Heteroaryl heterocyclic compounds and uses thereof

Abstract

Provided herein are heteroaryl heterocyclic compounds of formula (I), pharmaceutical compositions comprising same, methods for preparing same, and uses thereof, wherein the variables are as defined in the description.

Description

HETEROARYL HETEROCYCLIC COMPOUNDS AND USES THEREOF Field of the Invention The present invention relates to heteroaryl heterocyclic compounds, pharmaceutical compositions comprising same, methods for preparing same, and uses thereof. Background of the Invention Bruton’s Tyrosine kinase (BTK), a member of non-receptor tyrosine protein Tec family (including BTK, LTK, TEC, BMX, TXK and the like), is widely expressed in hematopoietic cells except for T cells, NK cells and differentiated plasma cells. BTK plays an important role in signaling mediated by B cell antigen receptor (BCR) and Fey receptor (FcyR) in B cells and myeloid cells, respectively. It is a key regulator on the B cell development, activation, signaling and survival, BTK can control the development and differentiation of B cells by activating positive regulatory factors and differentiation factors of cell cycle, and can also control the survival and proliferation of B cells by regulating the expressions of pro-apoptotic proteins and anti-apoptotic proteins. BTK also plays an important role in the migration and adhesion of B lymphoma cells. In addition, BTK plays a role in many other hematopoietic signaling pathways, such as Toll-like receptor (TLR) and cytokine receptor-mediated TNF-a production in macrophages, signaling mediated by IgE receptor (FceRI) in mast cells, inhibition of Fas / APO-1 induced apoptotic signal in B-type lymphoid cells, and collagen induced platelet aggregation. In humans, BTK gene mutation would lead to a hereditary immunodeficiency disease, X- linked agammaglobulinaemia (XLA). Point mutation of BTK gene is implicated in human XLA patients, associated with low to undetective BTK mRNA level and BTK protein expression, as a consequence, almost completely lack of the maturation and the development of B cells and immunoglobulins, and significant attenuation of persistent calcium signal in response to BCR. stimulation. The effect of BTK mutation is only restricted on B cell populations, no significant development defects in other immune cells found in XLA patients. Spontaneous mutations of BTK gene were also found in X-linked immunodeficiency (xid) mice, showing a similar but less severe phenotype. In xid mice or mutation induced BTK gene knock-out mice, B cell differentiation was partially blocked at the B cell stage, with reduced number of mature B cells in blood circulation, and resistance to models of collagen-induced arthritis and staphylococcus- induced arthritis. It has been indicated by a large amount of evidences that BTK is abundantly expressed in the circulating B cells in the patients with autoimmune diseases such as rheumatoid arthritis (RA), primary Sjogren’s syndrome (pSS) and systemic lupus erythematosus (SLE), as well as B-cell leukemia and lymphoma. The aberrant activation of BCR signaling has been confirmed in these autoimmune diseases and B cell related diseases. Inhibition of B cells, BCR signaling pathway and BTK may slow down the progression of the diseases to varying degrees. Based on the key role of BTK in the development and functions of B cells, BTK is considered as a potential target for the treatment of B cell malignancies and autoimmune diseases. A variety of BTK inhibitors are being developed for the clinical research of hematologic malignancies and autoimmune diseases. Small molecule BTK inhibitors (such as ibrutinib, acalabrutinib, zanubrutinib, PRN1008, GDC-0853) have shown promising therapeutic efficacies. For example, ibrutinib, an irreversible BTK inhibitor, with a relatively high durable efficacy and low toxicity in clinical studies, has been approved by U.S. Food and Drug Administration (FDA) for the treatment of relapsed mantle cell lymphoma (MCL) in 2013, chronic lymphocytic leukemia (CLL) in 2014, Waldenstrém’s macroglobulinaemia (WM) in 2015, and relapsed / refractory marginal zone lymphoma (MZL) in 2017. In particular, the approved indications were extended to chronic graft-versus-host disease (GVHD) in 2017, demonstrating the mechanism of BTK in the treatment of chronic autoimmune diseases. In addition, the irreversible BTK inhibitor acalabrutinib was approved for the treatment of adult MCL in 2017 and for CLL in 2019; zanubrutinib was approved by FDA for the treatment of MCL in November 2019; and a phase 3 study of PRN1008 against pemphigus is ongoing. Some irreversible BTK inhibitors (tirabrutinib, spebrutinib, and evobrutinib) and reversible BTK. inhibitors (GDC-0853, ARQ-531 and LOX0-305) have been on the stage of pre-clinical and clinical development. Therefore, BTK inhibitors represent attractive therapy for the treatment of related diseases, especially cancer, inflammatory diseases or autoimmune diseases. Summary of the Invention Provided is a compound of formula (I): Rs {n NN Rs nthe & ww XE NR, Bo 0 N X;: \ “SONNY hl S 0 ; ZN Vey? (I or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Xi and X; are each independently CH or N; or, Xj is N, X; is CRy4, wherein Rus is chosen from Ci alkyl; X3 and X, are each independently C or N; Y, and Y; are each independently CR or N; Ri and R; are each independently chosen from hydrogen, deuterium, halogen, Cy. alkyl, Ca. alkynyl, Ci haloalkyl, Cs cycloalkyl and phenyl; or Ry and R, together with the carbon atoms to which they are attached form the following structures: tea 4 zy, J Sen # a + [Re oD (1) CS (-1) (2 (-3) (1-4) or (9) wherein Rg is independently chosen from deuterium, halogen, hydroxyl, Cs alkyl, Ca.6 alkynyl, Cs deuteroalkyl and C).4 haloalkyl; or two Ry together with the carbon atoms to which they are attached form 3-6 membered cycloalkyl; mis 0,1,2,3 or4; pis 1,2,3 or 4; Z is N or CR7; R; is chosen from hydrogen, deuterium, C6 alkyl, halogen and C,. haloalkyl; Hes or R; and R; together with the carbon atoms to which they are attached form (16) provided that Rj is halogen, or both X; and X are not CH at the same time; Rj is hydrogen, deuterium, halogen or C,_¢ haloalkyl; Ry is hydrogen, halogen, -CN, C, alkyl, C,.¢ alkynyl, -(C,.; alkyl)-OH, -(C,.3 alkyl)-O- (Cy alkyl), -O~(C; alkyl), -CHO, -C(O)NH,, -C(O)NHCH3, -C(O)N(CHj3); or 3-hydroxyl- oxetan-3-yl, wherein the C.¢ alkyl or C,.3 alkyl is each optionally substituted with one or more deuteriom or halo; Ru =w J) oy YY No N he) NN SN Cyis x u A or x =, wherein Ry; is chosen from hydrogen, Cy. alkyl and Cs. cycloalkyl, wherein the Cy. alkyl is optionally substituted with one or more deuterium or halo; U, V and W are each independently N or CR12; Ryz is hydrogen, deuterium or halogen; Rs is hydrogen, C.6 alkyl, -C(O)-(C.6 alkyl), -C(0)-(Cs. cycloalkyl), -C(O)-phenyl, - C(O)NH-(Cy alkyl), -C(O)NH-(Cs.6 cycloalkyl), -C(O)N(Cr alkyl), phenyl. 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the Cys alkyl, Cs. cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) Ci¢alkyl; 5) Cig alkenyl; 6) Cigalkynyl; 7) Cj alkoxy; 8) C., haloalkyl; 9) -(Cysalkyl)-OH; 10) -(Ci. alkyl)-O-(C 6 alkyl); 11) Cj, cycloalkyl; 12) 3-12 membered heterocyclyl optionally substituted with one or more groups chosen from: deuterium, halogen, hydroxyl, oxo, -CN, C;.¢ alkyl, C;.¢ haloalkyl, Cs.6 cycloalkyl, Cag alkynyl, Cy. alkoxy, -(Cy.¢ alky])-CN, -(Cy.6 alkyD)-O-(Cy.6 alkyl), -(C,.6 alkyl)-OH, 4-6 membered heterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the Cy alkyl, Cs. cycloalkyl or 4-6 membered heterocyclyl is each optionally substituted with one or more groups chosen from: deuterium, halogen, -NH,, -OH, -NH(C.¢ alkyl), -N(C1.¢ alkyl); and -NH(Cs.¢ cycloalkyl): 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more groups chosen from: halogen, -CN, -(C, alkyl)-CN, -(C, alkyl)-OH, C,. alkyl, Cas cycloalkyl, C16 alkoxy, ~(C).s alkyl)-O-(C.¢ alkyl), -(C).6 alkyl)-NH,, -(C 1s alkyl)-NH(C\.¢ alkyl), -(C 1. alkyl)-N(C}.¢ alkyl)s, -(C1.¢ alkyl)-NH(C3.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more groups chosen from: halogen, -CN, (C6 alkyl)-CN, (Cg alkyl)-OH, C, alkyl, Ci. cycloalkyl, Ci. alkoxy, (C4 alkyl)-O-(C).¢ alkyl), -(C).s alkyl)-NHj, -(C.¢ alkyl)-NH(C,.¢ alkyl), ~(C\.¢ alkyl)-N-(Cy.s alkyl), -(C1.¢ alkyl)-NH(C3.4 cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR,;'R,’’, wherein R,’ and R,’” are each independently chosen from hydrogen, C6 alkyl, Ca cycloalkyl, -(C.¢ alkyl)-O-(C).s alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(C,.¢ alkyl)-OH, the C).¢ alkyl is optionally substituted with one or more -NR.'R,’’, and R.’ and R.”" are each independently chosen from hydrogen, C,.¢ alkyl, -(C,. alkyl)-OH and 4-6 membered heterocyclyl; 16) -C(O)NRy'Ry’*, wherein Ry’ and Rp’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl optionally substituted with one or more groups chosen from: deuterium, halogen, -OH, Cy. alkyl, -(C,.4 alkyl)-NH,, ~(C1.6 alkyl)-NH(C).¢ alkyl), -(C1.¢ alkyl)-N(C1.¢ alkyl), -(C1.6 alkyl}-NH(C3.¢ cycloalkyl), -NHz, -NH(C.6 alkyl), -N(C1.¢ alkyl)a, -NH(Cs.6 cycloalkyl) and - (C1. alkyl}-OH; and 17) -C(O)R., wherein R. is chosen from hydrogen, Cy.¢ alkyl, C26 alkenyl, Cs. alkynyl, -(C.s alkyl)-OH and -(C.¢ alkyl)-0O-(C.¢ alkyl); Ryo is hydrogen, deuterium, halogen, CN, Cy. alkyl or Cy. haloalkyl; provided that if R; and R; together with the carbon atoms to which they are attached form the following structures: Wm fRa) SE hi: ArT Re ten Ris yy . 3 “y i (-3) (i-4) or U8 andCyis HUE , then the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with Ci. alkyl at both 2- and 6- positions, The above compounds and the active compounds (including general structural formula compounds and specific compounds) disclosed in the context of the present invention, including pharmaceutically acceptable salts thereof, or solvates, racemic mixtures, enantiomers, diastereomers or tautomers thereof, which are covered by the above scope, are collectively referred to herein as “compounds of the present invention”. Also provided is a pharmaceutical composition, comprising the compounds of the present invention, and optionally comprising a pharmaceutically acceptable excipient. Also provided is a method of in vivo or in vitro inhibiting the activity of BTK, comprising contacting BTK with an effective amount of the compounds of the present invention. Also provided is a method of treating or preventing a disease mediated by BTK or at least in part by BTK, comprising administering to the subject in need thereof an effective amount of the compounds of the present invention. Also provided is a method of treating or preventing cancer, an inflammatory disease or autoimmune disease, comprising administering to the subject in need thereof an effective amount of the compounds of the present invention. Also provided is a use of the compounds of the present invention for treating or preventing a disease mediated by BTK or at least in part by BTK. Also provided is a use of the compounds of the present invention for treating or preventing cancer, an inflammatory disease or autoimmune disease. Also provided is a use of the compounds of the present invention in the manufacture of a medicament for treating or preventing a disease mediated by BTK or at least in part by BTK. Also provided is a use of the compounds of the present invention in the manufacture of a medicament for treating or preventing cancer, an inflammatory disease or autoimmune disease. Also provided are the compounds of the present invention for in vivo or in vitro inhibiting the activity of BTK. Also provided are the compounds of the present invention for use as a medicament, Also provided is a use of the compounds of the present invention for use as a medicament for treating or preventing a disease mediated by BTK or at least in part by BTK, especially for treating or preventing cancer, an inflammatory disease or autoimmune disease. Also provided is a pharmaceutical combination, comprising the compounds of the present invention and at least one additional therapeutic agent, wherein the therapeutic agent is preferably chosen from: an anti-inflammatory agent, an immunomedulator or an anti-tumor active agent, wherein the anti-tumor active agent includes a chemotherapeutic agent, an immune checkpoint inhibitor or agonist, and a targeted therapeutic agent, Also provided is a kit for treating or preventing a disease mediated by BTK or at least in part by BTK. The kit can comprise the pharmaceutical composition of the present invention and instructions for use, and the pharmaceutical composition comprises the compounds of the present invention. Brief Description of the Drawings Figure 1: Growth curve of subcutaneous transplanted tumor TMDS. Figure 2: The inhibiting effect of the compounds of the present invention on B cell activation in mouse whole blood induced by anti-IgD antibodies. Figure 3: The inhibiting effect of the compounds of the present invention on B cell activation in mouse whole blood induced by anti-IgD antibodies. Figure 4: Effects of the compounds of the present invention on the arthrosis paw volume in CIA (collagen induced arthritis) rats (the hind paw volume was measured by a Paw Volume Meter, the data were represented by mean + standard error, and each group respectively represented a normal group, a vehicle control group (i.e., the model group in the figure), compound 19 QD groups in different doses, and a 4 mg / kg GDC-0853 group (normal group: n= 3, other groups: n = 8)). Detailed Description of the Invention Definitions As used in the present application, the following words, phrases and symbols are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise, A dash (“-”) that is not between two letters or symbols is used Lo indicate a point of attachment for a substituent. For example, -OR refers to the attachment of R® to the rest of the molecule through an oxygen atom, The term “alkyl” as used herein refers to a straight or branched saturated hydrocarbon radical containing 1-18 carbon atoms (C5), preferably 1-10 carbon atoms (Cj.10), more preferably 1-6 carbon atoms (C).e), and further more preferably 1-4 carbon atoms (C,.4) or 1-3 carbon atoms (C).;). When the term “alkyl” is prefixed with “C”, it means the number of carbon atoms. For example, “C.¢ alkyl” refers to an alkyl containing 1-6 carbon atoms, “C5 alkyl” refers to an alkyl containing 1-3 carbon atoms, Examples of Ci. alkyl include, but are not limited to, methyl, ethyl, propyl (e.g. n-propyl, i-propyl), butyl (eg. n-butyl, i-butyl, s-butyl and t-butyl), pentyl (e.g. n-pentyl, i-pentyl, neo-pentyl), and hexyl, and the like. The term “alkenyl” as used herein refers to a straight or branched unsaturated hydrocarbon radical containing one or more, for example 1, 2, or 3 carbon-carbon double bonds (C=C) and 2- 18 carbon atoms (Css), preferably 2-10 carbon atoms (Cs.1g), more preferably 2-6 carbon atoms (C26), and further more preferably 2-4 carbon atoms (Cs). When the term “alkenyl” is prefixed with “C”, it means the number of carbon atoms. For example, “Ca.¢ alkenyl” refers to an alkenyl containing 2-6 carbon atoms, “Ca.4 alkenyl” refers to an alkenyl containing 2-4 carbon atoms, Examples of Ca alkenyl include, but are not limited to, vinyl, propenyl (eg. 2-propenyl), and butenyl (eg. 2-butenyl), and the like. The point of attachment for the alkenyl can be on or not on the double bonds. The term “alkynyl” as used herein refers to a straight or branched unsaturated hydrocarbon radical containing one or more, for example 1, 2, or 3, carbon-carbon triple bonds (C=C) and 2- 18 carbon atoms (C-.1s), preferably 2-10 carbon atoms (Cs.10), more preferably 2-6 carbon atoms (Ca.6), and further more preferably 2-4 carbon atoms (C.4). When the term “alkynyl” is prefixed with “C”, it means the number of carbon atoms. For example, “Ca.¢ alkynyl” refers to an alkynyl containing 2-6 carbon atoms. “Ca. alkynyl” refers to an alkynyl containing 2-4 carbon atoms. Examples of Cp alkynyl include, but are not limited to, ethynyl, propynyl (eg. 2-propynyl), and butynyl (eg. 2-butynyl), and the like. The point of attachment for the alkynyl can be on or not on the triple bonds. The term “halogen” or “halo” as used herein means fluoro, chloro, bromo, and iodo, preferably fluoro, chloro and bromo, more preferably fluoro and chloro. The term “haloalkyl” as used herein refers to an alkyl radical, as defined herein, in which one or more, for example 1, 2, 3, 4, or 5, hydrogen atoms are replaced with halogen atom, and when more than one hydrogen atoms are replaced with halogen atoms, the halogen atoms may be the same or different from each other. In one embodiment, the term “haloalkyl” as used herein refers to an alkyl radical, as defined herein, in which two or more, such as 2, 3, 4, or 5 hydrogen atoms are replaced with halogen atoms, wherein the halogen atoms are identical to each other. In another embodiment, the term “haloalkyl” as used herein refers to an alkyl radical, as defined herein, in which two or more hydrogen atoms, such as 2, 3, 4, or 5 hydrogen atoms are replaced with halogen atoms, wherein the halogen atoms are different from cach other. When the term “haloalkyl” is prefixed with “C”, it means the number of carbon atoms. For example, “C.¢ haloalkyl” refers to a haloalkyl as defined herein containing 1-6 carbon atoms. “C4 haloalkyl” refers to a haloalkyl as defined herein containing 1-4 carbon atoms, Examples of Cy. haloalkyl include, but are not limited to -CFs, ~-CHF3, -CH,F, -CH,CF3, -CH(CF:),, and the like. The term “cycloalkyl” as used herein refers to saturated or partially unsaturated cyclic hydrocarbon radical having 3-12 ring carbon atoms (Cs.y,), such as 3-8 ring carbon atoms (Cs.g), 5-7 ring carbon atoms (Cs), 4-7 ring carbon atoms (C47) or 3-6 ring carbon atoms (Cs.), which may have one or more rings, such as 1, 2, or 3 rings, preferably 1 or 2 rings. When the term “cycloalkyl” is prefixed with “C”, it means the number of carbon atoms. For example, “Cs.¢ cycloalkyl” or “3-6 membered cycloalkyl” refers to a cycloalkyl containing 3-6 ring carbon atoms. The cycloalkyl may include a fused or bridged ring, or a spirocyclic ring. The rings of the cycloalkyl may be saturated or has one or more, for example, one or two double bonds (i.e. partially unsaturated), but not fully conjugated, and not an aryl as defined herein, Examples of Ca. cycloalkyl include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[2.2]pentyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, ete. The term “heterocyclyl” or “heterocyclic” as used herein can be used interchangeably and each refers to saturated or partially unsaturated cyclic radicals having 3-12 ring atoms, such as 3- 8 ring atoms, 4-8 ring atoms, 4-6 ring atoms or 4-3 ring atoms, and containing one or more, for example 1, 2 or 3, preferably 1 or 2 heteroatorns independently chosen from N, O and § in the rings, with the remaining ring atoms being carbon; it may have one or more rings, for example 1, 2 or 3, preferably 1 or 2 rings. The heterocyclyl also includes those wherein the N or S heteroatom are optionally oxidized to various oxidation states. The point of attachment of heterocyclyl can be on the N heteroatom or carbon, For example, “4-8 membered heterocyclyl” represents a heterocyclyl having 4-8 (4, 5, 6, 7 or 8) ring atoms comprising at least one, such as 1, 2 or 3, preferably 1 or 2 heteroatoms independently chosen from N, O and S; “4-6 membered heterocyclyl” represents a heterocyclyl having 4-6 (4, 5 or 6) ring atoms comprising at least one, preferably 1 or 2 heteroatoms independently chosen from N, O and S (preferably N and O), which is preferably a monocyclic ring; and “4-5 membered heterocyclyl” represents a heterocyclyl having 4-5 ring atoms comprising at least one, preferably 1 or 2 heteroatoms independently chosen from N, O and S (preferably N and O), which is a monocyclic ring. The heterocyclyl also includes a fused or bridged ring, or a spirocyclic ring. The rings of the heterocyclyl may be saturated or has one or more, for example, one or two double bonds (i.e. partially unsaturated), but not fully conjugated, and not a heteroaryl as defined herein. Examples of heterocyclyl include, but are not limited to: 4-8 membered heterocyclyl, 4-6 membered heterocyclyl and 4-5 membered heterocyclyl, such as oxetanyl, azetidinyl, pyrrolidyl, tetrahydrofuranyl, dioxolanyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperidyl, piperazinyl, tetrahydropyridyl, pyrazinyl, pyrazolidinyl and oxaspiro[3.3]heptyl, preferably oxetanyl (such as oxetan-3-yl), azetidinyl, tetrahydropyranyl, morpholinyl (such as morpholino), piperazinyl (such as piperazin-1-yl), tetrahydropyridyl (such as 1,2,3,6-tetrahydropyridyl). The term “aryl” or “aromatic ring” as used herein can be used interchangeably and each refers to carbocyclic hydrocarbon radical of 6 to 14 carbon atoms consisting of one ring or more fused rings, wherein at least one ring is an aromatic ring. Examples of aryl include, but are not limited to phenyl, naphthalenyl, 1,2,3,4-tetrahydronaphthalenyl, phenanthryl, indenyl, indanyl, azulenyl, preferably phenyl and naphthalenyl. The term “heteroaryl” or “heteroaromatic ring” as used herein can be used interchangeably and each refers to: mono-, bi-, or tri- ring system having 5-15 ring atoms, preferably 5-12 ring atoms, more preferably 5-10 ring atoms, and most preferably 5-6 or 8-10 ring atoms, wherein at least one ring is 5- or 6-membered aromatic ring containing one or more, for example 1 to 4, heteroatoms independently chosen from N, O, and S, wherein S and N may be optionally oxidized to various oxidation states. When the total number of S and O atoms in the heteroaryl group exceeds 1, said S and O heteroatoms are not adjacent to one another. Preferably, the heteroaryl is 5-12 membered heteroaryl. For example, the heteroaryl includes: a 5-6 membered monocyclic heteroaryl, i.e., a monocyclic ring aromatic hydrocarbyl having 5 or 6 ring atoms, wherein the ring atoms include one or more, such as 1, 2 or 3 heteroatoms independently chosen from N, O and § (preferably N), and the remaining ring atoms are carbon atoms; and the heteroaryl is preferably triazolyl, pyridyl, pyrazinyl, pyrimidyl, pyrazolyl, imidazolyl, isoxazolyl, triazinyl, oxazolyl, thiadiazolyl, and pyridazinyl, more preferably triazolyl (such as 1H-1,2,3-triazole), pyridyl (such as pyridin-2-yl), pyrazinyl, and pyrimidyl, and a 8-10 membered bicyclic heteroaryl, i.e., a bicycle aromatic hydrocarbyl having 8, 9 or 10 ring atoms, wherein the ring atoms include one or more, such as 1, 2, 3 or 4, preferably 1, 2 or 3 heteroatoms independently chosen from N, O and S (preferably N), and the remaining ring atoms are carbon atoms, wherein at least one ring is an aromatic ring; which is preferably 4,5,6,7- tetrahydropyrazolo[1,5-a]pyrazine. such as 4.,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl. Examples ol heteroaryl include, but are not limited to: 5-6 membered monocyclic heteroaryl, such as pyridyl, N-oxide pyridyl, pyrazinyl, pyrimidyl, triazinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl (such as 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl and 1,3,4-oxadiazolyl), thiazolyl, isothiazolyl, thiadiazolyl, tetrazolyl, triazolyl, thienyl, furanyl, pyranyl, pyrrolyl, and pyridazinyl; and a 8-10 membered bicyclic heteroaryl, such as benzooxazolyl, benzisoxazolyl, benzothienyl, benzoisothienyl, benzothiazolyl, benzoisothiazolyl, imidazopyridyl (such as imidazo[1,2-a]pyridyl), imidazopyridazinyl (such as imidazo[1,2-b]pyridazinyl), pyrrolopyridyl (such as 1H-pyrrolo[2,3-b]pyridyl), pyrrolopyrimidyl (such as pyrrolo[3,4-d]pyrimidyl), pyrazolopyridyl (such as 1H-pyrazolo[3,4-b]pyridyl), pyrazolopyrimidyl (such as pyrazolo[1,5-a] pyrimidyl), triazolopyridyl (such as [1,2,4]triazolo[4,3-a]pyridyl and [1,2,4] triazolo[1,5- a]pyridyl), tetrazolopyridyl (such as tetrazolo[1,5-a]pyridyl), benzofuranyl, indolyl, indazolyl, purinyl, quinolyl, isoquinolinyl, and 6,7-dihydro-4H-pyrazolo[5,1-¢][1,4]oxazine. The term “-OH" as used herein refers to hydroxyl radical. The term “-CN” as used herein refers to cyano radical, The term “oxo” as used herein refers to =0. Any asymmetric atom (e.g. carbon, etc.) of a compound of formula (I) may exist in an racemic or enantiomeric rich form, for example in (R) -, (S) - or (RS) - configuration. In some embodiments, asymmetric atoms have at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, or 100% enantiomeric excess in (R) - or (S) configurations, respectively. When a structural formula or chemical name herein contains “(RS)”, it means any mixture of (R) configuration and (S) configuration of the compound, The term “optional” or “optionally” as used herein means that the subsequently described event or circumstance may or may not occur, and the description includes instances wherein the event or circumstance occur and instances in which it does not occur. For example, “optionally substituted with one or more” includes unsubstituted and substituted with 1, 2, 3 or more substituents as described. It will be understood by those skilled in the art, with respect to any group containing one or more substituents, that such groups are not intended to introduce any substitution or substitution patterns that are sterically impractical, chemically incorrect, synthetically non-feasible and / or inherently unstable. The term “substituted” or “substituted with...”, as used herein, means that one or more (such as, 1, 2, 3 or 4) hydrogens on the designated atom or group are replaced with one or more (such as 1, 2, 3 or 4) substituents, preferably the substituents chosen from the indicated group of substituents or radicals, provided that the designated atom’s normal valence is not exceeded. The said substituents may be the same or different from each other. The term “substituted with one or more groups chosen from” or “substituted with one or more” as used herein means that one or more hydrogens on the designated atom or group are independently replaced with one or more radicals from the indicated group of substituents or radicals, wherein the said radicals may be the same or different from each other. Preferably, “substituted with one or more groups chosen from” or “substituted with one or more” means that the designated atom or group is substituted with 1, 2, 3, or 4 radicals independently chosen from the indicated group of substituents or radicals, wherein the said radicals may be the same or different from each other. In some embodiments, when a substituent is oxo (i.e., =O), then 2 hydrogens on a single atom are replaced by the oxo. An optional substituent can be any radicals, provided that combinations of substituents and / or variables result in a chemically correct and stable compound. A chemically correct and stable compound is meant to imply a compound that is sufficiently robust to survive sufficient isolation from a reaction mixture to be able to identify the chemical structure of the compound. Preferably, substituents are those exemplified in the compounds of the embodiment of the present application. Unless otherwise specified, substituents are named into the core structure, For example, it is to be understood that when (cycloalkyl)alkyl is listed as a possible substituent, the point of attachment of this substituent to the core structure is in the alkyl portion. It will be appreciated by the person of ordinary skill in the art (“POSITA”) that some of the compounds of formula (I) may contain one or more chiral centers and therefore exist in two or more stereoisomeric forms. The racemates of these isomers, the individual isomers and mixtures enriched in one enantiomer, as well as diastereomers when there are two chiral centers, and mixtures partially enriched with specific diastereomers are within the scope of the present invention. It will be further appreciated by the POSITA that the present invention includes all the individual stereoisomers (¢.g. enantiomers), racemic mixtures or partially resolved mixtures of the compounds of formula (I) and, where appropriate, the individual tautomeric forms thereof. The racemates can be used as such or can be resolved into their individual isomers. The resolution can afford stereochemically pure compounds or mixtures enriched in one or more isomers. Methods for separation of isomers arc well known (cf. Allinger N. L. and Eliel E. L. in “Topics in Stereochemistry”, Vol. 6, Wiley Interscience, 1971) and include physical methods such as chromatography using a chiral adsorbent. Individual isomers can be prepared in chiral form from chiral precursors. Alternatively, individual isomers can be separated chemically [rom a mixture by: forming diastercomeric salts with a chiral acid (such as the individual enantiomers of 10-camphorsulfonic acid, campheoric acid, alpha-bromocamphoric acid, tartaric acid, diacetyltartaric acid, malic acid, pyrrolidone-5-carboxylic acid, and the like), fractionally crystallizing the salts, and then freeing one or both of the resolved bases, optionally repeating the process, so as obtain either or both substantially free of the other; i.e., in a form having an optical purity of > 95%. Alternatively, the racemates can be covalently linked to a chiral compound (auxiliary) to produce diastereomers which can be separated by chromatography or by fractional crystallization after which time the chiral auxiliary is chemically removed to afford the pure enantiomers, as is known to the POSITA. The term “tautomer” as used herein refers to constitutional isomers of compounds generaled by rapid movement of an atom in two positions in a molecule. Tautomers readily interconvert into each other, e.g., enol form and ketone form are tipical tautomers. A “pharmaceutically acceptable salt” is intended to mean a salt of a free acid or base of a compound of Formula (I) that is non-toxic, biologically tolerable, or otherwise biologically suitable for administration to the subject. For example, an acid addition salt includes such as a salt derived from an inorganic acid and an organic acid. Said inorganic acid includes such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, and nitric acid; said organic acid includes such as p-toluenesulfonic acid, salicylic acid, methanesulfonic acid, oxalic acid, succinic acid, citric acid, malic acid, lactic acid, fumaric acid, and the like. For examples, see, generally, S. M. Berge, et al., “Pharmaceutical Salts”, I. Pharm. Sci., 1977, 66:1- 19, and Handbook of Pharmaceutical Salts, Properties, Selection, and Use, Stahl and Wermuth, Eds., Wiley-VCH and VHCA, Zurich, 2002. In addition, if a compound of the present invention herein is obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid addition salt. Conversely, if the product is a free base, an acid addition salt, particularly a pharmaceutically acceptable acid addition salt, may be produced by dissolving the free base in a suitable solvent and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds. The POSITA will recognize various synthetic methodologies that may be used without undue experimentation to prepare non-toxic pharmaceutically acceptable acid addition salts or base addition salts. The term “deuterated compound” or “deuterates™ refers to a compound in which one or more hydrogen atoms, such as 1, 2, 3, 4 or 5 hydrogen atoms, are replaced by deuterium atoms (D). The term “solvates” means solvent addition forms that contain either stoichiometric or non- stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the solid state, thus forming a solvate. If the solvent is water, the solvate formed is a hydrate, when the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of one or more molecules of water, or less than one molecule of water, with one molecule of the substances in which the water retains its molecular state as H>0, such combination being able to form one or more hydrates, for example, hemihydrate, monohydrate, and dihydrate. As used herein, the terms “group(s)” and “radical(s)” are synonymous and are intended to indicate functional groups or fragments of molecules attachable to other fragments of molecules. The term “active ingredient” is used to indicate a chemical substance which has biological activity. In some embodiments, an “active ingredient” is a chemical substance having pharmaceutical utility. The term “pharmaceutical combination” as used herein means a product obtained by mixing or combining two or more active ingredients, including fixed and non-fixed combinations of active ingredients, such as a kit, and a pharmaceutical composition, The term “fixed combination” means that two or more active ingredients (such as compounds of the present invention and additional therapeutic agents) are administered simultaneously to a patient in the form of a single entity or dose. The term “non-fixed combination” means that two or more active ingredients (such as compounds of the present invention and additional therapeutic agents) are administered simultaneously, in parallel or successively to a patient in separate entities, wherein the administration provides the patient with a therapeutically effective level of the compound. The terms “treating” or “treatment” or “prevention” of a disease or disorder, in the context of achieving therapeutic benefit, refer to administering one or more pharmaceutical substances, especially a compound of formula (I) described herein to a subject that has the disease or disorder, or has a symptom of a disease or disorder, or has a predisposition toward a disease or disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disease or disorder, the symptoms of the disease or disorder, or the predisposition toward the disease or disorder. In some embodiments, the disease or disorder is cancer, such as solid tumors or hematologic malignancies, including lymphoma, leukemia and myeloma. In another embodiment, the disease or disorder is an inflammatory diseases or autoimmune disease. The terms “treating”, “contacting” and “reacting,” in the context of a chemical reaction, mean adding or mixing two or more reagents under appropriate conditions to produce the indicated and / or the desired product. It should be appreciated that the reaction which produces the indicated and / or the desired product may not necessarily result directly from the combination of two reagents which were initially added, i.e., there may be one or more intermediates which are produced in the mixture which ultimately Jead to the formation of the indicated and / or the desired product. The term “effective amount” as used herein refers to an amount or dose of an BTK inhibiting agent sufficient to generally bring about a therapeutic benefit in patients in need of treatment for a disease or disorder mediated by BTK or at least in part by BTK. Effective amounts or doses of the active ingredient of the present disclosure may be ascertained by methods such as modeling, dose escalation studies or clinical trials, and by taking into consideration factors, e.g., the mode or route of administration or drug delivery, the pharmacokinetics of the agent, the severity and course of the disease or disorder, the subject’s previous or ongoing therapy, the subject’s health status and response Lo drugs, and the judgment of the attending physician. An exemplary dose is in the range of from about 0.0001 to about 200 mg of active agent per kg of subject’s body weight per day, such as from about 0.001 to 100 mg / kg / day, or about 0.01 to 35 mg / kg / day, or about 0.1 to 10 mg / kg daily in single or divided dosage units (e.g.. BID, TID, QID). For a 70-kg human, an illustrative range for a suitable dosage amount is from about 0.05 to about 7 g / day, or about 0.2 to about 5 g / day. Once improvement of the patient’s disease or disorder has occurred, the dose may be adjusted for maintenance treatment. For example, the dosage or the frequency of administration, or both, may be reduced as a function of the symptoms, to a level at which the desired therapeutic effect is maintained. Of course, if symptoms have been alleviated to an appropriate level, treatment may cease. Patients may, however, require intermittent treatment on a long-term basis upon any recurrence of symptoms. The term “inhibition” or “inhibiting” indicates a decrease in the baseline activity of a biological activity or process. The term “inhibition of BTK activity” is a practical pharmaceutical activity for purposes of this disclosure and refers to a decrease in the activity of BTK as a direct or indirect response to the presence of the compound of the present invention, relative to the activity of BTK in the absence of the compound of the present invention. The decrease in activity may be due to the direct interaction of the compound of the present invention with BTK, or due to the interaction of the compound of the present invention, with one or more other [actors that in turn affect the BTK activity. For example, the presence of the compound of’ the present invention may decrease the BTK activity by directly binding to the BTK, by causing (directly or indirectly) another factor to decrease the BTK activity, or by (directly or indirectly) decreasing the amount of BTK present in the cell or organism. The term “subject” or “patient” as used herein means mammals and non-mammals, Mammals means any member of the mamimalia class including, but not limited to, humans; non- human primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, and swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice, and guinea pigs; and the like, Examples of non-mammals include, but are not limited to, birds, and the like. The term “subject” or “patient” does not denote a particular age or sex. In some embodiments, the subject or patient is a human. In general, the term “about” is used herein to modify a numerical value above or below the stated value by a variance of 20%. Technical and scientific terms used herein and not specifically defined have the meaning commonly understood by the POSITA to which the present disclosure pertains. All numerical ranges herein shall be interpreted as disclosing each numerical value and subset of numerical values within the range, regardless of whether they are specifically otherwise disclosed. For example, when referring to any range of values, it should be regarded as referring to every value within the range of values, for example, every integer within the range of values. For example, C.¢ as used herein represents the inclusion of 1, 2, 3, 4, 5 or 6 C. The invention relates to all values falling within the ranges, all smaller ranges and the upper or lower limits of the numerical range. Detailed Description of Embodiments (I): Embodiment 1. A compound of formula (I); Rs {0 rr A Ry X Ry XP SE . | 2 i 2 Reng” SL X42 Fo TN Yo. oN © La 0) or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein X and X5 are each independently CH or N; or, X; is N, X; is CRy4, wherein Ry4 is Cig alkyl; Xs and X4 are each independently C or N; Y, and Y are each independently CR,y or N; R} and R; are each independently chosen from hydrogen, deuterium, halogen, Cy. alkyl, C16 alkynyl, C1. haloalkyl, Cs. cycloalkyl and phenyl; or R; and R; together with the carbon atoms to which they are attached form the following structures: ae WG! rp # Ng C(1) (2) (1-3) (1-4) or (8) wherein Rg is independently chosen from deuterium, halogen, hydroxyl, C,. alkyl, Ca. alkynyl, C\.¢ deuteroalkyl and Cs haloalkyl; or two Re together with the carbon atoms to which they are attached form 3-6 membered cycloalkyl; mis 0,1,2,3 or4; pis 1,2,3 or 4; Z is N or CR7; Ry is chosen from hydrogen, deuterium, Ci.6 alkyl, halogen and C,.¢ haloalkyl; T Br or R; and R; together with the carbon atoms to which they are attached form (1-6) provided that R; is halogen, or both X, and X> are not CH at the same time; R; is hydrogen, deuterium, halogen or Cy. haloalkyl; Ry is hydrogen, halogen, -CN, Cy alkyl, Ca. alkynyl, ~(C\.; alkyl)-OH, -(C,.z alkyl)-O- (Cus alkyl), -O-(Cy.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCH3, -C(O)N(CH3); or 3-hydroxyl- oxetan-3-yl, wherein the Cy.¢ alkyl or Cy.3 alkyl is each optionally substituted with one or more deuterium or halo; mW Rut = x, x ; Cyis x vu A or * = wherein Ry; is chosen from hydrogen, C.s alkyl and Cs. cycloalkyl, wherein the Cs alkyl is optionally substituted with one or more deuterium or halo; U, V and W are each independently N or CR 5; R11 is hydrogen, deuterium or halogen: Rs is hydrogen, C6 alkyl, -C(O)~(C1.s alkyl), -C(0)-(Cs.5 cycloalkyl), -C(O)-phenyl, - C(O)NH-(C 1.6 alkyl), -C(O)NH-(Cs.6 cycloalkyl), -C(O)N(C\.6 alkyl),, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the C4 alkyl, Cs. cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) Cie alkyl; 5) Cj. alkenyl; 6) Cag alkynyl; 7) Cie alkoxy; 8) Ci. haloalkyl; 9) -(C,.¢alkyl)-OH; 10) -(C,. alkyl)-O-(C,.6 alkyl); 11) Ci cycloalkyl; 12) 3-12 membered heterocyclyl optionally substituted with one or more groups chosen from: deuterium, halogen, hydroxyl, oxo, -CN, Cy. alkyl, C,.