HETEROCYCLIC COMPOUND WITH FUSION RINGS, ITS COMPOSITION AND APPLICATION

Abstract

The present invention relates to a compound of formula (I), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof, a pharmaceutical composition thereof, and a use thereof in the treatment and / or prevention of diseases modulated by wild-type and / or mutant Bcr-Abl1 kinase.

Description

Heterocyclic compounds, compositions and uses thereof Technical Field

[0001] The present invention belongs to the field of medicine, and in particular relates to compounds that have an inhibitory effect on the tyrosine kinase activity of Abelson protein (Abl1), Abelson-related protein (Abl2) and related chimeric proteins, especially Bcr-Abl1 and its mutations, as well as pharmaceutical compositions containing the compounds, as well as their preparation methods and uses. Background Art

[0002] The pathogenesis of chronic myelogenous leukemia (CML) and some adult acute lymphoblastic leukemia (ALL) is caused by chromosomal translocation (9;22)(q34;q11), which causes the Bcr and Abl1 genes to fuse on the Philadelphia chromosome to form the Bcr-Abl1 fusion gene. The Bcr-Abl1 fusion gene translates into the Bcr-Abl1 fusion protein, which abnormally increases the activity of the Bcr-Abl1 tyrosine kinase, resulting in the effects of promoting cell proliferation, inhibiting apoptosis, and weakening cell adhesion. The emergence of Bcr-Abl1 tyrosine kinase inhibitors has completely changed the treatment of CML. They inhibit the Bcr-Abl1 pathway and significantly reduce the proliferation of CML cells expressing Bcr-Abl1. Currently, effective drugs for the treatment of CML that target the ATP binding site include imatinib, a type II tyrosine kinase inhibitor that binds to the DFG-out conformation. ) and nilotinib ( ), and the type I inhibitor dasatinib (dasatinib, ) and bosutinib ( However, continued drug treatment is due to the occurrence of Bcr-Abl1 T315I Although ponatinib (ponatinib, ) can significantly inhibit the T315M mutation, but it has adverse reactions on other kinases due to off-target effects.

[0003] In 2003, the research group of Kuriyan and SupertiFurga reported that myristoyl participates in the autoregulation of Abl1 kinase, inducing cross-linking of SH3-SH2-Kianse structure, playing a key role in negatively regulating Abl1 kinase activity and allowing normal cell proliferation. However, when the Bcr-Abl1 fusion protein is formed, Bcr occupies the myristoyl binding site of the N-terminal cap region of Abl1 and cannot induce cross-linking of SH3-SH2-Kinase domain, resulting in the structural activation of Bcr-Abl1, causing cells to undergo continuous differentiation and proliferation and become malignant. Asiciminib ( ) is an allosteric inhibitor that binds to the myristoyl pocket of Abl1. Assinib is active in the low nanomolar range against all catalytic ATP site mutations in Bcr-Abl1, including the T315I mutation. Some mutations in the myristoyl binding site (e.g., P465S, ​​V468F, I502L, A337V, A424T) confer resistance to assinib.

[0004] Therefore, it is necessary to further develop new Bcr-Abl1 allosteric inhibitors.

[0005] SUMMARY OF THE INVENTION

[0006] The present invention provides a novel hetero-fused ring compound, a composition containing the compound, and uses thereof. The compound exhibits high inhibitory activity, low side effects, and / or excellent pharmacodynamic / pharmacokinetic properties against Bcr-Abl1 and its catalytic ATP site mutations and / or allosteric site mutations, and can be used to treat diseases or conditions regulated by wild-type and / or mutant Bcr-Abl1 kinases.

[0007] To this end, the present invention adopts the following technical solutions:

[0008] In one aspect, the present invention provides a compound of formula (I), or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof:

[0009] in,

[0010] X1 is N or CR X1 ;

[0011] X2 is CR X2 R X2’ or C(O);

[0012] X3 for CR X3 R X3’ , CR X3 or NR X3 ;

[0013] X4 for CR X4 R X4’ , CR X4 ,NR X4 or C(O);

[0014] X5 is N or CR X5 ;

[0015] X6 is N or CR X6 ;

[0016] is a single bond or a double bond;

[0017] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0018] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0019] R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R X3 and R X3’ Together with the carbon atoms to which they are attached, they form C 1-6 wherein the above groups are optionally replaced by one or more R a replace;

[0020] R X4 and R X4’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally replaced by one or more R a replace;

[0021] Or, R X3 and R X4 Together with the atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6- 10Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R;

[0022] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0023] R X6 is H, D or halogen;

[0024] Y is CR Y or N;

[0025] R1 is a 3-10 membered heterocyclic group, which is optionally substituted by one or more R b replace;

[0026] R Y is H, D or halogen;

[0027] Alternatively, R1 and R Y Together with the carbon atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6- 10 aryl or 5-10 membered heteroaryl, optionally substituted with one or more R*;

[0028] R1' is H, D, halogen or -NH2;

[0029] W is CR W or N;

[0030] R W is selected from H, D, halogen or -NH2;

[0031] Y1 is CR Y1 or N;

[0032] Y2 is CR Y2 or N;

[0033] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally replaced by one or more R c replace;

[0034] Z is a chemical bond, O or S(O) 0-2 ;

[0035] R Z H, D, C 1-6 Alkyl or C 1-6wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0036] or -ZR Z Together they represent -SF5;

[0037] Each R a 、R b and R c are independently H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0038] Each R is independently H, D, halogen, -CN, -OR A , -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R';

[0039] Each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by one or more R';

[0040] Each R A 、R B and R CIndependently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein the above groups are optionally substituted by one or more R';

[0041] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R";

[0042] Or two adjacent R' together with the atoms they are connected to form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1- 6 haloalkoxy substituted; wherein the above groups are optionally substituted by one or more D, until fully deuterated;

[0043] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0044] The premise is that when X1 is N, X2 is CH2, and X3 is NR X3 , X4 is C(O), and X5 is CH, Y is not N.

[0045] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of the present invention, or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof, and a pharmaceutically acceptable excipient, and optionally, other therapeutic agents.

[0046] In another aspect, the present invention provides a unit dosage form comprising a pharmaceutical composition of a compound of the present invention.

[0047] In another aspect, the present invention provides a compound of the present invention, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate, or solvate thereof, or a pharmaceutical composition of the present invention, or a unit dosage form of the present invention for use in the preparation of a medicament for treating and / or preventing diseases regulated by wild-type and / or mutant Bcr-Abl1 kinases. Preferably, the mutant Bcr-Abl1 kinase has a mutation selected from one or more of the following: T315I, T315M, F317L, E355G, V299L, M244V, G250E, Q252H, Y253H, E255K, E255V, H396P, H396R, H396A, A397P, P223S, K294E, M351T, F359V, E459K, P465S, ​​V468F, I502L, A337V, and A424T. Preferably, the mutation in the mutant Bcr-Abl1 kinase is selected from the group consisting of: T315I and / or T315M. Preferably, the mutation in the mutant Bcr-Abl1 kinase is T315I. Preferably, the mutation in the mutant Bcr-Abl1 kinase is selected from one or more of the following: P465S, ​​V468F, I502L, A337V, and A424T.

[0048] In another aspect, the present invention provides a method for treating and / or preventing a disease regulated by wild-type and / or mutant Bcr-Abl1 kinase in a subject, comprising administering to the subject a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the present invention, or a unit dosage form of the present invention. Preferably, the mutation in the mutant Bcr-Abl1 kinase is selected from one or more of the following: T315I, T315M, F317L, E355G, V299L, M244V, G250E, Q252H, Y253H, E255K, E255V, H396P, H396R, H396A, A397P, P223S, K294E, M351T, F359V, E459K, P465S, ​​V468F, I502L, A337V, and A424T. Preferably, the mutation in the mutant Bcr-Abl1 kinase is selected from T315I and / or T315M. Preferably, the mutation in the mutant Bcr-Abl1 kinase is T315I. Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from one or more of the following: P465S, ​​V468F, I502L, A337V and A424T.

[0049] In another aspect, the present invention provides a compound of the present invention, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition of the present invention, or a unit dosage form of the present invention, for use in treating and / or preventing diseases regulated by wild-type and / or mutant Bcr-Abl1 kinases. Preferably, the mutant Bcr-Abl1 kinase has a mutation selected from one or more of the following: T315I, T315M, F317L, E355G, V299L, M244V, G250E, Q252H, Y253H, E255K, E255V, H396P, H396R, H396A, A397P, P223S, K294E, M351T, F359V, E459K, P465S, ​​V468F, I502L, A337V and A424T. Preferably, the mutation in the mutant Bcr-Abl1 kinase is selected from the group consisting of: T315I and / or T315M. Preferably, the mutation in the mutant Bcr-Abl1 kinase is T315I. Preferably, the mutation in the mutant Bcr-Abl1 kinase is selected from one or more of the following: P465S, ​​V468F, I502L, A337V, and A424T.

[0050] In a more specific aspect, the diseases regulated by wild-type and / or mutant Bcr-Abl1 kinases of the present invention are selected from the group consisting of leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myeloma, neurodegenerative disease, solid tumor, immune disease or fibrosis. In a more specific aspect, the diseases regulated by wild-type and / or mutant Bcr-Abl1 kinases of the present invention are selected from the group consisting of acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic lymphoma, chronic myeloid leukemia, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, acute undifferentiated leukemia, anaplastic large cell lymphoma, prolymphocytic leukemia, juvenile myelomonocytic leukemia, adult T-cell leukemia, acute myeloid leukemia with trilineage myelodysplasia, mixed lineage leukemia, myelodysplastic syndrome, amyotrophic lateral sclerosis, Parkinson's disease or Alzheimer's disease.

[0051] In more specific aspects, the wild-type and / or mutant Bcr-Abl1 kinases described herein are regulated in acute lymphoblastic leukemia or chronic myeloid leukemia.

[0052] Other objects and advantages of the present invention will be apparent to those skilled in the art from the following detailed description, examples and claims.

[0053] definition

[0054] Chemical definition

[0055] Definitions of specific functional groups and chemical terms are described in more detail below.

[0056] When a numerical range is listed, it is intended to include every value and sub-range within the stated range. For example, "C 1-6 "Alkyl" includes C1, C2, C3, C4, C5, C6, C 1-6 、C 1-5 、C 1-4 、C 1-3 、C 1-2 、C 2-6 、C 2-5 、C 2-4 、C 2-3 、C 3-6 、 C 3-5 、C 3-4 、C 4-6 、C 4-5 and C 5-6 alkyl.

[0057] “C 1-6 "Alkyl" refers to a straight or branched chain saturated hydrocarbon group having 1 to 6 carbon atoms, also referred to herein as "lower alkyl". In some embodiments, C 1-4 Alkyl and C 1-3 Alkyl is particularly preferred. Examples of the alkyl include, but are not limited to, methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3-pentyl (C5), pentyl (C5), neopentyl (C5), 3-methyl-2-butyl (C5), tert-pentyl (C5) and n-hexyl (C6). Regardless of whether the alkyl group is modified with "substituted", each of the alkyl groups is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent, and suitable substituents are defined as follows.

[0058] “C 1-6 "Alkylene" refers to =CRR, where R is H or C 1-5 alkyl.

[0059] “C 2-6 "Alkenyl" refers to a straight or branched chain hydrocarbon group having 2 to 6 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, or 3 carbon-carbon double bonds). The one or more carbon-carbon double bonds can be internal (e.g., in 2-butenyl) or terminal (e.g., in 1-butenyl). In some embodiments, C 2-4Alkenyl is particularly preferred. Examples of the alkenyl include, but are not limited to, vinyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Regardless of whether the alkenyl is modified with "substituted", each of the alkenyl groups is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, and suitable substituents are defined below.

[0060] “C 2-6 "Alkynyl" refers to a straight or branched chain hydrocarbon group having 2 to 6 carbon atoms, one or more carbon-carbon triple bonds (e.g., 1, 2, or 3 carbon-carbon triple bonds), and optionally one or more carbon-carbon double bonds (e.g., 1, 2, or 3 carbon-carbon double bonds). In some embodiments, C 2-4 Alkynyl is particularly preferred. In some embodiments, alkynyl does not contain any double bond. One or more carbon triple bonds can be internal (e.g., in 2-butynyl) or end (e.g., in 1-butynyl). Examples of the alkynyl include, but are not limited to, ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), pentynyl (C5), hexynyl (C6), and the like. Regardless of whether "substituted" is modified before the alkynyl, each of the alkynyl groups is optionally substituted independently, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, and suitable substituents are defined as follows.

[0061] “C 1-6 "Alkoxy" refers to a group -OR, where R is a substituted or unsubstituted C 1-6 In some embodiments, C 1-4 Alkoxy and C 1-3 Alkoxy groups are particularly preferred. Specific alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy.

[0062] "Halo" or "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), and iodine (I). In some embodiments, the halo group is F, Cl, or Br. In some embodiments, the halo group is F or Cl. In some embodiments, the halo group is F.

[0063] Therefore, “C 1-6 Haloalkyl" and "C 1-6 "Haloalkoxy" refers to the above-mentioned "C 1-6 Alkyl" and "C 1-6 Alkoxy", which is substituted by one or more halogen groups. In some embodiments, C1-4 Halogenated alkyl is particularly preferred, more preferably C 1- 3 haloalkyl and C 1-2 In some embodiments, C 1-4 Haloalkoxy is particularly preferred, more preferably C 1-3 Haloalkoxy and C 1-2 Halogenated alkoxy. Exemplary haloalkyl groups include, but are not limited to, -CF3, -CH2F, -CHF2, -CHFCH2F, -CH2CHF2, -CF2CF3, -CCl3, -CH2Cl, -CHCl2, 2,2,2-trifluoro-1,1-dimethyl-ethyl, and the like. Exemplary haloalkoxy groups include, but are not limited to, -OCH2F, -OCHF2, -OCF3, and the like.

[0064] “C 1-6 Alkylene" and "C 1-6 "Haloalkylene" refers to the removal of C 1-6 Alkyl and C 1-6 In some embodiments, C 1-4 Alkylene, C 2-4 Alkylene and C 1-2 Alkylene is preferred. In some embodiments, C 1-4 Halogenated alkylene, C 2-4 Halogenated alkylene and C 1- 2 haloalkylene groups are preferred. Unsubstituted alkylene groups include, but are not limited to, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), butylene (-CH2CH2CH2CH2-), pentylene (-CH2CH2CH2CH2CH2-), hexylene (-CH2CH2CH2CH2CH2CH2-), and the like. Exemplary substituted alkylene groups, for example, alkylene groups substituted with one or more alkyl (methyl) groups, include, but are not limited to, substituted methylene (-CH(CH3)-, -C(CH3)2-), substituted ethylene (-CH(CH3)CH2-, -CH2CH(CH3)-, -C(CH3)2CH2-, -CH2C(CH3) 2- ), substituted propylene (-CH(CH3)CH2CH2-, -CH2CH(CH3)CH2-, -CH2CH2CH(CH3)-, -C(CH3)2CH2CH2-, -CH2C(CH3)2CH2-, -CH2CH2C(CH3)2-), and the like.

[0065] “C 3-10"Cycloalkyl" refers to a non-aromatic cyclic hydrocarbon group having 3 to 10 ring carbon atoms and zero heteroatoms. In some embodiments, C 3-8 Cycloalkyl is preferred, C 3-6 Cycloalkyl is particularly preferred, more preferably C 5-6 Cycloalkyl. Cycloalkyl also includes ring systems in which the above-mentioned cycloalkyl ring is fused to one or more aryl or heteroaryl groups, wherein the point of attachment is on the cycloalkyl ring, and in such cases, the number of carbons continues to represent the number of carbons in the cycloalkyl system. Exemplary cycloalkyls include, but are not limited to, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptyl (C7), bicyclo[2.2.2]octyl (C8), cyclononyl (C9), cyclononenyl (C9), cyclodec ... 10 ), cyclodecenyl (C 10 ), octahydro-1H-indenyl (C9), decahydronaphthyl (C 10 ), spiro[4.5]decyl (C 10 ), etc. Regardless of whether the cycloalkyl group is preceded by "substituted", each of the cycloalkyl groups is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent, and suitable substituents are defined below.

[0066] "3-10 membered heterocyclyl" refers to a radical of a 3- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon. In heterocyclyl groups containing one or more nitrogen atoms, the point of attachment may be a carbon or nitrogen atom, as valence permits. In some embodiments, a 4- to 10-membered heterocyclyl is preferred, which is a 4- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms; in some embodiments, a 3- to 7-membered heterocyclyl is preferred, which is a 3- to 7-membered non-aromatic ring system having ring carbon atoms and 1 to 3 ring heteroatoms; in some embodiments, a 3- to 6-membered heterocyclyl is particularly preferred, which is a 3- to 6-membered non-aromatic ring system having ring carbon atoms and 1 to 3 ring heteroatoms; and more preferably a 5- to 6-membered heterocyclyl is a 5- to 6-membered non-aromatic ring system having ring carbon atoms and 1 to 3 ring heteroatoms. Heterocyclyl also includes ring systems in which the above-mentioned heterocyclyl ring is fused to one or more cycloalkyl, aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring; and in such cases, the number of ring members continues to represent the number of ring members in the heterocyclyl ring system. Regardless of whether the heterocyclyl group is preceded by "substituted", each of the heterocyclyl groups is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents or 1 substituent, suitable substituents being defined below.

[0067] Exemplary 3-membered heterocyclic groups containing one heteroatom include, but are not limited to, aziridine, oxirane, and thiorenyl. Exemplary 4-membered heterocyclic groups containing one heteroatom include, but are not limited to, azetidinyl, oxetane, and thietidinyl. Exemplary 5-membered heterocyclic groups containing one heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclic groups containing two heteroatoms include, but are not limited to, dioxolane, oxasulfuranyl, disulfuranyl, and Exemplary 5-membered heterocyclic groups containing three heteroatoms include, but are not limited to, triazolinyl, Exemplary 6-membered heterocyclic groups containing one heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclic groups containing two heteroatoms include, but are not limited to, piperazinyl, morpholinyl, dithian ... Alkyl. Exemplary 6-membered heterocyclic groups containing three heteroatoms include, but are not limited to, hexahydrotriazinyl (triazinanyl). Exemplary 7-membered heterocyclic groups containing one heteroatom include, but are not limited to, azepanyl, oxepanyl, and thiepanyl. Exemplary 8-membered heterocyclic groups containing one heteroatom include, but are not limited to, azocanyl, oxepanyl, and thiecanyl. Exemplary 5-membered heterocyclic groups fused to a C6 aryl ring (also referred to herein as 5,6-bicyclic heterocyclic groups) include, but are not limited to, dihydroindole, isoindole, dihydrobenzofuranyl, dihydrobenzothiophenyl, benzo Exemplary 6-membered heterocyclyl groups (also referred to herein as 6,6-bicyclic heterocyclyl groups) fused to a C6 aryl ring include, but are not limited to, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like.

[0068] “C 6-14 "Aryl" refers to a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic arrangement) having 6-14 ring carbon atoms and zero heteroatoms. In some embodiments, an aryl group has six ring carbon atoms ("C6 aryl"; e.g., phenyl). In some embodiments, an aryl group has ten ring carbon atoms ("C 10 In some embodiments, an aryl group has fourteen ring carbon atoms ("C 14 In some embodiments, C 6-10 Aryl is particularly preferred, with C6 aryl being more preferred. Aryl also includes ring systems in which the aforementioned aryl ring is fused to one or more cycloalkyl or heterocyclic groups, with the point of attachment being on the aryl ring. In this case, the number of carbon atoms continues to represent the number of carbon atoms in the aryl ring system. Regardless of whether the aryl group is preceded by "substituted," each aryl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. Suitable substituents are defined below.

[0069] "5-10 membered heteroaryl" refers to a group of a 5-10 membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 π electrons shared in a cyclic arrangement) having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In heteroaryl groups containing one or more nitrogen atoms, the point of attachment may be a carbon or nitrogen atom as long as valence permits. Heteroaryl bicyclic ring systems may include one or more heteroatoms in one or both rings. Heteroaryl also includes ring systems in which the above-mentioned heteroaryl rings are fused to one or more cycloalkyl or heterocyclyl groups, and the point of attachment is on the heteroaryl ring, in which case the number of carbon atoms continues to represent the number of carbon atoms in the heteroaryl ring system. In some embodiments, 5-6 membered heteroaryl is particularly preferred, which is a 5-6 membered monocyclic or bicyclic 4n+2 aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms. In some embodiments, 5-membered heteroaryl is particularly preferred, which is a 5-membered monocyclic or bicyclic 4n+2 aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms. Regardless of whether the heteroaryl group is preceded by "substituted", each of the heteroaryl groups is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, and suitable substituents are defined below.

[0070] Exemplary 5-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyrrolyl, furanyl, and thienyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, but are not limited to, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, but are not limited to, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, but are not limited to, tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, but are not limited to, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing three or four heteroatoms include, but are not limited to, triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing one heteroatom include, but are not limited to, azepine, oxepinyl, and thiepine. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzisothiazolyl, benzothiadiazolyl, indanyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl.

