 alkyl group is a C1-C4 alkyl group, and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group, an ethyl group, an isopropyl group or a tert-butyl group.

[0379] In a preferred embodiment, R 2-3-2 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group or an isopropyl group.

[0380] In a preferred embodiment, R 2-3-2 In this case, the C3-C6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group or a cyclobutyl group.

[0381] In a preferred embodiment, R 2-3-2 In this case, the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, an isopropoxy group.

[0382] In a preferred embodiment, R 2-3-2In this case, the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms can be 1 or 2, and preferably, it is oxetanyl, azetidinyl, oxirane, azolanyl, oxacyclohexanyl, azepanyl, pyrazinyl, thiazolidinyl, or oxabicyclohexyl. For example,

[0383] [Chemical formula]

[0384] it is.

[0385] In a preferred embodiment, R 2-3-2 In this case, the 5- to 10-membered heteroaryl group is a 5- or 6-membered heteroaryl group or a 5,6-fused heteroaryl group. The heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1 or 2. The heteroatom of the 5-membered heteroaryl group can be N and / or O, and the number of heteroatoms is 2. The heteroatom of the 6-membered heteroaryl group can be N, and the number of heteroatoms is 1. The heteroatom of the 5,6-fused heteroaryl group can be O, and the number of heteroatoms is 2.

[0386] In a preferred embodiment, each R 2-3-3 In this case, the C1-C6 alkyl group is a C1-C4 alkyl group, and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group. For example, it is a methyl group or an ethyl group.

[0387] In a preferred embodiment, each R 2-3-3 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and can also be a methyl group.

[0388] In a preferred embodiment, each R 2-3-4 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be an isopropyl group.

[0389] In a preferred embodiment, each R 2-3-5 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0390] In a preferred embodiment, each R 2-3-6 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0391] In a preferred embodiment, each R 2-3-7 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0392] In a preferred embodiment, each R 2-3-8 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group or an isopropyl group.

[0393] In a preferred embodiment, each R 2-3-8 wherein the C3-C6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group.

[0394] In a preferred embodiment, each R 2-3-9 wherein the C1-C6 alkyl group is a C1-C4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0395] In a preferred embodiment, each R 2-3-1-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0396] In a preferred embodiment, each R 2-3-1-2 wherein the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group.

[0397] In a preferred embodiment, each R 2-3-1-3 wherein the C1-C6 alkyl group is a C1-C4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0398] In a preferred embodiment, each R 2-3-2-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0399] In a preferred embodiment, each R 2-3-2-1 wherein the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group.

[0400] In a preferred embodiment, each R 2-3-2-1In this case, the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group. The heteroatom of the 5-membered heteroaryl group can be N, and the number of heteroatoms is 3.

[0401] In a preferred embodiment, each R 2-3-2-1-1 In this case, the C1-C6 alkyl group is a C1-C4 alkyl group, and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0402] In a preferred embodiment, each R 2-3-2-1-1 In this case, the 6- to 10-membered aryl group can be a phenyl group or a naphthalene group, for example, a phenyl group.

[0403] In a preferred embodiment, each R 2-3-2-1-2 In this case, the C1-C6 alkyl group is a C1-C4 alkyl group, and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0404] In a preferred embodiment, each R 2-3-2-1-3 In this case, the C1-C6 alkyl group is a C1-C4 alkyl group, and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0405] In a preferred embodiment, each R 2-3-2-2 In this case, the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine.

[0406] In a preferred embodiment, each R 2-3-2-2In this case, the C1-C6 alkyl group is a C1-C4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0407] In a preferred embodiment, each R 2-3-2-2 In this case, the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and can be a methoxy group or an ethoxy group or an n-propoxy group. In a preferred embodiment, each R 2-3-2-2-1 In this case, the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine.

[0408] In a preferred embodiment, each R 2-3-2-2-2 In this case, the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine.

[0409] In a preferred embodiment, each R 2-3-2-2-3 In this case, the C1-C6 alkyl group is a C1-C4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0410] In a preferred embodiment, each R 2-3-2-3-1 In this case, the 6-10 membered aryl group is a phenyl group or a naphthalene group, for example, a phenyl group.

[0411] In a preferred embodiment, each R 2-3-2-3-1-1 In this case, the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group.

[0412] In a preferred embodiment, each R 2-3-2-4 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine.

[0413] In a preferred embodiment, each R 2-3-2-5 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine.

[0414] In a preferred embodiment, each R 2-3-2-5 wherein the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group.

[0415] In a preferred embodiment, each R 2-3-2-5 wherein the C1-C6 alkyl group is a C1-C4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group.

[0416] In a preferred embodiment, each R 2-3-2-5-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine.

[0417] In a preferred embodiment, each R 2-3-2-6 wherein the C1-C6 alkyl group is a C1-C4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0418] In a preferred embodiment, each R 2-3-3-1-1In this case, the C1-C6 alkyl group is a C1-C4 alkyl group, and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0419] In a preferred embodiment, each R 2-4 In this case, the 4- to 10-membered heterocycloalkyl group can be monocyclic. The 4- to 10-membered heterocycloalkyl group can be a 4- to 6-membered heterocycloalkyl group. The heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1 or 2.

[0420] In a preferred embodiment, each R 2-4 In this case, the 5- to 10-membered heteroaryl group can be a 5,6-fused heteroaryl group. The heteroatom of the 5,6-fused heteroaryl group can be selected from N and / or O, the number of heteroatoms is 2, and the number of heteroatoms is 1, 2 or 3.

[0421] In a preferred embodiment, each R 2-4 In this case, the 6- to 10-membered aryl group can be a phenyl group or a naphthalene group, for example, a phenyl group.

[0422] In a preferred embodiment, each R 2-4 In this case, the C3-C6 cycloalkyl group can be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopentyl group.

[0423] In a preferred embodiment, each R 2-4-1 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0424] In a preferred embodiment, each R2-4-1 In this case, the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0425] In a preferred embodiment, each R 2-4-2 In this case, the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0426] In a preferred embodiment, each R 2-4-2 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0427] In a preferred embodiment, each R 2-4-3 In this case, the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0428] In a preferred embodiment, each R 2-4-3 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0429] In a preferred embodiment, each R 2-4-4 In this case, the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0430] In a preferred embodiment, each R 2-4-4 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0431] In a preferred embodiment, R 2-4-1-1In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group.

[0432] In a preferred embodiment, each R 2-4-1-2 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group.

[0433] In a preferred embodiment, each R 2-5 In this case, the 4- to 10-membered heterocycloalkyl group may be monocyclic. The 4- to 10-membered heterocycloalkyl group may be a 4- to 6-membered heterocycloalkyl group. The heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1 or 2.

[0434] In a preferred embodiment, each R 2-5 In this case, the 6- to 10-membered aryl group is a phenyl group or a naphthalene group, for example, a phenyl group.

[0435] In a preferred embodiment, each R 2-5 In this case, the C1-C6 alkyl group is a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0436] In a preferred embodiment, R 2-5-1-1 In this case, the C1-C6 alkyl group is a C1-C4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group.

[0437] In a preferred embodiment, R 2-5-1-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0438] In a preferred embodiment, each R 2-5-1-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group.

[0439] In a preferred embodiment, R 2-5-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group.

[0440] In a preferred embodiment, each R 2-5-3 wherein the C1-C6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group.

[0441] In a preferred embodiment, each R 2-6 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0442] In a preferred embodiment, each R 2-6In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0443] In a preferred embodiment, each R 2-6 In this case, the 4- to 10-membered heterocycloalkyl group may be monocyclic. The 4- to 10-membered heterocycloalkyl group may be a 4- to 6-membered heterocycloalkyl group. The heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1 or 2.

[0444] In a preferred embodiment, each R 2-6 In this case, the 5- to 10-membered heteroaryl group may be a 5- to 6-membered heteroaryl group. The heteroatom of the 5- to 6-membered heteroaryl group can be selected from N and / or S, the number of heteroatoms is 2, and the number of heteroatoms is 1 or 2.

[0445] In a preferred embodiment, each R 2-6-1 In this case, the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0446] In a preferred embodiment, each R 2-6-1 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0447] In a preferred embodiment, R 2-6-1-1 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0448] In a preferred embodiment, each R 2-6-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group.

[0449] In a preferred embodiment, each R 2-6-2 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0450] In a preferred embodiment, each R 2-7 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0451] In a preferred embodiment, each R 2-7 wherein the 4- to 10-membered heterocycloalkyl group may be monocyclic or spiro. The monocyclic group may be a 4- to 6-membered heterocycloalkyl group. The spiro ring may be a 4-ring spiro 6-ring, a 4-ring spiro 5-ring or a 4-ring spiro 4-ring. The heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1 or 2.

[0452] In a preferred embodiment, each R 2-7In this case, the 5- to 10-membered heteroaryl group can be a 5- or 6-membered heteroaryl group or a 5,6-fused heteroaryl group. The heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N and / or S, and the number of heteroatoms is 1 or 2. The heteroatom of the 5-membered heteroaryl group can be selected from N and / or S, and the number of heteroatoms is 2. The heteroatom of the 6-membered heteroaryl group can be N, and the number of heteroatoms is 1 or 2. The heteroatom of the 5,6-fused heteroaryl group can be selected from N and / or O, and the number of heteroatoms is 2, and the number of heteroatoms is 1, 2, or 3.

[0453] In a preferred embodiment, each R 2-7-1 In this case, the halogen can be fluorine, chlorine, bromine, or iodine, for example, fluorine.

[0454] In a preferred embodiment, each R 2-7-1 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and can also be a methyl group.

[0455] In a preferred embodiment, R 2-7-1-1 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and can also be a methyl group.

[0456] In a preferred embodiment, R 2-7-1-2 In this case, the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and can also be a methyl group.

[0457] In a preferred embodiment, each R 2-7-2 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0458] In a preferred embodiment, each R 2-7-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0459] In a preferred embodiment, each R 2-8 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0460] In a preferred embodiment, each R 2-8 wherein the 4-10 membered heterocycloalkyl group may be monocyclic. The monocyclic group may be a 4-6 membered heterocycloalkyl group. The heteroatom of the 4-10 membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1 or 2.

[0461] In a preferred embodiment, each R 2-8-1-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0462] In a preferred embodiment, each R 2-9In this case, the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group is N and / or S, the number of heteroatoms is 1 or 2, the heteroatom of the 5-membered heteroaryl group can be N, the number of heteroatoms is 2, and preferably it is a pyrazole group. For example,

[0463]

Chemical formula

[0464] it is.

[0465] In a preferred embodiment, each R 2-10 In this case, the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group is N and / or S, the number of heteroatoms is 1 or 2, the heteroatom of the 5-membered heteroaryl group can be N, the number of heteroatoms is 2, and preferably it is a pyrazole group. For example,

[0466]

Chemical formula

[0467] it is.

[0468] In a preferred embodiment, each R 2-11 In this case, the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group. The heteroatom of the 5-membered heteroaryl group can be N and / or S, the number of heteroatoms is 2, and preferably it is a thiazolyl group or an imidazole group. For example,

[0469]

Chemical formula

[0470] it is.

[0471] In a preferred embodiment, each R 2-11 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is O, the number of heteroatoms can be 1, preferably an oxirane group, for example,

[0472]

Chemical formula

[0473] is as follows.

[0474] In a preferred embodiment, each R 2-11-1 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0475] In a preferred embodiment, each R 2-11-2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group, which can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0476] In a preferred embodiment, for R 3 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, a 5,5-fused heteroaryl group or a 5,6-fused heteroaryl group. The heteroatoms of the 5- to 10-membered heteroaryl group are N and / or S, and the number of heteroatoms is 1, 2 or 3. The heteroatoms of the 5-membered heteroaryl group can be N and / or S, and the number of heteroatoms is 2 or 3. The heteroatoms of the 5,6-fused heteroaryl group can be N and / or O, and the number of heteroatoms is 2, and the number of heteroatoms is 1, 2 or 3. The heteroatoms of the 5,5-fused heteroaryl group can be N and / or O, and the number of heteroatoms is 2, and the number of heteroatoms is 1, 2 or 3.

[0477] In a preferred embodiment, R 3 wherein the 5- to 10-membered heteroaryl group can be a 5-membered heteroaryl group, a 5,5-fused heteroaryl group or a 5,6-fused heteroaryl group. The heteroatom of the 5- to 10-membered heteroaryl group is selected from one or more of N and / or S, and the number of heteroatoms is 1 or 2. The heteroatom of the 5-membered heteroaryl group can be selected from N and / or S, and the number of heteroatoms is 2. The heteroatom of the 5,6-fused heteroaryl group can be selected from N and / or O, and the number of heteroatoms is 2, and the number of heteroatoms is 1, 2 or 3. The heteroatom of the 5,5-fused heteroaryl group can be N and / or O, and the number of heteroatoms is 2, and the number of heteroatoms is 1, 2 or 3.

[0478] In a preferred embodiment, R 3 wherein the 3- to 10-membered heterocycloalkyl group can be monocyclic. The monocyclic ring can be a 4- to 6-membered heterocycloalkyl group. The heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from N, and the number of heteroatoms is 1 or 2.

[0479] In a preferred embodiment, each R 3-1 wherein the C1-C6 alkyl group can be a C1-C4 alkyl group, and can also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group.

[0480] In a preferred embodiment, each R 3-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0481] In a preferred embodiment, each R 3-1-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0482] In a preferred embodiment, R 3-1-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an ethyl group.

[0483] In a preferred embodiment, R 3-1-2 wherein the C2-C6 alkenyl group is

[0484]

Chemical formula

[0485] as follows.

[0486] In a preferred embodiment, R 3-2 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0487] In a preferred embodiment, R 3-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0488] In a preferred embodiment, R 3-2-1 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0489] In a preferred embodiment, R 3-2-2 wherein the C1-C6 alkyl group is a C1-C4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an ethyl group.

[0490] In a preferred embodiment, R 3-2-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0491] In a preferred embodiment, R 3-2-2 wherein the C2-C6 alkenyl group is

[0492]

Chemical formula

[0493] as follows.

[0494] In a preferred embodiment, R 4 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine or chlorine.

[0495] In a preferred embodiment, R 4 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, fluorine.

[0496] In a preferred embodiment, R 4 wherein the 4- to 10-membered heterocycloalkyl group is monocyclic or spirocyclic. The monocyclic group may be a 6-membered heterocycloalkyl group. The spirocyclic group may be a 4-ring spiro 6-ring, a 4-ring spiro 5-ring or a 4-ring spiro 4-ring. The heteroatom of the 4- to 10-membered heterocycloalkyl group may be N, and the number of heteroatoms may be 1 or 2.

[0497] In a preferred embodiment, R 4In this case, the 5- to 10-membered heterocycloalkyl group may be a spiro ring. The spiro ring may be a 4-ring spiro 6-ring, a 4-ring spiro 5-ring, or a 4-ring spiro 4-ring. The heteroatom of the 4- to 10-membered heterocycloalkyl group may be N, and the number of heteroatoms may be 1 or 2.

[0498] In a preferred embodiment, R 4 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and may also be a methyl group.

[0499] In a preferred embodiment, each R 4-2 In this case, the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group. The heteroatom of the 5-membered heteroaryl group can be selected from N and / or S, and the number of heteroatoms is 2.

[0500] In a preferred embodiment, R 4-1-1 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and may also be a methyl group or an isopropyl group.

[0501] In a preferred embodiment, each R 4-1-2 In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and may also be a methyl group.

[0502] In a preferred embodiment, each R 4-2-1In this case, the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

[0503] In a preferred embodiment, A is

[0504]

Chemical formula

[0505] wherein R A is hydrogen or a C1-C6 alkyl group, ring B is an unsubstituted or R B substituted 5,6-fused heteroaryl ring, the heteroatoms of the 5,6-fused heteroaryl ring are selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, and when the heteroatom of the 5,6-fused heteroaryl ring is only nitrogen, in the 5,6-fused heteroaryl ring, there is at least one N in the 6-membered ring or only one N in the 5-membered ring, and each R B is independently oxa, a hydroxy group, a halogen or a C1-C6 alkyl group, R 1 is a hydroxy group, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-1 a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-2 or a 3-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 1-3 the heteroatoms of the 3-6 membered heterocycloalkyl group are selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 1-1 is independently deuterium, a hydroxy group, a cyano group, a halogen or a C3-C6 cycloalkyl group, each R 1-2is, independently of each other, deuterium, a hydroxy group, a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-2-1 a C2-C6 alkynyl group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3 or an amino group which is unsubstituted or substituted by one or two R 1-2-5 , each R 1-2-1 being, independently of each other, a halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-1-1 , each R 1-2-1-1 being, independently of each other, a halogen, each R 1-2-3 being, independently of each other, a halogen, each R 1-2-5 being, independently of each other, a C1-C6 alkyl group,

[0506]

Chemical formula

[0507] or a C3-C6 cycloalkyl group, R 1-2-5-1 being a C1-C6 alkyl group or an amino group, each R 1-3 being, independently of each other, a C1-C6 alkyl group, or the atoms in R 1 and the atoms in A are linked to form a 5-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 0 , the hetero atoms of the 5-6 membered heterocycloalkyl group being selected from one or more of N, O, P and S, the number of hetero atoms being 3, 4 or 5, each R 0 being, independently of each other, a C1-C6 alkyl group or oxa, each R 2 being hydrogen, a 6-10 membered aryl group which is unsubstituted or substituted by one or more R 2-1 or a 5-6 membered heteroaryl group which is unsubstituted or substituted by one or more R 2-2a 5- to 10-membered heteroaryl group replaced by 2-3 a 4- to 10-membered heterocycloalkyl group replaced by

[0508]

Chemical Structure

[0509] a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 2-6

[0510]

Chemical Structure

[0511] and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. each R 2-1 is independently a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 2-1-1

[0512]

Chemical Structure

[0513] or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs 2-1-4 each R 2-1-1 is independently a cyano group or a halogen, R 2-1-2 is hydrogen or a C1-C6 alkyl group, each R 2-1-3 is independently hydrogen or a C1-C6 alkyl group, each R 2-1-4 is independently a halogen.​​​ Each R 2-2 is, independently of one another, a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-2-1 groups,

[0514]

Chemical formula

[0515] and each R 2-2-1 is, independently of one another, a cyano group or a halogen, R 2-2-2 is hydrogen or a C1-C6 alkyl group, and each R 2-2-3 is, independently of one another, hydrogen or a C1-C6 alkyl group, each R 2-3 is, independently of one another, a cyano group, oxa, a hydroxy group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-1 groups,

[0516]

Chemical formula

[0517] unsubstituted or a 3-6 membered heterocycloalkyl group substituted by one or more R 2-3-4 groups, or a C1-C6 alkoxy group substituted by one or more R 2-3-5 groups, wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-3-1 is, independently of one another, a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-1-1 groups, R 2-3-2 is hydrogen or a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-2-1 groups, each R2-3-3 is, independently of each other, hydrogen or a C1-C6 alkyl group, each R 2-3-4 is, independently of each other, a C1-C6 alkyl group, each R 2-3-5 is, independently of each other, a halogen, each R 2-3-1-1 is, independently of each other, a halogen, each R 2-3-2-1 is, independently of each other, a halogen, each R 2-4 is unsubstituted or a 4-10 membered heterocycloalkyl group substituted by one or more R 2-4-1 , an unsubstituted or 5-10 membered heteroaryl group substituted by one or more R 2-4-2 , an unsubstituted or 6-10 membered aryl group substituted by one or more R 2-4-3 , or a C3-C6 cycloalkyl group substituted by one or more R 2-4-4 , wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, and each R 2-4-1 is, independently of each other, a hydroxy group, a halogen, a C1-C6 alkyl group,

[0518]

Chemical formula

[0519] and each R 2-4-2 is, independently of each other, a hydroxy group, a halogen or a C1-C6 alkyl group, and each R 2-4-3 is, independently of each other, a hydroxy group, a halogen or a C1-C6 alkyl group, and each R 2-4-4 is, independently of each other, a hydroxy group, a halogen or a C1-C6 alkyl group, and R 2-4-1-1 is a C1-C6 alkyl group, and each R 2-4-1-2 is a C1-C6 alkyl group, each R 2-5is, independently of each other, hydrogen, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-5-1 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3,

[0520]

Chemical formula

[0521] and each R is, independently of each other, 2-5-1 and each R

[0522]

Chemical formula

[0523] and R is hydrogen or a C1-C6 alkyl group, 2-5-1-1 and each R is, independently of each other, hydrogen or a C1-C6 alkyl group, 2-5-1-2 and R is a C1-C6 alkyl group, 2-5-2 and each R is, independently of each other, halogen, a C1-C6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-6 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, 2-6-1 or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-6-2 and each R is, independently of each other, halogen, a C1-C6 alkyl group or 2-6-1 and each R

[0524] [Chemical formula]

[0525] and R 2-6-1-1 is a C1-C6 alkyl group, each R 2-6-2 is independently a halogen or a C1-C6 alkyl group, each R 2-7 is independently a C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-7-1 to form a 4- to 10-membered heterocycloalkyl group, or unsubstituted or substituted by one or more R 2-7-2 to form a 5- to 10-membered heteroaryl group, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. each R 2-7-1 is independently a halogen, a C1-C6 alkyl group,

[0526] [Chemical formula]

[0527] and R 2-7-1-1 is a C1-C6 alkyl group, and R 2-7-1-2 is a C1-C6 alkyl group, each R 2-7-2 is independently a halogen or a C1-C6 alkyl group, each R 2-8 is independently a C1-C6 alkyl group, or two R 2-8 together with the atom to which it is attached form an unsubstituted or substituted by one or more R 2-8-1a 4- to 10-membered heterocycloalkyl group substituted by , wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-8-1 is, independently of one another,

[0528]

Chemical formula

[0529] and R 2-8-1-1 is hydrogen or a C1-C6 alkyl group.

[0530] R 3 is unsubstituted or a 5- to 10-membered heteroaryl group substituted by one or more R 3-1 or a 3- to 10-membered heterocycloalkyl group substituted by one or more R 3-2 , wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, and the heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 3-1 is, independently of one another, a hydroxy group, a halogen, or a C1-C6 alkyl group substituted by one or more R 3-1-1 each R 3-1-1 is, independently of one another, a halogen each R 3-2 is, independently of one another, a hydroxy group, a halogen, a C1-C6 alkyl group substituted by one or more R 3-2-1 or

[0531]

Chemical formula

[0532] and each R 3-2-1 is independently a halogen, and R 3-2-2 is a C1-C6 alkyl group or a C2-C4 alkenyl group, R 4 is hydrogen, a halogen, a 5-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 s, or a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 4-2 s, wherein the heteroatom of the 5-10 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 4-1 is independently

[0533]

Chemical formula

[0534] and each R 4-2 is independently a 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more R 4-2-1 s, wherein the heteroatom of the 5-10 membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, R 4-1-1 is a C1-C6 alkyl group, each R 4-1-2 is independently a C1-C6 alkyl group, and each R 4-2-1 is independently a C1-C6 alkyl group.

[0535] In a preferred embodiment, Y is C or N, X is C or N, and at least one of X and Y is N, W is N, CH or CR 4 and Z is CH or N, A is

[0536] [Chemical formula]

[0537] wherein R A is hydrogen or a C1-C6 alkyl group, R 1 is a hydroxy group, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-1 , a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-2 , or a 3-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 1-3 , wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 1-1 is independently deuterium, a hydroxy group, a cyano group, a halogen or a C3-C6 cycloalkyl group, each R 1-2 is independently deuterium, a hydroxy group, a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-2-1 , a C2-C6 alkynyl group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3 , or an amino group which is unsubstituted or substituted by one or two R 1-2-5 , each R 1-2-1 is independently a halogen, a hydroxy group or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-1-1 , each R 1-2-1-1 is independently a halogen, each R 1-2-3 is independently a halogen, each R 1-2-5 is independently a C1-C6 alkyl group,

[0538] [Chemical formula]

[0539] or a C3-C6 cycloalkyl group, and R 1-2-5-1 is a C1-C6 alkyl group or an amino group, each R 1-3 is independently a C1-C6 alkyl group, or the atoms in R 1 and the atoms in A are linked to form a 5- or 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 0 wherein the heteroatom of the 5- or 6-membered heterocycloalkyl group is selected from one or more of N, O, P and S, the number of heteroatoms is 3, 4 or 5, and each R 0 is independently a C1-C6 alkyl group or oxa, each R 2 is hydrogen, a 6- to 10-membered aryl group which is unsubstituted or substituted by one or more R 2-1 a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-2 a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3 a C1-C6 alkyl group which is unsubstituted or substituted by one or more R

[0540]

Chemical formula

[0541] a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-6

Chemical formula

[0542]

Chemical formula

[0543] and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-1 is independently a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-1-1 groups,

[0544]

Chemical formula

[0545] or a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-1-4 groups, Each R 2-1-1 is independently a cyano group or a halogen, R 2-1-2 is hydrogen or a C1-C6 alkyl group, each R 2-1-3 is independently hydrogen or a C1-C6 alkyl group, each R 2-1-4 is independently a halogen, Each R 2-2 is independently a cyano group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-2-1 groups,

[0546]

Chemical formula

[0547] and Each R 2-2-1 is independently a cyano group or a halogen, R 2-2-2 is hydrogen or a C1-C6 alkyl group, each R 2-2-3 is independently hydrogen or a C1-C6 alkyl group, Each R 2-3is, independently of each other, a cyano group, oxa, hydroxy group, halogen, C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 2-3-1 substituted by 2-3-4

[0548]

Chemical formula

[0549] 3-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more Rs 2-3-4 C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs 2-3-5 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 each R 2-3-1 is, independently of each other, a cyano group, halogen, C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 2-3-1-1 substituted by 2-3-2 R 2-3-2 is hydrogen or C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 2-3-2-1 substituted by 2-3-3 each R 2-3-3 is, independently of each other, hydrogen or C1-C6 alkyl group each R 2-3-4 is, independently of each other, C1-C6 alkyl group each R 2-3-5 is, independently of each other, halogen each R 2-3-1-1 is, independently of each other, halogen each R 2-3-2-1 is, independently of each other, halogen each R 2-4 is 4-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more Rs 2-4-1 5-10 membered heteroaryl group which is unsubstituted or substituted by one or more Rs 2-4-2 substituted by 2-4-3 2-4-3a 6- to 10-membered aryl group substituted by [[ID=]], or an unsubstituted or one or more R 2-4-4 a C3-C6 cycloalkyl group substituted by [[ID=]], wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-4-1 is independently a hydroxy group, a halogen, a C1-C6 alkyl group,

[0550]

Chemical formula

[0551] and each R 2-4-2 is independently a hydroxy group, a halogen, or a C1-C6 alkyl group, each R 2-4-3 is independently a hydroxy group, a halogen, or a C1-C6 alkyl group, each R 2-4-4 is independently a hydroxy group, a halogen, or a C1-C6 alkyl group, R 2-4-1-1 is a C1-C6 alkyl group, each R 2-4-1-2 is a C1-C6 alkyl group, each R 2-5 is independently hydrogen, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-5-1 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3,

[0552]

Chemical formula

[0553] wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-5-1 is independently,

[0554]

Chem.

[0555] and is R 2-5-1-1 is hydrogen or a C1-C6 alkyl group, each R 2-5-1-2 is independently hydrogen or a C1-C6 alkyl group, R 2-5-2 is a C1-C6 alkyl group, each R 2-6 is independently halogen, a C1-C6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-6-1 or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-6-2 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, each R 2-6-1 is independently halogen, a C1-C6 alkyl group or

[0556]

Chem.

[0557] and R 2-6-1-1 is a C1-C6 alkyl group, each R 2-6-2 is independently halogen or a C1-C6 alkyl group, each R 2-7 is independently a C1-C6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-7-1 or a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R2-7-2 A 5- to 10-membered heteroaryl group substituted by, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-7-1 is independently a halogen, a C1-C6 alkyl group,

[0558]

Chemical formula

[0559] and R 2-7-1-1 is a C1-C6 alkyl group, R 2-7-1-2 is a C1-C6 alkyl group. Each R 2-7-2 is independently a halogen or a C1-C6 alkyl group. Each R 2-8 is independently a C1-C6 alkyl group, or two Rs 2-8 together with the atom to which it is attached form an unsubstituted or 4- to 10-membered heterocycloalkyl group substituted by one or more Rs 2-8-1 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-8-1 is independently

[0560]

Chemical formula

[0561] and R 2-8-1-1 is hydrogen or a C1-C6 alkyl group.

[0562] R 3 is unsubstituted or one or more Rs3-1 a 5- to 10-membered heteroaryl group substituted by 3-1 , or unsubstituted or substituted by one or more Rs 3-2 a 3- to 10-membered heterocycloalkyl group substituted by 3-2 , wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 each R 3-1 is independently a hydroxy group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 3-1-1 3-1-1 each R 3-1-1 is independently a halogen each R 3-2 is independently a hydroxy group, a halogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 3-2-1 or

[0563]

Chemical formula

[0564] and each R 3-2-1 is independently a halogen, R 3-2-2 is a C1-C6 alkyl group or a C2-C4 alkenyl group R 4 is hydrogen, a halogen, a 5- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more Rs 4-1 or a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs, wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 4-2 4-2 each R 4-1 is independently

[0565] [Chemical]

[0566] and, each R 4-2 is, independently of one another, an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 4-2-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, R 4-1-1 is a C1-C6 alkyl group, and each R 4-1-2 is, independently of one another, a C1-C6 alkyl group, and each R 4-2-1 is, independently of one another, a C1-C6 alkyl group.

[0567] In certain embodiments, R 1 is an unsubstituted or C3-C6 cycloalkyl group substituted by one or more R 1-2 or an unsubstituted or 3- to 6-membered heterocycloalkyl group substituted by one or more R 1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is N, O, or S, and the number of heteroatoms is 1, each R 1-2 is, independently of one another, a cyano group or a C1-C6 alkyl group unsubstituted or substituted by one or more R 1-2-1 and each R 1-2-1 is, independently of one another, a halogen, each R 1-3 is, independently of one another, an unsubstituted or C1-C6 alkyl group substituted by one or more R 1-3-1 and each R 1-3-1 is, independently of one another, a halogen, R 2 is hydrogen or unsubstituted or one or more R 2-3is a 4- to 10-membered heterocycloalkyl group substituted by, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is N, O or S, the number of heteroatoms is 1 or 2, each R 2-3 is, independently of one another,

[0568]

Chemical formula

[0569] and R 2-3-2 is a C1-C6 alkyl group, R 3 is unsubstituted or a 5- to 10-membered heteroaryl group substituted by one or more R 3-1 or a 5- to 10-membered heterocycloalkyl group substituted by one or more R 3-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1 or 2, each R 3-1 is, independently of one another, a hydroxy group, a halogen, or a C1-C6 alkyl group substituted by one or more R 3-1-1 each R 3-1-1 is, independently of one another, a halogen, each R 3-2 is, independently of one another,

[0570]

Chemical formula

[0571] and R 3-2-2 is a C1-C6 alkyl group or a C2-C4 alkenyl group, R 4 is unsubstituted or one or more R​4-1 a 5- to 10-membered heterocycloalkyl group substituted by 4-1 , wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1, 2 or 3, each R 4-1 is, independently of one another,

[0572]

Chemical formula

[0573] and R 4-1-1 is a C1-C6 alkyl group, each R 4-1-2 is, independently of one another, a C1-C6 alkyl group.

[0574] In a specific embodiment, R 1 is an unsubstituted or C3-C6 cycloalkyl group or 4-membered heterocycloalkyl group substituted by one or more R 1-2 wherein the heteroatom of the 4-membered heterocycloalkyl group is O and the number of heteroatoms is 1, each R 1-2 is, independently of one another, a cyano group or a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-2-1 each R 1-2-1 is, independently of one another, a halogen, R 2 is hydrogen or a 6- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 6- to 10-membered heterocycloalkyl group is N and the number of heteroatoms is 1 or 2, each R 2-3 is, independently of one another,

[0575]

Chemical formula

[0576] and R 2-3-2 is a C1-C6 alkyl group, R 3 is unsubstituted or a 5-6 membered heteroaryl group substituted by one or more Rs 3-1 or an unsubstituted or a 5-6 membered heterocycloalkyl group substituted by one or more Rs 3-2 wherein the heteroatom of the 5-6 membered heteroaryl group is N and / or S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-10 membered heterocycloalkyl group is N, and the number of heteroatoms is 1, each R 3-1 is independently halogen or a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 3-1-1 ; each R 3-1-1 is independently halogen, each R 3-2 is independently

[0577]

Chemical formula

[0578] ; R 3-2-2 is a C2-C4 alkenyl group, R 4 is unsubstituted or a 5-10 membered heterocycloalkyl group substituted by one or more Rs 4-1 wherein the heteroatom of the 5-10 membered heterocycloalkyl group is N, and the number of heteroatoms is 1 or 2, each R 4-1 is independently

[0579]

Chemical formula

[0580] ; R 4-1-1is a C1-C6 alkyl group, each R 4-1-2 is independently a C1-C6 alkyl group.