¢ haloalkyl, Cs cycloalkyl, Cy.g alkynyl, Cy alkoxy, -(Ci. alkyl)-CN, ~(C i alkyl)-O-(C).s alkyl), -(C).¢ alkyl)-OH, 4-6 membered heterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the C,¢ alkyl, C3. cycloalkyl or 4-6 membered heterocyclyl is each optionally substituted with one or more groups chosen from: deuterium, halogen, -NH., -OH, ~-NH(C,.¢ alkyl), -N(C,.¢ alkyl), and -NH(Cs.¢ cycloalkyl); 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more groups chosen from: halogen, -CN, -(Cy.¢ alkyl)-CN, -(C,.¢ alkyl)-OH, C¢ alkyl, Ca cycloalkyl, Cy. alkoxy, ~(Cy.s alky)-O-(C1.¢ alkyl), ~(C1.s alkyl)-NHa, -(C16 alkyl)-NH(C\.s alkyl), -(C).¢ alkyl)-N(C.¢ alkyl),, -(C1.¢ alkyl)-NH(Ca.6 cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more groups chosen from: halogen, -CN, ~(C1.6 alkyl)-CN, ~(C1.¢ alkyl)-OH, Ci alkyl, Cas cycloalkyl, Cy. alkoxy, ~(C1s alkyl)-O-(C.s alkyl), (Cs alkyl)-NHa, -(C.s alkyl)-NH(C,_ alkyl), -(C).¢ alkyl)-N-(C).¢ alkyl}, (C16 alkyl)-NH(C1.¢ cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR:'R,’’, wherein R,” and R,’" are each independently chosen from hydrogen, Cs alkyl, Cs cycloalkyl, -(Cy.4 alkyl)-O-(C.s alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(Cy.¢ alkyl)-OH, the C; alkyl is optionally substituted with one or more -NR.’R."’, and R.” and R.’” are each independently chosen from hydrogen, C1. alkyl, ~(Cy alkyl)-OH and 4-6 membered heterocyclyl; 16) -C(O)NRy’R},”’, wherein Ry’ and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl optionally substituted with one or more groups chosen from: deuterium, halogen, -OH, Cy alkyl, ~(C.¢ alkyl)-NHa, -(C\.6 alkyl)-NH(C).¢ alkyl), -(C 1. alkyl)-N(C).¢ alkyl),, -(C).¢ alkyl)-NH(C.¢ cycloalkyl), -NH,, -NH(C 1. alkyl), -N(C}.¢ alkyl),, -NH(C3.¢ cycloalkyl) and - (C.6 alkyl)-OH; and 17) -C(O)R., wherein R; is chosen from hydrogen, Cs alkyl, C1 alkenyl, Cas alkynyl, -(C,.¢ alkyl}-OH and -(C,.¢ alkyl)-O-(C1.¢ alkyl); Ry is hydrogen, deuterium, halogen, CN, C,.¢ alkyl or C6 haloalkyl; provided that if R; and R; together with the carbon atoms to which they are attached form the following structures: oy : In} ‘ wg eran fp se Riz FeniReiy Fey ATR ET : ri 1 Rah | 2 i I . Oy -N v (1-1) {1-3) {i-4) (BY Lai. SE TY” (4-3) {-4) (1-8) or ’ ne v ) , and Cy is U7 **, then the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C6 alkyl at both 2- and 6- positions; for example, X, and X; are each independently CH or N; or, Xj is N, X; is CRya, wherein Ry4 is Cr. alkyl; X3is N, and X4 is C; both Y{ and Y» are CH; Rj is hydrogen, deuterium or halogen; R; and R; together with the carbon atoms to which they are attached form the following structures: Trea 1 (3) or (1-4) ; wherein Re is independently chosen from halogen, hydroxyl, C6 alkyl and C,.¢ haloalkyl; mis0,1or2;pis1,2 or 3; Li A or R; and R; together with the carbon atoms to which they are attached form (1-6) provided that R; is halogen, or both X; and X; are not CH at the same time; Ry is -(C 3 alkyD)-OH; Cyis Ri pe x, + SU, pnerein Ru i Cue alkyl; IT and V are CH: and both U and V are CH; and Rs is chosen from 1 Wy Haphe 1 Ry Ny XN \ N » SN 7 » 7 J » Fal \ \ J N=N N—N N— N— TN anha x Fas \ , RZ» v4 tL lo / ‘ Rzy Ry Rp R2; Yo— and wherein Ry is chosen from C, alkyl; Ra: is independently chosen from C6 alkyl, -(C 1.6 alkyl)-O-(C,.¢ alkyl) or 4-6 membered heterocyclyl; A, A; and A; are each independently CH: and R,3 is a 6 membered heterocyclyl optionally substituted with one or more substituents chosen from C.s alkyl and 4 membered heterocyclyl; provided that the 6 membered heterocyclyl, when substituted, is not a piperazin-1-yl substituted with C,_g alkyl at both 2- and -6 positions, preferably, R; and R; together with the carbon atoms to which they are attached form for example, or R; and Rj together with the carbon atoms to which they are attached form the following structure: Ape Lb (5) ; wherein Rg is independently chosen from deuterium, halogen, hydroxyl, Cis alkyl, Cag alkynyl, Cys deuteroalkyl and Cy. haloalkyl; mis 0, 1 or 2; preferably, mis 0. Embodiment 2. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein R; and R; together with the carbon atoms to which they are attached ih eo (1) ha ayy ss 1 aN. form 1) , le. the compound is a compound of formula (1A): Rs (IA) i ly Nf Rom Ah Li An wy 2 Xo. ~ rr LT N Xy A NY he . © ! Yo oN Yi (18) Embodiment 3. The compound of embodiment 2, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein R, and R, together with the carbon atoms to which they are attached 5 =W ¥ [Rs [N Lp he) fans (I=1) Whe WR Ye VE ET PY Wt TE Hsien asc Rm NUN so J form (1 ,X3isN, X4is C,Y,is CH, Cyis ~ ~, and the compound is a compound of formula (11): J=W (Rem fT 7 NN X; YN woe Rosy x ~~ =, H | % NUN ~ 3 H I. Il E v. .N AO Rs Yo zN © ny wherein X) and X; are each independently CH or N; or, X; is N, X; is CRy4, wherein Ry is chosen from C4 alkyl; Y,isCHorN; R; is hydrogen, deuterium, halogen or C,_ haloalkyl; Ry is hydrogen, halogen, -CN, C\ alkyl, -(C).3 alkyl)-OH, -(C,.; deuteroalkyl)-OH, - (Cy.3 alkyl)-0-(Cy.3 alkyl), -O-(Cy.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCH3, -C(O)N(CH3), or 3-hydroxyl-oxetan-3-yl, wherein the Cy. alkyl is optionally substituted with one or more halo: W is N or CR)», and R)» is hydrogen or halogen; Rs is hydrogen, Cy. alkyl, -C(O)-(C). alkyl), -C(O)-(C3.6 cycloalkyl), -C(O)-phenyl, - C(O)NH-(C.¢ alkyl), -C(O)NH-(Cs.¢ cycloalkyl), -C(OIN(C,¢ alkyl). phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the Cys alkyl, Cs. cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) Cigalkyl; 5) Cag alkenyl; 6) Cig alkynyl; 7) Cj. alkoxy; 8) Ci haloalkyl; 9) (Cre alkyD-OH; 10) -(C.6 alky)-O~(C1.¢ alkyl); 11) Cs, cycloalkyl; 12) 3-12 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, Cy.¢ alkyl, C1. haloalkyl, C;.¢ cycloalkyl, Co. alkynyl, C). alkoxy, -(C1.6 alkyl)}-CN, -(C}.¢ alkyl)-O-(C 6 alkyl), ~(Cy.¢ alky])-OH, 4-6 membered heterocyclyl, 4-6 membered fluoroheterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the Cp. alkyl is optionally substituted with one or more -OH; 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen from halogen, -CN, -(C, alky])-CN, ~(C,.¢ alkyl)-OH, C4 alkyl, Cs. cycloalkyl, Ci alkoxy, -(Ci alkyl)-O-(C 6 alkyl), -(C1.6 alkyl)-NHa, ~(C1.¢ alkyl)-NH(C.¢ alkyl), -(C1.¢ alkyl)-N(C1. alkyl), -(C1.6 alkyl)-NH(C3.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more substituents chosen from halogen, -CN, -(C\.¢ alkyl}-CN, -(C}.¢ alkyl)-OH, C, alkyl, Cs.¢ cycloalkyl, C,.¢ alkoxy, - (C16 alkyD)-O(C 1.6 alkyl), -(C).s alkyl)-NHj, -(C.s alkyl)-NH(C.s alkyl), -(C1.6 alkyl)-N(C.¢ alkyl),, ~(C1.6 alkyl)-NH(C1.6 cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR,’R.’’, wherein R.’ and R,’" are cach independently chosen from hydrogen, C1 alkyl, C3 cycloalkyl, -(C).s alkyl)-O-(C,.¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(C,¢ alkyl)-OH, the C,.¢ alkyl is optionally substituted with one or more -NR.'R.’’, and R.." and R.’’ arc each independently chosen from hydrogen, C.¢ alkyl, -(C, alkyl)-OH and 4-6 membered heterocyclyl; 16) -C(O)NRy'Ry’’, wherein Ry’ and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from halogen, -OH, C, alkyl. «(Cs alkyl)-NH>, ~(C .¢ alkyl)-NH(C_s alkyl), -(C.¢ alkyl)-N(C).¢ alkyl),, -(C).s alkyl)-NH(C3.¢ cycloalkyl) and -(C).¢ alkyl)-OH; and 17) -C(O)R,, wherein R. is chosen from hydrogen, C,.¢ alkyl, C,. alkenyl, Cy. alkynyl and -(C.¢ alkyl)-O~(C.¢ alkyl); Rg is halogen, Cs alkyl or hydroxyl; and mis 0, 1,2 or3; preferably, W is N or CR 3, and Ry; is halogen; and / or preferably, Rs is 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl optionally substituted with one or more groups chosen from: 1) Cig alkyl; and 2) 4-6 membered heterocycloalkyl, which is optionally substituted with Cj. alkyl and 4-6 membered heterocyclyl; preferably, 5-6 membered monocyclic heteroaryl is 5 membered monocyclic heteroaryl, more preferably triazolyl; preferably, 8-10 membered bicyclic heteroaryl is 8 membered bicyclic heteroaryl, more preferably 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl. Embodiment 4. The compound of embodiment 2, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein R; and R. together with the carbon atoms to which they are attached Rip Ok = (1) NR), \ % NE fom ) X;isN,X,isC, Y,is CH, Cyis “% U” *>, and the compound is a compound of formula (III): fan {Rg)m 0} N. X; 7 X i! tr hi J | HN SAA = Nl | ll \ 1 1 1 1 R. Rs Y2 oN © 3 nny wherein Xi and X; are each independently CH or N; or, X; is N, X; is CRy4, wherein Rus is chosen from C6 alkyl; Y,isCHorN; Rj; is hydrogen, deuterium, halogen or C4 haloalkyl; Ry is hydrogen, halogen, -CN, C\ alkyl, -(C).3 alkyl)-OH, -(C,.; deuteroalkyl)-OH, - (Cy.3 alkyl)-0-(Cy.3 alkyl), -O-(Cy.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCH3, -C(O)N(CH3), or 3-hydroxyl-oxetan-3-yl, wherein the Cy. alkyl is optionally substituted with one or more halo: U and V are each independently chosen from N or CH; Rs is hydrogen, Cy. alkyl, -C(O)-(C). alkyl), -C(O)-(C3.6 cycloalkyl), -C(O)-phenyl, - C(O)NH-(C.¢ alkyl), -C(O)NH-(Cs.¢ cycloalkyl), -C(OIN(C,¢ alkyl). phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the Cys alkyl, Cs. cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) Cigalkyl; 5) Cag alkenyl; 6) Cig alkynyl; 7) Cj. alkoxy; 8) Ci. haloalkyl; 9) (Crs alkyD-OH; 10) (C6 alkyl)-O-(C).¢ alkyl); 11) Cs. cycloalkyl; 12) 3-12 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, Cy alkyl, C1. haloalkyl, Cs. cycloalkyl, Co.6 alkynyl, C.s alkoxy, -(Ci.s alkyl)-CN, -(C1.s alkyl)-O-(C,.6 alkyl), -(C,_ alkyl}-OH, 4-6 membered heterocyclyl, 4-6 membered fluoroheterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the C6 alkyl is optionally substituted with one or more -OH; 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen from halogen, -CN, -(C) alky])-CN, -(C,_ alky])-OH, Cs alkyl, Ci cycloalkyl, Cs alkoxy, -(C). alkyl)-O-(C 1.6 alkyl), -(C1.¢ alkyl)-NHj, -(C\.¢ alkyl}-NH(C1.¢ alkyl}, -(C.¢ alkyl)-N(C1.¢ alkyl),, -(C;.¢ alkyl)-NH(C;.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more substituents chosen [rom halogen, -CN, ~(C, alkyl)-CN, (C1. alkyl)-OH, C, alkyl, Cs. cycloalkyl, C,.¢ alkoxy, - (C16 alkyl)-O(C\.¢ alkyl), -(C).¢ alkyl}-NHa, -(C 1.6 alkyl)-NH(C 1.6 alkyl), -(Ci.¢ alkyl)-N(C1.¢ alkyl)z, -(C1.6 alkyl)-NH(C;.¢ cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR,’R."", wherein R.’ and R,” are each independently chosen from hydrogen, C6 alkyl, Cs. cycloalkyl, -(C1.6 alkyl)-O-(C,. alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(Cj.¢ alkyl)}-OH, the C,. alkyl is optionally substituted with one or more -NR.’R.’’, and R.’ and R..’* are each independently chosen from hydrogen, C,.¢ alkyl, -(C,.¢ alkyl)-OH and 4-6 membered heterocyclyl; 16) -C(O)NR,'Ry’’, wherein Ry” and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen [rom halogen, -OH, Cs alkyl, (Cs alkyl}-NHa, ~(C alkyl)-NH(C, alkyl), -(C,¢ alkyl)-N(C.¢ alkyl),, -(C 1.6 alkyl)-NH(C1.¢ cycloalkyl) and -(C,. alkyl)-OH; and 17) -C(O)R,, wherein R. is chosen from hydrogen, C,.¢ alkyl, Cs. alkenyl, Cy alkynyl and ~(C.¢ alkyl)-O-(Cy.¢ alkyl); Rg is halogen, Cg alkyl or hydroxyl; mis 0, 1,2 or 3; and Ry; is hydrogen, C1. alkyl or C.¢ deuteroalkyl; provided that the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C.¢ alkyl at both 2- and 6- positions; preferably, U is CH, and V is N or CH; more preferably, both U and V are CH; preferably, Ry; is C1.3 alkyl, preferably methyl or ethyl, and more preferably methyl; preferably, 5-6 membered monocyclic heteroaryl is 6 membered monocyclic heteroaryl, more preferably pyridyl, pyrazinyl and pyrimidyl; preferably, 5-6 membered monocyclic heteroaryl is 5 membered monocyclic heteroaryl, more preferably triazolyl; preferably, 8-10 membered bicyclic heteroaryl is 9 membered bicyclic heteroaryl, more preferably 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl; and / or preferably, 3-12 membered heterocyclyl is 4-8 membered heterocyclyl, more preferably 4-6 membered heterocyclyl; provided that the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C,.¢ alkyl at both 2- and 6- positions; more preferably, 3-12 membered heterocyclyl is oxetanyl, azetidinyl, tetrahydropyranyl, morpholinyl, piperazinyl or tetrahydropyridyl; provided that the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C4 alkyl at both 2- and 6- positions. Embodiment 5. The compound of any one of embodiments 1-4, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein both X; and X; are CH, or one of X; and Xj is N, and the other is CH; and preferably, both X, and X, are CH. Embodiment 6. The compound of any one of embodiments 1-4, or a pharmaceutically acceptable salt thereof, or a solvale, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein X is N, Xz is CR 4, wherein R 4 is chosen from Cj. alkyl. Embodiment 7. The compound of any one of embodiments 1-6, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Y» is CH. Embodiment 8. The compound of any one of embodiments 1-7, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rj is hydrogen or halogen. Embodiment 9. The compound of any one of embodiments 1-8, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein R4 is Cy. alkyl, -(Cy.2 alkyl)-OH, -(C,.3 deuteroalkyl)-OH, -(C.3 alkyl}-0-(C,.z alkyl) or -CHO, wherein the C6 alkyl is optionally substituted with one or more halo; preferably, Ry is Cy. alkyl or -(C.3 alkyD)-O-~(C).3 alkyl), wherein the C6 alkyl is substituted with one or more halo; preferably, Ry is hydroxymethyl, hydroxy deuteromethyl, hydroxyethyl, methoxymethyl or fluoromethyl; more preferably, Ry is hydroxymethyl or hydroxy deuteromethyl; and more preferably, Ry is hydroxymethyl. Embodiment 10. The compound of any one of embodiments 1-9, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rj is hydrogen, and Ry is -(Cy.3 alkyl)-OH. Embodiment 11. The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diasterecomer or a tautomer thereof, wherein Rs is hydrogen, -C(0)-(C.¢ alkyl), -C(0)-(Cs.¢ cycloalkyl), -C(O)- phenyl, -C(OYNH-(C,.s alkyl), -C(O)NH-(Ci.¢ cycloalkyl) or -C(O)N(C\.6 alkyl). Embodiment 12. The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: Ci. cycloalkyl; 3-12 membered heterocyclyl optionally substituted with one or more Cy. alkyl, wherein the C1. alkyl is substituted with one or more -OH; and -NR.'R,"’, wherein Ra’ and R,"" are each independently chosen from hydrogen and Cy. alkyl, wherein the C).¢ alkyl is optionally substituted with -NR.'R.”’, and R.’ and R.’’ are each independently chosen from Cy.¢ alkyl, (Cy. alkyl)-OH and 4-6 membered heterocyclyl; provided that if R; and R; together with the carbon atoms to which they are attached form the following structures: Hey RE Rg H i Vem \ ’ rn A TA Te HY ae fr 3 Fr TRG i [ y A Pp Bn & Jw 7 sn 3 Rit Wo fRe} FRG Ee 311 ; 4 Bm FY Re) * Fm ili \ ON, Co. ot Tob LL a TY * - " . why Ag (+1) 3) (4) or 08) andeyis HUTA in 3) 4) or U8) and Cyis UE , then the 3- 12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C;.¢ alkyl at both 2- and 6- positions. Embodiment 13. The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from ™» § Jz Rar \ -- 0 i x / / C1 N ] SN orl \ fos * & 7 N \_ 0 NZ N— N— \ Ry; Rau Ry "ill Ry \ N— / > Raz / / N / N 7 - (Ra Ry Rat Ry Raz Rb o— A ASN 1" Paphos R and 13 wherein Ry is chosen from Cy. alkyl, C1. haloalkyl and -(C\.¢ alkyl)-O-(C\. alkyl); nis0,1or2; R22 and Ra; are each independently chosen from hydrogen, -CN, Cys alkyl, Ci. haloalkyl, - (C1 alkyl)-O~(C 6 alkyl), 4-6 membered heterocyclyl or -C(O)R,, and R. is chosen from hydrogen, Cy. alkyl or -(C).¢ alkyl)-O-(C 1.6 alkyl); Ry4 is chosen from hydrogen, Cy. alkyl, -(C 1 alkyl)-O-(C ys alkyl), or -C(O)NRy'Ry,”, wherein Ry" and Ry’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl; preferably, Rj; is Aj, Aj and Aj; are each independently CH or N; and Ry; is chosen from: 1) hydrogen; 2) Ciealkyl; 3) Cy. alkoxy; 4) halogen; 5) Cigcycloalkyl; 6) 3-12 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, -CN, Cs alkyl, C.¢ alkoxy, -(C,.¢ alkyl)-CN, -(C,.¢ alkyl)-O- (C1 alkyl), 4-6 membered heterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the C6 alkyl is optionally substituted with one or more - OH; 7) phenyl optionally substituted with one or more substituents chosen from 4-6 membered heterocyclyl; 8) -NR.’'R.”’, wherein R,’ and R;’’ are each independently chosen from hydrogen, Cr alkyl, ~(Cy6 alkyl)-O-(C¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with -(C).¢ alkyl)-OH, the C1. alkyl is optionally substituted with one or more -NR.’R,”’, and R,’ and R.”’ are each independently chosen from hydrogen, C,.6 alkyl, -(C,.¢ alky)-OH and 4- 6 membered heterocyclyl; and 9) -C(O)NRy'Ry,’’, wherein Ry,’ and Ry,’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more C6 alkyl; provided that if Ry and R: together with the carbon atoms to which they are attached form the following structures: Rai of ny at A if T } 3 tx. oo YL ~y fm : o . i Rsk she ar (Rg) TL ws (1-1) 3) 4) 8 ” Ru 0 On Ny, ) and Cyis “€ UT then the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with Cy alkyl at both 2- and 6- positions, Embodiment 14. The compound of embodiment 13, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, ope pil A L_o wherein R 3 is 3-12 membered heterocyclyl, preferably provided that if R; and R» together with the carbon atoms to which they are attached form the following structures: on [Rel A § I 1 Sa? 5 J. Y SE SFR) EL dy Ref i" a TN WN Wy of TN BT ay {1-1 NR 5 gem ip ; oe Ry [CRIP {Rely [EN Wa TRE Tope 1 eR » 7 oy © Lm 4 1 wins wh Reh 1 ’ do Oxy Moy No EO Bed RT he Hos (1) 4-3 (4) or (® ,and Cyis Sy , then the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C.s alkyl at both 2- and 6- positions. Embodiment 15. The compound of embodiment 13, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Ry is piperazinyl optionally substituted with one or more substituents chosen from C1. alkyl and 4-5 membered heterocyclyl; provided that if R; and Rs together with the carbon atoms to which they are attached form the following structures: RG), (1-3) (4) or (8) oF Lod nf wp ref Fo Ru EentRely Fey TTR Ee ; HE To 3 Os .N. nw. gs Reh N T . J 1 4 yy k; RT CA yr Le Hg 4 3 (4) or ® and Cyis Hy , then the piperazinyl, when substituted, is not piperazin-1-yl substituted with C.¢ alkyl at both 2- and 6- positions, Embodiment 16. The compound of any one of embodiments 1-13, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from SoA NTN Y TN To OF ONT NY N” “Rys' | ! b Som ” “Ae N° Lo wy? S and wherein Ros, Roa’, Ros, Ras”, Roy and Ry” are each independently chosen from hydrogen, oxo and Cg alkyl; Rig is Cy alkyl, -(Cj alkyl)-O-~(C, alkyl) or tetrahydrofuranyl; Rog is Cr. alkoxy; Ry is hydrogen or (Cy. alkyl)-OH: Rig is Cy. alkyl; Al, A; and A; are each independently CH or N; preferably, both A, and A, are CH, or one of A, and A; is N, and the other is CH; and more preferably, both A; and A are CH. Embodiment 17. The compound of any one of embodiments 1-16, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a Eo = Sy So ~ tautomer thereof, wherein Rs is hed , whereinA |, A, and A; are each independently CH or N, and Ry4 and Ry4’ are each independently chosen from hydrogen, oxo and Ci alkyl; and preferably, when Rpg is Ci.6 alkyl (such as C5; alkyl, more preferably methyl), Rs hn Sy le Rzan, ANN NE. So is preferably 0° , wherein A, A; and Aj are each independently CH or N, and Ry4’ is Clg alkyl (such as C.z alkyl, more preferably methyl), and more preferably Rats, ANN & Embodiment 18. The compound of embodiments 16 or 17, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rj4 and Ray’ are each independently chosen from hydrogen and C6 alkyl. Embodiment 19. The compound of any one of embodiments 13-18, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Ay, A» and Aj are all CH, or A, is N and both A; and Aj are CH, or A; is N and both A, and A, are CH. Embodiment 20. The compound of any one of embodiments 1-13, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from: A, Zz Ra &~ ZN I N—N 7 4 N il Raz or R21 = Rg and wherein Ry is Cj.6 alkyl: R»» is chosen from hydrogen, Cs alkyl and 4 membered heterocyclyl; A; and A; are respectively CH; and Rj4 and Ros” are each independently chosen from hydrogen and C,_¢ alkyl. Embodiment 21. The compound of any one of embodiments 4-20, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rit R11 ; HN £ or HS A wherein Ryq Ry Og No Oy N 3 NG is nt Ri is Cr.¢ alkyl or C.¢ deuteroalkyl; preferably, Ry; is C).; alkyl, preferably methyl or ethyl, and more preferably methyl; and preferably, Ry; is C;.; deuteroalkyl, preferably trideuteromethyl. Embodiment 22, The compound of any one of embodiments 4-21, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X, and X, are CH, or one of X; and X5 is N, and the other is CH; Y; is CH; R; is hydrogen; Ry is ~(Cy.; alkyl)-OH; U is CH, Vis N or CH, and Ry; is Cp3 X, Rs Rep BF Lm oO Bn alkyl; Rs is chosen from 0 , whereinR,4 and Ra,’ are each independently chosen from hydrogen, oxo and C, alkyl, both A; and A; are CH, or A; is N and A; is CH; Re is C,. ¢ alkyl; and mis 0 or 2. Embodiment 23. The compound of any one of embodiments 4-22, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both U and V are CH, and R; is methyl. Embodiment 24. The compound of any one of embodiments 1-23, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rg is Cj; alkyl; and m is 2, Embodiment 25. The compound of any one of embodiments 1-24, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rg is Cj: alkyl; and mis 1, Embodiment 26. The compound of any one of embodiments 1-24, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rg is C1. alkyl or hydroxyl; and m is 3. Embodiment 27. The compound of any one of embodiments 1-26, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Re together with the five-membered ring to which they are I< attached forms X Embodiment 28. The compound of any one of embodiments 1-27, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein 3-12 membered heterocyclyl is chosen from oxetanyl, azetidinyl, tetrahydropyranyl, morpholinyl, piperazinyl, tetrahydropyridyl, azaoxaspiro[5.3]nonyl, diazabicyclo[2.2.1]heptyl, diazaspiro[5.2]octyl, diazaoxabicyclo[4.4.0]decyl, azaoxaspiro[5.4]decyl and diazabicyclo[3.1.1]heptyl, provided that if Ry and R; together with the carbon atoms to which they are attached form the following structures: Fer yr ~N REN Rg fens Ji ~ pe ry Nn Po 7 Rg. | ’ EN ET oe SN ¥F ad “Re ¥ y ; wh oe {Rel oh RR Rit ty i Wr “yA {D +3 4 or 8 andcyis YT , then the 3- 12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C,.¢ alkyl at both 2- and 6- positions ; preferably, 3-12 membered heterocyclyl is chosen from: ANS de be N Sy” A 3 and 4 4 Ny Hug. oe wa ] yo Ql pe ne . 5 } - “ Ny dN Lode a Heh ul + CE QB Es A00 TDK H » ’ s » provided that if R; and Rj together with the carbon atoms to which they are attached form the following structures: We iRaly oy —iRg ly I Fo # 1 1 ol Wo yg 7 nr HS Y Ro 1 what sh Se NENT Fr on. sh a en wt NY wh - y . Cn (+3) (4) or ® andcyis AUT then the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C;.¢ alkyl at both 2- and 6- positions. Embodiment 29. The compound of embodiment 4, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X; and X; are CH; Y, is CH; R; is hydrogen; Ry is -(C;.3 alky)-OH; both U 2 Ne Rau, NN & oO and V are CH, and R,, is methyl; Rs is chosen from oo , wherein Ry4 is Cy3 alkyl, and both A, and A; are CH; and Rg together with the five-membered ring to which they are OX attached forms X Embodiment 30. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein the compound is a compound of formula (IB) Rs {IB) 18 a compound of formula (15) Z=\ ARg)m X; Re PEN / Rox SI AM AR H | b kN 0 % (18) Embodiment 31. The compound of embodiment 30, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein the compound is a compound of formula (IV): Rat z==y ARM ON, Xe. X VR FTN / | % Ay AA = Re Y, .N O Rs (IV) wherein Xi and X; are each independently CH or N; or, Xj is N, X; is CRy4, wherein Ry4 is chosen from Cy. alkyl; Y,is CH or N; R; is hydrogen, deuterium, halogen or C_¢ haloalkyl; Ry is hydrogen, halogen, -CN, C4 alkyl, -(C\.2 alkyl)-OH, -(C\.; deuteroalkyl)-OH, - (C13 alkyl)-O-(Cy.3 alkyl), -O-(Cy.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCHj3, -C(O)N(CHs)2 or 3-hydroxyl-oxetan-3-yl, wherein the Cy. alkyl is optionally substituted with one or more halo; U and V are cach independently chosen from N or CH; Z isN or CH; Rs is hydrogen, C.¢ alkyl, -C(O)-(C.¢ alkyl), -C(O)-(Cs. cycloalkyl), -C(O)-phenyl, - C(O)NH-(Cy.6 alkyl), -C(O)NH-(Cs.¢ cycloalkyl), -C(O)N(Cy.¢ alkyl). phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the Ci.6 alkyl, Cs.6 cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) C¢alkyl; 5) Cy alkenyl; 6) Cy.galkynyl; 7) Cie alkoxy; 8) C, haloalkyl; 9) (Cys alkyl)-OH; 10) -(C1.6 alkyl)-O-(Cr¢ alkyl); 11) Cig cycloalkyl; 12) 3-12 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, Cys alkyl, C6 haloalkyl, C3. cycloalkyl, Cas alkynyl, Cy.s alkoxy, -(Ci.6 alkyl)-CN, -(C1.¢ alkyl)-O-(C1.6 alkyl), -(C).6 alkyl}-OH, 4-6 membered heterocyclyl, 4-6 membered fluoroheterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the Cs alkyl is optionally substituted with one or more -OH; 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen from halogen, -CN, (Cys alkyl)-CN, -(C.¢ alkyl)-OH, C16 alkyl, Cs. cycloalkyl, C6 alkoxy, -(C,.g alkyl)-O-(C alkyl), ~(C alkyl)-NH,, -(C1. alkyl)-NH(C, alkyl), -(C.¢ alkyl)-N(C).5 alkyl),, (C1. alkyl)-NH(C3.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more substituents chosen from halogen, -CN, ~(C.¢ alkyl)-CN, ~(C; alkyl)-OH, C, alkyl, Cs cycloalkyl, C,.¢ alkoxy, - (C1.6 alkyl)-O(C 1.6 alkyl), (C16 alkyl)-NH,, (C1. alkyl)-NH(C.¢ alkyl), -(C1.¢ alkyl)-N(C1.¢ alkyl),, -(C1. alkyl)}-NH(C;.¢ cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR:'R,’’, wherein R,” and R,’" are each independently chosen from hydrogen, C6 alkyl, Ca. cycloalkyl, -(Ci.6 alkyl)-O-(C,. alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(C.¢ alkyl)-OH, the C1. alkyl is optionally substituted with one or more -NR.'R.”’, and R.’ and R,’’ are each independently chosen from hydrogen, Ci. alkyl, -(Ci.s alkyl)-OH and 4-6 membered heterocyclyl; 16) -C(O)NRy'Rp’’, wherein Ry’ and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from halogen, -OH, C alkyl, -(C). alkyl)}-NH,, -(C,.¢ alkyl)-NH(C,.¢ alkyl), -(C.6 alkyl)-N(C 1.5 alkyl),, -(C1.¢ alkyl)-NH(C3.4 cycloalkyl) and -(C.¢ alkyl)-OH; and 17) -C(O)R., wherein R. is chosen from hydrogen, C.¢ alkyl, Ca. alkenyl, C16 alkynyl and -(C.¢ alkyl)-O-(Cy.6 alkyl); Rg is halogen, Cy. alkyl or hydroxyl; mis0,1,2or3; and R,; is hydrogen, C.¢ alkyl or C|.¢ deuteroalkyl; preferably, both X; and X; are CH, or one of X; and X; is N, and the other is CH; preferably, both X, and X, are CH: preferably, Y; is CH; preferably, Rs is hydrogen or halogen; preferably, Rs is Cy.6 alkyl, -(C,.3 alkyl)-OH, -(C,.3 deuteroalkyl)-OH, -(C.5 alkyl)-O- (C3 alkyl) or -CHO, wherein the Cs alkyl is optionally substituted with one or more halogen; more preferably R, is -(C).; alkyl)-OH; preferably, Ry is C6 alkyl or -(Cy.3 alkyl)-O-(C.; alkyl), wherein the Cy. alkyl is substituted with one or more halo; preferably, Ry is hydroxymethyl, hydroxy deuteromethyl, hydroxyethyl, methoxymethyl or fluoromethyl; ; more preferably, Ry is hydroxymethyl; preferably, Rs is hydrogen, and R, is -(C,_; alkyl}-OH; Rqq Ry Raq Og NN. Le Ry ON yl oo ASE I JL Fed Lats NL ha! XO 1 x x x preferably, * u A is * N _ * A or * onan RiisCis alkyl or C).¢ deuteroalkyl; preferably, Z is CH; preferably, U is CH, and V is N or CH; more preferably, both U and V are CH; preferably, both U and V are CH, and R,; is methyl; preferably, Ry; is C).3 alkyl, preferably methyl or ethyl, and more preferably methyl; preferably, R,; is C.3 deuteroalkyl, preferably trideuteromethyl; preferably, Ry is halogen; preferably, Rg is C3 alkyl; preferably, mis 0 or 1; preferably, 5-6 membered monocyclic heteroaryl is 6 membered monocyclic heteroaryl, more preferably pyridyl, pyraziny] and pyrimidyl; preferably, 5-6 membered monocyclic heteroaryl is 5 membered monocyclic heteroaryl, more preferably triazolyl; preferably, 8-10 membered bicyclic heteroaryl is 9 membered bicyclic heteroaryl, more preferably 4,5,6,7-tetrahydropyrazolo[ 1,5-a]pyrazinyl; and / or and preferably, 3-12 membered heterocyclyl is 4-6 membered heterocyclyl, more preferably oxetanyl, azetidinyl, tetrahydropyranyl, morpholinyl, piperazinyl or tetrahydropyridyl. Embodiment 32. The compound of any one of embodiments 30-31, or a pharmaceutically acceptable salt thereof, or a solvale, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Y, is CH. Embodiment 33, The compound of any one of embodiments 30-32, or a pharmaceutically acceplable salt thereof, or a solvale, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein Rs is hydrogen, -C(0)-(C, alkyl), -C(O)~(Cs.¢ cycloalkyl), -C(O)- phenyl, -C(O)NH-(C,.¢ alkyl), -C(O)NH-(C3., cycloalkyl) or -C(O)N(C,.¢ alkyl). Embodiment 34, The compound of any one of embodiments 30-32, or a pharmaceutically acceplable salt thereof, or a solvale, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein Rs is 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: Cag cycloalkyl; 3-12 membered heterocyclyl optionally substituted with one or more Cs alkyl, wherein the Cy. alkyl is substituted with one or more -OH; and -NR4’R.’’, wherein Ry’ and R,”’ are each independently chosen from hydrogen and C6 alkyl, wherein the C|.¢ alkyl is optionally substituted with -NR.’R.”’, and R.’ and R."" are each independently chosen from C.¢ alkyl, -(C.¢ alkyl)-OH and 4-6 membered heterocyclyl, Embodiment 35. The compound of any one of embodiments 30-34, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein Rx is chosen from; 1 x, 1 & SN A N—N 7 NN d,, Raq “ N A a / R21 24 ge RY, Yo N — = ann KOS n | Fash and Ris wherein Ra; is chosen from Cig alkyl, Ci haloalkyl and (Cs alkyl)-O-(Cy.6 alkyl); nis 0,1 or2; Ry; and Ros are cach independently chosen from hydrogen, -CN, C,.¢ alkyl, Ci. haloalkyl, -(Cy.6 alkyl)-O-(C 1.6 alkyl), 4-6 membered heterocyclyl or -C(O)R,, and R. is chosen from hydrogen, Cy. alkyl or -(C, alkyl)-O-(C .6 alkyl); Ry is chosen from hydrogen, Cy. alkyl, (C1 alkyl)-O~(C .¢ alkyl), or -C(O)NRy'Ry,”’, wherein Ry’ and Ry," together with the N atoms to which they are attached form 4-6 membered heterocyclyl; Al, A; and Aj; are each independently CH or N; and R;;3 is chosen [rom: 1) hydrogen; 2) Cre alkyl; 3) Cy.6 alkoxy; 4) halogen; 5) Ca. cycloalkyl; 6) 4-8 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, -CN, C; alkyl, C.¢ alkoxy, -(C. alkyl)-CN, -(C}.¢ alkyl)-O-(C,.6 alkyl), 4-6 membered heterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the C,., alkyl is optionally substituted with one or more -OH; 7) phenyl optionally substituted with one or more substituents chosen from 4-6 membered heterocyclyl; 8) -NR,’R;”’, wherein R,’ and R;”’ are each independently chosen from hydrogen, Ci.6 alkyl, -(C\.¢ alkyl)-O-(C).¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more -(C;¢ alkyl)-OH, the Cy alkyl is optionally substituted with one or more -NR.’R.”’, and R.” and R.”’ are each independently chosen [rom hydrogen, Ci. alkyl, -(C,. alkyl)-OH and 4-6 membered heterocyclyl; and 9) -C(O)NR,'Ry’’, wherein Ry,’ and Ry,’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more Cy.6 alkyl; Ris preferably, Rs is B , wherein A, and A, are each independently CH or N, and R3 is 4-6 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, Cy alkyl, Cy. alkoxy, -(Ci alkyl)-O-(Cy.s alkyl) and 4-6 membered heterocyclyl; & A 7 preferably, Rs is Ra” Re wherein A, and A, are each independently CH or N;R,” and R."" together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from oxo, Cy.¢ alkyl, C1.¢ alkoxy and 4-6 membered heterocyclyl; SN \ X preferably, Rs is Rez 3 \ ee : preferably. Rs is Re , wherein Ry; is chosen from hydrogen, -CN, C¢ alkyl, Ci. haloalkyl, -(C,.s alkyl}-O-(C, alkyl), 4-6 membered heterocyclyl or -C(O)R., and R; is chosen from hydrogen, C. alkyl or -(C.¢ alkyl)-O-(C,.s alkyl); preferably, R,3 is piperazinyl optionally substituted with one or more substituents chosen from Cj alkyl and 4-5 membered heterocyclyl; 5 R; N. Fs Ny Shes TY TL “NA i. SoM Ru Res NA =X oO and wherein Rag, Ras’, Ras, Rys”, Roy and Ry” are each independently chosen from hydrogen, oxo and C4 alkyl; Rag is Cr. alkyl, -(Cy.6 alkyl)-O-(Cy.¢ alkyl) or tetrahydrofuranyl; Rag is Cr.g alkoxy; Rao is hydrogen or -(Cy.s alkyl)-OH; Rj is Cr alkyl; and A), A; and A; are each independently CH or N; Ll = & " CO 3 preferably, Rs is 0 , whereinAj, Az and A; are each independently CH or N, and Ray and Ry4” are each independently chosen from hydrogen, oxo and C,.¢ alkyl; preferably, when Ry4 is Cy.6 alkyl (such as C.3 alkyl, more preferably methyl), Rs is Ras. oN ~N Bn Lr o ) preferably oo , wherein A), A; and Aj; are each independently CH or N, and Ruy’ is Cy. alkyl (such as C3 alkyl, more preferably methyl), and more preferably & preferably, Ro, and Ry,” are each independently chosen from hydrogen and Cy alkyl; preferably, Aj, A, and A; are all CH, or A; is N and both A; and A; are CH, or Az is N and both A; and A; are CH; and preferably, Aj, A; and A; are all CH, Embodiment 36. The compound of any one of embodiments 30-33, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X; and X; are CH, or one of X; and X5 is N, and the other is CH; Y, is CH; Rs is hydrogen; Ry is ~(C1.5 alkyl)-OH; Zis CH; Uis CH, and Vis N or CH; & \ X Riz W— / or Raz Rs is ~ or Re wherein A; and A; are each independently CH or N, and Rs is 4-6 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, Cy. alkyl, C1. alkoxy, -(C,.s alkyl)-O-(C..6 alkyl) and 4-6 membered heterocyclyl; Rs; is chosen from hydrogen, -CN, Cy. alkyl, Cy.6 haloalkyl, -(C.s alkyl)-O- (Cy. alkyl), 4-6 membered heterocyclyl or -C(O)R.. and R. is chosen from hydrogen, C.¢ alkyl or -(C.¢ alkyl)-O-(Ci.6 alkyl); Rg is hydrogen or halogen; mis 0,1 or2; and Ry; is Cra alkyl; x, og Ran NS LT preferably, Rs is chosen from bd . whereinRa4 and Rs” are each independently chosen from hydrogen, oxo and C, alkyl, both A; and A; are CH, or A, is N and A, is CH; and more preferably, both A; and A; are CH. Embodiment 37. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, which is chosen from: 3 No. Structural formula No. Structural formula | 2 | Og N ] OH 4 Og, N. OHA 4 HS MN Nos NS ANA AN oN © A Lh 8 N / (J | haat | EK : Ea 7 CL ef 8 {i | L Pe — —_— i 3 oh oH my 4 rh oH HN WA = HSN Ny A OE) An Add > jd 5 [ by “ox 6 oh OH oy AES ~ PIE J 2 Aw #N © ga =~ Q 7 TE 8 ack ono. rte NON 2 | Oty { HN’ i = N. = Au ZN © N-N | be 9 10 11 Cy oo pl 12 | | ON. Lo Oy HN Sd A AN © IC) S | fe €) oe 13 wok “ost HN x SN N. = = or! | 15 og Co Faden 16 N— | 5° oh Hn J AN As " [Ah Oo SN J 5 19 A 20 17 ON 18 ON LN ) OH 4 NN ) OH 4 HN = i xX N. xy IE = Joy =zN © An zN © N, N-N 52 = 19 XC os 20 XQ os rn why ei N O N ¢ 6 7 J 21 . Pod 3 uy rr 3% No EC oF BB N 24 et OH ost GY N HN i Aw Sen HN’ Ry | A Lh 8 -N ¢ 25 | Sle 26 CN 5 Tah, ow pd IE = | A zN © N-N I< AY | rm &) —— = ot oH = \ OH ] ZN N ] r oN A NTS B® ka HN NS QO PL] An [ NO N-N | “El, 7 3 29 TM i N a 30 | ach j Og N OH N “ON HN 8 Ay NO 1 | Hy @ T 29 i 30 | 2 4 N. OH 0. Noy He { on SN HN oy Hy [4 & An ZN © Or ’ N-N | NN « FF 32 | 3 oN oH An o Roy oH Ay J N= LI LA =, HN SNS HN’ Tr I or _ | 31 | 32 | o NS on ry [ Foy on om An ZN © An NO Nf NH ¢ ¢ z / F F 33 | an 34 | pn 4: , tL & F 34 | oo 2 o dy oH o * 1 ~~ No As SAAN " & Lh $8 2N © AN & X MN | X 5 F 5 = g o ee 35 i od 36 rr “38 = lp 37 ONL Con 8 oy-P bv ooh Bu Hm ES % HN’ N A ln © gg LS ao | a, N. | 0) A oO 0 tr 29 ID. | An 39 Bm 40 ofo pn d OH ] 8 HN x B N. w= TUT Mago ot OH ] ‘ PN HN ad 5 A oN 0 1 | ty Sn? 2 | “pt oH oy HNN © Ny Ar ZN © N-N [= / = 7 “0 { 43 0 ~ Ew 44 - 41 | 42 | NSS SL NP HNN iY A ln © Or #N © Ng | ~ N Ob \ 43 | 44 | 0; N OHA 4 ©; * OHA 4 A ZN 0 NPN ZN 0 | J N° N° & & 45 [VE 46 45 | 46 | o ty oH o " oH HN " = NS AN ~ AN oN © AN ZN © Ng n HN ° HN, _ _ on 47 1 [em 48 1 al 4 A oH 43 aN oH oh JOO HN i = HN i A | Q ZN © | Q Noe x bi) S "a __I"G 49 OH Co sul 50 | ad pe OPIN | ALN 50 on OH 1 CS HN eM = AN ow J | So NT ! $ Y en ee 51 fn 37 I fe EJ 9 51 | HN’ i = a 2N o OQ | N a 1 _ 2 53 oN oH ony 54 oN OHA 9 N= | G8 HN » B INS ANNA An ZN © _y § 7) 0) 2 su, N. ~ &) $ 33 — J Tse Fe i oy™ Hn RES St = A ZN © J 57 0 ~ / A 58 3 en oF n., N &) Q EC — TAA “60 3 sg : &2 \ 0 N. OH ACEC LC HN il NTS XN Nr o; No F a. 1 “ZN ) $ a, & wb ON ©) © _Q 63 | pad 64 a 1 oO ~~ & oh OH a oh oH ] NS ] ZN HNN N NTS oS NA ZN NzN © An sN © NA $ nN wk ® .. & ©) A N ¢ A oO ~ = og hy Hl I 7 N. OH A) Py ’ ] xs AK s . ZN 0 HN i x C 7 N . X x ©) = N Q a 2 LF 0 : 69 2 | 70 | ON OH Oy N OH Ie oN 2 ] Ig $8 NS NGL NS OS N. SN LA ° On #N © \ x N \ \ \ ’ / x N— / d \ 71 =N / 73 a =N Ng N. OH LTS " (hd A MN 73 — Co Je 74 o 5 OH N x EN N. =x " 2N O Au N-N Zz 75 ob yo fp 76 Clap N Fda 78 | ON oH LCOS HN ~~ = a 79 ad 80 Ce | Ox UN. OH ] NS HN oS = N O oy NA x 0 Rt 3 oN OH 2 A OH LCE LCOS ANTS ™ HN ™ oN © AN © N? nN? / / N° rp: Ng 3 34 o n “rd | " “r 0; M = IE I x x ’g "y A Q =) AN ¢ Zh < wo A Cr ~ x ” Bagh ea | " i) NN = N. AN 0 ] Ie $8 7 L ; x x y a A Q | ZN E x N 87 IE Bh Pde 88 -_e-g Y [7 87 0; N OH 88 0; \ 9 Oy { * cost N = x N=, a Of! x CY NY ° ” 0 89 | 90 | 0, HN i HN x rs N. x oe oN © A oN © 9 fssnillicimiiimm—— ei RR] 91 4 on 92 \ ~~ PAGE en A, LEE ANSON Ng J ZN © on N. gy &) oY g 8) N _ _ 93 Co oo . 04 Co B dls 95 | in 96 | Og N. OH i IL LS HN ry A zN 0 0 S FL 97 alo 98 | o " of om ©. M rH Jagr I e ZN © LA o nN ® & oe _ 99 | ~~ 100 or ~~ | o h OH HN ae = A ZN © 4 \ / Nb 4 “oud 101 Co dln: 102 a ww 1072 1 Cg 1NA 1 1 of 103 | pl a 104 oO 105 out . 106 | ) NS Ny he ANSI My HN HB NG a #N © An ZNO xy N 1] wk © N. & Rev Id _ 107 | nl 108 ok oo pid Sw CQ | o. MN Oy ANTS Sy Ns An (nO jo { { J Q \ 109 1 ln 110 0 Sv I N ah, JAAD HN mY SN ZN © jo 8) = d \ A OH 112 n OH UO CO0 UCC HN ( N HN’ ( je Ay ZN © Av ZN © hy jo 5) ©) ©) { | A | qd 114 Ht tt 115 | | 0, My “ost “yh “or es [) NT ol 3 ° 2 2zN 0 & N 0) CD ) / 116 o & )od om (RS) Pp; 116 { 3 — . & 0; hs Hy 4 o. = Ory { 117 wh 5 FN AN A Ow ZN © An (a) | 5 3) o » =) N q 5 oN J x od oN Herp 121 oN OHA { Sn ZN © A #N © x { o w np ¢ ( 119 Z ; / d J q \ \ & nN | 120 oh oT 122 N— ( / Q | 0, A Hyg { eS NA o > N £ 0) { dq ¢ r — a 122 " “ OH N #N © g wi | 123 ; 124 | : gr OH ot ON OH 98 HA TY HN N " No \ hd ¢ 2 Reo \ 05 og 19 1 7 11g N I 125 1 Co - ~ / _ 1 126 “po 5%? 05 00 ¢ 0 12% oN oH we oh oH LOS 1 NTS SNS HN i AN nv & A (nb . | | IN 127 Obie on 130 Bh Con Os 27 0; 0 Hy 130 0 x OH 4 “ & =N 0 9 | #0, NH FE 2 131 Ty . ea 132 | ot o> 7 —t——————————— 133 | o hy (Oy { HN x x N. Ry An (a 5 LN 135 | pad | Oy N. OH 1 CN HN x NN N. xy go [Ln o N / N 136 W— 2 | WV & 138 Cy Co on 137 | 0, ™ MAN 3 HN x BY N. [A 0 Aa N-N Va 139 | oo] 140 v 141 | ] 142 | oo Pa 141 °° | bo142 | o. " Oh o M A I = INS ™ NA ZN 0 zN o a x \ )” N / & [# a 143 | il 144 op I~ N— << Pp & 4 o 144 143 Bech OH o, » OH < HN J ry NH HN ry Ns L ZN © SN #N © = i» N, $7 ©) ¥ |g 145 we A ~~ 146 | o, n a IE An ZN © OQ Oo LT ) 7 Ke - | Pipe OH LCOS HN x, ry N. ey N © Nn = & 2s) to) / q N 147 143 Og N OH CLL ys MN rE HN’ i HN’ > > N = An ZNO Ly ZN © AN dn \ N— / / Ce 149 AL 150 151 se ob oo IN 152 153 | 154 | Og N OH Oy N. OH FN ZN OLS OLC0 HN’ i ¥ HN’ ( N 0 N © 2 NO ‘ 0 / 0, 18% 1 i 1564 | / ARR ye a. IRE 155 ol cu ~~ 156 5 Oy N OH LL HN x x N = ~ ln a N / \ o— NZ Nl pe AN 156 | o, 5 Oy < HN x rs N. xy A ZN © N Sy o— 157 ww 3 2X 158 159 1 ~t 160 ve 4 | 4 & OOOO 161 oh, oH 1 adh ) 98 4 on HN \ HN > 9; N © & ad S \ x 3 nn, N gil, 2} oO ©) Q 163 1 oo N\ 164 1 0 ~L Sn Le | ON. OH,» HN Sy 8 46 {J \ W— l | or ——snp—— 164 oh S15 = Sr 2 5 ZN o | / Q \ 165 | —~d 166 on 1 ©, 5 Oh { HN Nn x N. = A ZN © N / Vv N—™ l / Q _ \ | o, MN hy { HN x Bi N. Sy Cw #N © N NW l 167 ob PE ..") 168 Yl 1d 168 | Og MN N— / 4 OH ] 8 HN x i N. “oy ( Cr ZN © N 4? { Sold |g 78 | ™ Hey 4 HN x © N. xy | Jo ZN © > Ff { 4 169 | 170 | 0, 5 (OH < o A, Hy PA = PE \ ZN © a ZN © = * es 171 = Judo 172 d” mn bon LLCO HN x EN N. a ZN © I SA os - oh, oe JD HN’ i NN A 2N © fa J | 4 i 174 ~ oN CO oH oy A NO “ Or ys ® A NO ; fo 17 175 Co Tos 176 A) N oH IL COS HN © NO 3 N-N ‘ / Q A <n RE N-N / ___|Z Fe ON OH r PN A RN A Ns * © _N © N | \ o—’ 177 PR PN 178 | Og. OH J Cy HN rt i A N o F SS TE Oy N. OH LLY HN St =x N Oo F Sy Z ~ ££ dq IN N— 1 180 Ny { “ 179 | 180 | 0; » Hn { 0; M a 4 HN x 0S N. oy HN x N N. = #N © N oo F ™ < Py es 181 oq Co a 182 HO Re OLN OH ] 1 CS HN x EN N x | o oN © 0 4 \ j 183 ol RP i 7] 184 | ON OH Cy IS i = An «NN o F J] & Po] sa 185 Cy - ~l_ 186 HCOOH 187 oh OH ~~ a 188 k OH oy 9; ZN 0 ; ZN © = J || tn, N. | = N. © &) : 3 189 ol fo 190 191 er yc, TI 91 o by SN 122 oN OH \ IE = PE = oN sN © vt ZN © x oA ae nN — 193 | 194 | Og N o ON OH _N.. DL Crs PES HN rS HN ~N ZN gN © x [ zN © (J Ey N tm, oN Nid Gall # S | - . oO . \ - © { 195 h Hy 196 o. h Hn SY ZN © An ZN © 0 Q "E) gy "0 "0 197 198 200 7 & 199 oO ov 208 \ “or JLT > HN = N N. ay TTY & 0 201 z 0 nis 202 203 i il 204 205 a Pal 206 1 oo -_ ee -g a87 EE: : - po 208 08 oN 3 i OH ( \ PIE % | An ZN © | Mt | oy 209 Ly Co nm 210 311 fa oJ 212 213 I: B . 