[0071] Exemplary substituents on carbon atoms include, but are not limited to, halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR aa 、-ON(R bb )2、-N(R bb )2、-N(R bb )3 + X - 、-N(OR cc )R bb 、-SH、-SR aa 、-SSR cc 、-C(=O)R aa 、-CO2H、-CHO、-C(OR cc )2, -CO2R aa 、-OC(=O)R aa 、-OCO2R aa 、-C(=O)N(R bb )2、-OC(=O)N(R bb )2. -NR bb C(=O)R aa 、-NR bb CO2R aa 、-NR bb C(=O)N(R bb )2、-C(=NR bb )R aa 、-C(=NR bb )OR aa 、-OC(=NR bb )R aa 、-OC(=NR bb )OR aa 、-C(=NR bb )N(R bb )2、-OC(=NR bb )N(R bb )2、-NR bb C(=NR bb )N(R bb )2, -C(=O)NR bb SO2R aa 、-NR bb SO2R aa 、-SO2N(R bb )2, -SO2R aa 、-SO2OR aa 、-OSO2R aa 、-S(=O)R aa 、-OS(=O)R aa 、-Si(R aa)3、-OSi(R aa )3、-C(=S)N(R bb )2, -C(=O)SR aa 、-C(=S)SR aa 、-SC(=S)SR aa 、-SC(=O)SR aa 、-OC(=O)SR aa 、-SC(=O)OR aa 、-SC(=O)R aa 、-P(=O)2R aa 、-OP(=O)2R aa 、-P(=O)(R aa )2、-OP(=O)(R aa )2、-OP(=O)(OR cc )2、-P(=O)2N(R bb )2、-OP(=O)2N(R bb )2、-P(=O)(NR bb )2、-OP(=O)(NR bb )2、-NR bb P(=O)(OR cc )2、-NR bb P(=O)(NR bb )2、-P(R cc )2、-P(R cc )3、-OP(R cc )2、-OP(R cc )3、-B(R aa )2、-B(OR cc )2, -BR aa (OR cc ), alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently replaced by 0, 1, 2, 3, 4 or 5 R dd group substitution;

[0072] Or the two geminal hydrogen atoms on the carbon atom are replaced by groups =O, =S, =NN(R bb )2, =NNR bb C(=O)R aa 、=NNR bb C(=O)OR aa 、=NNR bb S(=O)2R aa 、=NR bb or = NOR cc replace;

[0073] R aa Each of R is independently selected from alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two R aa The groups are combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl group is independently replaced by 0, 1, 2, 3, 4 or 5 R dd group substitution;

[0074] R bb Each of the following is independently selected from: hydrogen, -OH, -OR aa 、-N(R cc )2, -CN, -C(=O)R aa 、-C(=O)N(R cc )2, -CO2R aa 、-SO2R aa 、-C(=NR cc )OR aa 、-C(=NR cc )N(R cc )2、-SO2N(R cc )2, -SO2R cc 、-SO2OR cc 、-SOR aa 、-C(=S)N(R cc )2, -C(=O)SR cc 、-C(=S)SR cc 、-P(=O)2R aa 、-P(=O)(R aa )2、-P(=O)2N(R cc )2、-P(=O)(NR cc )2, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl and heteroaryl, or two R bb The groups are combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl group is independently replaced by 0, 1, 2, 3, 4 or 5 R dd group substitution;

[0075] R cc Each of R is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two R cc The groups are combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl group is independently replaced by 0, 1, 2, 3, 4 or 5 R dd group substitution;

[0076] R ddEach of the is independently selected from: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR ee 、-ON(R ff )2、-N(R ff )2,、-N(R ff )3 + X - 、-N(OR ee )R ff 、-SH、-SR ee 、-SSR ee 、-C(=O)R ee 、-CO2H、-CO2R ee 、-OC(=O)R ee 、-OCO2R ee 、-C(=O)N(R ff )2、-OC(=O)N(R ff )2、-NR ff C(=O)R ee 、-NR ff CO2R ee 、-NR ff C(=O)N(R ff )2、-C(=NR ff )OR ee 、-OC(=NR ff )R ee 、-OC(=NR ff )OR ee 、-C(=NR ff )N(R ff )2、-OC(=NR ff )N(R ff )2、-NR ff C(=NR ff )N(R ff )2、-NR ff SO2R ee 、-SO2N(R ff )2, -SO2R ee 、-SO2OR ee 、-OSO2R ee 、-S(=O)R ee 、-Si(R ee )3、-OSi(R ee )3、-C(=S)N(R ff )2, -C(=O)SR ee 、-C(=S)SR ee 、-SC(=S)SR ee 、-P(=O)2Ree 、-P(=O)(R ee )2、-OP(=O)(R ee )2、-OP(=O)(OR ee )2, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently substituted by 0, 1, 2, 3, 4 or 5 R gg Group substitution, or two geminal R dd Substituents may combine to form =O or =S;

[0077] R ee Each of R is independently selected from alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, aryl, heterocyclyl and heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl is independently replaced by 0, 1, 2, 3, 4 or 5 R gg group substitution;

[0078] R ff Each of R is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two R ff The groups are combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl group is independently replaced by 0, 1, 2, 3, 4 or 5 R gg group substitution;

[0079] R gg Each of the independently: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OC 1-6 Alkyl, -ON(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)3 + X - 、-NH(C 1-6 Alkyl)2 + X - 、-NH2(C 1-6 alkyl) + X - 、-NH3 + X - 、-N(OC 1-6 Alkyl)(C 1-6 Alkyl), -N(OH)(C 1-6 Alkyl), -NH(OH), -SH, -SC 1-6 Alkyl, -SS(C 1-6 alkyl), -C(=O)(C 1-6alkyl), -CO2H, -CO2(C 1-6 alkyl), -OC(=O)(C 1-6 Alkyl), -OCO2(C 1- 6 alkyl), -C(=O)NH2, -C(=O)N(C 1-6 alkyl)2, -OC(=O)NH(C 1-6 alkyl), -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 Alkyl), -NHCO2(C 1-6 alkyl), -NHC(=O)N(C 1-6 alkyl)2, -NHC(=O)NH(C 1-6 alkyl), -NHC(=O)NH2, -C(=NH)O(C 1-6 alkyl), -OC(=NH)(C 1-6 alkyl), -OC(=NH)OC 1-6 Alkyl, -C(=NH)N(C 1-6 Alkyl)2, -C(=NH)NH(C 1-6 alkyl), -C(=NH)NH2, -OC(=NH)N(C 1-6 Alkyl)2, -OC(NH)NH(C 1-6 alkyl), -OC(NH)NH2, -NHC(NH)N(C 1-6 Alkyl)2, -NHC(=NH)NH2, -NHSO2(C 1-6 Alkyl), -SO2N(C 1-6 Alkyl)2, -SO2NH(C 1-6 alkyl), -SO2NH2, -SO2C 1-6 Alkyl, -SO2OC 1-6 Alkyl, -OSO2C 1-6 Alkyl, -SOC 1-6 Alkyl, -Si(C 1-6 alkyl)3, -OSi(C 1-6 alkyl)3, -C(=S)N(C 1-6 alkyl)2、C(=S)NH(C 1-6 alkyl), C(=S)NH2, -C(=O)S(C 1-6 alkyl), -C(=S)SC 1- 6-alkyl, -SC(=S)SC 1-6 Alkyl, -P(=O)2(C 1-6 alkyl), -P(=O)(C 1-6 alkyl)2, -OP(=O)(C 1-6alkyl)2, -OP(=O)(OC 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 carbocyclic group, C6-C 10 Aryl, C3-C7 heterocyclic, C5-C 10 heteroaryl; or two geminal R gg Substituents may combine to form =O or =S; wherein X - For the counter ion.

[0080] Exemplary substituents on nitrogen atoms include, but are not limited to, hydrogen, -OH, -OR aa 、-N(R cc )2, -CN, -C(=O)R aa 、-C(=O)N(R cc )2, -CO2R aa 、-SO2R aa 、-C(=NR bb )R aa 、-C(=NR cc )OR aa 、-C(=NR cc )N(R cc )2、-SO2N(R cc )2, -SO2R cc 、-SO2OR cc 、-SOR aa 、-C(=S)N(R cc )2, -C(=O)SR cc 、-C(=S)SR cc 、-P(=O)2R aa 、-P(=O)(R aa )2、-P(=O)2N(R cc )2、-P(=O)(NR cc )2, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl, or two R attached to the nitrogen atom cc The groups are combined to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl group is independently replaced by 0, 1, 2, 3, 4 or 5 R dd group substituted, and wherein R aa 、R bb 、R cc and R dd As mentioned above.

[0081] "Deuterated" or "D" refers to a compound or group in which one or more hydrogen atoms are replaced by deuterium; deuteration can be mono-, di-, poly-, or per-substituted. The term "deuterated" and "deuterated one or more times" are used interchangeably.

[0082] A "non-deuterated compound" refers to a compound that contains deuterium atoms in a proportion not greater than the natural deuterium isotope content (0.015%).

[0083] The deuterium isotope content of deuterium at the deuterated position is at least 0.015% greater than the natural deuterium isotope content, preferably greater than 30%, more preferably greater than 50%, more preferably greater than 75%, more preferably greater than 95%, and more preferably greater than 99%.

[0084] The term "pharmaceutically acceptable salt" refers to salts that are suitable for contact with the tissues of humans and lower animals without excessive toxicity, irritation, allergic reaction, etc., and are commensurate with a reasonable benefit / risk ratio, within the scope of sound medical judgment. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66: 1-19. Pharmaceutically acceptable salts of the compounds of the present invention include salts derived from suitable inorganic and organic acids and inorganic and organic bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid, or salts formed with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid. Salts formed using conventional methods in the art, such as ion exchange methods, are also included. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, gluconate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, and the like. Pharmaceutically acceptable salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N + (C 1-4Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Other pharmaceutically acceptable salts include non-toxic ammonium salts, quaternary ammonium salts, and amine cations formed with counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates, if appropriate.

[0085] "Subjects" to be administered include, but are not limited to, humans (i.e., males or females of any age group, e.g., pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults, or older adults)) and / or non-human animals, e.g., mammals, e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. The terms "human," "patient," and "subject" are used interchangeably herein.

[0086] "Disease," "disorder," and "condition" are used interchangeably herein.

[0087] As used herein, and unless otherwise indicated, the term "treating" includes actions that occur while a subject has a particular disease, disorder, or condition that reduce the severity of, or delay or slow the development of, the disease, disorder, or condition ("therapeutic treatment"), as well as actions that occur before a subject becomes ill with a particular disease, disorder, or condition ("prophylactic treatment").

[0088] "Combination" and related terms refer to the simultaneous or sequential administration of therapeutic agents of the invention. For example, a compound of the invention can be administered simultaneously or sequentially with another therapeutic agent in separate unit dosage forms, or simultaneously with another therapeutic agent in a single unit dosage form. DETAILED DESCRIPTION

[0089] Compound

[0090] Herein, "compounds of the present invention" refers to the compounds of the following formula (I) (including subsets of each formula), or tautomers, stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, hydrates or solvates thereof.

[0091] In one embodiment, the present invention relates to a compound of formula (I), or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof:

[0092] in,

[0093] X1 is N or CR X1 ;

[0094] X2 is CR X2 R X2’ or C(O);

[0095] X3 for CR X3 R X3’ , CR X3 or NR X3 ;

[0096] X4 for CR X4 R X4’ , CR X4 ,NR X4 or C(O);

[0097] X5 is N or CR X5 ;

[0098] X6 is N or CR X6 ;

[0099] is a single bond or a double bond;

[0100] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0101] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0102] R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R X3 and R X3’ Together with the carbon atoms to which they are attached, they form C 1-6 wherein the above groups are optionally replaced by one or more R a replace;

[0103] R X4 and R X4’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally replaced by one or more R a replace;

[0104] Or, R X3 and R X4 Together with the atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6- 10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R;

[0105] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0106] R X6 is H, D or halogen;

[0107] Y is CR Y or N;

[0108] R1 is a 3-10 membered heterocyclic group, which is optionally substituted by one or more R b replace;

[0109] R Y is H, D or halogen;

[0110] Alternatively, R1 and R Y Together with the carbon atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6- 10 aryl or 5-10 membered heteroaryl, optionally substituted with one or more R*;

[0111] R1' is H, D, halogen or -NH2;

[0112] W is CR W or N;

[0113] R W is selected from H, D, halogen or -NH2;

[0114] Y1 is CR Y1 or N;

[0115] Y2 is CR Y2 or N;

[0116] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C1-6 wherein the above groups are optionally replaced by one or more R c replace;

[0117] Z is a chemical bond, O or S(O) 0-2 ;

[0118] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0119] or -ZR Z Together they represent -SF5;

[0120] Each R a 、R b and R c are independently H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0121] Each R is independently H, D, halogen, -CN, -OR A , -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R';

[0122] Each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by one or more R';

[0123] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein the above groups are optionally substituted by one or more R';

[0124] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R";

[0125] Or two adjacent R' together with the atoms they are connected to form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1- 6 haloalkoxy substituted; wherein the above groups are optionally substituted by one or more D, until fully deuterated;

[0126] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0127] The premise is that when X1 is N, X2 is CH2, and X3 is NR X3 , X4 is C(O), and X5 is CH, Y is not N.

[0128] X1-X6, R a , R, R A -R C and P1-P4

[0129] In one embodiment, X1 is N; in another embodiment, X1 is CR X1 .

[0130] In one embodiment, X1 is CR X1 , and where R X1 H, D, halogen, C 1-6 Alkyl or C 1- 6 haloalkyl; wherein the above groups are optionally substituted by one or more D, until fully deuterated. In another embodiment, X1 is CR X1 , and where R X1 In one embodiment, X1 is CR X1 , and where R X1 is H, D or F. In one embodiment, X1 is CR X1 , and where R X1 It is H or D.

[0131] In one embodiment, X2 is CR X2 R X2’ ; In another embodiment, X2 is C(O).

[0132] In one embodiment, X2 is CR X2 R X2’ , and where R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration. In another embodiment, X2 is CR X2 R X2’ , and where R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, X2 is CR X2 RX2’ , and where R X2 and R X2’ are independently H, D, halogen, -OH, C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, X2 is CR X2 R X2’ , and where R X2 and R X2’ In another embodiment, X2 is CR X2 R X2’ , and where R X2 and R X2’ is independently H, D, -F or -OH.

[0133] In one embodiment, X3 is CR X3 R X3’ In another embodiment, X3 is CR X3 In another embodiment, X3 is NR X3 .

[0134] In one embodiment, X3 is CR X3 R X3’ , and where R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R X3 and R X3’ Together with the carbon atoms to which they are attached, they form C 1-6 wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is CR X3 R X3’ , and where R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is CR X3 R X3’ , and where R X3 and R X3’are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above group is optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is CR X3 R X3’ , and where R X3 and R X3’ are independently H, D, halogen, C 1-3 Alkyl, C 1-3 Haloalkyl or C 3-6 Cycloalkyl; wherein the above group is optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is CR X3 R X3’ , and where R X3 and R X3’ are independently H, D, halogen, C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is CR X3 R X3’ , and where R X3 and R X3’ are independently H, D or F. In another embodiment, X3 is CR X3 R X3’ , and where R X3 and R X3’ are independently H or D.

[0135] In one embodiment, X3 is CR X3 , and where R X3 H, D, halogen, C 1-6 Alkyl, C 1- 6 haloalkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is CR X3 , and where R X3 H, D, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above group is optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R aIn another embodiment, X3 is CR X3 , and where R X3 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is CR X3 , and where R X3 H, D, halogen, C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is CR X3 , and where R X3 In another embodiment, X3 is CR X3 , and where R X3 is H, D or F. In another embodiment, X3 is CR X3 , and where R X3 It is H or D.

[0136] In one embodiment, X3 is NR X3 , and where R X3 H, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is NR X3 , and where R X3 H, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above group is optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is NR X3 , and where R X3 C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above group is optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X3 is NR X3 , and where R X3 C 1-6Alkyl, C 1-6 Haloalkyl or C 3-6 wherein the above groups are optionally substituted by one or more D, up to full deuteration. In another embodiment, X3 is NR X3 , and where R X3 C 1-3 Alkyl, C 1-3 Haloalkyl or C 3-6 wherein the above groups are optionally substituted by one or more D, up to full deuteration. In another embodiment, X3 is NR X3 , and where R X3 In another embodiment, X3 is NR X3 , and where R X3 is CH3, CD3 or cyclopropane.

[0137] In one embodiment, X4 is CR X4 R X4’ In another embodiment, X4 is CR X4 In another embodiment, X4 is NR X4 ; In another embodiment, X4 is C(O).

[0138] In one embodiment, X4 is CR X4 R X4’ , and where R X4 and R X4’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X4 is CR X4 R X4’ , and where R X4 and R X4’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X4 is CR X4 R X4’ , and where R X4 and R X4’ are independently H, D, halogen, C 1-3 Alkyl or C 1-3wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X4 is CR X4 R X4’ , and where R X4 and R X4’ are independently H or D.

[0139] In one embodiment, X4 is CR X4 , and where R X4 H, D, halogen, C 1-6 Alkyl, C 1- 6 haloalkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X4 is CR X4 , and where R X4 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X4 is CR X4 , and where R X4 It is H or D.

[0140] In one embodiment, X4 is NR X4 , and where R X4 H, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X4 is NR X4 , and where R X4 H, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X4 is NR X4 , and where R X4 C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a In another embodiment, X4 is NRX4 , and where R X4 C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R a replace.

[0141] In a specific embodiment, R X3 and R X4 Together with the atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R. In another specific embodiment, R X3 and R X4 Together with the atoms to which they are attached, they form C 3-8 Cycloalkyl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R. In another specific embodiment, R X3 and R X4 Together with the atoms to which they are attached, they form a 4-10 membered heterocyclyl group, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R. In another embodiment, R X3 and R X4 Together with the atoms to which they are attached, they form C 6-10 Aryl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R. In another embodiment, R X3 and R X4 Together with the atoms to which they are attached, they form a 5-10 membered heteroaryl group, which is optionally substituted with 1-6 (eg, 1, 2, 3, 4, 5, or 6) R groups.

[0142] In another specific embodiment, R X3 and R X4 Together with the atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R. In another specific embodiment, R X3 and R X4 Together with the atoms to which they are attached, they form a phenyl group or a 5-10 membered heteroaryl group; wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R. In another embodiment, R X3 and R X4Together with the atoms to which they are attached, they form a phenyl group or a 5-membered heteroaryl group; wherein the above groups are optionally substituted with 1-3 (e.g., 1, 2, or 3) groups. In another embodiment, R X3 and R X4 Together with the atoms to which they are attached, they form a 5-membered heteroaryl group, which is optionally substituted with 1-3 (e.g., 1, 2, or 3) R. In another embodiment, R X3 and R X4 Together with the atoms they are connected to form R X3 and R X4 Together with the atoms they are connected to form In another specific embodiment, R X3 and R X4 Together with the atoms they are connected to form In another specific embodiment, R X3 and R X4 Together with the atoms they are connected to form In another specific embodiment, R X3 and R X4 Together with the atoms they are connected to form

[0143] In one embodiment, X5 is N; in another embodiment, X5 is CR X5 .

[0144] In one embodiment, X5 is CR X5 , and where R X5 H, D, halogen, C 1-6 Alkyl or C 1- 6 haloalkyl; wherein the above groups are optionally substituted by one or more D, until fully deuterated. In another embodiment, X5 is CR X5 , and where R X5 In another embodiment, X5 is CR X5 , and where R X5 is H, D or F. In another embodiment, X5 is CR X5 , and where R X5 It is H or D.

[0145] In one embodiment, X6 is N; in another embodiment, X6 is CR X6 .

[0146] In one embodiment, X6 is CRX6 , and where R X6 In another embodiment, X6 is CR X6 , and where R X6 is H, D or F. In another embodiment, X6 is CR X6 , and where R X6 It is H or D.

[0147] In one embodiment, each R a H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 Alkyl, C 1- 6 haloalkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R a H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R a H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1- 6 alkyl) 2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R a H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R a H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R a H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R a H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl or -N(C 1-6 wherein the above groups are optionally substituted by one or more Ds up to full deuteration.

[0148] In one embodiment, each R is independently H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R'. In another embodiment, each R is independently H, D, -C(O)R A , -NR B R C , -NR AC(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R'. In another embodiment, each R is independently H, D, -C(O)R A , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R'. In another embodiment, each R is independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R'. In another embodiment, each R is independently H, D, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 3-6 cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R'. In another embodiment, each R is independently C 1- 3 alkyl, C 1-3 Halogenated alkyl, C 3-6 cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R'. In another embodiment, each R is independently 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R'.

[0149] In one embodiment, R is in,

[0150] P1 is N or CR P1 ;

[0151] P2 is N or CR P2 ;

[0152] P3 is N or CR P3 ;

[0153] P4 is N or CR P4 ;

[0154] R P1 , R P2 , R P3 and R P4 are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0155] or R P1 and R P2 、R P2 and R P3 or R P3 and R P4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[0156] In another specific embodiment, R is in,

[0157] P1 is N or CR P1 ;

[0158] P2 is N or CR P2 ;

[0159] P3 is N or CR P3 ;

[0160] P4 is N or CR P4 ;

[0161] R P1 , R P2 , R P3 and R P4 are independently H, D, halogen, -CN, C1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0162] or R P1 and R P2 、R P2 and R P3 or R P3 and R P4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[0163] In another specific embodiment, R is in,

[0164] P1 is CR P1 ;

[0165] P2 is N or CR P2 ;

[0166] P3 is N or CR P3 ;

[0167] P4 is N or CR P4 ;

[0168] And preferably, at least one of P3 and P4 is N;

[0169] R P1 、R P2 、R P3 and R P4 are independently H, D, halogen, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, halogen, -CN, C 1-6 Alkyl or C 1-6wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0170] or R P1 and R P2 、R P2 and R P3 or R P3 and R P4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[0171] In another specific embodiment, R is in,

[0172] P1 is CR P1 ;

[0173] P2 is CR P2 ;

[0174] P3 is N or CR P3 ;

[0175] P4 is N or CR P4 ;

[0176] and at least one of P3 and P4 is N;

[0177] R P1 H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0178] R P2 is H, D, halogen or -CN;

[0179] R P3 H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0180] R P4 It is H or D.

[0181] In another specific embodiment, R is in,

[0182] P1 is CR P1 ;

[0183] P2 is CR P2 ;

[0184] P3 is N or CR P3 ;

[0185] P4 is N or CR P4 ;

[0186] and at least one of P3 and P4 is N;

[0187] R P1 is H, D, -CN or Me;

[0188] R P2 is H, D, F or -CN;

[0189] R P3 is H, D or Me;

[0190] R P4 It is H or D.

[0191] In another specific embodiment, R is in,

[0192] P1 is CR P1 ;

[0193] P2 is N or CR P2 ;

[0194] P3 is N or CR P3 ;

[0195] P4 is CR P4 ;

[0196] R P1 、R P2 、R P3 and R P4 are independently H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0197] In another specific embodiment, R is in,

[0198] P1 is CR P1 ;

[0199] P2 is N or CR P2 ;

[0200] P3 is N or CR P3 ;

[0201] P4 is CR P4 ;

[0202] R P1 H or D;

[0203] R P2 H or D;

[0204] R P3 H or D;

[0205] R P4 It is H or D.

[0206] In another specific embodiment, R is in,

[0207] R P1 , R P2 and R P3 are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0208] or R P1 and R P2 or R P2 and R P3 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[0209] In another specific embodiment, R is in,

[0210] R P1 , R P2 and R P3 are independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0211] or R P1 and R P2 or R P2 and R P3 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[0212] In another specific embodiment, R is in,

[0213] R P1 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0214] R P2 is H;

[0215] R P3 H, C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R".

[0216] In another specific embodiment, R is in,

[0217] R P1 and R P3 is H;

[0218] RP2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R".

[0219] In another specific embodiment, R is in,

[0220] R P1 and R P3 is H;

[0221] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy, 3-7 membered heterocyclyl or phenyl; wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R".

[0222] In another specific embodiment, R is in,

[0223] R P1 and R P3 is H;

[0224] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0225] In one embodiment, each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R CTogether with the N atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R's. In another embodiment, each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, or R B and R C Together with the N atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R's. In another embodiment, each R A 、R B and R C Independently H, D, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R B and R C Together with the N atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R's. In another embodiment, each R A 、R B and R C Independently H, D, C 1-3 Alkyl, C 1-3 Haloalkyl or C 3-6 Cycloalkyl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R's.

[0226] Y, W, R Y , R1, R1', R b , R* and Q1-Q3

[0227] In one embodiment, Y is CR Y ; In one embodiment, Y is N.

[0228] In one embodiment, Y is CR Y , and where R Y In another embodiment, Y is CR Y , and where R Yis H, D or F. In another embodiment, Y is CR Y , and where R Y It is H or D.

[0229] In one embodiment, W is CR W ; In one embodiment, W is N.

[0230] In one embodiment, W is CR W , and where R W is H, D, halogen or -NH2. In another embodiment, W is CR W , and where R W In another embodiment, W is CR W , and where R W is H, D or F. In another embodiment, W is CR W , and where R W It is H or D.

[0231] In one embodiment, R1 is a 3-10 membered heterocyclyl group, which is optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R b In another embodiment, R1 is a 4-10 membered heterocyclyl group, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R b In another embodiment, R1 is a 4-7 membered heterocyclyl group, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R b In another embodiment, R1 is a 5-membered heterocyclyl group, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R b In another embodiment, R1 is a tetrahydropyrrole ring, which is optionally substituted with 1-4 (e.g., 1, 2, 3, or 4) R b In another embodiment, R1 is wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) R b In another embodiment, R1 is wherein the above groups are optionally substituted by 1-4 (e.g. 1, 2, 3 or 4) R b replace.

[0232] In one embodiment, R1' is H, D, halogen, or -NH2. In another embodiment, R1' is H, D, or -NH2. In another embodiment, R1' is H or -NH2. In another embodiment, R1' is H. In another embodiment, R1' is -NH2. In another embodiment, R1' is -F.

[0233] In another embodiment, each R b H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R b H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1- 6 haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R b H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R b H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6-membered cycloalkyl or 3-7-membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration. In another embodiment, each R b H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R b H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl or -N(C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R b Halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl or -N(C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R b Halogen, -OH, -NH2, -NHC 1-6 Alkyl or -N(C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R b Halogen, -OH, -NH2, -NHC 1-3 Alkyl or -N(C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R b In another embodiment, each R b In another embodiment, each R b It is -OH.