[0581] In certain embodiments, R 1 is an unsubstituted or C3-C6 cycloalkyl group substituted by one or more R 1-2 ; each R is independently a cyano group or a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 1-2 ; each R 1-2-1 is independently a halogen; each R 1-2-1 is independently a hydrogen or a 6-10 membered heterocycloalkyl group that is unsubstituted or substituted by one or more R R 2 ; the heteroatom of the 6-10 membered heterocycloalkyl group is N, and the number of heteroatoms is 1 or 2; 2-3 each R is independently 2-3 ;

[0582]

Chemical formula

[0583] ; R 2-3-2 is a C1-C6 alkyl group; R 3 is an unsubstituted or 5-6 membered heteroaryl group substituted by one or more R 3-1 ; the heteroatoms of the 5-6 membered heteroaryl group are N and / or S, and the number of heteroatoms is 3; each R 3-1 is independently a halogen or a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 3-1-1 ; each R 3-1-1 is independently a halogen; R 4is unsubstituted or has one or more R 4-1 wherein the heteroatom of the 7-9 membered heterocycloalkyl group is N and the number of heteroatoms is one; Each R 4-1 However, each independently,

[0584] [ka]

[0585] and R 4-1-1 is a C1-C6 alkyl group; Each R 4-1-2 are each independently a C1-C6 alkyl group.

[0586] In certain embodiments, R 1 is unsubstituted or has one or more R 1-2 or a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-3 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1.

[0587] In certain embodiments, each R 1-2 each independently represents a cyano group or is unsubstituted or represents one or more R 1-2-1 is a C1-C6 alkyl group substituted by

[0588] In certain embodiments, each R 1-2-1 are each independently a halogen.

[0589] In certain embodiments, each R 1-3 are each independently unsubstituted or one or more R 1-3-1 is a C1-C6 alkyl group substituted by

[0590] In certain embodiments, each R1-3-1 is, independently of each other, a halogen.

[0591] In certain embodiments, R 2 is hydrogen or a 4- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is N, O, or S, and the number of heteroatoms is 1 or 2.

[0592] In certain embodiments, each R 2-3 is, independently of each other,

[0593]

Chemical formula

[0594] is.

[0595] In certain embodiments, R 2-3-2 is a C1-C6 alkyl group.

[0596] In certain embodiments, R 3 is a 5- to 10-membered heteroaryl group that is unsubstituted or substituted by one or more R 3-1 or a 5- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 3-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, O, or S, and the number of heteroatoms is 1 or 2.

[0597] In certain embodiments, each R 3-1 is, independently of each other, a hydroxy group, a halogen, or a C1-C6 alkyl group that is unsubstituted or substituted by one or more R 3-1-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, O, or S, and the number of heteroatoms is 1 or 2.

[0598] In certain embodiments, each R3-1-1 is, independently of one another, a halogen.

[0599] In certain embodiments, each R 3-2 is, independently of one another,

[0600] [Chemical formula]

[0601] is as follows.

[0602] In certain embodiments, R 3-2-2 is a C1-C6 alkyl group or a C2-C4 alkenyl group.

[0603] In certain embodiments, R 4 is an unsubstituted or substituted by one or more R 4-1 5-10 membered heterocycloalkyl group, wherein the heteroatom of the 5-10 membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1, 2 or 3.

[0604] In certain embodiments, each R 4-1 is, independently of one another,

[0605] [Chemical formula]

[0606] is as follows.

[0607] In certain embodiments, R 4-1-1 is a C1-C6 alkyl group.

[0608] In certain embodiments, each R 4-1-2 is, independently of one another, a C1-C6 alkyl group.

[0609] In certain embodiments, R 1 is unsubstituted or substituted by one or more R 1-2is a C3-C6 cycloalkyl group or a 4-membered heterocycloalkyl group substituted by, wherein the heteroatom of the 4-membered heterocycloalkyl group is O and the number of heteroatoms is 1.

[0610] In certain embodiments, R 2 is hydrogen or a 6-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 6-10 membered heterocycloalkyl group is N and the number of heteroatoms is 1 or 2.

[0611] In certain embodiments, R 3 is a 5-6 membered heteroaryl group which is unsubstituted or substituted by one or more R 3-1 or a 5-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 3-2 wherein the heteroatom of the 5-6 membered heteroaryl group is N and / or S and the number of heteroatoms is 1, 2 or 3, and the heteroatom of the 5-10 membered heterocycloalkyl group is N and the number of heteroatoms is 1.

[0612] In certain embodiments, R 3-2-2 is a C2-C4 alkenyl group.

[0613] In certain embodiments, R 4 is a 5-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 wherein the heteroatom of the 5-10 membered heterocycloalkyl group is N and the number of heteroatoms is 1 or 2.

[0614] In certain embodiments, R 1 is a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-2 In certain embodiments, R 2 is hydrogen or a 6-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R

[0615] is hydrogen or a 6-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R2-3 A 6- to 10-membered heterocycloalkyl group substituted by 2-3 , wherein the heteroatom of the 6- to 10-membered heterocycloalkyl group is N, and the number of heteroatoms is 1 or 2.

[0616] In certain embodiments, R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3.

[0617] In certain embodiments, R 4 is an unsubstituted or 7- to 9-membered heterocycloalkyl group substituted by one or more R 4-1 wherein the heteroatom of the 7- to 9-membered heterocycloalkyl group is N, and the number of heteroatoms is 1.

[0618] In certain embodiments, R 1 is a C3-C6 cycloalkyl group substituted by one or more R 1-2 , an unsubstituted or 3- to 6-membered heterocycloalkyl group substituted by one or more R 1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3.

[0619] In certain embodiments, each R 1-2 is independently a C2-C6 alkynyl group.

[0620] In certain embodiments, each R 1-3 is independently a cyano group, an unsubstituted or C1-C6 alkyl group substituted by one or more R 1-3-1 , or a C2-C6 alkynyl group.

[0621] In certain embodiments, each R 1-3-1 is independently a halogen.

[0622] In certain embodiments, R 2 is a 4- to 12-membered heterocycloalkyl group substituted by one or more R 2-3 , wherein the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3.

[0623] In certain embodiments, each R 2-3 is independently

[0624]

Chemical formula

[0625] a 5- to 10-membered heteroaryl group, wherein the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 2 or 3.

[0626] In certain embodiments, R 2-3-2 is a C1-C6 alkyl group substituted by one or more R 2-3-2-1 , a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-2-2 ,

[0627]

Chemical formula

[0628] a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3-2-5 , a 5- to 10-membered heteroaryl group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, and the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1 or 2.

[0629] In certain embodiments, each R 2-3-2-1is, independently of each other, a hydroxy group,

[0630]

Chemical formula

[0631] and is as follows.

[0632] In certain embodiments, each R 2-3-2-1-1 is, independently of each other, a C1-C6 alkyl group.

[0633] In certain embodiments, each R 2-3-2-2 is, independently of each other, halogen, a hydroxy group, a C1-C6 alkyl group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-2-2-2 or an amino group.

[0634] In certain embodiments, each R 2-3-2-2-2 is, independently of each other, deuterium.

[0635] In certain embodiments, each R 2-3-2-3 is, independently of each other, hydrogen or

[0636]

Chemical formula

[0637] and is as follows.

[0638] In certain embodiments, each R 2-3-2-3-1 is, independently of each other, a 6-10 membered aryl group which is unsubstituted or substituted by one or more R 2-3-2-3-1-1 and each R 2-3-2-3-1-1 is, independently of each other, a C1-C6 alkoxy group.

[0639] In certain embodiments, each R 2-3-2-5 is, independently of each other, halogen, a C1-C6 alkoxy group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-2-5-1is a C1-C6 alkyl group replaced by

[0640] In certain embodiments, each R 2-3-2-5-1 is independently a halogen.

[0641] In certain embodiments, R 3 is an unsubstituted 5- or 6-membered heteroaryl group, the heteroatoms of the 5- or 6-membered heteroaryl group being N and / or S, and the number of heteroatoms being 3.

[0642] In certain embodiments, R 3 ,

[0643]

Chemical formula

[0644] is as follows.

[0645] In certain embodiments, R 4 is deuterium, a cyano group, an unsubstituted or 5- to 10-membered heterocycloalkyl group substituted by one or more R 4-1 , the heteroatoms of the 5- to 10-membered heterocycloalkyl group being selected from one or more of N, O, and S, and the number of heteroatoms being 1 or 2.

[0646] In certain embodiments, each R 4-1 is independently

[0647]

Chemical formula

[0648] is as follows, and R 4-1-1 is a C1-C6 alkyl group.

[0649] In certain embodiments, R 1 is unsubstituted or one or more R 1-2is a C3-C6 cycloalkyl group substituted by, each R 1-2 is, independently of one another, a cyano group, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 1-2-1 or a C2-C6 alkynyl group, each R 1-2-1 is, independently of one another, deuterium, a halogen, a hydroxy group, R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatoms of the 4- to 10-membered heterocycloalkyl group are N and / or O, the number of heteroatoms is 1, 2 or 3, and the 4- to 10-membered heterocycloalkyl group is a 4- to 6-membered saturated monocyclic ring, a 7- to 10-membered saturated spiro ring or a 7- to 10-membered saturated bridged ring, each R 2-3 is, independently of one another,

[0650]

Chemical formula

[0651] a 5- to 10-membered heteroaryl group, wherein the heteroatoms of the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 2 or 3, R 2-3-2 is a C1-C6 alkyl group substituted by one or more R 2-3-2-1 or a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-2-2 and,

[0652]

Chemical formula

[0653] is unsubstituted or substituted by one or more R 2-3-2-5a 3- to 6-membered heterocycloalkyl group or a 5- to 10-membered heteroaryl group, which is substituted by, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the 3- to 6-membered heterocycloalkyl group is a 3- to 6-membered saturated monocyclic ring, the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1 or 2, each R 2-3-2-1 is independently a hydroxy group,

[0654]

Chemical formula

[0655] and each R 2-3-2-1-1 is independently a C1-C6 alkyl group, each R 2-3-2-2 is independently a halogen, a hydroxy group, a C1-C6 alkyl group, a C1-C6 alkoxy group substituted by one or more R 2-3-2-2-2 or an amino group, each R 2-3-2-2-2 is independently deuterium, each R 2-3-2-3 is independently hydrogen or

[0656]

Chemical formula

[0657] and each R 2-3-2-3-1 is independently a 6- to 10-membered aryl group, which is unsubstituted or substituted by one or more R 2-3-2-3-1-1 and each R 2-3-2-3-1-1 is independently a C1-C6 alkoxy group, each R 2-3-2-5 is independently a halogen, a C1-C6 alkoxy group, a 6- to 10-membered aryl group, which is unsubstituted or substituted by one or more R 2-3-2-5-1is a C1-C6 alkyl group substituted by, each R 2-3-2-5-1 is, independently of one another, halogen, R 3 is unsubstituted or a 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3, each R 3-1 is, independently of one another, a C1-C6 alkyl group substituted by one or more R 3-1-1 wherein, each R 3-1-1 is, independently of one another, halogen, R 4 is hydrogen, a cyano group, halogen, a C1-C6 alkyl group, unsubstituted or a 5- to 10-membered heterocycloalkyl group substituted by one or more R 4-1 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1 or 2, and the 5- to 10-membered heterocycloalkyl group is a 7- to 10-membered unsaturated spiro ring, each R 4-1 is, independently of one another,

[0658] [Chemical formula]

[0659] and R 4-1-1 is a C1-C6 alkyl group.

[0660] In certain embodiments, R 1 is unsubstituted or a C3-C6 cycloalkyl group substituted by one or more R 1-2 wherein, each R 1-2 is, independently of one another, a cyano group, a C1-C6 alkyl group unsubstituted or substituted by one or more R 1-2-1 or a C2-C6 alkynyl group, each R1-2-1 is, independently, deuterium, halogen, or a hydroxy group, R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is N and / or O, and the number of heteroatoms is 1, 2, or 3, each R 2-3 is, independently,

[0661]

Chemical formula

[0662] a 5- to 10-membered heteroaryl group, wherein the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 2 or 3, R 2-3-2 is a C1-C6 alkyl group substituted by one or more R 2-3-2-1 or a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-2-2 ,

[0663]

Chemical formula

[0664] an unsubstituted or 3- to 6-membered heterocycloalkyl group substituted by one or more R 2-3-2-5 or a 5- to 10-membered heteroaryl group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1 or 2, each R 2-3-2-1 is, independently, a hydroxy group,

[0665]

Chemical formula

[0666] and each R 2-3-2-1-1 is, independently of one another, a C1-C6 alkyl group, each R 2-3-2-2 is, independently of one another, halogen, a hydroxy group, a C1-C6 alkyl group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-2-2-2 or an amino group, each R 2-3-2-2-2 is, independently of one another, deuterium, each R 2-3-2-3 is, independently of one another, hydrogen or

[0667] [Chemical formula]

[0668] and each R 2-3-2-3-1 is, independently of one another, a 6-10 membered aryl group which is unsubstituted or substituted by one or more R 2-3-2-3-1-1 and each R 2-3-2-3-1-1 is, independently of one another, a C1-C6 alkoxy group, each R 2-3-2-5 is, independently of one another, halogen, a C1-C6 alkoxy group, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-2-5-1 or an amino group, each R 2-3-2-5-1 is, independently of one another, halogen, R 3 is a 5-6 membered heteroaryl group which is unsubstituted or substituted by one or more R 3-1 and the heteroatom of the 5-6 membered heteroaryl group is N and / or S and the number of heteroatoms is 3, each R 3-1 is, independently of one another, a C1-C6 alkyl group substituted by one or more R 3-1-1 or an amino group, each R 3-1-1each independently is a halogen, R 4 is hydrogen, a cyano group, a halogen, a C1-C6 alkyl group, a 5-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 wherein the heteroatom of the 5-10 membered heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2, each R 4-1 is independently

[0669]

Chemical formula

[0670] and R 4-1-1 is a C1-C6 alkyl group.

[0671] In a preferred embodiment, R 1 is an unsubstituted or C3-C6 cycloalkyl group substituted by one or more R 1-2 wherein each R 1-2 is independently a cyano group, an unsubstituted or C1-C6 alkyl group substituted by one or more R 1-2-1 wherein each R 1-2-1 is independently deuterium, a halogen, R 2 is a 4-10 membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from N and / or O, the number of heteroatoms is 1, 2 or 3, and the 4-10 membered heterocycloalkyl group is a 4-6 membered saturated monocyclic ring or a 7-10 membered saturated spiro ring, each R 2-3 is independently

[0672]

Chemical formula

[0673] and is R 2-3-2 is a C3-C6 cycloalkyl group substituted by one or more R 2-3-2-2 is a 3-6 membered heterocycloalkyl group substituted by one or more R 2-3-2-5 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the 3-6 membered heterocycloalkyl group is a 3-6 membered saturated monocyclic ring, the heteroatom of the 5-10 membered heteroaryl group is N and / or O, the number of heteroatoms is 1 or 2, each R 2-3-2-2 is independently a C1-C6 alkyl group, an unsubstituted or C1-C6 alkoxy group substituted by one or more R 2-3-2-2-2 each R 2-3-2-2-2 is independently deuterium, each R 2-3-2-5 is independently a C1-C6 alkyl group, R 3 is an unsubstituted or 5-6 membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5-6 membered heteroaryl group is N and / or S, and the number of heteroatoms is 3, each R 3-1 is independently a C1-C6 alkyl group substituted by one or more R 3-1-1 each R 3-1-1 is independently halogen, R 4 is hydrogen, cyano group, C1-C6 alkyl group.

[0674] In a preferred embodiment, R 1 is an unsubstituted or C3-C6 cycloalkyl group substituted by one or more R 1-2 each R 1-2 ​​​is, independently of one another, a cyano group, a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 1-2-1 wherein the Rs are, independently of one another, deuterium, halogen each R 1-2-1 is, independently of one another, deuterium, halogen R 2 is a 4-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more Rs 2-3 wherein the heteroatom of the 4-10 membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1, 2 or 3 each R 2-3 is, independently of one another

[0675]

Chemical formula

[0676] and R 2-3-2 is a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more Rs 2-3-2-2 a 3-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more Rs 2-3-2-5 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-10 membered heteroaryl group is N and / or O, and the number of heteroatoms is 1 or 2 each R 2-3-2-2 is, independently of one another, a C1-C6 alkyl group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs 2-3-2-2-2 wherein the Rs are, independently of one another, deuterium, halogen each R 2-3-2-2-2 is, independently of one another, deuterium each R 2-3-2-5 is, independently of one another, a C1-C6 alkyl group R 3 is unsubstituted or substituted by one or more Rs 3-1is a 5- to 6-membered heteroaryl group substituted by, wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3, Each R 3-1 is independently a C1-C6 alkyl group substituted by one or more R 3-1-1 groups, Each R 3-1-1 is independently halogen, R 4 is hydrogen, a cyano group, or a C1-C6 alkyl group.

[0677] In certain embodiments, R 1 is unsubstituted or a 3- to 6-membered heterocycloalkyl group substituted by one or more R 1-3 groups, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is O, the number of heteroatoms is 1, and the 3- to 6-membered heterocycloalkyl group is a 3- to 6-membered saturated monocyclic ring, Each R 1-3 is independently a cyano group, a C1-C6 alkyl group unsubstituted or substituted by one or more R 1-3-1 groups, or a C2-C6 alkynyl group, Each R 1-3-1 is independently halogen or deuterium, R 2 is unsubstituted or a 4- to 12-membered heterocycloalkyl group substituted by one or more R 2-3 groups, wherein the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and the 4- to 12-membered heterocycloalkyl group is a 4- to 6-membered saturated monocyclic ring, a 7- to 10-membered saturated fused ring, or a 7- to 10-membered saturated spiro ring, Each R 2-3-3 is independently oxa, a C1-C6 alkyl group unsubstituted or substituted by one or more R 2-3-1 groups,

[0678]

Chemical Structure

[0679] and each R 2-3-1 is, independently of one another, a hydroxy group, a halogen, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-1-1 a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-1-3 an amino group which is unsubstituted or substituted by one or more R each R 2-3-1-1 is, independently of one another, deuterium, each R 2-3-1-3 is, independently of one another, a C1-C6 alkyl group, R 2-3-2 is a C1-C6 alkyl group, a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-2-2 a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R each R 2-3-2-2 is, independently of one another, a C1-C6 alkyl group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-2-2-2 a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R each R 2-3-2-2-2 is, independently of one another, deuterium, each R 2-3-3 is, independently of one another, hydrogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-3-1 a C1-C6 alkyl group which is unsubstituted or substituted by one or more R each R 2-3-3-1 is, independently of one another, an amino group which is unsubstituted or substituted by one or more R 2-3-3-1-1 an amino group which is unsubstituted or substituted by one or more R each R 2-3-3-1-1 is, independently of one another, a C1-C6 alkyl group, R 3 is a 5-6 membered heteroaryl group which is unsubstituted or substituted by one or more R 3-1 a 5-6 membered heteroaryl group in which the heteroatoms are N and / or S and the number of heteroatoms is 3, each R 3-1 is, independently of one another, a C1-C6 alkyl group which is substituted by one or more R 3-1-1 a C1-C6 alkyl group which is substituted by one or more R Each R 3-1-1 is, independently of one another, halogen, R 4 is hydrogen, deuterium, halogen, a C1-C6 alkyl group.

[0680] In a specific embodiment, R 1 is an unsubstituted or 3-6 membered heterocycloalkyl group substituted by one or more R 1-3 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is O, and the number of heteroatoms is 1, Each R 1-3 is, independently of one another, a cyano group, an unsubstituted or C1-C6 alkyl group substituted by one or more R 1-3-1 or a C2-C6 alkynyl group, Each R 1-3-1 is, independently of one another, halogen or deuterium, R 2 is an unsubstituted or 4-12 membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatom of the 4-12 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-3-3 is, independently of one another, oxa, an unsubstituted or C1-C6 alkyl group substituted by one or more R 2-3-1 or a C1-C6 alkoxy group,

[0681]

Chemical formula

[0682] and Each R 2-3-1 is, independently of one another, a hydroxy group, halogen, an unsubstituted or C1-C6 alkoxy group substituted by one or more R 2-3-1-1 or an amino group substituted by one or more R 2-3-1-3 and Each R 2-3-1-1is, independently of one another, deuterium, each R 2-3-1-3 is, independently of one another, a C1-C6 alkyl group, R 2-3-2 is a C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-3-2-2 and is a C3-C6 cycloalkyl group, each R 2-3-2-2 is, independently of one another, a C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-3-2-2-2 and is a C1-C6 alkoxy group, each R 2-3-2-2-2 is, independently of one another, deuterium, each R 2-3-3 is, independently of one another, hydrogen, a C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-3-3-1 and is a C1-C6 alkyl group, each R 2-3-3-1 is, independently of one another, an amino group, unsubstituted or substituted by one or more R 2-3-3-1-1 and is a C1-C6 alkyl group, each R 2-3-3-1-1 is, independently of one another, a C1-C6 alkyl group, R 3 is a 5-6 membered heteroaryl group, unsubstituted or substituted by one or more R 3-1 wherein the heteroatom of the 5-6 membered heteroaryl group is N and / or S, and the number of heteroatoms is 3, each R 3-1 is, independently of one another, a C1-C6 alkyl group, substituted by one or more R 3-1-1 and is a C1-C6 alkyl group, each R 3-1-1 is, independently of one another, a halogen, R 4 is hydrogen, deuterium, a halogen, or a C1-C6 alkyl group.

[0683] In a preferred embodiment, R 1 is unsubstituted or substituted by one or more R 1-3is a 3- to 6-membered heterocycloalkyl group substituted by, the heteroatom of the 3- to 6-membered heterocycloalkyl group being O, the number of heteroatoms being 1, and the 3- to 6-membered heterocycloalkyl group being a 3- to 6-membered saturated monocyclic ring, each R 1-3 is, independently of one another, a cyano group, a C1-C6 alkyl group unsubstituted or substituted by one or more R 1-3-1 or a C2-C6 alkynyl group, each R 1-3-1 is, independently of one another, a halogen, R 2 is a 4- to 12-membered heterocycloalkyl group unsubstituted or substituted by one or more R 2-3 the heteroatom of the 4- to 12-membered heterocycloalkyl group being selected from one or more of N, O and S, the number of heteroatoms being 1, 2 or 3, and the 4- to 12-membered heterocycloalkyl group being a 4- to 6-membered saturated monocyclic ring, a 7- to 10-membered saturated condensed ring or a 7- to 10-membered saturated spiro ring, each R 2-3-3 is, independently of one another, oxa, a C1-C6 alkyl group unsubstituted or substituted by one or more R 2-3-1 or,

[0684]

Chemical formula

[0685] and is, each R 2-3-1 is, independently of one another, a hydroxy group, a C1-C6 alkoxy group unsubstituted or substituted by one or more R 2-3-1-1 or, each R 2-3-1-1 is, independently of one another, deuterium, R 2-3-2 is a C1-C6 alkyl group, a C3-C6 cycloalkyl group unsubstituted or substituted by one or more R 2-3-2-2 or, each R 2-3-2-2is, independently of each other, a C1-C6 alkyl group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more Rs 2-3-2-2-2 and is each R 2-3-2-2-2 is, independently of each other, deuterium each R 2-3-3 is, independently of each other, hydrogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 2-3-3-1 and is each R 2-3-3-1 is, independently of each other, an amino group which is unsubstituted or substituted by one or more Rs 2-3-3-1-1 and is each R 2-3-3-1-1 is, independently of each other, a C1-C6 alkyl group R 3 is a 5-6 membered heteroaryl group which is unsubstituted or substituted by one or more Rs 3-1 wherein the heteroatom of the 5-6 membered heteroaryl group is N and / or S and the number of heteroatoms is 3 each R 3-1 is, independently of each other, a C1-C6 alkyl group which is substituted by one or more Rs 3-1-1 and is each R 3-1-1 is, independently of each other, a halogen R 4 is hydrogen, deuterium, a halogen or a C1-C6 alkyl group

[0686] In a preferred embodiment, R 1 is a 3-6 membered heterocycloalkyl group which is unsubstituted or substituted by one or more Rs 1-3 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is O and the number of heteroatoms is 1 each R 1-3 is, independently of each other, a cyano group, a C1-C6 alkyl group which is unsubstituted or substituted by one or more Rs 1-3-1 or a C2-C6 alkynyl group each R 1-3-1 is, independently of each other, a halogen R 2 is a 4- to 12-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, each R 2-3-3 is independently oxa, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-1 and,

[0687]

Chemical formula

[0688] and, each R 2-3-1 is independently a hydroxy group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-1-1 and, each R 2-3-1-1 is independently deuterium, R 2-3-2 is a C1-C6 alkyl group, a C3-C6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-2-2 and, each R 2-3-2-2 is independently a C1-C6 alkyl group, a C1-C6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-2-2-2 and, each R 2-3-2-2-2 is independently deuterium, each R 2-3-3 is independently hydrogen, a C1-C6 alkyl group which is unsubstituted or substituted by one or more R 2-3-3-1 and, each R 2-3-3-1 is independently an amino group which is unsubstituted or substituted by one or more R 2-3-3-1-1 and, each R 2-3-3-1-1each independently is a C1-C6 alkyl group, R 3 is unsubstituted or a 5-6 membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5-6 membered heteroaryl group is N and / or S, and the number of heteroatoms is 3, each R 3-1 is independently a C1-C6 alkyl group substituted by one or more R 3-1-1 ; each R 3-1-1 is independently halogen, R 4 is hydrogen, deuterium, halogen, a C1-C6 alkyl group.

[0689] In certain embodiments, ring B is

[0690]

Chemical formula

[0691] ;

[0692]

Chemical formula

[0693] or the atoms in R 1 and the atoms in A are linked to form

[0694]

Chemical formula

[0695] ;

[0696] In certain embodiments, R 2 is hydrogen, a methyl group,

[0697]

Chemical formula

[0698] is.

[0699] In certain embodiments, R 3 is

[0700]

Chem.

[0701] is.

[0702] In certain embodiments, R 4 is hydrogen, deuterium, Cl, F, CN, a methyl group,

[0703]

Chem.

[0704] is.

[0705] In certain embodiments, the compound represented by Formula I is any of the following compounds:

[0706]

Chem.

[0707] 。

[0708] The present invention also provides a pharmaceutical composition comprising substance Z and a pharmaceutical excipient, wherein the substance Z is a compound represented by formula I, a pharmaceutically acceptable salt or an isotopic compound thereof.

[0709] The present invention also provides the use of Substance Z in the preparation of a PARG inhibitor and a medicament for treating and / or preventing PARG-related diseases, wherein Substance Z is a compound represented by Formula I, a pharmaceutically acceptable salt thereof, or an isotope compound.

[0710] The present invention also provides a method for treating and / or preventing PARG-related diseases, comprising administering an effective amount of Substance Z to a patient, wherein Substance Z is a compound represented by Formula I, a pharmaceutically acceptable salt thereof, or an isotope compound.

[0711] In a preferred embodiment, the PARG-related disease can be breast cancer, for example, triple-negative breast cancer and other PARG-related diseases.

[0712] The present invention also provides the use of Substance Z in the preparation of a medicament for treating and / or preventing breast cancer, wherein Substance Z is a compound represented by Formula I, a pharmaceutically acceptable salt thereof, or an isotope compound.

[0713] In a preferred embodiment, the breast cancer can be triple-negative breast cancer.

[0714] The present invention also provides a compound represented by Formula II, III, IV or V or a salt thereof,

[0715]

Chemical formula

[0716] and provides wherein R 5 is hydrogen or PMB, R 6 is halogen, deuterium, R 7 is R 3 hydrogen or

[0717]

Chemical formula

[0718] and; R 8 is hydrogen or a C1-C6 alkyl group, and R 9 is

[0719]

Chemical formula

[0720] or halogen, and R 1 and R 2 and R 3 and the bodies of X, Y, Z and W are as shown above.

[0721] The present invention also provides a compound represented by formula II, III, IV or V or a salt thereof,

[0722]

Chemical formula

[0723] and wherein R 5 is hydrogen or PMB, R 6 is halogen, R 7 is R 3 hydrogen or

[0724]

Chemical formula

[0725] and R 8 is hydrogen or a C1-C6 alkyl group, and R 9 is

[0726]

Chemical formula

[0727] or halogen, and R 1 and R 2 and R3 The bodies of X, Y, Z, and W are as shown above.

[0728] In a preferred embodiment, R 6 wherein the halogen may be fluorine, chlorine, bromine, or iodine, for example, chlorine or bromine.

[0729] In a preferred embodiment, R 8 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and may also be a methyl group or an ethyl group.

[0730] In a preferred embodiment, R 9 wherein the halogen may be fluorine, chlorine, bromine, or iodine, for example, chlorine or bromine.

[0731] In a preferred embodiment, the compound represented by Formula II is

[0732]

Chemical formula

[0733] any of the following structures.

[0734] In a preferred embodiment, the compound represented by Formula III is

[0735]

Chemical formula

[0736] any of the following structures.

[0737] In a preferred embodiment, the compound represented by Formula IV is

[0738]

Chemical formula

[0739] It has any one of the following structures.

[0740] In a preferred embodiment, the compound represented by the formula V is

[0741]

Chemical formula

[0742] It has any one of the following structures.

[0743] Term Explanation The term "a group B which is unsubstituted or substituted by a plurality of groups A" means that one or more hydrogen atoms in the group B are each independently substituted by the group A or B. At the same time, when a plurality of A groups appear, unless otherwise specified, their definitions are independent of each other and do not affect each other. For example, "a C6-C 10 aryl group substituted by 3 halogens" means that the C6-C 10 aryl group is substituted by 3 halogens, and the definitions of the 3 halogens are independent of each other and do not affect each other,

[0744]

Chemical formula

[0745] etc. are included, but not limited thereto.

[0746]

Chemical formula

[0747] is a double bond or a single bond.

[0748] The term "a plurality of" refers to two or more, for example, 2, 3, 4, 5.

[0749] The term "pharmaceutically acceptable" refers to being relatively non-toxic, safe, and suitable for use by patients.

[0750] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When a compound contains a relatively acidic functional group, the base addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, sodium salts, potassium salts, calcium salts, aluminum salts, magnesium salts, bismuth salts, ammonium salts, etc. When a compound contains a relatively basic functional group, the acid addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochloride salts, sulfate salts, formate salts, methanesulfonate salts, etc. Specifically, refer to Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition).

[0751] The "-" of a group indicates that the group is bonded to another part of the molecule through this site. For example, CH3-C(=O)- refers to an acetyl group.

[0752] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. In the present invention, halogen substitution includes, but is not limited to, being substituted by one halogen, being substituted by two halogens, being substituted by three halogens, and usually, multiple substitutions occur on the same carbon atom.

[0753] The term "oxa" refers to =O, indicating that two hydrogens on the same carbon atom are substituted by an oxygen atom, that is, substituting a methylene group with a carbonyl group.

[0754] The term "alkyl group" refers to a straight-chain or branched-chain saturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C1-C6). Alkyl groups include, but are not limited to, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, n-hexyl group, etc.

[0755] The term "alkoxy group" refers to an R X -O- group, where the definition of R X is the same as the term "alkyl group". Alkoxy groups include, but are not limited to, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, etc.

[0756] The term "alkenyl group" refers to a straight-chain or branched-chain unsaturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C2-C6) and one or more (e.g., 1, 2 or 3) carbon-carbon sp 2 double bonds. Alkenyl groups include, but are not limited to, vinyl group,

[0757]

Chem.