214 315 . wo if 216 a17 Co - ln 218 219 I sale 220 | On ; iid 23y | oo \ 222 | cd F 253 Co PL Poin ANA 35 0 Nn I 226 | fy Hy Pn HN ad = An sN oo F a) AN | On & 0 a9 Co oo rN = 238 | ON oH 1 CC HN ~~" = es ZN F | 1 oN 5 10 HN x x N x, A NO £) 229 | ~~ 230 I Ox N OH LL HN xn rs N. 2 a 2N 0 ne) ANY 3 © bod — — o En ANTS NN ay [ 2N © J DANS Nw 4 0 233 . ow] 234 | Oy N OH LTS HN 7 a zN © 9g NY oS 7135 | / 236 0 —_~ eg Embodiment 38. A pharmaceutical composition, comprising the compound of any one of embodiments 1-37 and / or a pharmaceutically acceptable salt thereof, and optionally comprising a pharmaceutically acceptable excipient, Embodiment 39. A method of in vivo or in vitro inhibiting the activity of BTK, comprising contacting BTK with an effective amount of the compound of any one of embodiments 1-37, and / or a pharmaceutically acceptable salt thereof, Embodiment 40. Use of the compound of any one of embodiments 1-37 and / or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating or preventing a disease mediated by BTK or at least in part by BTK, preferably for treating or preventing cancer, an inflammatory disease or autoimmune disease, wherein the cancer is preferably solid tumor or hematologic malignancy, including lymphoma, leukemia and myeloma; the cancer is more preferably chosen from B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, ‘Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt’s lymphoma, non- Burkitt's highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lymphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukemia, myeloma (such as multiple myeloma) or grafl versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermatitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma (also referred to as systemic sclerosis), multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, diseases associated with kidney transplantation. Embodiment 41. A method of treating or preventing a disease in a subject, comprising administering to the subject in need thereof an effective amount of the compound of any one of embodiments 1-37, and / or a pharmaceutically acceptable salt thereol, wherein the disease is a disease mediated by BTK or at least in part by BTK; the disease is preferably cancer, an inflammatory disease or autoimmune disease; the cancer is preferably solid tumor or hematologic malignancy, including lyraphoma, leukemia and myeloma; the cancer is more preferably chosen [rom B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt's lymphoma, non-Burkitt’s highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lymphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukemia, myeloma (such as multiple myeloma) or graft versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermatitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma, multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, and diseases associated with kidney transplantation. Embodiment 42. The compound of any one of embodiments 1-37 and / or a pharmaceutically acceptable salt thereof, for use as a medicament, Embodiment 43, The compound of any one of embodiments 1-37 and / or a pharmaceutically acceptable salt thereof, for use in treating or preventing a disease mediated by BTK or at least in part by BTK, and preferably for use in treating or preventing cancer, an inflammatory disease or autoimmune disease, wherein the cancer is preferably solid tumor or hematologic malignancy, including lymphoma, leukemia and myeloma; the cancer is more preferably chosen from B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin’s lymphoma, Hodgkin's lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt’s lymphoma, non-Burkitt’s highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lymphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukemia, myeloma (such as multiple myeloma) or graft versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermatitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma, multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, and diseases associated with kidney transplantation. Embodiment 44. A pharmaceutical combination, comprising the compound of any one of embodiments 1-37 and / or a pharmaceutically acceptable salt thereof, and at least one additional therapeutic agent, wherein the therapeutic agent is preferably chosen from: an anti-inflammatory agent, an immunomodulator or an anti-tumor active agent, wherein the anti-tumor active agent includes a chemotherapeutic agent, an immune checkpoint inhibitor or agonist, and a targeted therapeutic agent. Embodiment 45. A compound of formula (VI): TE Te A Sr Ri Ye. Ret XP X57) | IL)" Rap. XN NS \ LV bk {VI VI) or a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein Xj, Xa, X35, Xs, Ry, Ry and R; are as defined in any one of embodiments 1-34; Rs1- is -CHO, -C,.3 alkyl-OH, -C, 3 alkyl-OAc, C,.; alkyl, -C(0)-Cy.; alkyl or C3 haloalkyl, and o— Lf —IB tN . o— ; 04 Ry o— Rg, -I-B i "0 Ra “iB X Rj; is halogen, -B(OH),, -B(OC\. alkyl), Rs or o— Ra, and Rg is rogen or Cj. alkyl. Embodiment 46. The compound of embodiment 45, which is Ror Fn \ Ray a 2 Raz i nN =, Raz oN = NN Oo Re PE] Ra (V-1% ALON (V-1) V-2) R Z==N 8 Rat { re RS \, ZN © (V-3) ~ x Rr 7 52 EN N = N CONE Raf FN N Rat VZ NTN = Ra mS N =, Rap Bi N. R: ZNO Ra ZN © s \ N f \ Ra ZN A Raz C- IAN z= Ray’ NEN \_ / Raz oN =, ZN 0 Rs w-7) V-7) (V-8) TN \ Raq gy NN Ret NZ ON | N Rap oN = _N © Ry {(V-10) gai ON Ry NZ ON a A Raz NN = Ly bk (v-10) (v-9) or oo , wherein Z is N or CR7; Ry an Rg are cach independently hydrogen or halogen; Ry is halogen or Ci. alkyl; and nis 1 or 2. Embodiment 47. The compound of embodiment 45, which is chosen from: ALLIS 4 fe LUC AALUMULLIM UL SLHUULLILLIGLUL HY), WILALTL 19 WLIUSWIL LULL. 0 0 0 © Pn © or des | NA | one ss on AN ~ ZN © NN © | N © a oH OMAN A | CT" = ZN 0 TET fe} Ed Rs a: — SO o PO A 2 Ay 2 AN | on = F | on = on ow ZN © N 0 F ZN © ot — = tt © ANN 2 PN | eA As | on AN As © PA a! lv 0 Jo A = (— F © AN F | a AK (Lh 6 LA | of SS | c .N 0 F | a |e ANAS ZN Oo Br -—_ a i. ii ~~ OF - E un oF {Nn 0 Br (RS) oN. o 77 ZN 0 AN A 2 NPN A | en ANAS | en ANAS | on ANAS lv © ln 0 ln © ET TN ~ 75 o o AN { 0 AN { 2 oN A | cl N= | cl Ny Clap Noir oN 0 ZN © 2N © 0 Zn 0 PN ps 0 PONE | a ANA | d = | &f SN LA & ZN 0 ZN © 2° AN LO Ay OAG ~~, | cl El = | Br I'S © or % ol. ( > Ea ZN © “© _N 0 7 a eer OAc, oops p00 eed ” | ho SNS | Ho 7S | oN < ZN 0 2 © ZN © i N. © Nn A PNA 20 NAN | oA ~ | on = |e ANA N F #2N © ZN QO oh o nf we Tg: jay re a rN =~ = rN FON #0 NPN FONT | oA = |e LN - | on =~ ~N o F Li 4 ZN © NTN 2 A NN | o ANA | o Ne As | en A = ln © [hd [A o F F | AO Zz A or CE 7° FN 2M F Oo F oO NT - | 2 ZN | ei AN A ln oO ® FPN | |e ANAS | c Detailed Description of Embodiments (II): Embodiment 1. A compound of formula (I); ny vib da LG sg Rs Ha. TL Ro N Nr ! | NO Rs Yo 2 Rd 0 or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein X, and X are each independently CH or N; X; and X, are each independently C or N; Y, and Y are each independently CR;g or N; Ri and R; are each independently chosen from hydrogen, deuterium, halogen, Cs alkyl, Ca. alkynyl, Ci. haloalkyl, Cs. cycloalkyl and phenyl: or R; and R, together with the carbon atoms to which they are attached [orm the following structures: Tre + z S Joan 1 hy! RN Na i (1-1) BR (G)] C2) (1-3) (1-4) or (8) wherein Rg is independently chosen from deuterium, halogen, Cs alkyl, Ca. alkynyl, Ci.¢ deuteroalkyl and C.¢ haloalkyl; or two Re together with the carbon atoms to which they are attached form 3-6 membered cycloalkyl; mis 0,1,2,3 ord; pis 1,2,3 or4; Zis N or CRy; R7 is chosen from hydrogen, deuterium, C6 alkyl, halogen and C,. haloalkyl; Rs is hydrogen, deuterium, halogen or C.¢ haloalkyl; Ry is hydrogen, halogen, -CN, Cy alkyl, Ca. alkynyl, (C,.3 alkyl}-OH, -(C}.3 alkyl)-O- (C3 alkyl), -O-(C. alkyl), -CHO, -C(O)NH,, -C(O)NHCH3, -C(O)N(CH3) or 3-hydroxyl- oxetan-3-yl, wherein the C6 alkyl or C,.3 alkyl is each optionally substituted with one or more deuterium or halo; [=W Ris / =W Oy N. Ny N AGEN! X, x Cyis x uU A or * +, wherein Ry; is chosen from hydrogen, C,.¢ alkyl and C3. cycloalkyl, wherein the C alkyl is optionally substituted with one or more deuterium or halo; U,V and W are each independently N or CR 2; Ry; is hydrogen, deuterium or halogen; Rs is hydrogen, Cj alkyl, -C(O)-(C,.s alkyl), -C(O)-(Cs.5 cycloalkyl), -C(O)NH-(C,4 alkyl), -C(O)NH-(C;.¢ cycloalkyl), -C(O)N(C 1.4 alkyl)», phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the C.¢ alkyl, Cs.6 cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN: 4) Ciealkyl; 5) Cag alkenyl; 6) Ci. alkynyl; 7y Cre alkoxy; 8) Cy haloalkyl; 9) ~(C,.alkyl)-OH; 10) -(C 1.6 alkyl)-O-(C, alkyl); 11) 4-8 membered heterocyclyl optionally substituted with one or more groups chosen from: deuterium, halogen, hydroxyl, oxo, -CN, Cy alkyl, C,.¢ haloalkyl, Ci cycloalkyl, Cog alkynyl, Cj. alkoxy, -(C. alkyl)-CN, ~(C.s alkyl)-O-(C,.s alkyl), -(C).¢ alkyl)-OH and 4-6 membered heterocyclyl, wherein the Cy.¢ alkyl, Cs.6 cycloalkyl or 4-6 membered heterocyclyl is each optionally substituted with one or more groups chosen from: deuterium, halogen, -NH;, -NH(C.¢ alkyl), - N(C1.6 alkyl); and -NH(Cs.6 cycloalkyl); 12) 5-6 membered monocyclic heteroaryl optionally substituted with one or more groups chosen from: halogen, -CN, ~(C,. alkyl)-CN, -(C,.¢ alkyl)-OH, C, alkyl, Cs. cycloalkyl, Cy. alkoxy, -(Ci.¢ alkyl)-O-(C 1.6 alkyl), -(C).¢ alkyl)-NH,, (C16 alkyl)-NH(C.g alkyl), -(C1. alkyl)-N(C1.¢ alkyl),, -(C1.¢ alkyl)-NH(Cs.¢ cycloalkyl) and 4-6 membered heterocyclyl; 13) phenyl optionally substituted with one or more groups chosen from: halogen, -CN, -(C).6 alkyl)-CN, -(C.¢ alkyl)-OH, Cs alkyl, Ci.¢ cycloalkyl, C,.¢ alkoxy, -(C 5 alkyl)-0-(C.4 alkyl), ~(C 1.6 alkyl)-NHa, -(C.¢ alkyl)-NH(C1. alkyl), -(C1.¢ alkyl)-N-(Cy.6 alkyl), -(C 1.6 alky}-NH(Cs.¢ cycloalkyl) and 4-6 membered heterocyclyl: 14) -NR,'R,’’, wherein R,’ and R,’’ are each independently chosen from hydrogen, C16 alkyl, C3. cycloalkyl, -(Cy.g alkyl)-O-(C.¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(C,.¢ alkyl)-OH, 15) -C(O)NR,'Ry"’, wherein Ry,’ and Ry," together with the N atoms to which they are attached form 4-6 membered heterocyclyl optionally substituted with one or more groups chosen from: deuterium, halogen, -OH, Cy.¢ alkyl, -(Cy.¢ alkyl)-NHa, -(C1.6 alkyl)-NH(C.6 alkyl), ~(C1s alkyl)-N(C).¢ alkyl), -(C).s alkyl}-NH(Cs.6 cycloalkyl), -NH;, -NH(C|_s alkyl), -N(Cj.¢ alkyl);, -NH(Cs.¢ cycloalkyl) and - (C1. alkyl}-OH; and 16) -C(O)R.. wherein R, is chosen from hydrogen, C1.¢ alkyl, C1. alkenyl, Cy. alkynyl, -(C. alkyD)-OH and -(C.s alkyl)-O-(C 1.6 alkyl); Ry is hydrogen, deuterium, halogen, CN, C,.¢ alkyl or C, haloalkyl Embodiment 2. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein the compound is a compound of formula (IA): Ra Heb pe SA Rom adil dd 2 | Xa. = Re XP x 3 ie A Rew, SH xn Y . ¥ | NO ’ Yo 2 Yi Embodiment 3. The compound of embodiment 2, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein the compound is a compound of formula (II): wherein X; and Xj are each independently CH or N; Y,is CH or N; Rj is hydrogen, deuterium, halogen or C6 haloalkyl; Rs is hydrogen, halogen, -CN, Ci alkyl, -(C1.3 alkyl)-OH, -(C,.3 deuteroalkyl)-OH, - (C).3 alkyD)-O-(C\.3 alkyl), -O-(Cy.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCHj3, -C(O)N(CHas)» or 3-hydroxyl-oxetan-3-yl; W is N or CR)3, and Ry; is hydrogen or halogen; Rs is Cig alkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, each of which is optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) Cigalkyl; 5) Cigalkenyl; 6) Cag alkynyl; 7) Cig alkoxy; 8) (1. haloalkyl; 9) -(Cp.salkyl)-OH; 10) ~(Ci.6 alkyl)-O-~(C 6 alkyl); 11) 4-8 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, C6 alkyl, C).¢ haloalkyl, Cs.¢ cycloalkyl, Cag alkynyl, C1. alkoxy, -(C1. alkyl)-CN, -(C,.¢ alkyl)-O-(C1¢ alkyl), ~(C,.6 alky])-OH, 4-6 membered heterocyclyl and 4-6 membered {luoroheterocyclyl; 12) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen from halogen, -CN, -(C;.¢ alkyl)-CN, -(Cy.¢ alkyl)-OH, Ci. alkyl, Css cycloalkyl, C6 alkoxy, -(Cy.¢ alkyl)-O-(C 6 alkyl), -(C;.6 alkyl)-NH,, -(C 6 alkyl)-NH(C _¢ alkyl), ~(C 1s alkyl)-N(C,.¢ alkyl),, -(C,.s alkyl}-NH(C3.4 cycloalkyl) and 4-6 membered heterocyclyl; 13) phenyl optionally substituted with one or more substituents chosen from halogen, -CN, (C6 alkyl}-CN, (C6 alky])-OH, C¢ alkyl, Cs. cycloalkyl, C,.¢ alkoxy, - (C6 alkyD)-O(C.¢ alkyl), (Cs alkyl)-NH,, ~(C. alkyl)-NH(C,.¢ alkyl), ~(C.¢ alkyl)-N(C.¢ alkyl), ~(C1.6 alkyl)-NH(C;.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) -NR,’R,"’, wherein R," and R,’’ are each independently chosen from hydrogen, C16 alkyl, Ci cycloalkyl, -(Ci.s alkyl)-O-(C1.¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(C ys alkyl)-OH; 15) -C(O)NRy'Ry”’, wherein Ry,’ and Ry,’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from halogen, -OH, C4 alkyl, ~(C,. alkyl)-NH,, ~(C.¢ alkyl)-NH(C,_g alkyl). (Cs alkyl)-N(C 1.6 alkyl), -(C).¢ alkyl)-NH(C;.¢ cycloalkyl) and -(C).¢ alkyl)-OH; and 16) -C(O)R.. wherein R, is chosen from hydrogen, C1. alkyl, Ca. alkenyl, Cy. alkynyl and -(C).s alkyl)-O-(Cy.¢ alkyl); Rg is halogen or C6 alkyl; and mis 0,1 or2; preferably, W is N or CR, and Ry; is halogen; preferably, Rs is 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl optionally substituted with one or more groups chosen from: 1) Cie alkyl; and 2) 4-6 membered heterocycloalkyl, which is optionally substituted with Cy. alkyl and 4-6 membered heterocyclyl; preferably, 5-6 membered monocyclic heteroaryl is 5 membered monocyclic heteroaryl, more preferably triazolyl; preferably, 8-10 membered bicyclic heteroaryl is 8 membered bicyclic heteroaryl, more preferably 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, Embodiment 4. The compound of embodiment 2, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein the compound is a compound of formula (III): Raq (Rg)m oN % ” X WORF NY | > N. x, POSS Rs YooN 0 Rs ny wherein Xi and X; are each independently CH or N; Y,isCHorN; R; is hydrogen, deuterium, halogen or C,_¢ haloalkyl; Ry is hydrogen, halogen, -CN, C\ alkyl, -(C).3 alkyl)-OH, -(C,.; deuteroalkyl)-OH, - (C13 alkyl)-O-(Cy3 alkyl), -O-(C1.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCH3, -C(O)N(CH3), or 3-hydroxyl-oxetan-3-yl; U and V are each independently chosen from N or CH; Rs is Cy.6 alkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, each of which is optionally substituted with one or more groups chosen from: 1) halogen, 2) oxo; 3) -CN: 4) Cgalkyl; 5) Cig alkenyl; 6) Ci. alkynyl; 7) Cre alkoxy; 8) C1. haloalkyl; 9) (Ci. alkyl)-OH; 10) -(C 1s alkyl)-O-(Cy¢ alkyl); 11) 4-8 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, Cys alkyl, Cy.¢ haloalkyl, C36 cycloalkyl, Ca. alkynyl, Cy. alkoxy, ~(C 1. alky)-CN, (C1. alkyl)-O-(C\.¢ alkyl), -(C.s alkyl)-OH, 4-6 membered heterocyclyl and 4-6 membered fluoroheterocyclyl; 12) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen from halogen, -CN, (Cys alkyl)-CN, -(C.¢ alkyl)-OH, C16 alkyl, Cs. cycloalkyl, C6 alkoxy, -(C,.g alkyl)-O-(C alkyl), ~(C alkyl)-NH,, -(C1. alkyl)-NH(C, alkyl), -(C.¢ alkyl)-N(C).5 alkyl),, (C1. alkyl)-NH(C3.¢ cycloalkyl) and 4-6 membered heterocyclyl; 13) phenyl optionally substituted with one or more substituents chosen from halogen, -CN, ~(C.¢ alkyl)-CN, ~(C; alkyl)-OH, C, alkyl, Cs cycloalkyl, C,.¢ alkoxy, - (C1.6 alkyl)-O(C 1.6 alkyl), (C16 alkyl)-NH,, (C1. alkyl)-NH(C.¢ alkyl), -(C1.¢ alkyl)-N(C1.¢ alkyl),, -(C1. alkyl)}-NH(C;.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) -NR;'R,"’, wherein R,” and R,”” are each independently chosen from hydrogen, C6 alkyl, Ca. cycloalkyl, -(Ci.6 alkyl)-O-(C,. alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(C.¢ alkyl)-OH; 15) -C(O)NRy’Ry”’, wherein Ry’ and Ry’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from halogen, -OH, C1. alkyl, -(C1.6 alkyl)-NHj, -(C1.¢ alkyl)-NH(Cy.¢ alkyl), -(C1.s alkyl)-N(C 1.6 alkyl),, ~(C 16 alkyl)-NH(Cs.¢ cycloalkyl) and -(C,.6 alkyl)-OH; and 16) -C(O)R., wherein R. is chosen from hydrogen, Cg alkyl, Co.6 alkenyl, Cy. alkynyl and -(C,_¢ alkyl)-O-(C,.¢ alkyl); Rg is halogen or Cy. alkyl; mis 0,1 or2; and Ry; is hydrogen, C..¢ alkyl or C1.¢ deuteroalkyl; preferably, U is CH, and V is N or CH; more preferably, both U and V are CH; preferably, Ry is C3 alkyl, preferably methyl or ethyl, and more preferably methyl; preferably, 5-6 membered monocyclic heteroaryl is 6 membered monocyclic heteroaryl, more preferably pyridyl, pyrazinyl and pyrimidyl; preferably, 5-6 membered monocyclic heteroaryl is 5 membered monocyclic heteroaryl, more preferably triazolyl; preferably, 8-10 membered bicyclic heteroaryl is 9 membered bicyclic heteroaryl, more preferably 4,5,6,7-tetrahydropyrazolo[ 1,5-a]pyrazinyl; and preferably, 4-8 membered heterocyclyl is 4-6 membered heterocyclyl, more preferably oxetanyl, azetidinyl, tetrahydropyranyl, morpholinyl, piperazinyl or tetrahydropyridyl. Embodiment 5, The compound of any one of embodiments 1-4, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X, and X, are CH, or one of X; and X; is N, and the other is CH; and preferably, both X; and X; are CH. Embodiment 6. The compound of any one of embodiments 1-3, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Y, is CH. Embodiment 7. The compound of any one of embodiments 1-6, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rj is hydrogen or halogen. Embodiment 8. The compound of any one of embodiments 1-7, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Ry is Cy. alkyl, ~(C,.1 alkyl)-OH, ~(C,.3 deuteroalkyl)-OH or - CHO; and preferably, Ry is hydroxymethyl or hydroxy deuteromethyl. Embodiment 9. The compound of any one of embodiments 1-8, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein Rs is hydrogen, and Ry is -(C.3 alkyl)-OH. Embodiment 10. The compound of any one of embodiments 1-9, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from A fio ha A \ Not | Rig ; Rgz Ras and wherein Roy is chosen from Cg alkyl, Cy. haloalkyl and ~(C.¢ alkyl}-O~(C alkyl); nis 0,1 or2; Ra» and Roz are each independently chosen from hydrogen, Cy. alkyl, Cy.¢ haloalkyl, (C16 alkyl)-O-(C,.¢ alkyl), 4-6 membered heterocyclyl or -C(O)R., and R, is chosen from hydrogen, Cs alkyl or -(C / . alkyl}-O-(C | alkyl); A, and A» are each independently CH or N; and R; is chosen from: 1) hydrogen; 2) Cigalkyl; 3) 4-6 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, Cs alkyl, Cy. alkoxy, -(Ci.s alkyl)-O-(Cs alkyl) and 4-6 membered heterocyclyl; 4) phenyl optionally substituted with one or more substituents chosen from 4-6 membered heterocyclyl; 5) -NR.'R.”’, wherein R,’ and R,’* are each independently chosen from hydrogen, Cp. alkyl, -(C 6 alkyl)-O~(C, alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with -(Cy.¢ alkyl)-OH; and 6) -C(ONRy’Ry’’, wherein Ry,” and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more Cy. alkyl; preferably, Rs is Embodiment 11. The compound of embodiment 10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Ry; is piperazinyl optionally substituted with one or more substituents chosen from C16 alkyl and 4-5 membered heterocyclyl. Embodiment 12. The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from > oC x, rv 7 ReneS Z RNS Sv Ary i Sr So yp EL So ry wherein Ras, Raa’, Rys, Ros’, Ry7 and Ros” are each independently chosen from hydrogen, oxo and C.¢ alkyl; Rag is Cy alkyl, -(Cy.6 alkyl)-O-(C 16 alkyl) or tetrahydrofuranyl; Rag is Cl.s alkoxy; Rpg is hydrogen or -(C.6 alkyl)-OH; Rig is Cg alkyl; Aj and A are each independently CH or N; preferably, both A, and A; are CH, or one of A; and A, is N, and the other is CH; and more preferably, both A) and A, are CH. Embodiment 13. The compound of any one of embodiments 1-12, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a 5 o™ tautomer thereof, wherein Rs is chosen from 0 , whereinRy4 and R,4’ are each independently chosen from hydrogen, oxo and Cj. alkyl; preferably, when Ras is C16 alkyl (such as C).; alkyl, more preferably methyl), x X, ho he Re Rags, NN ! 1 Se Ra Sr S is preferably S i is preferably or , wherein Ry4’ is Cig alkyl (such as C,.3 alkyl, AON An Roa, NN pe 0 more preferably methyl), and more preferably Embodiment 14. The compound of embodiments 12 or 13, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiorer, a diastereomer or a tautomer thereof, wherein Raq and Rpg” are each independently chosen from hydrogen and Cys alkyl, Embodiment 15. The compound of any one of embodiments 10-14, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both A, and A are CH, or A; is N and A, is CH. Embodiment 16. The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from: Ay 2 wr Lo and wherein Ry; is Cig alkyl; Ra; is chosen from hydrogen, Cy. alkyl and 4 membered heterocyclyl; A, and A; are respectively CH; and Ra4 and Ra” are each independently chosen from hydrogen and C6 alkyl, Embodiment 17. The compound of any one of embodiments 4-16, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a Ri Og N- ; i, Ry Oy N LL oo HSNR tautomer thereof, wherein Ry Ri Xn AS Nn ; * A or * A wherein Ry; is Cy. alkyl or C,.¢ deuteroalkyl; preferably, Ry; is C).3 alkyl, preferably methyl or ethyl, and more preferably methyl; and preferably, Ry is C,_; deuteroalkyl, preferably trideuteromethyl, Embodiment 18. The compound of any one of embodiments 4-17, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X, and X, are CH, or one of X, and X; is N, and the other is CH; Y; is CH; Rj is hydrogen; R, is (C3 alkyl)-OH; U is CH, Vis Nor CH, and R;, is C}.a & i Ran A Lo alkyl; Rs is chosen from or , whereinRy4 and Ry,” are each independently chosen from hydrogen, oxo and C,¢ alkyl, both A; and A, are CH, or A; is N and A- is CH; Rg is Cy. s alkyl; and mis QO or 2. Embodiment 19. The compound of any one of embodiments 4-18, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein both U and V are CH, and Ry is methyl. Embodiment 20. The compound of any one of embodiments 1-19, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rg is Cy; alkyl; and mis 2. Embodiment 21. The compound of any one of embodiments 1-20, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein Rg together with the five-membered ring to which they are 2X attached forms x Embodiment 22. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein the compound is a compound of formula (IB) Embodiment 23. The compound of embodiment 22, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein the compound is a compound of formula (IV): Rat 2=y AReIM ON, Xe X Re ENN / Xn o AA = Re Y, .N O Rj Rs Ya zN (Iv) wherein X and X; are each independently CH or N; Y>isCHorN: Rj is hydrogen, deuterium, halogen or C6 haloalkyl; Ra is hydrogen, halogen, -CN, Cy. alkyl, -(C1.; alkyl)-OH, -(Cy.; deuteroalkyl)-OH, - (C3 alkyl)-0-(C\5 alkyl), -O-(Cy.5 alkyl), -CHO, -C(O)NH;, -C(O)NHCH3, -C(O)N(CH3), or 3-hydroxyl-oxetan-3-yl; U and V are each independently chosen from N or CH; ZisN or CH; Rs is C6 alkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, each of which is optionally substituted with one or more groups chosen from: 1) halogen, 2) oxo; 3) -CN; 4) Cjealkyl; 5) Cy alkenyl; 6) Cagalkynyl; 7) Cie alkoxy; 8) Ci haloalkyl; 9) -(Cyalkyl)-OH; 10) -(Ci.¢ alkyl)-O-(C1. alkyl); 11) 4-8 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, Cys alkyl, C,.¢ haloalkyl, Cas cycloalkyl, Cy. alkynyl, C. alkoxy, -(Ci.¢ alkyl)-CN, ~(C1. alkyl)-O-(C).s alkyl), -(C.¢ alkyl)-OH, 4-6 membered heterocyclyl and 4-6 membered fluoroheterocyclyl; 12) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen from halogen, -CN, ~(Cy.¢ alkyl)-CN, -(C 1 alkyl)-OH, C1.6 alkyl, Ca. cycloalkyl, Cy.¢ alkoxy, -(C.s alkyl)-O-(C.¢ alkyl), -(C,.¢ alkyl)-NHa, -(C.s alkyl)-NH(C alkyl), ~(C1.¢ alkyl)-N(C, alkyl), «(C6 alkyl)-NH(C1.¢ cycloalkyl) and 4-6 membered heterocyclyl; 13) phenyl optionally substituted with one or more substituents chosen from halogen, -CN, ~(Cy.¢ alkyl)-CN, (Cy. alkyl)-OH, Cy.¢ alkyl, Ca. cycloalkyl, Cy. alkoxy, - (Cy.6 alkyl)-O(C 1.5 alkyl), ~(C¢ alkyl}-NHa, ~(C_¢ alkyl)-NH(C,.¢ alkyl), -(C,.¢ alkyl)-N(C .¢ alkyl),, -(C1.¢ alkyl)-NH(Cs.4 cycloalkyl) and 4-6 membered heterocyclyl: 14) -NR,’R,"’, wherein R," and R,’’ are each independently chosen from hydrogen, C1. alkyl, Cs. cycloalkyl, ~(Ci.¢ alkyl)-O-(C .¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(Cy.¢ alkyl}-OH; 15) -C(O)NRy’Ry’*, wherein Rp’ and Rp” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from halogen, -OH, C). alkyl, -(C1. alkyl}-NH,, -(C 1.6 alkyl)-NH(C).s alkyl), (C16 alkyl)-N(C 1.6 alkyl)z, (C1. alkyl)-NH(C;.¢ cycloalkyl) and -(Ci. alkyl)-OH; and 16) -C(O)R., wherein R; is chosen from hydrogen, Cs alkyl, C1 alkenyl, Ca alkynyl and ~(C,_¢ alkyl)-O-(C .¢ alkyl); Rg is halogen or Ci alkyl; mis 0, 1or2; and R1; is hydrogen, C).s alkyl or C,.¢ deuteroalkyl; preferably, both X; and X; are CH, or one of X, and X; is N, and the other is CH; preferably, both X; and X, are CH; preferably, Y, is CH; preferably, R; is hydrogen or halogen; preferably, Ry is Cie alkyl, -(C 1.3 alkyl)-OH, -(C,.z deuteroalkyl)-OH or -CHO; more preferably Ry is -(C 1.3 alkyl)-OH; preferably, Ry is hydroxymethyl or hydroxy deuteromethyl; preferably, Rs is hydrogen, and Ry is ~(C,; alkyl)-OH; Ry Og -N- NG R11 ON “is oe Rit Ru Ri Rig X 5 x x x , : preferably, *u # is * N ~ x A or x A wherein Ruy is Crs alkyl or Cy. deuteroalkyl; preferably, Z is CH; preferably, U is CH, and V is N or CH; more preferably, both U and V are CH; preferably, both U and V are CH, and R,; is methyl; preferably, Ry; is Ci.3 alkyl, preferably methyl or ethyl, and more preferably methyl; preferably, Ry is C,.; deuteroalkyl, preferably trideuteromethyl; preferably, Rg is halogen; preferably, mis 0 or 1; preferably, 5-6 membered monocyclic heteroaryl is 6 membered monocyclic heteroaryl, more preferably pyridyl, pyrazinyl and pyrimidyl; preferably, 5-6 membered monocyclic heteroaryl is 5 membered monocyclic heteroaryl, more preferably triazolyl; preferably, 8-10 membered bicyclic heteroaryl is 9 membered bicyclic heteroaryl, more preferably 4,5,6,7-tetrahydropyrazolo[ 1,5-a]pyrazinyl; and preferably, 4-8 membered heterocyclyl is 4-6 membered heterocyclyl, more preferably oxetanyl, azetidinyl, tetrahydropyranyl, morpholinyl, piperazinyl or tetrahydropyridyl. Embodiment 24. The compound of any one of embodiments 22-23, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein Y, is CH. Embodiment 25, The compound of any one of embodiments 22-24, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein Rs is chosen from: J A N=—N (Rz))™ i , (SE Ryz = = § roy N, N \ o \ A N= MN Raz Ras and wherein Ry; is chosen from Cy. alkyl, C,. haloalkyl and -(C).¢ alkyl)-O-(C).¢ alkyl); nis 0, 1or2; Raz and Ry; are each independently chosen from hydrogen, C.¢ alkyl, Ci. haloalkyl, - (Cy.6 alkyl)-O~(C ys alkyl), 4-6 membered heterocyclyl or -C(O)R,, and R. is chosen from hydrogen, C6 alkyl or -(C, alkyl)-O-(C,.¢ alkyl); A; and A; are each independently CH or N; and R3 is chosen from: 1) hydrogen; 2) C6 alkyl; 3) 4-6 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, Cy.¢ alkyl, C16 alkoxy, -(Cy.6 alkyl)-O-(C.¢ alkyl) and 4-6 membered heterocyclyl; 4) phenyl optionally substituted with one or more substituents chosen from 4-6 membered heterocyclyl; 5)-NR,'R,”’, wherein R," and R,”’ are each independently chosen from hydrogen, C,.¢ alkyl, -(C).¢ alkyl)-O-(C1.s alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more -(C,.s alkyl)-OH; and 6) -C(O)NRy’'Ry’*, wherein Ry,’ and Ry,’’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more Ci.¢ alkyl; & A 7 . Td Ny " . . ~ s preferably, Rs is Ral Ra", wherein A; and A; are each independently CH or N;R,’ and R,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from oxo, Cy.¢ alkyl, Ci. alkoxy and 4-6 membered heterocyclyl; preferably, Rs is piperazinyl optionally substituted with one or more substituents chosen from C\.¢ alkyl and 4-5 membered heterocyclyl; = LC ~N x pe FS BE Ek Se ry og EF Soy , wherein Raa, R24’, Ras, Ras, Ray and Ray” are each independently chosen from hydrogen, oxo and C,¢ alkyl; Ry is C6 alkyl, -(C 4 alkyl)-O-(C 6 alkyl) or tetrahydrofuranyl; Rag is Cy. alkoxy; Ry is hydrogen or -(C).4 alkyl)-OH; R3o is Cp. alkyl; and A) and A; are each independently CH or N; © LT preferably, Rs is chosen from or , whereinRy4 and Ray’ are each independently chosen from hydrogen, oxo and C4 alkyl; more preferably, when Ras is Ci alkyl (such as C5 alkyl, more preferably methyl), x x ho he Rasp Rass, AN ! 1 Se Ry Sera > 1s nreferablyv > g is preferably or , wherein Ras” is C6 alkyl (such as C).3 alkyl, J iD nr Roan, oN NS Sv S more preferably methyl), and more preferably preferably, Ras and Ra,” are each independently chosen from hydrogen and Cy. alkyl; preferably, one of A; and As is N, and the other is CH; preferably, A is N and A» is CH; and preferably, both A; and A, are CH. Embodiment 26. The compound of any one of embodiments 22-25, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X; and X- are CH, or one of X; and X- is N, and the other is CH; Y, is CH: R; is hydrogen; Ry is -(C 3 alkyl)-OH; Z is CH; Uis CH, and V is N or CH; 0 Lr Rs is chosen from 0 , whereinRo4 and Ry’ are each independently chosen from hydrogen, oxo and C,.¢ alkyl, both A; and A, are CH, or A; is N and A; is CH; Rs is hydrogen or halogen; mis 0, 1 or2; and Ry, is Cy alkyl; and preferably, both A; and A, are CH. Embodiment 27. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, which is chosen from: No. | Structural formula No. | Structural formula 1 | 2 I N. ) OHA 4 Og, N. Hen 4 HVS B N. xy HN SS NN pe AN oH © 2 (A J ¢) | ~N to, N. 1, | Call oN Yk oH |< | 5 ry “os 6 o, , Hn SAY sSNA oy 7 ZN © 3 X Cal = oS 7 AL 8 wb ~L SNS 2 7 | Au NO I< | oL BB on od ean Pl 10 rr ~~ 12 i 1 55” 3 J lc & 0 GJ oe BUS ort HN x N. ss, = Ee 15 | 16 ~N 0, i OHA Ae OHA HN © Nos eS Ne A \ ZN © LA 3 {3 (oN ” [odd 3 » Se’ 17 =N 7 1@ =N 7 17 Noh OH 18 Noh A oy { a oH ry HN 5 = NTS ry Ny Jo #N © An N © N N-N OO |< 9 on 2 Li SIEGE SAE oO N J NO nN. *upll Id I$ 1 1 S | T° 1 Se ° el | x 1! WSN YT | 8 8) 23 — 24 in oH $ ©. n OHA { a C am I AAS O N An oN © | a Y 35 A: ad 26 1 ele ON 25 0. A Hw 4 SAAN a A 6 Cr ¢ 27 - rhe 1 2B I \ | re & = k OH 28 0, n OH ] IN 1 NN NTS mS Nos RES oS Ns 9; NN 0 A _N © N N-N | a / ( 3 29 I: - tl 30 " J. i ON OH NOT AN OLS HN mS a LEX ANS en i | / | A _ er 31 | 2 | 0. ™ OHA { Qo, on OHA $ en oe 2 N-N N-N ¢ ? / / [3 F 33 | pad 34 \ ids {0 ¢ ¥ ¢ 33 a L on 34 | y 1S o M oH HN mY HN ry No An sN © Poy oN © Jeb N . [ot ¢ ™ | / ¥ J S o 35 . ot 36 0 Eset arrrl Tae Db _ 37 lh ona 38 O30 Onli Og MN, D. CH 9 N, [3 HN » AN ZN 0 9g Ie 5 ; o.lo } 4 hon, x bY os Ba ph ( ON OA < Pe oh ] IC = x a (no ZN @ Or “eM o | IN & S TN Q ar Ta | 41 ak oH ON oH | 3 1) Ns S Ns NSN O) A OE An AN © on Y I~ T Ns Wf A * “0 reemerged] A \ ny AA | / 43 ee Peles 1 44 45 ~~ 46 45 | 46 | ON oH ny { ON Hy < HN mS N= PI = 0; ZN © ; _N 8 Ny a HN _ ew 47 CC Bh ~~ 48 | la 47 | 48 | Oy N OH Og N. OH J rst Ces Hy ~ HN my Is ZN 0 0 NO Ny J | oN oPON ESS a 49 CR oo ~~ 50 | ail 4 oN 50 0; b OH ] G8 HN SS oN = An ow " [* So re all 9 51 | HN’ i ™ AN zN © J | N he \ 1 © 53 o h oH 5 OLN Hn | TIE oT HN SAAS & 3 & (YY x wl " N N & & 33 TT 56 “Eg Cr 0, % Hn ANT ~ x, An ZN © fo) 57 | A 8 ! o b OH | oN eA x HN x N N. =, HN x NN N. = 0 LV Ek Ay no iy | Ig) <Q 59 ol ny BN 60 or uN 0 F OJ un 0 F x I x J ‘0, oN: He N Gal, &) 9 © 61 oie tm LS | 62 Buc oN ona | a 9 | 63 ak OH oo ~ 64 ON. OH _~..{ 1) 65 oN OH 66 oN OH LCOS LCOS HN SONS HS NN O NN © CO 4 1 x gg i N ® “a N Sp ©) & N A 67 N= 68 | o b, OH | NS A fr ~N © N TN J [od i 70 | o. " Hn { o, by On HN rt =~ HN ~~" = Ay ZN © A ZN © 0 N \ | fr Ia) \. 7 N— £ | / / Q \ 71 73 WN N oH NS A N= An oN © N-N 7 73 0 Co a 74 | 0, M HAN 4 HN a © N =, aL N-N rt 75 wm 3 is FPN 76 77 B dw O98 | N OH LCOS HTS St = O ZN © Tog B Fone 80 Q . Embodiment 28. A pharmaceutical composition, comprising the compound of any one of embodiments 1-27 and / or a pharmaceutically acceptable salt thereof, and optionally comprising a pharmaceutically acceptable excipient. Embodiment 29. A method of in vive or in vitro inhibiting the activity of BTK, comprising contacting BTK with an effective amount of the compound of any one of embodiments 1-27, and / or a pharmaceutically acceptable salt thereof, Embodiment 30. Use of the compound of any one of embodiments 1-27 and / or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating or preventing a disease mediated by BTK or at least in part by BTK, preferably [or treating or preventing cancer, an inflammatory disease or autoimmune disease, wherein the cancer is preferably solid tumor or hematologic malignancy, including lymphoma, leukemia and myeloma; the cancer is more preferably chosen from B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin’s lymphoma, Hodgkin's lymphoma, ‘Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt's lymphoma, non- Burkitt's highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lymphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukemia, myeloma (such as multiple myeloma) or graft versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermatitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma (also referred to as systemic sclerosis), multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, diseases associated with kidney transplantation. Embodiment 31. A method of treating or preventing a disease in a subject, comprising administering to the subject in need thereof an effective amount of the compound of any one of embodiments 1-27, and / or a pharmaceutically acceptable salt thereof, wherein the disease Pp! y P is a disease mediated by BTK or at least in part by BTK; the disease is preferably cancer, an inflammatory disease or autoimmune disease; the cancer is preferably solid tumor or hematologic malignancy, including lymphoma, leukemia and myeloma; the cancer is more preferably chosen from B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin's lymphoma, Hodgkins lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt's lymphoma, non-Burkitt’s highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lvmphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukemia, myeloma (such as multiple myeloma) or graft versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermatitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma, multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, and diseases associated with kidney transplantation. Embodiment 32. The compound of any one of embodiments 1-27 and / or a pharmaceutically acceptable salt thereof, for use as a medicament. Embodiment 33. The compound of any one of embodiments 1-27 and / or a pharmaceutically acceptable salt thereof, for use in treating or preventing a disease mediated by BTK or at least in part by BTK, and preferably for use in treating or preventing cancer, an inflammatory disease or autoimmune disease, wherein the cancer is preferably solid tumor or hematologic malignancy, including lymphoma, leukemia and myeloma; the cancer is more preferably chosen from B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin’s lymphoma, Hodgkin's lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt’s lymphoma, non-Burkitt’s highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lymphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukemia, myeloma (such as multiple myeloma) or graft versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermalitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma, multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, and diseases associated with kidney transplantation. Embodiment 34. A pharmaceutical combination, comprising the compound of any one of embodiments 1-27 and / or a pharmaceutically acceptable salt thereof, and at least one additional therapeutic agent, wherein the therapeutic agent is preferably chosen from: an anti-inflammatory agent, an immunomodulator or an anti-tumor active agent, wherein the anti-tumor active agent includes a chemotherapeutic agent, an immune checkpoint inhibitor or agonist, and a targeted therapeutic agent. Embodiment 35. A compound of [ormula (V): dll lia TL Ry Ray Xa. ~~ xg IL Ra N - Ru A by UN © Rs Vv) Tra an stantinmar 8 diacteraniia or a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein X,, Xs, Xs, Xu, Ry, Ry and Rj are as defined in any one of embodiments 1-27; Rs) is -OH, oxo (=0), or -O-(C, alkyl), and gL , ps Ag BR Ye Rg 0] OJ Ra p Ry HH Tr eX o [aN . R32 is halogen, -B(OH),, -B(OC\.¢ alkyl), Rs or o— Rg ,and Rq is hydrogen or Cg alkyl, Embodiment 36. The compound of embodiment 35, which is R; i oy Q Rs), Ran ALAN = ®! h r (v-4) . or 4 , and Z is N or CR7:R; and Ry are each independently hydrogen or halogen; Rg is halogen or C.¢ alkyl; and nis 1 or 2. Embodiment 37. A compound, which is chosen from: 0 ZN 2° PNA 2 An | a oN = | oA = |e LA N | Hd ZN © NN © A Py ( | on FON | | ot rs =~ B eS OY | ~Y" | Wl Cr x = | OH AANA | | ho'® A Ns ZN 0 I a oT —_ . Sp . SE 20 AN 22 AN LF a c OC y » : CS on = ZN © N Oo F ZN © _ —_— — “N= = F © ANA AL PN Cl. N = Cl N. = 0 | N | & 27 PON l zN © #N © | oA =, | ON nn UF A PA | os =, ZN © Seo © . 0 F | OAC PN A A PN , oo | Ch ANS | OANA | NS oN © | ~-N © F | NA o F LN & Br ’ | PORE EE ANA ZN Oo Br (RS) oO 2 NN | on = zN © 1 ~eN © SoM 0 SN 0 Ly 0 2 NIN | onset = ZN 0 1 22 Mon |e A ~ NO J —— The various embodiments of the present invention (including the following examples) and the features of the various embodiments should be interpreted as being arbitrarily combined with each other, and the various solutions obtained by these mutual combinations are all included in the scope of the present invention, just like the solutions obtained by listing these mutual combinations specifically and individually herein, unless clearly stated otherwise in the context. General synthetic methods The compound of formula (I) and / or a pharmaceutically acceptable salt thereof described herein can be synthesized using commercially available starting materials, by methods known in the art, or methods disclosed in the patent application. The synthetic routes shown in Scheme 1 to Scheme 2 illustrate the general synthetic methods for preparing the compounds of the present invention, and the synthetic routes shown in Scheme 3 to Scheme 6 illustrate the general synthetic methods for preparing the material 1-1 used in Scheme 1 to Scheme 2. Scheme 1: vy Hal Hal Ry Ry Ry x " Xe. OH, Xa. xx YN Ho XEN (He HA Xie? Ry {1 ro A Rey — — Hal A DV A Y | TT [ he J. YagoN © s Yo oN ORs ¥ Yi 1 +3 14 A . H 17 Rs Re oxen Has A Da YY Ya 2N © s v7 1.5 1.5 14s 18 Ry Ri OAc OAs a a xa ok lr Rw on NK Re HO” NY Ne permet. ~ ™y hd YN © Re rgpN OT v7 Y3 146 18 Ry ara 2 Ree, AN X27 TTT Yo. oN © Yi {1.1} As shown in Scheme 1, a compound of formula 1-1 is reacted with a dihaloarylaldehyde compound of formula 1-2 under the catalysis of cuprous iodide to obtain a compound of formula 1-3. The carbon-nitrogen coupling reaction catalyzed by cuprous iodide is carried out under suitable conditions. The solvent used can be chosen from polar solvents such as 1,4-dioxane, DMF, etc., and the base used can be chosen from Cs,COs, Na,COs, K3PO,, etc. Under suitable conditions, a compound of formula 1-4 is obtained by reducing the compound of formula 1-3. The reducing agent used can be chosen from sodium borohydride, potassium borohydride, lithium borohydride, etc., and the solvent used can be chosen from polar solvents, such as methanol, ethanol or mixed solvent of methanol and dichloromethane. A compound of formula 1-5 is obtained by acetylating the hydroxyl on the compound of formula 1-4. The compound of formula 1-5 is reacted with bis(pinacolato)diboron under suitable conditions to obtain a boracic acid or boronic acid ester compound of formula 1-6. The compound of formula 1-6 is reacted with a halide of formula 1-7 by Suzuki coupling reaction under the catalysis of appropriate palladium reagent to obtain a compound of formula 1-8. Palladium catalyzed Suzuki coupling reaction is carried out under suitable conditions. The solvent used can be chosen from polar solvents such as 1,4-dioxane, DMF, THF or mixed solvent of 1,4-dioxane and water. The base used can be chosen from Cs2C0Os, NayCOs, K3POq, etc., and the catalyst used can be chosen from Pd(dppf)Cly*CH,Cls, Pd(PPha)4, PA(OAc),, etc. A compound of formula (I-1) of the present invention is obtained by deacetylating the compound of formula 1-8 under appropriate alkaline conditions. The base used can be chosen from potassium carbonate, sodium carbonate, lithium hydroxide, etc., and the solvent used can be chosen from polar solvents, such as methanol, ethanol or mixed solvent of methanol and water. Scheme 2: %, %, Re Xe ; ; suo XA Soran, ao xx onan Hal. N. 7 2-1 7 ‘2 se ~N NR idm Reo A Ee a Tig © Re Hon oo Re hon Re ; 3% vi 13 22 (+) Ait iim Rr ren ran San Boe ann inn PY bon nanan rr vanod rm i vaman am my So po le Sa Wo Re As shown in Scheme 2, the compound of formula 1-3 is reacted with a boracic acid or boric acid ester of formula 2-1 by Suzuki coupling reaction under the catalysis of appropriate palladium reagent to obtain a compound of formula 2-2, Palladium catalyzed Suzuki coupling reaction is carried out under suitable conditions. The solvent used can be chosen from polar solvents such as 1,4-dioxane, DMF, THF or mixed solvent of 1,4-dioxane and water, the base used can be chosen from Cs:COs, NayCOs, K3POy, etc, and the catalyst used can be chosen from Pd(dppf)Cly' CHCl, Pd(PPha)s, PA(OAc),, ete. Under suitable conditions, the compound of formula (I-1) is obtained by reducing the compound of formula 2-2. The reducing agent used can be chosen from sodium borohydride, potassium borohydride, lithium borohydride, etc., and the solvent used can be chosen from polar solvents, such as methanol, ethanol or mixed solvent of methanol and dichloromethane, Scheme 3: Rs Ry A HR F o Rs o Rs | 1 4 J ! | Ry [Ne o_o o_o HN TR T Br T A) sm \ vw A _ 2 oo ATR Nr, re - Ne It oh HO. a A o Re o Re o AF Co oo 31 32 33 34 Ry ZONE SI o Rs ee 3-5 As shown in Scheme 3, the compound of formula 3-1 is subjected to a substitution reaction with bromoacetaldehyde diethyl acetal under suitable conditions to obtain a compound of formula 3-2. The base used can be chosen from cesiurn carbonate, etc., and the solvent used can be chosen [rom polar solvents such as DMF or 1,4-dioxane. The compound of formula 3-2 is hydrolyzed in an alkaline solution to obtain a compound of formula 3-3. The base used can be chosen from lithium hydroxide, potassium carbonate, sodium carbonate, etc., and the solvent used can be chosen from polar solvents, such as methanol, ethanol or mixed solvent of methanol and water, The compound of formula 3-3 is subjected to a condensation reaction with HATU and aqueous ammonia to obtain a compound of formula 3-4. The compound of formula 3-4 is subjected to ring closure in acetic acid to obtain a compound of formula 3-5. Scheme 4: A 1 o..0 N° Ry Rs Ry ZONA LH 0 Rs 3.2 3-5 Oy-© Ry Sh oR 0 Rs 32 As shown in Scheme 4, the compound of formula 3-2 can be subjected to a ring closure reaction with ammonium acetate in acetic acid to obtain a compound of formula 3-5. Scheme 5: 31 51 5.2 Scheme 5: Rq Rq Ry HN. N. = NY ZN o JE nT wo vT £20 ~ ~~ o Rs 0 Ra o Ra 31 51 5.2 As shown in Scheme 5, the compound of formula 3-1 is reacted with O-(2,4- dinitrophenyl)hydroxylamine to obtain a compound of formula 5-1. The compound of formula 5- 1 is subjected to a ring closure reaction with anunonium acetate in formamide solution to obtain a compound of formula 5-2, Scheme 6: 3. 