[0234] In one embodiment, R1 and R Y Together with the carbon atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*. In another embodiment, R1 and R Y Together with the carbon atoms to which they are attached, they form C 3-8 Cycloalkyl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*. In another embodiment, R1 and R YTogether with the carbon atoms to which they are attached, they form a 4-10 membered heterocyclyl group, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*. In another embodiment, R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 Aryl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*. In another embodiment, R1 and R Y Together with the carbon atom to which they are attached, they form a 5-10 membered heteroaryl group, which is optionally substituted with 1-6 (eg, 1, 2, 3, 4, 5, or 6) R*.

[0235] In another embodiment, R1 and R Y Together with the carbon atoms to which they are attached, they form a 4-10 membered heterocyclyl or a 5-10 membered heteroaryl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*. In another embodiment, R1 and R Y Together with the carbon atoms to which they are attached, they form a 5-membered heteroaryl group, which is optionally substituted with 1-3 (e.g., 1, 2, or 3) R*. In another embodiment, R1 and R Y Together with the carbon atoms to which they are attached, they form where p is 0, 1, 2, 3, 4, 5, or 6.

[0236] In one embodiment, each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6- 10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5, or 6) R'. In another embodiment, each R* is independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R'. In another embodiment, each R* is independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or two R* together with the atoms to which they are attached form C 3-8 wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R'. In another embodiment, each R* is independently C 1-6 Alkyl or C 1-6 Haloalkyl, or two R* together with the atoms to which they are attached form a C 3-8 wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R'. In another embodiment, two R* together with the atoms to which they are attached form C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R'.

[0237] In another embodiment, two R* together with the atoms to which they are attached form wherein Q1 is C(R')2 or C(R')2C(R')2; Q2 is C(R')2, O, S, S(O) or S(O)2; and Q3 is C(R')2, C(R')2C(R')2, O, S, S(O) or S(O)2. In another embodiment, the two R* together with the atoms to which they are attached form wherein R' is CH3, Q1 is (CH2)2, CHD, (CHD)2, CD2 or (CD2)2; Q2 is CH2, CHD, CD2, O, S, S(O) or S(O)2; Q3 is C(R')2, S or S(O)2;

[0238] In another embodiment, the two R* together with the atoms to which they are attached form wherein R' is CH3, Q1 is CH2, CHD or CD2; Q2 is O, S, CH2, CHD or CD2; Q3 is O, S, CH2, CHD or CD2. In another embodiment, the two R* together with the atoms to which they are attached form Wherein, R' is CH3, Q1 is CH2, CHD or CD2; Q2 is O, S, CH2, CHD or CD2; Q3 is O, S, CH2, CHD or CD2.

[0239] Y1, Y2 and R2

[0240] In one embodiment, Y1 is CR Y1 ; In another embodiment, Y1 is N.

[0241] In one embodiment, Y2 is CR Y2 ; In another embodiment, Y2 is N.

[0242] In one embodiment, R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) R c In another embodiment, R Y1 、R Y2 and R2 are independently H, D or halogen. In another embodiment, R Y1 、R Y2 and R2 are independently H or D.

[0243] In another embodiment, each R c H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R c H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1- 6 haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R c H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R c H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3- 6-membered cycloalkyl or 3-7-membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration. In another embodiment, each R c H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R c H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl or -N(C 1-6 wherein the above groups are optionally substituted by one or more Ds up to full deuteration.

[0244] Z and R z

[0245] In one embodiment, Z is a chemical bond; in one embodiment, Z is O; in one embodiment, Z is S(O) 0-2 , for example, S(O), S(O)1, and S(O)2.

[0246] In one embodiment, R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D. In one embodiment, R Z H, D, C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted with one or more D. In one embodiment, R Z C 1-3 wherein the above groups are optionally substituted with one or more D. In one embodiment, RZ It is CF2Cl.

[0247] In one embodiment, -ZR Z Together they represent -SF5.

[0248] R' and R"

[0249] In one embodiment, each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R'. In another embodiment, each R' is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R". In one embodiment, each R' is independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration. In another embodiment, each R' is independently H, D, F or -OH. In another embodiment, each R' is independently H, D or F.

[0250] In another embodiment, two adjacent R's together with the atoms to which they are attached form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more D, up to full deuteration. In another embodiment, two adjacent R' together with the atoms to which they are attached form C 6-10 Aryl; wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more D, up to full deuteration. In another embodiment, two adjacent R' together with the atoms to which they are attached form a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[0251] In one embodiment, each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration. In another embodiment, each R "is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0252] Any technical solution or any combination thereof in any of the above specific embodiments can be combined with any technical solution or any combination thereof in other specific embodiments. a , R, R A -R C , P1-P4, Y, W, R Y , R1, R b , R*, Q1-Q3, Y1, Y2, R2, Z, R z , R' and R" or any combination thereof. The present invention is intended to include combinations of all these technical solutions, which are not listed one by one due to space limitations.

[0253] In a more specific embodiment, the present invention relates to the following technical solutions:

[0254] 1. A compound of formula (I), or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof:

[0255] in,

[0256] X1 is N or CR X1 ;

[0257] X2 is CR X2 R X2’ or C(O);

[0258] X3 for CR X3 R X3’ , CR X3 or NR X3 ;

[0259] X4 for CR X4 R X4’ , CR X4 ,NR X4 or C(O);

[0260] X5 is N or CR X5 ;

[0261] X6 is N or CR X6 ;

[0262] is a single bond or a double bond;

[0263] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0264] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0265] R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R X3 and R X3’ Together with the carbon atoms to which they are attached, they form C 1-6 wherein the above groups are optionally replaced by one or more R a replace;

[0266] R X4 and R X4’ are independently H, D, halogen, C1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group; wherein the above groups are optionally replaced by one or more R a replace;

[0267] Or, R X3 and R X4 Together with the atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6- 10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R;

[0268] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0269] R X6 is H, D or halogen;

[0270] Y is CR Y or N;

[0271] R1 is a 3-10 membered heterocyclic group, which is optionally substituted by one or more R b replace;

[0272] R Y is H, D or halogen;

[0273] Alternatively, R1 and R Y Together with the carbon atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6- 10 aryl or 5-10 membered heteroaryl, optionally substituted with one or more R*;

[0274] R1' is H, D, halogen or -NH2;

[0275] W is CR W or N;

[0276] R W is selected from H, D, halogen or -NH2;

[0277] Y1 is CR Y1 or N;

[0278] Y2 is CR Y2 or N;

[0279] R Y1 、R Y2and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally replaced by one or more R c replace;

[0280] Z is a chemical bond, O or S(O) 0-2 ;

[0281] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0282] or -ZR Z Together they represent -SF5;

[0283] Each R a 、R b and R c are independently H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0284] Each R is independently H, D, halogen, -CN, -OR A , -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R';

[0285] Each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by one or more R';

[0286] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclic group or a 5-10 membered heteroaryl group; wherein the above groups are optionally substituted by one or more R';

[0287] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more R";

[0288] Or two adjacent R' together with the atoms they are connected to form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1- 6 haloalkoxy substituted; wherein the above groups are optionally substituted by one or more D, until fully deuterated;

[0289] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0290] The premise is that when X1 is N, X2 is CH2, and X3 is NR X3 , X4 is C(O), and X5 is CH, Y is not N.

[0291] 2. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0292] X1 is N or CR X1 ;

[0293] X2 is CR X2 R X2’ or C(O);

[0294] X3 for CR X3 R X3’ or NR X3 ;

[0295] X4 is C(O);

[0296] X5 is N or CR X5 ;

[0297] X6 is N or CR X6 , preferably CR X6 ;

[0298] is a single bond;

[0299] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0300] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0301] R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R X3 and R X3’ Together with the carbon atoms to which they are attached, they form C 1-6wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R a replace;

[0302] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0303] R X6 is H, D or halogen, preferably H or D;

[0304] Y is CR Y ;

[0305] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl, optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*;

[0306] R1' is H, D, halogen or -NH2, preferably H or D;

[0307] W is CR W or N, preferably CR W ;

[0308] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0309] Y1 is CR Y1 or N;

[0310] Y2 is CR Y2 or N;

[0311] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0312] Z is a chemical bond, O or S(O) 0-2 ;

[0313] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0314] or -ZRZ Together they represent -SF5;

[0315] Each R a are independently H, D, halogen, -CN or -NR B R C ;

[0316] Each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl or C 1-6 Haloalkyl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0317] where R A , R B and R C Independently H, D, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0318] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0319] 3. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0320] X1 is N or CR X1 ;

[0321] X2 is CR X2 R X2’ or C(O);

[0322] X3 for CR X3 ;

[0323] X4 for CR X4 ;

[0324] X5 is N or CR X5 ;

[0325] X6 is N or CR X6 , preferably CR X6 ;

[0326] is a single bond or a double bond;

[0327] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0328] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0329] R X3 and R X4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R;

[0330] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0331] R X6 is H, D or halogen, preferably H or D;

[0332] Y is CR Y or N;

[0333] R1 is a 3-10 membered heterocyclic group, which is optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R b replace;

[0334] R Y is H, D or halogen;

[0335] Alternatively, R1 and R Y Together with the carbon atoms to which they are attached, they form C 3-8 Cycloalkyl, 4-10 membered heterocyclic group, C 6- 10aryl or 5-10 membered heteroaryl, optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*;

[0336] R1' is H, D, halogen or -NH2, preferably H or D;

[0337] W is CR W or N, preferably CR W ;

[0338] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0339] Y1 is CR Y1 or N;

[0340] Y2 is CR Y2 or N;

[0341] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0342] Z is a chemical bond, O or S(O) 0-2 ;

[0343] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0344] or -ZR Z Together they represent -SF5;

[0345] Each R b are independently H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0346] Each R is independently H, D, halogen, -CN, -OR A , -C(O)R A , -NRB R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0347] Each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0348] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0349] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0350] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0351] 4. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0352] X1 is N or CR X1 ;

[0353] X2 is CR X2 R X2’ or C(O);

[0354] X3 for CR X3 R X3’ or NR X3 ;

[0355] X4 is C(O);

[0356] X5 is N or CR X5 ;

[0357] X6 is N or CR X6 , preferably CR X6 ;

[0358] is a single bond;

[0359] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0360] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0361] R X3 and R X3’are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R X3 and R X3’ Together with the carbon atoms to which they are attached, they form C 1-6 wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R a replace;

[0362] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0363] R X6 is H, D or halogen, preferably H or D;

[0364] Y is CR Y ;

[0365] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with two or more R*;

[0366] R1' is H, D, halogen or -NH2, preferably H or D;

[0367] W is CR W or N, preferably CR W ;

[0368] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0369] Y1 is CR Y1 or N;

[0370] Y2 is CR Y2 or N;

[0371] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0372] Z is a chemical bond, O or S(O) 0-2 ;

[0373] R Z H, D, C 1-6 Alkyl or C 1-6wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) D, up to full deuteration;

[0374] or -ZR Z Together they represent -SF5;

[0375] Each R a are independently H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2- 6 alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0376] Each R* is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0377] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0378] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0379] 5. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0380] X1 is N or CR X1 ;

[0381] X2 is CR X2 R X2’ or C(O);

[0382] X3 for NR X3 ;

[0383] X4 is C(O);

[0384] X5 is N or CR X5 ;

[0385] X6 is N or CR X6 , preferably CR X6 ;

[0386] is a single bond;

[0387] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0388] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0389] R X3 H, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0390] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0391] R X6is H, D or halogen, preferably H or D;

[0392] Y is CR Y ;

[0393] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with two or more R*;

[0394] R1' is H, D, halogen or -NH2, preferably H or D;

[0395] W is CR W or N, preferably CR W ;

[0396] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0397] Y1 is CR Y1 or N;

[0398] Y2 is CR Y2 or N;

[0399] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0400] Z is a chemical bond, O or S(O) 0-2 ;

[0401] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0402] or -ZR Z Together they represent -SF5;

[0403] Two adjacent R* together with the atoms to which they are connected form C 3-8 Cycloalkyl or 4-10 membered heterocyclic group, other R* are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0404] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0405] 6. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0406] X1 is N or CR X1 ;

[0407] X2 is CR X2 R X2’ ;

[0408] X3 for NR X3 ;

[0409] X4 is C(O);

[0410] X5 is N or CR X5 ;

[0411] X6 is N or CR X6 , preferably CR X6 ;

[0412] is a single bond;

[0413] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0414] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0415] R X3 H, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0416] R X5 H, D, halogen, C 1-6Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0417] R X6 is H, D or halogen, preferably H or D;

[0418] Y is CR Y ;

[0419] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with two or more R*;

[0420] R1' is H, D, halogen or -NH2, preferably H or D;

[0421] W is CR W or N, preferably CR W ;

[0422] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0423] Y1 is CR Y1 or N;

[0424] Y2 is CR Y2 or N;

[0425] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0426] Z is a chemical bond, O or S(O) 0-2 ;

[0427] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0428] or -ZR Z Together they represent -SF5;

[0429] Two adjacent R* together with the atoms to which they are connected form C 3-8 Cycloalkyl or 4-10 membered heterocyclic group, other R* are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0430] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0431] 7. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0432] X1 is N or CR X1 ;

[0433] X2 is CR X2 R X2’ or C(O);

[0434] X3 for CR X3 ;

[0435] X4 for CR X4 ;

[0436] X5 is N or CR X5 ;

[0437] X6 is N or CR X6 , preferably CR X6 ;

[0438] is a single bond or a double bond;

[0439] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0440] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0441] R X3 and R X4Together with the atoms to which they are attached, they form a 5-membered heteroaryl group; which is optionally substituted with 1-3 (e.g., 1, 2, or 3) R;

[0442] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0443] R X6 is H, D or halogen, preferably H or D;

[0444] Y is CR Y or N;

[0445] R1 is a 3-10 membered heterocyclic group, which is optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R b replace;

[0446] R Y is H, D or halogen;

[0447] Alternatively, R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*;

[0448] R1' is H, D, halogen or -NH2, preferably H or D;

[0449] W is CR W or N, preferably CR W ;

[0450] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0451] Y1 is CR Y1 or N;

[0452] Y2 is CR Y2 or N;

[0453] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0454] Z is a chemical bond, O or S(O) 0-2 ;

[0455] R Z H, D, C 1-6 Alkyl or C1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0456] or -ZR Z Together they represent -SF5;

[0457] Each R b are independently H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2- 6 alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0458] Each R is independently H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6- 10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0459] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R CTogether with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0460] Each R* is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0461] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0462] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0463] 8. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0464] X1 is N;

[0465] X2 is CR X2 R X2’ or C(O);

[0466] X3 for CR X3 ;

[0467] X4 for CR X4 ;

[0468] X5 is N or CR X5 ;

[0469] X6 is N or CR X6 , preferably CR X6 ;

[0470] is a single bond;

[0471] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0472] R X3 and R X4 Together with the atoms to which they are attached, they form a 5-membered heteroaryl group; which is optionally substituted with 1-3 (e.g., 1, 2, or 3) R;

[0473] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0474] R X6 is H, D or halogen, preferably H or D;

[0475] Y is CR Y or N;

[0476] R1 is a 5-6 membered heterocyclic group, which is optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) R b replace;

[0477] R1' is H, D, halogen or -NH2, preferably H or D;

[0478] W is CR W or N, preferably CR W ;

[0479] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0480] R Y is H, D or halogen;

[0481] Y1 is CR Y1 or N;

[0482] Y2 is CR Y2 or N;

[0483] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0484] Z is a chemical bond, O or S(O) 0-2 ;

[0485] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0486] or -ZR Z Together they represent -SF5;

[0487] Each R b are independently H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2- 6 alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0488] Each R is independently H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6- 10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0489] Each R A 、R B and RC Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0490] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0491] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0492] 9. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0493] X1 is N;

[0494] X2 is CR X2 R X2’ or C(O);

[0495] X3 for CR X3 ;

[0496] X4 for CR X4 ;

[0497] X5 is N or CR X5 ;

[0498] X6 is N or CR X6 , preferably CR X6 ;

[0499] is a single bond;

[0500] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0501] R X3 and R X4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R;

[0502] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0503] R X6 is H, D or halogen, preferably H or D;

[0504] Y is CR Y ;

[0505] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with two or more R*;

[0506] R1' is H, D, halogen or -NH2, preferably H or D;

[0507] W is CR W or N, preferably CR W ;

[0508] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0509] Y1 is CR Y1 or N;

[0510] Y2 is CR Y2 or N;

[0511] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C1-6 alkyl halide;

[0512] Z is a chemical bond, O or S(O) 0-2 ;

[0513] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0514] or -ZR Z Together they represent -SF5;

[0515] Each R is independently H, D, halogen, -CN, -C(O)R A , C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0516] Two adjacent R* together with the atoms to which they are connected form C 3-8 Cycloalkyl or 4-10 membered heterocyclic group, other R* are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0517] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0518] R A H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group.

[0519] 10. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0520] X1 is N or CR X1 N;

[0521] X2 is CRX2 R X2’ or C(O);

[0522] X3 for CR X3 ;

[0523] X4 for CR X4 ;

[0524] X5 is N or CR X5 ;

[0525] X6 is N or CR X6 , preferably CR X6 ;

[0526] is a single bond;

[0527] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0528] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0529] R X3 and R X4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R;

[0530] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0531] R X6 is H, D or halogen, preferably H or D;

[0532] Y is CR Y ;

[0533] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with two or more R*;

[0534] R1' is H, D, halogen or -NH2, preferably H or D;

[0535] W is CR W or N, preferably CR W ;

[0536] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0537] Y1 is CR Y1 or N;

[0538] Y2 is CR Y2 or N;

[0539] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0540] Z is a chemical bond, O or S(O) 0-2 ;

[0541] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0542] or -ZR Z Together they represent -SF5;

[0543] Each R is independently H, D, -C(O)R A , halogen, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R'; wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0544] Two adjacent R* together with the atoms to which they are connected form C 3-8 Cycloalkyl or 4-10 membered heterocyclic group, other R* are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0545] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0546] R A H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0547] 11. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0548] X1 is N;

[0549] X2 is CR X2 R X2’ or C(O);

[0550] X3 for CR X3 ;

[0551] X4 for CR X4 ;

[0552] X5 is N or CR X5 ;

[0553] X6 is N or CR X6 , preferably CR X6 ;

[0554] is a single bond;

[0555] R X2 and R X2’ are independently H, D, OH, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0556] R X3 and R X4 Together with the atoms to which they are attached, they form C 6-10Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R;

[0557] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0558] R X6 is H, D or halogen, preferably H or D;

[0559] Y is CR Y ;

[0560] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with two or more R*;

[0561] R1' is H, D, halogen or -NH2, preferably H or D;

[0562] W is CR W or N, preferably CR W ;

[0563] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0564] Y1 is CR Y1 or N;

[0565] Y2 is CR Y2 or N;

[0566] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0567] Z is a chemical bond, O or S(O) 0-2 ;

[0568] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0569] or -ZR Z Together they represent -SF5;

[0570] One of the R groups is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, and the other R groups are independently H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0571] Two adjacent R* together with the atoms to which they are connected form C 3-8 Cycloalkyl or 4-10 membered heterocyclic group, other R* are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0572] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0573] Or two adjacent R' together with the atoms they are connected to form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[0574] 12. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0575] X1 is N;

[0576] X2 is CR X2 R X2’ or C(O);

[0577] X3 for CR X3 ;

[0578] X4 for CR X4 ;

[0579] X5 is N or CR X5 ;

[0580] X6 is N or CR X6 , preferably CR X6 ;

[0581] is a single bond;

[0582] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0583] R X3 and R X4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R;

[0584] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0585] R X6 is H, D or halogen, preferably H or D;

[0586] Y is CR Y ;

[0587] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with two or more R*;

[0588] R1' is H, D, halogen or -NH2, preferably H or D;

[0589] W is CR W or N, preferably CR W ;

[0590] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0591] Y1 is CR Y1 or N;

[0592] Y2 is CR Y2 or N;

[0593] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0594] Z is a chemical bond, O or S(O) 0-2 ;

[0595] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0596] or -ZR Z Together they represent -SF5;

[0597] One of R is pyridin-2-yl, pyrimidin-4-yl or pyrazin-2-yl, and the other R are independently H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0598] Two adjacent R* together with the atoms to which they are connected form C 3-8 Cycloalkyl or 4-10 membered heterocyclic group, other R* are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0599] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0600] 13. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0601] X1 is N;

[0602] X2 is CR X2 R X2’ ;

[0603] X3 for CR X3 ;

[0604] X4 for CR X4 ;

[0605] X5 is N or CR X5 ;

[0606] X6 is N or CR X6 , preferably CR X6 ;

[0607] is a single bond;

[0608] R X2 and R X2’ are independently H, D, halogen, OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0609] R X3 and R X4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R;

[0610] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0611] R X6 is H, D or halogen, preferably H or D;

[0612] Y is CR Y ;

[0613] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, which is optionally substituted with two or more R*;

[0614] R1' is H, D, halogen or -NH2, preferably H or D;

[0615] W is CR W or N, preferably CR W ;

[0616] R Wis selected from H, D, halogen or -NH2, preferably H or D;

[0617] Y1 is CR Y1 or N;

[0618] Y2 is CR Y2 or N;

[0619] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0620] Z is a chemical bond, O or S(O) 0-2 ;

[0621] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0622] or -ZR Z Together they represent -SF5;

[0623] One of R is pyrimidin-2-yl, and the other R are independently H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0624] Two adjacent R* together with the atoms to which they are connected form C 3-8 Cycloalkyl or 4-10 membered heterocyclic group, other R* are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 Haloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0625] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0626] Or two adjacent R' together with the atoms they are connected to form C 6-10Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[0627] 14. The compound of technical solution 1, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0628] X1 is N or CR X1 ;

[0629] X2 is CR X2 R X2’ or C(O);

[0630] X3 for CR X3 ;

[0631] X4 for CR X4 ;

[0632] X5 is N or CR X5 ;

[0633] X6 is N or CR X6 , preferably CR X6 ;

[0634] is a single bond;

[0635] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) D, up to full deuteration;

[0636] R X2 and R X2’ are independently H, D, halogen, OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0637] R X3 and R X4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R;

[0638] R X5 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0639] R X6 is H, D or halogen, preferably H or D;

[0640] Y is CR Y ;

[0641] And R1 and R Y Together with the carbon atoms to which they are attached, they form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, which is optionally substituted with two or more R*;

[0642] R1' is H, D, halogen or -NH2, preferably H or D;

[0643] W is CR W or N, preferably CR W ;

[0644] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0645] Y1 is CR Y1 or N;

[0646] Y2 is CR Y2 or N;

[0647] R Y1 、R Y2 and R2 are independently H, D, halogen, -CN, -NO2, C 1-6 Alkyl or C 1-6 alkyl halide;

[0648] Z is a chemical bond, O or S(O) 0-2 ;

[0649] R Z H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0650] or -ZR Z Together they represent -SF5;

[0651] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NRA C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0652] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0653] Each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0654] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0655] 15. The compound of any one of technical solutions 1 to 14, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (II):

[0656] Wherein, X1-X6, Y, W, R1 and R1' are as defined in any one of technical solutions 1-14.