[0758] etc.

[0759] The term "alkynyl group" refers to a straight-chain or branched-chain unsaturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C2-C6) and one or more (e.g., 1, 2 or 3) carbon-carbon sp 3 triple bonds. Alkynyl groups include, but are not limited to, ethynyl group,

[0760]

Chem.

[0761] including, but not limited to, the following.

[0762] In the present invention, unless otherwise specified, the term "cycloalkyl group" refers to a cyclic saturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C3 - C 10 ), which may be monocyclic or polycyclic (e.g., bicyclic or tricyclic, bridged ring, spiro ring, fused ring), and where monocyclic rings share two or more carbon atoms. Monocyclic rings include

[0763]

Chemical formula

[0764] including, but not limited to, the following. Bridged ring cycloalkyl groups include

[0765]

Chemical formula

[0766] including, but not limited to, the following. Spiro ring cycloalkyl groups include

[0767]

Chemical formula

[0768] including, but not limited to, the following. Fused ring cycloalkyl groups include

[0769]

Chemical formula

[0770] including, but not limited to, the following.

[0771] In the present invention, unless otherwise specified, the term "cycloalkenyl group" refers to a "cycloalkyl group" having one or more carbon-carbon double bonds, and the definition of "cycloalkyl group" is as shown above. For example,

[0772]

Chemical formula

[0773] is.

[0774] In the present invention, unless otherwise specified, the term "aryl group" refers to a cyclic saturated monovalent hydrocarbon group having a specified number of carbon atoms (for example, C6 to C 10 ), which is monocyclic or polycyclic (for example, 2 or 3 rings), and in the case of polycyclic, the monocyclic rings share 2 carbon atoms and 1 bond, and (at least one ring / each ring) is aromatic. The aryl group is bonded to other parts of the molecule via an aromatic or non-aromatic ring. The aryl group includes, but is not limited to, a phenyl group, a naphthalene group,

[0775]

Chemical formula

[0776] and the like.

[0777] In the present invention, unless otherwise specified, the "heterocycloalkyl group" refers to a group having a specified number of ring atoms (for example, 3 to 10 members), a specified number of heteroatoms (for example, 1, 2 or 3), and a specified type of heteroatoms (any one or more of N, O and S), having a monocyclic, bridged ring, spiro ring or fused ring, and the heterocycloalkyl group can be saturated or unsaturated. The (monocyclic) heterocycloalkyl group is bonded to other parts of the molecule via a carbon atom or a heteroatom. The monocyclic heterocycloalkyl group includes,

[0778]

Chemical formula

[0779] include, but are not limited to, etc. The spirocyclic heterocycloalkyl group includes

[0780]

Chemical formula

[0781] include, but are not limited to, etc. The bridged-ring heterocycloalkyl group includes

[0782]

Chemical formula

[0783] include, but are not limited to, etc. The fused-ring heterocycloalkyl group includes

[0784]

Chemical formula

[0785] include, but are not limited to, etc. Heterocycloalkyl group unsaturation means that the ring of the heterocycloalkyl group has a carbon-carbon double bond or a carbon-carbon triple bond. For example,

[0786]

Chemical formula

[0787] is.

[0788] In the present invention, unless otherwise specified, the term "heteroaryl group" refers to a cyclic unsaturated monovalent group having a specified number of ring atoms (e.g., 5 to 10 members), a specified number of heteroatoms (e.g., 1, 2 or 3), and a specified type of heteroatoms (any one or more of O and S), which is monocyclic or polycyclic, and the monocyclic rings share two carbon atoms and one bond, and at least one ring is aromatic. The heteroaryl group is bonded to other parts of the molecule via a carbon atom or a heteroatom, and the heteroaryl group is bonded to other parts of the molecule via a ring having a heteroatom or a ring having no heteroatom, and the heteroaryl group is bonded to other parts of the molecule via an aromatic or non-aromatic ring. The heteroaryl group includes

[0789] [Chemical formula]

[0790] and the like, but are not limited thereto.

[0791] The term "isotope compound" refers to a compound in which the isotope abundance of one or more atoms is different from its natural abundance. For example, one or more atoms in the compound are replaced by atoms with a smaller natural mass number, such that a hydrogen atom in the compound is replaced by deuterium, or C is 13 replaced by C.

[0792] Each of the above preferred conditions can be combined in any manner consistent with the common general knowledge of those skilled in the art to obtain preferred embodiments of the present invention.

[0793] The reagents and raw materials used in the present invention are available from commercial sources.

[0794] Positive and progressive effects of the present invention: The compounds of the present invention have relatively good PARG inhibitory activity. In addition, the permeability and / or solubility of the compounds of the present invention have also been greatly improved compared to existing inventions.

[0795] 〔Specific Embodiments〕 The present invention will be further described below by way of examples, but the present invention is not limited to the scope of these examples. In the following examples, experimental methods for which specific conditions are not indicated should be selected according to conventional methods and conditions, or the product handling instructions.

[0796] All compounds of the present invention can be synthesized by various methods by those skilled in the art of organic chemistry. General synthetic embodiments for preparing the compounds of the present invention are described as follows. These methods are generally applicable in nature, but do not limit the techniques that can be used by those skilled in the art to prepare the compounds disclosed herein. Different methods for preparing the compounds of the present invention will be apparent to those skilled in the art. Further, the individual steps in the synthesis can be carried out alternately to obtain the desired one or more compounds. The sections on preparations and examples described below show examples of preparing the compounds of the present invention by the methods described in the general embodiments. The preparation of compounds of embodiments containing chiral centers can be carried out by techniques known to those skilled in the art. For example, chiral compounds can be prepared by separating racemic products by chiral resolution using HPLC, or exemplary compounds can be prepared by known methods to obtain chiral compounds.

[0797] The chemical reactions and synthetic techniques described in this application are carried out in the reagents and corresponding solvents described in this application, and the corresponding reaction yields are also affected by the reagents and solvents used. Furthermore, in the synthetic methods described below, it should be easily conceivable to those skilled in the art that all of the reaction conditions mentioned, including the selection of solvents, reaction atmosphere, reaction temperature, experimental duration, and reaction input order, should be regarded as the operating condition criteria for the reaction. At the same time, it can also be conceived by those skilled in the field of organic synthesis. The functional groups present in each part of the molecule must be compatible with the reagents used and the reaction itself. It should be easily conceivable to those skilled in the art that alternative methods are required for the limitation that some of the functional groups present in each part of the molecule are not compatible with the reaction conditions. It is obvious that it is necessary to make a judgment in order to adjust the order of the synthetic steps or select a specific synthetic step embodiment to obtain the desired compound of the present invention. This can be understood and easily recognized by those skilled in the field of organic synthesis. Also, it should be recognized that reasonably selecting a protecting group to protect the resistance of the reactive functional groups present in the compounds described in the present invention is another major consideration in any synthetic route devised in the art. Specifically, refer to (Protective Groups in Organic Synthesis, Third Edition, Wiley and Sons (1999)) by Greene et al., authorities in the field of chemistry.

[0798] 〔Exemplification〕 The preparation of the compounds and the intermediates used in the compound preparation can be adjusted using the procedures shown in the following exemplifications and related procedures. The methods and conditions used in these examples, and the actual compounds prepared in these examples, are not limiting and are illustrative of the methods for preparing related compounds. If the starting materials and reagents used in these exemplifications are not prepared by the procedures described in this application, they can usually be commercially available, reported in related chemical literature, or prepared by the procedures described in chemical literature.

[0799] In the examples described in this application, the term "drying and concentration" usually refers to adding a dry solution of sodium sulfate anhydrous or magnesium sulfate to an organic solvent, then filtering, and removing the solvent from the filtrate (usually carried out under reduced pressure and at a temperature suitable for the stability of the prepared compound). The column method usually involves performing column separation and purification by conventional column chromatography or flash column chromatography, or using a medium-pressure chromatograph (Biotage IsolaOne) pre-packed with a silica gel column and eluting with a specified solvent or solvent mixture. In some cases, the final product is rapidly purified by preparative thin-layer chromatography using a 20 cm x 20 cm x 0.5 mm or 20 cm x 20 cm x 1 mm silica gel plate in a suitable solvent system. Preparative high-performance liquid chromatography (HPLC) is carried out using a reverse-phase column (Waters Sunfire C18, Waters Xbridge C18 or equivalents) of a size suitable for the amount of compound to be separated, usually eluting by adding a concentration gradient of methanol or acetonitrile to the aqueous phase, and the eluent contains 0.05% or 0.1% formic acid, trifluoroacetic acid or 10 mM ammonium acetate. The elution rate depends on the size of the reverse-phase column used and the resolution of the preparation. The chemical names described in this application are generated by ChemDraw Professional version 19.1 and then translated into Chinese for use.

[0800]

Table 1

[0801] Example 1: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-3-(2-methylthiazol-5-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0802]

Chemical formula

[0803] Procedure 1: 5-Bromo-6-chloro-N-(1-cyanocyclopropyl)pyridine-3-sulfonamide At 0 °C, 5-bromo-6-chloropyridine-3-sulfonyl chloride (3.3 g, 27.5 mmol) was added portionwise to a solution of 1-aminocyclopropane-1-carbonitrile hydrochloride (4 g, 13.7 mmol) in pyridine (20 mL). Then the mixture was stirred at room temperature for 1 h. The mixture was acidified to pH ~ 5 with 1 N hydrochloric acid and extracted twice with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (yellow solid, 4 g, yield 86.4%). LC / MS (ESI) m / z: 336 [M+H] + 。

[0804] Procedure 2: 5-Bromo-N-(1-cyanocyclopropyl)-6-((3,4-dimethoxybenzyl)amino)pyridine-3-sulfonamide To a solution of 5-bromo-6-chloro-N-(1-cyanocyclopropyl)pyridine-3-sulfonamide (4 g, 11.9 mmol) in N-methylpyrrolidone (40 mL) were slowly added N,N-diisopropylethylamine (4.6 g, 35.6 mmol) and (3,4-dimethoxyphenyl)methylamine (3.0 g, 17.8 mmol). The mixture was reacted for 2 h with stirring at 100 °C under nitrogen gas protection. After completion of the reaction, it was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 50% ethyl acetate) to give the title compound (yellow solid, 5.1 g, yield 91.7%). LC / MS (ESI) m / z: 469 [M+H] + 。

[0805] Procedure 3: 6-Amino-5-bromo-N-(1-cyanocyclopropyl)pyridine-3-sulfonamide At 0 °C, 5-bromo-N-(1-cyanocyclopropyl)-6-((3,4-dimethoxybenzyl)amino)pyridine-3-sulfonamide (5.0 g, 10.7 mmol) was dissolved in trifluoroacetic acid (20 mL). The reaction mixture was stirred at room temperature for 16 hours. The mixture was concentrated under reduced pressure to give the title compound (yellow solid, 3.39 g, yield 100.0%), which was used directly in the next reaction without purification. LC / MS (ESI) m / z: 319 [M+H] + 。

[0806] Procedure 4: 8-Bromo-N-(1-cyanocyclopropyl)imidazo[1,2-a]pyridine-6-sulfonamide To a solution of 6-amino-5-bromo-N-(1-cyanocyclopropyl)pyridine-3-sulfonamide (3.39 g, 10.7 mmol) in ethanol (100 mL) were slowly added sodium bicarbonate (2.7 g, 32.1 mmol) and 2-chloroacetaldehyde (8.5 mL, 53.5 mmol, 40% aqueous solution), and the reaction mixture was stirred at 90 °C overnight. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure until dry. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 60% ethyl acetate) to give the title compound (yellow solid, 1.5 g, yield 41.1%). 1 HNMR (400 MHz, DMSO-d6) δ 9.37 (d, J = 1.6 Hz, 1H), 8.31 (d, J = 1.2 Hz, 1H), 7.80 (d, J = 1.2 Hz, 1H), 7.74 (d, J = 1.6 Hz, 1H), 1.49 - 1.45 (m, 2H), 1.38 - 1.33 (m, 2H). LC / MS (ESI) m / z: 343 [M+H] + 。

[0807] Procedure 5: 8-Bromo-N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide To a solution of 8-bromo-N-(1-cyanocyclopropyl)imidazo[1,2-a]pyridine-6-sulfonamide (650 mg, 1.9 mmol) in N,N-dimethylformamide (5 mL) were added potassium carbonate (790 mg, 5.7 mmol) and 1-(chloromethyl)-4-methoxybenzene (454 mg, 2.9 mmol). The reaction mixture was stirred at 45 °C for 2 hours under a nitrogen gas atmosphere. After completion of the reaction, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 35% ethyl acetate) to obtain the title compound (yellow solid, 720 mg, yield 81.9%). LC / MS (ESI) m / z: 461 [M+H] + 。

[0808] Procedure 6: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide To a solution of 8-bromo-N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (570 mg, 1.24 mmol) and 2-methyl-1-(piperazin-1-yl)propan-1-one (386 mg, 2.47 mmol) in 1,4-dioxane (12 mL) were added cesium carbonate (805 mg, 2.47 mmol), RuPhos (115 mg, 0.25 mmol), and RuPhosPdG3 (103 mg, 0.12 mmol). The reaction mixture was reacted at 110 °C for 3 hours with stirring under a nitrogen gas atmosphere. After completion of the reaction, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0 - 4% methanol) to obtain the title compound (yellow solid, 530 mg, yield 79.9%). LC / MS (ESI) m / z: 537 [M+H] + 。

[0809] Procedure 7: 3-Bromo-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide At -10 °C, a solution of N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (530 mg, 0.99 mmol) in tetrahydrofuran (15 mL) was slowly added to a solution of N-bromosuccinimide (176 mg, 0.99 mmol) in tetrahydrofuran (7.5 mL). The mixture was stirred at room temperature for 30 minutes. The reaction solution was filtered and the filtrate was concentrated. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0 - 4% methanol) to obtain the title compound (yellow solid, 430 mg, yield 70.7%). LC / MS (ESI) m / z: 617 [M+H] + 。

[0810] Procedure 8: N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)-3-(2-methylthiazol-5-yl)imidazo[1,2-a]pyridine-6-sulfonamide 3-Bromo-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (50 mg, 0.08 mmol) and 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (37 mg, 0.16 mmol) were sequentially added to a mixed solution of 1,4-dioxane (3 mL) and water (0.6 mL), followed by potassium phosphate (52 mg, 0.24 mmol), XPhos (4 mg, 0.008 mmol), and XPhosPdG2 (6 mg, 0.008 mmol). The reaction mixture was stirred at 100 °C for 16 h under nitrogen gas protection. After completion of the reaction, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0 - 5% methanol) to obtain the title compound (yellow solid, 17 mg, yield 34.0%). LC / MS (ESI) m / z: 634 [M+H] + 。

[0811] Procedure 9: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-3-(2-methylthiazol-5-yl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, trifluoroacetic acid (0.1 mL) and trifluoromethanesulfonic acid (0.1 mL) were slowly added dropwise to a solution of N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)-3-(2-methylthiazol-5-yl)imidazo[1,2-a]pyridine-6-sulfonamide (17 mg, 0.03 mmol) in dichloromethane (0.5 mL). The mixture was stirred at room temperature for 30 min. The mixture was concentrated, and the residue was purified by preparative HPLC to obtain the title compound (white solid, 5 mg, yield 36.3%). 1HNMR(400MHz,DMSO-d6)δ8.38(d,J=1.2Hz,1H),8.01(s,1H),7.92(s,1H),6.77(d,J=1.1Hz,1H),3.77 - 3.57(m,8H),2.95(dt,J=13.5,6.7Hz,1H),2.78(s,3H),1.46(dd,J=8.3,5.4Hz,2H),1.33(dd,J=8.4,5.5Hz,2H),1.04(d,J=6.7Hz,6H).LC / MS(ESI)(m / z):514[M + H] + 。

[0812] Example 2: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-3-(5-methyl-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0813]

Chem.

[0814] Procedure 1: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)-3-(5-methyl-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide At room temperature, to a solution of 3-bromo-N-(1-cyanocyclopropyl)-N-[(4-methoxyphenyl)methyl]-8-[4-(2-methylpropionyl)piperazin-1-yl]imidazo[1,2-a]pyridine-6-sulfonamide (100 mg, 0.16 mmol) and 2-bromo-5-methyl-1,3,4-thiadiazole (58 mg, 0.32 mmol) in DMF (3 mL) were successively added hexamethylditin (0.067 mL, 0.324 mmol), CsF (49 mg, 0.32 mmol) and CuI (6.2 mg, 0.032 mmol). The reaction mixture was evacuated with nitrogen gas three times and then reacted with stirring at 100 °C for 16 h under nitrogen gas protection. After completion of the reaction, the mixture was cooled to room temperature, quenched by adding water, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: dichloromethane / methanol, gradient 0 - 3% methanol) to obtain the title compound (yellow solid, 30 mg, yield 29.1%). LC / MS (ESI) m / z: 635 [M+H] + 。

[0815] Procedure 2: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-3-(5-methyl-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide The title compound was obtained by referring to the preparation method of Step 9 of Example 1. 1 HNMR (400 MHz, DMSO-d6) δ 9.78 (s, 1H), 9.42 (s, 1H), 8.44 (s, 1H), 7.02 - 6.91 (m, 1H), 3.81 - 3.71 (m, 4H), 3.69 - 3.59 (m, 4H), 3.01 - 2.91 (m, 1H), 2.83 (s, 3H), 1.53 - 1.33 (m, 4H), 1.09 - 0.99 (m, 6H). LC / MS (ESI) (m / z): 515 [M+H] + 。

[0816] Example 3: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-3-(5-methylthiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0817] [Chem.]

[0818] Procedure 1: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)-3-(5-methylthiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide At room temperature, CuI (2 mg, 0.008 mmol), CsF (37 mg, 0.24 mmol) and Pd(PPh3)4 (9 mg, 0.008 mmol) were sequentially added to a solution of 3-bromo-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (50 mg, 0.08 mmol) and 5-methyl-2-(tri-n-butylstannyl)thiazole (63 mg, 0.16 mmol) in DMF (2 mL). After the mixture was replaced with nitrogen gas three times, the reaction was carried out for 2 hours with stirring at 100 °C under nitrogen gas protection. After completion of the reaction, it was cooled to room temperature, quenched by adding water, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: dichloromethane / methanol, gradient 0 - 4% methanol) to obtain the title compound (yellow solid, 30 mg, yield 58.2%). LC / MS (ESI) m / z: 634 [M+H] + .

[0819] Procedure 2: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-3-(5-methylthiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide The title compound was obtained by referring to the synthesis method of Step 9 of Example 1. 1HNMR(400MHz,DMSO-d6)δ9.80(s,1H),8.29(s,1H),7.76(s,1H),6.88(s,1H),3.80 - 3.56(m,8H),3.01 - 2.91(m,1H),2.54(s,3H),1.49 - 1.42(m,2H),1.40 - 1.33(m,2H),1.04(d,J = 6.3Hz,6H).LC / MS(ESI)(m / z):514[M + H] + 。

[0820] The following examples refer to the preparation methods of Examples 1, 2, and 3, starting from appropriate starting materials, synthesizing according to a similar route to obtain a crude product, separating the crude product by reverse-phase HPLC, and obtaining the title compound after lyophilization.

[0821]

Table 2

[0822] Example 7: N-(1-Cyanocyclopropyl)-3-(4-hydroxy-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0823]

Chem.

[0824] Procedure 1: Methyl 3-bromo-1-(4-ethoxy-4-oxobutyl)-1H-pyrazole-5-carboxylate At 0 °C, potassium carbonate (2 g, 14.6 mmol) and ethyl 4-bromobutyrate (2.3 g, 12 mmol) were added to a solution of methyl 3-bromo-1H-pyrazole-5-carboxylate (2.0 g, 9.7 mmol) in acetonitrile (20 mL). The mixture was reacted for 8 hours with stirring at 80 °C. After completion of the reaction, it was cooled to room temperature, ice water was added to quench the reaction, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 50% ethyl acetate) to obtain the title compound (white solid, 3.0 g, yield 96.4%).

[0825] Procedure 2: Methyl 2-bromo-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-5-carboxylate At 0 °C, potassium tert-butoxide (1.6 g, 14 mmol) was added to a solution of methyl 3-bromo-1-(4-ethoxy-4-oxobutyl)-1H-pyrazole-5-carboxylate (3 g, 9.4 mmol) in tetrahydrofuran (30 mL). After the mixture was replaced with nitrogen gas three times, it was reacted for 8 hours with stirring at 50 °C. After completion of the reaction, it was cooled to room temperature, the reaction solution was poured into ice water, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 20% ethyl acetate) to obtain the title compound (white solid, 1.4 g, yield 54.5%).

[0826] Procedure 3: 2-Bromo-6,7-dihydropyrazolo[1,5-a]pyridin-4(5H)-one At room temperature, methyl 2-bromo-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-5-carboxylate (1.4 g, 5.1 mmol) was added to concentrated hydrochloric acid (20 mL), and the reaction mixture was stirred at 90 °C for 16 h. After completion of the reaction, the reaction mixture was neutralized with 1 N aqueous sodium hydroxide solution at 0 °C and extracted twice with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 20% ethyl acetate) to obtain the title compound (colorless oil, 0.53 g, yield 48.1%). 1 HNMR(400MHz,CDCl3)δ6.77(s,1H),4.35-4.22(m,2H),2.69-2.57(m,2H),2.37-2.24(m,2H).LC / MS(ESI)m / z:216[M+H] + 。

[0827] Procedure 4: 2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydropyrazolo[1,5-a]pyridin-4(5H)-one Under a nitrogen gas atmosphere at room temperature, potassium acetate (760 mg, 7.5 mmol), XPhos (250 mg, 0.5 mmol) and Pd2(dba)3 (225 mg, 0.2 mmol) were added to a solution of 2-bromo-6,7-dihydropyrazolo[1,5-a]pyridin-4(5H)-one (530 mg, 2.5 mmol) and bis(pinacolato)diboron (1.25 g, 4.9 mmol) in 1,4-dioxane (10 mL). After the reaction mixture was replaced with nitrogen gas three times, the reaction was carried out with stirring at 80 °C for 3 h under nitrogen gas protection. After completion of the reaction, the reaction mixture was cooled to room temperature, ice water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 20% ethyl acetate) to obtain the title compound (colorless oil, 380 mg, yield 48.0%). LC / MS(ESI) m / z: 263 [M + H] + 。

[0828] Procedure 5: N-(1-Cyanochloropropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)-3-(4-carbonyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide Under protection of nitrogen gas at room temperature, potassium carbonate (120 mg, 0.8 mmol) and Pd(dppf)Cl2 (25 mg, 0.03 mmol) were added to a mixed solution of 3-bromo-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (150 mg, 0.26 mmol) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydropyrazolo[1,5-a]pyridin-4(5H)-one (120 mg, 0.5 mmol) in 1,4-dioxane (5 mL) and water (0.5 mL). The reaction solution was replaced with nitrogen gas three times, and then reacted at 90 °C for 3 hours under protection of nitrogen gas. After completion of the reaction, the reaction solution was diluted with ethyl acetate, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 20% ethyl acetate) to obtain the title compound (yellow solid, 110 mg, yield 28.7%). LC / MS (ESI) m / z: 671 [M+H] + 。

[0829] Procedure 6: N-(1-Cyanocyclopropyl)-3-(4-hydroxy-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide A solution of N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)-3-(4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide (100 mg, 0.1 mmol) in methanol (2 mL) was added sodium borohydride (10 mg, 0.3 mmol). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction was quenched with 1N dilute hydrochloric acid, and the reaction solution was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-20% ethyl acetate) to obtain the title compound (yellow solid, 70 mg, yield 80%). LC / MS (ESI) m / z: 673 [M+H] + 。

[0830] Procedure 7: N-(1-Cyanocyclopropyl)-3-(4-hydroxy-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide To a solution of N-(1-cyanocyclopropyl)-3-(4-hydroxy-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (30 mg, 0.04 mmol) in dichloromethane (0.5 mL) at 0 °C was added TfOH (0.1 mL), and the reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the mixture was concentrated until dry, and the residue was purified by preparative HPLC to obtain the title compound (white solid, 6.3 mg, yield 25.6%). 1HNMR (400 MHz, DMSO-d6) δ 9.58 (s, 1H), 8.08 (s, 1H), 6.76 (s, 1H), 6.75 (s, 1H), 5.58 (d, J = 5.5 Hz, 1H), 4.84 - 4.75 (m, 1H), 4.20 - 4.14 (m, 2H), 3.77 - 3.69 (m, 4H), 3.68 - 3.56 (m, 4H), 3.00 - 2.91 (m, 1H), 2.27 - 2.15 (m, 1H), 2.10 - 1.93 (m, 2H), 1.82 - 1.69 (m, 1H), 1.47 - 1.30 (m, 4H), 1.05 (d, J = 6.5 Hz, 6H). LC / MS (ESI) (m / z): 553 [M + H] + 。

[0831] Example 8: N-(1-Cyanocyclopropyl)-3-(4-fluoro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0832]

Chem.

[0833] Procedure 1: N-(1-Cyanocyclopropyl)-3-(4-fluoro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, diethylaminosulfur trifluoride (18 mg, 0.11 mmol) was added dropwise to a solution of N-(1-cyanocyclopropyl)-3-(4-hydroxy-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (40 mg, 0.06 mmol) in dichloromethane (0.5 mL). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was quenched with saturated aqueous sodium bicarbonate at 0 °C and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the title compound (yellow oil, 25 mg, yield 74.9%). The crude product was used directly in the next reaction. LC / MS (ESI) (m / z): 675 [M+H] + 。

[0834] Procedure 2: N-(1-Cyanocyclopropyl)-3-(4-fluoro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, TfOH (0.1 mL) was slowly added to a solution of N-(1-cyanocyclopropyl)-3-(4-fluoro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (20 mg, 0.03 mmol) in dichloromethane (0.5 mL). The reaction mixture was stirred at room temperature for 10 minutes. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and the crude product was purified by preparative HPLC to obtain the title compound (white solid, 0.5 mg, yield 2.4%). LC / MS (ESI) m / z: 555 [M+H] + 。

[0835] Example 9: N-(1-Cyanocyclopropyl)-3-(5-hydroxy-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-yl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0836]

Chem.

[0837] Procedure 1: 3-[(tert-Butyldimethylsilyl)oxy]-4-chlorobutyronitrile At 0 °C, imidazole (19 g, 281.0 mmol) and tert-butyldimethylchlorosilane (32 g, 210.7 mmol) were slowly added to a solution of 4-chloro-3-hydroxybutanenitrile (24 g, 200.7 mmol) in DMF (200 mL). After the reaction solution was replaced with nitrogen gas three times, the reaction was allowed to proceed overnight with stirring at room temperature under nitrogen gas protection. After completion of the reaction, the reaction solution was quenched with a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 10% ethyl acetate) to obtain the title compound (colorless oil, 45 g, yield 95.8%). 1 HNMR(400MHz,CDCl3)δ4.11 - 4.09(m,1H),3.55 - 3.43(m,2H),2.72 - 2.60(m,2H),0.89(d,J = 3.0Hz,9H),0.14(d,J = 3.0Hz,3H),0.11(d,J = 2.9Hz,3H).

[0838] Procedure 2: Ethyl 5-[(tert-butyldimethylsilyl)oxy]-6-chloro-3-oxohexanoate 3-[(tert-Butyldimethylsilyl)oxy]-4-chlorobutyronitrile (20 g, 85.5 mmol) was dissolved in tetrahydrofuran (200 mL), zinc powder (7.8 g, 119 mmol) and methanesulfonic acid (820 mg, 0.86 mmol) were added, and the reaction mixture was stirred at 75 °C for 10 minutes under nitrogen gas protection. Then, ethyl 2-bromoacetate (11.4 mL, 102.6 mmol) was added. The reaction mixture was further stirred at 75 °C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, poured into ice water, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 10% ethyl acetate) to obtain the title compound (colorless oil, 25 g, yield 90.5%).

[0839] Procedure 3: 5-(2-((tert-Butyldimethylsilyl)oxy)-3-chloropropyl)-1,2-dihydro-3H-pyrazol-3-one Hydrazine hydrate (3 mL) was added to ethyl 5-[(tert-butyldimethylsilyl)oxy]-6-chloro-3-oxohexanoate (12 g, 37.1 mmol). After the reaction mixture was replaced with nitrogen balloon three times, it was stirred at 65 °C for 3 hours under nitrogen gas protection. After completion of the reaction, the mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 50% ethyl acetate) to obtain the title compound (white solid, 8 g, yield 78.3%). 1 HNMR (400 MHz, DMSO-d6) δ 5.30 (s, 1H), 4.08 (dd, J = 11.0, 5.5 Hz, 1H), 3.59 - 3.54 (m, 1H), 3.52 - 3.48 (m, 1H), 2.72 (dd, J = 14.6, 5.7 Hz, 1H), 2.63 (dd, J = 14.6, 6.8 Hz, 1H), 0.83 (s, 9H), 0.04 (d, J = 2.9 Hz, 3H), -0.07 (s, 3H). LC / MS (ESI) (m / z): 289 [M + H] + 。

[0840] Step 4: 5-((tert-Butyldimethylsilyl)oxy]-5,6-dihydro-1H-pyrrolo[1,2-b]pyrazol-2(4H)-one At room temperature, cesium carbonate (5.0 g, 15.5 mmol) was added to a solution of 5-(2-((tert-butyldimethylsilyl)oxy)-3-chloropropyl)-1,2-dihydro-3H-pyrazol-3-one (3.8 g, 12.8 mmol) in acetonitrile (70 mL). The reaction solution was replaced with nitrogen balloon three times, and then reacted at 60 °C for 8 hours with stirring under nitrogen gas protection. After completion of the reaction, it was cooled to room temperature, diluted by adding water, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 50% ethyl acetate) to obtain the title compound (white solid, 2.5 g, yield 76.5%). 1 HNMR(400MHz,CDCl3)δ5.26(s,1H),4.86 - 4.81(m,1H),4.06(dd,J = 10.3,6.4Hz,1H),3.71(dd,J = 10.3,3.8Hz,1H),3.02(dd,J = 16.2,7.0Hz,1H),2.64(dd,J = 16.2,3.8Hz,1H),0.79(s,9H),0.00(s,6H).LC / MS(ESI)(m / z):255[M + H] + 。

[0841] Step 5: 5-((tert-Butyldimethylsilyl)oxy)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-yl-trifluoromethanesulfonate At 0 °C, triethylamine (1.8 mL, 12.9 mmol) was added to a solution of 5-((tert-butyldimethylsilyl)oxy)-5,6-dihydro-1H-pyrrolo[1,2-b]pyrazol-2(4H)-one (1.1 g, 4.3 mmol) in dichloromethane (10 mL), and trifluoromethanesulfonic anhydride (1.1 mL, 6.5 mmol) was slowly added dropwise. The reaction mixture was stirred at room temperature for 1.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 10% ethyl acetate) to obtain the title compound (colorless oil, 1.3 g, yield 77.8%). LC / MS (ESI) (m / z): 387 [M+H] + 。

[0842] Procedure 6: 5-((tert-Butyldimethylsilyl)oxy]-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole At room temperature, bis(pinacolato)diboron (591 mg, 2.3 mmol), potassium acetate (457 mg, 4.6 mmol), XPhos (148 mg, 0.3 mmol) and Pd2(dba)3 (142 mg, 0.16 mmol) were successively added to a solution of 5-((tert-butyldimethylsilyl)oxy)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-yl-trifluoromethanesulfonate (600 mg, 1.5 mmol) in 1,4-dioxane (10 mL). After the reaction solution was replaced with nitrogen gas three times, the reaction was carried out with stirring at 80 °C for 8 hours under nitrogen gas protection. After completion of the reaction, it was cooled to room temperature, diluted by adding water, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 30% ethyl acetate) to obtain the title compound (white solid, 400 mg, yield 70.7%). LC / MS (ESI) (m / z): 365 [M+H] + 。

[0843] Procedure 7: 3-(5-((tert-Butyldimethylsilyl)oxy)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-yl)-N-(1-cyanocyclopropyl)-8-4-(isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide The title compound was obtained with reference to the preparation method of Step 5 in Example 7 (white solid, 160 mg, yield 48.9%). LC / MS (ESI) (m / z): 774 [M+H] + 。

[0844] Procedure 8: N-(1-Cyanocyclopropyl)-3-(5-hydroxy-5,6-dihydro-4H-pyrrolo[1,2-a]pyrazol-2-yl)-8-4-(isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, tetra-n-butylammonium fluoride (108 mg, 0.4 mmol) was added to a solution of 3-(5-((tert-butyldimethylsilyl)oxy)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-yl)-N-(1-cyanocyclopropyl)-8-4-(isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (160 mg, 0.2 mmol) in tetrahydrofuran (2 mL). After that, the reaction solution was stirred at room temperature for 30 minutes. The reaction solution was diluted with ethyl acetate, washed successively with saturated aqueous ammonium chloride solution and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 50 - 100% ethyl acetate) to obtain the title compound (white solid, 120 mg, yield 88%). 1HNMR (400 MHz, CD3OD) δ 9.68 (s, 1H), 7.95 (s, 1H), 7.24 (d, J = 7.8 Hz, 2H), 6.82 - 6.78 (m, 3H), 6.52 (s, 1H), 5.08 - 5.04 (m, 1H), 4.53 - 4.51 (m, 2H), 4.47 - 4.43 (m, 1H), 4.12 - 4.08 (m, 2H), 3.87 - 3.84 (m, 4H), 3.75 - 3.73 (m, 3H), 3.56 - 3.52 (m, 2H), 3.47 - 3.44 (m, 2H), 3.04 - 2.99 (m, 1H), 2.91 - 2.86 (m, 1H), 1.49 - 1.43 (m, 4H), 1.14 (d, J = 6.6 Hz, 6H). LC / MS (ESI) (m / z): 660 [M + H] + 。

[0845] Procedure 9: N-(1-Cyanocyclopropyl)-3-(5-hydroxy-5,6-dihydro-4H-pyrrolo[1,2-a]pyrazol-2-yl)-8-(4-isobutyrylpiperazin-1-yl)-imidazo[1,2-a]pyridine-6-sulfonamide Prepared with reference to the preparation method of Procedure 7 of Example 7 to obtain the title compound (white solid, 4 mg, yield 25.4%). 1 HNMR (400 MHz, DMSO-d6) δ 9.55 (s, 1H), 8.04 (s, 1H), 6.76 (s, 1H), 6.59 (s, 1H), 5.67 - 5.62 (m, 1H), 4.98 - 4.93 (m, 1H), 4.45 - 4.40 (m, 1H), 4.02 - 3.97 (m, 1H), 3.76 - 3.69 (m, 4H), 3.66 - 3.53 (m, 5H), 2.98 - 2.93 (m, 1H), 2.79 - 2.74 (m, 1H), 1.44 - 1.39 (m, 2H), 1.33 - 1.28 (m, 2H), 1.04 (d, J = 6.3 Hz, 6H). LC / MS (ESI) (m / z): 539 [M + H] + 。

[0846] Example 10: N-(1-Cyanocyclopropyl)-3-(5-fluoro-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-yl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0847]

Chem.