81 8-2 MAMAN AT. Ry Ry Ry - - Zp o. Dr, EE _— es" ~~ HAN o Ry 0 Rs o Rg 341 6-1 62 As shown in Scheme 6, the compound of formula 3-1 is subjected to a substitution reaction with hydrazine hydrate to obtain a compound of formula 6-1. The compound of formula 6-1 is subjected to a ring closure reaction with triethyl orthoformate in DMF solution to obtain a compound of formula 6-2. The substituents of the compounds thus obtained can be further modified to provide other desired compounds. Synthetic chemistry transformations are described, for example. in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989): L. Fieser and M. Fieser, Fieser and Fieser 's Reagents for Organic Synthesis, John Wiley and Sons (1994); L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995) and subsequent editions thereof. Before use, the compound(s) of the present invention can be purified by column chromatography, high performance liquid chromatography, crystallization or other suitable methods. Pharmceutical Compositions and Utility The compound of the present invention herein (e.g., a compound of any of the embodiments as described herein) is used, alone or in combination with one or more additional therapeutic agents, to formulate pharmaceutical compositions. A pharmaceutical composition comprises: (a) an effective amount of the compounds of the present invention; (b) a pharmaceutically acceptable excipient (e.g., one or more pharmaceutically acceptable carriers); and optionally (c) at least one additional therapeutic agent. A pharmaceutically acceptable excipient refers (o an excipient that is compatible with active ingredients of the composition (and in some embodiments, capable of stabilizing the active ingredients) and not deleterious to the subject to be treated. For example, solubilizing agents, such as cyclodextrins (which form specific, more soluble complexes with the compounds of the present invention), can be utilized as pharmaceutical excipients for delivery of the active ingredients. Examples of other excipients or carries include colloidal silicon dioxide, magnesium stearate, cellulose, sodium lauryl sulfate, and pigments such as D&C Yellow # 10. Suitable pharmaceutically acceptable excipients are disclosed in Remington’s Pharmaceutical Sciences, A. 0sol, a standard reference text in the art, A pharmaceutical composition comprising a compound of the present invention herein can be administered in various known manners, such as orally, topically, rectally, parenterally, by inhalation spray, or via an implanted reservoir. The term “parenteral” as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques. A pharmaceutical composition described herein can be prepared in the form of tablet, capsule, sachet, dragee, powder, granule, lozenge, powder for reconstitution, liquid preparation, or suppository. In some embodiments, a pharmaceutical composition comprising a compound of the present invention herein is formulated for intravenous infusion, topical administration, or oral administration. An oral composition can be any orally acceptable dosage form including, but not limited to, tablets, capsules, emulsions, and aqueous suspensions, dispersions and solutions, Commonly used carriers for tablets include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added to tablets. For oral administration in a capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions or emulsions are administered orally, the active ingredient can be suspended or dissolved in an oily phase combined with emulsifying or suspending agents. If desired, certain sweetening, flavoring, or coloring agents can be added. In some embodiments, the compound of the present invention can be present in an amount of 1, 5,10, 15, 20, 25, 50, 75, 80, 85, 90, 95, 100, 125, 150, 200, 250, 300, 400 and 500 mg in a tablet. In some embodiments, the compound of the present invention can be present in an amount of 1, 3, 10, 15, 20, 25, 50, 75, 80, 85, 90, 95, 100, 125, 150, 200, 250, 300, 400 and 500 mg in a capsule. A sterile injectable composition (e.g., aqueous or oleaginous suspension) can be formulated according to techniques known in the art using suitable dispersing or wetting agents (for example, Tween 80) and suspending agents. The sterile injectable composition can also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the pharmaceutically acceptable vehicles and solvents that can be employed are mannitol, water, Ringer’s solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium (e.g., synthetic mono- or di-glycerides). Fatty acids, such as oleic acid and its glyceride derivatives, and natural pharmaceutically acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions, can be used as sterile injectable medium. These oil solutions or suspensions can also contain a long-chain alcohol diluent or dispersant, or carboxymethyl cellulose or similar dispersing agents. An inhalation composition can be prepared according to techniques well known in the art of pharmaceutical formulation and can be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and / or other solubilizing or dispersing agents known in the art, A topical composition can be formulated in form of oil, cream, lotion, ointment, and the like. Suitable carriers for the composition include vegetable or mineral oils, white petrolatum (white soft paraffin), branched chain fats or oils, animal fats and high molecular weight alcohols (greater than C12). In some embodiments, the pharmaceutically acceptable carrier is one in which the active ingredient is soluble. Emulsifiers, stabilizers, humectants and antioxidants may also be included as well as agents imparting color or fragrance, if desired. Additionally, transdermal penetration enhancers may be eraployed in those topical formulations, Examples of such enhancers can be found in U.S, Patent Nos, 3,989,816 and 4,444,762. Creams may be formulated from a mixture of mineral oil, self-emulsifying beeswax and water in which mixture the active ingredient, dissolved in a small amount of an oil, such as almond oil, is admixed. An example of such a cream is one which includes, by weight, about 40 parts water, about 20 parts beeswax, about 40 parts mineral oil and about 1 part almond oil. Ointments may be formulated by mixing a solution of the active ingredient in a vegetable oil, such as almond oil, with warm soft paraffin and allowing the mixture to cool. An example of such an ointment is one which includes about 30% by weight almond oil and about 70% by weight white soft paraffin. Suitable in vitro assays can be used to evaluate the effect of the compounds of the present invention in inhibiting the activity of BTK. The compounds of the present invention can further be examined for additional effects in preventing or treating cancer by in vivo assays. For example, the compound of the present invention can be administered to an animal (e.g., a mouse model) having cancer and its therapeutic effects can be accessed. If the pre-clinical results are successful, the dosage range and administration route for animals, such as humans, can be projected. The compound of the present invention can be shown to have sufficient pre-clinical practical utility to merit clinical trials hoped to demonstrate a beneficial therapeutic or prophylactic effect, for example, in subjects with cancer. As used herein, the term “cancer” refers to a cellular disorder characterized by uncontrolled or disregulated cell proliferation, decreased cellular differentiation, inappropriate ability to invade surrounding tissue, and / or ability to establish new growth at ectopic sites. The term “cancer” includes, but is not limited to, solid tumors and hematologic malignancies, such as leukemia, lymphoma or myeloma. The term “cancer” encompasses diseases of skin, tissues, organs, bone, cartilage, blood, and vessels. The term “cancer” further encompasses primary cancer, and metastatic cancer, recurrent cancer and refractory cancer. Non-limiting examples of solid tumors include pancreatic cancer; bladder cancer; colorectal cancer; breast cancer, including metastatic breast cancer; prostate cancer, including androgen- dependent and androgen-independent prostate cancer; testicular cancer; renal cancer, including, e.g. metastatic renal cell carcinoma; urothelial carcinoma; liver cancer; hepatocellular cancer; lung cancer, including, e.g., non-small cell lung cancer (NSCLC), bronchioloalveolar carcinoma (BAC), and adenocarcinoma of the lung; ovarian cancer, including, e.g., progressive epithelial or primary peritoneal cancer: cervical cancer: endometrial cancer; gastric cancer: esophageal cancer: head and neck cancer, including, e.g., squamous cell carcinoma of the head and neck; skin cancer, including, e.g., melanoma and basal carcinoma; neuroendocrine cancer, including metastatic neuroendocrine tumors; brain tumors, including, e.g., glioma, anaplastic oligodendroglioma, adult glioblastoma multiforme, and adult anaplastic astrocytoma; bone cancer; sarcoma, including, e.g., Kaposi's sarcoma; adrenal carcinoma; mesothelial carcinoma; choriocarcinoma; muscle carcinoma; connective tissue carcinoma; and thyroid carcinoma. Non-limiting examples of hematologic malignancies include acute myelogenous leukemia (AML); chronic myelogenous leukemia (CML), including accelerated phase CML and CML blastic phase (CML-BP); acute lymphocytic leukemia (ALL); chronic lymphocytic leukemia (CLL), including high risk CLL; human acute monocytic leukemia (M(5)); hairy cell leukemia; lymphocytic leukemia; chronic lymphoid leukemia; myelogenous leukemia; myelodysplastic syndrome or acute lymphoblastic leukemia; small lymphotic lymphoma (SLL), lymphoblastic lymphoma, and Hodgkin's lymphoma; non-Hodgkin's lymphoma (NHL); follicular lymphoma; mantle cell lymphoma (MCL); B-cell lymphoma; T cell lymphoma; diffuse large B-cell lymphoma (DLBCLY); large B-cell lymphoma (LBCL); follicular lymphorna, marginal zone lymphoma, Burkitt's lymphoma, non-Burkilt’s highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma; multiple myeloma (MM); Waldenstrom macroglobulinemia; myelodysplastic syndrome (MDS), including refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory anemia with excess of blast (RAEB) and refractory anemia with excess blasts in transformation (RAEB-T); and myeloproliferative syndrome. In some embodiments, hematologic malignancy is recurrent or refractory diffuse large B- cell lymphoma (DLBCL), recurrent or refractory mantle cell lymphoma, recurrent or refractory follicular lymphoma, recurrent or refractory CLL, recurrent or refractory SLL, and recurrent or refractory multiple myeloma, The compound of the present invention can be used to achieve a beneficial therapeutic or prophylactic effect, for example, in subjects with cancer. The compound of the present invention can be used to achieve a beneficial therapeutic or prophylactic effect, for example, in subjects with an autoimmune disease, or in subjects with inflammatory diseases. The term “autoimmune disease” refers to a disease or disorder arising from and / or directed against an individual’s own tissues or organs, or a co-segregate or manifestation thereof, or resulting condition therefrom, Examples of autoimmune diseases include, but are not limited to: chronic obstructive pulmonary disease (COPD), allergic rhinitis, lupus erythematosus, myasthenia gravis, Sjogren syndrome, multiple sclerosis (MS), scleroderma (also referred to as systemic sclerosis), multiple sclerosis osteoporosis, arthritis (such as rheumatoid arthritis (RA), and collagen-induced arthritis), psoriasis, inflammatory bowel disease, asthma, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary discase, sicca syndrome, pemphigus valgaris, and diseases associated with kidney transplantation and myeloproliferative disease, such as myelofibrosis, and post-polycythemia vera / essential thrombocytosis myelofibrosis (post-PV / ET myelofibrosis). In some embodiment, autoimmune disease is chosen from arthritis, such as, rheumatoid arthritis (RA), collagen induced arthritis, and the like. The term “inflammatory disease” or “inflammatory condition” refers to a pathological state that leads to inflammation, especially due to neutrophil chemotaxis. Non-limiting examples of inflammatory diseases include systemic inflammation and local inflammation, inflammation associated with immunosuppression, organ-graft refection, allergic disease, inflammatory skin disease (including psoriasis and atopic dermatitis); systemic scleroderma and sclerosis; reactions associated with inflammatory bowel diseases (IBD, such as Crohn's disease and ulcerative colitis); ischemia reperfusion injury, including reperfusion injury of tissue caused by surgery, myocardial ischemia, such as myocardial infarction, cardiac arrest, reperfusion after heart operation and abnormal contractile response of coronary vessel after percutaneous transluminal coronary angioplasty, surgical tissue reperfusion injury of stroke and abdominal aortic aneurysm; cerebral edema secondary to stroke; cranial injury, and hemorrhagic shock; suffocation; adult respiratory distress syndrome; acute lung injury; Behcet's disease; dermatomyositis; polymyositis; multiple sclerosis (MS); dermatitis; meningitis; encephalitis; uveitis; osteoarthritis; lupus nephritis; autoimmune disease such as rheumatoid arthritis (RA), Sjorgen’s syndrome, and vasculitis; diseases involving leukopedesis; septicemia or central nervous system (CNS) inflammatory disease secondary to trauma, and multiple organ injury syndrome; alcoholic hepatitis; bacterial pneumonia; antigen-antibody complex mediated disease, including glomerulonephritis; pyaemia; sarcoidosis; immunopathologic responses to tissue / organ transplantation; lung inflammation, including pleurisy, alveolitis, vasculitis, pneumonia, chronic bronchitis, bronchiectasia, diffuse panbronchiolitis, hypersensitivity pneumonitis, idiopathic pulmonary fibrosis (IPF), cystic fibrosis, etc. Preferably indications include, but are not limited to, chronic inflammation, autoimmune diabetes, rheumatoid arthritis (RA), rheumatoid spondylitis, gouty arthritis and other arthrosis conditions, multiple sclerosis (MS), asthma, systemic lupus erythematosus, adult respiratory distress syndrome, Behcet’s disease, psoriasis, chronic pulmonary inflammatory disease, graft versus host reaction, Crohn’s disease, ulcerative colitis, inflammatory bowel disease (IBD), Alzheimer’s disease and pyresis, and any diseases associated with inflammation and related conditions. In addition, the compounds of the present invention (e.g., a compound of any of the embodiments as described herein) can be administered in combination with additional therapeutic agents for the treatment of diseases or disorders described herein, such as cancer, an inflammatory disease or autoimmune disease. The additional active ingredients may be administered separately with the compound of the present invention or included with such an ingredient in a pharmaceutical composition according to the disclosure, such as a fixed-dose combination drug product. In some embodiments, additional active ingredients are those that are known or discovered to be effective in the treatment of diseases mediated by BTK or at least in part by BTK, such as another BTK inhibitor or a compound active against another target associated with the particular disease. The combination may serve to increase efficacy (e.g., by including in the combination a compound potentiating the potency or effectiveness of the compound of the present invention), decrease one or more side effects, or decrease the required dose of the compound of the present invention. In some embodiments, the compounds of the present invention (such as any compound herein) can be administered in combination with additional therapeutic agents, such as anti- inflammatory agents, immunomodulators or anti-tumor active agents, wherein the anti-tumor active agents include chemotherapeutic agents, immune checkpoint inhibitors or agonists, and targeted therapeutic agents. The term “anti-tumor active agent” as used herein refers to any agent that is administered to a subject suffering from cancer for the purposes of treating the cancer, such as a chemotherapeutic agent, an immune checkpoint inhibitor or agonist, and a targeted therapeutic agent, Non-limiting examples of chemotherapeutic agents include topoisomerase I inhibitors (e.g., irinotecan, topotecan, camptothecin and analogs or metabolites thereof, and doxorubicin); topoisomerase 11 inhibitors (e.g., etoposide, teniposide, mitoxantrone, idarubicin, and daunorubicin); alkylating agents (¢.g., melphalan, chlorambucil, busulfan, thiotepa, ifosfamide, carmustine, lomustine, semustine, streptozocin, decarbazine, methotrexate, mitomycin C, and cyclophosphamide); DNA intercalators (e.g., cisplatin, oxaliplatin, and carboplatin); and free radical generators such as bleomycin; nucleoside mimetics (e.g., 3-fluorouracil, capecitabine, gemcitabine, fludarabine, cytarabine, azacitidine, mercaptopurine, thioguanine, pentostatin, and hydroxyurea); paclitaxel, docetaxel, and related analogs; vincristine, vinblastin, and related analogs; thalidomide and related analogs (e.g., CC-5013 and CC-4047), Non-limiting examples of immune checkpoint inhibitors or agonists include PD-1 inhibitors, for example, anti-PD-1 antibodies, such as pembrolizumab and nivolumab; PD-L1 inhibitors, for example, anti-PD-L1 antibodies, such as atezolizumab, durvalumab, and avelumab; CTLA-4 inhibitors, such as anti- CTLA-4 antibody, for example ipilimumab; and BTLA inhibitors, LAG- 3 inhibitors, TIM3 inhibitors, TIGIT inhibitors, VISTA inhibitors, OX-40 agonists, and the like, Targeted therapeutic agents include various small molecule or macromolecular targeted therapeutic agents, and non-limiting examples thereof include: protein tyrosine kinase inhibitors (such as imatinib mesylate and gefitinib); proteasome inhibitors (such as bortezomib); NF-kB inhibitors, including IkB kinase inhibitors; PI3K8 inhibitors; SYK inhibitors; Bel2 inhibitors; antibodies that bind to proteins overexpressed in cancer to down-regulate cell replication, such as anti-CD20 antibody (such as rituximab, ibritumomab tiuxetan, and tositumomab), anti-Her2 monoclonal antibody (trastuzumab), anti-EGFR antibody (cetuximab) and anti-VEGFR antibody (bevacizumab); anti-angiogenic drugs, such as lenalidomide; and other protein or enzyme inhibitors, these proteins or enzymes are known to be upregulated, overexpressed or activated in cancers, and the inhibiting on them can down-regulate cell replication, EXAMPLES The examples below are intended to be purely exemplary and should not be considered to be limiting in any way. Efforts have been made to ensure the accuracy with respect to numbers used (for example, amounts, temperature, etc.), but those skilled in the art should understand that some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric, All MS data were determined by Agilent 6120 or Agilent 1100. All NMR data were generated using a Varian 400 MR machine. All reagents and materials, except synthesized intermediates, used in the present invention are commercially available. The reference GDC- 0853 (fenebrutinib) was purchased from Shanghai Linkchem Medical Technology Co., Ltd. All compound names except the reagents are generated by Chemdraw 16.0. If there is any atom with empty valence(s) in any one of the structures disclosed herein, the empty balance(s) is (are) the hydrogen atom(s) which is (are) omitted for convenience purpose. In the present application, in the case of inconsistency of the name and structure of a compound, when the two of which are both given for the compound, it is subject to the structure of the compound, unless the context shows that the structure of the compound is incorrect and the name is correct. In the following examples, the abbreviations are used: Ac Acetyl AcOK Potassium acetate BINAP Bis-(diphenylphosphino)-1,1'-binaphthyl CDI N,N'-carbonyldiimidazole CD,OD Deuterated methanol DCM Dichloromethane DIAD Diisopropyl azedicarboxylate DIEA N N-diisopropylethylamine DMF N,N-dimethylformamide DMSO Dimethyl sulfoxide DMSO-d¢ Deuterated dimethyl sulfoxide EA / EtOAc Ethyl acetate EtN Triethylamine EtOH Ethanol g Gram HATU 2-(7-azabenzotriazole)-N,NN',N'-tetramethyluronium hexafluorophosphate HMDSLI Lithium hexamethyldisilazide L Liter M Mole / liter MeOH Methanol mg Milligram mL Milliliter mmol Millimole mol Mole NBS N-bromosuccinimide Pdy(dba)s Tris(dibenzylidene acetone)dipalladium Pd(dppf)Cl, CHCl [1,1'-bis(diphenylphosphino) ferrocene Jpalladium dichloride dichloromethane complex PE Petroleum ether TFA Trifluoroacetic acid THF Tetrahydrofuran Xphos 2-dicyclohexylphosphine-2',4',6'-triisopropyl biphenyl Xant-phos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene Example 1 Synthesis of Compounds Intermediate 1-1 4-chloro-2-(1-0x0-1,6,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2- yDnicotinaldehyde Step 1 # $ hg Sept Co B®P2 No _Swps eo eT cl { we 4 fy \.¢ 0 oO anep 4 ns op § oy ———— \ —— x ~~ Pl i mn a , CIO A SL £Yy o— / Step 4 NO Step \ Lk « No Vd wf Vo { ~ al / ~~ 7 NH ~~ I So x. N Q Step 8 Neem Step 5 Ny Y c Step 7 A pl 7 NA ap 8 3 —— Cie NS RE of — \ x8 £2 o pe jp i hi ena 1-1 Step 1: 2-chlorocyclopentan-1-ene-1-carbaldehyde At 0-5°C, phosphorus oxychloride (4.45 mL, 47.7 mmol) was dropwise added to DMF (4.6 mL, 59.6 mmol) under nitrogen. The reaction solution was stirred at 0-5°C for 10 minutes, and then further stirred at room temperature for 15 minutes. Cyclopentanone (2.5 g, 29.8 mmol) was dropwise added to the above-mentioned reaction solution at 0-5°C, which was reacted at room temperature for 1 hour, and then poured into ice water (the pH value was adjusted to 5 with an aqueous sodium carbonate solution), and 100 mL of water was added. The reaction solution was extracted with petroleum ether / ethyl acetate = 10 / 1 (100 mL x 2), and the organic phase was collected and combined, washed with saturated brine (100 mL), dried with anhydrous sodium sulfate, and concentrated to give the target product (2.4 g, yield 62%), which was directly used in the next step. Step 2: (E)-3-(2-chlorocyclopenta-1-ene-1-yl)ethyl acrylate Under nitrogen, 2-chlorocyclopentan-1-ene-1-carbaldehyde (2.4 g, 18.4 mmol) and cthoxy(formylmethylene)triphenylphosphorane (6.4 g, 18.4 mmol) were placed in dichloromethane (30 mL), which was reacted at the reflux temperature for 6 hours. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (3.3 g, yield 89%). [M+H]" 201.1 Step 3: Ethyl 1.4,5,6-tetrahydrocyclopentadieno[bd|pyrrole-2-carboxylate Under nitrogen, to a solution of (E)-3-(2-chlorocyclopenta-1-ene-1-yl)ethyl acrylate (3.3 g, 16.5 mmol) in DMSO (20 mL) was added sodium azide (1.6 g, 24 mmol), which was reacted at 65°C for 16 hours, Water (200 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (50 mL x 2). The organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (700 mg, yield 24%). [M-+H]" 180.1. 'H NMR (400 MHz, CDCl): 5 8.81 (s, 1H), 6.65 (s, 1H), 4.30- 4.26 (m, 2H), 2.75-2.55 (m, 4H), 2.42-2.40 (m, 2H), 1.35-1.31 (m, 3H). Step 4: Ethyl 1-(2,2-diethoxyethyl)-1,4,5,6-tetrahydrocyclopentadieno[b]pyrrole-2- carboxylate To a solution of ethyl 1,4,5,6-tetrahydrocyclopentadieno[b]pyrrole-2-carboxylate (700 mg, 3.9 mmol) in DMF(5 mL) was added cesium carbonate (3.2 g, 9.7 mmol) and bromoacetaldehyde diethyl acetal (1.55 g, 7.8 mmol), which was reacted at 100°C for 16 hours. Water (50 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL x 2). The organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (1.0 g, yield 92%). [M+Na]" 318.1 Step 5: 1-(2,2-diethoxyethyl)-1,4,5,6-tetrahydrocyclopentadieno[5]pyrrole-2-carboxylic acid To a solution of ethyl 1-(2,2-diethoxyethyl)-1,4,5,6-letrahydrocyclopentadieno[b]pyrrole-2- carboxylate (1.0 g, 3.6 mmol) in ethanol (10 mL) and water (10 mL) was added lithium hydroxide monohydrate (650 mg, 14.4 mmol), which was reacted at 80°C for 12 hours. Ethanol was removed in vacuum under reduced pressure, and the pH was adjusted to 5-6 with concentrated hydrochloric acid, and water (20 mL) was added, The reaction solution was extracted with ethyl acetate (20 mL x 2), the organic phase was collected and combined, dried with anhydrous sodium sulfate, and concentrated to give the target product (800 mg, yield 83%). [M-H] 266.1 Step 6: 1-(2,2-diethoxyethyl)-1.4,5,6-tetrahydrocyclopentadieno[5]pyrrole-2-carboxamide At 0-5°C, under nitrogen, to a solution of 1-(2,2-diethoxyethyl)-1,4,5,6- tetrahydrocyclopentadieno[ b]pyrrole-2-carboxylic acid (800 mg, 3 mmol) in DMF(S mL) was added triethylamine (0.84 mL, 6 mmol) and HATU (1.7 g, 4.5 mmol). After reacting at room temperature for 30 minutes, the reaction solution was poured into concentrated aqueous ammonia (20 mL) and stirred for 10 minutes. Water (20 mL) was added, the reaction solution was extracted with dichloromethane (20 mL x 2), and the organic phase was collected and combined, and concentrated to give the target product (1.0 g, yield 125%), which was directly used in the next step. Step 7: 7,8-dihydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one 1-(2,2-diethoxyethyl)-1,4,5,6-tetrahydrocyclopentadieno[ b]pyrrole-2-carboxamide (1.0 g, 3.75 mmol) was dissolved in acetic acid (10 mL), which was reacted at 100°C for 4 hours (acetic acid was removed in vacuum under reduced pressure, the pH value was adjusted to 8 with aqueous ammonia), water (20 mL) was added, and the mixture was extracted with dichloromethane (20 mL x 2). The organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (dichloromethane / methanol) to give the target product (600 mg, yield 92%). [M+H]" 175.1 Step 8: 4-chloro-2-(1-oxo0-1,6,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]|pyrazin-2- yDnicotinaldehyde Under nitrogen, to a solution of 7,8-dihydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin- 1(6H)-one (600 mg, 3.5 mmol) and 2-bromo-4-chloronicotinaldehyde (1.1 g, 5.1 mmol) in 1,4- dioxane (30 mL) was added cuprous iodide (665 mg, 3.5 mmol), 4,7-dimethoxy-1,10- phenanthroline (580 mg, 2.45 mmol) and cesium carbonate (2.2 g, 7.0 mmol). The mixture was reacted at 90°C for 12 hours, and then cooled to room temperature. The mixture was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (400 mg, yield 37%). [M+H]" 314.0 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediate I-1: Intermedi Structural formula LC-MS ate [M+H]” | ss la EO [3420 | @ NN Lo, ani fr m—————— —- ~ Co [343.0 [kes jo CX TT 7 AQ os [= NN © ) [1-77 aaa [328.0 ne E aN = ln & TTT = TN [179 [en fo Fm [3420 20 Ay ( GS ; zN 0 mn — | 1-80 | 330.0 ee e—— 0 A \ 0 E cod lv 0 1-84 - [bss oa LED asst 0 El oN =x, lho [roo Ja LAX a LAID [3281 0 ZN A = | @ NN = (n o cere r——————— | 1.95 NT 2» oN Ae | 19s | ong fe 341.8 —~ ~ oN SA | & = ow | 1-96 | a ANS | 338.0 20 ZN | Cl NN = | zN © | 1-98 386.0, 388.0 © An [SF 3 lL J N Intermediate I-2 (5-((5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-1-methyl-6- 0x0-1,6-dihydropyridin-3-yl)boracic acid HN : ON Ey Step 1 eh Step 2 wz, TN x Step 2 EN a Boon Supt AEN ey 7 Po iS l ’ “NNO, A ww Pore, ne Is ° iS 1} Step 3 TNT Step NT SERS es Sy Send, Aen wn » 1 SN no, Po | py! HN Ree ge On ~ N Step 5 WJ Step 6 —_— NT —_— ® al \ N 12 Step 1: t-butyl (2R,58)-2,5-dimethyl-4-(6-nitropyridin-3-yl)piperazin-1-carboxylate Under nitrogen, to a solution of S-bromo-2-nitropyridine (7.0 g, 32.7 mmol) and t-butyl (2R,58)-2,5-dimethylpiperazin-1-carboxylate (10.0 g, 49.0 mmol) in 1,4-dioxane (150 mL) was added Xant-phos (3.8 g, 0.64 mmol), Pda(dba); (3.0 g, 0.32 mmol) and cesium carbonate (21.3 g, 65.3 mmol). The mixture was reacted at 100°C for 16 hours, and then cooled to room temperature. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product. [M+H] 337.1 Step 2: (2R,58)-2,5-dimethyl-1-(6-nitropyridin-3-yl)piperazine Under nitrogen, to a solution of t-butyl (2R,55)-2,5-dimethyl-4-(6-nitropyridin-3- yl)piperazin-1-carboxylate obtained from step 1 in methanol (10 mL) was added concentrated hydrochloric acid (3 mL). The reaction was stirred at room temperature for 30 minutes, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product (3.3 g, two-step yield 43%). [M+H]™ 237.1 Step 3: (28,5R)-2,5-dimethyl-1-(6-nitropyridin-3-yl)-4-(oxetan-3-yl)piperazine Under nitrogen, to a solution of (2R,58)-2,5-dimethyl-1~(6-nitropyridin-3-yl) piperazine (3.3 g, 14.0 mmol) and oxetan-3-one (3.1 g, 42.0 mmol) in methanol (20 mL) was added zinc chloride (5.7 g, 42.0 mmol) and sodium cyanoborohydride (2.6 g, 42.0 mmol). The reaction was stirred at 50°C for 5 hours, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product (3.3 g, yield 80%). [M+H]" 293.1 Step 4: 5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-amine At room temperature, to a mixture of (28,5R)-2,5-dimethyl-1-(6-nitropyridin-3-yl)-4- (oxetan-3-yl)piperazine (3.3 g, 11.3 mmol) and 10% palladium-carbon (with 50% water, 400 mg) in methanol (50 mL) was introduced with hydrogen, which was reacted at room temperature for 12 hours. The reaction solution was filtered, and the filtrate was collected, and concentrated in vacuum under reduced pressure to give the target product (2.94 g, yield 99%), which was directly used in the next step. [M+H]" 263.1 Step 5: 5-bromo-3-((5-((28,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2- yl)amino)-1-methylpyridin-2(1H)-one Under nitrogen, to a solution of 5-((28,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1- yl)pyridin-2-amine (2.94 g, 11.2 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (3.0 g, 11.2 mmol) in 1,4-dioxane (150 mL) was added Xant-phos (325 mg, 0.56 mmol). Pda(dba); (515 mg, 0.56 mmol) and cesium carbonate (7.3 g, 22.5 mmol), The mixture was reacted at 100°C for 16 hours, and then cooled to room temperature. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / dichloromethane) to give (4.7 g, yield 93%). [M+H]" 448.1, 450.0 Step 6: (5-((5-((28,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amine)-1- methyl-6-0x0-1,6-dihydropyridin-3-yl)boracic acid Under nitrogen, to a solution of 5-bromo-3-((5-((2S,5R)-2,5-dimethyl-4-(oxetan-3- yl)piperazin-1-yl)pyridin-2-yl)amino)- 1-methylpyridin-2(1 H)-one (4.7 g, 10.5 mmol), bis(pinacolato)diboron (13.3 g, 52.4 mmol) in 1,4-dioxane (200 mL) was added Xphos (500 mg, 1.05 mmol), Pdy(dba); (480 mg, 0.52 mmol) and potassium acetate (3.0 g, 31.4 mmol). The mixture was reacted at 60°C for 16 hours, and then cooled to room temperature. The reaction solution was filtered, and the filtrate was collected and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target compound (2.3 g, yield 53%). [M+H]™ 414.2 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediate 1-2: Intermediate | Soca! LC-MS | mediate | Structural LC-MS lili formula [M+H]* formula [M+H]* 7 N ZN | 7 5 |40s.1 [1m | 4 420.1, EN | NG 422.1 — > / =N N | TL J HN XA" Ng I 434.1 [be NT fs (Oh [3460 1 aN 436 1 N 434.1, 436.1 SN | HN Ng A £ il 3 ARAN, SN HN’ | 18 | Ay ¢ 3041 [133 ® | ee \ ~N | On Noy ’ AY oN ey» | 5H pel | 1-54 5 | 4823 | 1-56 NS gH | 2611 | dy N on ) J ov 17% EE ne, | 57 | Sg OH | 246.0 4 | TL | HN x Ca a OH If [167 er oC [47122 | 169 | mS eo 3321 Jl He [173 | So | 327.1 | 176 5H OH [178 @ oh | 485.3 | 1134 $8 | 3480 | 1134 | XL | HN x 5H OH £3 N \ MM NN 7 N— £ |< \ | OL | NG NC | OH | 1136 On on | 3460 | 1144 § bi N \ oN ! pel N | mn J Io Re 3 373.0 [1-145 MEX |3450 [1146 NN ” [439.0 ° A ! pe ) ) | a! I~ — le | 1-145 | he |3450 [1146 J one 1" XL - yyy ve ON ON. | 41 ao HN 0 Z N OH ASN 0. | | L162 N | 414.0 1-166 SN 496.2 4, N. “9 AVL & 0 HN Sp 0, Ney | xn [1-167 N 4962 | 1168 od 293.1 | a, oe Na | 1-167 De | 496.2 | 1-168 | " N | 293.1 ig. 1s) | ~ ) &) S Boc oO _— NH. | L169 | oN £) [266.1 [1170 a 3 | ae | 249.1 1-171 " | |2231 [172 < Coy [267.0 | eon OH S Oo NH, AN i ¢ NH xX “ZN 2 L173 | oN 267.0 [1174 @: 249.1 | ©) | | ds PN a OH OH | 1-175 | , N 250.2 -176 N. 264.2 ©) | ’ | & | “®) | o 0 &S -177 | N 236 78 220 [1 1 | r N | 5 | 1-1 he PAN | 1 NH; NL J NH, Q o 1179 HAN ) gh |2470 [1180 | AN [2611 & 0 “ hd Ne, Ne ZN ZN A [L181 } A |2351 [1182 A [234.1 | 235.1 Ces Cs , 0, N . | |1 183 "®) | 263.1 1-184 | & | 247.1 © © oN a 15 J 5 | 1185 Lon he |249.1 [1186 CY 483.3 Intermediate 1-3 S-bromo-3-((5-ethyl(2-methoxyethyl)amino)pyridin-2-yl)amino)-1-methylpyridin-2(1H)- Step 1 J Step 2 NO, Cs . HNL NO; 7X i N vg? F So So | Og No, i oak ~ Step + Step 3 A P eee J Xi J oN oN ~ So So Step 1: N-(2-methoxyethyl)-6-nitropyridin-3-amine To a solution of 5-fluoro-2-nitropyridine (4.26 g, 30 mmol) and 2-methoxyethylamine (2.48 8, 33 mmol) in DMSO (30 mL) was added triethylamine (21.2 g, 210 mmol). The mixture was reacted at 100°C for 4 hours, and then cooled to room temperature. The reaction solution was poured into water (200 mL), and extracted with ethyl acetate (200 mL x 2). The organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / dichloromethane} to give the target product (5.92 g, yield 100%). [M+H]™ 198.1 Step 2: N-ethyl-N-(2-methoxyethyl)-6-nitropyridin-3-amine At 0-5°C, under nitrogen, to a solution of N-(2-methoxyethyl)-6-nitropyridin-3-amine (986 mg, 5.0 mmol) in DMF (10 mL) was added 60% sodium hydride (mineral oil dispersion) (240 mg, 6.0 mmol), and stirred at this temperature for 1 hour. Bromoethane was added to the mixture, and the mixture was reacted at 60°C for 2 hours, and cooled to room temperature, The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was dissolved in dichloromethane (100 mL), and washed with water (50 mL). The organic phase was collected, and concentrated in vacuum under reduced pressure to give the target product (1.13 g, yield 100%), which was directly used in the next step. [M+H]" 226.1 Step 3: N'-ethyl-N’-(2-methoxyethyl)pyridin-2,5-diamine p y vethyl)py At room temperature, to a mixture of N-ethyl-N-(2-methoxyethyl)-6-nitropyridin-3-amine (1.13 g, 5.0 mmol) and 10% palladium-carbon (with 50% water, 200 mg) in methanol (20 mL) was introduced with hydrogen, which was reacted at room temperature for 16 hours. The reaction solution was filtered, and the filtrate was collected and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product (875 mg, yield 90%). [M+H]" 196.1 Step 4: 5-bromo-3-((5-ethyl(2-methoxyethyl)amino)pyridin-2-yl)amino)-1-methylpyridin- 2(1H)-one Under nitrogen, to a solution of N'-ethyl-N"-(2-methoxyethyl)pyridin-2,5-diamine (195 mg, 1.0 mmol), 3,5-dibromo-1-methylpyridin-2(14)-one (267 mg, 1.0 mmol) in 1,4-dioxane (5 mL) was added Xant-phos (58 mg, 0.1 mmol), Pdx(dba); (92 mg, 0.1 mmol) and cesium carbonate (652 mg, 2.0 mmol), The mixture was reacted at 100°C for 16 hours, and then cooled to room temperature. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / dichloromethane) to give the larget product (257 mg, yield 67%). [M+H]" 381.1, 383.1 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediate 1-3: | Intermediate Structural LC-MS | Intermediate Structural LC-MS formula [M+H] formula [M-+H] HN” gr 312.0, HN” 7c) | 1-8 A 213 0 | 1-9 A 269.0 312.0, 313.9 [L J AN Br re 436.1, ye 379.0, |r-10 ot |= 12 S$ 381.0 LN | &) ou 352.0, 354.0 | =A OL NON , nn Sy, HN’ Br HN Cl 352.0, | L17 be | 1310 1-19 j& | 390.0 \ \ |e rl W— / Bod —~N ~—N / =N [120 a | 278.0 | 21 Mra | 264.0 XL, J HN Sg Au |< Fa [1-22 N | 5% Wi ON Jos | 1:23 CN | 400.1 434.9, 436.9 | 124 J | 3911 | 125 $i 481.4, ) . ’ “ N 463.1 Ne oT HN™ "gr 293.0, HN "cl 5 -27 5. | 1-26 1 A 200 0 | 1-2 | A 255.0 HN SN Au 298.0, 300.0 0202020202020 1 | - 0 | 392.1, | 12 ws, | 2840, 394.1 | Ay 286.0 | A Nn Hr fs | 30 ate | 2410 136 Oo [| A 245.0, 247.0 | ps) J > i RG | | x | 10 YL 245.0, = Ho Br 365.0, 2c Br 247.0 < 367.0 N # [= AN An 367.0 1-49 O 5072 | 150 | S | ’ xX | p, | | 369.0 | L | HN > Br ZN S | | “NS So -—_ ye AN 395.1, | I-51 Cl | 297 1 | 1-81 395.1, ZN 437.1, 1-81 | | 397.1 | } 0 | 439.1 So 4. 0; N 1 x 283.0, N 297.0, I-1 HN Br 1-101 HN Br oo we ; ily | N") | ¥ J MN > | 1 | F102 | | a |1-103 we me ZN Md ZEN 10s NS 295.0, [1105 aos, 283.0, An 297.0 CA 285.0 295.0, 297.0 | AN | | | 106 as, | 2840, [1.109 | Sg | 298.0, LA 286.0 Au 300.0 J 448.1 $i 435.1 | 110 SN | oo 1111 S | oo 4 450.1 a 1 437.1 “ZN ZN 448.1 417.1 | 1-112 J : 1-113 0 : i 450.1 ir 419.1 & oO | | HN Xp, 382.1, 384.1 SN 382.1 oN 403.1 [115 i Cen O ’ | N | 384.1 | # 405.1 i. | wn NL Ny. N— / / Q |< nn], 1S 446.1 396.1 > N i § A, 2 (0! 1, 17 l | | oy 398.1 | NN x / Q \ | TL J HN Xp, | HNN pr A N £ £ yy \ 396.1, 398.1 / Q \ ae Br 394.1 Sn 396.1 -119 ON ’ 1-120 jo ’ | Mn | 396.1 | N 398.1 rs ) N— N — 4 / oO RY 1 aN ur 380.0, 1-122 oN ’ 1-123 | fr | 382.0 | 294.0, 296.0 | TL | HN x Br ! N £ / \ I 1124 HNN, 310.0, [1130 | Cy 391.0, } A 312.0 . 393.0 pp, J | L131 moss |3270, | Se 325.0 L132 - 3200 | On 327.0 ! i OL | HN pS Br Le | 7 No A - 366.1 noe 352.0 ZN 1, ~ 2.0, | 133 | e: | 368.0 | 13s On | 354.0 \ oN OL ) AN Br NSA 311.0, | 3s L 378.1, | 137 A 313.0 _ 380.1 | HN x Br ! N yo» £ *% id” AN Br 1 [1139 & ‘ | 364.0, [L140 NS | 207.0, \ N 366.0 A 299.0 AN | Ned |< ANN Sg 311.0, | 18 x By | no | I-14 A 313.0 ¢) 4 N-N / [of i / HN > “Br 3 AN = Br 27.0 379.0, 1-143 7 ’ 1-147 AN ’ | 0 | 329.0 | 0 | 381.0 af ro oN | whe 1-148 XJ, 367.0, || 149 o 448.1, je oo "1369.0 |= a 0s 0 nn ~~ |3s00 1) 435.1 NPN : - 3 x | 1-150 J | 382.0 [1151 | YX a | CR 4207 $i | F152 SM “0 | 1-153 N | 405.1 4227 Lok | rn, oN | YL | HN" aS Br “ZN [115s ¢ 448.1, cn 449 ln NL 450.1 | 1s YX > Lak 451.1 | J HN XA Ng, ~~ °N CN j 436.1 450.1 1-156 UJ Cs UJ ’ | [ A | 2 | [ oN 452.1 nN nN oo oo ¢ 462.1 SO 380.2 L158 SN | 1159 AN = | io | 464.1 | Ct 3822 a Ee LA i oh aXe 1 “ [160 Cr 435.1, [1161 Se 393.8, i 437.1 oH 5 ) LN 395.8 ! 