[0657] 16. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (III):

[0658] in,

[0659] X1 is N or CR X1 , preferably N;

[0660] X2 is CR X2 R X2’ or C(O), preferably CR X2 R X2’ ;

[0661] X3 for CR X3 R X3’ or NR X3 ;

[0662] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0663] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0664] R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R X3 and R X3’Together with the carbon atoms to which they are attached, they form C 1-6 wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R a replace;

[0665] Each R a are independently H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2- 6 alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0666] R1' is H, D, halogen or -NH2, preferably H or D;

[0667] Each R* is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0668] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0669] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0670] 17. The compound of technical solution 16, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0671] X1 is N or CH;

[0672] X2 is CH2, CHD, CD2 or C(O);

[0673] X3 for CR X3 R X3’ or NR X3 ;

[0674] R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, or R X3 and R X3’ Together with the carbon atoms to which they are attached, they form C 1-6 wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R a replace;

[0675] Each R a are independently H, D, halogen, -NH2, -NHC 1-6 Alkyl or -N(C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration;

[0676] R1' is H, D, halogen or -NH2, preferably H or D;

[0677] Each R* is independently H, D, halogen, C 1-6 Alkyl or C 1-6 haloalkyl, or two R* together with the atoms to which they are attached form a 4-10 membered heterocyclyl; wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0678] Each R' is independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0679] 18. The compound of technical solution 16, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0680] X1 is N or CH;

[0681] X2 is CH2 or CD2;

[0682] X3 for CR X3 R X3’ or NR X3 ;

[0683] R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0684] R1' is H, D, halogen or -NH2, preferably H or D;

[0685] Each R* is independently H, D, halogen, C 1-6 Alkyl or C 1-6 haloalkyl, or two R* together with the atoms to which they are attached form a 4-10 membered heterocyclyl; wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0686] Each R' is independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0687] 19. The compound of technical solution 16, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0688] X1 is N;

[0689] X2 is CR X2 R X2’ ;

[0690] X3 for CR X3 R X3’ or NR X3 ;

[0691] R X2 and R X2’ Independently H, D, C 1-6 Alkyl or C 1-6wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0692] R X3 and R X3’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, or R X3 and R X3’ Together with the carbon atoms to which they are attached, they form C 1-6 wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R a replace;

[0693] Each R a are independently H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted with one or more Ds, up to full deuteration;

[0694] R1' is H, D, halogen or -NH2, preferably H or D;

[0695] Each R* is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 Haloalkyl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0696] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 Halogenated alkyl.

[0697] 20. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (III-1):

[0698] in,

[0699] R X3 H, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6Cycloalkyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0700] R1' is H, D, halogen or -NH2, preferably H or D;

[0701] Q1 is C(R')2 or C(R')2C(R')2;

[0702] Q2 is C(R')2, O, NR', S, S(O) or S(O)2;

[0703] Q3 is C(R')2, C(R')2C(R')2, O, NR', S, S(O) or S(O)2;

[0704] Each R' is independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0705] 21. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (III-2):

[0706] in,

[0707] X1 is N or CR X1 , preferably N;

[0708] X2 is CR X2 R X2’ or C(O), preferably CR X2 R X2’ ;

[0709] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0710] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0711] R X3 H, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl, preferably C 1-6 Alkyl or C1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0712] R1' is H, D, halogen or -NH2, preferably H or D;

[0713] Q1 is C 1-2 Alkylene or C 1-2 wherein the above groups are optionally substituted with one or more Ds up to full deuteration;

[0714] Q2 and Q3 are independently O, S, S(O), S(O)2, NR', C 1-2 Alkylene or C 1-2 Halogenated alkylene, preferably O, S, C 1-2 Alkylene or C 1-2 Haloalkylene; wherein the above groups are optionally substituted with 1-4 (e.g., 1, 2, 3, or 4) halogen or OH; wherein the above groups are further optionally substituted with one or more D, up to full deuteration;

[0715] Each R' is independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 Halogenated alkyl.

[0716] 22. The compound of technical solution 21, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0717] X1 is N;

[0718] X2 is CR X2 R X2’ ;

[0719] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0720] R X3 for Me;

[0721] R1' is H, D, halogen or -NH2, preferably H or D;

[0722] Q1 is CH2, CHD or CD2;

[0723] Q2 is O, S, CH2, CHD or CD2;

[0724] Q3 is O, S, CH2, CHD or CD2.

[0725] 23. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (III-2a):

[0726] in,

[0727] R X3 independently H, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0728] R1' is H, D, halogen or -NH2, preferably H or D;

[0729] Q1 is C(R')2 or C(R')2C(R')2;

[0730] Q2 is C(R')2, O, S, S(O) or S(O)2;

[0731] Q3 is C(R')2, C(R')2C(R')2, O, S, S(O) or S(O)2;

[0732] Each R' is independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0733] 24. The compound of technical solution 23, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0734] R X3 independently H, C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0735] R1' is H, D, halogen or -NH2;

[0736] Q1 is CH2, (CH2)2, CHD, (CHD)2, CD2 or (CD2)2;

[0737] Q2 is CH2, CHD, CD2, O, S, S(O) or S(O)2;

[0738] Q3 is C(R')2, S or S(O)2;

[0739] Each R' is independently H, D, F or -OH.

[0740] 25. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (III-3):

[0741] in,

[0742] X1 is N or CR X1 , preferably N;

[0743] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0744] R X3 H, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group, preferably C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0745] R1' is H, D, halogen or -NH2, preferably H or D;

[0746] Q2 is O, S or NR', preferably O or S;

[0747] R' is H, D, halogen, OH, C 1-6 Alkyl or C 1-6 Halogenated alkyl, preferably H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0748] 26. The compound of technical solution 25, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0749] X1 is N;

[0750] R X3 is Me, CD3 or cyclopropyl;

[0751] R1' is H, D, halogen or -NH2, preferably H or D;

[0752] Q2 is 0;

[0753] R' is H or D.

[0754] 27. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (III-3a):

[0755] in,

[0756] R X3 C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0757] R1' is H, D, halogen or -NH2, preferably H or D;

[0758] Q2 is CH2, CD2 or O;

[0759] R' is H, D or F.

[0760] 28. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV):

[0761] in,

[0762] X1 is N or CR X1 ;

[0763] X2 is CR X2 R X2’ or C(O), preferably CR X2 R X2’ ;

[0764] X6 is N or CR X6 , preferably CR X6 ;

[0765] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0766] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0767] R X6 is H, D or halogen, preferably H or D;

[0768] Ring A is phenyl or 5-6 membered heteroaryl, which is optionally substituted with 1-4 (eg, 1, 2, 3 or 4) R;

[0769] Y is CR Y or N, preferably CR Y ;

[0770] R1 is a 3-10 membered heterocyclic group, which is optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R b replace;

[0771] R Y is H, D or halogen;

[0772] Alternatively, R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*;

[0773] R1' is H, D, halogen or -NH2, preferably H or D;

[0774] W is CR W or N, preferably CR W ;

[0775] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0776] Each R b are independently H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2- 6 alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0777] Each R is independently H, D, halogen, -CN, -OH, -C(O)R A, -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6- 10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0778] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0779] Each R* is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0780] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0781] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0782] 29. The compound of technical solution 28, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein ring A is

[0783] 30. The compound of technical solution 28, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0784] X1 is N or CR X1 ;

[0785] X2 is CR X2 R X2’ ;

[0786] X6 is N or CR X6 , preferably CR X6 ;

[0787] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0788] R X2 and R X2’ Independently H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0789] R X6 is H, D or halogen, preferably H or D;

[0790] Ring A is a 5-membered heteroaryl group, which is optionally substituted with 1-3 (eg, 1, 2 or 3) R;

[0791] Y is CR Y ;

[0792] R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-6 membered heteroaryl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R*;

[0793] R1' is H, D, halogen or -NH2, preferably H or D;

[0794] W is CR W or N, preferably CR W ;

[0795] R W is selected from H, D, halogen or -NH2, preferably H or D;

[0796] Each R is independently H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , C 1- 6 alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0797] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl or C 1-6 Haloalkyl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0798] Each R* is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 Haloalkoxy, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0799] Each R' is independently H, D, halogen, -CN, -OH, C1-6 Alkyl or C 1-6 Halogenated alkyl.

[0800] 31. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV-1):

[0801] in,

[0802] X1 is N or CR X1 ;

[0803] X2 is CR X2 R X2’ or C(O);

[0804] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[0805] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0806] Y is CR Y or N;

[0807] R1 is a 3-10 membered heterocyclic group, which is optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R b replace;

[0808] R Y is H, D or halogen;

[0809] Alternatively, R1 and R Y Together with the carbon atoms to which they are attached, they form C 6-10 aryl or 5-10 membered heteroaryl, optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*;

[0810] R1' is H, D, halogen or -NH2, preferably H or D;

[0811] Each R b are independently H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2- 6 alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0812] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0813] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0814] Each R* is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0815] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0816] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0817] 32. The compound of any one of technical solutions 28-31, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein R1 is a 4-10 membered heterocyclic group, which is optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R b replace;

[0818] Preferably, R1 is wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) R b replace.

[0819] 33. The compound of any one of technical solutions 28-32, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein R1 and R Y Together with the carbon atom to which they are attached, they form a 5-membered heterocyclyl or 5-membered heteroaryl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5, or 6) R*;

[0820] Preferably, R1 and R Y Together with the carbon atoms to which they are attached, they form

[0821] 34. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV-2):

[0822] in,

[0823] R1' is H, D, halogen or -NH2, preferably H or D;

[0824] X2 is CR X2 R X2’ or C(O);

[0825] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0826] m is 0, 1, 2 or 3;

[0827] n is 0, 1, 2, 3, 4 or 5;

[0828] Each R b are independently H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2- 6 alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0829] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0830] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0831] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0832] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0833] 35. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV-2a):

[0834] in,

[0835] R1' is H, D, halogen or -NH2, preferably H or D;

[0836] X2 is CR X2 R X2’ or C(O);

[0837] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0838] R b H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1- 6 haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0839] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0840] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R CTogether with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0841] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0842] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0843] 36. The compound of technical solution 35, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0844] R1' is H, D, halogen or -NH2, preferably H or D;

[0845] R b H, D, halogen, -OH, -NH2, -NHC 1-6 Alkyl or -N(C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration;

[0846] Preferably,

[0847] R b is halogen or -OH.

[0848] 37. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV-2a):

[0849] in,

[0850] R1' is H, D, halogen or -NH2, preferably H or D;

[0851] X2 is CRX2 R X2’ or C(O), preferably CR X2 R X2’ ;

[0852] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 Halogenated alkyl, preferably H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) D, up to full deuteration;

[0853] R b H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1- 6 haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) D, up to full deuteration;

[0854] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, C 1-6 Alkyl, C1-6 Halogenated alkyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0855] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0856] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0857] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0858] 38. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV-2b):

[0859] in,

[0860] W is CR W or N;

[0861] R Wis selected from H, D, halogen or -NH2, preferably H or D;

[0862] R1' is H, D, halogen or -NH2, preferably H or D;

[0863] X2 is CR X2 R X2’ or C(O);

[0864] X6 is N or CR X6 , preferably CR X6 ;

[0865] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0866] R X6 is H, D or halogen, preferably H or D;

[0867] Ring A is phenyl or 5-6 membered heteroaryl, which is optionally substituted with 1-4 (eg, 1, 2, 3 or 4) R;

[0868] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0869] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or RB and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0870] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0871] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0872] 39. The compound of technical solution 38, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein ring A is

[0873] 40. The compound of technical solution 38, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted by 1-3 (e.g., 1, 2 or 3) R'.

[0874] 41. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV-2c):

[0875] in,

[0876] R1' is H, D, halogen or -NH2, preferably H or D;

[0877] X2 is CR X2 R X2’ or C(O);

[0878] RX2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0879] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0880] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0881] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0882] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0883] 42. The compound of technical solution 41, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0884] R1' is H, D, halogen or -NH2, preferably H or D;

[0885] X2 is CR X2 R X2’ ;

[0886] R X2 and R X2’ are independently H, D, halogen or -OH;

[0887] R is H, D, -C(O)R A , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0888] Each R A Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0889] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0890] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 Alkoxy C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0891] 43. The compound of technical solution 42, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0892] R1' is H, D, halogen or -NH2, preferably H or D;

[0893] X2 is CR X2 R X2 ';

[0894] R X2 and R X2’ are independently H, D, halogen or -OH;

[0895] R is H, D, -C(O)R A , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0896] Each R A Independently C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0897] Each R' is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0898] Each R" is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 Alkoxy C1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0899] 44. The compound of technical solution 43, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0900] R1' is H, D, halogen or -NH2, preferably H or D;

[0901] X2 is CR X2 R X2’ ;

[0902] R X2 and R X2’ are independently H, D, halogen or -OH;

[0903] R is H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0904] Each R' is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0905] Each R" is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0906] 45. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV-2d):

[0907] in,

[0908] R1' is H, D, halogen or -NH2, preferably H or D;

[0909] X2 is CRX2 R X2’ or C(O);

[0910] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0911] P1 is N or CR P1 ;

[0912] P2 is N or CR P2 ;

[0913] P3 is N or CR P3 ;

[0914] P4 is N or CR P4 ;

[0915] R P1 , R P2 , R P3 and R P4 are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0916] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0917] 46. ​​The compound of technical solution 45, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0918] R1' is H, D, halogen or -NH2, preferably H or D;

[0919] X2 is CR X2 R X2’;

[0920] R X2 and R X2’ are independently H, D, halogen or -OH;

[0921] P1 is N or CR P1 ;

[0922] P2 is N or CR P2 ;

[0923] P3 is N or CR P3 ;

[0924] P4 is N or CR P4 ;

[0925] R P1 , R P2 , R P3 and R P4 are independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0926] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0927] 47. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (IV-2e):

[0928] in,

[0929] R1' is H, D, halogen or -NH2, preferably H or D;

[0930] X2 is CR X2 R X2’ or C(O);

[0931] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0932] R P1 , R P2 and R P3 are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0933] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0934] 48. The compound of technical solution 47, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0935] R1' is H, D, halogen or -NH2, preferably H or D;

[0936] X2 is CR X2 R X2’ ;

[0937] R X2 and R X2’ are independently H, D, halogen or -OH;

[0938] R P1 , R P2 and R P3 are independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0939] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0940] 49. The compound of technical solution 47, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0941] R1' is H, D, halogen or -NH2, preferably H or D;

[0942] X2 is CR X2 R X2’ ;

[0943] R X2 and R X2’ are independently H, D, halogen or -OH;

[0944] R P1 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0945] R P2 is H;

[0946] R P3 H, C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0947] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0948] 50. The compound of technical solution 47, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0949] R1' is H, D, halogen or -NH2, preferably H or D;

[0950] X2 is CRX2 R X2’ ;

[0951] R X2 and R X2’ are independently H, D, halogen or -OH;

[0952] R P1 and R P3 is H;

[0953] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0954] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0955] 51. The compound of technical solution 50, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0956] R1' is H, D, halogen or -NH2, preferably H or D;

[0957] X2 is CR X2 R X2’ ;

[0958] R X2 and R X2’ are independently H, D, halogen or -OH;

[0959] R P1 and R P3 is H;

[0960] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy, 3-7 membered heterocyclyl or phenyl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0961] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0962] 52. The compound of technical solution 51, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0963] R1' is H, D, halogen or -NH2, preferably H or D;

[0964] X2 is CR X2 R X2’ ;

[0965] R X2 and R X2’ are independently H, D, halogen or -OH;

[0966] R P1 and R P3 is H;

[0967] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[0968] 53. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V):

[0969] in,

[0970] R1' is H, D, halogen or -NH2, preferably H or D;

[0971] X2 is CR X2 R X2’ or C(O);

[0972] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0973] Ring B is a 4-10 membered heterocyclyl, which is optionally substituted with 1-6 (eg, 1, 2, 3, 4, 5 or 6) R's;

[0974] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0975] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0976] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0977] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0978] 54. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-1):

[0979] in,

[0980] R1' is H, D, halogen or -NH2, preferably H or D;

[0981] X2 is CR X2 R X2’ or C(O);

[0982] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[0983] Q1 is C(R')2 or C(R')2C(R')2;

[0984] Q2 is C(R')2, O, NR', S, S(O) or S(O)2;

[0985] Q3 is C(R')2, C(R')2C(R')2, O, NR', S, S(O) or S(O)2;

[0986] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[0987] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[0988] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[0989] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[0990] 55. The compound of technical solution 54, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[0991] R1' is H, D, halogen or -NH2, preferably H or D;

[0992] Q1 is CH2, (CH2)2, CHD, (CHD)2, CD2 or (CD2)2;

[0993] Q2 is CH2, CHD, CD2, O, S, S(O) or S(O)2;

[0994] Q3 is CH2, CHD, CD2, CHF, CDF, CH(OH), CD(OH), S or S(O)2;

[0995] Preferably,

[0996] R b is halogen or -OH;

[0997] Q1 is CH2 or CD2;

[0998] Q2 is CH2, CHD, CD2, O or S;

[0999] Q3 is CH2, CHD, CD2, CHF, CDF, CH(OH), CD(OH).

[1000] 56. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-2):

[1001] in,

[1002] W is CR W or N;

[1003] R W is selected from H, D, halogen or -NH2, preferably H or D;

[1004] R1' is H, D, halogen or -NH2, preferably H or D;

[1005] X2 is CR X2 R X2’ or C(O);

[1006] X6 is N or CR X6 , preferably CR X6 ;

[1007] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1008] R X6 is H, D or halogen, preferably H or D;

[1009] Ring A is phenyl or 5-6 membered heteroaryl, which is optionally substituted with 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R;

[1010] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1011] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1012] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1013] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1014] 57. The compound of technical solution 56, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein ring A is

[1015] 58. The compound of technical solution 56, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted by 1-3 (e.g., 1, 2 or 3) R'.

[1016] 59. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-3):

[1017] in,

[1018] X1 is N or CR X1 , preferably N;

[1019] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1020] X2 is CR X2 R X2’ or C(O), preferably CR X2 R X2’ ;

[1021] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl or C 1-6 Halogenated alkyl, preferably H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1022] R1' is H, D, halogen or -NH2, preferably H or D;

[1023] Q2 is O, S or NR', preferably O or S, more preferably O;

[1024] R' is H, D, -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, -CN or halogen; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1025] R is H, D, -C(O)R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R'; wherein the above groups are further optionally substituted by one or more D, up to full deuteration;

[1026] R A H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1027] 60. The compound of technical solution 59, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1028] X1 is N;

[1029] X2 is CR X2 R X2’ ;

[1030] R X2 and R X2’ independently H or D;

[1031] R1' is H, D, halogen or -NH2, preferably H or D;

[1032] Q2 is 0;

[1033] R is H, D, Et, CH2CF3, isopropyl, CD(CD3)2, cyclopropyl, oxetanyl, pyrazin-2-yl, pyridin-2-yl or pyrimidin-5-yl.

[1034] 61. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-4):

[1035] in,

[1036] R1' is H, D, halogen or -NH2, preferably H or D;

[1037] X2 is CR X2 R X2’ or C(O);

[1038] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1039] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1040] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and RC Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1041] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1042] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1043] 62. The compound of technical solution 61, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1044] R1' is H, D, halogen or -NH2, preferably H or D;

[1045] X2 is CR X2 R X2’ ;

[1046] R X2 and R X2’ are independently H, D, halogen or -OH;

[1047] R is H, D, -C(O)R A , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1048] Each R A Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1049] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1050] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 Alkoxy C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1051] 63. The compound of technical solution 62, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1052] R1' is H, D, halogen or -NH2, preferably H or D;

[1053] X2 is CR X2 R X2’ ;

[1054] R X2 and R X2’ are independently H, D, halogen or -OH;

[1055] R is H, D, -C(O)R A , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1056] Each R A Independently C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1057] Each R' is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1058] Each R" is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 Alkoxy C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1059] 64. The compound of technical solution 63, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1060] R1' is H, D, halogen or -NH2, preferably H or D;

[1061] X2 is CR X2 R X2’ ;

[1062] R X2 and R X2’ are independently H, D, halogen or -OH;

[1063] R is H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1064] Each R' is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1065] Each R" is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1066] 65. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-4):

[1067] in,

[1068] R1' is H, D, halogen or -NH2, preferably H or D;

[1069] X2 is CR X2 R X2’ or C(O), preferably CR X2 R X2’ ;

[1070] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1071] R is H, D, -C(O)R A , C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1072] R A H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclic group.

[1073] 66. The compound of technical solution 65, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1074] R1' is H, D, halogen or -NH2, preferably H or D;

[1075] X2 is CR X2 R X2’ ;

[1076] R X2 and R X2’ independently H or D;

[1077] R is H, D, Et, CH2CF3, isopropyl or CD(CD3)2.

[1078] 67. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-5):

[1079] in,

[1080] R1' is H, D, halogen or -NH2, preferably H or D;

[1081] X2 is CR X2 R X2’ or C(O);

[1082] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1083] P1 is N or CR P1 ;

[1084] P2 is N or CR P2 ;

[1085] P3 is N or CR P3 ;

[1086] P4 is N or CR P4 ;

[1087] R P1 , R P2 , R P3 and R P4 are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1088] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1089] 68. The compound of technical solution 67, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1090] R1' is H, D, halogen or -NH2, preferably H or D;

[1091] X2 is CR X2 R X2’ ;

[1092] R X2 and R X2’ are independently H, D, halogen or -OH;

[1093] P1 is N or CR P1 ;

[1094] P2 is N or CR P2 ;

[1095] P3 is N or CR P3 ;

[1096] P4 is N or CR P4 ;

[1097] R P1 , R P2 , R P3 and R P4 are independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1098] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1099] 69. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-5):

[1100] in,

[1101] R1' is H, D, halogen or -NH2, preferably H or D;

[1102] X2 is CR X2 R X2’ ;

[1103] R X2 and R X2’ are independently H, D, OH, halogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl, preferably H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1104] P1 is CR P1 ;

[1105] P2 is N or CR P2 ;

[1106] P3 is N or CR P3 ;

[1107] P4 is N or CR P4 ;

[1108] And preferably, at least one of P3 and P4 is N;

[1109] R P1 、R P2 、R P3 and R P4 are independently H, D, halogen, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1110] or R P1 and RP2 、R P2 and R P3 or R P3 and R P4 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[1111] 70. The compound of technical solution 69, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1112] R1' is H, D, halogen or -NH2, preferably H or D;

[1113] X2 is CR X2 R X2’ ;

[1114] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1115] P1 is CR P1 ;

[1116] P2 is CR P2 ;

[1117] P3 is N or CR P3 ;

[1118] P4 is N or CR P4 ;

[1119] and at least one of P3 and P4 is N;

[1120] R P1 H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1121] R P2 is H, D, halogen or -CN;

[1122] R P3H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1123] R P4 It is H or D.

[1124] 71. The compound of technical solution 69, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1125] R1' is H, D, halogen or -NH2, preferably H or D;

[1126] X2 is CR X2 R X2’ ;

[1127] R X2 and R X2’ independently H or D;

[1128] P1 is CR P1 ;

[1129] P2 is CR P2 ;

[1130] P3 is N or CR P3 ;

[1131] P4 is N or CR P4 ;

[1132] and at least one of P3 and P4 is N;

[1133] R P1 is H, D, -CN or Me;

[1134] R P2 is H, D, F or -CN;

[1135] R P3 is H, D or Me;

[1136] R P4 It is H or D.

[1137] 72. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-5):

[1138] in,

[1139] R1' is H, D, halogen or -NH2, preferably H or D;

[1140] X2 is CRX2 R X2’ ;

[1141] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1142] P1 is CR P1 ;

[1143] P2 is N or CR P2 ;

[1144] P3 is N or CR P3 ;

[1145] P4 is CR P4 ;

[1146] R P1 、R P2 、R P3 and R P4 are independently H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1147] 73. The compound of technical solution 72, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1148] R1' is H, D, halogen or -NH2, preferably H or D;

[1149] X2 is CR X2 R X2’ ;

[1150] R X2 and R X2’ independently H or D;

[1151] P1 is CR P1 ;

[1152] P2 is N or CR P2 ;

[1153] P3 is N or CR P3 ;

[1154] P4 is CR P4 ;

[1155] R P1 H or D;

[1156] R P2 H or D;

[1157] R P3 H or D;

[1158] R P4 It is H or D.