[0848] Prepared with reference to the preparation method of Example 8 to obtain the title compound (white solid, 6 mg, yield 24.4%). 1 HNMR(400MHz,DMSO-d6)δ9.57(s,1H),9.28(s,1H),8.09(s,1H),6.77(s,1H),6.69(s,1H),5.92(d,J=52.3Hz,1H),4.62 - 4.41(m,2H),3.76 - 3.65(m,6H),3.60 - 3.54(m,2H),3.47 - 3.39(m,1H),3.18 - 3.11(m,1H),2.98 - 2.91(m,1H),1.48 - 1.43(m,2H),1.37 - 1.33(m,2H),1.04(d,J=6.4Hz,6H).LC / MS(ESI)(m / z):541[M + H] + 。

[0849] Example 11: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0850]

Chem.

[0851] Procedure 1: 8-Bromo-N-(1-cyanocyclopropyl)-3-formylimidazo[1,2-a]pyridine-6-sulfonamide To a solution of 6-amino-5-bromo-N-(1-cyanopropyl)pyridine-3-sulfonamide (1.5 g, 4.7 mmol) in acetonitrile (15 mL) was slowly added 2-bromomalonaldehyde (710 mg, 4.7 mmol). The reaction mixture was stirred at room temperature for 16 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 60% ethyl acetate) to give the title compound (yellow solid, 960 mg, yield 59.5%). 1 HNMR (400 MHz, DMSO-d6) δ 10.07 (s, 1H), 9.84 (d, J = 1.6 Hz, 1H), 9.60 (s, 1H), 8.76 (s, 1H), 8.17 (d, J = 1.6 Hz, 1H), 1.54 - 1.47 (m, 2H), 1.40 - 1.35 (m, 2H). LC / MS (ESI) m / z: 369 [M + H] + 。

[0852] Procedure 2: 8-Bromo-N-(1-cyanopropyl)-3-formyl-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide To a solution of 8-bromo-N-(1-cyanopropyl)-3-formylimidazo[1,2-a]pyridine-6-sulfonamide (960 mg, 2.6 mmol) in N,N-dimethylformamide (8 mL) were slowly added K2CO3 (1.1 g, 7.8 mmol) and 4-methoxybenzyl chloride (611 mg, 3.9 mmol). The reaction mixture was reacted for 16 h with stirring at 45 °C under nitrogen gas protection. After completion of the reaction, it was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure until dry. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 45% ethyl acetate) to give the title compound (yellow solid, 800 mg, yield 62.9%). LC / MS (ESI) m / z: 489 [M + H] + 。

[0853] Procedure 3: 8-Bromo-6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)imidazo[1,2-a]pyridine-3-carboxylic acid At 0 °C, 8-bromo-N-(1-cyanocyclopropyl)-3-formyl-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (800 mg, 1.6 mmol) was dissolved in a mixed solution of tert-butanol (6 mL), tetrahydrofuran (3 mL) and water (2 mL), and sodium dihydrogen phosphate (981 mg, 8.2 mmol), 2-methylbut-2-ene (917 mg, 13.1 mmol) and sodium chlorite (370 mg, 4.1 mmol) were added successively. The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, water was added, the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0 - 4% methanol) to obtain the title compound (yellow solid, 400 mg, yield 48.2%). LC / MS (ESI) m / z: 505 [M+H] + 。

[0854] Procedure 4: 2-(8-Bromo-6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)imidazo[1,2-a]pyridine-3-carbonyl)hydrazine-1-carboxylic acid tert-butyl ester At room temperature, to a solution of 8-bromo-6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)imidazo[1,2-a]pyridine-3-carboxylic acid (400 mg, 0.79 mmol) and N'-[(tert-butoxy)carbonyl](tert-butoxy)formylhydrazide (115 mg, 0.87 mmol) in N,N-dimethylformamide (4 mL) were successively added N,N-diisopropylethylamine (307 mg, 2.38 mmol) and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (331 mg, 0.87 mmol). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 45% ethyl acetate) to obtain the title compound (yellow solid, 260 mg, yield 53.1%). LC / MS(ESI)(m / z): 619[M+H] + 。

[0855] Procedure 5: 8-Bromo-N-(1-cyanocyclopropyl)-3-(hydrazinecarbonyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, trifluoroacetic acid (1 mL) was slowly added to a solution of tert-butyl 2-(8-bromo-6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)imidazo[1,2-a]pyridine-3-carbonyl)hydrazine-1-carboxylate (260 mg, 0.42 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, it was concentrated under reduced pressure to obtain the title compound (yellow oil, 220 mg, yield 100%). LC / MS(ESI)(m / z): 519[M+H] + 。

[0856] Procedure 6: 8-Bromo-N-(1-cyanocyclopropyl)-3-(2-(2,2-difluoroacetyl)hydrazine-1-carbonyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, 2,2-difluoroacetyl-2,2-difluoroacetate (62 mg, 0.47 mmol) was slowly added dropwise to a solution of 8-bromo-N-(1-cyanocyclopropyl)-3-(hydrazinecarbonyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (220 mg, 0.42 mmol) in dichloromethane (3 mL). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, it was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 50% ethyl acetate) to obtain the title compound (yellow solid, 195 mg, yield 77.1%). LC / MS (ESI) (m / z): 597 [M+H] + 。

[0857] Procedure 7: 8-Bromo-N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide Under nitrogen gas protection at room temperature, Lawesson's reagent (52 mg, 0.13 mmol) was added to a solution of 8-bromo-N-(1-cyanocyclopropyl)-3-(2-(2,2-difluoroacetyl)hydrazine-1-carbonyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (70 mg, 0.12 mmol) in toluene (1 mL). The reaction mixture was reacted at 110 °C for 4 hours under nitrogen gas protection. After completion of the reaction, it was cooled to room temperature, the reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate solution and saturated brine respectively, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 55% ethyl acetate) to obtain the title compound (yellow solid, 35 mg, yield 50%). LC / MS (ESI) (m / z): 595 [M+H] + 。

[0858] Step 8: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide Under nitrogen gas protection at room temperature, cesium carbonate (38 mg, 0.12 mmol), RuPhos (5 mg, 0.012 mmol) and RuPhosPdG3 (5 mg, 0.006 mmol) were added to a solution of 8-bromo-N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (35 mg, 0.06 mmol) and 2-methyl-1-(piperazin-1-yl)propan-1-one (18 mg, 0.12 mmol) in 1,4-dioxane (1 mL). After the reaction solution was replaced with nitrogen gas three times, the reaction was carried out with stirring at 110 °C for 3 hours under nitrogen gas protection. After the reaction was completed, it was cooled to room temperature, water was added, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0 - 4% methanol) to obtain the title compound (yellow solid, 24 mg, yield 60%). LC / MS (ESI) m / z: 671 [M+H] + 。

[0859] Step 9: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, trifluoroacetic acid (0.5 mL) and trifluoromethanesulfonic acid (0.1 mL) were slowly added to a solution of N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (24 mg, 0.04 mmol) in dichloromethane (0.5 mL). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, it was concentrated under reduced pressure. The residue was purified by preparative HPLC (C 18 , an H2O solution of 10 - 80% acetonitrile and 0.1% HCOOH) to obtain the title compound (white solid, 3 mg, yield 15.2%). 1 1H NMR (400 MHz, DMSO-d6) δ 9.75 (d, J = 1.2 Hz, 1H), 8.66 (s, 1H), 7.70 (t, J = 53.2 Hz, 1H), 7.00 (s, 1H), 3.81 - 3.59 (m, 8H), 3.00 - 2.91 (m, 1H), 1.50 - 1.41 (m, 2H), 1.41 - 1.34 (m, 2H), 1.05 (s, 3H), 1.03 (s, 3H). LC / MS (ESI) (m / z): 551 [M + H] + .

[0860] Example 12: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0861]

Chemical Structure

[0862] Procedure 1: tert-Butyl 4-(6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridin-8-yl)-3,6-dihydropyridine-1(2H)-carboxylate At room temperature, to a mixed solution of 8-bromo-N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(4-methoxybenzyl)imidazo[1,2]pyridine-6-sulfonamide (60 mg, 0.10 mmol) in 1,4-dioxane (2.4 mL) and water (0.4 mL) were successively added sodium carbonate (32 mg, 0.30 mmol), N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester (62 mg, 0.20 mmol), and Pd(dppf)Cl2 (7 mg, 0.01 mmol). After the reaction solution was replaced with nitrogen gas three times, the reaction was carried out for 4 hours with stirring at 90 °C under nitrogen gas protection. After completion of the reaction, the reaction solution was cooled to room temperature, diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate / petroleum ether, gradient 0 - 50% ethyl acetate) to obtain the title compound (yellow oil, 65 mg, yield 92.4%). LC / MS(ESI)(m / z): 698[M+H] + 。

[0863] Procedure 2: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(4-methoxybenzyl)-8-(1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine-6-sulfonamide In an ice bath, trifluoroacetic acid (0.4 mL) was slowly added to a solution of tert-butyl 4-(6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridin-8-yl)-3,6-dihydropyridine-1(2H)-carboxylate (65 mg, 0.09 mmol) in dichloromethane (1.2 mL), and the reaction solution was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction solution was directly concentrated to obtain the title compound (yellow oil, 60 mg, yield 100%). The product was directly used in the next reaction. LC / MS(ESI)(m / z): 598[M+H]+ .

[0864] Procedure 3: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, triethylamine (0.02 mL, 0.16 mmol) and isobutyryl chloride (0.01 mL, 0.12 mmol) were successively added to a solution of N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(4-methoxybenzyl)-8-(1,2,3),6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine-6-sulfonamide (60 mg, 0.09 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, it was cooled to room temperature, quenched by adding water, extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to obtain the title compound (yellow solid, 35 mg, yield 56.3%). LC / MS (ESI) (m / z): 668 [M+H] + .

[0865] Procedure 4: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(1-isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine-6-sulfonamide The title compound was obtained by referring to the synthesis method of Procedure 11 in Example 11. 1HNMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 9.56 (s, 1H), 8.79 (s, 1H), 7.86 - 7.58 (m, 2H), 7.38 (d, J = 29.4 Hz, 1H), 4.33 (d, J = 54.7 Hz, 2H), 3.81 (d, 2H), 3.04 - 2.91 (m, 1H), 2.74 (d, J = 51.4 Hz, 2H), 1.48 (d, J = 4.0 Hz, 2H), 1.40 (d, J = 4.6 Hz, 2H), 1.07 (d, J = 6.6 Hz, 6H). LC / MS (ESI) (m / z): 548 [M + H] + 。

[0866] Example 13: 8-(2-Acetyl-2-azaspiro[3.4]oct-6-en-6-yl)-N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0867]

Chemical formula

[0868] The title compound was obtained by referring to the synthesis method of Example 12 and substituting 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-azaspiro[3.4]oct-6-ene-2-carboxylic acid tert-butyl ester with N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester to obtain the target molecule. 1 HNMR (400 MHz, DMSO-d6) δ 10.08 (d, J = 1.7 Hz, 1H), 8.81 (s, 1H), 7.87 - 7.55 (m, 3H), 4.30 (d, J = 8.4 Hz, 1H), 4.18 (d, J = 8.3 Hz, 1H), 3.97 (d, J = 9.5 Hz, 1H), 3.90 (d, J = 9.5 Hz, 1H), 2.95 (t, J = 6.8 Hz, 2H), 2.36 (t, 2H), 1.80 (s, 3H), 1.52 - 1.46 (m, 2H), 1.43 - 1.35 (m, 2H). LC / MS (ESI) (m / z): 546 [M + H] + 。

[0869] Example 14: 3-(5-(Difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-(fluoromethyl)cyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0870]

Chemical formula

[0871] Procedure 1: Ethyl 8-bromo-6-iodoimidazo[1,2-a]pyridine-3-carboxylate Ethyl 2-chloro-3-oxopropionate (4 g, 13.4 mmol) was added dropwise to a mixed solution of 3-bromo-5-iodopyridin-2-amine (4 g, 13.4 mmol) in ethanol (20 mL) and water (20 mL). The reaction system was stirred at 90 °C overnight under nitrogen gas protection. Then it was cooled to room temperature, the mixture was filtered, and the filter cake was dried under reduced pressure to obtain the target molecule (white solid, 4 g, yield 75.7%), and this product was directly used in the next reaction. 1 HNMR(400MHz,CDCl3)δ9.54(d,J=1.4Hz,1H),8.21(s,1H),7.84(d,J=1.4Hz,1H),4.45-4.32(m,2H),1.39(t,J=7.1Hz,3H).LC / MS(ESI)(m / z):395[M+H] + 。

[0872] Procedure 2: Ethyl 6-(benzylthio)-8-bromoimidazo[1,2-a]pyridine-3-carboxylate To a solution of ethyl 8-bromo-6-iodoimidazo[1,2-a]pyridine-3-carboxylate (4 g, 10.1 mmol) in 1,4-dioxane (80 mL) was added dropwise N,N-diisopropylethylamine (3.9 g, 30.3 mmol), and then benzenethiol (1.3 g, 10.1 mmol), XantPhos (579 mg, 1.0 mmol) and Pd2(dba)3 (467 mg, 0.51 mmol) were added under nitrogen gas protection, respectively. The mixture was replaced with nitrogen gas three times, and reacted for 2 hours with stirring at 70 °C under nitrogen gas protection. The reaction solution was diluted with ethyl acetate, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to obtain a crude product. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient 0 - 15% ethyl acetate) to obtain the title compound (yellow solid, 3.5 g, yield 88.3%). LC / MS(ESI)(m / z): 393 [M+H] + 。

[0873] Procedure 3: 6-(Benzylthio)-8-bromoimidazo[1,2-a]pyridine-3-carboxylic acid At 0 °C, sodium hydroxide (82 mg, 2.04 mmol) was added to a solution of ethyl 6-(benzylthio)-8-bromoimidazo[1,2-a]pyridine-3-carboxylate (400 mg, 1.02 mmol) in methanol (1.5 mL), tetrahydrofuran (1.5 mL) and water (1.5 mL), and the reaction solution was reacted for 1 hour with stirring at 45 °C. The reaction solution was diluted with water, acidified to pH ~ 5 with 1N hydrochloric acid, and extracted twice with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the target molecule (yellow solid, 350 mg, yield 94.3%), and the crude product was directly used in the next reaction. LC / MS(ESI)(m / z): 365 [M+H] + 。

[0874] Procedure 4: 2-(6-(Benzylthio)-8-bromoimidazo[1,2-a]pyridine-3-carbonyl)hydrazine-1-carboxylic acid tert-butyl ester To a solution of 6-(benzylthio)-8-bromoimidazo[1,2-a]pyridine-3-carboxylic acid (350 mg, 0.96 mmol) and tert-butyl carbazate (127 mg, 0.96 mmol) in DMF (4 mL), N,N-diisopropylethylamine (373 mg, 2.89 mmol) and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (403 mg, 1.06 mmol) were sequentially added, and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate / petroleum ether, gradient 0 - 50% ethyl acetate) to obtain the title compound (yellow solid, 440 mg, yield 95.7%). LC / MS (ESI) (m / z): 479 [M+H] + 。

[0875] Procedure 5: 6-(Benzylthio)-8-bromoimidazo[1,2-a]pyridine-3-carbohydrazide At 0 °C, trifluoroacetic acid (1 mL) was added dropwise to a solution of tert-butyl 2-(6-(benzylthio)-8-bromoimidazo[1,2-a]pyridine-3-carbonyl)hydrazine-1-carboxylate (440 mg, 0.92 mmol) in dichloromethane (3 mL), and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure to obtain the target product (yellow oil, 348 mg, yield 100%), and the crude product was used directly in the next reaction. LC / MS (ESI) (m / z): 379 [M+H] + 。

[0876] Procedure 6: 6-(Benzylthio)-8-bromo-N'-(2,2-difluoroacetyl)imidazo[1,2-a]pyridine-3-carbohydrazide At 0 °C, 2,2-difluoroacetyl-2,2-difluoroacetate (160 mg, 0.92 mmol) was added dropwise to a solution of 6-(benzylthio)-8-bromoimidazo[1,2-a]pyridine-3-carbohydrazide (348 mg, 0.92 mmol) in dichloromethane (4 mL). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was diluted with dichloromethane, washed successively with saturated sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated until dry. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient 0 - 50% ethyl acetate) to obtain the target product (yellow solid, 350 mg, yield 83.3%). LC / MS (ESI) (m / z): 457 [M+H] + 。

[0877] Procedure 7: 2-(6-(Benzylthio)-8-bromoimidazo[1,2-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole Under nitrogen gas protection, Lawesson's reagent (326 mg, 0.81 mmol) was added to a solution of 6-(benzylthio)-8-bromo-N'-(2,2-difluoroacetyl)imidazo[1,2-a]pyridine-3-carbohydrazide (350 mg, 0.77 mmol) in toluene (4 mL). The reaction mixture was replaced with nitrogen gas three times, and then reacted with stirring at 110 °C for 2 hours under nitrogen gas protection. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient 0 - 30% ethyl acetate) to obtain the target product (yellow solid, 310 mg, yield 89%). LC / MS (ESI) (m / z): 455 [M+H] + 。

[0878] Procedure 8: 8-Bromo-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonyl chloride At 0 °C, acetic acid (0.1 mL) and water (0.05 mL) were successively added to a solution of 2-(6-(benzylthio)-8-bromoimidazo[1,2-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole (310 mg, 0.68 mmol) in dichloromethane (3 mL), and then sulfonyl chloride (369 mg, 2.74 mmol) was slowly added dropwise. The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with dichloromethane, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to obtain the target product (yellow oil, 294 mg, yield 100%), and the crude product was directly used in the next reaction. LC / MS (ESI) (m / z): 431 [M+H] + .

[0879] Procedure 9: 8-Bromo-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-(fluoromethyl)cyclopropyl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, 8-bromo-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,2-a]pyridine-6-sulfonyl chloride (294 mg, 0.68 mmol) was added to a solution of 1-(fluoromethyl)cyclopropyl-1-amine hydrochloride (172 mg, 1.37 mmol) in pyridine (3 mL), and then the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient 0 - 45% ethyl acetate) to obtain the target molecule (yellow solid, 100 mg, yield 30.3%). LC / MS (ESI) m / z: 484 [M+H] + .

[0880] Procedure 10: 8-Bromo-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-(fluoromethyl)cyclopropyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide A solution of 8-bromo-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-(fluoromethyl)cyclopropyl)imidazo[1,2-a]pyridine-6-sulfonamide (100 mg, 0.21 mmol) in N,N-dimethylformamide (2 mL) was sequentially added with potassium carbonate (86 mg, 0.63 mmol) and 1-(chloromethyl)-4-methoxybenzene (49 mg, 0.31 mmol), and the reaction mixture was stirred at 45 °C for 2 hours. The mixture was diluted with ethyl acetate, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient 0 - 35% ethyl acetate) to obtain the target product (yellow solid, 75 mg, yield 60%). LC / MS (ESI) m / z: 604 [M+H] + 。

[0881] Procedure 11: 3-(5-(Difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-(fluoromethyl)cyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide Under nitrogen gas protection, to a solution of 8-bromo-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-(fluoromethyl)cyclopropyl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (75 mg, 0.12 mmol) in 1,4-dioxane (2 mL), 2-methyl-1-(piperazin-1-yl)propan-1-one (39 mg, 0.25 mmol), cesium carbonate (81 mg, 0.25 mmol), RuPhos (12 mg, 0.02 mmol) and RuPhosPdG3 (10 mg, 0.01 mmol) were added successively. The reaction mixture was replaced with nitrogen gas three times and reacted at 100 °C for 3 hours with stirring under nitrogen gas protection. The reaction mixture was diluted with ethyl acetate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient 0 - 75% ethyl acetate) to obtain the target product (yellow solid, 60 mg, yield 71.1%). LC / MS (ESI) m / z: 678 [M+H] + 。

[0882] Procedure 12: 3-(5-(Difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-(fluoromethyl)cyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, to a solution of 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1-(fluoromethyl)cyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (60 mg, 0.09 mmol) in dichloromethane (0.5 mL), trifluoroacetic acid (0.5 mL) and trifluoromethanesulfonic acid (0.1 mL) were added successively. Then the reaction mixture was reacted at room temperature for 30 minutes with stirring. The mixture was concentrated until dry, and the residue was purified by preparative HPLC to obtain the target molecule (white solid, 16 mg, yield 32.4%). 1HNMR(400MHz,DMSO-d6)δ9.64(s,1H),8.79(s,1H),8.61(s,1H),7.83 - 7.51(m,1H),7.00(s,1H),4.27(s,1H),4.15(s,1H),3.67(dd,J = 50.5,26.4Hz,8H),2.95(dt,J = 13.4,6.6Hz,1H),1.04(d,J = 6.7Hz,6H),0.85 - 0.80(m,2H),0.80 - 0.74(m,2H). LC / MS(ESI)(m / z):558[M + H] + 。

[0883] The following examples refer to the preparation method of Example 14, starting from appropriate starting materials, synthesizing according to a similar route to obtain a crude product, separating the crude product by reverse-phase HPLC, and obtaining the title compound after lyophilization.

[0884]

Table 3

[0885] Example 18: 3-(1-Acryloyl-2,5-dihydro-1H-pyrrol-3-yl)-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0886]

Chemical formula

[0887] Procedure 1: tert-Butyl 3-(6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridin-3-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate At room temperature, to a mixed solution of 3-bromo-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (100 mg, 0.16 mmol), 1-tert-butoxycarbonyl-2,5-dihydro-1H-pyrrole-3-boronic acid pinacol ester (65 mg, 0.21 mmol) in 1,4-dioxane (3 mL) and water (1 mL), potassium carbonate (67 mg, 0.48 mmol) and Pd(dppf)Cl2 (11 mg, 0.02 mmol) were sequentially added. After the reaction solution was replaced with nitrogen gas three times, the reaction was carried out for 4 hours with stirring at 80 °C under nitrogen gas protection. After the reaction was completed, it was cooled to room temperature, diluted by adding water, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient 0 - 55% ethyl acetate) to obtain the target product (white solid, 80 mg, yield 69.9%). LC / MS(ESI)(m / z): 704[M+H] + 。

[0888] Procedure 2: N-(1-Cyanocyclopropyl)-3-(2,5-dihydro-1H-pyrrol-3-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide trifluoroacetate At 0 °C, trifluoroacetic acid (1 mL) was slowly added dropwise to a solution of tert-butyl 3-(6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridin-3-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate (80 mg, 0.11 mmol) in dichloromethane (2 mL). The reaction solution was stirred at room temperature for 1.5 hours. After the reaction was completed, the reaction solution was directly concentrated under reduced pressure to obtain the title compound (yellow oil, 80 mg, yield 100%), and the crude product was directly used in the next reaction. LC / MS(ESI)(m / z): 604[M+H] + 。

[0889] Step 3: 3-(1-Acryloyl-2,5-dihydro-1H-pyrrol-3-yl)-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, triethylamine (0.1 mL, 0.3 mmol) and acryloyl chloride (0.01 mL, 0.15 mmol) were added dropwise to a solution of N-(1-cyanocyclopropyl)-3-(2,5-dihydro-1H-pyrrol-3-yl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide trifluoroacetate (80 mg, 0.11 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 1.5 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (using ethyl acetate / petroleum ether as the eluent, gradient 0 - 50% ethyl acetate) to obtain the target product (white solid, 40 mg, yield 61.19%). LC / MS (ESI) (m / z): 658 [M+H] + 。

[0890] Step 4: 3-(1-Acryloyl-2,5-dihydro-1H-pyrrol-3-yl)-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide At 0 °C, trifluoroacetic acid (0.05 mL) and trifluoromethanesulfonic acid (0.05 mL) were slowly added dropwise to a solution of 3-(1-acryloyl-2,5-dihydro-1H-pyrrol-3-yl)-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-N-(4-methoxybenzyl)imidazo[1,2-a]pyridine-6-sulfonamide (40 mg, 0.06 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at 0 °C for 2 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to obtain the title compound (white solid, 12 mg, yield 36.7%). 1HNMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 8.59 (dd, J = 3.7, 1.3 Hz, 1H), 7.88 (d, J = 26.9 Hz, 1H), 6.80 (s, 1H), 6.74 - 6.62 (m, 1H), 6.39 (s, 1H), 6.25 (dd, J = 16.8, 2.2 Hz, 1H), 5.81 - 5.75 (m, 1H), 4.96 - 4.86 (m, 1H), 4.70 (d, J = 9.4 Hz, 2H), 4.51 - 4.46 (m, 1H), 3.77 - 3.66 (m, 6H), 3.60 - 3.55 (m, 2H), 2.98 - 2.93 (m, 1H), 1.51 - 1.46 (m, 2H), 1.39 - 1.35 (m, 2H), 1.04 (d, J = 6.7 Hz, 6H). LC / MS (ESI) (m / z): 538 [M + H] + 。

[0891] Example 19: 3-(1-Allylpiperidin-3-yl)-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0892]

Chem.

[0893] Procedure 1: tert-Butyl 3-{6-[(1-cyanocyclopropyl)[(4-methoxyphenyl)methyl]sulfamoyl]-8-[4-(2-methylpropanoyl)piperazin-1-yl]imidazo[1,2-a]pyridin-3-yl}pyrrolidine-1-carboxylate Under nitrogen gas protection, Pd / C (12 mg, mass fraction 10%) was slowly added to a solution of tert-butyl 3-(6-(N-(1-cyanocyclopropyl)-N-(4-methoxybenzyl)sulfamoyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridin-3-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate (80 mg, 0.11 mmol) in methanol (5 mL). After the reaction solution was replaced with nitrogen gas three times, the reaction was carried out for 9 hours with stirring at room temperature under a hydrogen balloon. After completion of the reaction, the mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (white solid, 78 mg, yield 95.8%). LC / MS (ESI) m / z: 706 [M+H] + 。

[0894] Procedure 2-4: 3-(1-Allyl-3-pyrrolidinyl)-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide Referring to the synthetic method of Procedure 2-4 in Example 18, the title compound (white solid, yield 36.7%) was obtained. 1 HNMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 7.0 Hz, 1H), 8.54 - 8.46 (m, 1H), 7.57 (d, J = 7.9 Hz, 1H), 6.69 - 6.67 (m, 1H), 6.67 - 6.58 (m, 1H), 6.21 - 6.13 (m, 1H), 5.73 - 5.65 (m, 1H), 4.19 - 3.88 (m, 2H), 3.83 - 3.63 (m, 8H), 3.59 - 3.53 (m, 2H), 3.50 - 3.42 (m, 1H), 2.98 - 2.91 (m, 1H), 2.46 - 2.31 (m, 1H), 2.15 - 2.01 (m, 1H), 1.49 - 1.43 (m, 2H), 1.41 - 1.34 (m, 2H), 1.04 (d, J = 6.7 Hz, 6H). LC / MS (ESI) (m / z): 540 [M+H] + 。

[0895] Example 20: N-(1-Cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)-3-(1-propionyl-2,5-dihydro-1H-pyrrol-3-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0896]

Chem.

[0897] Referring to the synthetic method of Step 3-4 of Example 18, acryloyl chloride was replaced with propionyl chloride to obtain the title compound (white solid, yield 20.4%). 1 HNMR(400MHz, DMSO-d6) δ 8.56 (d, J = 5.1Hz, 1H), 7.84 (d, J = 22.2Hz, 1H), 6.79 (s, 1H), 6.36 (s, 1H), 4.76 (s, 1H), 4.58 (s, 2H), 4.40 (s, 1H), 3.79 - 3.68 (m, 4H), 3.66 - 3.54 (m, 4H), 2.96 - 2.89 (m, 1H), 2.40 - 2.33 (m, 2H), 1.43 (s, 2H), 1.35 - 1.29 (m, 2H), 1.08 - 1.02 (m, 9H). LC / MS(ESI) (m / z): 540 [M + H] + 。

[0898] Example 21: 3-(1-Acryloyl-1,2,3,6-tetrahydropyridin-4-yl)-N-(1-cyanocyclopropyl)-8-(4-isobutyrylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide

[0899]

Chem.

[0900] Referring to the synthetic method of Example 18, 1-tert-butoxycarbonyl-2,5-dihydro-1H-pyrrole-3-boronic acid pinacol ester was replaced with N-tert-butoxycarbonyl-3,6-dihydro-2H-pyridine-4-boronic acid pinacol ester to obtain the title compound (white solid, yield 28.5%).1 HNMR (400 MHz, DMSO-d6) δ 9.28 (s, 1H), 8.48 (s, 1H), 7.73 (s, 1H), 6.98 - 6.81 (m, 1H), 6.70 (s, 1H), 6.25 - 6.14 (m, 2H), 5.80 - 5.70 (m, 1H), 4.44 - 4.25 (m, 2H), 3.90 - 3.79 (m, 2H), 3.76 - 3.66 (m, 4H), 3.66 - 3.52 (m, 4H), 2.98 - 2.91 (m, 1H), 2.64 - 2.54 (m, 2H), 1.51 - 1.44 (m, 2H), 1.39 - 1.33 (m, 2H), 1.04 (d, J = 6.7 Hz, 6H). LC / MS (ESI) (m / z): 552 [M + H] + 。

[0901] Example 22: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-1-(2-azaspiro[3.4]oct-6-en-6-yl)-imidazo[1,5-a]pyridine-6-sulfonamide

[0902]

Chem.