8 So ’ a ~N 450.1, 450.1, | 1-163 Y | his 1 | ict 5 | 452.1 [ No . NN : Sn ! Ou | 1-187 424.1, 426.1 | XL | HN Sar A N ~ ™ W _ / Bod Intermediate 1-4 (3-(acetoxymethyl)-2-(7,7-dimethyl-1-0x0-1,6,7,8-tetrahydro-2 H- cyclopenta[4,5]pyrrolo[1,2-4]pyrazin-2-yl)pyridin-4-yl)boracic acid Lav On J Cl A NA ZNO cyclopental[4,5]pyrrolo[1,2-a]pyrazin-2-yl)pyridin-4-yl)boracic J Lo #0 nS Step 1 ron 1T Step 2 ci Jk 1D a A NL —_— Ny CS To IY ry 155 OH Step 3 PLIYSN for Os ory on er - ok N= il ry k (un © fd Step 1: 2-(4-chloro-3-(hydroxymethyl)pyridin-2-yl)-7,7-dimethyl-7.8-dihydro-2 H- cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one At 0-5°C, under nitrogen, to a solution of 4-chloro-2-(7,7-dimethyl-1-0x0-1.6,7,8- tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl) nicotinaldehyde (1.71 g, 5.0 mmol) (intermediate I-55) in methanol (5 mL) and dichloromethane (15 mL) was added sodium borohydride (0.13 g, 3.5 mmol), and the mixture was reacted at this temperature for 10 minutes, A saturated aqueous ammonium chloride solution (5 mL) was added to the reaction solution, and the mixture was extracted with dichloromethane (30 mL x 2). The organic phase was collected and combined, and concentrated in vacuum under reduced pressure to give the target product (1.72 g, yield 100%), which was directly used in the next step, [M+H]™ 344.1 Step 2: Acetic acid (4-chloro-2-(7,7-dimethyl-1-0x0-1,6,7,8-tetrahydro-2H- cyclopenta[4.5]pyrrolo[1,2-¢] pyrazin-2-yl)pyridin-3-ylymethyl ester At 0-5°C, under nitrogen, to a solution of 2-(4-chloro-3-(hydroxymethyl)pyridin-2-y1)-7,7- dimethyl-7,8-dihydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one (1.72 g, 5.0 mmol) and triethylamine (2.53 g, 25 mmol) in dichloromethane (30 mL) was added acetylchloride (1.18 8, 15 mmol), and the mixture was reacted at this temperature for 1 hour, Water (20 mL) and dichloromethane (30 mL) were added to the reaction solution, the organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (1.65 g, yield 86%), [M+H]™ 386.1 Step 3: (3-(acetoxymethyl)-2-(7,7-dimethyl-1-0x0-1,6,7,8-tetrahydro-2H- cyclopenta|4,5|pyrrolo[1,2-a]pyrazin-2-yD)pyridin-4-yl)boracic acid Under nitrogen, to a solution of acetic acid (4-chloro-2~(7,7-dimethyl-1-0x0-1,6,7,8- tetrahydro-2H-cyclopenta[4,3]pyrrolo[1,2-a]pyrazin-2-yl)pyridin-3-yl)methyl ester (3.0 g, 7.79 mmol), bis(pinacolato)diboron (5.9 g, 23.3 mmol) in 1,4-dioxane (120 mL) was added Xphos (333 mg, 0.7 mmol), Pd(dppf)Cl> CH,Cl, (570 mg, 0.7 mmol) and potassium acetate (2.3 g, 23.3 mmol). The mixture was reacted at 30°C for 16 hours, and then cooled to room temperature. The reaction solution was concentrated in vacuwm under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product (2.9 g, yield 94%). [M+H] 396.1 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediate 1-4: LC-MS Intermediate | Structural formula LO oF OH (TT NTNT | I-114 | CR | 397.1 or (NS | Ho™B N N. x, ZN O EF L OH NTN [2 FNC [411.1 on 8 | Hort = AN © reese eer uA “IN [1129 wort ANAT | 268.1 | TT ~~ on PM | Ho SNS ln & Intermediate 1-5 5-bromo-3-((1-ethyl-1H-1,2,3-triazole-4-yl)amino)-1-methylpyrazin-2(1 H)-one NH, m————————— An \ N-N / ON TL HN N Br An ) N-N / 1-5 Under nitrogen, 3,5-dibromo-1-methylpyrazin-2(1H)-one (3.0 g, 18.7 mmol) and 1-ethyl- 1H-1,2,3-triazole-4-amine (2.1 g, 18.7 mmol) were dissolved in N-methylpyrrolidone (7 mL). The mixture was reacted at 120°C for 3 hours, and cooled to room temperature. The mixture was filtered, and the filter cake was washed with methanol (5 mL), to give the target product (3.9 g, yield 50%). [M+H]™ 299.0, 301.0 The intermediate in the following table was prepared with corresponding materials and reagents according to the preparation steps of intermediate I-5: LC-M | Intermediate | Structural formula pe NE 313.0,315.0 | 6 be | | wef aN OOOOOOOOOOOOO__________4 Intermediate 1-13 (S)-5-bromo-1,6-dimethyl-3-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2- yl)amino)pyridin-2(1H)-one | YY HN [yt Br OQ 0 ? St B i 1 & Step 1 es Stepz Br Aye NH ———— i —_— N LAL A ar re Br Br & 1-13 Step 1: 3,5-dibromo-6-methylpyridin-2(1H)-one Under nitrogen, to a solution of 6-methylpyridin-2(1H)-one (949 mg, 8.7 mmol) in DMF(30 mL) was added NBS (3.1 g, 17.4 mmol). The mixture was reacted at room temperature for 4 hours. The reaction solution was poured into water (50 mL), and the precipitated solid was collected, and then washed with methanol to give the target product, which was directly used in the next step. Step 2: 3,5-dibromo-1,6-dimethylpyridin-2(1H)-one Under nitrogen, to a solution of 3,5-dibromo-6-methylpyridin-2(14)-one (2.3 g, 8.7 mmol) in DMF(30 mL) was added iodomethane (1.3 g, 8.7 mmol) and cesium carbonate (1.6 g, 11.3 mmol). The mixture was reacted at room temperature for 2 hours. The reaction solution was poured into water (50 mL), the precipitated solid was collected, and then the solid was washed with methanol to give the target product (2.2 g, two-step yield 92%). [M+H]" 281.8 Step 3: (S)-5-bromo-1,6-dimethyl-3-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2- yl)amino)pyridin-2(1H)-one The intermediate I-13 was prepared with 3,5-dibromo-1,6-dimethylpyridin-2(1H)-one and corresponding reagents according to the corresponding steps of intermediate 1-2. [M+H]™ 448.1, 450.1 Intermediate I-16 (S)-6-chloro-2-ethyl-4-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino) pyridazine-3(2H)-one 0 HN SN Step 1 Oui Step 2 — H x 8r A ~ci “™y Br” sohg wn, N or! CI] So 1-18 Step 1: 4-bromo-6-chloro-2-ethylpyridazine-3(2H)-one At 0-5°C, under nitrogen, to a solution of 4-bromo-6-chloro-3(2H)-one (1.0 g, 4.8 mmol) in DMF(20 mL) was added 60% sodium hydride (mineral oil dispersion) (0.46 g, 11.5 mmol). The mixture was reacted at 0-5°C for 30 minutes, then iodocthene (1.5 g, 9.6 mmol) was added, and the reaction was continued at room temperature for 5 minutes. The reaction solution was poured into water, extracted with ethyl acetate, the organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) lo give the target product (0.91 g, yield 80%). [M+H] 238.9 Step 2: (S)-6-chloro-2-ethyl-4-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-y)pyridin-2- yDamino) pyridazine-3(2H)-one The intermediate I-16 was prepared with 4-bromo-6-chloro-2-ethylpyridazine-3(2H)-one and corresponding reagents according to the corresponding steps of intermediate I-2. [M+H]" 405.1 Intermediate I-31 S-bromo-1-methyl-3-((1-(2,2,2-trifluoroethyl)-1 H-1,2,3-triazole-4-yl)amino)pyridin-2(1 H)- one ¥ Oy, No Ty an Br NO, Au 3 ZN Step 1 CN Step: srererererererrrerrrrrerere lity: N—N npwrrrecrrrrrsrararararares Yi NO, An R= Ng . PTR hi Sp 2 z / N HNN \ N-N Sef 7 AF Fe rn 1.3% Step 1: 4-nitro-1-(2,2,2-trifluoroethyl)-1H-1,2,3-triazole At 0-5°C, under nitrogen, to a solution of 4-nitro-1H-1,2,3-triazole (4.0 g, 35.1 mmol), 2- trifluoroethanol (5.12 mL, 43.8 mmol) and triphenylphosphine (18.4 g,43.8 mmol) in tetrahydrofuran (180ml) was added DIAD (13.9 g, 43.8 mmol), The mixture was reacted at 60°C for 16 hours, and then cooled to room temperature, concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (4.61 g, yield 68%). [M+H]™ 197.0 Step 2: 5-bromo-1-methyl-3-((1-(2,2,2-trifluoroethyl)-1H-1,2,3-triazole-4-yl)amino)pyridin- 2(1H)-one The intermediate I-31 was prepared with 4-nitro-1-(2,2,2-trifluoroethyl)-14-1,2,3-triazole and corresponding reagents according to the corresponding steps of intermediate I-3. [M+H]" 352.0, 353.9 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediates 1-31, I-3 and 1-3: | Intermediate Structural LC-MS termediate Structural LC-MS formula [M+H]" formula [M+H]" ] HN gr Aa y HN" Br 316.0 HN Spr 317.0 | 52 An 318.0 | 3:33 On 319.0 ‘N-N ‘N-N N-N [I N-N / / Fe |e 353.0, 354.9 SA ETT) 5 he 343.0, 1.34 oo | > 1a N | | ie 354.9 | Cd 345.0 N-N ad Va ny 0 Intermediate 1-37 5-bromo-1-methyl-3-((1'-(oxetan-3-yl)-1',2',3',6'-tetrahydro-[3,4'-bispyridin]-6- yl)amino)pyridin-2(1H)-one Ou -N HN TA, “ed 0.0 B S$ Lo Stepr NF Seep 1 ® & w oe Bat {-37 Step 1: t-butyl 6-nitro-3°,6°-dihydro-[3,4*-bispyridin]-1°(2’ H)carboxylate Under nitrogen, to a solution of 1-nitrogen-tert-butyl-4,5-cyclohexene-4-borate (4.41 g, 15 mmol), 5-fluoro-2-nitropyridine (3.03 g, 15 mmol) in 1,4-dioxane (20 mL) and water (2 mL) was added Pd(dppf)Cl, CHCl, (612 mg, 0.75 mmol} and sodium carbonate (3.18 g, 30 mmol). The mixture was reacted at 100°C for 3 hours, and then cooled to room temperature, concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (4.58 g, yield 100%). [M+H] 306.1 Step 2: 5-bromo-1-methyl-3-((1'-(oxetan-3-yl)-1',2',3",6'"-tetrahydro-[3,4'-bispyridin]-6- yl)amino)pyridin-2(1H)-one The intermediate I-37 was prepared with z-buty! 6-nitro-3’,6’-dihydro-[3,4°-bispyridin ]- 1°(2'H) carboxylate and corresponding reagents according to the corresponding steps of intermediate 1-2. [M+H] 417.0, 419.0 The intermediate in the following table was prepared with corresponding materials and reagents according to the preparation steps of intermediate I-37: LC-M | Intermediate Structural formula C s [M+H] | 1.38 | 5 | 412.0,414.0 Intermediate 1-43 (S)-5-bromo-1-methyl-3-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyrazin-2- yl)amino)pyridin-2(1H)-one | BY HN NO; A Step ¢ i Step 2 } i Ny ~~ 23 Boo 1-43 Step 1: t-buryl (S)-3-methyl-4-(5-nitropyrazin-2-yl)piperazin-1-carboxylate To a solution of 2-bromo-5-nitropyrazine (1.22 g, 6.0 mmol), r-buzvl (S)-3- methylpiperazin-1-carboxylate (1.00 g, 5.0 mmol) in DMF(10 mL) was added potassium carbonate (1.38 g, 10 mmol). The mixture was reacted at 80°C for 4 hours, and then cooled to room temperature, concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (1.50 g, yield 93%). [M+H-56] 268.1 Step 2: (S)-5-bromo-1-methyl-3-((5-(2-methyl-4-(oxetan-3-ylpiperazin-1-yl)pyrazin-2- yl)amino)pyridin-2(1H)-one The intermediate 1-43 was prepared with #-buty! (8)-3-methyl-4-(5-nitropyrazin-2-yl) piperazin-1-carboxylate and corresponding reagents according to the corresponding steps of intermediate 1-2. [M+H]™ 435.1, 437.1 Intermediate I-44 (S)-5-bromo-1-methyl-3-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyrimidin-2- yl)amino)pyridin-2(1H)-one PMB. PMB PMB. PMB NN NH, NPN i % I Step 3 e J Step 2 aA Steps Non PE he _O%PS —_— A BP) —_— To i “ / —_— 5 J Br 0 “uN PAN 0 “NT Boe ol | HN JL Br NH NPN NPN Step 4 SN Step s ——— — rk en. NJ NJ a. .N yt | a 3 I) ] nN N” NY < J HH hi. N |-44 Step 1: 5-bromo-N,N-bis(4-methoxy benzyl)pyrimidin-2-amine At 0-5°C, under nitrogen, to a solution of 5-bromopyrimidin-2-amine (3.48 g, 20 mmol) in tetrahydrofuran (60 mL) was added 60% sodium hydride (mineral oil dispersion) (1.72 g, 43 mmol). The mixture was reacted at 0-5°C for 30 minutes, then p-methoxybenzy] chloride (7.83 g, 50 mmol) was added, and the reaction was continued at 75°C for 8 hours, The reaction solution was poured into water, extracted with ethyl acetate, the organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (2.07 g, yield 25%). [M+H] 414.1, 416.1 Step 2: t-butyl (S)-4-(2-(bis(4-methoxy benzyDamino)pyrimidin-5-yl)-3-methylpiperazin-1- carboxylate Under nitrogen, to a solution of 5-bromo-N,N-bis(4-methoxy benzyl)pyrimidin-2-amine (2.07 g, 5.0 mmol) and #-buty! (S)-3-methylpiperazin-1-carboxylate (10.0 g, 49.0 nunol) in toluene (30 mL) was added BINAP (311 mg, 0.50 mmol), Pd;(dba); (229 mg, 0.25 mmol) and tert-butoxysodium (960 mg, 10 mmol). The mixture was reacted at 80°C for 8 hours, and then cooled to room temperature. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (1.60 g, yield 30%). [M+H]™ 534.3 Step 3: (S)-3-(2-methylpiperazin-1-yl)pyrimidin-2-amine Under nitrogen, a solution of t-butyl (S)-4-(2-(bis(4-methoxy benzyl)amino)pyrimidin-5- y1)-3-methylpiperazin-1-carboxylate (1.60 g, 3.0 mmol) in trifluoroacetic acid (10 mL) was stirred at room temperature for 30 minutes, concentrated in vacuum under reduced pressure, to give the target product, which was directly used in the next step. [M+H]" 194.1 Step 4: t-butyl (S)-4-(2-aminopyrimidin-5-yl)-3-methylpiperazin-1-carboxylate To a solution of (S)-5-(2-methylpiperazin-1-yl)pyrimidin-2-amine obtained from the previous step and di-tert-butyl dicarbonate (720 mg, 3.3 mmol) in dichloromethane (10 mL) was added triethylamine (455 mg, 4.5 mmol). The mixture was reacted at room temperature for 1 hours. The mixture was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (dichloromethane / methanol) to give the target product (880 mg, two-step yield 100%). [M+H]™ 294.1 Step 5: (S)-5-bromo-1-methyl-3-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyrimidin-2- yhamino)pyridin-2(1H)-one The intermediate I-44 was prepared with z-bury! (S)-4-(2-aminopyrimidin-5-yl)-3- methylpiperazin-1-carboxylate and corresponding reagents according to the corresponding steps of intermediate [-2, [M+H]™ 435.0, 437.0 Intermediate 1-45 5-bromo-1-methyl-3-((5-((tetrahydro-2H-pyran-3-yl)amino)pyridin-2-yl)amino)pyridin- 2(1H)-one he! HN Xe Ng Step 1 Step 2 rewoveassmemossssssenre li oy Aon J Y HN LA hy HN 0 A 1-45 Step 1: 6-nitro-N-(tetrahydro-2H-pyran-3-yl)pyridin-3-amine Under nitrogen, to a solution of tetrahydro-2H-pyran-3-amine (0.61 g, 6.0 mmol) and 5- bromo-2-nitropyridine (1.46 g, 7.2 mmol) in 1,4-dioxane (50 mL) was added BINAP (0.37 g, 0.60 mmol), Pda(dba); (0.55 g, 0.60 mmol) and cesium carbonate (3.91 g, 12 mmol). The mixture was reacted at 100°C for 16 hours, and then cooled to room temperature, The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (dichloromethane / methanol) to give the target product (0.72 g, yield 54%). [M+H]™ 224.1 Step 2: 5-bromo-1-methyl-3-((5-((tetrahydro-2 H-pyran-3-yl)amino)pyridin-2- yh)amino)pyridin-2(1H)-one The intermediate I-45 was prepared with 6-nitro-N-( tetrahydro-2H-pyran-3-yl) pyridin-3- amine and corresponding reagents according to the corresponding steps of intermediate 1-3. [M+H]" 379.0, 381.0 The intermediate in the following table was prepared with corresponding materials and reagents according to the preparation steps of intermediate I-45: Intermediate | Structural formul LC-MS ntermediate ructural iormula [M+H] | | 1-46 | @ | 409.0, 411.0 ht N. © ol. ji OH Intermediate 1-47 5S-bromo-1-methyl-3-((5-(morpholin-4-carbonyDpyridin-2-yl)amino)pyridin-2(1H)-one Step 1 ) Step 2 NH, Oy Aa He Ay (J on ~ L_o 1.47 Step 1: (6-aminopyridin-3-yl)(morpholino)ketone Under nitrogen, a solution of 6-aminonicotinic acid (1.38 g, 10 mmol), CDI(1.95 g, 12 mmol) in DMF (12 mL) was reacted at 70°C for 1 hour, and then stirred at room temperature for 1 hour. Morpholine (1.74 g, 20 mmol) was added to the mixture, and the mixture was reacted at room temperature for 16 hours. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (dichloromethane / methanol) to give the target product (1.05 g, yield 51%). [M+H]" 208.1 Step 2: 5-bromo-1-methyl-3-((5-(morpholin-4-carbonyl)pyridin-2-yl)amino)pyridin-2(1 H)- one The intermediate I-47 was prepared with (6-aminopyridin-3-yl}(morpholino)ketone and corresponding reagents according to the corresponding steps of intermediate 1-3. [M+H]" 393.0, 395.0 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediate I-47: LC-MS | Intermediate | Structural formula [MH] | 148 | oN | 406.0, 408.0 HN" 7 “Br ” | 1-165 | | 396.0, 398.0 oN J ws 2 | 4 J NP ee fy A 4 Intermediate I-52 4-chloro-2-(6-fluoro-1-oxopyrazino[1,2-a]indol-2(1H)-ylnicotinaldehyde “a F | Qe + FE Step 1 F he Step 2 ——; aK a a ee J Ee i H Ao Sd % ™~N oO ou Ao F No AN 2 Step 3 1-52 RR _ er 2° FA Ch AN ad Lah 0 1-52 Step 1: Ethyl 1-(2,2-diethoxyethyl)-7-fluoro-1H-indol-2-carboxylate To a solution of ethyl 7-fluoro-1H-indol-2-carboxylate (2.07 g, 10 mmol) in DMF(15 mL) was added 2-bromo-1,1-diethoxyethane (4.0 g, 20 mmol) and cesium carbonate (8.2 g, 25 mmol), The mixture was reacted at 110°C for 16 hours, and then cooled to room temperature, poured into water, and extracted with ethyl acetate. The organic phase was collected and combined, and concentrated in vacuurn under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (2.5 g, yield 77%). [M+H-EtOH]™ 278.1 Step 2: 6-fluoropyrazino|1,2-a|indol-1(2H)-one To a solution of ethyl 1-(2,2-diethoxyethyl)-7-fluoro-1H-indol-2-carboxylate (2.5 g, 7.7 mmol) in acetic acid (50 mL) was added ammonium acetate (12 g, 154 mmol). The mixture was reacted at 110°C for 16 hours, and then cooled to room temperature, concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (2.5 g, yield 77%). [M+H]™ 203.0 Step 3: 4-chloro-2-(6-fluoro-1-oxepyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde The intermediate I-52 was prepared with 6-fluoropyrazino[1,2-a] indol-1(2H)-one and corresponding reagents according to the corresponding steps of intermediate I-1. [M+H]" 342.0 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediates I-52 and I-1: LC-MS | Intermediate Structural formula [M+H)* | 1-53 | 342.0 2 An | oA ~ / ZN © cit tii eee rt CT a | 159 | a JAIL | 342.0 40 A | Cl XN N. x NN oo F | 1-66 | 325.0 — -= PANY | o oN = [_~ 0 | 1-70 la LAK | 324.0 | o oN = a — _ | 1-71 at AIO | 342.0 PL Ay F Jon An [4 o Intermediate 1-58 4-chloro-2-(7,7-difluoro-1-0x0-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)- yhnicotinaldehyde ; 3 2% 3 Step 1 il Step 2 0 LS 7m " X F OA oO Fo F Step 3 — Step « F r INN ol 0 br 0 A y FE EINT Cin, (a oo ° 1.58 1-58 Step 1: 7,7-difluoro-8,9-dihydropyrazine|1,2-«|indel-1,6(2H,7H)-dione The target compound was prepared with ethyl 6,6-fluoro-7-0x0-4,5,6,7-tetrahydro-1H- indol-2-carboxylate according to the corresponding steps of intermediate I-1, [M+H]™ 239.0 Step 2: 7,7-difluoro-6-hydroxyl-6,7,8,9-tetrahydropyrazino[1,2-a]indol-1(2H)-one At 0-5°C, under nitrogen, to a solution of 7,7-difluoro-8,9-dihydropyrazino[ 1,2-a]indol~ 1,6(2H,7H)-dione (500 mg, 2.1 mmol) in methanol (10 mL) was added sodium borohydride (239 mg, 6.3 mmol), and the mixture was reacted at this temperature for 10 minutes. A saturated aqueous ammonium chloride solution (5 mL) was added to the reaction solution, and the mixture was extracted with dichloromethane (10 mL x 2), The organic phase was collected and combined, and concentrated in vacuum under reduced pressure to give the target product, which was directly used in the next step. Step 3: 7,7-difluoro-6,7,8,9-tetrahydropyrazino[1,2-¢]indol-1(2H)-one Under nitrogen, to a solution of 7,7-difluoro-6-hydroxyl-6,7,8,9-tetrahydropyrazino[1,2- alindol-1(2H)-one obtained from the previous step in trifluoroacetic acid (5 mL) was added triethylsilane (771 mg, 6.3 mmol). The mixture was reacted at room temperature for 1 hour, and concentrated in vacuurn under reduced pressure, a saturated aqueous sodium bicarbonate solution (10 mL) was added to the resulting residue, and the mixture was extracted with dichloromethane (10 mL x 2). The organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product (120) mg, two-step yield 26%). [M+H]" 225.0 Step 4: 4-chloro-2-(7,7-difluore-1-0x0-6,7,8,9-tetrahydropyrazino|1,2-¢]indol-2(1H)- yDnicotinaldehyde The intermediate I-58 was prepared with 7,7-difluoro-6,7,8,9-tetrahydropyrazino[1,2- alindol-1(2H)-one and corresponding reagents according to the corresponding steps of’ intermediate 1-1. [M+H]" 364.0 The intermediate in the following table was prepared with corresponding materials and reagents according to the preparation steps of intermediate I-58: LC-MS Intermediate | Structural formula svcurtormis | IM+H] — FE | 1-60 | 364.0 TT ~~ F © PN F | @ oN A lh & Intermediate 1-61 4-chloro-2-(8,10-difluoro-1-oxopyrazino[1,2-g]indol-2(1H)-ylnicotinaldehyde r F Step 1 Purtuol, JP Step 2 { Step 2 = ee Fre, 2 Step1 Ra SU “ LA » Ps “4 p U0 ~ iN 0— “81 Step 2 2 nA —_— LA Ass Try 61 Step 1: Ethyl 3,5-difluoro-1H-indol-2-carboxylate At 0-5°C, under nitrogen, to a solution of ethyl 5-fluoro-1H-indol-2-carboxylate (4.14 g, 20 mmol) in acetonitrile (100 mL) was added Selectfluor (7.08 g, 20 mmol), and the mixture was reacted at this temperature for 16 hours, A saturated aqueous ammonium chloride solution (20 mL) and water (100 mL) were added to the reaction solution, and the mixture was extracted with ethyl acetate (50 mL x 2). The organic phase was collected and combined, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (ethyl acetate / petroleum ether) to give the target product (2.4 g, yield 53%). [M+H]" 226.0. Step 2: 4-chloro-2-(8,10-difluoro-1-oxopyrazino[1,2-a]indol-2(1 H)-yl)nicotinaldehyde The intermediate I-61 was prepared with ethyl 3,5-difluoro-1H-indol-2-carboxylate and corresponding reagents according to the corresponding steps of intermediate 1-52. [M+H]™ 360.0 Intermediate I-62 Acetic acid (2-(9-bromo-7,7-dimethyl-1-0x0-1,6,7,8-tetrahydro-2H- cyclopenta[4,5]pyrrolo[1,2-a] pyrazin-2-yl)-4-chloropyridin-3-ylymethyl ester OR < Ory < OANA — Ch ANAS ln 0 Ln o Br 1-62 At 0°C, to a solution of acetic acid (4-chloro-2-(7,7-dimethyl-1-0x0-1,6,7,8-tetrahydro-2H- cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)pyridin-3-y)methyl ester (800 mg, 2.07 mmol) in dichloromethane (30 mL) was added NBS (367 mg, 2,07mmol). The mixture was reacted at room temperature for 16 hours, quenched with a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The organic phase was collected and combined, dried with anhydrous sodium sulfate, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (800 mg, yield 83%). [M+H]™ 464.0, 466.0 Intermediate 1-63 4-chloro-2-(7,7-dimethyl-4-0x0-4,6,7.8-tetrahydro-3H-cyclopenta[4,5|pyrrolo|2,1- 111,24] triazin-3-yl)nicotinaldehyde Pp Step 2 TN Step1 SCTH-4 Stepz —— gh, Sen ST >A) Gn = XL HN NH, Step 3 / © Myf EN ad oN 0 +53 Step 1: Ethyl 1-amino-5,5-dimethyl-1,4,5,6-tetrahydrocyclopentadieno[s] pyrrole-2- carboxylate At 0-5°C, under nitrogen, to a solution of ethyl 5,5-dimethyl-1,4,5,6- tetrahydrocyclopentadieno[ b]pyrrole-2-carboxylate (5.0 g, 24.1 mmol) in DMF(30 mL) was added 60% sodium hydride (mineral oil dispersion) (1.06 g, 26.5 nunol). The mixture was reacted at 0-5°C for 30 minutes, then O-(2,4-dinitrophenyl) hydroxylamine (5.3 g, 26.5 mmol) was added to the reaction solution, and the mixture was reacted at room temperature for 3 hours. The mixture was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (4.3g, yield 75%). [M+H]™ 223.0 Step 2: 7,7-dimethyl-7,8-dihydro-3H-cyclopenta[4,5]pyrrolo[2,1-f][1,2,4] triazin-4(6 H)-one Under nitrogen, to a mixture of ethyl 1-amino-5,5-dimethyl-1,4,5,6- tetrahydrocyclopentadieno[b]pyrrole-2-carboxylate (4.3g, 19.3 mmol) and formamide (30 mL) was added ammonium acetate (7.4 g, 96.5 mmol). The mixture was reacted at 140°C for 16 hours, and then cooled to room temperature, The mixture was filtered, and the filter cake was collected and washed with methanol to give the target product (3.1 g, yield 80%). [M+H]" 204.0 Step 3: 4-chloro-2-(7,7-dimethyl-4-0x0-4,6,7.8-tetrahydro-3H-cyclopenta|4,5| pyrrolo|2,1- f1[1,2,4]triazin-3-yD)nicotinaldehyde The intermediate 1-63 was prepared with 7,7-dimethyl-7,8-dihydro-3 / i-cyclopenta [4,5] pyrrolo [2,1-f][1,2,4] triazin-4(6H)-one and corresponding reagents according to the corresponding steps of intermediate 1-1, [M+H]" 343.1 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediate 1-63: LC-M | Intermediate | Structural formula Ee | 1.93 | 329.0 © My | @ ANAS lh © | 97 la LA AN {9 | 347.0 © Now | a AN Lh & oF Intermediate I-68 (8-((tert-butoxycarbonyl) (1-ethyl-1H-1,2,3-triazole-4-yl)amino)-[1,2,4] triazolo|1,5- a]pyridin-6-yl)boracic acid iN EN AN 1: 3% Fr OF jr 3 bY Be "YM _ Neg Step 1 Boos, Ax A, Step 2 Boo. A Ap OH Step 2 1 DE 0 nn —— bo AON AN Au A AN on OH NN N-N N-N / 2, J 1-21 1-68 The intermediate I-68 was prepared with intermediate I-21 and corresponding reagents according to step 1 of intermediate 1-74 and step 6 of intermediate 1-2. [M+H] 374.1 The intermediate in the following table was prepared with corresponding materials and reagents according to the preparation steps of intermediate I-68: | 1-72 o Sv | 501.2 LC-MS Intermediate | Structural formula [MHI | Noy | Bog. Ax oH Ay oH | | 172 S | 5012 "E) & Xo Intermediate I-74 4-chloro-2-(7-methyl-1-0x0-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1 H)- ylhnicotinaldehyde Step soc. Step 2 Ny) —4m4@8m EE . Qo oO Step 3 Step 4 o RazN 0 rr WNT, - oS 5 & 0 r NY Ch As Ln ° 1-74 Step 1: 7-0x0-4,5,6,7-tetrahydro-1H-indol-1,2-dicarboxylic acid 1-(tert-butyl)ester 2-ethyl ester To a solution of ethyl 7-0x0-4,5,6,7-tetrahydro-1H-indol-2-carboxylate (2.07 g, 10 mmol) and di-tert-butyl dicarbonate (7.51 g, 30 mmol} in tetrahydrofuran (30 mL) was added 4- dimethylaminopyridine (0.12 g, 1.0 mmol). The mixture was reacted at room temperature for 16 hours. The mixture was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (3.07 g, yield 100%). [M+Na]™ 330.3 Step 2: Ethyl 6-methyl-7-0x0-4,5,6,7-tetrahydro-1H-indol-2-carboxylate AL-78°C, under nitrogen, to a solution of 7-0x0-4,5,6,7-tetrahydro-1#-indol-1,2- dicarboxylic acid 1-(tert-butyl)ester 2-ethyl ester (3.07 g, 10 mmol) in tetrahydrofuran (50 mL) was dropwise added 1M HMDSLi / tetrahydrofuran solution (24 mL, 24 mmol), the mixture was naturally warmed to 0°C, and the reaction was continued for 30 minutes. At -78°C, iodomethane (3.41 g, 24 mmol) was dropwise added to the reaction solution, the mixture was naturally warmed to room temperature, and the reaction was continued for 4 hours. The reaction solution was cooled to 0°C, and quenched by adding a saturated aqueous ammonium chloride solution, extracted with ethyl acetate (50 mL x 2). The organic phase was collected and combined, dried with anhydrous sodium sulfate, and concentrated in vacuum under reduced pressure. Under nitrogen, the resulting residue trifluoroacetic acid (10 mL) solution was stirred at room temperature for 30 minutes, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (water / methanol) to give the target product (1.19 g, yield 54%). [M+H]™ 221.1 Step 3: Ethyl 6-methyl-4,5,6,7-tetrahydro-1H-indol-2-carboxylate Under nitrogen, to a solution of ethyl 6-methyl-7-0x0-4,5,6,7-tetrahydro-1H-indol-2- carboxylate (1.19 g, 5.38 mmol) in trifluoroacetic acid (10 mL) was added triethylsilane (2.5 mL). The mixture was reacted at room temperature for 16 hours, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product (980 mg, yield 88%). [M+H]" 208.1 Step 4: 4-chloro-2-(7-methyl-1-0x0-6,7.8,9-tetrahydropyrazino[1.2-a|indol-2(1H)- yDnicotinaldehyde The intermediate I-74 was prepared with ethyl 6-methyl-4,5,6,7-tetrahydro-1 / -indol-2- carboxylate and corresponding reagents according to the corresponding steps of intermediate I-1. [M+H]™ 342.0 Intermediate I-75 4-chloro-2-(7,7-dimethyl-1-0x0-1,6,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2- d|[1,2,4]triazin-2-yl)nicotinaldehyde Step 1 ~ wld Step 2 —_— ~ + ¥ 0 WEL LTTE ACL gotdrone rasgiin fom me 1 Steps wT Or —— 0 0 A np Ne o 0 Step 3 Q TY 1-75 Step 1: 5,5-dimethyl-1,4,5,6-tetrahydrocyclopentadieno| b|pyrrole-2-carbohydrazide A solution of ethyl 5,5-dimethyl-1,4,5,6-tetrahydrocyclopentadieno[ b]pyrrole-2- carboxylate (2.49 g, 12 mmol), an aqueous hydrazine hydrate solution (20 mL, 36 mmol) in ethanol (8 mL) was reacted in microwave reactor at 150°C for 2 hours, and then cooled to room temperature. The reaction was filtered and washed with water, and the filter cake was collected, and dried in vacuum under reduced pressure to give the target product (2.09 g, yield 90%). [M+HT 194.1 Step 2: 7,7-dimethyl-7,8-dihydro-2H-cyclopenta[4,5]pyrrolo[1,2-d][1,2,4]triazin-1(6H)-one Under nitrogen, a solution of §,5-dimethyl-1,4,5,6-tetrahydrocyclopentadieno[b]pyrrole-2- carbohydrazide (2.09 g, 10.5 mmol), triethyl orthoformate (3.11 g, 21.0 mmol) in DMF(8 mL) was reacted at 160°C for 16 hours. The reaction was cooled to room temperature, filtered, and washed with methanol, and the filter cake was collected, and dried in vacuum under reduced pressure to give the target product (1.65 g, yield 77%). [M+H]™ 204.1 Step 3: 4-chloro-2-(7,7-dimethyl-1-ox0-1,6,7,8-tetrahydro-2H-cyclopenta|4,5| pyrrolo[1,2- d}[1,2,4]triazin-2-yDnicotinaldehyde The intermediate 1-75 was prepared with 7,7-dimethyl-7,8-dihydro-2H- cyclopenta[4,5]pyrrolo[1,2-d][1.2,4]triazin-1(6 / ])-one and corresponding reagents according to the corresponding steps of intermediate I-1. [M+H]™ 343.1 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediate 1-75: LC-MS | Intermediate Structural formula MH] oN] | o x N. xy [~ a -—t Tang = NN NY | 18s | a AAA | 3428 20 NPN | a Ne A lh & F rN C Hi | 343.0 le Ja LAX 0 NENA | o OS NG A ZN © | 187 | 325.0 © NN | Cl. N N = MN © st i ee —— Ee AO | 328.8 ls [a Ld 0 2 Cl CVO oY zN © (NO [343.0 [19 Ja LAK 20 nA | @ ~~" iS zN © | 1-94 a ANIL | 347.0 0 ZN CNT | a ~* -N o F Intermediate 1-83 2-(4-chloro-3-(fluoromethyl)pyridin-2-yl)-7,7-dimethyl-7,8-dihydro-2 H- cyclopenta[4,5]pyrrolo[1,2-g]pyrazin-1(6 H)-one PREL TJ REAM] Ras BS RESERVE oH ” OMs Step 2 Ig Step + or - Step 2 Nn [ai Step a ——— —— — Ch Br ———— on A Br A x — Ct , BY ah IY 1-83 Step 1: (2-bromo-4-chloropyridin-3-yl)methanol At 0-5°C, to a solution of 2-bromo-4-chloronicotinaldehyde (2.7 g, 12.2 mmol) in dichloromethane (30 mL) and methanol (10 mL) was added sodium borohydride (325 mg, 8.6 mmol), and stirred at this temperature for 30 minutes, The reaction was quenched by adding water to the reaction solution, and extracted with dichloromethane, the organic phase was collected, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (2.5 g, yield 92%). Step 2: (2-bromo-4-chloropyridin-3-yl)methyl methanesulfonate At 0-5°C, to a solution of (2-bromo-4-chloropyridin-3-yl) methanol (1.0 g, 4.5 mmol) in dichloromethane (30 mL) was added methanesulfonyl chloride (573 mg, 5,0 mmol), and stirred at this temperature for 30 minutes. The reaction was quenched by adding water to the reaction solution, and extracted with dichloromethane, the organic phase was collected, and dried with anhydrous sodium sulfate. The reaction solution was filtered, and the filtrate was collected, concentrated in vacuum under reduced pressure to give the target product (1.35 g, yield 100%), which was directly used in the next step. [M+H]™ 299.9, 301.9 Step 3: 2-bromo-4-chloro-3-(fluoromethyl)pyridine To a solution of (2-bromo-4-chloropyridin-3-yl) methyl methanesulfonate (1.35 g, 5.0 mmol) in dried tetrahydrofuran (20 mL) was added 1M tetrabutylammonium fluoride / tetrahydrofuran (5.0 mL, 5.0 mmol), and stirred at 65°C for 2 hours. The reaction was quenched by adding water to the reaction solution, and extracted with ethyl acetate, the organic phase was collected, and concentrated in vacuum under reduced pressure, and the resulting residue was treated with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (700 mg, yield 62%). [M+H]™ 223.9, 225.9 2-(4-chloro-3-(fluoromethyl) pyridin-2-y1)-7,7-dimethyl-7,8-dihydro-2 H-cyclopenta [4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one was prepared with corresponding materials and reagents according to preparation step 8 of intermediate 1-1. [M+H]™ 346.1 Intermediate 1-91 4-chloro-2-(10-fluoro-1-0x0-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1 H)- yDnicotinaldehyde Step 1 ny J Stepe JINR OLE ATUL] Y UL = = ~ 4 wh J Sep my J) Stepe wd IN —_— " —_ - SONS “OA oA o co F o F _ — , F o F ~~ ° ov Oh, Iq a 1-81 Step 1: Ethyl 3-fluoro-1H-indol-2-carboxylate To a solution of ethyl 1H-indol-2-carboxylate (35.0 g, 185 mmol) in acetonitrile (1.75 L) was added 1-chloromethyl-4-fluoro-1,4-diazobicyclo[2.2.2]octanedi (tetrafluoroboric acid)salt (65.5 g, 1185 mmol), and stirred at room temperature for 45 minutes. The reaction was quenched by adding saturated brine, the organic phase was collected, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (petroleum ether / ethyl acetate) to give the target product (18.0 g, yield 47%). Step 2: Ethyl 3-fluoro-4,5,6,7-tetrahydro-1H-indol-2-carboxylate To a solution of ethyl 3-fluoro-1H-indol-2-carboxylate (10.5 g, 50.7 mmol) in acetic acid (210 mL) was added platinum dioxide (1,57 g, 1185 mmol). Under stirring at room temperature, the reaction solution was introduced with hydrogen, and reacted for 8 hours. The reaction solution was filtered, the filtrate was collected, and concentrated in vacuum under reduced pressure, and the resulting residue was diluted by adding water, and neutralized to pH = 8 with aqueous ammonia. The reaction solution was extracted with ethyl acetate, and the organic phase was collected, and concentrated in vacuum under reduced pressure, to give the target product (10.5 g, yield 98%). [M+H]" 212.0 4-chloro-2-(10-fluoro-1-0x0-6,7,8,9-tetrahydropyrazino[ 1,2-a]indol-2(1H)-yl) nicotinaldehyde was prepared with corresponding materials and reagents according to preparation steps 5-8 of intermediate I-1, [M+H]™ 346.0 Intermediate I-92 (RS)-2-(4-chloro-3-pyridine carboxaldehyde-2-y1)-7,7-dimethyl-1-0x0-1,6,7,8-tetrahydro- 2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-6-yl acetate 20 A Cl N N. =, (no 1-55 1-82 ,5]pyrrolo[1,2-a]pyrazin: AQ ®s) 20 AN { CANS ln 0 192 To a solution of intermediate 1-55 (1.0 g, 3.0 mmol) in 1,4-dioxane (15 mL) was added lead acetate (2.0 g, 4.5 mmol), and the reaction was stirred at room temperature for 3 hours. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was diluted by adding water, and neutralized to pH = 8 with aqueous ammonia. The reaction solution was extracted with ethyl acetate, the organic phase was collected, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product (600 mg, yield 50%). [M+H]™ 400.0 Intermediate I-99 (5-bromo-2'-(7,7-dimethyl-1-oxo-1,6,7,8-tetrahydre-2 H-cyclopenta[4,5|pyrrolo[1,2- a|pyrazin-2-yl)-1-methyl-6-0x0-1,6-dihydro-[3,4'-bispyridin]-3'-yl)methyl acetate 1 J Br XN | | N oH CREAN 4 0 ™ rR 4 A, Hori Sys Br SONNY yS NO NO on OR Ho ® ™ LT ZN © 1-4 1-89 Under nitrogen, a solution of 3-bromo-5-iodo-1-methylpyridin-2(14)-one (626 mg, 2.0 mmol), intermediate 1-4 (790 mg, 2.0 mmol), Pd(dppf)Cl> CHCl, (162 mg, 0.20 mmol), Xphos (94 mg, 0.20 mmol) and potassium phosphate (848 mg, 4.0 mmol) in acetonitrile (40 mL) and water (2 mL) was reacted at 30°C for 3 hours. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product. [M+H]" 537.1, 539.1 Intermediate 1-107 N-(5-bromo-1-methyl-2-o0x0-1,2-dihydropyridin-3-yl)propanamide A | XO | HN Spr | XO | HN Sgr Ao 1-107 Under nitrogen, to a solution of 3-amino-5-bromo-1-methylpyridin-2(1H)-one (609 mg, 3.0 mmol), propionyl chloride (416 mg, 4.5 mmol} in dichloromethane (20 mL) was dropwise added triethylamine (455 mg, 4.5 mmol), and reacted at room temperature for 1 hour. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / dichloromethane) to give the target product, [M+H]™ 259,0, 261.0 The intermediates in the following table were prepared with corresponding materials and reagents according to the preparation steps of intermediate I-107: Intermediate | Suc! LC-MS [| mediate | Structural LC-MS formula [M+H]* formula [M+H]* 1 : A IN. he IN. ] 259.0, TL 285.0, | 1-108 LOL, | 1-127 HN Spr A 261.0 A 287.0 259.0, 261.0 — 1 WS ve | 128 307.0, 309.0 t I | XL | HN Sgr co Compound 1 2-(5-((5-(ethyl (2-methoxyethyl)amino)pyridin-2-yl)amino)-3'-(hydroxymethyl)-1-methyl-6- 0x0-1,6-dihydro-[3.4'-bispyridin]-2'-yI)-7,7-dimethyl-7,8-dihydro-2 H- cyclopenta|4,5]|pyrrolo[1,2-a]pyrazin-1(6H)-one 1 Oy N OL Step 1 —_—— SN. ~ | LasN © / Lome on Ap T LBA NA HO Ny yo wN © “o 4 3 — Se oN i fm | de or 3 Om °y A pe A | HN SAA I i gy Ne A Ay SeN © Step 2 Ay Lon © 3 —_— e v SN rl, x 2 So on Step 1: Acetic acid (2'-(7,7-dimethyl-1-o0x0-1,6,7,8-tetrahydro-2 H- cyclopenta[4,5]pyrrolo[1,2-a] pyrazin-2-y1)-5-((5-(ethyl (2-methoxyethyl)amino)pyridin-2- yl)amino)-1-methyl-6-0x0-1,6-dihydro-[3,4'-bispyridin]-3'-y)methyl ester Under nitrogen, to a solution of intermediate 1-3 (126 mg, 0.33 mmol) and intermediate [-4 (134 mg, 0.33 mmol) in 1,4-dioxane (5.0 mL} and water (0.5 mL) was added Xphos (31 mg, 0.066 mmol}, Pd(dppf)Cl CH>Cl; (27 mg, 0.033 mmol) and potassium phosphate trihydrate (264 mg, 0.99 mmol). The mixture was reacted at 100°C for 4 hours, and then cooled to room temperature, The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) to give the target product. [M+H]™ 652.3 Step 2: 2-(5-((5-(ethyl (2-methoxyethyl)amino)pyridin-2-yljamine)-3'-(hydroxymethyl)-1- methyl-6-oxo-1,6-dihydro-[3,4'-bispyridin]-2'-yl)-7,7-dimethyl-7,8-dihydro-2 H- cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one To a solution of acetic acid (2'-(7,7-dimethyl-1-0x0-1.6,7,8-tetrahydro-2H- cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3-((5-(ethyl (2-methoxyethyl)amino)pyridin-2- yl)amino)-1-methyl-6-ox0-1,6-dihydro-[3,4"-bispyridin]-3'-y[)methyl ester obtained from step 1 in methanol (5 mL) was added potassium carbonate (137 mg, 0.99 mmol), which was reacted at room temperature for 2 hours. The reaction solution was concentrated in vacuum under reduced pressure, and the resulting residue was purified with thin layer chromatography (methanol / dichloromethane = 1 / 20} to give the target product (100 mg, two-step yield 50%). [M+H]" 610.3. 'H NMR (400 MHz, CD;0D): & 8.57-8.51 (m, 1H), 8.42-8.37 (m, 1H), 7.77-7.74 (m, 1H), 7.60-7.57 (m, 1H), 7.48-7.45 (m, 1H), 7.23-7.19 (m, 2H), 7.01-6.97 (m, 1H), 6.95-6.91 (m, 1H), 6.80-6.76 (m, 1H), 4.61-4.57 (m, 1H), 4.50-4.45 (m, 1H), 3.69 (s, 3H), 3.53-3.50 (m, 2H), 3.44-3.40 (m, 2H), 3.39- 3.34 (m, 2H), 3.32 (s, 3H), 2.78-2.69 (m, 2H), 2.66-2.57 (m. 2H), 1.30-1.27 (m, 6H), 1.13-1.08 (m, 3H). 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IIS Nad EC Eh gE y le er or Pe a ade _ wm ON a ses Es] ITER E Frost gg o-oo BT ww O AD rome NE ~ re 2 Te = 0 La Rn £3 wo AT hr J - St sdgand TIEZicse ) } -g ex ged de BZIERD “2g ha BHTTDS wT EL weg Nad SESE a= Eat a= 2a a dan ZT QR Rea EZ! mv oT BY or wm MY Szdan D = wn Zoe E NY Yea oR r= fF S383 Cl EN oT MY em eT Com NN en fetes | GERaZg QE = LE: =~ = 2-5 ESS Sear Ta Coxe gg or ~="Tg BREE > : 4 E SRST) Non2ss && = : EHE3Ed §9E£233 SEN A= = 1 =e ag ) > ot ~~ oe Ta oy pm AS a Tv Hat Riel ge Sx aTas 8 gfeo83 §33igs F£i2%% Zz3g8% TEEN RRC =< EEcesgg | £53528 Zot ~T z=tfg z8ict: gent St gg TEES T g mE 32g m2 = “ong ~ EE [-%] | 4 Fried EE] F228 EE ! 3 = kd Fal © = eo No | | | & a 0 | = \ { 7 [== ~ -Z) J! = : RE 20a Wawel 3 5 N 1 ~ el Compound 2 2-(5-((5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-y)pyridin-2-yl)amino)-3'- (hydroxymethyl)-1-methyl-6-0x0-1,6-dihydro-[3,4'-bispyridin]-2'-yl)-7,8-dihydro-2 H- cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6 H)-one Step 1 eee 0 LYLIupentd|s, pyri i,~=a o ~ gf 0 gl | vp A Cx $ Evry Ol A Ny (nan = Eh 8 Neg _B. Ke 0 ~ 4 na Beon 4 O— 1-1 2 Step 2 io ® on EL Hoy -C ] cy NO J 2 Step 1: 5-((5-((28,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-1-methyl-6- 0x0-2'-(1-0x0-1,6,7,8-tetrahydro-2 H-cyclopenta[4,5]pyrrolo[1,2-a] pyrazin-2-yl)-1,6-dihydro-[3,4'- bispyridin]-3'-carbaldehyde Under nitrogen, to a solution of (5~((5~((25,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1- yDpyridin-2-yl)amino)- | -methyl-6-oxo-1,6-dibydropyridin-3-yl)boracic acid (171 mg, 0.41 mmol) and 4-chloro-2-(1-0x0-1,6,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[ 1,2-a]pyrazin-2-yl)nicotinaldehyde (100 mg, 0.32 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was added Xphos (20 mg, 0.03 mmol), Pd(dppfH)Cl> CH>Cl, (25 mg, 0.03 mmol) and cesium carbonate (260 mg, 0.8 mmol), The mixture was reacted at 90°C for 4 hours, and then cooled to room temperature. Water (30 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (30 mL x 2). The organic phase was collected and combined, and concentrated in vacuum under reduced pressure to give the target product (180 mg, yield 68%), which was directly used in the next step. [M+H]" 647.3 Step 2: 2-(5-((5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-3'- (hydroxymethyl)-1-methyl-6-0x0-1,6-dihydro-[3,4'-bispyridin]-2'-y1)-7,8-dihydro-2 H- cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6 H)-one At 0-5°C, under nitrogen, to a solution of 5-((5-((25,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1- yl)pyridin-2-yl)amino)- | -methyl-6-o0x0-2'-(1-0x0-1,6,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[ 1,2- a]pyrazin-2-yl)-1,6-dihydro-[3,4"-bispyridin]-3'-carbaldebyde (180 mg, 0.28 mmol) in methanol (4 mL) and dichloromethane (10 mL) was added sodium borohydride (16 mg, 0.42 mmol), and reacted at room temperature for 15 minutes. The reaction was quenched by adding water (0.5 mL) to the reaction solution, and concentrated in vacuum under reduced pressure, and the resulting residue was purified with silica gel column chromatography (methanol / water) and purified with thin layer chromatography (methanol / dichloromethane =1 / 20) to give the target product (80 mg, yield 44%). [M+H]" 649.3. 'H 1H), 4.77-4.55 (m, SH), 4.49-4.47 (m, 1H), 3.81-3.64 (m, 4H), 3.20-3.18 (m, 1H), 2.91-2.87 (m, 3H), 2.77-2.73 (m, 4H), 2.62-2.42 (m, 3H), 1.94-1.92 (m, 1H), 0.89-0.86 (m, 6H). 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TLR Eng N y53 E233 Ete df §83Z44% Fam s=E ESSEC STS BRE 22m3048% F-TgRine EE Pa 2 §TEZIRIY gZgpe 3S gEfasg= §5ILZeg §Zfcszz23 fg 8:8 Zand l 852% x SEER] ErCE3 Ed — Ta Ta Ly t LY EZET STEZETS LP 222% oo 0 © o a wv Hi + aN << 0 o re 0 ud -4) |—Z 7 NN TR RIS 2) FN © <4 Cp < Z= eX 4p Co | uw z: / “ 3 3 3 = ~ | ¢ =) = |e |= NA —' ooo Loe vor ol = ra 3 = : an : §o% E85 «22888 7c n28y Ege Eac de had ON 2G eA ZEZIsagR NZ E 23 nEZ= 2" S=dg Eg Iz s54 So Ese - ~ -p ~~ TomTom Dx E g = == wv eG nT Aw |= Ny JL = CO oe Oy TT ~~ n et Pt NO mE d& g-2EZ838 E ~~ Cent 2 Noo 8 Fl CESERES Szeged ag led [ga Zl |[§8aD Tae 26 oo = 2 or LY YY eh em ni Ee ear No - ~~ I Rom [I CSTs [Eze EnEEZsesE dF TA ETE Aa << Ll = — maT oem yn 2 oe — Non ZL »;, TT = i on ot oc "Ze y I~ I oe gq Zee ZF om (Ze SS a SF «IT Na EE QL 4 © == as 7 C2 Ns ee C3 BF | mT eT & || |e PS =n = | | -_— UN a Se -ihg OC ono a 5 y = 3 0 - . = RRR, i f= = SSE TE so. 2 Td2E8s SEZ Zod ho SE 5 e= Og rN oS — E=5 = 8 a5 Pn BO <2 Ee B08 28 GHZ EZ Ze gENT 2 < E23 ERS I = 3 TA SlZigzz =IE22%2 SgS3InC B3nizE’ TALES ER Sree SgnZgh- Zrd3q8% I-E2 Eg dageiEg =n Ao 5 SdZd9g"= TRL ZZ EE E=nZEqE HELA B Riggs Ssugeas £3559 E el SE) SEs arn Taszgs SZIgdcsds: T8& 2g dn Sele me = Eres é Sahay IRN 23 Nemes Le TES 2d 4 = ah og Sad a 4 ~ = wo 2 -« © a sg S280 = =3d cE YE ExLS : - a x - poy : : — T FZE¥fc ig ZEdnEaa SRCLZEST EsZaaER sig 288 ElEs3Iesh ERS 23 8328397 2o=2TEES i Io E wEB od ELE EET PEERS 23 > E S=24888% Ene 3 2oieqsr SEIS EE A == " = = 2 > z 3 21E3e%5% Bg358a3 NEG 2203; 2onBegag SESESSY Bama s = N TTR § oe IT 2d m $1 == a 8zd3¥ge $£83z83 SE15icen Ip mn PY =~ =~ fg =sz IN TX SS og . 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Claims