[1159] 74. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-6):

[1160] in,

[1161] R1' is H, D, halogen or -NH2, preferably H or D;

[1162] X2 is CR X2 R X2’ or C(O);

[1163] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1164] R P1 , R P2 and R P3 are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1165] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1166] 75. The compound of technical solution 74, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1167] R1' is H, D, halogen or -NH2, preferably H or D;

[1168] X2 is CR X2 R X2’ ;

[1169] R X2 and R X2’ are independently H, D, halogen or -OH;

[1170] R P1 , R P2 and R P3 are independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1171] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1172] 76. The compound of technical solution 74, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1173] R1' is H, D, halogen or -NH2, preferably H or D;

[1174] X2 is CR X2 R X2’ ;

[1175] R X2 and R X2’ are independently H, D, halogen or -OH;

[1176] R P1 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 3-6Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1177] R P2 is H;

[1178] R P3 H, C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1179] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1180] 77. The compound of technical solution 74, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1181] R1' is H, D, halogen or -NH2, preferably H or D;

[1182] X2 is CR X2 R X2’ ;

[1183] R X2 and R X2’ are independently H, D, halogen or -OH;

[1184] R P1 and R P3 is H;

[1185] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1186] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1187] 78. The compound of technical solution 77, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1188] R1' is H, D, halogen or -NH2, preferably H or D;

[1189] X2 is CR X2 R X2’ ;

[1190] R X2 and R X2’ are independently H, D, halogen or -OH;

[1191] R P1 and R P3 is H;

[1192] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy, 3-7 membered heterocyclyl or phenyl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1193] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1194] 79. The compound of technical solution 78, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1195] R1' is H, D, halogen or -NH2, preferably H or D;

[1196] X2 is CR X2 R X2’ ;

[1197] R X2 and R X2’ are independently H, D, halogen or -OH;

[1198] R P1 and R P3 is H;

[1199] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1200] 80. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (V-6):

[1201] in,

[1202] R1' is H, D, halogen or -NH2, preferably H or D;

[1203] X2 is CR X2 R X2’ ;

[1204] R X2 and R X2’ are independently H, D, halogen, OH, C 1-6 Alkyl or C 1-6 Halogenated alkyl, preferably H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1205] R P1 、R P2 and R P3 are independently H, D, halogen, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1206] or R P1 and RP2 , or R P2 and R P3 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[1207] 81. The compound of technical solution 80, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1208] R1' is H, D, halogen or -NH2, preferably H or D;

[1209] X2 is CR X2 R X2’ ;

[1210] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1211] R P1 H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1212] R P2 is H, D, halogen or -CN;

[1213] R P3 H, D, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1214] 82. The compound of technical solution 80, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1215] R1' is H, D, halogen or -NH2, preferably H or D;

[1216] X2 is CR X2 R X2’ ;

[1217] R X2 and R X2’ independently H or D;

[1218] R P1 is H, D, -CN or Me;

[1219] R P2 is H, D, F or -CN;

[1220] R P3 It is H, D or Me.

[1221] 83. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (VI):

[1222] in,

[1223] W is CR W or N;

[1224] R W is selected from H, D, halogen or -NH2, preferably H or D;

[1225] R1' is H, D, halogen or -NH2, preferably H or D;

[1226] X2 is CR X2 R X2’ or C(O);

[1227] X6 is N or CR X6 , preferably CR X6 ;

[1228] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1229] R X6 is H, D or halogen, preferably H or D;

[1230] Ring A is phenyl or 5-6 membered heteroaryl, which is optionally substituted with 1-4 (eg, 1, 2, 3 or 4) R;

[1231] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NRA C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1232] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1233] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1234] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1235] 84. The compound of technical solution 83, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein ring A is

[1236] 85. The compound of technical solution 83, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted by 1-3 (e.g., 1, 2 or 3) R'.

[1237] 86. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (VI-1):

[1238] in,

[1239] R1' is H, D, halogen or -NH2, preferably H or D;

[1240] X2 is CR X2 R X2’ or C(O);

[1241] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1242] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1243] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1244] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1245] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1246] 87. The compound of technical solution 86, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1247] R1' is H, D, halogen or -NH2, preferably H or D;

[1248] X2 is CR X2 R X2’ ;

[1249] R X2 and R X2’ are independently H, D, halogen or -OH;

[1250] R is H, D, -C(O)R A , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1251] Each R A Independently C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1252] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1253] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Haloalkyl or C 1-6 Alkoxy C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1254] 88. The compound of technical solution 87, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1255] R1' is H, D, halogen or -NH2, preferably H or D;

[1256] X2 is CR X2 R X2’ ;

[1257] R X2 and R X2’ are independently H, D, halogen or -OH;

[1258] R is H, D, -C(O)R A , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1259] Each R A Independently C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 Cycloalkyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1260] Each R' is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1261] Each R" is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Haloalkyl or C 1-3 Alkoxy C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1262] 89. The compound of technical solution 88, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1263] R1' is H, D, halogen or -NH2, preferably H or D;

[1264] X2 is CR X2 R X2’ ;

[1265] R X2 and R X2’ are independently H, D, halogen or -OH;

[1266] R is H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1267] Each R' is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1268] Each R" is independently H, D, halogen, -CN, -OH, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1269] 90. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (VI-2):

[1270] in,

[1271] R1' is H, D, halogen or -NH2, preferably H or D;

[1272] X2 is CR X2 R X2’ or C(O);

[1273] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1274] P1 is N or CR P1 ;

[1275] P2 is N or CR P2 ;

[1276] P3 is N or CR P3 ;

[1277] P4 is N or CR P4 ;

[1278] R P1 , R P2 , R P3 and R P4 are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1279] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1280] 91. The compound of technical solution 90, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1281] R1' is H, D, halogen or -NH2, preferably H or D;

[1282] X2 is CR X2 R X2’ ;

[1283] R X2 and R X2’ are independently H, D, halogen or -OH;

[1284] P1 is N or CR P1 ;

[1285] P2 is N or CR P2 ;

[1286] P3 is N or CR P3 ;

[1287] P4 is N or CR P4 ;

[1288] R P1 , R P2 , R P3 and R P4 are independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1289] Each R" is independently H, D, halogen, -CN, C 1-3Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1290] 92. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (VI-3):

[1291] in,

[1292] R1' is H, D, halogen or -NH2, preferably H or D;

[1293] X2 is CR X2 R X2’ or C(O);

[1294] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1295] R P1 , R P2 and R P3 are independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1296] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1297] 93. The compound of technical solution 92, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1298] R1' is H, D, halogen or -NH2, preferably H or D;

[1299] X2 is CR X2 R X2’ ;

[1300] R X2 and R X2’ are independently H, D, halogen or -OH;

[1301] R P1 , R P2 and R P3 are independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1302] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1303] 94. The compound of technical solution 92, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1304] R1' is H, D, halogen or -NH2, preferably H or D;

[1305] X2 is CR X2 R X2’ ;

[1306] R X2 and R X2’ are independently H, D, halogen or -OH;

[1307] R P1 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1308] RP2 is H;

[1309] R P3 H, C 1-3 Alkyl or C 1-3 wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1310] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1311] 95. The compound of technical solution 92, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1312] R1' is H, D, halogen or -NH2, preferably H or D;

[1313] X2 is CR X2 R X2’ ;

[1314] R X2 and R X2’ are independently H, D, halogen or -OH;

[1315] R P1 and R P3 is H;

[1316] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1317] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1318] 96. The compound of technical solution 95, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1319] R1' is H, D, halogen or -NH2, preferably H or D;

[1320] X2 is CR X2 R X2’ ;

[1321] R X2 and R X2’ are independently H, D, halogen or -OH;

[1322] R P1 and R P3 is H;

[1323] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 haloalkoxy, 3-7 membered heterocyclyl or phenyl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1324] Each R" is independently H, D, halogen, -CN, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1325] 97. The compound of technical solution 96, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein:

[1326] R1' is H, D, halogen or -NH2, preferably H or D;

[1327] X2 is CR X2 R X2’ ;

[1328] R X2 and R X2’ are independently H, D, halogen or -OH;

[1329] R P1 and R P3 is H;

[1330] R P2 H, D, halogen, -CN, C 1-3 Alkyl, C1-3 Halogenated alkyl, C 1-3 Alkoxy, C 1-3 wherein the above groups are optionally substituted with one or more D, up to full deuteration.

[1331] 98. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (VII):

[1332] in,

[1333] W is CR W or N;

[1334] R W is selected from H, D, halogen or -NH2, preferably H or D;

[1335] R1' is H, D, halogen or -NH2, preferably H or D;

[1336] X1 is N or CR X1 , preferably N;

[1337] X6 is N or CR X6 , preferably CR X6 ;

[1338] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1339] X2 is CR X2 R X2’ or C(O), preferably CR X2 R X2’ ;

[1340] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1341] R X6 is H, D or halogen, preferably H or D;

[1342] Ring A is phenyl or 5-6 membered heteroaryl, which is optionally substituted with 1-4 (eg, 1, 2, 3 or 4) R;

[1343] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1344] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1345] Each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1346] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1347] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1348] 99. The compound of technical solution 98, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein ring A is

[1349] 100. The compound of technical solution 98, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted by 1-3 (e.g., 1, 2 or 3) R'.

[1350] 101. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (VII-1):

[1351] in,

[1352] R1' is H, D, halogen or -NH2, preferably H or D;

[1353] X1 is N or CR X1 , preferably N;

[1354] R X1 H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1355] X2 is CR X2 R X2’ or C(O), preferably CR X2 R X2’ ;

[1356] R X2 and RX2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1357] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1358] Each R* is independently H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1359] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl;

[1360] Each RA 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R'.

[1361] 102. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (VII-2):

[1362] in,

[1363] R1' is H, D, halogen or -NH2, preferably H or D;

[1364] X2 is CR X2 R X2’ or C(O), preferably CR X2 R X2’ ;

[1365] R X2 and R X2’ are independently H, D, halogen, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1366] Each R* is independently H, D, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, or two R* together with the atoms to which they are attached form a C 3-8 Cycloalkyl or 4-10 membered heterocyclyl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1367] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl or C 1-6 alkyl halide;

[1368] R P1 、R P2 and R P3are independently H, D, halogen, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, preferably H, D, halogen, -CN, C 1-6 Alkyl or C 1-6 wherein the above groups are optionally substituted by 1-6 (eg 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted with one or more D, up to full deuteration;

[1369] or R P1 and R P2 , or R P2 and R P3 Together with the atoms to which they are attached, they form C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g. 1, 2, 3, 4, 5 or 6) -CN, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy or C 1-6 wherein the above groups are optionally substituted by one or more Ds, up to full deuteration.

[1370] 103. The compound of technical solution 15, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, which is a compound of formula (VIII):

[1371] in,

[1372] W is CR W or N;

[1373] R W is selected from H, D, halogen or -NH2, preferably H or D;

[1374] R1' is H, D, halogen or -NH2, preferably H or D;

[1375] X2 is CR X2 R X2’ or C(O);

[1376] X6 is N or CR X6, preferably CR X6 ;

[1377] R X2 and R X2’ are independently H, D, halogen, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration;

[1378] R X6 is H, D or halogen, preferably H or D;

[1379] Ring A is phenyl or 5-6 membered heteroaryl, which is optionally substituted with 1-4 (eg, 1, 2, 3 or 4) R;

[1380] R is H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (eg, 1, 2, 3, 4, 5 or 6) R';

[1381] Each R A 、R B and R C Independently H, D, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 2-6 Alkenyl, C 2-6 Alkynyl, C 6-10 Aryl or 5-10 membered heteroaryl, or R B and R C Together with the nitrogen atom to which they are attached, they form a 3-7 membered heterocyclyl or a 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R';

[1382] Each R' is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 Cycloalkyl, 3-7 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the above groups are optionally substituted by 1-6 (e.g., 1, 2, 3, 4, 5 or 6) R";

[1383] Each R" is independently H, D, halogen, -CN, -OH, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Alkoxy C 1-6 Haloalkoxy, C 3-6 Cycloalkyl or 3-7 membered heterocyclyl; wherein the above groups are optionally substituted by one or more D, up to full deuteration.

[1384] 104. The compound of technical solution 103, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein ring A is

[1385] 105. The compound of technical solution 103, or its tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate, wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted by 1-3 (e.g., 1, 2 or 3) R'.

[1386] 106. A compound, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein the compound is selected from:

[1387] 107. A pharmaceutical composition comprising a compound of any one of technical solutions 1 to 106, or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof, and a pharmaceutically acceptable excipient, and optionally, other therapeutic agents.

[1388] 108. A unit dosage form comprising the pharmaceutical composition of technical solution 107.

[1389] 109. Use of the compound of any one of technical solutions 1-106, or its tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate, or the pharmaceutical composition of technical solution 107, or the unit dosage form of technical solution 108 in the preparation of a medicament for treating and / or preventing diseases regulated by wild-type and / or mutant Bcr-Abl1 kinase;

[1390] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: T315I, T315M, F317L, E355G, V299L, M244V, G250E, Q252H, Y253H, E255K, E255V, H396P, H396R, H396A, A397P, P223S, K294E, M351T, F359V, E459K, P465S, ​​V468F, I502L, A337V or A424T;

[1391] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from: T315I or T315M;

[1392] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: T315I;

[1393] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: P465S, ​​V468F, I502L, A337V or A424T.

[1394] 110. A method for treating and / or preventing a disease regulated by wild-type and / or mutant Bcr-Abl1 kinase in a subject, the method comprising administering to the subject a compound of any one of technical solutions 1-106 or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or the pharmaceutical composition of technical solution 107, or the unit dosage form of technical solution 108;

[1395] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: T315I, T315M, F317L, E355G, V299L, M244V, G250E, Q252H, Y253H, E255K, E255V, H396P, H396R, H396A, A397P, P223S, K294E, M351T, F359V, E459K, P465S, ​​V468F, I502L, A337V or A424T;

[1396] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from: T315I or T315M;

[1397] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: T315I;

[1398] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: P465S, ​​V468F, I502L, A337V or A424T.

[1399] 111. The compound of any one of technical solutions 1-106, or a tautomer, stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, hydrate or solvate thereof, or the pharmaceutical composition of technical solution 107, or the unit dosage form of technical solution 108, for treating and / or preventing diseases regulated by wild-type and / or mutant Bcr-Abl1 kinase;

[1400] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: T315I, T315M, F317L, E355G, V299L, M244V, G250E, Q252H, Y253H, E255K, E255V, H396P, H396R, H396A, A397P, P223S, K294E, M351T, F359V, E459K, P465S, ​​V468F, I502L, A337V or A424T;

[1401] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from: T315I or T315M;

[1402] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: T315I;

[1403] Preferably, the mutation of the mutant Bcr-Abl1 kinase is selected from the group consisting of: P465S, ​​V468F, I502L, A337V or A424T.

[1404] 112. The use of technical solution 108 or the method of technical solution 109 or the use of the compound or composition of technical solution 110, wherein the disease regulated by the wild-type and / or mutant Bcr-Abl1 kinase is selected from: leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myeloma, neurodegenerative disease, solid tumor, immune disease or fibrosis.

[1405] 113. The use of technical solution 108 or the method of technical solution 109 or the use of the compound or composition of technical solution 110, wherein the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic lymphoma, chronic myeloid leukemia, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, acute undifferentiated leukemia, anaplastic large cell lymphoma, prolymphocytic leukemia, juvenile myelomonocytic leukemia, adult T-cell leukemia, acute myeloid leukemia with trilineage myelodysplasia, mixed lineage leukemia, myelodysplastic syndrome, amyotrophic lateral sclerosis, Parkinson's disease or Alzheimer's disease; preferably, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from acute lymphoblastic leukemia or chronic myeloid leukemia.

[1406] 114. A method for preparing the compound of any one of technical solutions 1-106.

[1407] 115. An intermediate compound or a salt thereof, which is the following compound:

[1408] The compounds of the present invention may include one or more asymmetric centers and may therefore exist in a variety of stereoisomeric forms, for example, enantiomers and / or diastereomeric forms. For example, the compounds of the present invention may be individual enantiomers, diastereomers, or geometric isomers (e.g., cis and trans isomers), or may be in the form of mixtures of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomers. Isomers may be separated from the mixture by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers may be prepared by asymmetric synthesis.

[1409] "Tautomer" refers to a functional group in certain compounds that changes its structure to become another functional group isomer, and can rapidly convert into each other, forming two isomers in dynamic equilibrium, and these two isomers are called tautomers.

[1410] Those skilled in the art will appreciate that organic compounds can form complexes with solvents in which they react or from which they precipitate or crystallize. These complexes are referred to as "solvates." When the solvent is water, the complex is referred to as a "hydrate." The present invention encompasses all solvates of the compounds of the present invention.

[1411] The term "solvate" refers to a form of a compound or its salt that is combined with a solvent, usually formed by a solvolysis reaction. This physical association may include hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, etc. The compounds described herein can be prepared, for example, in a crystalline form and can be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include stoichiometric solvates and non-stoichiometric solvates. In some cases, the solvate will be able to separate, for example, when one or more solvent molecules are incorporated into the crystal lattice of the crystalline solid. "Solvate" includes solvates in the solution state and separable solvates. Representative solvates include hydrates, ethanolates, and methanolates.

[1412] The term "hydrate" refers to a compound that is combined with water. Generally, the ratio of the number of water molecules contained in the hydrate of a compound to the number of molecules of the compound in the hydrate is determined. Therefore, the hydrate of a compound can be represented by the general formula R×xH2O, for example, where R is the compound and x is a number greater than 0. A given compound can form more than one type of hydrate, including, for example, monohydrates (x is 1), lower hydrates (x is a number greater than 0 and less than 1, for example, hemihydrates (R×0.5H2O)) and polyhydrates (x is a number greater than 1, for example, dihydrates (R×2H2O) and hexahydrates (R×6H2O)).

[1413] The compounds of the present invention can be in amorphous or crystalline form (crystal form or polymorph). In addition, the compounds of the present invention can exist in one or more crystalline forms. Therefore, the present invention includes all amorphous or crystalline forms of the compounds of the present invention within its scope. The term "polymorph" refers to the crystalline form (or its salt, hydrate or solvate) of a compound with a specific crystal packing arrangement. All polymorphs have the same elemental composition. Different crystalline forms typically have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, photoelectric properties, stability and solubility. Recrystallization solvent, crystallization rate, storage temperature and other factors can cause one crystalline form to dominate. Various polymorphs of a compound can be prepared by crystallization under different conditions.

[1414] The present invention also includes isotopically labeled compounds which are identical to those described in formula (I) but in which one or more atoms are replaced by atoms having an atomic mass or mass number different from the atomic mass or mass number normally found in nature. Examples of isotopes that can be introduced into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, for example 2 H. 3 H. 13 C. 11 C. 14 C. 15 N. 18 O. 17 O. 31 P. 32 P. 35 S. 18 F and 36 Cl. Compounds of the present invention containing the above-mentioned isotopes and / or other isotopes of other atoms, their prodrugs and pharmaceutically acceptable salts of the compounds or prodrugs are within the scope of the present invention. Certain isotopically labeled compounds of the present invention, such as those in which radioactive isotopes (e.g. 3 H and 14 C) can be used in drug and / or substrate tissue distribution assays. 3 H and carbon-14, i.e. 14 C isotopes are particularly preferred because they are easy to prepare and detect. 2 H, because greater metabolic stability can provide therapeutic benefits, such as prolonged in vivo half-life or reduced dosage requirements, and thus may be preferred in some cases. Isotopically labeled compounds of formula (I) of the present invention and their prodrugs can generally be prepared by substituting readily available isotopically labeled reagents for non-isotopically labeled reagents when carrying out the processes disclosed in the following schemes and / or the Examples and Preparations.

[1415] In addition, prodrugs are also included in the context of the present invention. The term "prodrug" as used herein refers to a compound that is converted in vivo, for example by hydrolysis in the blood, into its active form that has a medical effect. Pharmaceutically acceptable prodrugs are described in T. Higuchi and V. Stella, Prodrugs as Novel Delivery Systems, Vol. 14 of the ACSSymposium Series, Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, and D. Fleisher, S. Ramon and H. Barbra, "Improved oral drug delivery: solubility limitations overcome by the use of prodrugs", Advanced Drug Delivery Reviews (1996) 19 (2) 115-130, each of which is incorporated herein by reference.

[1416] A prodrug is any covalently bonded compound of the present invention that releases the parent compound in vivo when such a prodrug is administered to a patient. Prodrugs are typically prepared by modifying functional groups in such a way that the modification can be cleaved to produce the parent compound by conventional manipulation or in vivo. Prodrugs include, for example, compounds of the present invention in which a hydroxyl, amino, or sulfhydryl group is bonded to any group that, when administered to a patient, can be cleaved to form a hydroxyl, amino, or sulfhydryl group. Thus, representative examples of prodrugs include, but are not limited to, acetate / amide, formate / amide, and benzoate / amide derivatives of the hydroxyl, sulfhydryl, and amino functional groups of compounds of formula (I). Additionally, in the case of carboxylic acids (-COOH), esters such as methyl esters, ethyl esters, and the like can be used. Esters themselves can be active and / or can be hydrolyzed under human in vivo conditions. Suitable pharmaceutically acceptable in vivo hydrolyzable ester groups include those that readily decompose in the human body to release the parent acid or its salt.

[1417] Pharmaceutical compositions, preparations and kits

[1418] In another aspect, the present invention provides pharmaceutical compositions comprising a compound of the invention (also referred to as an "active ingredient") and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises an effective amount of the active ingredient. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the active ingredient. In some embodiments, the pharmaceutical composition comprises a prophylactically effective amount of the active ingredient.

[1419] The pharmaceutically acceptable excipient for the present invention refers to a non-toxic carrier, adjuvant or vehicle that does not destroy the pharmacological activity of the compound prepared together. The pharmaceutically acceptable carrier, adjuvant or vehicle that can be used in the present composition include, but are not limited to, ion exchangers, aluminum oxide, aluminum stearate, lecithin, serum proteins (such as human serum albumin), buffer substances (such as phosphates), glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salt or electrolytes (such as protamine sulfate), disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, silica gel, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based materials, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and lanolin.

[1420] The present invention also includes kits (e.g., pharmaceutical packaging). The kits provided may include a compound of the invention, other therapeutic agents, and first and second containers (e.g., vials, ampoules, bottles, syringes, and / or dispersible packaging or other suitable containers) containing the compound of the invention and other therapeutic agents. In some embodiments, the kit provided may also optionally include a third container containing a pharmaceutical excipient for diluting or suspending the compound of the invention and / or other therapeutic agents. In some embodiments, the compound of the invention and other therapeutic agents provided in the first and second containers are combined to form a unit dosage form.

[1421] Pharmaceutical compositions provided by the invention can be administered by many routes, including but not limited to: oral administration, parenteral administration, inhalation administration, topical administration, rectal administration, nasal administration, oral administration, vaginal administration, administration by implant or other modes of administration. For example, parenteral administration used herein includes subcutaneous administration, intradermal administration, intravenous administration, intramuscular administration, intraarticular administration, intraarterial administration, intrasynovial administration, intrasternal administration, intrathecal administration, intralesional administration, and intracranial injection or infusion technology.

[1422] Typically, an effective amount of the compounds provided herein is administered. The amount of compound actually administered can be determined by a physician based on the relevant circumstances, including the condition being treated, the route of administration selected, the compound actually administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the like.

[1423] When used to prevent the conditions described herein, the compounds provided herein are administered to a subject at risk of developing the condition, typically based on the advice and under the supervision of a physician, at dosage levels as described above. Subjects at risk of developing a particular condition typically include those with a family history of the condition, or those identified by genetic testing or screening as being particularly susceptible to developing the condition.