[0903] Procedure 1: N-((5-Bromopyridin-2-yl)methylene)-2-methylpropane-2-sulfinamide At room temperature, cesium carbonate (21 g, 64.5 mmol) and tert-butylsulfinamide (6.5 g, 53.8 mmol) were successively added to a solution of 5-bromo-2-pyridinecarboxaldehyde (10 g, 53.7 mmol) in dichloromethane (110 mL). The reaction mixture was stirred at 40 °C for 1 hour. After completion of the reaction, the reaction mixture was cooled to room temperature and quenched by adding ice water. The mixture was extracted twice with dichloromethane, and the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 15% ethyl acetate) to obtain the title compound (white solid, 12 g, yield 77.2%). LC / MS (ESI) (m / z): 289 [M + H]+ .

[0904] Procedure 2: N-((5-Bromopyridin-2-yl)methyl)-2-methylpropane-2-sulfinamide Under an ice bath, sodium borohydride (2.1 g, 62.2 mmol) was added portionwise to a solution of N-((5-bromopyridin-2-yl)methylene)-2-methylpropane-2-sulfinamide (12 g, 41.5 mmol) in methanol (120 mL). Then, the reaction mixture was stirred at 30 °C for 30 minutes. After completion of the reaction, the reaction mixture was quenched with a saturated aqueous ammonium chloride solution under an ice bath and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate / petroleum ether, gradient: 0 - 20% ethyl acetate) to obtain the title compound (yellow liquid, 10.5 g, yield 86.9%). 1 HNMR(400MHz,CDCl3)δ8.61(d,J=2.2Hz,1H),7.79(dd,J=8.3,2.3Hz,1H),7.28-7.26(s,1H),4.42-4.36(m,2H),4.18(t,J=5.6Hz,1H),1.26(s,9H).LC / MS(ESI)(m / z):291[M+H] + .

[0905] Procedure 3: (5-Bromopyridin-2-yl)methylamine Under an ice water bath, a hydrochloric acid / 1,4-dioxane solution (50 mL, 4 M) was slowly added to a solution of N-((5-bromopyridin-2-yl)methyl)-2-methylpropane-2-sulfinamide (12 g, 64.5 mmol) in methanol (120 mL). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, a saturated aqueous sodium bicarbonate solution was added for neutralization, and the mixture was directly concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 10 - 20% methanol) to obtain the title compound (white solid, 4.5 g, yield 70.0%). 1HNMR (400 MHz, CDCl3) δ 8.61 (d, J = 2.1 Hz, 1H), 7.77 (dd, J = 8.3, 2.3 Hz, 1H), 7.21 (d, J = 8.3 Hz, 1H), 3.94 (s, 2H). LC / MS (ESI) (m / z): 187 [M + H] + 。

[0906] Procedure 4: 2 - (((5 - Bromopyridin - 2 - yl)methyl)amino)-2 - oxoacetate At 0 °C, triethylamine (5 mL, 36 mmol) was added to a solution of (5 - bromopyridin - 2 - yl)methylamine (4.5 g, 24 mmol) in anhydrous tetrahydrofuran (45 mL), and then oxalyl chloride monomethyl ester (2.4 mL, 26.5 mmol) was slowly added dropwise. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, ice - water was added to the reaction mixture, and it was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the title compound (yellow solid, 4.5 g, yield 68.4%) was obtained. LC / MS (ESI) (m / z): 273 [M + H] + 。

[0907] Procedure 5: Methyl 6 - bromoimidazo[1,5 - a]pyridine - 3 - carboxylate At room temperature, 2 - (((5 - bromopyridin - 2 - yl)methyl)amino)-2 - oxoacetate (4.5 g, 16.5 mmol) was divided and added to phosphorus oxychloride (45 mL). The reaction mixture was stirred at 110 °C for 16 hours under nitrogen gas protection. After completion of the reaction, it was concentrated under reduced pressure. Saturated aqueous sodium bicarbonate solution was added to the residue for neutralization, and it was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate / petroleum ether, gradient: 30 - 50% ethyl acetate) to obtain the title compound (yellow solid, 3.0 g, yield 71.3%). 1HNMR (400 MHz, CDCl3) δ 9.53 (s, 1H), 7.64 (s, 1H), 7.54 (d, J = 9.4 Hz, 1H), 7.15 (dd, J = 9.4, 1.3 Hz, 1H), 4.03 (s, 3H). LC / MS (ESI) (m / z): 255 [M+H] + 。

[0908] Procedure 6: 6-Bromoimidazo[1,5-a]pyridine-3-carboxylic acid At room temperature, methyl 6-bromoimidazo[1,5-a]pyridine-3-carboxylate (3 g, 11.8 mmol) was dissolved in a mixture of methanol (15 mL), tetrahydrofuran (15 mL), and water (15 mL), and then sodium hydroxide (520 mg, 12.9 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the pH of the reaction mixture was adjusted to 6 with 3N hydrochloric acid, and then concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0 - 20% methanol) to obtain the title compound (white solid, 2.8 g, yield 98.7%). LC / MS (ESI) (m / z): 241 [M+H] + 。

[0909] Procedure 7: 2-(6-Bromoimidazo[1,5-a]pyridine-3-carbonyl)hydrazine-1-carboxylic acid tert-butyl ester At room temperature, to a solution of 6-bromoimidazo[1,5-a]pyridine-3-carboxylic acid (2.8 g, 11.6 mmol) and tert-butyl carbazate (4.8 g, 12.8 mmol) in N,N-dimethylformamide (30 mL), N,N-diisopropylethylamine (5.7 mL, 34.8 mmol) and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (6.6 g, 17.4 mmol) were added sequentially. The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 20% ethyl acetate) to obtain the title compound (white solid, 2 g, yield 48.4%). LC / MS (ESI) (m / z): 355 [M+H] + 。

[0910] Procedure 8: 6-Bromoimidazo[1,5-a]pyridine-3-carbohydrazide trifluoroacetate At 0 °C, trifluoroacetic acid (5 mL) was slowly added to a solution of tert-butyl 2-(6-bromoimidazo[1,5-a]pyridine-3-carbonyl)hydrazine-1-carboxylate (2 g, 5.63 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at 25 °C for 1 hour. After completion of the reaction, it was concentrated to obtain the title compound (yellow liquid, 1.9 g, yield 100%), and the crude product was directly used in the next reaction. LC / MS (ESI) (m / z): 255 [M+H] + 。

[0911] Procedure 9: 6-Bromo-N'-(2,2-difluoroacetyl)imidazo[1,5-a]pyridine-3-carbohydrazide At 0 °C, 2,2-difluoroacetyl 2,2-difluoroacetate (0.7 mL, 5.64 mmol) was slowly added dropwise to a solution of 6-bromoimidazo[1,5-a]pyridine-3-carbohydrazide trifluoroacetate (1.9 g, 5.63 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate / petroleum ether, gradient: 0 - 50% ethyl acetate) to obtain the title compound (yellow solid, 1.0 g, yield 65.1%). LC / MS (ESI) (m / z): 333 [M+H] + 。

[0912] Procedure 10: 2-(6-Bromoimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole At room temperature, Lawesson's reagent (1.4 g, 3.37 mmol) was added to toluene (10 mL) of 6-bromo-N'-(2,2-difluoroacetyl)imidazo[1,5-a]pyridine-3-carbohydrazide (1 g, 3.06 mmol). The reaction mixture was stirred at 110 °C for 16 hours under nitrogen gas protection. After completion of the reaction, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate / petroleum ether, gradient: 0 - 55% ethyl acetate) to obtain the title compound (yellow liquid, 676 mg, yield 66.6%). LC / MS (ESI) (m / z): 331 [M+H] + 。

[0913] Procedure 11: 2-(6-(Benzylthio)imidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole At room temperature, to a solution of 2-(6-bromoimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole (676 mg, 2.04 mmol) in anhydrous dioxane (7 mL) were sequentially added N,N-diisopropylethylamine (1 mL, 6.12 mmol), XantPhos (236 mg, 0.41 mmol), Pd2(dba)3 (187 mg, 0.20 mmol), and benzyl mercaptan (0.4 mL, 3.06 mmol). After the reaction solution was replaced with nitrogen gas three times, the reaction was carried out with stirring at 100 °C for 2 hours under nitrogen gas protection. After completion of the reaction, the reaction solution was cooled to room temperature, diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate / petroleum ether, gradient: 0 - 30% ethyl acetate) to obtain the title compound (yellow liquid, 700 mg, yield 91.5%). LC / MS (ESI) (m / z): 375 [M+H] + .

[0914] Procedure 12: 2-(6-(Benzylthio)-1-bromoimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole At 0 °C, N-bromosuccinimide (366 mg, 2.06 mmol) was slowly added to a solution of 2-(6-(benzylthio)imidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole (700 mg, 1.87 mmol) in N,N-dimethylformamide (7 mL). The reaction was carried out with stirring at 0 °C for 30 minutes. After completion of the reaction, it was quenched with ice water, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate / petroleum ether, gradient: 0 - 55% ethyl acetate) to obtain the title compound (yellow solid, 800 mg, yield 94.4%). LC / MS (ESI) (m / z): 453 [M+H] + .

[0915] Procedure 13: 1-Bromo-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonyl chloride At 0 °C, acetic acid (0.12 mL, 1.98 mmol) was added to a solution of 2-(6-(benzylthio)-1-bromoimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole (450 mg, 0.99 mmol) in acetonitrile (10 mL), and then dichlorohydantoin (489 mg, 2.48 mmol) was added portionwise. The reaction mixture was stirred at 0 °C for 30 minutes. After completion of the reaction, the reaction mixture was diluted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the title compound (yellow solid, 350 mg, yield 82.1%), which was used directly in the next reaction. LC / MS (ESI) (m / z): 429 [M+H] + 。

[0916] Procedure 14: 1-Bromo-N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonamide At 0 °C, 1-bromo-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonyl chloride (350 mg, 0.81 mmol) was added portionwise to a solution of 1-amine-1-cyclopropyl cyanide hydrochloride (193 mg, 1.63 mmol) in pyridine (7 mL). The reaction mixture was stirred at room temperature for 30 minutes. After completion of the reaction, it was quenched with ice water, extracted with ethyl acetate, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate / petroleum ether, gradient: 0 - 60% ethyl acetate) to obtain the title compound (yellow solid, 230 mg, yield 59.4%). LC / MS (ESI) (m / z): 475 [M+H] + 。

[0917] Procedure 15: tert-Butyl 6-(6-(N-(1-cyanocyclopropyl)aminosulfonyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridin-1-yl)-2-azaspiro[3.4]oct-6-ene-2-carboxylate At room temperature, potassium phosphate (205 mg, 0.96 mmol) and XphosPdG2 (76 mg, 0.10 mmol) were added to a mixture of 1-bromo-N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonamide (230 mg, 0.48 mmol) and tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-azaspiro[3.4]oct-6-ene-2-carboxylate (162 mg, 0.48 mmol) in a mixture of 1,4-dioxane (18 mL) and water (4.5 mL). The reaction mixture was purged with nitrogen gas three times and then reacted at 80 °C for 2 hours with stirring under nitrogen gas protection. After completion of the reaction, the reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate / petroleum ether, gradient: 0 - 55% ethyl acetate) to obtain the title compound (yellow solid, 210 mg, yield 71.9%). LC / MS (ESI) (m / z): 604 [M+H] + 。

[0918] Procedure 16: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-1-(2-azaspiro[3.4]oct-6-en-6-yl)imidazo[1,5-a]pyridine-6-sulfonamide A solution of tert-butyl 6-(6-(N-(1-cyanocyclopropyl)aminosulfonyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridin-1-yl)-2-azaspiro[3.4]oct-6-ene-2-carboxylate (30 mg, 0.05 mmol) in dichloromethane (1 mL) was slowly added dropwise with trifluoroacetic acid (0.2 mL). The reaction mixture was stirred at 25 °C for 1 h under nitrogen protection. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (C 18 , aqueous solution of 10 - 50% acetonitrile (containing 0.1% formic acid)) to obtain the title compound (white solid, 8 mg, yield 32%). 1 1H NMR (400 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.18 (d, J = 8.3 Hz, 1H), 8.17 - 8.15 (m, 1H), 7.63 (t, J = 53.1 Hz, 1H), 7.43 (d, J = 8.7 Hz, 1H), 6.67 (s, 1H), 3.90 - 4.15 (m, 5H), 2.97 - 2.90 (m, 2H), 2.39 - 2.33 (m, 2H), 1.32 - 1.25 (m, 2H), 1.21 - 1.14 (m, 2H). LC / MS (ESI) (m / z): 504 [M + H] + 。

[0919] Example 23: 1-(2-Acetyl-2-azaspiro[3.4]oct-6-en-6-yl)-N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0920]

Chemical Structure

[0921] At 0 °C, triethylamine (0.04 mL, 0.26 mmol) and acetyl chloride (0.006 mL, 0.09 mmol) were added to a solution of N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-1-(2-azaspiro[3.4]oct-6-en-6-yl)imidazo[1,5-a]pyridine-6-sulfonamide (43 mg, 0.09 mmol) in anhydrous dichloromethane (1 mL). The reaction mixture was stirred at room temperature for 10 minutes. After completion of the reaction, ice water was added and the mixture was extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrated product was dissolved in methanol (1 mL), and then an aqueous lithium hydroxide solution (0.3 mL, 0.3 mmol, 1 M) was added. The reaction mixture was stirred at room temperature for 10 minutes and then concentrated under reduced pressure. Purification by preparative HPLC (C 18 , 10 - 50% aqueous acetonitrile solution (containing 0.1% formic acid)) gave the title compound (white solid, 16.9 mg, yield 36.2%). 1 HNMR (400 MHz, DMSO-d6) δ 9.99 (s, 1H), 9.65 (s, 1H), 8.37 (d, J = 9.6 Hz, 1H), 7.76 (t, J = 53.2 Hz, 1H), 7.41 (dd, J = 9.6, 1.3 Hz, 1H), 6.68 (s, 1H), 4.25 (d, J = 8.3 Hz, 1H), 4.15 (d, J = 8.3 Hz, 1H), 3.98 (d, J = 9.5 Hz, 1H), 3.87 (d, J = 9.5 Hz, 1H), 2.97 (t, J = 6.8 Hz, 2H), 2.34 - 2.29 (m, 2H), 1.79 (s, 3H), 1.52 - 1.47 (m, 2H), 1.38 - 1.34 (m, 2H). LC / MS (ESI) (m / z): 546 [M + H] + .

[0922] Example 24: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-1-(2-isobutyryl-2-azaspiro[3.4]oct-6-en-6-yl)-imidazo[1,5-a]pyridine-6-sulfonamide

[0923] [Chemical formula]

[0924] The title compound was prepared by substituting acetyl chloride with isobutyryl chloride with reference to the synthesis method of Example 23 to obtain the target molecule. 1 HNMR(400MHz,DMSO-d6)δ10.00(s,1H),9.67(s,1H),8.38(d,J = 9.6Hz,1H),7.69(t,J = 54.4,52.0Hz,1H),7.41(d,J = 9.6Hz,1H),6.70(s,1H),4.29(d,J = 8.1Hz,1H),4.20(d,J = 8.2Hz,1H),3.99(d,J = 9.3Hz,1H),3.88(d,J = 9.4Hz,1H),2.99 - 2.94(m,2H),2.49 - 2.44(m,1H),2.37 - 2.30(m,2H),1.52 - 1.48(m,2H),1.39 - 1.35(m,2H),1.03 - 0.99(m,6H).LC / MS(ESI)(m / z):574[M + H] + 。

[0925] Example 25: 6-(6-(N-(1-Cyanocyclopropyl)sulfamoyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridin-1-yl)-N,N-dimethyl-2-azaspiro[3.4]oct-6-ene-2-carboxamide

[0926] [Chemical formula]

[0927] At 0 °C, 4-Nitrophenyldimethylcarbamate (33 mg, 0.16 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (36 mg, 0.24 mmol) were slowly added to a solution of N-(1-cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-1-(2-azaspiro[3.4]oct-6-en-6-yl)imidazo[1,5-a]pyridine-6-sulfonamide (40 mg, 0.079 mmol) in tetrahydrofuran (2 mL). The reaction mixture was stirred at 80 °C for 1 hour. After completion of the reaction, the reaction mixture was diluted with ethyl acetate, washed successively with saturated aqueous potassium carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (white solid, 5.5 mg, yield 12.1%). 1 HNMR(400MHz,DMSO-d6)δ9.98(s,1H),8.37(d,J=9.1Hz,1H),7.69(t,J=53.1Hz,1H),7.40(dd,J=9.6,1.5Hz,1H),6.65(s,1H),4.03(d,J=8.1Hz,2H),3.90(d,J=8.1Hz,2H),2.95(t,J=6.3Hz,2H),2.78(s,6H),2.30(t,J=7.1Hz,2H),1.48(M,2H),1.36-1.29(m,2H).LC / MS(ESI)(m / z):575[M+H] + 。

[0928] Example 26: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-1-(2-azaspiro[3.4]octan-6-yl)imidazo[1,5-a]pyridine-6-sulfonamide

[0929]

Chemical formula

[0930] Procedure 1: tert-Butyl 6-(6-(N-(1-cyanocyclopropyl)sulfamoyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridin-1-yl)-2-azaspiro[3.4]octane-2-carboxylate At room temperature, Pd / C (5 mg, 10% by mass) was added to a methanol solution (1 mL) of tert-butyl 6-(6-(N-(1-cyanocyclopropyl)aminosulfonyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridin-1-yl)-2-azaspiro[3.4]oct-6-ene-2-carboxylate (30 mg, 0.05 mmol). After the reaction solution was replaced with nitrogen gas three times, the reaction was carried out at room temperature for 5 hours with stirring under a hydrogen balloon. After the reaction was completed, the mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (yellow solid, 25 mg, yield 83.2%). LC / MS (ESI) m / z: 606 [M + H] + 。

[0931] Procedure 2: N-(1-Cyanocyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-1-(2-azaspiro[3.4]octan-6-yl)imidazo[1,5-a]pyridine-6-sulfonamide Referring to the preparation method of Procedure 16 of Example 22, the title compound (white solid, 4 mg, yield 19.2%) was obtained. 1 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.32 (s, 1H), 7.99 (d, J = 9.6 Hz, 1H), 7.79 - 7.53 (m, 1H), 7.28 (d, J = 8.7 Hz, 1H), 3.95 - 3.83 (m, 4H), 3.67 - 3.64 (m, 1H), 2.38 - 2.30 (m, 2H), 2.18 - 2.12 (m, 2H), 2.03 - 1.98 (m, 1H), 1.86 - 1.82 (m, 1H), 1.18 - 1.12 (m, 2H), 1.07 - 1.02 (m, 2H). LC / MS (ESI) (m / z): 506 [M + H] + 。

[0932] Example 27: N-(1-Cyanochloropropyl)-3-(2-methyl-1,3-thiazol-5-yl)-7-[4-(2-methylpropyl)piperazin-1-yl]pyrazolo[1,5-a]pyridine-5-sulfonamide

[0933]

Chemical formula

[0934] Procedure 1: Ethyl 5-(tert-butoxycarbonyl)amino)pyrazolo[1,5-a]pyridine-3-carboxylate At room temperature, 2,4-dinitrophenylhydroxylamine (16.4 g, 82.5 mmol) was added portionwise to a solution of 4-(tert-butoxycarbonylamino)pyridine (16 g, 82.5 mmol) in acetonitrile (50 mL). The reaction mixture was stirred at 40 °C for 4 hours. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylformamide (160 mL). Then, potassium carbonate (22.8 g, 165 mmol) and ethyl propionate (8.3 mL, 82.5 mmol) were added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction solution was diluted with ethyl acetate, washed successively with saturated aqueous potassium carbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 20 - 50% ethyl acetate) to obtain the title compound (yellow solid, 8.5 g, yield 33.9%). LC / MS (ESI) m / z: 306 [M+H] + .

[0935] Procedure 2: Ethyl 7-bromo-5-(tert-butoxycarbonyl)amino)pyrazolo[1,5-a]pyridine-3-carboxylate At -78 °C, 2,2,6,6-tetramethylpiperidinylmagnesium chloride·lithium chloride complex (57 mL, 57 mmol, 1 M in THF) was slowly added dropwise to a solution of ethyl 5-(tert-butoxycarbonyl)amino)pyrazolo[1,5-a]pyridine-3-carboxylate (7 g, 23.0 mmol) in tetrahydrofuran (90 mL). The reaction mixture was stirred at -78 °C for 20 minutes, then 1,1,2,2-tetrachloro-1,2-dibromoethane (11.2 g, 34.5 mmol) was added dropwise, and then the reaction solution was warmed to room temperature and stirred for 2 hours. Ice water was slowly added dropwise to the reaction solution to quench it, and it was extracted with ethyl acetate and separated. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 20 - 50% ethyl acetate) to obtain the title compound (yellow solid, 6.5 g, yield 73.9%). 1 HNMR(400MHz,CDCl3)δ8.40(s,1H),7.93(d,J=2.1Hz,1H),7.80(s,1H),6.80(s,1H),4.37(q,J=7.1Hz,2H),1.55(s,9H),1.41(t,J=7.1Hz,3H).LC / MS(ESI)m / z:384 / 386[M+H] + 。

[0936] Procedure 3: 7-Bromopyrazolo[1,5-a]pyridin-5-amine Ethyl 7-bromo-5-(tert-butoxycarbonyl)amino)pyrazolo[1,5-a]pyridine-3-carboxylate (3 g, 7.8 mmol) was dissolved in dilute sulfuric acid (40 mL, 40% by mass fraction), and then reacted at 100 °C with stirring for 4 hours. After the reaction solution was cooled to room temperature, the pH was adjusted to 7 - 8 with a 4 mol / L aqueous sodium hydroxide solution, and extracted three times with ethyl acetate. The combined organic layers were washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 50% ethyl acetate) to obtain the title compound (yellow solid, 1.4 g, yield 84.7%). LC / MS (ESI) (m / z): 212 [M+H] + 。

[0937] Procedure 4: 7-Bromopyrazolo[1,5-a]pyridine-5-sulfonyl chloride At -10 °C, an aqueous sodium nitrite solution (322 mg, 4.67 mmol dissolved in 1 mL of water) was slowly added dropwise to a mixed solution of 7-bromopyrazolo[1,5-a]pyridine)-5-amine (900 mg, 4.2 mmol) in acetic acid (5 mL) and concentrated hydrochloric acid (5 mL), and the reaction solution was reacted at -10 °C with stirring for 45 minutes. In another three-necked flask, cuprous chloride (105 mg, 1.1 mmol) was dissolved in acetic acid (5 mL), and sulfur dioxide was passed through the mixture at 0 - 5 °C for 30 minutes of bubbling. The prepared diazonium salt mixed solution was added dropwise to the cupric chloride·sulfur dioxide·acetic acid solution, and the reaction solution was reacted at 10 °C with stirring for 30 minutes. The reaction solution was poured into ice water and extracted twice with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the title compound (yellow solid, 1.1 g, yield 100%), and the crude product was directly used in the next reaction. LC / MS (ESI) m / z: 295 [M+H] + 。

[0938] Procedure 5: 7-Bromo-N-(1-cyanocyclopropyl)pyrazolo[1,5-a]pyridine-5-sulfonamide At 0 °C, 7-bromopyrazolo[1,5-a]pyridine-5-sulfonyl chloride (1.1 g, 4.2 mmol) was added portionwise to a solution of 1-amino-1-cyclopropyl cyanide hydrochloride (500 mg, 4.2 mmol) in pyridine (10 mL). The reaction mixture was stirred at room temperature for 30 minutes. The reaction solution was diluted with ethyl acetate, washed with water and saturated brine respectively, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 50% ethyl acetate) to obtain the title compound (yellow solid, 620 mg, yield 43.2%). LC / MS(ESI)(m / z): 343 [M+H] + 。

[0939] Procedure 6: N-(1-Cyanocyclopropyl)-7-[4-isobutyrylpiperazin-1-yl]pyrazolo[1,5-a]pyridine-5-sulfonamide At room temperature, 1-(2-methylacetonyl)-piperazine (110 mg, 0.7 mmol) and N,N-diisopropylethylamine (0.3 mL, 1.75 mmol) were sequentially added to a solution of 7-bromo-N-(1-cyanocyclopropyl)pyrazolo[1,5-a]pyridine-5-sulfonamide (200 mg, 0.58 mmol) in N-methylpyrrolidone (3 mL). The reaction mixture was stirred at 120 °C for 16 hours. The reaction solution was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by...

Claims

1. 【Fig. 1】 and R A is hydrogen or a C 1 -C 6 alkyl group, Ring B is a 5,6-fused heteroaromatic ring that is unsubstituted or substituted by one or two Rs B or a 5,5-fused heteroaromatic ring that is unsubstituted or substituted by one or two Rs B wherein the heteroatom of the 5,6-fused heteroaromatic ring is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5,5-fused heteroaromatic ring is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and Rs B are each independently oxa, a hydroxy group, a halogen, or a C 1 -C 6 alkyl group, or two Rs B together with the atoms to which they are attached form a 3- to 6-membered cycloalkyl group R 1 is a hydroxy group, a C 1-1 -C 1 -alkyl group which is unsubstituted or substituted by one or more R 6 a C 1-2 -C 3 -cycloalkyl group which is unsubstituted or substituted by one or more R 6 a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 1-3 ​ [Chemical Formula 2] or is unsubstituted or is an amino group substituted by one or two R 1-5 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 1-1 is, independently of one another, deuterium, a hydroxy group, a cyano group, a halogen, a 3- to 6-membered heterocycloalkyl group, C 1-1-1 which is unsubstituted or substituted by one or more R 3 -C 6 cycloalkyl group, C 1-1-2 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, or C 1-1-3 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, and each R 1-1-1 is, independently of one another, deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-2 is, independently of one another, deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-3 is, independently of one another, deuterium, a hydroxy group, a cyano group or a halogen, Each R 1-2 is, independently of one another, deuterium, a hydroxy group, a cyano group, a halogen, C which is unsubstituted or substituted by one or more R 1-2-1 -C 1 -C 6 alkyl group, C which is unsubstituted or substituted by one or more R 1-2-2 -C 2 -C 6 alkynyl group, C which is unsubstituted or substituted by one or more R 1-2-3 -C 1 -C 6 alkoxy group, C which is unsubstituted or substituted by one or more R 1-2-4 -C 2 -C 6 alkenyl group, an amino group which is unsubstituted or substituted by one or two R 1-2-5 or [Chemical 3] and each R 1-2-1 is, independently of one another, deuterium, halogen, a hydroxy group or a C 1-2-1-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, each R 1-2-1-1 is, independently of one another, halogen, each R 1-2-2 is, independently of one another, halogen, a hydroxy group or a C 1-2-2-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, each R 1-2-2-1 is, independently of one another, halogen, each R 1-2-3 is, independently of one another, halogen, a hydroxy group or a C 1-2-3-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, each R 1-2-3-1 is, independently of one another, halogen, each R 1-2-4 is, independently of one another, halogen, a hydroxy group or a C 1-2-4-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, each R 1-2-4-1 is, independently of one another, halogen, each R 1-2-6 is, independently of one another, an amino group, each R 1-2-5 is, independently of one another, [Chemical Formula 4] and each R 1-2-5-1 is, independently of one another, C 1 -C 6 an alkyl group, and each R 1-3 is, independently of one another, a cyano group, deuterium, a hydroxy group, an amino group, a halogen, C which is unsubstituted or substituted by one or more R 1-3-1 -C 1 an alkyl group, C which is unsubstituted or substituted by one or more R 6 -C 1-3-2 an alkoxy group, or C 1 -C 6 an alkynyl group, and each R 2 -C 6 is, independently of one another, a halogen, and each R 1-3-1 is, independently of one another, a halogen, and 1-3-2 is, independently of one another, a halogen R 1-4 is C 1 -C 6 an alkyl group, Each R 1-5 is, independently of one another, C 1 -C 6 alkyl group, 【Chemical Formula 5】 or C 3 -C 6 is a cycloalkyl group, R 1-5-1 is C 1 -C 6 an alkyl group or an amino group, or R 1 the atom in R and the atom in A are linked to form a 5- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 0 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from one or more of N, O, P, and S, the number of heteroatoms is 3, 4, or 5, and each R 0 is independently C 1 -C 6 an alkyl group or oxa, R 2 is a 6- to 10-membered aryl group that is hydrogen, unsubstituted, or substituted by one or more R 2-1 is a 5- to 10-membered heteroaryl group that is hydrogen, unsubstituted, or substituted by one or more R 2-2 is a 4- to 12-membered heterocycloalkyl group that is hydrogen, unsubstituted, or substituted by one or more R 2-3 and 【Chemical Formula 6】 is non-replaceable or is replaced by one or more R 2-6 C replaced by 1 -C 6 an alkyl group [Chemical Formula 7] unsubstituted or C substituted by one or more R 2-9 -C 3 -C 6 a cycloalkyl group, unsubstituted or C substituted by one or more R 2-10 -C 3 -C 6 a cycloalkenyl group 【Chemical 8】 and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Each R 2-1 is, independently of one another, a cyano group, a halogen, C 2-1-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, 【Chemical Formula 9】 or is unsubstituted or is substituted by one or more R 2-1-4 C substituted by 1 -C 6 is an alkoxy group, Each R 2-1-1 is, independently of one another, a cyano group or a halogen, and R 2-1-2 is hydrogen or C 1 -C 6 alkyl group, and each R 2-1-3 is, independently of one another, hydrogen or C 1 -C 6 alkyl group, and each R 2-1-4 is, independently of one another, a halogen, Each R 2-2 is, independently of one another, a cyano group, a halogen, a C 2-2-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, 【Chemical 10】 C 1 -C 6 an alkoxy group or 【Chemical 11】 and Each R 2-2-1 is, independently of one another, a cyano group or a halogen, and R 2-2-2 is hydrogen or C 1 -C 6 alkyl group, and each R 2-2-3 is, independently of one another, hydrogen or C 1 -C 6 alkyl group, and each R 2-2-4 is, independently of one another, C 1 -C 6 alkyl group or C 3 -C 6 cycloalkyl group, Each R 2-3 is, independently of one another, a cyano group, oxa, hydroxy group, halogen, or a C 2-3-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 【Chemical Formula 12】 unsubstituted or substituted by one or more R 2-3-4 3- to 6-membered heterocycloalkyl group substituted by unsubstituted or one or more R 2-3-5 C substituted by 1 -C 6 alkoxy group, C substituted by unsubstituted or one or more R 2-3-6 -C 3 -C 6 cycloalkyl group, amino group substituted by unsubstituted or one or more R 2-3-7 substituted by 【Chemical 13】 A 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more Rs 2-3-9 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 2-3-1 is, independently of one another, a hydroxy group, a cyano group, a halogen, a C 2-3-1-1 -C 1 -C 6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-1-2 -C 3 -C 6 cycloalkyl group which is unsubstituted or substituted by one or more R 2-3-1-3 or an amino group which is unsubstituted or substituted by one or more R, R 2-3-2 is hydrogen, unsubstituted or C 2-3-2-1 substituted by one or more R 1 -C 6 alkyl group, unsubstituted or C 2-3-2-2 substituted by one or more R 3 -C 6 cycloalkyl group, 【Chemical 14】 either non-substituted or C substituted by one or more Rs 2-3-2-4 -C 1 -C 6 an alkoxy group, either non-substituted or a 3- to 6-membered heterocycloalkyl group substituted by one or more Rs 2-3-2-5 a 5- to 10-membered heteroaryl group substituted by one or more Rs, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 2-3-2-6 ​ Each R 2-3-3 is, independently of one another, hydrogen, C 2-3-3-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, Each R 2-3-4 is independently a C 1 -C 6 alkyl group or oxa, Each R 2-3-5 is independently a halogen or deuterium, Each R 2-3-6 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-7 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-8 is, independently of one another, C 1 -C 6 alkyl group, or C 3 -C 6 cycloalkyl group, and Each R 2-3-9 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-1-1 is, independently of one another, a halogen, and Each R 2-3-1-2 is, independently of one another, C 1 -C 6 an alkoxy group, Each R 2-3-1-3 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-2-1 is, independently of one another, halogen, a carboxyl group, a hydroxy group, oxa, C 1 -C 6 an alkoxy group, 【Chemical Formula 15】 unsubstituted or an amino group substituted by one or more R 2-3-2-1-2 unsubstituted or a 5- to 10-membered heteroaryl group substituted by one or more R 2-3-2-1-3 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 2-3-2-1-1 is, independently of one another, C 1 -C 6 an alkyl group or a 6- to 10-membered aryl group, Each R 2-3-2-1-2 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-2-1-3 is, independently of one another, C 1 -C 6 alkyl group, Each R 2-3-2-2 is, independently of one another, halogen, a hydroxy group, C 2-3-2-2-1 -C 1 -C 6 alkyl which is unsubstituted or substituted by one or more R 2-3-2-2-2 -C 1 -C 6 alkoxy which is unsubstituted or substituted by one or more R 2-3-2-2-3 or an amino group which is unsubstituted or substituted by one or more R, Each R 2-3-2-2-1 is independently a halogen or a hydroxy group, Each R 2-3-2-2-2 is, independently of one another, a carboxyl group, a halogen, deuterium, oxa or a hydroxy group, Each R 2-3-2-2-3 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-2-3 is, independently of one another, hydrogen or 【Chemical Formula 16】 and each R 2-3-2-3-1 is, independently of one another, unsubstituted or a 6-10 membered aryl group substituted by one or more R 2-3-2-3-1-1 and each R 2-3-2-3-1-1 is, independently of one another, a C 1 -C 6 alkoxy group, Each R 2-3-2-4 is independently a halogen, and Each R 2-3-2-5 is, independently of one another, halogen, a hydroxy group, oxa, C 1 -C 6 an alkoxy group, C which is unsubstituted or substituted by one or more R 2-3-2-5-1 -C 1 -C 6 an alkyl group, and each R 2-3-2-5-1 is, independently of one another, halogen, Each R 2-3-2-6 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-3-1 is, independently of one another, an unsubstituted or amino group substituted by one or more R 2-3-3-1-1 groups, and each R 2-3-3-1-1 is, independently of one another, a C 1 -C 6 alkyl group, Each R 2-4 is unsubstituted or has one or more R 2-4-1 a 4-10 membered heterocycloalkyl group, unsubstituted or substituted by one or more R 2-4-2 a 5-10 membered heteroaryl group unsubstituted or substituted by one or more R 2-4-3 or a 6-10 membered aryl group which is unsubstituted or substituted by one or more R 2-4-4 C replaced by 3 -C 6 a cycloalkyl group, the heteroatoms of said 4-10 membered heterocycloalkyl group being selected from any one or more of N, O and S, and the number of heteroatoms being 1, 2 or 3; the heteroatoms of said 5-10 membered heteroaryl group being selected from any one or more of N, O and S, and the number of heteroatoms being 1, 2 or 3; Each R 2-4-1 is independently a hydroxy group, a halogen, C 1 -C 6 alkyl group, 【Chemical 17】 and each R 2-4-2 is, independently of one another, a hydroxy group, a halogen or a C 1 -C 6 alkyl group, and each R 2-4-3 is, independently of one another, a hydroxy group, a halogen or a C 1 -C 6 alkyl group, and each R 2-4-4 is, independently of one another, a hydroxy group, a halogen or a C 1 -C 6 alkyl group, R 2-4-1-1 is a C 1 -C 6 alkyl group, and each R 2-4-1-2 is a C 1 -C 6 alkyl group, Each R 2-5 is, independently of one another, hydrogen, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more 2-5-1 R 【Chemical 18】 unsubstituted or substituted by one or more R 2-5-3 a 6- to 10-membered aryl group, C 1 -C 6 is an alkyl group, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 2-5-1 is, independently, 【Chemical Formula 19】 and R 2-5-1-1 is hydrogen or a C 1 -C 6 alkyl group, Each R 2-5-1-2 is, independently of one another, hydrogen or a C 1 -C 6 alkyl group, R 2-5-2 is, independently, C 1 -C 6 an alkyl group, Each R 2-5-3 is, independently of one another, C 1 -C 6 an alkoxy group, Each R 2-6 is, independently of one another, halogen, C 1 -C 6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-6-1 or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-6-2 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-6-1 is, independently of one another, halogen, C 1 -C 6 alkyl group or 【Chemical 20】 and R 2-6-1-1 is C 1 -C 6 is an alkyl group, Each R 2-6-2 is, independently of one another, halogen or C 1 -C 6 an alkyl group, Each R 2-7 is, independently of one another, C 1 -C 6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-7-1 s, or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-7-2 s, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. Each R 2-7-1 is, independently of one another, halogen, C 1 -C 6 alkyl group 【Chemical 21】 and R 2-7-1-1 is C 1 -C 6 an alkyl group, and R 2-7-1-2 is C 1 -C 6 an alkyl group, Each R 2-7-2 is, independently of one another, halogen or C 1 -C 6 alkyl group, Each R 2-8 is, independently of one another, C 1 -C 6 alkyl group, or two Rs 2-8 together with the atom to which it is attached form an unsubstituted or substituted by one or more Rs 2-8-1 4- to 10-membered heterocycloalkyl group, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-8-1 is, independently of one another, 【Chemical 22】 and R 2-8-1-1 is hydrogen or C 1 -C 6 is an alkyl group, Each R 2-9 is, independently of one another, an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 2-9-1 groups, wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, Each R 2-9-1 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-10 is, independently of one another, an unsubstituted or substituted 5- to 10-membered heteroaryl group having one or more R 2-10-1 groups, wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-10-1 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-11 is, independently of one another, an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 2-11-1 is, independently of one another, an unsubstituted or 5- to 10-membered heterocycloalkyl group substituted by one or more R 2-11-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 2-11-1 is, independently of one another, C 1 -C 6 alkyl group, and each R 2-11-2 is, independently of one another, C 1 -C 6 alkyl group, R 3 is an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 3-1 or an unsubstituted or 3- to 10-membered heterocycloalkyl group substituted by one or more R 3-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 3-1 is, independently of one another, a hydroxy group, a halogen, an unsubstituted or C 3-1-1 substituted by one or more R 1 -C 6 alkyl group or 【Chemical 23】 and Each R 3-1-1 is, independently of one another, a halogen or a hydroxy group, and R 3-1-2 is a C 1 -C 6 alkyl group or a C 2 -C 6 alkenyl group, Each R 3-2 is, independently of one another, a hydroxy group, a halogen, an unsubstituted or C 3-2-1 substituted by one or more R 1 -C 6 alkyl group or 【Chemical 24】 and Each R 3-2-1 is, independently of one another, halogen, and R 3-2-2 is C 1 -C 6 alkyl group or C 2 -C 4 alkenyl group, R 4 is hydrogen, deuterium, a halogen, a cyano group, a 5- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 or a C 4-2 -C 1 alkyl group which is unsubstituted or substituted by one or more R 6 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 4-1 is, independently, 【Chemical 25】 and Each R 4-2 is, independently of one another, an unsubstituted or substituted 5- to 10-membered heteroaryl group having one or more R 4-2-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, R 4-1-1 is C 1 -C 6 an alkyl group, and each R 4-1-2 is independently C 1 -C 6 an alkyl group, and each R 4-2-1 is independently C 1 -C 6 an alkyl group, ring B is 【Chemical 26】 When it is the case, R 2 is 【Chemical 27】 A compound represented by formula I, a pharmaceutically acceptable salt thereof, or an isotope compound, characterized in that it is as described above.