CLAIMS 1. A compound of formula (I): mn Ry AT. w XP NR, Re | IA N. Xs: NNN T \ ; ZN Yeu {1 or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein X, and X; are each independently CH or N; or, X, is N, X; is CRy4, wherein R4 is Ci alkyl; Xs and X4 are each independently C or N; Y, and Y: are each independently CR yp or N; R, and R; are each independently chosen from hydrogen, deuterium, halogen, C,.¢ alkyl, Ca. alkynyl, Cy. haloalkyl, Cs cycloalkyl and phenyl; or R; and R; together with the carbon atoms to which they are attached form the following structures: Tre dL LN J Ren Al BN AA Lig! wl Td a (1-1) C1) (2) (-3) (1-4) or (FB) wherein Ry is independently chosen from deuterium, halogen, hydroxyl, Cs alkyl, Ca. alkynyl, Cy. deuteroalkyl and C.¢ haloalkyl; or two Re together with the carbon atoms to which they are attached form 3-6 membered cycloalkyl; mis 0,1,2,3 or4;pis1,2,3 or4; Z is N or CR7; R; is chosen from hydrogen, deuterium, C6 alkyl, halogen and C,_¢ haloalkyl; i ng or R; and R; together with the carbon atoms to which they are attached form (-6) provided that Rs is halogen, or both X, and X; are not CH at the same time: R; is hydrogen, deuterium, halogen or C,_¢ haloalkyl; Ry is hydrogen, halogen, -CN, C alkyl, Ca. alkynyl, -(C.: alkyl)-OH, -(C,.z alkyl)-O- (Cy. alkyl), -O~(C\.; alkyl), -CHO, -C(O)NH,, -C(O)NHCH,, -C(O)N(CH3); or 3-hydroxyl- oxetan-3-yl, wherein the Cy. alkyl or Cy.3 alkyl is each optionally substituted with one or more deuterium or halo; Ru ,=w LE I y 1 NL _N he) sy Cyis x u % or HN * wherein Rj is chosen from hydrogen, C,. alkyl and Ci. cycloalkyl, wherein the C.¢ alkyl is optionally substituted with one or more deuterium or halo; U, V and W are each independently N or CR 5; Ry; is hydrogen, deuterium or halogen; Rs is hydrogen, Cy. alkyl, -C(O)-(C). alkyl), -C(O)~(Cs.¢ cycloalkyl), -C(O)-phenyl, - C(O)NH-(C 1.6 alkyl), -C(O)NH-(Cs.6 cycloalkyl), -C(O)N(C1.6 alkyl)z, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the Cs alkyl, Cs. cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) C¢alkyl; 5) Cy alkenyl; 6) Cy.galkynyl; 7) Cie alkoxy; 8) C, haloalkyl; 9) (Cys alkyl)-OH; 10) -(C1.6 alkyl)-O-(Cr.¢ alkyl); 11) Cig cycloalkyl; 12) 3-12 membered heterocyclyl optionally substituted with one or more groups chosen from: deuterium, halogen, hydroxyl, oxo, -CN, C, alkyl, C,.¢ haloalkyl, Cs.6 cycloalkyl, Cag alkynyl, Cy. alkoxy, -(Cy.¢ alky])-CN, -(Cy.6 alkyD)-O-(Crs alkyl), -(C 1.6 alkyl }-OH, 4-6 membered heterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the C16 alkyl, Cs.¢ cycloalkyl or 4-6 membered heterocyclyl is each optionally substituted with one or more groups chosen from: deuterium, halogen, -NH,, -OH, -NH(C.¢ alkyl), -N(C1.¢ alkyl); and -NH(Cs.¢ cycloalkyl); 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more groups chosen from: halogen, -CN, -(C 1. alkyl)-CN, -(C,.s alkyl)-OH, C, alkyl, Cs. cycloalkyl, Cy.¢ alkoxy, ~(C.¢ alky])-O-(Cy. alkyl), -(C.¢ alkyl)-NH,, -(C.¢ alkyl)-NH(C\.s alkyl), -(C 1.6 alkyl)-N(C\.¢ alkyl)z, (C,.¢ alkyl)-NH(Cs.6 cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more groups chosen from: halogen, -CN, -(C1.¢ alkyl)-CN, ~(C.¢ alkyl)-OH, Ci alkyl, Cs. cycloalkyl, C}.¢ alkoxy, (Ci. alkyl)-O-(C.¢ alkyl), (Cs alkyl)-NHg, -(C 1.5 alkyl)-NH(C\.s alkyl), -(C1.¢ alkyl)-N-(C\.s alkyl)z, ~(C 1. alkyl)}-NH(Cs.6 cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR,’R,"’, wherein R," and R;’" are each independently chosen from hydrogen, C16 alkyl, Ci.6 cycloalkyl, -(Cy.g alkyl)-O-(C1.¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(C.¢ alkyl)-OH, the C6 alkyl is optionally substituted with one or more -NR'R,”’, and R,’ and R,’* are each independently chosen from hydrogen, C1. alkyl, -(C1.¢ alkyl)-OH and 4-6 membered heterocyclyl; 16) -C(O)NRy'Ry’’, wherein Ry,’ and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl optionally substituted with one or more groups chosen from: deuterium, halogen, -OH, Cy. alkyl, -(C;.¢ alkyl)-NH,, -(C 1.6 alkyl)-NH(C.6 alkyl), -(C1.¢ alkyl)-N(C).¢ alkyl)a, -(C}.s alkyl)-NH(C3.6 cycloalkyl), -NHa, -NH(C 1.6 alkyl), -N(Cy.¢ alkyl)s, -NH(C3.6 cycloalkyl) and - (C1. alkyl)-OH; and 17) -C(O)R,, wherein R, is chosen from hydrogen, Cis alkyl, Ca alkenyl, Cag alkynyl, -(C\.¢ alkyl)-OH and -(C,.¢ alkyl)-O-(C 1.6 alkyl); Ryo is hydrogen, deuterium, halogen, CN, Cy. alkyl or Cy. haloalkyl: provided that if R; and R; together with the carbon atoms to which they are attached form the following structures: Wom f Rs). SE FN Rg), Wo” J > wg oP ’ Lod vee A, Aad Tom Wd By fey 3 ETRY 6 hs 1-1) Ris ON. yh . WX A, & | Ch +3) 0-4) or (-8} ,and Cy is HUY , then the 3- 12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C,.¢ alkyl at both 2- and 6- positions, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantionier, a diastereomer or a tautomer thereof, wherein R; and R, HnlRel, spd together with the carbon atoms to which they are attached form -n , ie. the compound is a compound of formula (1A): {IA} AA AA fr us Re X# HE \ Hore NH “NY he \ ! Y, 2N © Yi (1A) 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein R; and R HnfRal,, sh together with the carbon atoms to which they are attached form (-1) , X3isN, X4is C, [mW NG N LL x Y,is CH, Cy is x ES and the compound is a compound of formula (IT): wherein X, and X; are each independently CH or N; or, X; is N, X; is CRy4, wherein Ry4 is chosen from Cy. alkyl; Y-isCHorN; Rj; is hydrogen, deuterium, halogen or Ci. haloalkyl; Ry is hydrogen, halogen, -CN, C, alkyl, -(C 3 alkyl)-OH, -(C,.; deuteroalkyl)-OH, - (Cy.3 alkyl)-O-(Cy.3 alkyl), -O-(Cy.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCHj3, -C(O)N(CH3)2 or 3-hydroxyl-oxetan-3-yl, wherein the C,.¢ alkyl is optionally substituted with one or more halo: W is N or CR)», and R)> is hydrogen or halogen; Rs is hydrogen, Cy. alkyl, -C(O)-(C}. alkyl), -C(O)-(C3.6 cycloalkyl), -C(O)-phenyl, - C(O)NH-(C 6 alkyl), -C(OYNH-(Cs. cycloalkyl), -C(OIN(C, alkyl). phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the Cj. alkyl, Cs. cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) Cisalkyl; 5) Cagalkenyl; 6) Cig alkynyl; 7y Cj. alkoxy; 8) Ci haloalkyl; 9) (Cre alkyD-OH; 10) -(C1.s alkyl)-O~(C1.¢ alkyl); 11) Cj, cycloalkyl; 12) 3-12 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, Cy.¢ alkyl, C.¢ haloalkyl, C;.¢ cycloalkyl, Coe alkynyl, C;¢ alkoxy, -(C1.s alkyl)-CN, -(C.¢ alkyl)-O-(C1.6 alkyl), ~(Cy.¢ alky])-OH, 4-6 membered heterocyclyl, 4-6 membered fluoroheterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the C4 alkyl is optionally substituted with one or more -OH; 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen [rom halogen, -CN, -(C, alkyl)-CN, -(C,.¢ alkyl)-OH, C4 alkyl, Cs. cycloalkyl, C)¢ alkoxy, -(Ci alkyl)-O-(C 6 alkyl), -(C1.6 alkyl)-NHa, ~(C1.6 alkyl)-NH(C. alkyl), -(C1.¢ alkyl)-N(C1. alkyl), -(C.6 alkyl)-NH(Cs.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more substituents chosen from halogen, -CN, (C6 alkyl}-CN, (Cy. alky])-OH, Cy alkyl, Cs. cycloalkyl, Cy. alkoxy, - (C16 alky])}-O(C 1.6 alkyl), -(C.6 alkyl)-NHg, ~(C.s alkyl)-NH(C .¢ alkyl), ~(C,.¢ alkyl)-N(C .s alkyl)y, ~(C ys alkyl)-NH(C;.6 cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR,’R,”’, wherein R,’ and R,’” are each independently chosen from hydrogen, C6 alkyl, C36 cycloalkyl, -(Cy.s alkyl)-O-(C,.¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(C).¢ alkyl)-OH, the C,. alkyl is optionally substituted with one or more -NR.'R.’’, and R,.” and R.”’ are each independently chosen from hydrogen, C,.s alkyl, -(C,¢ alkyl)-OH and 4-6 membered heterocyclyl: 16) -C(O)NRy'Ry’’, wherein Ry,’ and Ry,’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from halogen, -OH, C1. alkyl, ~(C 1. alkyl)-NHj, ~(C. alkyl}-NH(C,.¢ alkyl), (C16 alkyl)-N(C .s alkyl)s, (C6 alkyl)-NH(C;.¢ cycloalkyl) and -(C,.s alkyl)-OH; and 17) -C(O)R., wherein R; is chosen from hydrogen, C4 alkyl, C1 alkenyl, Co alkynyl and -(C1.¢ alkyl)-O-(C1.¢ alkyl); Re is halogen, Ci.s alkyl or hydroxyl; and mis0,1,2o0r3.