[1424] The pharmaceutical compositions provided herein can also be administered long-term ("chronic administration"). Long-term administration refers to administration of a compound or pharmaceutical composition thereof over an extended period of time, e.g., 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, etc., or administration can continue indefinitely, e.g., for the remainder of the subject's life. In some embodiments, long-term administration is intended to provide a constant level of the compound in the blood over an extended period of time, e.g., within the therapeutic window.

[1425] Various methods of administration can be used to further deliver the pharmaceutical composition of the present invention. For example, in some embodiments, the pharmaceutical composition can be administered by push injection, for example, in order to rapidly increase the concentration of the compound in the blood to an effective level. The push dose depends on the target systemic level of the active ingredient, for example, an intramuscular or subcutaneous push dose slowly releases the active ingredient, and a push (for example, by IV intravenous drip) delivered directly to the vein can be delivered more rapidly so that the concentration of the active ingredient in the blood is rapidly increased to an effective level. In other embodiments, the pharmaceutical composition can be given in a continuous infusion form, for example, by IV intravenous drip, so as to provide a steady-state concentration of the active ingredient in the subject's body. In addition, in other embodiments, the pharmaceutical composition of the push dose can be first given, and then continuous infusion.

[1426] Oral compositions can be in the form of bulk liquid solutions or suspensions or bulk powders. However, more generally, in order to facilitate accurate dosing, the compositions are provided in unit dosage form. The term "unit dosage form" refers to a physically discrete unit suitable as a unit dose for human patients and other mammals, each unit containing a predetermined amount of active substance suitable for producing the desired therapeutic effect and a suitable pharmaceutical excipient. Typical unit dosage forms include pre-filled, pre-measured ampoules or syringes of liquid compositions, or pills, tablets, capsules, etc. in the case of solid compositions. In such compositions, the compound is typically a minor component (about 0.1 to about 50% by weight, or preferably about 1 to about 40% by weight), with the remainder being various carriers or excipients and processing aids useful for forming the desired dosage form.

[1427] For oral dosage, a representative regimen is one to five oral doses per day, particularly two to four oral doses, typically three oral doses. Using these dosage administration modes, each dose provides about 0.01 to about 20 mg / kg of the compound of the invention, with preferred doses each providing about 0.1 to about 10 mg / kg, particularly about 1 to about 5 mg / kg.

[1428] To provide blood levels similar to, or lower than, those obtained with an injectable dose, a transdermal dose is typically selected in an amount of about 0.01 to about 20% by weight, preferably about 0.1 to about 20% by weight, preferably about 0.1 to about 10% by weight, and more preferably about 0.5 to about 15% by weight.

[1429] From about 1 to about 120 hours, and particularly from 24 to 96 hours, the injected dose level is in the range of about 0.1 mg / kg / hour to at least 10 mg / kg / hour. To achieve adequate steady-state levels, a preload bolus of about 0.1 mg / kg to about 10 mg / kg or more may also be administered. For a 40 to 80 kg human patient, the maximum total dose may not exceed about 2 g / day.

[1430] Liquid forms suitable for oral administration may include a suitable aqueous or non-aqueous carrier and buffers, suspending and dispersing agents, colorants, flavorings, etc. Solid forms may include, for example, any of the following components, or compounds of a similar nature: binders such as microcrystalline cellulose, tragacanth, or gelatin; excipients such as starch or lactose; disintegrants such as alginic acid, Primogel, or corn starch; lubricants such as magnesium stearate; glidants such as colloidal silicon dioxide; sweeteners such as sucrose or saccharin; or flavorings such as peppermint, methyl salicylate, or orange flavor.

[1431] Injectable compositions are typically based on sterile saline or phosphate buffered saline for injection, or other injectable excipients known in the art. As previously mentioned, in such compositions, the active compound is typically a minor component, often about 0.05 to 10% by weight, with the remainder being injectable excipients and the like.

[1432] Typically, transdermal compositions are formulated as topical ointments or creams containing the active ingredient. When formulated as an ointment, the active ingredient is typically combined with a paraffin or water-miscible ointment base. Alternatively, the active ingredient can be formulated into a cream together with, for example, an oil-in-water cream base. Such transdermal formulations are well known in the art and typically include other components that enhance the stable skin penetration of the active ingredient or formulation. All such known transdermal formulations and components are included within the scope provided by the present invention.

[1433] The compounds of the present invention may also be administered by transdermal devices.Thus, transdermal administration may be achieved using patches of the reservoir or porous membrane type, or various solid matrices.

[1434] The above components for oral administration, injection or topical administration are representative only. Other materials and processing techniques are described in Part 8 of Remington's Pharmaceutical Sciences, 17th edition, 1985, Mack Publishing Company, Easton, Pennsylvania, which is incorporated herein by reference.

[1435] The compounds of the invention can also be administered in sustained release form or from a sustained release delivery system. Descriptions of representative sustained release materials can be found in Remington's Pharmaceutical Sciences.

[1436] The present invention also relates to pharmaceutically acceptable formulations of the compounds of the present invention. In one embodiment, the formulation comprises water. In another embodiment, the formulation comprises a cyclodextrin derivative. The most common cyclodextrins are α-, β-, and γ-cyclodextrins consisting of 6, 7, and 8 α-1,4-linked glucose units, respectively, which optionally include one or more substituents on the linked sugar portion, including but not limited to: methylated, hydroxyalkylated, acylated, and sulfoalkyl ether substitutions. In some embodiments, the cyclodextrin is a sulfoalkyl ether β-cyclodextrin, for example, sulfobutyl ether β-cyclodextrin, also known as Captisol. See, for example, US5,376,645. In some embodiments, the formulation includes hexapropyl-β-cyclodextrin (e.g., in water, 10-50%).

[1437] Indications

[1438] In another aspect, provided is the use of a compound of formula (I) disclosed herein (including all individual embodiments and generic subsets disclosed herein) or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof as a medicament.

[1439] In one embodiment, the compounds of the present invention are useful for treating and / or preventing diseases regulated by wild-type Bcr-Abl1 kinase.

[1440] In another embodiment, the compounds of the present invention are allosteric inhibitors of Bcr-Abl1 that target the myristoyl pocket (a type IV pocket, distal to the ATP site), potentially addressing the resistance to type I and type II Bcr-Abl1 inhibitors that bind to the ATP site. The primary causes of resistance to type I and type II Bcr-Abl1 inhibitors include Bcr-Abl1 point mutations, gene amplification, overexpression of ABC transporters, or Bcr-Abl1-independent mechanisms. The development of drug resistance, which can lead to relapse in patients, is thought to be primarily linked to mutations in the Bcr-Abl1 kinase domain, with point mutations in the abl1 kinase domain found in 30%-90% of patients who develop resistance.

[1441] In another embodiment, the compounds of the present invention can be used to treat and / or prevent diseases regulated by mutant Bcr-Abl1 kinases. In one embodiment, the mutation in the mutant Bcr-Abl1 kinase may be located in the ATP binding site. In a more specific embodiment, the mutation in the ATP binding site is selected from T315I, T315M, F317L, E355G, or V299L. In a more specific embodiment, the mutation in the ATP binding site is selected from T315I. In a more specific embodiment, the mutation in the ATP binding site is selected from T315M. In another embodiment, the mutation in the mutant Bcr-Abl1 kinase may be located in the P-binding loop. In a more specific embodiment, the mutation in the P-binding loop is selected from M244V, K247R, L248V, G250E, G250R, Q252H, Q252R, Y253F, Y253H, E255K, or E255V. In a more specific embodiment, the mutation in the P-binding loop is selected from M244V, G250E, Q252H, Y253H, E255K, or E255V. In another specific embodiment, the mutation in the mutant Bcr-Abl1 kinase may be located in the A-binding loop. In a more specific embodiment, the mutation in the A-binding loop is selected from V379I, A380T, F382L, L384M, L387M, L387F, L387V, M388L, Y393C, H396P, H396R, H396A, or A397P. In a more specific embodiment, the mutation in the A-binding loop is selected from H396P, H396R, H396A, or A397P. In another specific embodiment, the mutation in the mutant Bcr-Abl1 kinase may be located in the SH2 domain interface or the SH3 domain interface. In a more specific embodiment, the mutation located at the SH2 domain interface or the SH3 domain interface is selected from P223S, K294E, M351T or F359V. In another specific embodiment, the mutation of the mutant Bcr-Abl1 kinase is selected from T315I, Y253F, Y253H, E255K, E255V, M351T, G250E, F359C, F359V, H396P, H396R, M244V, E355G, F317L, M237I, Q252H, Q252R, D276G, L248V or F486S.

[1442] In another embodiment, the compounds of the present invention can address the resistance problem developed by aspartame.

[1443] In another embodiment, the compounds of the present invention can be used to treat and / or prevent diseases regulated by mutant Bcr-Abl1 kinases. In a specific embodiment, the mutation in the mutant Bcr-Abl1 kinase can be located in the myristoyl binding site. In a more specific embodiment, the mutation in the myristoyl binding site is selected from E459K, P465S, ​​V468F, I502L, C464W, A337V, or A424T. In an even more specific embodiment, the mutation in the myristoyl binding site is selected from E459K, P465S, ​​V468F, I502L, A337V, or A424T.

[1444] In another embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, myeloma, neurodegenerative disease, solid tumor, immune disease or fibrosis.

[1445] In a specific embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma or myeloma, for example, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic lymphoma (CLL), chronic myeloid leukemia (CML), chronic myelomonocytic leukemia (CMML), chronic neutrophilic leukemia (CNL), acute undifferentiated leukemia (AUL), anaplastic large cell lymphoma (ALCL), prolymphocytic leukemia (PML), juvenile myelomonocytic leukemia (JMML), adult T-cell leukemia (ATCL), leukemia (ERL), leukemia (ERL), and leukemia. LL), acute myeloid leukemia with trilineage myelodysplastic disorder (AML / TMDS), mixed lineage leukemia (MLL), myelodysplastic syndrome (MDS), myeloproliferative disorders (MPD), diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma (e.g., splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma), Burkitt's lymphoma, Waldenstrom's macroglobulinemia (lymphoplasmacytic lymphoma), primary central nervous system lymphoma, small lymphocytic lymphoma, precursor B-cell lymphoblastic leukemia, hairy cell leukemia, mucosa-associated lymphoid tissue lymphoma, plasma cell myeloma, plasmacytoma, and multiple myeloma. Other examples of hematological cancers include myelodysplastic disorders (MPDs), such as polycythemia vera (PV), essential thrombocytopenia (ET), and idiopathic primary myelofibrosis (IMF / IPF / PMF). In another specific embodiment, the disease regulated by wild-type Bcr-Abl1 kinase and mutant Bcr-Abl1 kinase is selected from acute myeloid leukemia (AML) or chronic myeloid leukemia (CML).

[1446] In another specific embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from a neurodegenerative disease, e.g., amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Alzheimer's disease (AD), frontotemporal dementia (FTD), Pick's disease and Niemann-Pick disease type C (NPC).

[1447] In another embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from solid tumors, e.g., bone cancer, bone metastasis, breast cancer, gastro-esophageal cancer, pancreatic cancer, ovarian cancer, prostate cancer, lung cancer, colon cancer and head and neck cancer.

[1448] In another embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from immune diseases, e.g., arthritis, multiple sclerosis, osteoporosis, irritable bowel syndrome, inflammatory bowel disease, Crohn's disease, lupus, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, Still's disease, juvenile arthritis, diabetes, myasthenia gravis, Hashimoto's thyroiditis, Ord's thyroiditis, Graves' disease, Sjögren's syndrome, Guillain-Barré syndrome, acute Disseminated encephalomyelitis, Addison's disease, opsoclonus syndrome, ankylosing spondylitis, antiphospholipid antibody syndrome, aplastic anemia, autoimmune hepatitis, celiac disease, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Reiter's syndrome, Takayasu's arteritis, warm autoimmune hemolytic anemia, Wegener's granulomatosis, psoriasis, alopecia universalis, Behcet's disease, chronic fatigue, dysautonomia, endometriosis Disease, interstitial cystitis, neuromyotonia, scleroderma and vulvodynia, asthma, appendicitis, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, colitis, conjunctivitis, colitis, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, hepatitis, inflammatory enteritis, suppurative inflammation, laryngitis, mastitis, meningitis, myelitis, Myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, mumps, pericarditis, peritonitis, pharyngitis, pleurisy, phlebitis, pneumonia, pneumonitis, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, uveitis, vaginitis, vasculitis, vulvitis, graft-versus-host disease, transplantation, blood transfusion, anaphylactic reaction, allergic reaction, type I hypersensitivity reaction, allergic conjunctivitis, allergic rhinitis, and atopic dermatitis.

[1449] In another specific embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from inflammatory diseases, such as arthritis, asthma, appendicitis, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, colitis, conjunctivitis, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, hepatitis, hidradenitis suppurativa, laryngitis, mastitis, meningitis, osteomyelitis, myocarditis, myositis, nephritis, oophoritis, orchitis, Osteitis, otitis, pancreatitis, mumps, pericarditis, peritonitis, pharyngitis, pleurisy, phlebitis, pneumonia, pneumonitis, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, uveitis, vaginitis, vasculitis and vulvitis.

[1450] In another embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from autoimmune diseases, e.g., lupus and Sjögren's syndrome, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, Still's disease, juvenile arthritis, diabetes, myasthenia gravis, Hashimoto's thyroiditis, Ord's thyroiditis, Graves' disease, Sjögren's syndrome, Guillain-Barré syndrome, acute disseminated encephalomyelitis, Addison's disease, opsoclonus-myoclonus syndrome , ankylosing spondylitis, antiphospholipid antibody syndrome, aplastic anemia, autoimmune hepatitis, celiac disease, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Reiter's syndrome, Takayasu's arteritis, hemolytic anemia, Wegener's granulomatosis, psoriasis, alopecia universalis, Behçet's disease, chronic fatigue, dysautonomia, endometriosis, interstitial cystitis, neuromyotonia, scleroderma, and vulvodynia.

[1451] In another specific embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from the group consisting of xenoimmune diseases, e.g., graft-versus-host disease, transplantation, transfusion, anaphylaxis, allergic reactions, type I hypersensitivity reactions, allergic conjunctivitis, allergic rhinitis, and atopic dermatitis.

[1452] In another specific embodiment, the disease regulated by wild-type and / or mutant Bcr-Abl1 kinase is selected from fibrosis, e.g., pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), usual interstitial pneumonia (UIP), interstitial lung disease, cryptogenic fibrosing alveolitis (CFA), bronchiolitis obliterans, bronchiectasis, fatty liver disease, steatosis (e.g., non-alcoholic steatohepatitis (NASH), cholestatic liver disease (e.g., primary biliary cirrhosis (PBC)), cirrhosis, alcohol-induced liver fibrosis, bile duct damage, biliary fibrosis, cholestasis and bile duct disease.

[1453] In the therapeutic method of the present invention, " effective amount " is intended to refer to the amount or dosage that is enough to produce the desired therapeutic benefit in the individuality of the treatment in need.The effective amount or dosage of the compounds of this invention can be determined by conventional methods (such as modeling, dose escalation or clinical trials) and conventional factors (such as the mode or approach of drug delivery, the pharmacokinetics of medicament, the severity and process of infection, the health status and body weight of the individual and the judgment of the treating physician).Exemplary dosage is in the range of about 0.1mg to 1g per day or about 1mg to 50mg per day or about 50mg to 250mg per day or about 250mg to 1g per day.Total dose can be single or separate dosage units (for example, BID, TID, QID).

[1454] After the patient's disease improves, the dosage can be adjusted for preventive or maintenance treatment. For example, the dosage or frequency of administration or both can be reduced to the amount required to maintain the desired treatment or preventive effect, depending on the symptoms. Of course, if the symptoms have been alleviated to an appropriate degree, treatment can be stopped. However, when any symptom recurs, the patient may need long-term intermittent treatment. The patient may also need long-term slow treatment.

[1455] Drug combinations

[1456] The compounds of the present invention described herein can be used in combination with one or more other active ingredients in pharmaceutical compositions or methods to treat the diseases and conditions described herein. Other additional active ingredients include other therapeutic agents or agents that mitigate the adverse effects of the therapeutic agent on the intended disease target. The combination can be used to increase efficacy, improve other disease symptoms, reduce one or more negative effects, or reduce the required dose of the compounds of the present invention. The additional active ingredients can be formulated into a pharmaceutical composition separate from the compounds of the present invention or can be included in a single pharmaceutical composition with the compounds of the present invention. The additional active ingredients can be administered simultaneously with, before, or after the administration of the compounds of the present invention.

[1457] Combination agents include those additional active ingredients known or observed to be effective in treating the diseases and conditions described herein, including those effective against another target associated with the disease. For example, the compositions and formulations of the present invention, as well as the methods of treatment, may further comprise other drugs or pharmaceuticals, such as other active agents useful for treating or alleviating the target disease or associated symptoms or conditions. For cancer indications, such other such agents include, but are not limited to, kinase inhibitors, such as EGFR inhibitors (e.g., erlotinib, gefitinib); Raf inhibitors (e.g., vemurafenib), VEGFR inhibitors (e.g., sunitinib); standard chemotherapeutic agents, such as alkylating agents, antimetabolites, antitumor antibiotics, topoisomerase inhibitors, platinum drugs, mitotic inhibitors, antibodies, hormone therapy, or corticosteroids. For pain indications, suitable combination agents include anti-inflammatory agents, such as NSAIDs. The pharmaceutical compositions of the present invention may additionally comprise one or more of the aforementioned active agents, and the methods of treatment may additionally comprise administering an effective amount of one or more of the aforementioned active agents.

[1458] Example

[1459] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which no specific conditions are specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, parts and percentages are by weight.

[1460] Typically, in the preparation process, each reaction is carried out in an inert solvent at room temperature to reflux temperature (e.g., 0°C to 100°C, preferably 0°C to 80°C). The reaction time is typically 0.1-60 hours, preferably 0.5-24 hours.

[1461] The abbreviations used herein have the following meanings:

[1462] Pd(dppf)Cl2:[1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride

[1463] Pd2(dba)3: tris(dibenzylideneacetone)dipalladium

[1464] XPhos Pd G2: Chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II)

[1465] NBS: N-bromosuccinimide

[1466] PTSA: p-toluenesulfonic acid

[1467] HATU: O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate

[1468] DMAP: 4-dimethylaminopyridine

[1469] B2Pin2: Pinacol borate

[1470] t-Bu XPhos: 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl

[1471] DAST: Diethylaminosulfur trifluoride

[1472] TEA: triethylamine

[1473] DIEA: N,N-diisopropylethylamine

[1474] TFA: trifluoroacetic acid

[1475] HCOOH: Formic acid

[1476] AcOH: acetic acid

[1477] K2CO3: Potassium carbonate

[1478] KOAc: potassium acetate

[1479] EtOH: ethanol

[1480] DCM: dichloromethane

[1481] THF: Tetrahydrofuran

[1482] DMF: N,N-dimethylformamide

[1483] DMSO: dimethyl sulfoxide

[1484] TsCl: p-Toluenesulfonyl chloride

[1485] AIBN: Azobisisobutyronitrile

[1486] SOCl2: thionyl chloride

[1487] LiHMDS: lithium bis(trimethylsilyl)amide

[1488] TBAF: Tetrabutylammonium fluoride

[1489] m-CPBA: meta-chloroperbenzoic acid

[1490] Preparation of Intermediate A-1(R)-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-fluoropyrrolidin-1-yl)nicotinamide

[1491] The following synthetic route is adopted:

[1492] Step 1 Synthesis of compound 5-bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide

[1493] 6-Chloro-5-bromonicotinic acid (24.4 g, 103.62 mmol), toluene (160 mL) and DMF (2 mL, 15.07 mmol) were added to the reaction flask, and thionyl chloride (50 mL, 688.4 mmol) was added dropwise at zero degrees Celsius. After completion of the addition, the temperature was raised to 80°C and the reaction was allowed to proceed for 5 hours. The reaction was completed after monitoring by TLC. The mixture was cooled to room temperature and concentrated under reduced pressure to remove toluene and excess thionyl chloride. Anhydrous THF (160 mL) was added to the residue, cooled to -20°C, and DIEA (26.72 g, 207.24 mmol) was added dropwise. A solution of 4-(chlorodifluoromethoxy)aniline (20 g, 103.62 mmol) in THF (40 mL) was then slowly added dropwise. The mixture was stirred at -20°C for 30 minutes, then warmed to room temperature for 18 hours. The reaction was complete as monitored by TLC. The mixture was concentrated under reduced pressure to remove tetrahydrofuran and diluted with 250 mL of methyl tert-butyl ether. The mixture was washed sequentially with 0.5 M hydrochloric acid (250 mL x 2), saturated sodium bicarbonate (250 mL x 2), and saturated sodium chloride (200 mL). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to afford 44.69 g of a pale yellow solid in a 99% yield. LC-MS (APCI): m / z = 410.9 (M+1). + .

[1494] Step 2 Synthesis of intermediate compound A-1

[1495] 5-Bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide (36.7 g, 89.36 mmol), (R)-3-fluoropyrrolidine hydrochloride (13.6 g, 107.23 mmol), DMF (250 mL), and DIEA (37 g, 268 mmol) were added to a reaction flask and stirred at 130°C for 2 hours. The reaction was complete after TLC monitoring. After cooling to room temperature, the reaction solution was poured into 500 mL of ice water, 300 mL of ethyl acetate was added, and the mixture was stirred at room temperature until the solid was completely dissolved. The aqueous layer was extracted twice with 200 mL of ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a yellow solid. 250 mL of n-heptane was added, stirred at room temperature for 10 minutes, filtered, and the filter cake was washed with petroleum ether and dried under vacuum to obtain 38 g of a white solid, with a yield of 92.0%. LC-MS (APCI): m / z = 464.3 (M+1). + .

[1496] Preparation of Intermediate A-2 7-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-1-isopropyl-1H-benzo[d]imidazole-5-carboxamide

[1497] The following synthetic route is adopted:

[1498] Step 1: Synthesis of methyl 3-bromo-4-(isopropylamino)-5-nitrobenzoate

[1499] To a reaction flask, add methyl 3-bromo-4-fluoro-5-nitrobenzoate (5.0 g, 18.0 mmol), isopropylamine (1.1 g, 18.0 mmol), triethylamine (2.7 g, 27.0 mmol), and ethanol (50 mL). Heat to 50°C under nitrogen and stir for 4-6 hours. TLC monitors the reaction for completion. The solvent is concentrated and the residue is purified by column chromatography and dried under vacuum to yield 5.1 g of the product as a pale yellow solid in an 89% yield. LC-MS (APCI): m / z = 317.2 (M+1). + .

[1500] Step 2: Synthesis of methyl 3-amino-5-bromo-4-(isopropylamino)benzoate

[1501] To the reaction flask, add methyl 3-bromo-4-(isopropylamino)-5-nitrobenzoate (4.5 g, 14.2 mmol), reduced iron powder (8.0 g, 142 mmol), ethanol (30 mL), and glacial acetic acid (2 mL). After addition, heat to 70°C and stir for 2 h. Monitor the reaction by TLC. Filter while hot, concentrate the filtrate, and directly use it in the next reaction. LC-MS (APCI): m / z = 287.4 (M+1) + .

[1502] Step 3: Synthesis of methyl 7-bromo-1-isopropyl-1H-benzo[d]imidazole-5-carboxylate

[1503] Methyl 3-amino-5-bromo-4-(isopropylamino)benzoate and trimethyl orthoformate (7.5 g, 71.0 mmol) were dissolved in 40 mL of anhydrous THF. PTSA (0.24 g, 1.4 mmol) was added and the mixture was heated to reflux with stirring under nitrogen overnight. Completion of the reaction was monitored by TLC. The reaction was quenched by adding saturated aqueous ammonium chloride solution and extracted 3-4 times with ethyl acetate. The organic phases were combined, washed 3 times with saturated brine, separated, concentrated, and purified by silica gel column chromatography to yield 2.74 g of a light yellow solid. The two-step yield was 65%. LC-MS (APCI): m / z = 297.2 (M+1). + .