2. 【Fig. 28】 and R A is hydrogen or a C 1 -C 6 alkyl group, Ring B is a 5,6-fused heteroaromatic ring that is unsubstituted or substituted by one or two Rs B or a 5,5-fused heteroaromatic ring that is unsubstituted or substituted by one or two Rs B wherein the heteroatom of the 5,6-fused heteroaromatic ring is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5,5-fused heteroaromatic ring is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and R B is each independently oxa, a hydroxy group, a halogen, or a C 1 -C 6 alkyl group, or two Rs B together with the atom to which it is attached form a 3- to 6-membered cycloalkyl group R 1 is a hydroxy group, a C 1-1 -C 1 alkyl group which is unsubstituted or substituted by one or more R 6 is a C 1-2 -C 3 cycloalkyl group which is unsubstituted or substituted by one or more R 6 is a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 1-3 ​ 【Chemical 29】 or unsubstituted or substituted by one or two Rs 1-5 is an amino group, the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, Each R 1-1 is, independently of one another, deuterium, a hydroxy group, a cyano group, a halogen, a 3- to 6-membered heterocycloalkyl group, C 1-1-1 -C 3 -C 6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-1-2 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 1-1-3 -C 1 -C 6 alkoxy group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, and each R 1-1-1 is, independently of one another, deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-2 is, independently of one another, deuterium, a hydroxy group, a cyano group or a halogen, and each R 1-1-3 is, independently of one another, deuterium, a hydroxy group, a cyano group or a halogen, Each R 1-2 is, independently of one another, deuterium, a hydroxy group, a cyano group, a halogen, a C 1-2-1 -C 1 alkyl group which is unsubstituted or substituted by one or more R 6 s, a C 1-2-2 -C 2 alkynyl group which is unsubstituted or substituted by one or more R 6 s, a C 1-2-3 -C 1 alkoxy group which is unsubstituted or substituted by one or more R 6 s, a C 1-2-4 -C 2 alkenyl group, or an amino group which is unsubstituted or substituted by one or two R 6 s, and each R 1-2-5 is, independently of one another, a halogen, a hydroxy group, or a C 1-2-1 -C 1-2-1-1 alkoxy group which is unsubstituted or substituted by one or more R 1 s, each R 6 is, independently of one another, a halogen, each R 1-2-1-1 is, independently of one another, a halogen, a hydroxy group, or a C 1-2-2 -C 1-2-2-1 alkoxy group which is unsubstituted or substituted by one or more R 1 s, each R 6 is, independently of one another, a halogen, each R 1-2-2-1 is, independently of one another, a halogen, a hydroxy group, or a C 1-2-3 -C 1-2-3-1 alkoxy group which is unsubstituted or substituted by one or more R 1 s, each R 6 is, independently of one another, a halogen, each R 1-2-3-1 is, independently of one another, a halogen, a hydroxy group, or a C 1-2-4 -C 1-2-4-1 alkoxy group which is unsubstituted or substituted by one or more R 1 s, each R 6 is, independently of one another, a halogen, and 1-2-4-1 each R is, independently of one another, a halogen Each R 1-3 is, independently of one another, a cyano group, deuterium, a hydroxy group, an amino group, a halogen, C which is unsubstituted or substituted by one or more R 1-3-1 -C 1 -C 6 alkyl group, or C which is unsubstituted or substituted by one or more R 1-3-2 -C 1 -C 6 alkoxy group, each R 1-3-1 is, independently of one another, a halogen, each R 1-3-2 is, independently of one another, a halogen, R 1-4 is C 1 -C 6 an alkyl group, Each R 1-5 is, independently of one another, C 1 -C 6 alkyl group, 【Chemical 30】 or C 3 -C 6 is a cycloalkyl group, R 1-5-1 is C 1 -C 6 an alkyl group or an amino group, and or R 1 the atom in R and the atom in A are linked to form a 5- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 0 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from one or more of N, O, P, and S, the number of heteroatoms is 3, 4, or 5, and each R 0 is independently C 1 -C 6 alkyl group or oxa, Each R 2 is a hydrogen, a 6- to 10-membered aryl group which is unsubstituted or substituted by one or more R 2-1 is a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-2 is a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3 and 【Chemical Formula 31】 either non-replaced or replaced by one or more R 2-6 C replaced by 1 -C 6 an alkyl group 【Chemical Formula 32】 and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Each R 2-1 is, independently of one another, a cyano group, a halogen, C 2-1-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, 【Chemical Formula 33】 or unsubstituted or substituted by one or more R 2-1-4 C substituted by 1 -C 6 is an alkoxy group, Each R 2-1-1 is independently a cyano group or a halogen, and R 2-1-2 is hydrogen or C 1 -C 6 alkyl group, and each R 2-1-3 is independently hydrogen or C 1 -C 6 alkyl group, and each R 2-1-4 is independently a halogen, Each R 2-2 is, independently of one another, a cyano group, a halogen, C 2-2-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, 【Chemical Formula 34】 and Each R 2-2-1 is, independently of one another, a cyano group or a halogen, and R 2-2-2 is hydrogen or C 1 -C 6 alkyl group, and each R 2-2-3 is, independently of one another, hydrogen or C 1 -C 6 alkyl group, Each R 2-3 is, independently of one another, a cyano group, oxa, hydroxy group, halogen, or a C 2-3-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 【Chemical 35】 Unsubstituted or substituted by one or more Rs 2-3-4 A 3- to 6-membered heterocycloalkyl group substituted or unsubstituted by one or more Rs 2-3-5 C substituted by 1 -C 6 An alkoxy group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 2-3-1 is, independently of one another, a cyano group, a halogen, an unsubstituted or C 2-3-1-1 substituted by one or more R 1 -C 6 alkyl group, R 2-3-2 is hydrogen, or a C 2-3-2-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R Each R 2-3-3 is, independently of one another, hydrogen or a C 1 -C 6 alkyl group, Each R 2-3-4 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-5 is independently a halogen, Each R 2-3-1-1 is independently a halogen, Each R 2-3-2-1 is independently a halogen, Each R 2-4 is unsubstituted or has one or more R 2-4-1 a 4-10 membered heterocycloalkyl group, unsubstituted or substituted by one or more R 2-4-2 a 5-10 membered heteroaryl group unsubstituted or substituted by one or more R 2-4-3 or a 6-10 membered aryl group which is unsubstituted or substituted by one or more R 2-4-4 C replaced by 3 -C 6 a cycloalkyl group, the heteroatoms of said 4-10 membered heterocycloalkyl group being selected from any one or more of N, O and S, and the number of heteroatoms being 1, 2 or 3; the heteroatoms of said 5-10 membered heteroaryl group being selected from any one or more of N, O and S, and the number of heteroatoms being 1, 2 or 3; Each R 2-4-1 is, independently of one another, a hydroxy group, a halogen, C 1 -C 6 alkyl group, 【Chemical 36】 and each R 2-4-2 is, independently of one another, a hydroxy group, a halogen or a C 1 -C 6 alkyl group, each R 2-4-3 is, independently of one another, a hydroxy group, a halogen or a C 1 -C 6 alkyl group, each R 2-4-4 is, independently of one another, a hydroxy group, a halogen or a C 1 -C 6 alkyl group, R 2-4-1-1 is a C 1 -C 6 alkyl group, each R 2-4-1-2 is a C 1 -C 6 alkyl group, Each R 2-5 is, independently of one another, hydrogen, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more 2-5-1 R 【Chemical 37】 and the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Each R 2-5-1 is, independently of one another, 【Chemical Formula 38】 and R 2-5-1-1 is hydrogen or a C 1 -C 6 alkyl group, and Each R 2-5-1-2 is, independently of one another, hydrogen or a C 1 -C 6 alkyl group, R 2-5-2 is, independently, C 1 -C 6 an alkyl group, Each R 2-6 is, independently of one another, halogen, C 1 -C 6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-6-1 s, or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-6-2 s, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-6-1 is, independently of one another, halogen, C 1 -C 6 alkyl group or 【Chemical Formula 39】 and R 2-6-1-1 is C 1 -C 6 an alkyl group, Each R 2-6-2 is, independently of one another, halogen or C 1 -C 6 an alkyl group, Each R 2-7 is, independently of one another, C 1 -C 6 alkyl group, an unsubstituted or one or more R 2-7-1 substituted 4- to 10-membered heterocycloalkyl group, or an unsubstituted or one or more R 2-7-2 substituted 5- to 10-membered heteroaryl group, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-7-1 is, independently of one another, halogen, C 1 -C 6 alkyl group, 【Chemical 40】 and R 2-7-1-1 is C 1 -C 6 an alkyl group, and R 2-7-1-2 is C 1 -C 6 an alkyl group, Each R 2-7-2 is, independently of one another, halogen or C 1 -C 6 alkyl group, Each R 2-8 is, independently of one another, C 1 -C 6 -alkyl group, or two Rs 2-8 together with the atom to which it is attached form an unsubstituted or one or more Rs 2-8-1 substituted 4- to 10-membered heterocycloalkyl group, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-8-1 is, independently of one another, 【Chemical 41】 and R 2-8-1-1 is hydrogen or C 1 -C 6 is an alkyl group, R 3 is a 5- to 10-membered heteroaryl group that is unsubstituted or substituted by one or more R 3-1 or is a 3- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 3-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 3-1 is, independently of one another, a hydroxy group, a halogen, a C 3-1-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 【Chemical 42】 and Each R 3-1-1 is, independently of one another, a halogen, and R 3-1-2 is a C 1 -C 6 alkyl group or a C 2 -C 6 alkenyl group, Each R 3-2 is, independently of one another, a hydroxy group, a halogen, an unsubstituted or C 3-2-1 substituted by one or more R 1 -C 6 alkyl group or 【Chemical 43】 and Each R 3-2-1 is, independently of one another, halogen, and R 3-2-2 is C 1 -C 6 an alkyl group or C 2 -C 4 an alkenyl group, R 4 is a hydrogen, halogen, 5- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 groups, or a C 4-2 -C 1 alkyl group which is unsubstituted or substituted by one or more R 6 groups, wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 4-1 is, independently, 【Chemical 44】 and Each R 4-2 is, independently of one another, an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 4-2-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 R 4-1-1 is C 1 -C 6 an alkyl group, and each R 4-1-2 is independently C 1 -C 6 an alkyl group, and each R 4-2-1 is independently C 1 -C 6 an alkyl group, ring B is 【Chemical 45】 When it is, R 2 is 【Chemical 46】 A compound represented by formula I, a pharmaceutically acceptable salt thereof, or an isotope compound according to claim 1, characterized in that it is as described above.

3. The compound represented by formula I according to claim 2, a pharmaceutically acceptable salt thereof, or an isotope compound, characterized in that the compound represented by formula I satisfies any one or more of the following conditions: (1) R A wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (2) In ring B, the heteroatom of the 5,5-fused heteroaromatic ring is N, and the number of heteroatoms can be 1, 2, or 3. For example, 【Chemical 47】 and (3) In ring B, the 3- to 6-membered cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, for example, a cyclopropyl group; (4) In ring B, the heteroatom of the 5,6-fused heteroaromatic ring is selected from N and / or O, and the number of heteroatoms can be 1, 2, or 3. For example, 【Chemical 48】 and (5) R 1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group or an isopropyl group, (6) R 1 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or bicyclopentane, for example, a cyclopropyl group, cyclobutane or bicyclopentane, (7) R 1 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is any one of N, O or S, the number of heteroatoms is 1 or 2, the heteroatom of the 3- to 6-membered heterocycloalkyl group can be O or N, and the number of heteroatoms can be 1, for example, 【Chemical 49】 and (8) R 1-1 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is any one of N, O or S, the number of heteroatoms is 1 or 2, the heteroatom of the 3- to 6-membered heterocycloalkyl group can be O or N, and the number of heteroatoms can be 1, for example, 【Chemical Formula 50】 and (9) Each R 1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (10) each R 1-1 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group or an isopropyl group, (11) Each R 1-1 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, In each R 1-1 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, (13) each R 1-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (14) each R 1-1-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (15) Each R 1-1-3 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (16) Each R 1-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (17) Each R 1-2 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group or an isopropyl group, (18) Each R 1-2 wherein the C 2 -C 6 alkynyl group is 【Chemical Formula 51】 and (19) Each R 1-2 wherein said C 2 -C 6 alkenyl group is 【Chemical 52】 and (20) R 1-2 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, (21) each R 1-2-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (22) Each R 1-2-1 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, (23) Each R 1-2-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (24) each R 1-2-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (25) Each R 1-2-2 In, the said C 1 -C 6 The alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and can be a methoxy group or an ethoxy group, (26) Each R 1-2-2-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (27) Each R 1-2-3 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 1-2-3 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, (29) Each R 1-2-3-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (30) each R 1-2-4 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 1-2-4 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, (32) Each R 1-2-4-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 1-2-5 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group or an isopropyl group, (34) Each R 1-2-5 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or bicyclopentane, for example, a cyclopropyl group, cyclobutane or bicyclopentane, (35) Each R 1-3 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 1-3 wherein, said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (37) Each R 1-3 wherein said C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, (38) Each R 1-3-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (39) Each R 1-3-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (40) R 1-4 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, In each R 1-5 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (42) Each R 1-5 In, the C 3 -C 6 The cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or bicyclopentane, for example, a cyclopropyl group, cyclobutane or bicyclopentane, (43) R 1-5-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group (44) R 1 When the atom in R and the atom in A are linked to form an unsubstituted or substituted 5- to 10-membered heterocycloalkyl group by one or more Rs 0 and the 5- to 10-membered heterocycloalkyl group is a 5- to 6-membered heterocycloalkyl group, for example 【Chemical 53】 and In each R 0 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (46) R 2 wherein the 6- to 10-membered aryl group is a phenyl group or a naphthalene group, for example, a phenyl group, (47) R 2 wherein the 5- to 10-membered heteroaryl group is a 5- or 6-membered heteroaryl group, or a 5,6-fused heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group can be selected from any one or more of N and / or S, the number of heteroatoms can be 1 or 2, the heteroatom of the 5-membered heteroaryl group can be selected from N and / or S, the number of heteroatoms is 2, the heteroatom of the 6-membered heteroaryl group can be selected from N, the number of heteroatoms is 1 or 2, the heteroatom of the 5,6-fused heteroaryl group can be selected from N and / or O, the number of heteroatoms is 2, and the number of heteroatoms is 1, 2 or 3, (48) R 2 wherein the 4- to 10-membered heterocycloalkyl group is a monocyclic, bridged ring, fused ring or spiro ring, the monocyclic ring can be a 4- to 6-membered heterocycloalkyl group, the fused ring can be a 5,6-fused heterocycloalkyl group or a 4,6-fused heterocycloalkyl group, the spiro ring can be a 4-ring spiro 6-ring, a 4-ring spiro 5-ring or a 4-ring spiro 4-ring, the heteroatom of the 4- to 10-membered heterocycloalkyl group can be selected from N and / or O, and the number of heteroatoms can be 1 or 2, (49) R 2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (50) Each R 2-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-1 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, In each R 2-1 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, (53) each R 2-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-1-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. In each R 2-1-3 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (56) Each R 2-1-4 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-2 wherein, said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group or an isopropyl group. In each R 2-2-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-2-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, In each R 2-2-3 wherein, the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (62) Each R 2-3 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-3 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (64) Each R 2-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is any one of N, O or S, the number of heteroatoms can be 1 or 2, the heteroatom of the 3- to 6-membered heterocycloalkyl group can also be O or N, and the number of heteroatoms can also be 1, for example, 【Chemical 54】 and In each R 2-3 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, (66) Each R 2-3-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (67) Each R 2-3-1 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group or an ethoxy group, and R 2-3-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group, In each R 2-3-3 wherein, said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. In each R 2-3-4 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be an isopropyl group (70) Each R 2-3-5 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (71) each R 2-3-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (72) Each R 2-3-2-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (73) Each R 2-4 wherein the 4- to 10-membered heterocycloalkyl group is monocyclic, the 4- to 10-membered heterocycloalkyl group can be a 4- to 6-membered heterocycloalkyl group, the heteroatom of the 4- to 10-membered heterocycloalkyl group can be selected from N and / or O, and the number of heteroatoms is 1 or 2, (74) Each R 2-4 wherein the 5- to 10-membered heteroaryl group is a 5,6-fused heteroaryl group, the heteroatom of the 5,6-fused heteroaryl group can be selected from N and / or O, and the number of heteroatoms is 1, 2 or 3, (75)Each R 2-4 wherein the 6- to 10-membered aryl group is a phenyl group or a naphthalene group, for example, a phenyl group, In each R 2-4 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopentyl group, In each R 2-4-1 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (78) each R 2-4-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (79)Each R 2-4-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-4-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. In each R 2-4-3 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-4-3 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (83) Each R 2-4-4 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-4-4 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (85)R 2-4-1-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group, In each R 2-4-1-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group, (87) each R 2-5 wherein the 4- to 10-membered heterocycloalkyl group is monocyclic, the 4- to 10-membered heterocycloalkyl group can be a 4- to 6-membered heterocycloalkyl group, the heteroatom of the 4- to 10-membered heterocycloalkyl group can be selected from N and / or O, and the number of heteroatoms can be 1 or 2, (88) R 2-5-1-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, In each R 2-5-1-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group, (90) R 2-5-2 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group, In each R 2-6 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-6 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and can also be a methyl group. (93) each R 2-6 wherein the 4- to 10-membered heterocycloalkyl group is monocyclic, the 4- to 10-membered heterocycloalkyl group can be a 4- to 6-membered heterocycloalkyl group, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from N and / or O, and the number of heteroatoms is 1 or 2, In each R 2-6 wherein the 5- to 10-membered heteroaryl group is a 5- to 6-membered heteroaryl group, the heteroatom of the 5- to 6-membered heteroaryl group can be selected from N and / or S, the number of heteroatoms is 2, and the number of heteroatoms is 1 or 2, (95) each R 2-6-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-6-1 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (97) R 2-6-1-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, In each R 2-6-2 wherein, said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may be a methyl group or an isopropyl group. (99)Each R 2-6-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-7 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. In each R 2-7 the 4- to 10-membered heterocycloalkyl group may be monocyclic or spirocyclic, the monocyclic group may be a 4- to 6-membered heterocycloalkyl group, the spirocyclic group may be a 4-ring spiro 6-ring, 4-ring spiro 5-ring or 4-ring spiro 4-ring, the heteroatom of the 4- to 10-membered heterocycloalkyl group may be selected from N and / or O, and the number of heteroatoms may be 1 or 2, (102) each R 2-7 wherein the 5- to 10-membered heteroaryl group is a 5- or 6-membered heteroaryl group, or a 5,6-fused heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group can be selected from any one or more of N and / or S, the number of heteroatoms can be 1 or 2, the heteroatom of the 5-membered heteroaryl group can be selected from N and / or S, the number of heteroatoms can also be 2, the heteroatom of the 6-membered heteroaryl group can be selected from N, the number of heteroatoms is 1 or 2, the heteroatom of the 5,6-fused heteroaryl group can be selected from N and / or O, the number of heteroatoms can be 2, the number of heteroatoms is 1, 2 or 3, (103) each R 2-7-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-7-1 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (105) R 2-7-1-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (106) each R 2-7-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-7-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. In each R 2-8 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (109) each R 2-8 wherein the 4- to 10-membered heterocycloalkyl group is monocyclic, the monocyclic group can be a 4- to 6-membered heterocycloalkyl group, the heteroatom of the 4- to 10-membered heterocycloalkyl group can be selected from N and / or O, and the number of heteroatoms can be 1 or 2, In each R 2-8-1-1 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (111) R 3 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, a 5,5-fused heteroaryl group, or a 5,6-fused heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group can be selected from any one or more of N and / or S, the number of heteroatoms can be 1 or 2, the heteroatom of the 5-membered heteroaryl group can be selected from N and / or S, the number of heteroatoms can be 2, the heteroatom of the 5,6-fused heteroaryl group can be selected from N and / or O, the number of heteroatoms is 2, the number of heteroatoms can be 1 or 2, the heteroatom of the 5,5-fused heteroaryl group can be selected from N and / or O, and the number of heteroatoms can be 2. (112) R 3 wherein the 3- to 10-membered heterocycloalkyl group is monocyclic, the monocyclic group can be a 4- to 6-membered heterocycloalkyl group, the heteroatom of the 3- to 10-membered heterocycloalkyl group can be selected from N, and the number of heteroatoms can be 1 or 2, In each R 3-1 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (114) each R 3-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (115) each R 3-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (116) R 3-1-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an ethyl group. (117) R 3-1-2 wherein the C 2 -C 6 alkenyl group is 【Chemical Formula 55】 and (118) R 3-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (119) R 3-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may be a methyl group. (120) R 3-2-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (121) R 3-2-2 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may be a methyl group, (122) R 3-2-2 wherein the C 2 -C 6 alkenyl group is 【Chemical Formula 56】 and (123) R 4 wherein the halogen can be fluorine such as fluorine, chlorine, bromine or iodine, (124) R 4 wherein the 5- to 10-membered heterocycloalkyl group is a spiro ring, the spiro ring is a 4-ring spiro 6-ring, 4-ring spiro 5-ring or 4-ring spiro 4-ring, the heteroatom of the 4- to 10-membered heterocycloalkyl group can be N, and the number of heteroatoms is 1 or 2, (125) R 4 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, (126) Each R 4-2 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, the heteroatom of the 5-membered heteroaryl group can be selected from N and / or S, and the number of heteroatoms can be 2, (127) R 4-1-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group, (128) Each R 4-1-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group. (129) Each R 4-2-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group (130) R 1-2-5-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an isopropyl group, and, (130)R 2-7-1-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group.

4. The compound represented by formula I according to claim 2, a pharmaceutically acceptable salt thereof, or an isotope compound, characterized in that the compound represented by formula I satisfies any one or more of the following conditions: (1) R 1 is unsubstituted or is C 1-2 substituted by one or more R 3 -C 6 -cycloalkyl group, or is unsubstituted or is a 3- to 6-membered heterocycloalkyl group substituted by one or more R 1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1 (2) Each R 1-2 is, independently of one another, a cyano group, or a C 1-2-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R (3) Each R 1-2-1 is independently a halogen, (4)Each R 1-3 is, independently of one another, unsubstituted or a C 1-3-1 -C 1 -C 6 alkyl group substituted by one or more R (5) Each R 1-3-1 is independently a halogen, (6) R 2 is a 4- to 10-membered heterocycloalkyl group that is hydrogen or unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1 or 2 (7) Each R 2-3 is, independently of one another, 【Chemical 57】 and (8) R 2-3-2 is C 1 -C 6 an alkyl group, (9) R 3 is an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 3-1 or an unsubstituted or 5- to 10-membered heterocycloalkyl group substituted by one or more R 3-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, O, or S, and the number of heteroatoms is 1 or 2, (10) Each R 3-1 is, independently of one another, a hydroxy group, a halogen or a C 3-1-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R (11) Each R 3-1-1 is, independently of one another, halogen, and (12) Each R 3-2 is, independently of one another, 【Chemical Formula 58】 and (13) R 3-2-2 is C 1 -C 6 an alkyl group or C 2 -C 4 an alkenyl group, (14) R 4 is an unsubstituted or 5- to 10-membered heterocycloalkyl group substituted by one or more R 4-1 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1, 2 or 3, (15) Each R 4-1 is, independently of one another, 【Chemical 59】 and (16) R 4-1-1 is C 1 -C 6 an alkyl group, and, (17) each R 4-1-2 is, independently of one another, C 1 -C 6 alkyl group.

5. The compound represented by formula I as claimed in claim 2, its pharmaceutically acceptable salt, or isotopic compound, characterized in that the compound represented by formula I satisfies any one or more of the following conditions: (1) R 1 is unsubstituted or is C 1-2 substituted by one or more R 3 -C 6 is a cycloalkyl group or a 4-membered heterocycloalkyl group, the heteroatom of the 4-membered heterocycloalkyl group is O, and the number of heteroatoms is 1 (2) R 2 is hydrogen or a 6- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 6- to 10-membered heterocycloalkyl group is N, and the number of heteroatoms is 1 or 2 (3)R 3 is an unsubstituted or 1- or more R 3-1 substituted 5- or 6-membered heteroaryl group or an unsubstituted or 1- or more R 3-2 substituted 5- or 6-membered heterocycloalkyl group, wherein the heteroatom of the 5- or 6-membered heteroaryl group is N and / or S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, and the number of heteroatoms is 1, (4) R 3-2-2 is C 2 -C 4 an alkenyl group, and (5) R 4 is an unsubstituted or 5- to 10-membered heterocycloalkyl group substituted by one or more R 4-1 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is N and the number of heteroatoms is 1 or 2.

6. The compound represented by formula I as claimed in claim 2, its pharmaceutically acceptable salt, or isotopic compound, characterized in that the compound represented by formula I satisfies any one or more of the following conditions: (1) R 1 is unsubstituted or C 1-2 substituted by three or more R 3 -C 6 is a cycloalkyl group, (2) R 2 is hydrogen or a 6- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 6- to 10-membered heterocycloalkyl group is N, and the number of heteroatoms is 1 or 2 (3)R 3 is an unsubstituted or 5-6 membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5-6 membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 and (4) R 4 is an unsubstituted or 7- to 9-membered heterocycloalkyl group substituted by one or more R 4-1 wherein the heteroatom of the 7- to 9-membered heterocycloalkyl group is N and the number of heteroatoms is 1.

7. The compound represented by formula I as claimed in claim 1, its pharmaceutically acceptable salt or isotopic compound, characterized in that the compound represented by formula I is a compound represented by formula I-a. 【Chemical Formula 60】 Y is C or N, X is C or N, W is N, CH, O, NR 4 or CR 4 and Z is CH, O or N, T 1 is C or N, and T 2 is C or N, and A, R 1 , R 2 , R 3 and R 4 are defined in any one of claims 1 to 6.

8. T 1 、T 2 wherein at least one of T, 1 , 2 , X and Y is N, or Y, W and Z contain only one heteroatom, the compound of formula I, a pharmaceutically acceptable salt or an isotopic compound thereof according to claim 7.

9. The compound represented by formula I-a can be a compound represented by formula I-A, formula I-B or formula I-C 【Chemical Formula 61】 and / or the compound represented by formula I is a compound represented by formula I-b, formula I-c, formula I-d, formula I-e, formula I-f, formula I-g, formula I-h, formula I-i, formula I-j, formula I-k, formula I-L or formula I-m The compound represented by formula I as claimed in claim 1, its pharmaceutically acceptable salt or isotopic compound, characterized in that it is so. 【Chemical Formula 62】

10. The compound represented by formula I as claimed in claim 2, its pharmaceutically acceptable salt or isotopic compound, characterized in that the compound represented by formula I is the following Scheme 1, Scheme 2 or Scheme 3: and is Scheme 1: R 1 is unsubstituted or is C substituted by one or more R 1-2 -C 3 -C 6 a cycloalkyl group, or is a 3-6 membered heterocycloalkyl group unsubstituted or substituted by one or more R 1-3 wherein the heteroatom of the 3-6 membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1 Each R 1-2 is, independently of one another, a cyano group or a C 1-2-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 1-2-1 which are, independently of one another, halogen, Each R 1-3 is, independently of one another, unsubstituted or a C 1-3-1 substituted by one or more R 1 -C 6 alkyl group, and each R 1-3-1 is, independently of one another, halogen, R 2 is a 4- to 10-membered heterocycloalkyl group that is hydrogen or unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is N, O, or S, and the number of heteroatoms is 1 or 2 Each R 2-3 is, independently, 【Chemical Formula 63】 and is R 2-3-2 is C 1 -C 6 an alkyl group, R 3 is a 5- to 10-membered heteroaryl group that is unsubstituted or substituted by one or more R 3-1 or is a 5- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 3-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, O, or S, and the number of heteroatoms is 1 or 2 Each R 3-1 is, independently of one another, a hydroxy group, a halogen, a C 3-1-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more Rs Each R 3-1-1 is, independently of one another, a halogen, and Each R 3-2 is, independently of one another, 【Chemical 64】 and is R 3-2-2 is C 1 -C 6 an alkyl group or C 2 -C 4 an alkenyl group, R 4 is an unsubstituted or 5- to 10-membered heterocycloalkyl group substituted by one or more R 4-1 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, O or S, and the number of heteroatoms is 1, 2 or 3, Each R 4-1 is, independently of one another, 【Chemical Formula 65】 and is R 4-1-1 is C 1 -C 6 an alkyl group, Each R 4-1-2 is, independently of one another, C 1 -C 6 an alkyl group, Scheme 2: R 1 is unsubstituted or C 1-2 substituted by one or more R 3 -C 6 is a cycloalkyl group or a 4-membered heterocycloalkyl group, the heteroatom of the 4-membered heterocycloalkyl group is O, and the number of heteroatoms is 1 Each R 1-2 is, independently of one another, a cyano group or a C 1-2-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 1-2-1 which are each, independently of one another, halogen, R 2 is a 6-10 membered heterocycloalkyl group that is hydrogen or unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 6-10 membered heterocycloalkyl group is N, and the number of heteroatoms is 1 or 2 Each R 2-3 is, independently, 【Chemical Formula 66】 and is R 2-3-2 is C 1 -C 6 an alkyl group, R 3 is a 5- or 6-membered heteroaryl group which is unsubstituted or substituted by one or more R 3-1 or a 5- or 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 3-2 wherein the heteroatom of the 5- or 6-membered heteroaryl group is N and / or S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, and the number of heteroatoms is 1 Each R 3-1 is, independently of one another, halogen or C 3-1-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R Each R 3-1-1 is independently a halogen, and Each R 3-2 is, independently of one another, 【Chemical 67】 and is R 3-2-2 is C 2 -C 4 an alkenyl group, R 4 is a 5- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 4-1 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is N, and the number of heteroatoms is 1 or 2, Each R 4-1 is, independently, 【Chemical Formula 68】 and is R 4-1-1 is C 1 -C 6 an alkyl group, Each R 4-1-2 is, independently of one another, C 1 -C 6 an alkyl group, Scheme 3: R 1 is unsubstituted or is C 1-2 substituted by one or more R 3 -C 6 is a cycloalkyl group, Each R 1-2 is, independently of one another, a cyano group or a C 1-2-1 alkyl group which is unsubstituted or substituted by one or more R 1 -C 6 and each R 1-2-1 is, independently of one another, a halogen, R 2 is a 6-10 membered heterocycloalkyl group which is hydrogen or unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 6-10 membered heterocycloalkyl group is N, and the number of heteroatoms is 1 or 2 Each R 2-3 is, independently of one another, 【Chemical Formula 69】 and is R 2-3-2 is C 1 -C 6 an alkyl group, R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is, independently of one another, halogen or a C 3-1-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R Each R 3-1-1 is, independently of one another, halogen, and R 4 is an unsubstituted or 7- to 9-membered heterocycloalkyl group substituted by one or more R 4-1 wherein the heteroatom of the 7- to 9-membered heterocycloalkyl group is N, the number of heteroatoms is 1, Each R 4-1 is, independently of one another, 【Chemical 70】

11. R 4-1-1 is C 1 -C 6 an alkyl group, Each R 4-1-2 is, independently of one another, C 1 -C 6 alkyl group. The compound represented by formula I as claimed in claim 1, its pharmaceutically acceptable salt, or isotopic compound, characterized in that the compound represented by formula I satisfies any one or more of the following conditions: and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. (1) R 1 is a hydroxy group, a C 1-1 -C 1 -alkyl group which is unsubstituted or substituted by one or more R 6 a C 1-2 -C 3 -cycloalkyl group which is unsubstituted or substituted by one or more R 6 a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 1-3 ​ 【Chemical Formula 71】 or is unsubstituted or is an amino group substituted by one or two R 1-5 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 1-1 is, independently of one another, deuterium, a hydroxy group, a cyano group, a halogen, a 3- to 6-membered heterocycloalkyl group, C 1-1-1 substituted by one or more R 3 -C 6 cycloalkyl group, C 1-1-2 substituted by one or more R 1 -C 6 alkyl group, or C 1-1-3 substituted by one or more R 1 -C 6 alkoxy group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and each R 1-1-1 is, independently of one another, deuterium, a hydroxy group, a cyano group, or a halogen, and each R 1-1-2 is, independently of one another, deuterium, a hydroxy group, a cyano group, or a halogen, and each R 1-1-3 is, independently of one another, deuterium, a hydroxy group, a cyano group, or a halogen, Each R 1-2 is, independently of one another, deuterium, a hydroxy group, a halogen, C which is unsubstituted or substituted by one or more R 1-2-2 -C 2 -C 6 an alkynyl group, C which is unsubstituted or substituted by one or more R 1-2-3 -C 1 -C 6 an alkoxy group, C which is unsubstituted or substituted by one or more R 1-2-4 -C 2 -C 6 an alkenyl group, an amino group which is unsubstituted or substituted by one or two R 1-2-5 or 【Chemical 72】 and each R 1-2-2-1 is, independently of one another, halogen, and each R 1-2-3 is, independently of one another, halogen, a hydroxy group or a C 1-2-3-1 -C 1 -C 6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-3-1 is, independently of one another, halogen, and each R 1-2-4 is, independently of one another, halogen, a hydroxy group or a C 1-2-4-1 -C 1 -C 6 alkoxy group which is unsubstituted or substituted by one or more R 1-2-4-1 is, independently of one another, halogen, and each R 1-2-6 is, independently of one another, an amino group, and each R 1-2-5 is, independently of one another, 【Chemical 73】 and each R 1-2-5-1 is, independently of one another, C 1 -C 6 an alkyl group, and each R 1-3 is, independently of one another, a cyano group, deuterium, a hydroxy group, an amino group, a halogen, C which is unsubstituted or substituted by one or more R 1-3-1 -C 1 an alkyl group, C which is unsubstituted or substituted by one or more R 6 -C 1-3-2 an alkoxy group or C 1 -C 6 an alkynyl group, and each R 2 is, independently of one another, a halogen, and each R 6 is, independently of one another, a halogen, and 1-3-1 1-3-2 ​​ R 1-4 is C 1 -C 6 an alkyl group, Each R 1-5 is, independently of one another, C 1 -C 6 alkyl group, 【Chemical 74】 or C 3 -C 6 is a cycloalkyl group, R 1-5-1 is C 1 -C 6 an alkyl group or an amino group, or R 1 the atom in R and the atom in A are linked to form a 5- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 0 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, P and S, the number of heteroatoms is 3, 4 or 5, and each R 0 is independently C 1 -C 6 an alkyl group or oxa, (2) R 2 is hydrogen, a 6- to 10-membered aryl group which is unsubstituted or substituted by one or more R 2-1 a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-2 a 4- to 12-membered heterocycloalkyl group substituted by one or more R 2-3 ​ 【Chemical 75】 is non-replaceable or is C replaced by one or more R 2-6 -C 1 -C 6 an alkyl group 【Chemical 76】 unsubstituted or C substituted by one or more R 2-9 -C 3 -C 6 a cycloalkyl group, unsubstituted or C substituted by one or more R 2-10 -C 3 -C 6 a cycloalkenyl group 【Chemical Formula 77】 and is Each R 2-1 is, independently of one another, a cyano group, a halogen, an unsubstituted or C 2-1-1 substituted by one or more R 1 -C 6 alkyl group, 【Chemical 78】 or is unsubstituted or is substituted by one or more R 2-1-4 C substituted by 1 -C 6 is an alkoxy group, Each R 2-1-1 is, independently of one another, a cyano group or a halogen, and R 2-1-2 is hydrogen or C 1 -C 6 alkyl group, and each R 2-1-3 is, independently of one another, hydrogen or C 1 -C 6 alkyl group, and each R 2-1-4 is, independently of one another, a halogen, Each R 2-2 is, independently of one another, a cyano group, a halogen, an unsubstituted or C 2-2-1 substituted by one or more R 1 -C 6 alkyl group 【Chemical 79】 C 1 -C 6 an alkoxy group or 【Chemical 80】 and is Each R 2-2-1 is, independently of one another, a cyano group or a halogen, and R 2-2-2 is hydrogen or C 1 -C 6 alkyl group, and each R 2-2-3 is, independently of one another, hydrogen or C 1 -C 6 alkyl group, and each R 2-2-4 is, independently of one another, C 1 -C 6 alkyl group or C 3 -C 6 cycloalkyl group, Each R 2-3 is independently a C 2-3-1 substituted by one or more R 1 -C 6 alkyl group 【Chemical Formula 81】 unsubstituted or substituted by one or more R 2-3-4 a 3- to 6-membered heterocycloalkyl group substituted by one or more R 2-3-7 an amino group substituted by one or more R 2-3-9 a 5- to 10-membered heteroaryl group substituted by one or more R, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 2-3-1 is, independently of one another, a cyano group, a C 2-3-1-2 which is unsubstituted or substituted by three or more R 3 -C 6 cycloalkyl group, R 2-3-2 is hydrogen or a C 2-3-2-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 2-3-2-2 -C 3 -C 6 cycloalkyl group, 【Chemical 82】 A 5- to 6-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 2-3-2-5 A 5- to 10-membered heteroaryl group that is unsubstituted or substituted by one or more R 2-3-2-6 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 2-3-4 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-7 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-9 is, independently of one another, oxa or C 1 -C 6 alkyl group, and Each R 2-3-1-2 is, independently of one another, C 1 -C 6 an alkoxy group, and each R 2-3-2-1 is, independently of one another, a hydroxy group, oxa, 【Chemical 83】 Unsubstituted or substituted by one or more Rs 2-3-2-1-3 is a 5- to 10-membered heteroaryl group, wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, Each R 2-3-2-1-1 is, independently of one another, C 1 -C 6 an alkyl group or a 6- to 10-membered aryl group, and each R 2-3-2-1-2 is, independently of one another, C 1 -C 6 an alkyl group, and each R 2-3-2-1-3 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-2-2 is, independently of one another, halogen, a hydroxy group, C 2-3-2-2-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 2-3-2-2-2 -C 1 -C 6 alkoxy group which is unsubstituted or substituted by one or more R 2-3-2-2-3 or an amino group which is unsubstituted or substituted by one or more R, Each R 2-3-2-2-1 is, independently of one another, a halogen or a hydroxy group, Each R 2-3-2-2-2 is, independently of one another, a halogen, deuterium, oxa or hydroxy group, Each R 2-3-2-2-3 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-2-3 is, independently of one another, hydrogen or 【Chemical 84】 and each R 2-3-2-3-1 is, independently of one another, an unsubstituted or a 6-10 membered aryl group substituted by one or more R 2-3-2-3-1-1 and each R 2-3-2-3-1-1 is, independently of one another, a C 1 -C 6 alkoxy group, Each R 2-3-2-4 is, independently of one another, halogen, and Each R 2-3-2-5 is, independently of one another, halogen, a hydroxy group, oxa, C 1 -C 6 an alkoxy group, C 2-3-2-5-1 substituted by one or more R 1 -C 6 an alkyl group, and each R 2-3-2-5-1 is, independently of one another, halogen, Each R 2-3-2-6 is, independently of one another, C 1 -C 6 alkyl group, and each R 2-4 is unsubstituted or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-4-1 , an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 2-4-2 , or an unsubstituted or 6- to 10-membered aryl group substituted by one or more R 2-4-3 . The heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. The heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-4-1 is, independently of one another, a hydroxy group, a halogen, C 1 -C 6 alkyl group, 【Chemical 85】 and each R 2-4-2 is independently a hydroxy group, a halogen or a C 1 -C 6 alkyl group, and each R 2-4-3 is independently a hydroxy group, a halogen or a C 1 -C 6 alkyl group, Each R 2-5 is, independently of one another, hydrogen, a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-5-1 groups 【Chemical 86】 unsubstituted or substituted by one or more R 2-5-3 a 6- to 10-membered aryl group, C 1 -C 6 is an alkyl group, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 2-5-1 is, independently of one another, 【Chemical 87】 and is R 2-5-1-1 is hydrogen or a C 1 -C 6 alkyl group, Each R 2-5-1-2 is, independently of one another, hydrogen or a C 1 -C 6 alkyl group, R 2-5-2 is, independently, C 1 -C 6 an alkyl group, Each R 2-5-3 is, independently of one another, C 1 -C 6 an alkoxy group, Each R 2-6 is, independently of one another, halogen, C 1 -C 6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-6-1 s, or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-6-2 s, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. Each R 2-6-1 is, independently of one another, halogen, C 1 -C 6 alkyl group or 【Chemical 88】 and R 2-6-1-1 is C 1 -C 6 an alkyl group, Each R 2-6-2 is, independently of one another, halogen or C 1 -C 6 alkyl group, and Each R 2-7 is, independently of one another, C 1 -C 6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-7-1 s, or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-7-2 s, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. Each R 2-7-1 is, independently of one another, halogen, C 1 -C 6 alkyl group, 【Chemical 89】 and R 2-7-1-1 is C 1 -C 6 an alkyl group, and R 2-7-1-2 is C 1 -C 6 an alkyl group, Each R 2-7-2 is, independently of one another, halogen or C 1 -C 6 alkyl group, Each R 2-8 is, independently of one another, C 1 -C 6 -alkyl group, or two Rs 2-8 together with the atom to which it is attached form an unsubstituted or one or more Rs 2-8-1 substituted 4- to 10-membered heterocycloalkyl group, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-8-1 is, independently, 【Chemical Formula 90】 and R 2-8-1-1 is hydrogen or C 1 -C 6 is an alkyl group, Each R 2-9 is, independently of one another, an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 2-9-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 2-9-1 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-10 is, independently of one another, an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 2-10-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-10-1 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-11 is, independently of one another, an unsubstituted or a 5- to 10-membered heteroaryl group substituted by one or more R 2-11-1 is, independently of one another, an unsubstituted or a 5- to 10-membered heterocycloalkyl group substituted by one or more R 2-11-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-11-1 is, independently of one another, C 1 -C 6 an alkyl group, and each R 2-11-2 is, independently of one another, C 1 -C 6 an alkyl group, (3) R 3 is an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 3-1 or an unsubstituted or 3- to 10-membered heterocycloalkyl group substituted by one or more R 3-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 3-1 is, independently of one another, a hydroxy group, a halogen, a C 3-1-1 substituted by one or more R 1 -C 6 alkyl group or 【Chemical Formula 91】 and is Each R 3-1-1 is independently a hydroxy group, and R 3-1-2 is a C 1 -C 6 alkyl group or a C 2 -C 6 alkenyl group, Each R 3-2 is, independently of one another, a hydroxy group, a halogen, an unsubstituted or C 3-2-1 substituted by one or more R 1 -C 6 alkyl group or 【Chemical Formula 92】 and is Each R 3-2-1 is, independently of one another, halogen, and R 3-2-2 is C 1 -C 6 an alkyl group or C 2 -C 4 an alkenyl group, (4) R 4 is deuterium, a cyano group, unsubstituted or a 5- to 10-membered heterocycloalkyl group substituted by one or more R 4-1 or a C 4-2 alkyl group substituted by one or more R 1 -C 6 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 4-1 is, independently of one another, 【Chemical Formula 93】

12. Each R 4-2 is, independently of one another, an unsubstituted or substituted 5- to 10-membered heteroaryl group having one or more R 4-2-1 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 R 4-1-1 is C 1 -C 6 an alkyl group, and each R 4-1-2 is independently C 1 -C 6 an alkyl group, and each R 4-2-1 is independently C 1 -C 6 an alkyl group. The compound represented by formula I as claimed in claim 2, its pharmaceutically acceptable salt, or isotopic compound, characterized in that the compound represented by formula I satisfies any one or more of the following conditions: ​ (1) R 1 is a hydroxy group, a C 1-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 1-2 -C 3 -C 6 cycloalkyl group which is unsubstituted or substituted by one or more R 1-3 or a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 【Chemical Formula 94】 or is unsubstituted or is substituted by one or two Rs 1-5 is an amino group, wherein the heteroatom of the 3-6 membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 1-1 is, independently of one another, deuterium, a hydroxy group, a cyano group, a halogen, a 3- to 6-membered heterocycloalkyl group, C 1-1-1 substituted by one or more R 3 -C 6 cycloalkyl group, C 1-1-2 substituted by one or more R 1 -C 6 alkyl group, or C 1-1-3 substituted by one or more R 1 -C 6 alkoxy group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and each R 1-1-1 is, independently of one another, deuterium, a hydroxy group, a cyano group, or a halogen, and each R 1-1-2 is, independently of one another, deuterium, a hydroxy group, a cyano group, or a halogen, and each R 1-1-3 is, independently of one another, deuterium, a hydroxy group, a cyano group, or a halogen, Each R 1-2 is, independently of one another, deuterium, a hydroxy group, a halogen, C which is unsubstituted or substituted by one or more Rs 1-2-2 -C 2 -C 6 an alkynyl group, C which is unsubstituted or substituted by one or more Rs 1-2-3 -C 1 -C 6 an alkoxy group, C which is unsubstituted or substituted by one or more Rs 1-2-4 -C 2 -C 6 an alkenyl group or an amino group which is unsubstituted or substituted by one or two Rs, and each R 1-2-5 is, independently of one another, a halogen, a hydroxy group or C which is unsubstituted or substituted by one or more Rs 1-2-2 -C 1-2-2-1 -C 1 -C 6 an alkoxy group, and each R 1-2-2-1 is, independently of one another, a halogen, and each R 1-2-3 is, independently of one another, a halogen, a hydroxy group or C which is unsubstituted or substituted by one or more Rs 1-2-3-1 -C 1 -C 6 an alkoxy group, and each R 1-2-3-1 is, independently of one another, a halogen, and each R 1-2-4 is, independently of one another, a halogen, a hydroxy group or C which is unsubstituted or substituted by one or more Rs 1-2-4-1 -C 1 -C 6 an alkoxy group, and each R 1-2-4-1 is, independently of one another, a halogen, and Each R 1-3 is, independently of one another, a cyano group, deuterium, a hydroxy group, an amino group, a halogen, C 1-3-1 -C 1 alkyl group which is unsubstituted or substituted by one or more R 6 or C 1-3-2 -C 1 alkoxy group which is unsubstituted or substituted by one or more R 6 , and each R 1-3-1 is, independently of one another, a halogen, and each R 1-3-2 is, independently of one another, a halogen. R 1-4 is C 1 -C 6 an alkyl group, Each R 1-5 is, independently of one another, C 1 -C 6 an alkyl group, 【Chemical Formula 95】 or C 3 -C 6 is a cycloalkyl group, R 1-5-1 is C 1 -C 6 an alkyl group or an amino group, or R 1 the atom in R and the atom in A are linked to form a 5-10 membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 0 wherein the heteroatom of the 5-10 membered heterocycloalkyl group is selected from any one or more of N, O, P and S, the number of heteroatoms is 3, 4 or 5, and each R 0 is independently C 1 -C 6 alkyl group or oxa, (2)Each R 2 is hydrogen, a 6- to 10-membered aryl group which is unsubstituted or substituted by one or more R 2-1 groups, a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-2 groups, or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-3 groups; 【Chemical Formula 96】 is non-replaceable or one or more Rs 2-6 C replaced by 1 -C 6 alkyl group, 【Chemical 97】 and the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-1 is, independently of one another, a cyano group, a halogen, a C 2-1-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more Rs 【Chemical Formula 98】 or is unsubstituted or is substituted by one or more R 2-1-4 C substituted by 1 -C 6 is an alkoxy group, Each R 2-1-1 is, independently of one another, a cyano group or a halogen, and R 2-1-2 is hydrogen or C 1 -C 6 alkyl group, and each R 2-1-3 is, independently of one another, hydrogen or C 1 -C 6 alkyl group, and each R 2-1-4 is, independently of one another, a halogen, Each R 2-2 is, independently of one another, a cyano group, a halogen, an unsubstituted or C 2-2-1 substituted by one or more R 1 -C 6 alkyl group, 【Chemical Formula 99】 and Each R 2-2-1 is, independently of one another, a cyano group or a halogen, and R 2-2-2 is hydrogen or C 1 -C 6 alkyl group, and each R 2-2-3 is, independently of one another, hydrogen or C 1 -C 6 alkyl group, Each R 2-3 is independently a C 2-3-1 -C 1 -C 6 alkyl group substituted by one or more Rs 【Chemical 100】 is non-replaceable or is replaced by one or more Rs 2-3-4 is a 3- to 6-membered heterocycloalkyl group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, Each R 2-3-1 is, independently of one another, a cyano group, R 2-3-2 is hydrogen, and each R 2-3-4 is independently a C 1 -C 6 alkyl group, Each R 2-4 is a 4- to 10-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 2-4-1 is a 5- to 10-membered heteroaryl group that is unsubstituted or substituted by one or more R 2-4-2 is a 6- to 10-membered aryl group that is unsubstituted or substituted by one or more R 2-4-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 2-4-1 is independently a hydroxy group, a halogen, C 1 -C 6 alkyl group, 【Chemical 101】 and each R 2-4-2 is independently a hydroxy group, a halogen or a C 1 -C 6 alkyl group, and each R 2-4-3 is independently a hydroxy group, a halogen or a C 1 -C 6 alkyl group, Each R 2-5 is, independently of one another, hydrogen, a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-5-1 groups 【Chemical Formula 102】 and the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Each R 2-5-1 is, independently of one another, 【Chemical Formula 103】 and R 2-5-1-1 is hydrogen or a C 1 -C 6 alkyl group, Each R 2-5-1-2 is, independently of one another, hydrogen or a C 1 -C 6 alkyl group, R 2-5-2 is, independently, C 1 -C 6 an alkyl group, Each R 2-6 is, independently of one another, halogen, C 1 -C 6 alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-6-1 s, or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-6-2 s, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. Each R 2-6-1 is, independently of one another, halogen, C 1 -C 6 alkyl group or 【Chemical 104】 and R 2-6-1-1 is C 1 -C 6 is an alkyl group, Each R 2-6-2 is, independently of one another, halogen or C 1 -C 6 alkyl group, and Each R 2-7 is, independently of one another, C 1 -C 6 an alkyl group, a 4- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 2-7-1 s, or a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 2-7-2 s, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. Each R 2-7-1 is, independently of one another, halogen, C 1 -C 6 alkyl group, 【Chemical 105】 and R 2-7-1-1 is C 1 -C 6 an alkyl group, and R 2-7-1-2 is C 1 -C 6 an alkyl group, Each R 2-7-2 is, independently of one another, halogen or C 1 -C 6 alkyl group, and Each R 2-8 is, independently of one another, C 1 -C 6 an alkyl group, or two Rs 2-8 together with the atom to which it is attached form an unsubstituted or one or more Rs 2-8-1 substituted 4- to 10-membered heterocycloalkyl group, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Each R 2-8-1 is, independently of one another, 【Chemical 106】 and R 2-8-1-1 is hydrogen or C 1 -C 6 is an alkyl group, (3) R 3 is an unsubstituted or 5- to 10-membered heteroaryl group substituted by one or more R 3-1 or an unsubstituted or 3- to 10-membered heterocycloalkyl group substituted by one or more R 3-2 wherein the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 3- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 Each R 3-1 is, independently of one another, a hydroxy group, a halogen or 【Chemical 107】 and R 3-1-2 is C 1 -C 6 an alkyl group or C 2 -C 6 an alkenyl group, Each R 3-2 is, independently of one another, a hydroxy group, a halogen, a C 3-2-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 【Chemical 108】 and Each R 3-2-1 is, independently of one another, halogen, and R 3-2-2 is C 1 -C 6 an alkyl group or C 2 -C 4 an alkenyl group, (4) R 4 is an unsubstituted or 5- to 10-membered heterocycloalkyl group substituted by one or more R 4-1 and is a C 4-2 -C 1 -alkyl group substituted by one or more R 6 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 4-1 is, independently of one another, 【Chemical 109】 and Each R 4-2 is, independently of one another, a 5- to 10-membered heteroaryl group which is unsubstituted or substituted by one or more R 4-2-1 groups, wherein the heteroatoms of the 5- to 10-membered heteroaryl group are selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, R 4-1-1 is C 1 -C 6 an alkyl group, and each R 4-1-2 is independently C 1 -C 6 an alkyl group, and each R 4-2-1 is independently C 1 -C 6 an alkyl group. Claim 13 The compound represented by the formula I according to claim 1, a pharmaceutically acceptable salt thereof, or an isotope compound, wherein the compound represented by the formula I satisfies any one or more of the following conditions: (1) In ring B, the heteroatom of the 5,6-fused heteroaromatic ring is N and / or O, and the number of heteroatoms can be 1, 2, or 3. For example, 【Chemical 110】 and (2) R 1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, an ethyl group, an isopropyl group or a tert-butyl group, (3) R 1 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, bicyclopentane or 【Chemical 111】 and, for example, a cyclopropyl group, cyclobutane, bicyclopentane, or 【Chemical 112】 and (4) R 1 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is N, O or S, the number of heteroatoms is 1 or 2, the heteroatom of the 3- to 6-membered heterocycloalkyl group can be O or N, the number of heteroatoms can also be 1, preferably, azetidinyl, oxetanyl, oxolane or azepanyl, for example, 【Chemical 113】 and (5) Each R 1-3 wherein the C 2 -C 6 alkynyl group is 【Chemical 114】 and (6) R 2 wherein the 5- to 10-membered heteroaryl group is a 5- or 6-membered heteroaryl group, a 5,5-fused heteroaryl group, or a 5,6-fused heteroaryl group; the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O, and S; the number of heteroatoms is 1, 2, or 3; the heteroatom of the 5-membered heteroaryl group may be N, and the number of heteroatoms is 2, and preferably, 【Chemical 115】 such as a pyrazole group, etc., the heteroatom of the 6-membered heteroaryl group can be N, the number of heteroatoms is 1, and preferably, 【Chemical 116】 such as a pyridinyl group, etc., the heteroatom of the 5,5-fused heteroaryl group can be N, the number of heteroatoms is 3, and preferably, 【Chemical 117】 such as a dihydropyrrolopyrazole group, etc., the heteroatom of the 5,6-fused heteroaryl group can be N and / or O, the number of heteroatoms is 1, 2, or 3, and preferably, it is benzofuranyl, dihydroimidazopyrazinyl, or benzimidazole. For example, 【Chemical 118】 and (7) R 2 wherein the 4- to 12-membered heterocycloalkyl group is any one or more of a monocyclic ring, a bridged ring, a fused ring, and a spiro ring, the heteroatom of the 4- to 12-membered heterocycloalkyl group can be N and / or O, and the number of heteroatoms can be 1, 2, or 3. The monocyclic ring can be a 4- to 6-membered heterocycloalkyl group, the fused ring can be a 5,6-fused heterocycloalkyl group, a 4,6-fused heterocycloalkyl group, or a 5,5-fused heterocycloalkyl group, the spiro ring can be a 4-ring spiro 6-ring, a 4-ring spiro 5-ring, a 4-ring spiro 4-ring, a 5-ring spiro 6-ring, or a 3-ring spiro 6-ring, and the bridged ring can be bicyclooctane or bicycloheptane, (8) R 2 wherein the 4- to 12-membered heterocycloalkyl group is a saturated heterocycloalkyl group or a heterocycloalkyl group containing 1 to 2 double bonds, (9) R 2 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopentyl group, (10) R 2 wherein said C 3 -C 6 The cycloalkenyl group is a cycloalkenyl group containing one double bond, and can be a 5-membered cycloalkenyl group. For example, 【Chemical 119】 and In each R 2-2 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group, (12) Each R 2-2-4 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (13) Each R 2-2-4 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group, (14) each R 2-3 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group, an ethyl group or an isopropyl group or a tert-butyl group, (15) each R 2-3 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, and may be a methoxy group, an ethoxy group or an isopropoxy group, (16) Each R 2-3 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group, (17) Each R 2-3 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group or a 6-membered heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group can be N and / or O, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-membered heteroaryl group can be N and / or O, the number of heteroatoms can be 2 or 3, preferably a triazolyl group, an oxadiazolyl group or an imidazole group, for example, 【Chemical 120】 and the heteroatom of the 6-membered heteroaryl group can be N, the number of heteroatoms is 1 or 2, and preferably, it is a pyridinyl group. For example, 【Chemical 121】 and (18) Each R 2-3-1 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group, (19) R 2-3-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group such as a methyl group, an ethyl group, an isopropyl group or a tert-butyl group, (20) R 2-3-2 wherein the C 3 -C 6 The cycloalkyl group is a cyclopropyl group such as a cyclopropyl group or a cyclobutyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, (21) R 2-3-2 wherein said C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, an isopropoxy group, (22) R 2-3-2 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1 or 2, preferably oxetanyl, azetidinyl, oxirane, azolanyl, oxacyclohexanyl, azepanyl, pyrazinyl, thiazolidinyl, or oxabicyclohexyl, for example, 【Chemical 122】 and (23) R 2-3-2 wherein the 5- to 10-membered heteroaryl group is a 5- or 6-membered heteroaryl group or a 5,6-fused heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group can be N and / or O, the number of heteroatoms can be 1 or 2, the heteroatom of the 5-membered heteroaryl group can be N and / or O, the number of heteroatoms is 2, the heteroatom of the 6-membered heteroaryl group can be N, the number of heteroatoms is 1, the heteroatom of the 5,6-fused heteroaryl group can be O, and the number of heteroatoms is 2, (24) each R 2-3-3 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group or an ethyl group, In each R 2-3-6 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, In each R 2-3-7 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (27) each R 2-3-8 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group or an isopropyl group, (28) Each R 2-3-8 wherein the C 3 -C 6 cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group, for example, a cyclopropyl group, (29) Each R 2-3-9 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and can be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (30) Each R 2-3-1-2 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group, In each R 2-3-1-3 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, In each R 2-3-2-1 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group, (33) Each R 2-3-2-1 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, the heteroatom of the 5-membered heteroaryl group may be N, and the number of heteroatoms is 3, (34) Each R 2-3-2-1-1 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (35) Each R 2-3-2-1-1 wherein the 6- to 10-membered aryl group is a phenyl group such as a phenyl group or a naphthalene group, (36) Each R 2-3-2-1-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (37) Each R 2-3-2-1-3 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (38) Each R 2-3-2-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-3-2-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, In each R 2-3-2-2 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group or an ethoxy group or an n-propoxy group, (41) each R 2-3-2-2-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (42) Each R 2-3-2-2-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-3-2-2-3 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, In each R 2-3-2-3-1 wherein the 6- to 10-membered aryl group is a phenyl group or a naphthalene group, for example, a phenyl group, (45)Each R 2-3-2-3-1-1 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group, (46) Each R 2-3-2-4 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, (47) Each R 2-3-2-5 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-3-2-5 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group, (49) Each R 2-3-2-5 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, an ethyl group, an n-propyl group or an isopropyl group, (50) each R 2-3-2-5-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine, In each R 2-3-2-6 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, In each R 2-3-3-1-1 wherein, said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (53) each R 2-5 wherein the 6- to 10-membered aryl group is a phenyl group or a naphthalene group, for example, a phenyl group, In each R 2-5 wherein the C 1 -C 6 alkyl group is a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (55) R 2-5-1-1 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group or an isopropyl group, In each R 2-5-3 wherein the C 1 -C 6 alkoxy group is a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group or a tert-butoxy group, for example, a methoxy group, In each R 2-9 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group can be N and / or S, the number of heteroatoms can be 1 or 2, the heteroatom of the 5-membered heteroaryl group can be N, the number of heteroatoms is 2, and preferably, it is a pyrazole group, for example, 【Chemical 123】 and In each R 2-10 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group can be N and / or S, the number of heteroatoms can be 1 or 2, the heteroatom of the 5-membered heteroaryl group can be N, the number of heteroatoms is 2, and preferably, it is a pyrazole group, for example, 【Chemical 124】 and (59) Each R 2-11 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, the heteroatom of the 5-membered heteroaryl group can be N and / or S, the number of heteroatoms is 2, preferably a thiazolyl or imidazole group, for example, 【Chemical 125】 or 【Chemical 126】 and In each R 2-11 wherein, the heteroatom of the 3- to 6-membered heterocycloalkyl group is O, the number of heteroatoms may be 1, preferably an oxirane group, for example, 【Chemical 127】 and In each R 2-11-1 wherein, said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, In each R 2-11-2 wherein the C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group, (63) R 3 wherein the 5- to 10-membered heteroaryl group is a 5-membered heteroaryl group, a 5,5-fused heteroaryl group or a 5,6-fused heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group can be N and / or S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5-membered heteroaryl group can be N and / or S, the number of heteroatoms is 2 or 3, the heteroatom of the 5,6-fused heteroaryl group is N and / or O, the number of heteroatoms is 2, the number of heteroatoms is 1, 2 or 3, the number of heteroatoms is 2, the number of heteroatoms is 1, 2 or 3, (64) R 3-2-2 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group or an ethyl group, (65) R 4 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine or chlorine, (66) R 4 wherein the 4- to 10-membered heterocycloalkyl group is a monocyclic or spiro ring, the monocyclic ring can be a 6-membered heterocycloalkyl group, the spiro ring can be a 4-ring spiro 6-ring, 4-ring spiro 5-ring or 4-ring spiro 4-ring, the heteroatom of the 4- to 10-membered heterocycloalkyl group can be N, and the number of heteroatoms is 1 or 2. Claim 14 The compound represented by the formula I according to claim 13, a pharmaceutically acceptable salt thereof, or an isotope compound, wherein the compound represented by the formula I satisfies any one or more of the following conditions: (1) The 4- to 12-membered heterocycloalkyl group is a 3-ring spiro 6,6-fused heterocycloalkyl group, and preferably, it is hexahydrospirocyclopropanepyrazinopyrazinyl. For example, 【Chemical 128】 and (2) The bicyclooctane is bicyclo[2.2.2]octane, for example, 【Chemical 129】 and (3) The bicycloheptane is bicyclo[3.1.1]heptane, for example, 【Chemical 130】 and (4) The 4- to 6-membered heteroalkyl group is azepanyl, tetrahydropyridyl, piperazinyl, azolanyl, or morpholinyl, for example, 【Chemical Formula 131】 and (5) The 5,6-fused heteroalkyl group is tetrahydrofuropyridinyl, hexahydropyrrolopyrazinyl, hexahydropyrazinooxazinyl, or hexahydroimidazopyrazinyl, for example, 【Chemical 132】 and (6) The 5,5-fused heteroalkyl group is tetrahydrofuropyrrole, for example, 【Chemical 133】 and (7) The 4-ring spiro 6-ring is oxaazaspirononanyl, dioxazaspirononanyl, or azaspirononanyl, for example, 【Chemical 134】 and (8) The 3-ring spiro 6-ring is diazaspirooctyl, for example, 【Chemical 135】 and (9) The 5-ring spiro 6-ring is diazaspirodecanil, for example, 【Chemical 136】 and

15. The compound represented by formula I according to claim 1, its pharmaceutically acceptable salt, or isotopic compound, characterized in that the compound represented by formula I satisfies any one or more of the following conditions: (1) R 1 is a C 1-2 substituted by one or more R 3 -C 6 cycloalkyl group, or a 3- to 6-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 (2)Each R 1-2 is, independently of one another, a C 2 -C 6 alkynyl group, (3)Each R 1-3 is, independently of one another, a cyano group, an unsubstituted or C 1-3-1 substituted by one or more R 1 -C 6 alkyl group, C 2 -C 6 alkynyl group, and (4)Each R 1-3-1 is independently a halogen, (5) R 2 is an unsubstituted or 4- to 12-membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 (6) Each R 2-3 is, independently of one another, 【Chemical 137】 It is a 5- to 10-membered heteroaryl group, the heteroatoms of the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 2 or 3, (7) R 2-3-2 is C 2-3-2-1 substituted by one or more R 1 -C 6 -alkyl group, unsubstituted or C 2-3-2-2 substituted by one or more R 3 -C 6 -cycloalkyl group, 【Chemical 138】 Non-replaceable or one or more R 2-3-2-5 is a 3- to 6-membered heterocycloalkyl group or a 5- to 10-membered heteroaryl group replaced by, the heteroatom of the 3- to 6-membered heterocycloalkyl group being selected from any one or more of N, O, and S, the number of heteroatoms being 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group being selected from N and / or O, and the number of heteroatoms being 1 or 2, (8) Each R 2-3-2-1 is, independently of one another, a hydroxy group, 【Chemical 139】 and (9) Each R 2-3-2-1-1 is, independently of one another, a C 1 -C 6 alkyl group, (10) Each R 2-3-2-2 is, independently of one another, halogen, a hydroxy group, C 1 -C 6 alkyl group, unsubstituted or C 2-3-2-2-2 substituted by one or more R 1 -C 6 alkoxy group, amino group, and (11) Each R 2-3-2-2-2 is independently deuterium, (12) Each R 2-3-2-3 is, independently of one another, hydrogen or 【Chemical 140】 and (13) Each R 2-3-2-3-1 is, independently of one another, an unsubstituted or 6- to 10-membered aryl group substituted by one or more R 2-3-2-3-1-1 and each R 2-3-2-3-1-1 is, independently of one another, a C 1 -C 6 alkoxy group, (14) Each R 2-3-2-5 is, independently of one another, halogen, C 1 -C 6 an alkoxy group, C which is unsubstituted or substituted by one or more R 2-3-2-5-1 -C 1 -C 6 an alkyl group, and (15) Each R 2-3-2-5-1 is independently a halogen, (16) R 3 is an unsubstituted 5- or 6-membered heteroaryl group, the heteroatom of the 5- or 6-membered heteroaryl group being N and / or S, and the number of heteroatoms being 3, (17) R 3 is 【Chemical 141】 and (18) R 4 is a deuterium, cyano group, 5- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 and is a 5- to 10-membered heterocycloalkyl group substituted by one or more R, wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1 or 2, (19) Each R 4-1 is, independently of one another, 【Chemical 142】 and R 4-1-1 is C 1 -C 6 is an alkyl group.

16. The compound represented by formula I according to claim 1, its pharmaceutically acceptable salt, or isotopic compound, characterized in that the compound represented by formula I is Scheme 4, Scheme 5, Scheme 6, Scheme 7, Scheme 8, Scheme 9, Scheme 10, or Scheme 11: Scheme 4: R 1 is unsubstituted or a C 1-2 substituted by three or more Rs 1 -C 6 cycloalkyl group, Each R 1-2 is, independently of one another, a cyano group, a C 1-2-1 substituted by a C 1 -C 6 alkyl group, a C 2 -C 6 alkynyl group, and Each R 1-2-1 is, independently of one another, deuterium, a halogen, or a hydroxy group, R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-3 groups, wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is N and / or O, and the number of heteroatoms is 1, 2 or 3, Each R 2-3 is, independently of one another, 【Chemical 143】 It is a 5- to 10-membered heteroaryl group, the heteroatoms of the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 2 or 3, R 2-3-2 is C substituted by one or more R 2-3-2-1 -C 1 -C 6 an alkyl group, unsubstituted or C substituted by one or more R 2-3-2-2 -C 3 -C 6 a cycloalkyl group, 【Chemical 144】 Non-replaceable or one or more R 2-3-2-5 is a 3- to 6-membered heterocycloalkyl group or a 5- to 10-membered heteroaryl group replaced by, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1 or 2, Each R 2-3-2-1 is independently a hydroxy group, 【Chemical 145】 and Each R 2-3-2-1-1 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-2-2 is, independently of one another, halogen, a hydroxy group, C 1 -C 6 alkyl group, unsubstituted or C 2-3-2-2-2 substituted by one or more R 1 -C 6 alkoxy group, an amino group, and Each R 2-3-2-2-2 is, independently of one another, deuterium, Each R 2-3-2-3 is, independently of one another, hydrogen or 【Chemical 146】 and Each R 2-3-2-3-1 is, independently of one another, an unsubstituted or substituted 6- to 10-membered aryl group having one or more R 2-3-2-3-1-1 substituents, and each R 2-3-2-3-1-1 is, independently of one another, a C 1 -C 6 alkoxy group, Each R 2-3-2-5 is, independently of one another, halogen, C 1 -C 6 an alkoxy group, C which is unsubstituted or substituted by one or more R 2-3-2-5-1 -C 1 -C 6 an alkyl group, Each R 2-3-2-5-1 is, independently of one another, halogen, and R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is, independently of one another, a C 3-1-1 -C 1 alkyl group which is substituted by one or more R 6 groups Each R 3-1-1 is, independently of one another, halogen, and R 4 is hydrogen, a cyano group, a halogen, C 1 -C 6 an alkyl group, a 5- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1 or 2, Each R 4-1 is, independently of one another, 【Chemical 147】 and R 4-1-1 is C 1 -C 6 is an alkyl group, Scheme 5: R 1 is unsubstituted or C 1-2 substituted by three or more R 1 -C 6 is a cycloalkyl group, Each R 1-2 is, independently of one another, a cyano group, a C 1-2-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R Each R 1-2-1 is, independently of one another, deuterium, a halogen, and R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is N and / or O, and the number of heteroatoms is 1, 2 or 3, Each R 2-3 is, independently of one another, 【Chemical 148】 and R 2-3-2 where one or more R 2-3-2-2 substitute C 3 -C 6 is a cycloalkyl group substituted by one or more R 2-3-2-5 is a 3- to 6-membered heterocycloalkyl group substituted by one or more R, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1, 2 or 3, the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1 or 2, Each R 2-3-2-2 is, independently of one another, C 1 -C 6 an alkyl group, a C which is unsubstituted or substituted by one or more R 2-3-2-2-2 -C 1 -C 6 an alkoxy group, Each R 2-3-2-2-2 is, independently of one another, deuterium, and Each R 2-3-2-5 is, independently of one another, C 1 -C 6 an alkyl group, R 3 is an unsubstituted or 5-6 membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5-6 membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is, independently of one another, a C 3-1-1 -C 1 alkyl group which is substituted by one or more R 6 groups Each R 3-1-1 is, independently of one another, halogen, R 4 is hydrogen, a cyano group, C 1 -C 6 is an alkyl group, Scheme 6: R 1 is an unsubstituted or 3- to 6-membered heterocycloalkyl group substituted by one or more R 1-3 groups, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is O, the number of heteroatoms is 1, Each R 1-3 is, independently of one another, a cyano group, a C 1-3-1 substituted by a C 1 -C 6 alkyl group, a C 2 -C 6 alkynyl group, and Each R 1-3-1 is, independently of one another, halogen or deuterium, R 2 is an unsubstituted or 4- to 12-membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 2-3-3 is, independently of one another, oxa, C which is unsubstituted or substituted by one or more R 2-3-1 -C 1 -C 6 alkyl group 【Chemical 149】 and Each R 2-3-1 is, independently of one another, a hydroxy group, a halogen, a C 2-3-1-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, an amino group which is unsubstituted or substituted by one or more R 2-3-1-3 and is Each R 2-3-1-1 is independently deuterium, and Each R 2-3-1-3 is, independently of one another, C 1 -C 6 an alkyl group, R 2-3-2 is C 1 -C 6 an alkyl group, unsubstituted or C 2-3-2-2 substituted by one or more R 3 -C 6 is a cycloalkyl group, Each R 2-3-2-2 is, independently of one another, C 1 -C 6 an alkyl group, a C which is unsubstituted or substituted by one or more R 2-3-2-2-2 -C 1 -C 6 an alkoxy group, and Each R 2-3-2-2-2 is independently deuterium, Each R 2-3-3 is, independently of one another, hydrogen, C 2-3-3-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, Each R 2-3-3-1 is, independently of one another, an unsubstituted amino group or an amino group substituted by one or more R 2-3-3-1-1 and is an amino group substituted by one or more R Each R 2-3-3-1-1 is, independently of one another, C 1 -C 6 an alkyl group, R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is, independently of one another, a C 3-1-1 -C 1 alkyl group substituted by one or more R 6 groups and is Each R 3-1-1 is independently a halogen, R 4 is hydrogen, deuterium, a halogen, C 1 -C 6 is an alkyl group, Scheme 7: R 1 is an unsubstituted or 3- to 6-membered heterocycloalkyl group substituted by one or more R 1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is O, the number of heteroatoms is 1 Each R 1-3 is, independently of one another, a cyano group, a C 1-3-1 -C 1 -C 6 alkyl group or a C 2 -C 6 alkynyl group which is unsubstituted or substituted by one or more R Each R 1-3-1 is independently a halogen, R 2 is a 4- to 12-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3 Each R 2-3-3 is, independently of one another, oxa, C 2-3-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more Rs 【Chemical 150】 and Each R 2-3-1 is, independently of one another, a hydroxy group, a C 2-3-1-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, Each R 2-3-1-1 is, independently of one another, deuterium, R 2-3-2 is C 1 -C 6 an alkyl group, unsubstituted or substituted by one or more R 2-3-2-2 to be C 3 -C 6 a cycloalkyl group, and Each R 2-3-2-2 is, independently of one another, C 1 -C 6 an alkyl group, a C 2-3-2-2-2 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, and Each R 2-3-2-2-2 is independently deuterium, Each R 2-3-3 is, independently of one another, hydrogen, C 2-3-3-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, Each R 2-3-3-1 is, independently of one another, an unsubstituted or substituted amino group having one or more R 2-3-3-1-1 groups, Each R 2-3-3-1-1 is, independently of one another, C 1 -C 6 an alkyl group, R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is, independently of one another, a C 3-1-1 -C 1 alkyl group which is substituted by one or more R 6 groups Each R 3-1-1 is independently a halogen, R 4 is hydrogen, deuterium, halogen, C 1 -C 6 is an alkyl group, Scheme 8: R 1 is unsubstituted or C 1-2 substituted by three or more R 1 -C 6 is a cycloalkyl group, Each R 1-2 is independently a cyano group, a C 1-2-1 -C 1 -C 6 alkyl group, a C 2 -C 6 alkynyl group which is unsubstituted or substituted by one or more R Each R 1-2-1 is, independently of one another, deuterium, a halogen, or a hydroxy group, R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is N and / or O, the number of heteroatoms is 1, 2 or 3, and the 4- to 10-membered heterocycloalkyl group is a 4- to 6-membered saturated monocyclic ring, a 7- to 10-membered saturated spiro ring or a 7- to 10-membered saturated bridged ring Each R 2-3 is, independently, 【Chemical 151】 It is a 5- to 10-membered heteroaryl group, the heteroatoms of the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 2 or 3, R 2-3-2 is C replaced by one or more R 2-3-2-1 -C 1 -C 6 an alkyl group, unsubstituted or C replaced by one or more R 2-3-2-2 -C 3 -C 6 a cycloalkyl group, 【Chemical 152】 Unsubstituted or substituted by one or more Rs 2-3-2-5 is a 3- to 6-membered heterocycloalkyl group or a 5- to 10-membered heteroaryl group substituted by 2-3-2-5 , wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the 3- to 6-membered heterocycloalkyl group is a 3- to 6-membered saturated monocyclic ring, the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1 or 2, Each R 2-3-2-1 is, independently of one another, a hydroxy group, 【Chemical 153】 and Each R 2-3-2-1-1 is, independently of one another, C 1 -C 6 an alkyl group, Each R 2-3-2-2 is, independently of one another, halogen, a hydroxy group, C 1 -C 6 alkyl group, unsubstituted or C 2-3-2-2-2 substituted by one or more R 1 -C 6 alkoxy group, an amino group, and Each R 2-3-2-2-2 is independently deuterium, and Each R 2-3-2-3 is, independently of one another, hydrogen or 【Chemical 154】 and Each R 2-3-2-3-1 is, independently of one another, an unsubstituted or 6- to 10-membered aryl group substituted by one or more R 2-3-2-3-1-1 groups, and each R 2-3-2-3-1-1 is, independently of one another, a C 1 -C 6 alkoxy group, Each R 2-3-2-5 is, independently of one another, halogen, C 1 -C 6 an alkoxy group, C which is unsubstituted or substituted by one or more R 2-3-2-5-1 -C 1 -C 6 an alkyl group, Each R 2-3-2-5-1 is, independently of one another, a halogen, and R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is, independently of one another, a C 3-1-1 -C 1 alkyl group which is substituted by one or more R 6 groups Each R 3-1-1 is independently a halogen, R 4 is hydrogen, a cyano group, a halogen, C 1 -C 6 an alkyl group, a 5- to 10-membered heterocycloalkyl group which is unsubstituted or substituted by one or more R 4-1 wherein the heteroatom of the 5- to 10-membered heterocycloalkyl group is selected from any one or more of N, O and S, the number of heteroatoms is 1 or 2, and the 5- to 10-membered heterocycloalkyl group is a 7- to 10-membered unsaturated spiro ring, Each R 4-1 is, independently of one another, 【Chemical 155】 and R 4-1-1 is C 1 -C 6 is an alkyl group, Scheme 9: R 1 is unsubstituted or a C 1-2 -C 1 -C 6 cycloalkyl group substituted by three or more R Each R 1-2 is, independently of one another, a cyano group, a C 1-2-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, Each R 1-2-1 is, independently of one another, deuterium, a halogen, and R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2-3 wherein the heteroatom of the 4- to 10-membered heterocycloalkyl group is selected from N and / or O, the number of heteroatoms is 1, 2 or 3, and the 4- to 10-membered heterocycloalkyl group is a 4- to 6-membered saturated monocyclic ring or a 7- to 10-membered saturated spiro ring, Each R 2-3 is, independently of one another, 【Chemical 156】 and R 2-3-2 wherein one or more R 2-3-2-2 substitute C 3 -C 6 a cycloalkyl group, one or more R 2-3-2-5 substitute a 3- to 6-membered heterocycloalkyl group, wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, the 3- to 6-membered heterocycloalkyl group is a 3- to 6-membered saturated monocyclic ring, the heteroatom of the 5- to 10-membered heteroaryl group is N and / or O, the number of heteroatoms is 1 or 2, Each R 2-3-2-2 is, independently of one another, C 1 -C 6 an alkyl group, C which is unsubstituted or substituted by one or more R 2-3-2-2-2 -C 1 -C 6 an alkoxy group, and Each R 2-3-2-2-2 is independently deuterium, Each R 2-3-2-5 is, independently of one another, C 1 -C 6 an alkyl group, R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is independently a C 3-1-1 -C 1 -C 6 alkyl group substituted by one or more Rs Each R 3-1-1 is, independently of one another, halogen, and R 4 is hydrogen, a cyano group, C 1 -C 6 is an alkyl group, Scheme 10: R 1 is an unsubstituted or 3- to 6-membered heterocycloalkyl group substituted by one or more R 1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is O, the number of heteroatoms is 1, and the 3- to 6-membered heterocycloalkyl group is a 3- to 6-membered saturated monocyclic ring Each R 1-3 is, independently of one another, a cyano group, a C 1-3-1 -C 1 -C 6 alkyl group, a C 2 -C 6 alkynyl group which is unsubstituted or substituted by one or more R Each R 1-3-1 is independently a halogen or deuterium, R 2 is a 4- to 12-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and the 4- to 12-membered heterocycloalkyl group is a 4- to 6-membered saturated monocyclic ring, a 7- to 10-membered saturated condensed ring, or a 7- to 10-membered saturated spiro ring Each R 2-3-3 is, independently of one another, oxa, C which is unsubstituted or substituted by one or more R 2-3-1 -C 1 -C 6 alkyl group, 【Chemical 157】 and Each R 2-3-1 is, independently of one another, a hydroxy group, a halogen, a C 2-3-1-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, an amino group which is unsubstituted or substituted by one or more R 2-3-1-3 and Each R 2-3-1-1 is, independently of one another, deuterium, and Each R 2-3-1-3 is, independently of one another, C 1 -C 6 an alkyl group, R 2-3-2 is C 1 -C 6 an alkyl group, unsubstituted or substituted by one or more R 2-3-2-2 groups, and is C 3 -C 6 a cycloalkyl group, Each R 2-3-2-2 is, independently of one another, C 1 -C 6 an alkyl group, a C which is unsubstituted or substituted by one or more R 2-3-2-2-2 -C 1 -C 6 an alkoxy group, and Each R 2-3-2-2-2 is, independently of one another, deuterium, Each R 2-3-3 is, independently of one another, hydrogen, C 2-3-3-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, Each R 2-3-3-1 is, independently of one another, an unsubstituted or amino group substituted by one or more R 2-3-3-1-1 and is a substituted amino group, Each R 2-3-3-1-1 is, independently of one another, C 1 -C 6 an alkyl group, R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is, independently of one another, a C 3-1-1 -C 1 -C 6 alkyl group which is substituted by one or more Rs Each R 3-1-1 is independently a halogen, R 4 is hydrogen, deuterium, halogen, C 1 -C 6 is an alkyl group, Scheme 11: R 1 is an unsubstituted or 3- to 6-membered heterocycloalkyl group substituted by one or more R 1-3 wherein the heteroatom of the 3- to 6-membered heterocycloalkyl group is O, the number of heteroatoms is 1, and the 3- to 6-membered heterocycloalkyl group is a 3- to 6-membered saturated monocyclic ring Each R 1-3 is, independently of one another, a cyano group, a C 1-3-1 -C 1 -C 6 alkyl group which is unsubstituted or substituted by one or more R 2 -C 6 alkynyl group, and Each R 1-3-1 is independently a halogen, and R 2 is a 4- to 12-membered heterocycloalkyl group that is unsubstituted or substituted by one or more R 2-3 wherein the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O, and S, the number of heteroatoms is 1, 2, or 3, and the 4- to 12-membered heterocycloalkyl group is a 4- to 6-membered saturated monocyclic ring, a 7- to 10-membered saturated condensed ring, or a 7- to 10-membered saturated spiro ring Each R 2-3-3 is, independently of one another, oxa, C which is unsubstituted or substituted by one or more R 2-3-1 -C 1 -C 6 alkyl group, 【Chemical 158】 and Each R 2-3-1 is, independently of one another, a hydroxy group, a C 2-3-1-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkoxy group, Each R 2-3-1-1 is independently deuterium, and R 2-3-2 is C 1 -C 6 an alkyl group, unsubstituted or substituted by one or more R 2-3-2-2 to form C 3 -C 6 a cycloalkyl group, and Each R 2-3-2-2 is, independently of one another, C 1 -C 6 an alkyl group, a C which is unsubstituted or substituted by one or more R 2-3-2-2-2 and is a C 1 -C 6 alkoxy group, Each R 2-3-2-2-2 is independently deuterium, Each R 2-3-3 is, independently of one another, hydrogen, C 2-3-3-1 which is unsubstituted or substituted by one or more R 1 -C 6 alkyl group, Each R 2-3-3-1 is, independently of one another, an unsubstituted or amino group substituted by one or more R 2-3-3-1-1 and is Each R 2-3-3-1-1 is, independently of one another, C 1 -C 6 an alkyl group, R 3 is an unsubstituted or 5- to 6-membered heteroaryl group substituted by one or more R 3-1 wherein the heteroatom of the 5- to 6-membered heteroaryl group is N and / or S, and the number of heteroatoms is 3 Each R 3-1 is, independently of one another, a C 3-1-1 -C 1 -C 6 alkyl group which is substituted by one or more Rs Each R 3-1-1 is, independently of one another, halogen, and R 4 is hydrogen, deuterium, a halogen, C 1 -C 6 and is an alkyl group.

17. The compound represented by the formula I-a can be a compound represented by the formula IV, characterized in that the compound represented by the formula I, its pharmaceutically acceptable salt or isotope compound according to claim 7, 【Chemical 159】 Ring D is a 3- to 6-membered heterocycloalkyl group, the heteroatom of the 3- to 6-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Ring C is a 4- to 12-membered heterocycloalkyl group, the heteroatom of the 4- to 12-membered heterocycloalkyl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, Ring A is a 5- to 10-membered heteroaryl group, the heteroatom of the 5- to 10-membered heteroaryl group is selected from any one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3, n is 0, 1 or 2, m is 0, 1 or 2, and k is 0, 1 or 2, R 1-3’ is hydrogen or R 1-3 and R 1-3 , R 2-3 and R 3-1 The definitions of are shown in any one of claims 1 to 6, 11 to 16.

18. The compound represented by the formula I-a can be a compound represented by the formula V, 【Chemical 160】 M is N, O or S, i is 0, 1 or 2, j is 0, 1 or 2, and is 0 when i and j are different, Ring C, ring A, R 1-3’ , R 1-3 , R 2-3 , R 3-1 , the definitions of n, m and k are shown in claim 17, Preferably, the compound represented by the formula I-a can be a compound represented by the formula VI, 【Chemical 161】 Ring C, Ring A, R 1-3’ , R 1-3 , R 2-3 , R 3-1 , the definitions of n, m, k, i and j are shown in claim 17, More preferably, the compound represented by the formula I-a can be a compound represented by the formula VII, 【Chemical 162】 V 1 is CH, N or O, and V 2 is CH, N or O, and V 1 and V 2 is CH when they are different, and R 3-1’ is hydrogen or R 3-1 and R V 1 is hydrogen or R 2-3 where R V 2 is hydrogen or R 2-3 where R 1-3’ 、R 1-3 、R 2-3 、R 3-1 The definitions of n, m, i and j are shown in claim 17, Or the compound represented by the formula I-a can be a compound represented by the formula VIII, 【Chemical 163】 R V 1 and R V 2 and R 1-3’ and R 1-3 and R 2-3 and R 3-1’ The definitions of n, m, i and j are shown in claim 17, Most preferably, the compound represented by the formula I-a can be a compound represented by the formula IX, 【Chemical 164】 U is CH, N or O, p is 0, 1 or 2, q is 0, 1 or 2, R 1-3’ 、R 1-3 、R 2-3 、R 3-1’ 、the definitions of n, m, i and j are shown in claim 17, Or the compound represented by the formula I-a can be a compound represented by the formula X, 【Chemical 165】 R G is R 2-3-2 or 【Chemical 166】 and R 1-3’ 、R 1-3 、R 2-3 、R 3-1’ 、R 2-3-2 、R 2-3-3 、V 1 、V 2 A compound of formula I, a pharmaceutically acceptable salt thereof, or an isotopic compound, as claimed in claim 17, wherein the definitions of R, 1-3’ , R, 1-3 , R, 2-3 , R, 3-1’ , R, 2-3-2 , R, 2-3-3 , V, 1 , V, 2 , n, m, i and j are as set forth in claim 17.

19. The compound represented by the formula I is characterized by satisfying any one or more of the following conditions: the compound represented by the formula I, its pharmaceutically acceptable salt, or isotope compound according to claim 1: (1) Ring B is 【Chemical 167】 and (2)R 1 is 【Chemical 168】 or R 1 the atom in 1 and the atom in A are linked 【Chemical 169】 forms (3) R 2 is hydrogen, a methyl group, 【Chemical 170】 【Chem.】 【Chem.】 [Chemical] and is (4)R 3 is 【Chemical 171】 and is and, (5) R 4 wherein R is hydrogen, deuterium, Cl, F, CN, a methyl group, 【Chemical 172】 .

20. The compound represented by the formula I is 【Chemical 173】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 [Chemical] 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 any one of the compounds, characterized in that the compound represented by the formula I, its pharmaceutically acceptable salt, or isotope compound according to claim 1.

21. A pharmaceutical composition comprising substance Z and a pharmaceutical excipient, wherein the substance Z is a compound represented by formula I, a pharmaceutically acceptable salt thereof, or an isotopic compound as described in any one of claims 1 to 20.

22. Use of substance Z in the preparation of a PARG inhibitor and a medicament for treating and / or preventing PARG-related diseases, wherein the substance Z is a compound represented by formula I, a pharmaceutically acceptable salt thereof, or an isotopic compound, and the PARG-related disease is breast cancer, for example, triple-negative breast cancer.

23. Use of substance Z in the preparation of a medicament for treating and / or preventing breast cancer, wherein the substance Z is a compound represented by formula I, a pharmaceutically acceptable salt thereof, or an isotopic compound as described in any one of claims 1 to 20, and the breast cancer is triple-negative breast cancer.

24. 【Fig. 174】 wherein Here, R 5 is hydrogen or PMB, and R 6 is halogen, deuterium, and R 7 is R 3 , hydrogen or 【Chemical 175】 and R 8 is hydrogen or C 1 -C 6 alkyl group, and R 9 is 【Chemical 176】 or a halogen, R 1 、R 2 、R 3 The definitions of R, 1 , R, 2 , R, 3 , X, Y, Z and W are shown in any one of claims 1 to 19, Preferably, R 6 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example, may be chlorine or bromine, (117) R 8-1-2 wherein said C 1 -C 6 alkyl group is a C 1 -C 4 alkyl group and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and may also be a methyl group or an ethyl group, and / or, R 9 In 9 , the halogen may be fluorine, chlorine, bromine or iodine, and for example, chlorine or bromine, and a compound represented by formula II, III, IV or V or a salt thereof.

25. The compound represented by formula II is 【Chemical 177】 any of the structures of and / or, the compound represented by formula III is 【Chemical 178】 any of the structures of and / or, the compound represented by formula IV is 【Chemical 179】 any of the structures of and / or, the compound represented by formula V is 【Chemical 180】 any of the structures of, characterized in that, the compound represented by formula II, III, IV or V or a salt thereof according to claim 24.

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