4. The compound of claim 2, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein R; and R, {Rel sn together with the carbon atoms to which they are attached form -1 ,X3is N, X4is C, Ri Y,isCH, Cyis | LX x S Sy LS and the compound is a compound of formula (III): Ru {Rg)m Rin {Rg)m Ox UN X & T Ry XP ONT 1 Nn EN ANA = Rs YaN © Rs nny wherein Xi and X; are each independently CH or N; or, X; is N, X; is CRy4, wherein Ris is chosen from C6 alkyl; Y,isCHorN; Rj; is hydrogen, deuterium, halogen or C, haloalkyl; Ry is hydrogen, halogen, -CN, C\ alkyl, -(C).3 alkyl)-OH, -(C,.; deuteroalkyl)-OH, - (Cy.3 alkyl)-0-(Cy.3 alkyl), -O-(Cy.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCH3, -C(O)N(CH3), or 3-hydroxyl-oxetan-3-yl, wherein the Cy. alkyl is optionally substituted with one or more halo: U and V are each independently chosen from N or CH; Rs is hydrogen, Cy. alkyl, -C(O)-(C). alkyl), -C(O)-(C3.6 cycloalkyl), -C(O)-phenyl, - C(O)NH-(C.¢ alkyl), -C(O)NH-(Cs.¢ cycloalkyl), -C(OIN(C,¢ alkyl). phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the Cys alkyl, Cs. cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen; 2) oxo; 3) -CN; 4) Cigalkyl; 5) Cag alkenyl; 6) Cig alkynyl; 7) Cj. alkoxy; 8) Ci. haloalkyl; 9) (Crs alkyD-OH; 10) (C6 alkyl)-O-(C).¢ alkyl); 11) Cs. cycloalkyl; 12) 3-12 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, Cy alkyl, C1. haloalkyl, Cs. cycloalkyl, Co.6 alkynyl, C.s alkoxy, -(Ci.s alkyl)-CN, -(C1.s alkyl)-O-(C,.6 alkyl), -(C,_ alkyl}-OH, 4-6 membered heterocyclyl, 4-6 membered fluoroheterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the C6 alkyl is optionally substituted with one or more -OH; 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen from halogen, -CN, -(C) alky])-CN, -(C,_ alky])-OH, Cs alkyl, Ci cycloalkyl, Cs alkoxy, -(C). alkyl)-O-(C 1.6 alkyl), -(C1.¢ alkyl)-NHj, -(C\.¢ alkyl}-NH(C1.¢ alkyl}, -(C.¢ alkyl)-N(C1.¢ alkyl),, -(C;.¢ alkyl)-NH(C;.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more substituents chosen from halogen, -CN, ~(C, alkyl)-CN, (C1. alkyl)-OH, C, alkyl, Cs. cycloalkyl, C,.¢ alkoxy, - (C16 alkyl)-O(C\.¢ alkyl), -(C).¢ alkyl}-NHa, -(C 1.6 alkyl)-NH(C 1.6 alkyl), -(Ci.¢ alkyl)-N(C1.¢ alkyl)z, -(C1.6 alkyl)-NH(C;.¢ cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR,’R."", wherein R.’ and R,’" are each independently chosen from hydrogen, C6 alkyl, Cs. cycloalkyl, -(C1.6 alkyl)-O-(C,. alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(Cj.¢ alkyl)}-OH, the C,. alkyl is optionally substituted with one or more -NR.’R.’’, and R.’ and R..’* are each independently chosen from hydrogen, C,.¢ alkyl, -(C,.¢ alkyl)-OH and 4-6 membered heterocyclyl; 16) -C(O)NR,'Ry’’, wherein Ry” and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen [rom halogen, -OH, Cs alkyl, (Cs alkyl}-NHa, ~(C 6 alkyl)-NH(C, alkyl), -(C¢ alkyl)-N(C 1.6 alkyl),, -(C 1.6 alkyl)-NH(C3. cycloalkyl) and -(C,.¢ alkyl)-OH; and 17) -C(O)R,, wherein R. is chosen from hydrogen, Cy. alkyl, Cs. alkenyl, Cy alkynyl and ~(C.¢ alkyl)-O-(Cy.¢ alkyl); Rg is halogen, Cg alkyl or hydroxyl; mis 0, 1,2 or 3; and Ry; is hydrogen, Ci. alkyl or C.¢ deuteroalkyl; provided that the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C.¢ alkyl at both 2- and 6~ positions.

5. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X,; and X; are CH, or one ol X; and X; is N, and the other is CH.

6. The compound of any one of claims 1-5, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Y2 is CH.

7. The compound of any one of claims 1-6, or a pharinaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein R; is hydrogen or halogen.

8. The compound of any one of claims 1-7, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein R4 is C16 alkyl, -(C1.3 alkyl)-OH, -(C,.3 deuteroalkyl)-OH, -(C,.z alkyD)-O-(C,_; alkyl) or -CHO, wherein the Cs alkyl is optionally substituted with one or more halo.

9. The compound of any one of claims 1-8, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is hydrogen, and Ry is ~(C,.z alkyl)-OH.

10. The compound of any one of claims 1-9, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from ¥F & \ W SN \ N i N—N / is 3 5 Y S Nn ! / Ry Rpt Ry Ra Ry Raz Rzo Yor 7 N \ N / Ry Ras X \ N— hi Raz Razz I Ay Rahs and Ria wherein Ris chosen from Cy alkyl, Cy. haloalkyl and -(C}.¢ alkyl)-O-(C 6 alkyl); nis 0,1 or2; Rz; and Ry; are each independently chosen from hydrogen, -CN, Cys alkyl, C, haloalkyl, - (Cy. alkyl)-O~(C,.6 alkyl), 4-6 membered heterocyclyl or -C(O)R,, and R. is chosen from hydrogen, Cy. alkyl or -(Cy.4 alkyl)-Q-(C.¢ alkyl}; Ras is chosen from hydrogen, Ci.¢ alkyl, -(Ci.6 alkyl)-O-(C,.¢ alkyl), or -C(O)NRp'Rp”’, wherein Ry,” and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl; Aq, As and A; are each independently CH or N; and R3 is chosen from: 1) hydrogen; 2) Cjgalkyl; 3) Ci.ealkoxy: 4) halogen; 5) Cs cycloalkyl; 6) 3-12 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, -CN, C, alkyl, C.¢ alkoxy, (Cs alkyl)-CN, -(C.¢ alkyl)-O- (C)-6 alkyl), 4-6 membered heterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the Cy.¢ alkyl is optionally substituted with one or more - OH; 7) phenyl optionally substituted with one or more substituents chosen from 4-6 membered heterocyclyl; 8) -NR,’'R,”’, wherein R," and R,’’ are each independently chosen from hydrogen, C16 alkyl, -(C1.6 alkyl)-O~(C.¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with ~(C.¢ alkyl)-OH, the C\.6 alkyl is optionally substituted with one or more -NR.'R."’, and R." and R.”’ are each independently chosen from hydrogen, C,¢ alkyl, -(C,.¢ alkyl)-OH and 4- 6 membered heterocyclyl; and 9) -C(O)NRy'Ry,’’, wherein Ry,’ and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more C,.¢ alkyl; provided that if R; and R; together with the carbon atoms to which they are attached form the following structures: wil’ Ris 3 fe % Rak Fey ata? “Sea ms oT PIE eg PR ng eed} Re I 2 eN gr St ENC he 1-1) SNe aRG FL Sher Sy li, Fem i JOT TT ee LT Os Ny " (1 ’ 0-3) | (4) or ’ (1-6) ,and Cy is x “y SA , then the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C.¢ alkyl at both 2- and 6- positions, 11. The compound of claim 10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is piperazinyl optionally substituted with one or more substituents chosen from C6 alkyl and 4-5 membered heterocyclyl; provided thatif R; and R; together with the carbon atoms to which they are attached form the following structures: Fe, ny pe TuRein FL PL $ EI Jem I ea wots Wt” (Rely se 0-9) NE rey wg Fr v Ryy RedReln We WT Ree He Jo Hwy LT TL Byty ed Ea ON Cd A Bs 0-1) 4-3) (4) or U9 ,and Cy is A TE , then the 3-12 membered heterocyclyl, when substituted, is not piperazin-1-yl substituted with C6 alkyl at both 2- and 6- positions.

12. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from Sr L, Lo “x oO i: & SoM ry , and wherein Raa, Raa’, Ras, Ras’, Roy and Ry” are each independently chosen from hydrogen, oxo and C.¢ alkyl; Rag is Ci. alkyl, -(C1.6 alkyl)-O-(C.¢ alkyl) or tetrahydrofuranyl; Rug is Cy. alkoxy; Rag is hydrogen or -(C 1.5 alkyl)-OH; Rip is Cy alkyl; and Aj, Az and Aj are each independently CH or N.

13. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs BP & " 0 i is or , whereinA, A, and A; are each independently CH or N, and R4 and Ry4’ are each independently chosen from hydrogen, oxo and C,. alkyl.

14. The compound of claim 13, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Ros and Ry4” are each independently chosen from hydrogen and C.¢ alkyl.

15. The compound of any one of claims 13-14, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Aj, A; and A; are all CH, or A; is N, and both A» and A; are CH, or A; is N, and both A; and A, are CH, 16. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs 1s chosen from: 1 > A 7 Ra id \ $ 3 iil Ryz or and wherein Ra is C16 alkyl: Raz is chosen from hydrogen, Cy. alkyl and 4 membered heterocyclyl; A; and A» are respectively CH; and Ra4 and Ros” are each independently chosen from hydrogen and C,_¢ alkyl.

17. The compound of any one of claims 4-16, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein Ry Ris Ox N Ck Ns EON Sy Riq Ris R11 Ri X X, xn x Hu # is XN A * A or * A herein Riyis Cre alkyl or Cg deuteroalkyl.

18. The compound of claim 4, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X; and X, are CH, or one of X; and X; is N, and the other is CH; Y, is CH; R; is hydrogen: Ry is - (C3 alkyl)-OH; U is CH, V is N or CH, and R; is C.3 alkyl; Rs is chosen from A, Ran No JS " , whereinRa4 and Ry” are each independently chosen from hydrogen, oxo and C1. alkyl, both A; and A, are CH, or A; is N and A, is CH; Rg is Cy alkyl; and mis 0 or 2.

19. The compound of any one of claims 4-18, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein both U and V are CH, and R;, is methyl.

20. The compound of any one of claims 1-19, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rg is C3 alkyl; and m is 2.

21. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, or a solvale, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rg x together with the five-membered ring to which they are attached forms X 22. The compound of claim 4, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastercomer or a tautomer thereof, wherein both X; and X, are CH; Y, is CH; Rj; is hydrogen; R, is -(C.3 alkyl)-OH; both U and V are CH, and Ry; XK Ap Rat, NN & is methyl; Rs is chosen from og , wherein Rp4 is Cy; alkyl, and both A and A; are CH; and Rg together with the five-membered ring to which they are attached forms x 23. The compound of claim 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein the compound is a compound of formula (IB) Ra (1B) a (1B) ZN ARs X; Ry id 0 Rs OV. No Xow) Ww YY TY H | % YouzN © vy (1B) 24. The compound of claim 23, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein the compound is a compound of formula (IV): . i z= ARgIM x XI Ry XZ N\_ / | 2 oy AA =~ Rs Yo oN © Rs (Iv) wherein Xi and X; are each independently CH or N; or, X{ is N, X» is CRy4, wherein Ry4 is chosen from C, alkyl; Y,is CHorN; Rj; is hydrogen, deuterium, halogen or Cy. haloalkyl; Ra is hydrogen, halogen, -CN, Cy. alkyl, -(C1.z alkyl}-OH, -(C.: deuteroalkyl)-OH, - (Cy.3 alkyD)-O-(Cy.3 alkyl), -O-(Cy.3 alkyl), -CHO, -C(O)NH,, -C(O)NHCH3, -C(O)N(CHjs), or 3-hydroxyl-oxetan-3-yl, wherein the Cy. alkyl is optionally substituted with one or more halo; U and V are each independently chosen from N or CH; Z is N or CH; Rs is hydrogen, C16 alkyl, -C(O)-(C1.6 alkyl), -C(0)-(Cs. cycloalkyl), -C(O)-phenyl, - C(O)NH-(Cy.6 alkyl), -C(O)NH-(C3.6 cycloalkyl), -C(O)N(Cy.6 alkyl),, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, wherein the Ci. alkyl, Cs.6 cycloalkyl, phenyl, 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl is each optionally substituted with one or more groups chosen from: 1) halogen, 2) oxo; 3) -CN; 4) Cj¢alkyl; 5) Cy alkenyl; 6) Ci.galkynyl; 7) Cpe alkoxy; 8) C,. haloalkyl; 9) -(Cy.6alkyl)-OH; 10) -(Ci.6 alkyl)-O-(C16 alkyl); 11) Ci cycloalkyl: 12) 3-12 membered heterocyclyl optionally substituted with one or more substituents chosen from halogen, hydroxyl, oxo, -CN, Cy.s alkyl, C,.¢ haloalkyl, Cs.¢ cycloalkyl, Ca.6 alkynyl, Cy. alkoxy, -(C 1. alkyl)-CN, ~(C.¢ alkyl)-O-(C1.¢ alkyl), -(C.¢ alkyl)-OH, 4-6 membered heterocyclyl, 4-6 membered fluoroheterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the Cg alkyl is optionally substituted with one or more -OH; 13) 5-6 membered monocyclic heteroaryl optionally substituted with one or more substituents chosen from halogen, -CN, ~(C,.¢ alkyl)-CN, -(C.¢ alkyl)-OH, Cs alkyl, Cs.¢ cycloalkyl, C1. alkoxy, ~(C1.s alkyl)-O-(C1 alkyl), ~(C1.s alkyl)-NHa, -(C1.¢ alkyl)-NH(C, alkyl), -(C.¢ alky)-N(C).5 alkyl),, -(C,.¢ alkyl)-NH(C3.¢ cycloalkyl) and 4-6 membered heterocyclyl; 14) phenyl optionally substituted with one or more substituents chosen from halogen, -CN, (C16 alkyl)-CN, ~(C1¢ alkyl)-OH, Ci. alkyl, Cs cycloalkyl, C,.¢ alkoxy, - (C 1.5 alkyD)-O(C.6 alkyl), -(Cy.¢ alkyl)-NH;, -(C).¢ alkyl)-NH(C 1.5 alkyl), -(C1.s alkyl)-N(C).¢ alkyl),, -(C 1.6 alkyl}-NH(C1 cycloalkyl) and 4-6 membered heterocyclyl; 15) -NR:'R,’’, wherein R,” and R,"” are each independently chosen from hydrogen, Cy.6 alkyl, Cs. cycloalkyl, (C).¢ alkyl)-O-(C1¢ alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents of -(Cy.¢ alkyl}-OH, the Cy alkyl is optionally substituted with one or more -NR.'R.”’, and R." and R,’’ are each independently chosen from hydrogen, Cs alkyl, ~(C.s alkyl)-OH and 4-6 membered heterocyclyl; 16) -C(O)NRy’R},”’, wherein Ry’ and Ry,” together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more substituents chosen from halogen, -OH, C,. alkyl, -(C). alkyl)-NHa,, -(C 1. alkyl)-NH(C.¢ alkyl), -(C1.¢ alkyl)-N(C 1. alkyl),, -(C.¢ alkyl)-NH(C3.¢ cycloalkyl) and -(C;. alkyl)-OH; and 17) -C(O)R,, wherein R. is chosen from hydrogen, C,.¢ alkyl, Co alkenyl, Coe alkynyl and -(C.¢ alkyl)-O-(Cj.6 alkyl); Rg is halogen, C |. alkyl or hydroxyl; mis 0, 1,2 or 3; and Rui is hydrogen, Ci.¢ alkyl or Cy. deuteroalkyl.

25. The compound of any one of claims 23-24, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Y2 1s CH.

26. The compound of any one of claims 23-25, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein Rs is chosen from: ! 2 °N I abe N-—N d, oe N? IN 7 SN 21, A > A fel HER Ry 24 Ry Raa YA b— b—s — N— Raz Rb > Sn i NY] 7 R and 13 wherein Rai is chosen from C6 alkyl, C1. haloalkyl and -(C.¢ alkyl)-O-(C,.¢ alkyl); nis 0, 1or2; Ra; and Ra; are each independently chosen from hydrogen, -CN, C6 alkyl, C,.¢ haloalkyl, (Cy alkyl)-O-(C\.6 alkyl), 4-6 membered heterocyclyl or -C(O)R,, and R. is chosen from hydrogen, Cy. alkyl or -(C, alkyl)-O-(C,.¢ alkyl); Ry4 is chosen from hydrogen, Cj. alkyl, -(C 1 alkyl)-O-(C 1 alkyl), or -C(O)NRy'Ry,”, wherein Ry’ and Ry," together with the N atoms to which they are attached form 4-6 membered heterocyclyl; A), A; and A; are each independently CH or N; and R;3 is chosen from: 1) hydrogen; 2) Crs alkyl; 3) Cy alkoxy; 4) halogen; 5) Cs.6 cycloalkyl: 6) 4-8 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, -CN, C,. alkyl, C,.¢ alkoxy, -(C .s alkyl)-CN, -(C 1. alkyl)-O-(C¢ alkyl), 4-6 membered heterocyclyl and deuterated 4-6 membered heterocyclyl, wherein the C6 alkyl is optionally substituted with one or more -OH; 7) phenyl optionally substituted with one or more substituents chosen from 4-6 membered heterocyclyl; 8) -NR,'R,’’, wherein R,’ and R,”’ are each independently chosen from hydrogen, Ci. alkyl, -(C¢ alkyl)-O-(C,.6 alkyl) and 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more -(C.¢ alkyl)-OH, the C).¢ alkyl is optionally substituted with one or more -NR.’R.”’, and R.” and R.”’ are each independently chosen from hydrogen, C,.e alkyl, -(C,. alkyl)-OH and 4-6 membered heterocyclyl; and 9) -C(O)NRy’'Ry’*, wherein Ry,’ and Ry,’’ together with the N atoms to which they are attached form 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with one or more Ci. alkyl, 27. The compound of any one of claims 23-26, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereomer or a tautomer thereof, wherein both X, and X, are CH, or one of X; and X, is N, and the other is CH; Y, is CH; R; is hydrogen; Ry is -(Cy.; alkyl)-OH; Z is CH; Uis CH, and Vis N or CH; 1 of SN SN AJM oF \ Ris \ N— / or Rz Rsis or Rz , wherein Aj and A; are each independently CH or N, and Ry3 is 4-6 membered heterocyclyl optionally substituted with one or more substituents chosen from oxo, Cis alkyl, Cs alkoxy, -(C,.s alkyl)-O-(C.. alkyl) and 4-6 membered heterocyclyl; Ro; is chosen from hydrogen, -CN, Cy alkyl, Ci. haloalkyl, -(C.6 alkyl)-O- (Cy alkyl), 4-6 membered heterocyclyl or -C(O)R.. and Rc is chosen from hydrogen, Ci. alkyl or -(Cy.¢ alkyl)-O-(C,.6 alkyl); Rg is hydrogen or halogen; mis 0, 1 or2; and Ry; is Cp. alkyl.

28. The compound of claim 1, or a pharmaceutically acceptable salt thereof, or a solvate, a racemic mixture, an enantiomer, a diastereonier or a tautomer thereof, which is chosen from: No. [Swcural forms No | formula No. Structural formula 1 | 7 | Oy N ) OH { Og N. ] OHA 4 SANA HSN Sys AN AN An sN © J J “UN ", I~ es. & ! | & 3 Ge “or 4 oN ot INA ] hy, gx BEF An oN © On f 1 hy on oF 6 A OH An x CY SOIT J Sue th | 2 EN a) _— 0 0; by Hew 4 HN oN No rs Au N © |< . Oo. | QO S HN A ny Cry dy 3 O [4 |g) ' | o 9 o he oH 10 o ho “og a Q oN e - b | ha 11 | 12 | 5 OH { o. ny pa ENTS rs N= PAS SN ZN © AN ZN © 2 : | og | ti 6) ® Q <Q 13 SN oo sls 14 YN - a | "Mm e) oe 13 oh “ort NTS SLIP = wv |& N— | 5 o 5 “rs Ns SN |= “¥r C / N TLE 7 Wh OH 2. Nh OH ] $8 lL CO NS NN AS NS ™ Nx, Jo NO An oN © N N-N Sl = & 3) N—" / 8 = Ny M OHA { HN SONA AS An (a N-N | = EE 19 oh io, pees 20 BT | Te 20 | TL ©, Ny xs Xx “of 6) "6 7 x HN’ [ X HN’ g J “E) | oe _& 23 ot 24 | _ CN 9 4 | ga & ry SE "pe i 23 ~" 24 ZX oH 4 ] OH A A IS = | HN BB Noss N N 7 ZN © 3 # an N 3 ttt 25 | 26 | o, Noy en o " Hey HN Bi N HVS r Py ZN © A ZN © 2 3 nn, N 1s} &) 27 or Co sid 28 0 Co ~~ I Sv 8 0; A Hz LC PN =~, | A =N 0 | My 0 “~O 1 7 “en v of S| EEE Q » oN oH Og Muy OH nl “1S Ng Ns HN SANS HN rS CY An ZN © or MN ¢ Sr ——— | 32 | 31 ot OH An o, Ny OH ors oN An ZN © on AY / | ¢ | ¥ Cg i od 34 | ON OH IN AN HN ( = An oN © N-N L | FF 35 i de 36 37 38 pPo Th ene 3% ode nl 0, N. D. Hy 4 x J N. ony HN [ = ZN 0 Ay | + A 39 52.5 40 ) odo | Ox N. QOH ] G8 HN xy i xy N wy ATU T Mago ok OH ] PN NS ro = A #N © J [ety “7 A 0 41 | poids 42 - | Og N. oH TI LOO HNN rS Ns LOY LH J / qd A | Oy N. HAN 4 od oN n ln & ZN a) N. I 43 Co N ds 44 | 46 | N. OH A ost o. 8 > HN 7 HN © AN oN © An N © gg gl HN o iN 1 | | | OH OH 47 0 4 OH 48 0; 4 OH ) OS 4 a rs HN » HN ry a zN © An ZN © Ng | 9g | NY oP oN TY __ a 49 ~~ H Co oid 50 Co N gal, | N. OH PUNT A HN’ al =N o P | My “o 1 ttt 51 Co Bh ol 52 R I fs 3 51 0; & “od 9 x N. = PN J | NS We L Q a4 oN OH 33 A OH Cron o xr i [Ln & i ov $ A ZN 3 " nN. fs) 3 1 © OOOO a 53 | 56 o hy Hen HN Sy Au (A & (J 57 or ab oo ~~ SR F 59 \ 60 HN’ ( = An sN 0 F a | nN (5), T 61 1 A 62 61 —T —_— _— —_— 0. 8 OH F 62 oN oH WAIL ] $8 | F NS id ili a ZN © 9; lv & ow x | x “oN ©) “nN 7 ©) 63 - © | 4 1 ON OH Noy { N ] OH 4 HN 7S No As HN [ Ns A oN © AN #N © J TH 4, N to, MN © ® €) E) S © 65 0; 4 OH 66 LCOS HN x mS N. =, An NaN © § sa, N. (8) G) Q 67 aa abi N= 68 | Og N OH 1 Cy HN eV = A ZN © N 0 oN | 0, " HANA HN xn I N. xy N =N © N / \ e > N o=<( Q “ ab OH 7 ou OH LCOS A C00 HN NN = HN A | gr No gor AN © N % ' i Ng \ — / N— N | 7 h / —— gp —m— ———— A 71 / ~=N ~~ 3 | 7 Noy JN OH 1 FS HN od == A ZN © NN l 73 ol aa ~~ 74 | ON OH TENN AEX HN il Au ZN © A N-N ; 75 oe ~ \ 76 | HN xX mS N. = a ZN Oo Q & 77 | ~ / _ 1 78 1 o b Hn HN ~ = A ZN © 0) 5) 3 0; N OH fe LCT HN x N N. = Ay 43 s | ty Sv & 0 0 80 0. b “rst Nos : 4 S ] ”) 3 E) Y Q 81 | spat {2 ONT S & $ 81 | 82 | 0: N. ] OH 4 0, N. OHA { Wy ZN © ow ZN © N 4 he 4 £ 4 83 | 84 | LT oh on LT Og Ne OH ~~ A NJ o NJ o wo S8 83 oN oH # oN oH LOS LO SAAN A SANA AN A ce} 8 A ln 6 Sd oN 85 | pail R6 | pak ZN ~zN ZN ~zNM CJ 3 85 | 86 | ON OH 0, oH oy 4 on HN FS Boi 55: NS Bi ZN zN 0 | A 2N Oo SN N-N / 87 | 88 | ON. OH Og N OH LCOS L CO HN ~ HN N 2 lv No ln & oA 80 Co nd [+11] 89 oN oH iF 30 oN OH ] YS ] r a NY oo oN © o NO J) v 91 ad 92 —_ 93 CL Co | 94 95 —d 06 oN ; AO | HN xn x N =, a ZN © 5 <; “&#N © Nn | 4, N & &) | 0. N OH [Gl I | van () 2N [] 99 | ~ / _ 100 | ON OH ] $8 HN x © N. xy 2 ZN © y {~~ / N © 4 ~ / 101 | ad 102 | Og MN. D._OH ] eo [7 NY ls we ~ N A “N © 103 0; N OH | 104 0; \ Of py 1 [0S Ny Oh HN SS B NGS ANS OS Ns F. zN © ZN o AN 0 J nN wh s) i ol ©) © $ 105 Co BN nm 106 | ~~ 105 oh . 106 oh o J_LCO0 LCs HN’ i Sy HN x N N. Sy a zN © A ZN 0 x J ie | a, JN. = N €) Ra oe _ 107 | - aad 108 on oo pn (5) SF 9 | 0, hy Hoy < HN Nn ry N. Sy ZN 0 SN fi > / Q \ NN ~ 109 i ~ / _ 110 - | N. OH ~~, OL COs HN » ZN © rs fe | Ox N OH L C00 HN NN = a lh o gy N. ¢ i Q X 0 / =~ q pee peepee 111 | 112 | 0 ™ OH 4 ™ OHA 4 HN SN HSS SM A hd A Lh 8 Lo Lo fo 0) Jd | =) 5 \ i i 3 N 114 | 115 | HN x NN N =, HN CY I 2 N | ZN Oo = |g | = “, N. (rs) 8) ) : S N & | Oy -N. Hw 4 ME 0 HN’ I 3 = w= 116 dq HN X x N. ws A a 5 | > Yr 116 4 HN x » N. xy, & 118 ~ tl © 117 Oy N. OH Cn lh ° | od | IN of \ 119 wr OF Co Pile 121 IN { Zl srr. a ——— 119 | 121 | % M Oey < o, M oH < HN SN eS ANA 120 An (4 L, ak W -™ n / 0) ¢ ( / o / A q NN | Og N. OH 2 N SN o & ©) { dq CoN { 2 | By OH HN aN = Sw [x 0 x "J & 124 Co Ants 125 | o. M Hn HN ry” =~ hs, ZN © & J) & a | = ln 8 or) ¢ 126 Tob Con [127 4 @ | Q " rN HN SNS An ln & i os 130 . 131 - Og N. OH LCOS HN x i oN oe CY 132 oe HN CY T n pin ; 133 1 JL LD LL oN Ja) x N. =, X N. = or SET 132 | 133 | Oy N. a 4 Og N. a 4 HN x nN =, HN x 7S N. xy . NO 0 a8 x -N ~ IN _ | LN 134 Og No LOH ~~) 135 ou M OH ~ | Oy N. OH 1 CO HN St = Sn ZN © / \ 7 TE aN 4 | ON OH ] oS HVS oe = ZN © SN £1 Nw, 5 | J TEs 13 8 J Ox N. HANA % A NN " [4 o Au Id & yesh of 136 & 136 g & | 17 x Los Sy [Lh & 6 : | 140 139 142 141 146 2 oN OH TF NN | 141 OLN PHL * 4 ~ p AACN i" : a ZN ©O Ad gr N \ P N— N J © 144 I on N An © N =" > HN bod N os Hy () he A [A 6 - ZN © ( VN 2 0) a N— a ¢ 5 146 A. OH .~ / 145 ONL OH pl Os N_ : 2 ) )~ 7 ILS | _ 0. N. OH 1 2S An (nv N yt | Og N. OH 146 OH oN 0 Z zN 0 < l / “ Q 147 ONL OH ~. 148 | Os N OH LL HN St =, Sn #N © Ax / \ | ON OH LO % HN ~~" zN © oe: NN od / / Q \ N | HN’ i ™ HN I xy 9 2N 0 F 0 ZN 0 x J x J uN. ao, N Ie 6) X g & Q Qo 151 o. \ Phy 12 oN Re N EH = I = 9; < a x @Y N Q °~ 153 oy oH 154 ou No Con = oN oH HN 7 QO oN © N 0, A 153 | 154 | o, M (HA { HN Xn rs N. = ZN © N? A [7 sn, 155 ONL CoH TY 156 (Ny NT | ! 155 | 3 156 ON HA < oN Hey HN x NN = x J N oO i HN [ = Ch ZN © SN oN © N a \ Y o— / bo’ 157 he ote LN 158 hy AW IM Oy No on A 159 oo on Co ~ 160 $< Y on Q 161 od om 162 a ON. OH PIES [3 PL . | HN’ = N 0 F | ZN A ZN © o A . \ iD) Yo & 0 163 ole oho dN 164 oh. ond ot 166 rom Rgf>"00 7 °_ _ 163 o 5 Hy 164 x ohh < HN mS No As HN rS N= ZN 0 A ZN © ( / \’ / 5 Ko _ 163 ET. = 166 ote ono dN | o, Oh HN 7S xy a #N © N y N— & Cg 63 oh. 0 Ls | SY Aw N © 8 5 < 67 oh dN 168 I<” I ] oS HN NN Sw Nv & OF J \— l x py N— 5 OLN. HANA J aN AS " ln & Y 8 / l N— N— / / { { | 170 | ON ome "hE J % hs Ns PA HN ry oN © 2 ZN 0 ( ¥ oN 3) N: Oo od N-N / N 171 | 172 N Oy < A OH Zn HN x rs N. = HN x NN = A ZN © Zz 2 oO N © ) ¢ 4 173 oh on 1 174 kh ame Fo 4 173 | 174 | "es NES HS mS Ny HN mS NA 2 ZN Oo 2N © |< ¢ 175 oh ona = 176 Ty Ta F :! 3 0 A OH Z LCOS HN mS A N © N-N £ | 0: ™ ANA eS AN 5 % ~ UN © N \ | — | = T17R 177 ole on LT) 178 oO 1 —— Og N. OH L(y HN x BY N. Ry | F N © 5 ” N N < JS |< | 0; ™ OH HN x ae ay Cn zN 0 F N, (J £ I | 180 [79 | ON OH LL OD NT rr A sN o F 7 N-N ¢ 182 181 | wy OH _ oe 1 \ ®s | HN (CY I N 2 5 \ o— / ke Lo 8 183 | Vay “184 Ox N AN HN xD N N. =x AN [A o F N | N < _ Fiss oh oa 186 CLES go « J “o) HCOOH \ | 187 oN HA JF 188 o. Ny OH Ay 9; oN © OU UN © N | #, N “ou, MN (S) 8) £) é) Q Q | 189 oh oH 190 ah onn LY I | 189 o OG orf 1190 HN x x N. x 0 zN 0 gg nd *3 MOT ob a 2 | o. % OH HN 2 xy N O N” # Q 193 93 obs oH 194 ON. OH _N, 1 et HN XN © N. = j~ zN 0 N LN Not / / Q { 195 ONL CoH 196 196 ak y Hi 3 yr N. © oH ON. 197 198 & 199 200 Ou OH oe 202 ET | 204 203 ON Const x J Nn N. = Cr nN €) > 206 205 Toh ona hd be = 207 One i CoH 208 Ne NN. > =N NN. OH Ay { ] NC An ZN © N-N ¢ be 209 210 4 on, x Te Ls x J N N. =, " : i | =N 0 / py Z N X NN % |g : Ea, 3 © SU 212 [2 N ed N. =, 21 o. C OH ee ° AAAs 4 [ zN © 0 R J ., N. J ¢ 1 #u,, N. | “f@ Y 213 214 [213 oh oe A HN ( I 9 oN [E Y — 216 215 Co ~ | 215 oo Ny 216 HN x i x N. xy 9; ZN o x “, N ea e _ 217 oh OH ~~ 218 <i noo og AN / | ou, ©) “al, © Q 219 oh ona ot 220 Ol. OH TY | oL os ¥ 221 ey OE 222 aT ~~ F | 0. ™ HN HN xX Sy N. =, An ZN © oN NN Sy & 2724 3 22 S 225 ob ona N26 EF AN, SeN oo | oy PHAN HN St = AN sN oOo F S$ Re) 38 Ht 1 & h 0 227 ONL Hd 228 We F oon pr | | [o} N. Oo Z aL HN’ 7 Ay ZN © | O, ™ ME A HN x oN =, a 2N © bh | 0 nT L232 234 3 23 235 - | ~~ 236 oO. N. OH 29. A pharmaceutical composition, comprising the compound of any one of claims 1-28 and / or a pharmaceutically acceptable salt thereof, and optionally comprising a pharmaceutically acceptable excipient.

30. A method of in vivo or ir vitro inhibiting the activity of BTK, comprising contacting BTK with an effective amount of the compound of any one of claims 1-28, and / or a pharmaceutically acceptable salt thereof, 31. Use of the compound of any one of claims 1-28 and / or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating or preventing a disease mediated by BTK or at least in part by BTK, preferably for treating or preventing cancer, an inflammatory disease or autoimmune disease, wherein the cancer is preferably solid tumor or hematologic malignancy, including lymphoma, leukemia and myeloma; the cancer is more preferably chosen from B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt's lymphoma, non-Burkitt’s highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lymphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukemia, myeloma (such as multiple myeloma) or graft versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermatitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma, multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, and diseases associated with kidney transplantation.

32. A method of treating or preventing a disease in a subject, comprising administering to the subject in need thereof an effective amount of the compound of any one of claims 1-28, and / or a pharmaceutically acceptable salt thereof, wherein the disease is a disease mediated by BTK or at least in part by BTK; the disease is preferably cancer, an inflammatory disease or autoimmune disease; the cancer is preferably solid tumor or hematologic malignancy, including lymphoma, leukemia and myeloma; the cancer is more preferably chosen from B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt’s lyvinphoma, non-Burkitt’s highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lymphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukemia, myeloma (such as multiple myeloma) or graft versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermatitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma, multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, and diseases associated with kidney transplantation.

33. The compound of any one of claims 1-28 and / or a pharmaceutically acceptable salt thereof, for use as a medicament.

34. The compound of any one of claims 1-28 and / or a pharmaceutically acceptable salt thereof, for use in treating or preventing a disease mediated by BTK or at least in part by BTK, and preferably for use in treating or preventing cancer, an inflammatory disease or autoimmune disease, wherein the cancer is preferably solid tumor or hematologic malignancy, including lymphoma, leukemia and myeloma; the cancer is more preferably chosen from B cell malignancy, diffuse large B-cell lymphoma (DLBCL), large B-cell lymphoma (LBCL), B- cell lymphoma, mantle cell lymphoma, follicular lymphoma, non-Hodgkin's lymphoma, Hodgkin’s lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, Burkitt's lymphoma, non-Burkitt’s highly degree B cell malignant lymphoma, extranodal marginal-zone B-cell lymphoma, small lymphotic lymphoma (SLL), lymphoblastic lymphoma, lymphocytic leukemia, myelogenous leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), human acute monocytic leukemia, acute lymphocytic leukemia (ALL), B cell acute lymphocytic leukemia (B-ALL), hairy cell leukemia, chronic lymphocytic leukemia (CLL) (such as high risk CLL), myelodysplastic syndrome, acute lymphoblastic leukernia, myeloma (such as multiple myeloma) or graft versus host disease; and the inflammatory disease or autoimmune disease is preferably chosen from: systemic inflammation and local inflammation, arthritis, rheumatoid arthritis, inflammation associated with immunosuppression, organ-graft refection, allergic disease, ulcerative colitis, Crohn’s disease, dermatitis, asthma, lupus erythematosus, Sjogren syndrome, multiple sclerosis, scleroderma, multiple sclerosis osteoporosis, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, antineutrophil cytoplasmatic antibody vasculitis, chronic obstructive pulmonary disease, psoriasis, sicca syndrome, pemphigus valgaris, and diseases associated with kidney transplantation.

35. A pharmaceutical combination, comprising the compound of any one of claims 1-28 and / or a pharmaceutically acceptable salt thereof, and at least one additional therapeutic agent, wherein the therapeutic agent is preferably chosen from: an anti-inflammatory agent, an immunomedulator or an anti-tumor active agent, wherein the anti-tumor active agent includes a chemotherapeutic agent, an immune checkpoint inhibitor or agonist, and a targeted therapeutic agent.

36. A compound of formula (VI): = Ri ZX, ’ X57) Rg © Fo Rez : i A YY ZN © Rs v1) or a solvate, a racemic mixture, an enantiomer, a diastereomer and a tautomer thereof, wherein Xi, Xa, Xs. X4, Ri, Ry and Rj are as defined in any one of claims 1-28; Rj is -CHO, -C,.3 alkyl-OH, -C,_; alkyl-OAc, Cy; alkyl, -C(O)-Cy.3 alkyl or C3 haloalkyl, and , oN Ry “B Xe 1 \ is Re 4 , 2° Ra FP Ry or ° Ry —iB, Rs, is halogen, -B(OH),, -B(OC.¢ alkyl), Rd or o— Ra and Rg is hydrogen or Cg alkyl, 37. The compound of claim 36, which is (V-3) (V-4) 2==y Re Ba PNT Be PNY Re), Rap x N. =, Raz x N. =, ZN 0 Ra ZNO Rs (V-3) (v-4) aN CONEY re (FON Rt NTN Raz mS N 52 7 ZNO Rs ZN © Rs {V-5) (V-6) I™% / N Nun A Rar ~ ” N. ne k, =N oO Ze Raf’ NN \ / Ran =, _N © Ry VT) v-7) (V-8) NN —\ Ry EN Ry NZ ON 3 | N Reem AN ==, ZN © Rs i N Ry NEN A Ran, AN Ly & & (V-10) (v-8) or oo , wherein Z is N or CRs; Ryan Rs are each independently hydrogen or halogen; Re is halogen or Cj. alkyl; and nis 1 or 2.

38. The compound of claim 36, which is chosen from:

38. The compound of claim 36, which is chosen from: 2 AN © AN PL ANA |e ~~ 2, | ons = an A = | A ZN © NN © | | Cc N. X x A he I~ SY IY NF CN # ! J “oN © NN © | OH a A | | Ho B oN x NO li ———————————) oO ge seg sp 0 = © Ay 27 PON | os = F [on = lo = AN © _N o F ~N © _ er pe N= 20 AN © ANN J |= cod | o NN = CY ow LF AL ANA | a NN Ln 0 ~&zN © —_ _ © A) 2 Ay F ore | aA a GP E (LN ZN © x he ~N OO ~.N OO | OMA | a ha Ne AS Ln o Br I NF DoH E - on oF nv 0 Br oN ro 2 0 al © a |e ANA | a Ns | o LN As ln © lv 0 ln © —_ yy 1 ~ 7 ~~ 0 0 ANN 2 Ay 22 PON | o os | o Coo | cod ln © [v6 nv © - 7 - a TT j RS) (Rs) 0 Ba Ah ZO oN A E ( I ss 0 PN N | o i! o X ’ = _~ o la X LA o - ot C0 ri LY TT | Cry - [= ZN | o BD N. > X | a. veg— se m— ZN © < | Oe © or { 07 el Ag BAN A oH iy [os ; BAN hi Ho" | A ] . td L 7 NY yy $ = | o N O ¢ NY la Cs N O NAS rr - 7 | @ N Ny - (Ab _ — TN 20 NPN | @ ANA [A Gg PB © NPA | o SO ~ ZN © 20 NPN | o Ns lh & 0 NN { _0 NN { 0 NPN 4 or =~ | o NAS E NN AS 2N © [A o ln 0 F ge Te ou rs Ie os | a N oo Ny N Oo F LN OO Zz J (uN oo °F Te IR ANA | | a NPLNZN |e Ino

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