[1504] Step 4: Synthesis of compound 7-bromo-1-isopropyl-1H-benzo[d]imidazole-5-carboxylic acid

[1505] To a reaction flask, add methyl 7-bromo-1-isopropyl-1H-benzo[d]imidazole-5-carboxylate (2.74 g, 9.3 mmol) and lithium hydroxide monohydrate (1.95 g, 46.5 mmol). Dissolve the mixture in 10 mL of tetrahydrofuran, 10 mL of methanol, and 10 mL of water. Stir the mixture overnight at room temperature and monitor the reaction completion by TLC. Adjust the pH to a weakly acidic state with 1N dilute hydrochloric acid. Extract the mixture 3-4 times with ethyl acetate. The organic phases are combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to yield 2.3 g of a white solid in an 88% yield. LC-MS (APCI): m / z = 283.6 (M+1). + .

[1506] Step 5 Synthesis of intermediate compound A-2

[1507] 7-Bromo-1-isopropyl-1H-benzo[d]imidazole-5-carboxylic acid (2.3 g, 8.2 mmol), 4-(chlorodifluoromethoxy)aniline (1.9 g, 9.8 mmol), HATU (4.7 g, 12.3 mmol), and DIEA (2.1 g, 16.4 mmol) were dissolved in 25 mL of anhydrous DMF. The mixture was stirred at room temperature under nitrogen for 5-6 hours. The reaction was monitored by TLC for completion. Water was added for dilution, and the mixture was extracted with ethyl acetate 3-4 times. The organic phases were combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to yield 2.8 g of a yellow solid in a 76% yield. LC-MS (APCI): m / z = 458.2 (M+1) + .

[1508] Preparation of Intermediate A-3 4-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-3,3-dimethyl-2-oxoindoline-6-carboxamide

[1509] The following synthetic route is adopted:

[1510] Step 1: Synthesis of methyl 3,3,4-tribromo-2-oxoindoline-6-carboxylate

[1511] Methyl 4-bromoindole-6-carboxylate (5.0 g, 19.7 mmol), pyridinium tribromide (19.2 g, 60 mmol), and tert-butanol (50 mL) were added to the reaction flask and stirred at room temperature overnight under nitrogen. The reaction was monitored for completion by TLC. The reaction was quenched by the addition of 50 mL of saturated aqueous citric acid solution. The mixture was extracted 3-4 times with ethyl acetate. The organic phases were combined, washed with saturated brine, and concentrated to remove the solvent. The residue was purified by column chromatography and dried under vacuum to obtain 5.3 g of a yellow solid in a 63% yield. LC-MS (APCI): m / z = 425.8 (M+1) + .

[1512] Step 2: Synthesis of methyl 4-bromo-2-oxoindoline-6-carboxylate

[1513] To a reaction flask, add methyl 3,3,4-tribromo-2-oxoindoline-6-carboxylate (4.2 g, 10 mmol), zinc powder (2.0 g, 30 mmol), and acetic acid (20 mL). Heat to 80°C with stirring and react overnight. TLC monitors the reaction for completion. Filter to remove the catalyst, concentrate to remove most of the acetic acid, dilute with water, and extract 3-4 times with ethyl acetate. The organic phases are combined and washed three times with saturated sodium bicarbonate and then saturated brine. Concentrate to remove the solvent, and purify by silica gel column chromatography to obtain 1.29 g of a light yellow solid in a 48% yield. LC-MS (APCI): m / z = 270.1 (M+1). + .

[1514] Step 3: Synthesis of methyl 4-bromo-3,3-dimethyl-2-oxoindoline-6-carboxylate

[1515] Methyl 4-bromo-2-oxoindoline-6-carboxylate (1.3 g, 4.8 mmol) was dissolved in 10 mL of anhydrous DMF. Sodium hydride (0.42 g, 10.6 mmol) was added portionwise under ice-cooling. After addition, the mixture was stirred for 0.5 hour. Methyl iodide (2.0 g, 14.4 mmol) was added, and the mixture was stirred at room temperature for 3-4 hours. The reaction was complete after TLC monitoring. The reaction solution was concentrated and purified by silica gel column chromatography to obtain 1.24 g of the product in an 87% yield. LC-MS (APCI): m / z = 298.7 (M+1). + .

[1516] Step 4: Synthesis of compound 4-bromo-3,3-dimethyl-2-oxoindoline-6-carboxylic acid

[1517] Methyl 4-bromo-3,3-dimethyl-2-oxoindoline-6-carboxylate (2.8 g, 9.3 mmol), lithium hydroxide monohydrate (1.95 g, 46.5 mmol), and 1,4-dioxane (15 mL) were added to the reaction flask and stirred overnight at room temperature. The reaction was monitored for completion by TLC. The pH was adjusted to a weak acidic state with 1N dilute hydrochloric acid. The mixture was extracted with ethyl acetate 3-4 times. The organic phases were combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to obtain 2.0 g of a yellow solid in a 77% yield. LC-MS (APCI): m / z = 283.9 (M+1) + .

[1518] Step 5 Synthesis of intermediate compound A-3

[1519] To a reaction flask, add 4-bromo-3,3-dimethyl-2-oxoindolin-6-carboxylic acid (2.32 g, 8.2 mmol), 4-(chlorodifluoromethoxy)aniline (1.9 g, 9.8 mmol), HATU (4.7 g, 12.3 mmol), and TEA (1.66 g, 16.4 mmol). Dissolve the mixture in 25 mL of anhydrous DMF and stir at room temperature under nitrogen for 5-6 hours. Completion is monitored by TLC. Dilute with water and extract with ethyl acetate 3-4 times. The organic phases are combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to yield 2.8 g of a yellow solid in a 74% yield. LC-MS (APCI): m / z = 459.2 (M+1). + .

[1520] Preparation of Intermediate A-4 4'-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-2'-oxospiro[cyclohexane-1,3'-indoline]-6'-carboxamide

[1521] The following synthetic route is adopted:

[1522] Step 1: Synthesis of methyl 4'-bromo-2'-oxospiro[cyclohexane-1,3'-indoline]-6'-carboxylate

[1523] Methyl 4-bromo-2-oxoindoline-6-carboxylate (1.3 g, 4.8 mmol) and anhydrous THF (15 mL) were added to the reaction flask. Under nitrogen, n-butyl lithium (6.6 mL, 10.6 mmol) was added dropwise at -78°C. After addition, the reaction was stirred for 0.5 hours. 1,5-diiodopentane (4.7 g, 14.4 mmol) was slowly added dropwise. The mixture was allowed to warm to room temperature and stirred for 3-4 hours. TLC monitored the reaction for completion. Saturated ammonium chloride was added to quench the reaction. The mixture was extracted with ethyl acetate 3-4 times. The organic phases were combined, washed with saturated brine, concentrated, and purified by silica gel column chromatography to yield 1.13 g of the product in a 70% yield. LC-MS (APCI): m / z = 338.7 (M+1). + .

[1524] Step 2 Synthesis of compound 4'-bromo-2'-oxospiro[cyclohexane-1,3'-indoline]-6'-carboxylic acid

[1525] To the reaction flask, methyl 4'-bromo-2'-oxospiro[cyclohexane-1,3'-indoline]-6'-carboxylate (3.1 g, 9.3 mmol), lithium hydroxide monohydrate (1.95 g, 46.5 mmol), and 1,4-dioxane (15 mL) were added. The reaction was stirred at room temperature overnight and monitored for completion by TLC. The pH was adjusted to a weak acidic state with 1N dilute hydrochloric acid. The mixture was extracted with ethyl acetate 3-4 times. The organic phases were combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to obtain 1.9 g of a yellow solid in a 64% yield. LC-MS (APCI): m / z = 324.4 (M+1) + .

[1526] Step 3 Synthesis of intermediate compound A-4

[1527] Dissolve 4'-bromo-2'-oxospiro[cyclohexane-1,3'-indoline]-6'-carboxylic acid (2.65 g, 8.2 mmol), 4-(chlorodifluoromethoxy)aniline (1.9 g, 9.8 mmol), HATU (4.7 g, 12.3 mmol), and TEA (1.66 g, 16.4 mmol) in 25 mL of anhydrous DMF. Stir at room temperature under nitrogen for 5-6 hours. Completion is monitored by TLC. Dilute with water and extract with ethyl acetate 3-4 times. The organic phases are combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to yield 2.2 g of a yellow solid in a 54% yield. LC-MS (APCI): m / z = 499.2 (M+1). + .

[1528] Preparation of Intermediate A-5: 3-acetylamino-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxamide

[1529] The following synthetic route is adopted:

[1530] Step 1 Synthesis of Compound 4-amino-3-(cyclopent-2-en-1-yl)benzoic acid methyl ester

[1531] To a reaction flask, methyl 3-iodo-4-aminobenzoate (5.0 g, 18 mmol), cyclopentene (1.84 g, 27 mmol), potassium acetate (3.5 g, 36 mmol), palladium acetate (0.2 g, 0.9 mmol), and triphenylphosphine (0.5 g, 1.8 mmol) were added. The mixture was dissolved in 20 mL of anhydrous DMF and stirred at 80°C under nitrogen overnight. Completion of the reaction was monitored by TLC. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution and extracted 3-4 times with ethyl acetate. The organic phases were combined, washed with saturated brine, concentrated, and purified by silica gel column chromatography to yield 1.83 g of a light yellow oily liquid in a 47% yield. LC-MS (APCI): m / z = 218.2 (M+1) + .

[1532] Step 2: Synthesis of methyl 3-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylate

[1533] To a reaction flask, methyl 4-amino-3-(cyclopent-2-en-1-yl)benzoate (1.8 g, 8.3 mmol), elemental iodine (4.2 g, 16.6 mmol), sodium bicarbonate (2.1 g, 24.9 mmol), and acetonitrile (20 mL) were added. The reaction was stirred at room temperature overnight. TLC monitored the reaction for completion. Saturated sodium sulfite solution was added to quench the reaction, and the mixture was extracted 3-4 times with ethyl acetate. The organic phases were combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to obtain 1.48 g of a light yellow oily solid in a 52% yield. LC-MS (APCI): m / z = 344.6 (M+1) + .

[1534] Step 3: Synthesis of methyl 3-iodo-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylate

[1535] To a reaction flask, add methyl 3-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylate (1.4 g, 4.1 mmol), acetone (0.5 g, 8.2 mmol), phenylsilane (0.97 g, 9.02 mmol), and anhydrous DCM (20 mL). Stir the mixture at room temperature for 4-6 hours. Completion of the reaction is monitored by TLC. The solvent is concentrated and the residue is purified by column chromatography and dried under vacuum to afford 1.2 g of the product as a pale yellow solid in a 77% yield. LC-MS (APCI): m / z = 386.3 (M+1). + .

[1536] Step 4: Synthesis of methyl 5-bromo-3-iodo-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylate

[1537] To a reaction flask, methyl 3-iodo-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylate (1.2 g, 3.1 mmol), NBS (0.83 g, 4.7 mmol), and 1,4-dioxane (20 mL) were added. The mixture was stirred overnight at room temperature under nitrogen atmosphere. Completion of the reaction was monitored by TLC. After concentration, the product was purified by column chromatography and dried under vacuum to afford 0.92 g of a pale yellow solid in a 64% yield. LC-MS (APCI): m / z = 464.4 (M+1). + .

[1538] Step 5: Synthesis of methyl 3-azido-5-bromo-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylate

[1539] Methyl 5-bromo-3-iodo-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylate (0.92 g, 2.0 mmol) and sodium azide (260 mg, 4.0 mmol) were dissolved in 10 mL of acetone and 5 mL of water. The mixture was heated to 50°C and stirred under nitrogen for 5-6 hours. The reaction was monitored for completion by TLC. Water was added for dilution, and the mixture was extracted with ethyl acetate 3-4 times. The organic phases were combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to yield 695 mg of a light yellow solid in a 92% yield. LC-MS (APCI): m / z = 379.2 (M+1) + .

[1540] Step 6: Synthesis of compound 3-azido-5-bromo-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylic acid

[1541] To the reaction flask, methyl 3-azido-5-bromo-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylate (3.5 g, 9.3 mmol), lithium hydroxide monohydrate (1.95 g, 46.5 mmol), THF (10 mL), and water (10 mL) were added. The reaction was stirred at room temperature overnight and monitored for completion by TLC. The pH was adjusted to a weak acidic state with 1N dilute hydrochloric acid. The mixture was extracted with ethyl acetate 3-4 times. The organic phases were combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to obtain 2.94 g of an off-white solid in an 87% yield. LC-MS (APCI): m / z = 365.6 (M+1) + .

[1542] Step 7: Synthesis of 3-azido-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxamide

[1543] To a reaction flask, add 3-azido-5-bromo-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxylic acid (2.99 g, 8.2 mmol), 4-(chlorodifluoromethoxy)aniline (1.9 g, 9.8 mmol), HATU (4.7 g, 12.3 mmol), and DIEA (2.1 g, 16.4 mmol). Dissolve the mixture in 25 mL of anhydrous DMF and stir at room temperature under nitrogen for 5-6 hours. Completion is monitored by TLC. Dilute with water and extract with ethyl acetate 3-4 times. The organic phases are combined, washed 3 times with saturated brine, concentrated to remove the solvent, and purified by silica gel column chromatography to yield 3.05 g of a yellow solid in a 69% yield. LC-MS (APCI): m / z = 540.6 (M+1). + .

[1544] Step 8: Synthesis of compound 3-amino-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxamide

[1545] To a reaction flask, 3-azido-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxamide (1.5 g, 2.8 mmol), triphenylphosphine (1.46 g, 5.6 mmol), and anhydrous THF (10 mL) were added. The mixture was heated to 60°C and allowed to react overnight. TLC monitored the reaction to be complete. After cooling to room temperature, lithium hydroxide monohydrate (0.47 g, 11.2 mmol) was added and the mixture was allowed to react at room temperature for 1 hour. TLC monitored the reaction to be complete. After concentration, the product was purified by silica gel column chromatography to obtain 488 mg of the product in a 34% yield. LC-MS (APCI): m / z = 514.7 (M+1). + .

[1546] Step 9 Synthesis of intermediate compound A-5

[1547] To a reaction flask, 3-amino-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-isopropyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-7-carboxamide (488 mg, 0.95 mmol), TEA (192 mg, 1.9 mmol), and anhydrous DCM (10 mL) were added dropwise. Acetyl chloride (89 mg, 1.14 mmol) was added dropwise under an ice bath. The mixture was stirred at room temperature for 1-2 hours and monitored for completion by TLC. The reaction was quenched with water, and the organic phase was separated, concentrated, and purified by silica gel column chromatography to yield 480 mg of the product in a 91% yield. LC-MS (APCI): m / z = 556.7 (M+1). + .

[1548] Preparation of Intermediate A-6 (1R)-9-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-hydroxy-1-methyl-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyridine-7-carboxamide

[1549] The following synthetic route is adopted:

[1550] Step 1: Synthesis of (R,E)-5-((tert-butylsulfinyl)imino)hexanoic acid ethyl ester

[1551] To a reaction flask, add 4-acetylbutyl ethyl ester (10.0 g, 63.3 mmol), (R)-tert-butylsulfe...

Claims

1. A compound of formula (I), or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof: (I) Where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 R X3’ , CR X3 or NR X3 ; X4 represents CR X4 R X4’ , CR X4 , NR X4 or C(O); X5 represents N or CR X5 ; X6 represents N or CR X6 ; represents a single or double bond; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 and R X3’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7 membered heterocyclyl, or R X3 , R X3’ and the carbon atom to which they are attached, together form C 1-6 alkylidene, wherein the above groups are optionally substituted by one or more R a ; R X4 and R X4’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, wherein the above groups are optionally substituted by one or more R a ; or R X3 , R X4and the atoms to which they are attached all together form C 3-8 cycloalkyl, 4-10-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted by one or more R; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 is H, D or halogen; Y represents CR Y or N; R1 is a 3- to 10-membered heterocyclyl, which is optionally substituted with one or more R substituents. b ; R Y is H, D or halogen; or R1, R Y and the carbon atoms to which they are attached all together form C 3-8 cycloalkyl, 4-10-membered heterocyclyl, C 6-10aryl or 5-10-membered heteroaryl, which is optionally substituted with one or more substituents R*; R1' is H, D, halogen or -NH2; W represents CR W or N; R W selected from H, D, halogen and -NH2; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted by one or more R c ; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; each of R a , R b and R c independently represents H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; each R independently represents H, D, halogen, -CN, -OR A , -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted by one or more substituents R'; each R* independently represents H, D, halogen, -CN, -OH, oxo, -NR AC(O)R B , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom(s) to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted by one or more substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with one or more substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted by one or more substituents R”; or two adjacent R's and the atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with one or more substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; provided that when X1 is N, X2 is CH2, X3 is NR X3 , X4 is C(O), and X5 is CH, Y is not N.

2. The compound according to claim 1, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the compound has one of the following definitions: i) where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 R X3’ or NR X3 ; X4 is C(O); X5 represents N or CR X5 ; X6 represents N or CR X6, alternatively CR X6 ; represents a simple connection; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 and R X3’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7 membered heterocyclyl, or R X3 , R X3’ and the carbon atom to which they are attached, together form C 1-6alkylidene, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R a ; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 3-8 cycloalkyl, 4-10-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl which is optionally substituted with 1, 2, 3, 4, 5 or 6 R* substituents; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; each R a independently represents H, D, halogen, -CN, or -NR B R C ; each R* independently represents H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 alkyl or C1-6 haloalkyl, or two R* and the atom(s) to which they are attached together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; where R A , R B and R C independently represent H, D, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; ii) where X1 represents N or CR X1 ; X2 represents CRX2 R X2’ or C(O); X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a single or double bond; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 , R X4 and the atoms to which they are attached all together form C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y or N; R1 is a 3- to 10-membered heterocyclyl that is optionally substituted with 1, 2, 3, 4, 5, or 6 R substituents b ; R Y is H, D or halogen; or R1, R Y and the carbon atoms to which they are attached all together form C 3-8 cycloalkyl, 4-10-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl which is optionally substituted with 1, 2, 3, 4, 5 or 6 R* substituents; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; each Rb independently represents H, D, halogen, -CN, -OR A , -NR B R C , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; each R independently represents H, D, halogen, -CN, -OR A , -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R* independently represents H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom(s) to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; iii) where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 R X3’ or NR X3 ; X4 is C(O); X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 and R X3’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7 membered heterocyclyl, or R X3 , R X3’and the carbon atom to which they are attached, together form C 1-6 alkylidene, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R a ; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, which is optionally substituted with two or more substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R Wselected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; each R a independently represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; each R* independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom(s) to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; iv) where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O); X3 is NR X3 ; X4 is C(O); X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X1 represents H, D, halogen, C 1-6 alkyl or C1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 represents H, C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, which is optionally substituted with two or more substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; where two adjacent R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10-membered heterocyclyl, and the remaining R* are independently H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; v) where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ ; X3 is NR X3 ; X4 is C(O); X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 represents H, C 1-6alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, which is optionally substituted with two or more substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R Wselected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; where two adjacent R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10-membered heterocyclyl, and the remaining R* are independently H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; vi) where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a single or double bond; R X1represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 , R X4 and the atoms to which they are attached together form a 5-membered heteroaryl; which is optionally substituted with 1, 2, 3, 4, 5, or 6 R substituents; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6represents H, D or halogen, alternatively H or D; Y represents CR Y or N; R1 is a 3- to 10-membered heterocyclyl that is optionally substituted with 1, 2, 3, 4, 5, or 6 R substituents b ; R Y is H, D or halogen; or R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl which is optionally substituted with 1, 2, 3, 4, 5 or 6 R* substituents; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; each R b independently represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; each R independently represents H, D, halogen, -CN, -OH, -C(O)RA , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R* independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom(s) to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; vii) where X1 represents N; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 , R X4and the atoms to which they are attached together form a 5-membered heteroaryl; which is optionally substituted with 1, 2, 3, 4, 5, or 6 R substituents; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y or N; R1 is a 5-6 membered heterocyclyl which is optionally substituted with 1, 2, 3, 4, 5 or 6 R substituents b ; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; R Y is H, D or halogen; Y1 represents CRY1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; each R b independently represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; each R independently represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R Cand the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; viii) where X1 represents N; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 , R X4 and the atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, which is optionally substituted with two or more substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; each R independently represents H, D, halogen, -CN, -C(O)R A , C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; where two adjacent R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10-membered heterocyclyl, and the remaining R* are independently H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R A represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl; ix) where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; RX1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 , R X4 and the atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; RX6 represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, which is optionally substituted with two or more substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; each R independently represents H, D, -C(O)R A , halogen, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R', wherein the above groups are optionally substituted with one or more D atoms, up to complete deuteration; where two adjacent R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10-membered heterocyclyl, and the remaining R* are independently H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R A represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; x) where X1 represents N; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X2 and R X2’ independently represent H, D, OH, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 , R X4 and the atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, which is optionally substituted with two or more substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; where one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, and the remaining R are independently H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where two adjacent R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10-membered heterocyclyl, and the remaining R* are independently H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or two adjacent R's and the atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; xi) where X1 represents N; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 , R X4 and the atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, which is optionally substituted with two or more substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; where one R is pyridin-2-yl, pyrimidin-4-yl or pyrazin-2-yl, and the remaining R are independently H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where two adjacent R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10-membered heterocyclyl, and the remaining R* are independently H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xii) where X1 represents N; X2 represents CR X2 R X2’ ; X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X2 and R X2’ independently represent H, D, halogen, OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3, R X4 and the atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, which is optionally substituted with two or more substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R Wselected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; where one R is pyrimidin-2-yl and the remaining R independently are H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where two adjacent R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10-membered heterocyclyl, and the remaining R* are independently H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or two adjacent R's and the atoms to which they are attached all together form C 6-10aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; xiii) where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O); X3 represents CR X3 ; X4 represents CR X4 ; X5 represents N or CR X5 ; X6 represents N or CR X6 , alternatively CR X6 ; represents a simple connection; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 , R X4 and the atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R; R X5 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; Y represents CR Y ; and R1, R Y and the carbon atoms to which they are attached all together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, which is optionally substituted by two or more R* substituents; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; Y1 represents CR Y1 or N; Y2 represents CR Y2 or N; R Y1 , R Y2 and R2 independently represent H, D, halogen, -CN, -NO2, C 1-6 alkyl or C 1-6 haloalkyl; Z represents a chemical bond, O or S(O) 0-2 ; R Z represents H, D, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; or -ZR Z together represents -SF5; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R Cand the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R* independently represents H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom(s) to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration.

3. The compound according to any one of claims 1, 2, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the compound is a compound of formula (II): (II) where X1-X6, Y, W, R1 and R1' have the meanings specified in any of paragraphs 1, 2.

4. The compound according to claim 3 or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the compound has one of the following definitions: i) where the compound is a compound of formula (III): (III) Where X1 represents N or CR X1 , alternatively N; X2 represents CR X2 R X2’ or C(O), alternatively CRX2 R X2’ ; X3 represents CR X3 R X3’ or NR X3 ; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 and R X3’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7 membered heterocyclyl, or R X3 , R X3’ and the carbon atom to which they are attached, together form C 1-6alkylidene, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R a ; each R a independently represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; each R* independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10-membered heteroaryl, or two R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, where X1 represents N or CH; X2 is CH2, CHD, CD2, or C(O); X3 represents CR X3 R X3’ or NR X3 ; R X3 and R X3’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7 membered heterocyclyl, or R X3 , R X3’ and the carbon atom to which they are attached, together form C 1-6 alkylidene, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R a ; each R a independently represents H, D, halogen, -NH2, -NHC 1-6 alkyl or -N(C 1-6 alkyl)2, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; each R* independently represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, or two R* and the atoms to which they are attached together form a 4- to 10-membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5, or 6 R' substituents; each R' independently represents H, D, halogen, -OH, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, where X1 represents N or CH; X2 is CH2 or CD2; X3 represents CR X3 R X3’ or NR X3 ; R X3 and R X3’ independently represent H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl or C 3-6cycloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; each R* independently represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, or two R* and the atoms to which they are attached together form a 4- to 10-membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5, or 6 R' substituents; each R' independently represents H, D, halogen, -OH, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, where X1 represents N; X2 represents CR X2 R X2’ ; X3 represents CR X3 R X3’ or NR X3 ; R X2 and RX2’ independently represent H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 and R X3’ independently represent H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, or R X3 , R X3’ and the carbon atom to which they are attached, together form C 1-6 alkylidene, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R a ; each R a independently represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; each R* independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl, or two R* and the atoms to which they are attached together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl; ii) wherein the compound is a compound of formula (III-1): (III-1) Where R X3 represents H, C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; Q1 is C(R')2 or C(R')2C(R')2; Q2 is C(R')2, O, NR', S, S(O) or S(O)2; Q3 is C(R')2, C(R')2C(R')2, O, NR', S, S(O), or S(O)2; each R' independently represents H, D, halogen, -OH, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; iii) wherein the compound is a compound of formula (III-2): (III-2) Where X1 represents N or CR X1 , alternatively N; X2 represents CR X2 R X2’ or C(O), alternatively CR X2 R X2’ ; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 represents H, C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, alternatively C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; Q1 represents C 1-2 alkylene or C 1-2 haloalkylene, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; Q2 and Q3 independently represent O, S, S(O), S(O)2, NR', C 1-2 alkylene or C 1-2 haloalkylene, alternatively O, S, C 1-2alkylene or C 1-2 haloalkylene, wherein the above groups are optionally substituted with 1, 2, 3 or 4 halogens or OH, wherein the above groups are also optionally substituted with one or more D atoms, up to complete deuteration; each R' independently represents H, D, halogen, -OH, C 1-6 alkyl or C 1-6 haloalkyl; alternatively, where X1 represents N; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 represents Me; R1' is H, D, halogen or -NH2, alternatively H or D; Q1 is CH2, CHD or CD2; Q2 is O, S, CH2, CHD, or CD2; Q3 is O, S, CH2, CHD, or CD 2; iv) wherein the compound is a compound of formula (III-2a): (III-2a) Where R X3 independently represents H, C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; Q1 is C(R')2 or C(R')2C(R')2; Q2 is C(R')2, O, S, S(O) or S(O)2; Q3 is C(R')2, C(R')2C(R')2, O, S, S(O), or S(O)2; each R' independently represents H, D, halogen, -OH, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, where R X3 independently represents H, C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2; Q1 is CH2, (CH2)2, CHD, (CHD)2, CD2, or (CD2)2; Q2 is CH2, CHD, CD2, O, S, S(O) or S(O)2; Q3 is C(R')2, S or S(O)2; each R' independently represents H, D, F, or -OH; v) where the compound is a compound of formula (III-3): (III-3) Where X1 represents N or CR X1 , alternatively N; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X3 represents H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, alternatively C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; Q2 is O, S, or NR', alternatively O or S; R' represents H, D, halogen, OH, C 1-6 alkyl or C 1-6 haloalkyl, alternatively H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, where X1 represents N; R X3 represents Me, CD3, or cyclopropyl; R1' is H, D, halogen or -NH2, alternatively H or D; Q2 represents O; R' represents H or D; vi) wherein the compound is a compound of formula (III-3a): (III-3a) Where R X3 represents C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; Q2 is CH2, CD2, or O; R' represents H, D or F; vii) wherein the compound is a compound of formula (IV): (IV) Where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O), alternatively CR X2 R X2’ ; X6 represents N or CR X6 , alternatively CR X6 ; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; ring A is phenyl or 5-6-membered heteroaryl, which is optionally substituted with 1, 2, 3 or 4 substituents R; Y represents CR Yor N, alternatively CR Y ; R1 is a 3- to 10-membered heterocyclyl that is optionally substituted with 1, 2, 3, 4, 5, or 6 R substituents b ; R Y is H, D or halogen; or R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl which is optionally substituted with 1, 2, 3, 4, 5 or 6 R* substituents; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; each R b independently represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; each R independently represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R* independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom(s) to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; optional where ring A represents , , , , , , , or ; alternatively, where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ ; X6 represents N or CR X6 , alternatively CR X6 ; R X1represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; ring A is a 5-membered heteroaryl which is optionally substituted with 1, 2, 3 or 4 R substituents; Y represents CR Y ; R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-6-membered heteroaryl, which is optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R*; R1' is H, D, halogen or -NH2, alternatively H or D; W represents CR W or N, alternatively CR W ; R W selected from H, D, halogen and -NH2, alternatively H or D; each R independently represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R* independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, or two R* and the atom(s) to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl; viii) wherein the compound is a compound of formula (IV-1): (IV-1) Where X1 represents N or CR X1 ; X2 represents CR X2 R X2’ or C(O); R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; Y represents CR Y or N; R1 is a 3- to 10-membered heterocyclyl that is optionally substituted with 1, 2, 3, 4, 5, or 6 R substituents b ; R Y is H, D or halogen; or R1, R Y and the carbon atoms to which they are attached all together form C 6-10 aryl or 5-10 membered heteroaryl which is optionally substituted with 1, 2, 3, 4, 5 or 6 R* substituents; R1' is H, D, halogen or -NH2, alternatively H or D; each R b independently represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of RA , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R* independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom(s) to which they are attached, together form C 3-8cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; optionally where R1 is a 4- to 10-membered heterocyclyl, which is optionally substituted with 1, 2, 3, 4, 5, or 6 R substituentsb ; alternatively, R1 represents , , , , , , , , , or , where the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R b ; not necessarily where R1, R Y and the carbon atoms to which they are attached together form a 5-membered heterocyclyl or 5-membered heteroaryl which is optionally substituted with 1, 2, 3, 4, 5 or 6 R* substituents; alternatively, R1, R Y and the carbon atoms to which they are attached all together form , , or ; ix) where the compound is a compound of formula (IV-2): (IV-2) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 RX2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; m is 0, 1, 2 or 3; n is 0, 1, 2, 3, 4 or 5; each R b independently represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NRB R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; x) where the compound is a compound of formula (IV-2a): (IV-2a) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R b represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; not necessarily where R1' is H, D, halogen or -NH2, alternatively H or D; R b represents H, D, halogen, -OH, -NH2, -NHC 1-6 alkyl or -N(C 1-6 alkyl)2, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, R b is a halogen or -OH; xi) where the compound is a compound of formula (IV-2a): (IV-2a) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O), alternatively CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl or C 1-6 haloalkyl, alternatively H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R b represents H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10aryl or 5-10 membered heteroaryl, alternatively H, D, halogen, -CN, -OH, -NH2, -NHC 1-6 alkyl, -N(C 1-6 alkyl)2, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, alternatively H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R Cindependently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xii) wherein the compound is a compound of formula (IV-2b): (IV-2b) Where W represents CR W or N; R W selected from H, D, halogen and -NH2, alternatively H or D; R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); X6 represents N or CR X6 , alternatively CR X6 ; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; ring A is phenyl or 5-6-membered heteroaryl, which is optionally substituted with 1, 2, 3 or 4 substituents R; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; optional where ring A represents , , , , , , , or ; optionally wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted with 1, 2 or 3 R' substituents; xiii) wherein the compound is a compound of formula (IV-2c): (IV-2c) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R Cand the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R is H, D, -C(O)R A , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each R A independently represents C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R is H, D, -C(O)R A , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6cycloalkyl, 3-7-membered heterocyclyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; where each R A independently represents C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xiv) wherein the compound is a compound of formula (IV-2d): (IV-2d) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; P1 represents N or CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; R P1 , R P2 , R P3 and R P4 independently represent H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; P1 represents N or CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; R P1 , R P2 , R P3 and R P4 independently represent H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xv) wherein the compound is a compound of formula (IV-2e): (IV-2e) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R P1 , R P2 and R P3 independently represent H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 , R P2 and R P3 independently represent H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; R P2 represents H; R P3 represents H, C 1-3 alkyl or C 1-3 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and R P3 represent H; R P2 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and R P3 represent H; R P2 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, 3-7-membered heterocyclyl or phenyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and R P3 represent H; R P2 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy or phenyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xvi) wherein the compound is a compound of formula (V): (V) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CRX2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; ring B is a 4- to 10-membered heterocyclyl which is optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R Band R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xvii) wherein the compound is a compound of formula (V-1): (V-1) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; Q1 is C(R')2 or C(R')2C(R')2; Q2 is C(R')2, O, NR', S, S(O) or S(O)2; Q3 is C(R')2, C(R')2C(R')2, O, NR', S, S(O), or S(O)2; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R Cand the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; not necessarily where R1' is H, D, halogen or -NH2, alternatively H or D; Q1 is CH2, (CH2)2, CHD, (CHD)2, CD2, or (CD2)2; Q2 is CH2, CHD, CD2, O, S, S(O) or S(O)2; Q3 is CH2, CHD, CD2, CHF, CDF, CH(OH), CD(OH), S, or S(O)2; alternatively, R b is a halogen or -OH; Q1 is CH2 or CD2; Q2 is CH2, CHD, CD2, O, or S; Q3 is CH2, CHD, CD2, CHF, CDF, CH(OH) or CD(OH); xviii) wherein the compound is a compound of formula (V-2): (V-2) Where W represents CR W or N; R W selected from H, D, halogen and -NH2, alternatively H or D; R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); X6 represents N or CR X6 , alternatively CR X6 ; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; ring A is phenyl or 5-6-membered heteroaryl, which is optionally substituted with 1, 2, 3 or 4 substituents R; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; optional where ring A represents , , , , , , , or ; optionally wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted with 1, 2 or 3 R' substituents; xix) where the compound is a compound of formula (V-3): (V-3) Where X1 represents N or CR X1 , alternatively N; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5, 6 or more D atoms, up to complete deuteration; X2 represents CR X2 R X2’ or C(O), alternatively CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl or C 1-6 haloalkyl, alternatively H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R1' is H, D, halogen or -NH2, alternatively H or D; Q2 is O, S, or NR', alternatively O or S, alternatively O; R' represents H, D, -CN, halogen, C 1-6 alkyl, C1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, alternatively H, D, -CN or halogen, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; R is H, D, -C(O)R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, alternatively H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R', wherein the above groups are also optionally substituted with one or more D atoms, up to complete deuteration; R A represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where X1 represents N; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H or D; R1' is H, D, halogen or -NH2, alternatively H or D; Q2 represents O; R is H, D, Et, CH2CF3, isopropyl, CD(CD3)2, cyclopropyl, oxetanyl, pyrazin-2-yl, pyridin-2-yl or pyrimidin-5-yl; xx) where the compound is a compound of formula (V-4): (V-4) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R is H, D, -C(O)R A , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each R A independently represents C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R is H, D, -C(O)R A , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; where each R A independently represents C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C3-6 cycloalkyl, 3-7-membered heterocyclyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xxi) where the compound is a compound of formula (V-4): (V-4) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O), alternatively CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R is H, D, -C(O)R A , C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R A represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H or D; R is H, D, Et, CH2CF3, isopropyl or CD(CD3)2; xxii) wherein the compound is a compound of formula (V-5): (V-5) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; P1 represents N or CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; R P1 , RP2 , R P3 and R P4 independently represent H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’independently represent H, D, halogen or -OH; P1 represents N or CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; R P1 , R P2 , R P3 and R P4 independently represent H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xxiii) wherein the compound is a compound of formula (V-5): (V-5) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, OH, halogen, C 1-6 alkyl or C 1-6 haloalkyl, alternatively H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; P1 represents CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; and alternatively, at least one of P3 and P4 is N; R P1 , R P2 , R P3 and R P4independently represent H, D, halogen, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, alternatively H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; or R P1 and R P2 , R P2 and R P3 , or R P3 and R P4 , and the atoms to which they are attached all together form C 6-10aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; P1 represents CR P1 ; P2 is a CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; and at least one of P3 and P4 is N; R P1 represents H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R P2 represents H, D, halogen or -CN; R P3 represents H, D, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R P4 represents H or D; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H or D; P1 represents CR P1 ; P2 is a CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; and at least one of P3 and P4 is N; R P1 represents H, D, -CN or Me; R P2 represents H, D, F, or -CN; R P3 represents H, D or Me; R P4 represents H or D; xxiv) wherein the compound is a compound of formula (V-5): (V-5) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; P1 represents CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 is a CR P4 ; R P1 , R P2 , R P3 and R P4 independently represent H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively, where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H or D; P1 represents CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 is a CR P4 ; R P1represents H or D; R P2 represents H or D; R P3 represents H or D; R P4 represents H or D; xxv) where the compound is a compound of formula (V-6): (V-6) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R P1 , R P2 and R P3 independently represent H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 , R P2 and R P3 independently represent H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; R P2 represents H; R P3 represents H, C 1-3 alkyl or C 1-3 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and RP3 represent H; R P2 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and R P3represent H; R P2 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, 3-7-membered heterocyclyl or phenyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and R P3 represent H; R P2represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy or phenyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xxvi) wherein the compound is a compound of formula (V-6): (V-6) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, OH, C 1-6 alkyl or C 1-6 haloalkyl, alternatively H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R P1 , R P2 and R P3 independently represent H, D, halogen, -CN, C 1-6alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, alternatively H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; or R P1 and R P2 , or R P2 and R P3 and the atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R P1 represents H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R P2 represents H, D, halogen or -CN; R P3 represents H, D, C 1-6 alkyl or C 1-6haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H or D; R P1 represents H, D, -CN or Me; R P2 represents H, D, F, or -CN; R P3 represents H, D or Me; xxvii) wherein the compound is a compound of formula (VI): (VI) Where W represents CR W or N; R W selected from H, D, halogen and -NH2, alternatively H or D; R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); X6 represents N or CR X6 , alternatively CR X6 ; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; ring A is phenyl or 5-6-membered heteroaryl, which is optionally substituted with 1, 2, 3 or 4 substituents R; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; optional where ring A represents , , , , , , , or ; optionally wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted with 1, 2 or 3 R' substituents; xxviii) wherein the compound is a compound of formula (VI-1): (VI-1) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R Cindependently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R is H, D, -C(O)R A , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each R A independently represents C 1-6 alkyl, C 1-6 haloalkyl, C 3-6cycloalkyl or 3-7-membered heterocyclyl, wherein the above groups are optionally substituted by one or more substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and RX2’ independently represent H, D, halogen or -OH; R is H, D, -C(O)R A , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; where each R A independently represents C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xxix) where the compound is a compound of formula (VI-2): (VI-2) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; P1 represents N or CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; R P1 , R P2 , R P3 and R P4 independently represent H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; P1 represents N or CR P1 ; P2 represents N or CR P2 ; P3 represents N or CR P3 ; P4 represents N or CR P4 ; R P1 , R P2 , R P3 and R P4 independently represent H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; xxx) where the compound is a compound of formula (VI-3): (VI-3) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R P1 , R P2 and R P3 independently represent H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 , R P2 and R P3 independently represent H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; R P2 represents H; R P3 represents H, C 1-3 alkyl or C 1-3 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3haloalkoxy, where the above groups are optionally substituted with 1, 2, 3, 4, 5, 6 or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and R P3 represent H; R P2 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, phenyl or 5- or 6-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and R P3 represent H; R P2 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, 3-7-membered heterocyclyl or phenyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3haloalkoxy, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen or -OH; R P1 and R P3 represent H; R P2 represents H, D, halogen, -CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy or phenyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; alternatively wherein the compound is a compound of formula (VII): (VII) Where W represents CR W or N; R Wselected from H, D, halogen and -NH2, alternatively H or D; R1' is H, D, halogen or -NH2, alternatively H or D; X1 represents N or CR X1 , alternatively N; X6 represents N or CR X6 , alternatively CR X6 ; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5, 6 or more D atoms, up to complete deuteration; X2 represents CR X2 R X2’ or C(O), alternatively CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6represents H, D or halogen, alternatively H or D; ring A is phenyl or 5-6-membered heteroaryl, which is optionally substituted with 1, 2, 3 or 4 substituents R; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R Cand the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R* independently represents H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom(s) to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; optional where ring A represents , , , , , , , or ; optionally wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted with 1, 2 or 3 R' substituents; xxxii) wherein the compound is a compound of formula (VII-1): (VII-1) Where R1' is H, D, halogen or -NH2, alternatively H or D; X1 represents N or CR X1 , alternatively N; R X1 represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5, 6 or more D atoms, up to complete deuteration; X2 represents CR X2 R X2’ or C(O), alternatively CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, alternatively H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R* independently represents H, D, halogen, -CN, -OH, oxo, -NR A C(O)R B , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl, or two R* and the atom to which they are attached, together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10-membered heteroaryl; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3-7-membered heterocyclyl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'.

5. The compound of claim 3, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the compound is a compound of formula (VII-2): (VII-2) Where R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O), alternatively CR X2 R X2’ ; R X2 and R X2’ independently represent H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; each R* independently represents H, D, halogen, C 1-6 alkyl or C 1-6 haloalkyl, or two R* and the atom to which they are attached together form C 3-8 cycloalkyl or 4-10 membered heterocyclyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R' substituents; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl or C 1-6 haloalkyl; R P1 , R P2 and R P3independently represent H, D, halogen, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, alternatively H, D, halogen, -CN, C 1-6 alkyl or C 1-6 haloalkyl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration; or R P1 and R P2 , or R P2 and R P3 and the atoms to which they are attached all together form C 6-10 aryl or 5-10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents representing -CN, halogen, C1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy, where the above groups are also optionally substituted by one or more D atoms, up to complete deuteration.

6. The compound of claim 3, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the compound is a compound of formula (VIII): (VIII) Where W represents CR W or N; R W selected from H, D, halogen and -NH2, alternatively H or D; R1' is H, D, halogen or -NH2, alternatively H or D; X2 represents CR X2 R X2’ or C(O); X6 represents N or CR X6 , alternatively CR X6 ; R X2 and R X2’ independently represent H, D, halogen, -OH, C 1-6 alkyl, C 1-6haloalkyl, C 3-6 cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration; R X6 represents H, D or halogen, alternatively H or D; ring A is phenyl or 5-6-membered heteroaryl, which is optionally substituted with 1, 2, 3 or 4 substituents R; R represents H, D, halogen, -CN, -OH, -C(O)R A , -NR B R C , -NR A C(O)R B , -S(O)2R A , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; where each of R A , R B and R C independently represents H, D, C 1-6 alkyl, C1-6 haloalkyl, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl or 5-10-membered heteroaryl, or R B , R C and the N atom to which they are attached, all together form a 3- to 7-membered heterocyclyl or a 5- to 10-membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 substituents R'; each R' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, 3-7-membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein the above groups are optionally substituted with 1, 2, 3, 4, 5 or 6 R” substituents; each R'' independently represents H, D, halogen, -CN, -OH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6cycloalkyl or 3-7-membered heterocyclyl, where the above groups are optionally substituted by one or more D atoms, up to complete deuteration.

7. The compound of claim 6, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein ring A is , , , , , , , or .

8. A compound according to claim 6 or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein one R is pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, triazinyl or tetrazinyl, which is optionally substituted with 1, 2 or 3 R' substituents.

9. The compound of claim 1 or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the compound is selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , And .

10. A pharmaceutical composition comprising a compound according to any one of claims 1 to 9 or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof and a pharmaceutically acceptable excipient, and optionally another therapeutically acceptable agent (or agents).

11. A dosage form containing the pharmaceutical composition according to paragraph 10.

12. Use of a compound according to any one of claims 1 to 9, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition according to claim 10, or a dosage form according to claim 11, in the manufacture of a medicament for the treatment and / or prevention of a disease mediated by wild-type and / or mutant Bcr-Abl1 kinase; or for the treatment and / or prevention of a disease mediated by wild-type and / or mutant Bcr-Abl1 kinase; optionally, wherein the mutation in the mutant Bcr-Abl1 kinase is selected from: T315I, T315M, F317L, E355G, V299L, M244V, G250E, Q252H, Y253H, E255K, E255V, H396P, H396R, H396A, A397P, P223S, K294E, M351T, F359V, E459K, P465S, ​​V468F, I502L, A337V and A424T; alternatively, wherein the mutation in the mutant Bcr-Abl1 kinase is selected from: T315I and T315M; alternatively, wherein the mutation in the mutant Bcr-Abl1 kinase is T315I; alternatively, wherein the mutation in the mutant Bcr-Abl1 kinase is selected from: P465S, ​​V468F, I502L, A337V and A424T.

13. The application of paragraph 12, where any of the following definitions is met: i) wherein the disease mediated by wild-type and / or mutant Bcr-Abl1 kinase is selected from leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myeloma, neurodegenerative diseases, solid tumors, immunopathological diseases and fibrosis; ii) wherein the disease mediated by wild-type and / or mutant Bcr-Abl1 kinase is selected from the following: acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic lymphoma, chronic myeloid leukemia, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, acute undifferentiated leukemia, anaplastic large cell lymphoma, prolymphocytic leukemia, juvenile myelomonocytic leukemia, adult T-cell leukemia, acute myeloid leukemia with myelodysplasia-related changes, leukemia of mixed lineage, myelodysplastic syndrome, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease; alternatively, the disease mediated by wild-type and / or mutant Bcr-Abl1 kinase is selected from acute lymphoblastic leukemia and chronic myeloid leukemia.

14. A method for treating and / or preventing a disease mediated by wild-type and / or mutant Bcr-Abl1 kinase in a subject, comprising administering to the subject a compound according to any one of claims 1-9, or a pharmaceutically acceptable salt, stereoisomer, solvate, gilrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition according to claim 10, or a dosage form according to claim 11; optionally, wherein the mutation in the mutant Bcr-Abl1 kinase is selected from: T315I, T315M, F317L, E355G, V299L, M244V, G250E, Q252H, Y253H, E255K, E255V, H396P, H396R, H396A, A397P, P223S, K294E, M351T, F359V, E459K, P465S, ​​V468F, I502L, A337V and A424T; alternatively, wherein the mutation in the mutant Bcr-Abl1 kinase is selected from: T315I and T315M; alternatively, wherein the mutation in the mutant Bcr-Abl1 kinase is T315I; alternatively, wherein the mutation in the mutant Bcr-Abl1 kinase is selected from: P465S, ​​V468F, I502L, A337V and A424T.

15. The method according to paragraph 14, where any of the following determinations is made: i) wherein the disease mediated by wild-type and / or mutant Bcr-Abl1 kinase is selected from leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myeloma, neurodegenerative diseases, solid tumors, immunopathological diseases and fibrosis; ii) wherein the disease mediated by wild-type and / or mutant Bcr-Abl1 kinase is selected from the following: acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic lymphoma, chronic myeloid leukemia, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, acute undifferentiated leukemia, anaplastic large cell lymphoma, prolymphocytic leukemia, juvenile myelomonocytic leukemia, adult T-cell leukemia, acute myeloid leukemia with myelodysplasia-related changes, leukemia of mixed lineage, myelodysplastic syndrome, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease; alternatively, the disease mediated by wild-type and / or mutant Bcr-Abl1 kinase is selected from acute lymphoblastic leukemia and chronic myeloid leukemia.

16. A method for producing a compound according to any of paragraphs 1-9.

17. An intermediate compound or its salt, which is one of the following compounds: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .