Heteroaromatic derivative regulator, preparation method and application thereof

Abstract

The present invention relates to heteroaromatic derivative modulators, preparation methods and applications thereof. In particular, the present invention relates to compounds represented by general formula (I), preparation methods thereof and pharmaceutical compositions containing the compounds, and uses thereof as Janus kinase inhibitors in the treatment of inflammatory-related diseases and tumor-related diseases, wherein each substituent in general formula (I-4) has the same definition as in the specification. #imgabs0#

Description

Technical Field

[0001] The present invention belongs to the field of drug synthesis, and in particular relates to a JAK inhibitor, a preparation method and application thereof. Background Art

[0002] Janus kinases (JAKs) are intracellular, non-receptor tyrosine kinases that mediate signaling and activation of various cytokines. The JAK kinase family comprises four subfamily members: JAK1, JAK2, JAK3, and TYK2. Each subfamily member mediates a distinct cytokine signaling pathway. JAK1, JAK2, and TYK2 are expressed in various tissues and cells throughout the body, while JAK3 is primarily expressed in hematopoietic tissues. Cytokine receptors share a common characteristic: they lack kinase activity, but possess binding sites for the tyrosine kinases JAK within their intracellular domains. Upon ligand binding, cytokine receptors activate the associated JAKs, leading to receptor phosphorylation. The phosphorylated tyrosine sites bind to STAT proteins containing SH2 domains, leading to STAT recruitment to the receptors and phosphorylation by JAKs. Subsequently, phosphotyrosine-mediated STAT dimerization occurs, and the activated STAT dimers translocate to the nucleus and activate transcription of their target genes, thereby regulating diverse cell functions, including growth, activation, and differentiation.

[0003] The JAK / STAT signaling pathway mediates the signal transduction of most cytokines within cells and plays a key role in biological processes such as immune regulation and immune cell proliferation. The JAK / STAT signaling pathway has a wide range of functions, participating in many important biological processes such as cell proliferation, differentiation, apoptosis, and immune regulation. It is closely related to various inflammatory diseases such as rheumatoid arthritis, dermatitis, psoriasis, and inflammatory bowel disease (ulcerative colitis and Crohn's disease). At the same time, the JAK / STAT signaling pathway is closely related to tumor diseases such as myelofibrosis, polycythemia vera, and essential thrombocythemia. Mutations in the JAK molecules themselves can also lead to tumor diseases such as acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), breast ductal carcinoma, and non-small cell lung cancer (NSCLC).

[0004] Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine, including ulcerative colitis (UC) and Crohn's disease (CD). Current medications for IBD primarily include aminosalicylic acid preparations, glucocorticoids, immunosuppressants, and antibiotics. The primary principles of UC treatment are to modulate the immune response and suppress inflammation. Currently, sulfasalazine is primarily used clinically to treat mild to moderate UC. For moderate to severe UC, glucocorticoids are commonly used, but they are not considered a long-term treatment because the risks outweigh the benefits. Monoclonal antibodies, on the other hand, present challenges such as high cost, the production of antibodies that affect drug safety and efficacy, and the inconvenience of intravenous administration. This area presents significant unmet medical needs. Many patients who receive treatment do not experience remission, with up to 80% of Crohn's disease patients and 30% of UC patients ultimately requiring surgery.

[0005] Tofacitinib (Xeljanz) is the first oral JAK inhibitor for the treatment of adult patients with moderately to severely active UC. It has significant inhibitory activity against JAK1, 2, and 3 subtypes, which increases the efficacy of tofacitinib, but also brings more serious side effects. Adverse reactions include infection, tuberculosis, tumors, anemia, liver damage, and increased cholesterol. There are many black box labels on the instructions for Tofacitinib: serious infections (tuberculosis, bacteria, fungi, viruses) and malignancies (lymphoma, etc.). Due to the wide range of functions mediated by each JAK, these side effects are caused by the drug inhibiting multiple JAKs at the same time. Since JAK is widely involved in the regulation of immune cells, JAK inhibitors will inevitably cause immunosuppression-related side effects, such as serious infections and even the occurrence of tumors. Even for the many highly selective inhibitors currently under development, such side effects caused by inhibiting the target are inevitable.

[0006] In view of the good efficacy of JAK inhibitors and the serious side effects related to multiple targets, the development of a safer JAK inhibitor drug has become an urgent problem to be solved. Since inflammatory bowel diseases occur on the intestinal surface of the gastrointestinal tract and do not require the drug to enter the blood system to work, developing a drug that reduces the systemic exposure of the drug in the blood circulation and increases the local exposure of the drug at the site of inflammation has become a good strategy to improve safety. International application WO2016191524A1 reported that Theravance Company synthesized a series of compounds that have extremely low systemic exposure and are enriched in intestinal inflammatory sites. They can effectively treat intestinal inflammation without causing serious side effects, indicating that this strategy is highly feasible and may have significant clinical application value. Summary of the Invention

[0007] The technical problem addressed by the present invention is to overcome the drawback of existing JAK inhibitors, which, while exhibiting therapeutic effects, suffer from severe side effects. The present invention provides heteroaromatic derivative modulators, their preparation methods, and uses. The heteroaromatic derivatives of the present invention exhibit potent inhibitory effects on JAK kinases and significantly increase local exposure at the treatment site, demonstrating excellent targeting.

[0008] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0009] A compound represented by general formula (I), its stereoisomers or pharmaceutically acceptable salts thereof:

[0010]

[0011] in:

[0012] L1 is selected from a bond, an alkylene group, an alkenylene group, an alkynyl group, a cycloalkyl group, a heterocyclic group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -、-NR aa (CH2) n1 -、-(CH2) n1 S(O) m1 -, or -(CH2) n1 S(O) m1 NR aa -;

[0013] L2 is selected from a bond, an oxygen atom, a sulfur atom, -CR aa R bb -、-(CH2) n1 C(O)-, -NR4-, or -(CH2) n1 S(O) m1 -;

[0014] L3 is selected from a bond, -NR aa -, or -C(O)NR aa -;

[0015] Ring A is a 6-14 membered heteroaryl group, wherein the 6-14 membered heteroaryl group is selected from a 6-14 membered fused heteroaryl group; preferably a 5-membered fused heteroaryl group, a 5-membered fused heteroaryl group or a 6-membered fused heteroaryl group;

[0016] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, a 6-14 membered fused heterocyclic group or a 6-14 membered spiroheterocyclic group;

[0017] Ring C is a heteroaryl group;

[0018] R1 is selected from hydrogen, deuterium, oxo, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxyl, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2)n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 NR cc C(O)R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0019] R2 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 O(CH2) m1 R aa 、-(CH2) n1 OR aa 、-(CH2) n1 NR aa (CH2) m1 R aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 Raa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 S-, -(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 Rdd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0020] R3 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bbwherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0021] R4 is selected from the group consisting of hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, and alkynyl;

[0022] R aa 、R bb 、R cc and R ddare the same or different and are each independently selected from the group consisting of hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, halogen, cyano, nitro, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl, wherein the alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

[0023] x is an integer of 0, 1, 2 or 3;

[0024] y is an integer of 0, 1, 2, 3, 4 or 5;

[0025] m1 is an integer of 0, 1 or 2;

[0026] m2 is an integer of 0, 1 or 2; and

[0027] n1 is an integer of 0, 1, 2, 3, 4 or 5.

[0028] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0029] L1 is selected from a bond, an alkylene group, a cycloalkyl group, a heterocyclic group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -、-NR aa (CH2) n1 -、-(CH2) n1 S(O) m1 -, or -(CH2) n1 S(O) m1 NR aa -;

[0030] L2 is selected from a bond, an oxygen atom, -CR aa R bb -、-(CH2) n1 C(O)-, -NR4-, or -(CH2) n1 S(O) m1 -;

[0031] R4 is selected from a hydrogen atom or an alkyl group;

[0032] L3 is selected from a bond, -NR aa -, or -C(O)NR aa -;

[0033] Ring A is a 6-14 membered fused heteroaryl group;

[0034] Ring B is selected from a 3-10 membered monoheterocyclyl, a 6-14 membered bridged heterocyclyl, a 6-14 membered fused heterocyclyl or a 6-14 membered spiroheterocyclyl;

[0035] Ring C is a heteroaryl group;

[0036] R1 is selected from hydrogen, alkyl, haloalkyl, alkoxy, halogen, amino, hydroxy, cyano, cycloalkyl, heterocyclic, aryl, or heteroaryl; wherein the alkyl, amino, heterocyclic, aryl, or heteroaryl group is optionally further substituted with one or more substituents selected from halogen, cyano, alkyl, or alkoxy;

[0037] R2 is selected from hydrogen, alkyl, alkoxy, halogen, amino, hydroxy, cyano, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 C(O)R cc 、-(CH2) n1 SR aa , or -(CH2) n1 NR aa R bb wherein the alkyl, alkoxy, amino, cycloalkyl, heterocyclyl, aryl, or heteroaryl group is optionally further substituted by one or more substituents selected from substituted or unsubstituted alkyl, unsubstituted alkoxy, unsubstituted cycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted heterocyclyl, or unsubstituted heteroaryl; wherein "substituted" refers to substitution by alkyl or halogen;

[0038] R cc is a heterocyclic group; the heterocyclic group is optionally substituted by an unsubstituted alkyl group;

[0039] R3 is selected from hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxy, halogen, hydroxy, cyano, cycloalkyl, heterocyclic, -(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 S(O) m1 R aa , or -(CH2) n1 S(O)m1 NR aa R bb ; wherein the alkyl, alkoxy, cycloalkyl, or heterocyclic group is optionally further substituted by one or more substituents selected from halogen, hydroxy, unsubstituted alkyl, or unsubstituted alkoxy;

[0040] R aa and R bb are the same or different and are each independently selected from a hydrogen atom, an alkyl group, an amino group, or a heteroaryl group; wherein the alkyl group and the amino group are optionally further substituted by one or more substituents selected from unsubstituted alkyl groups, substituted or unsubstituted heterocyclic groups, and unsubstituted heteroaryl groups; wherein "substituted" refers to substitution by an alkyl group or a halogen;

[0041] x is 0, 1, 2, or 3;

[0042] y is 0, 1, 2, or 3;

[0043] m1 is 0, 1, or 2;

[0044] m2 is 0, 1, or 2; and

[0045] n1 is 0, 1, or 2.

[0046] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0047] L1 is selected from a bond, an alkylene group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0048] L2 is selected from a bond, an oxygen atom, or -NR4-;

[0049] R4 is selected from a hydrogen atom or an alkyl group;

[0050] L3 is -NR aa -;

[0051] Ring A is a 6-14 membered fused heteroaryl group;

[0052] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group;

[0053] Ring C is a heteroaryl group;

[0054] R1 is selected from hydrogen, alkyl, haloalkyl, amino, heterocyclic, or heteroaryl; wherein the alkyl, amino, heterocyclic, or heteroaryl group is optionally further substituted with one or more substituents selected from halogen, cyano, alkyl, or alkoxy;

[0055] R2 is selected from hydrogen, alkyl, alkoxy, halogen, cycloalkyl, heterocyclic, or heteroaryl; wherein the heteroaryl is optionally further substituted with one or more substituents selected from unsubstituted alkyl, unsubstituted alkoxy, or unsubstituted cycloalkyl;

[0056] R3 is selected from hydrogen, alkyl, hydroxyalkyl, halogen, cyano, cycloalkyl, -(CH2) n1 C(O)R aa , or -(CH2) n1 C(O)NR aa R bb ; wherein the alkyl group is optionally further substituted by a hydroxyl group;

[0057] R aa and R bb are the same or different and are each independently selected from a hydrogen atom, an alkyl group, or an amino group;

[0058] x is 0, 1, 2, or 3;

[0059] y is 0, 1, 2, or 3;

[0060] m1 is 0, 1, or 2;

[0061] m2 is 0, 1, or 2; and

[0062] n1 is 0, 1, or 2.

[0063] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L1 is selected from a bond, an alkylene group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -.

[0064] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L2 is selected from a bond, an oxygen atom, or -NR4-.

[0065] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): R4 is selected from a hydrogen atom or an alkyl group.

[0066] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L3 is -NR aa -.

[0067] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): Ring A is a 6-14 membered fused heteroaryl group.

[0068] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group.

[0069] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): Ring C is a heteroaryl group.

[0070] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): R1 is selected from a hydrogen atom, an alkyl group, a halogenated alkyl group, an amino group, a heterocyclic group, or a heteroaryl group; wherein the alkyl group, amino group, heterocyclic group, or heteroaryl group is optionally further substituted by one or more substituents selected from halogen, cyano group, alkyl group, or alkoxy group.

[0071] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): R2 is selected from a hydrogen atom, an alkyl group, an alkoxy group, a halogen, a cycloalkyl group, a heterocyclic group, or a heteroaryl group; wherein the heteroaryl group is optionally further substituted by one or more substituents selected from an unsubstituted alkyl group, an unsubstituted alkoxy group, or an unsubstituted cycloalkyl group.

[0072] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): R3 is selected from hydrogen atom, alkyl, hydroxyalkyl, halogen, cyano, cycloalkyl, -(CH2) n1 C(O)R aa , or -(CH2) n1 C(O)NR aa R bb ; wherein the alkyl group is optionally further substituted by a hydroxy group.

[0073] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): R aa and R bb are the same or different and are each independently selected from a hydrogen atom, an alkyl group, or an amino group.

[0074] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): x is 0, 1, 2 or 3.

[0075] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): y is 0, 1, 2 or 3.

[0076] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): m1 is 0, 1 or 2.

[0077] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): m2 is 0, 1 or 2.

[0078] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): n1 is 0, 1 or 2.

[0079] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is an alkylene group, the alkylene group is preferably a C1-C4 alkylene group, such as -CH2-, -(CH2)2-, -(CH2)3- or -(CH2)4-, more preferably -CH2-, or -(CH2)2-.

[0080] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is a cycloalkyl group, the cycloalkyl group is preferably a C3-C8 cycloalkyl group, more preferably a C3-C6 cycloalkyl group, for example

[0081] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0082] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 C(O)(CH2) m1 -, the -(CH2) n1 C(O)(CH2) m1 -Preferably -C(O)-, -C(O)CH2-, or -CH2C(O)-.

[0083] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, the -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -Preferably -C(O)CH2NH-, -C(O)CH2N(CH3)-, -C(O)CH2NHCH2-, -C(O)CH2NH(CH2)2-, or -CH2C(O)N(CH3)-.

[0084] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -NR aa (CH2) n1 -, the -NR aa (CH2) n1 -Preferably -NH(CH2)2-.

[0085] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 S(O) m1 -, the -(CH2)n1 S(O) m1 -Preferably -S(O)2-.

[0086] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 S(O) m1 NR aa -, the -(CH2) n1 S(O) m1 NR aa -Preferably -S(O)2NH-.

[0087] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the left end of L1 is connected to ring B, and the right end of L1 is connected to R1.

[0088] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L2 is -CR aa R bb -, the -CR aa R bb -Preferably -CH2- or -CH(OH)-.

[0089] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L2 is -(CH2) n1 C(O)-, the -(CH2) n1 C(O)- is preferably -C(O)-.

[0090] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L2 is -NR4-, the -NR4- is preferably -NH- or -N(CH3)-.

[0091] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L2 is -(CH2) n1 S(O) m1 -, the -(CH2) n1 S(O) m1 -Preferably -S(O)2-.

[0092] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the left end of L2 is connected to ring A, and the right end of L2 is connected to ring B.

[0093] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R4 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as methyl, ethyl, propyl or isopropyl, further preferably a methyl group.

[0094] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L3 is -NR aa -, the -NR aa -Preferably -NH-.

[0095] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the L3 is -C(O)NR aa -, the -C(O)NR aa -Preferably -C(O)NH-.

[0096] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the left end of L3 is connected to ring C, and the right end of L3 is connected to ring B.

[0097] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring A is a 6-14 membered fused heteroaryl group, the 6-14 membered fused heteroaryl group is preferably a 6-14 membered fused heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 5- and 6-membered fused heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", or a 6- and 6-membered fused heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4". The 5- and 6-membered fused heteroaryl groups are preferably thienopyrimidinyl or pyrazolopyrimidinyl, benzopyrrole, pyrrolopyridinyl, imidazopyridinyl, triazolopyridinyl, imidazopyridazinyl, pyrrolopyrimidinyl, pyrazolopyrimidinyl, imidazopyrimidinyl, triazolopyrimidinyl, thienopyrimidinyl, thiazopyrimidinyl, pyrrolopyrazinyl, pyrazolopyrazinyl, imidazopyrazinyl, triazolopyrazinyl, pyrrolotriazinyl, imidazotriazinyl or imidazopyrazinone, and more preferably

[0098] Further optimization The 6-membered fused heteroaryl is preferably isoquinolinyl, naphthyridinyl, pyridopyrazinyl, pyridopyrimidinyl, quinazolinyl, pteridinyl, quinoxalinyl, dihydropyranopyrimidinyl, dihydrodioxadienepyrimidinyl, More preferred Further optimization The left end of loop A is connected to L3, and the right end of loop A is connected to L2.

[0099] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 3-10 membered monoheterocyclic group, the 3-10 membered monoheterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0100] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered bridged heterocyclic group, the 6-14 membered bridged heterocyclic group is preferably a 6-14 membered bridged heterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 7-10 membered bridged heterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example For example

[0101] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered fused heterocyclic group, the 6-14 membered fused heterocyclic group is preferably a 6-14 membered fused heterocyclic group in which "the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 7-10 membered fused heterocyclic group in which "the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0102] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered spiroheterocyclic group, the 6-14 membered spiroheterocyclic group is preferably a 6-14 membered spiroheterocyclic group having "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 7-10 membered spiroheterocyclic group having "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0103] In certain technical solutions of the present invention, in the compound represented by general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the upper end of ring B is connected to L1, and the lower end of ring B is connected to L2.

[0104] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring C is a heteroaryl group, the heteroaryl group is preferably a 6-14-membered heteroaryl group having "heteroatoms selected from one or more of N, O and S, with 1-4 heteroatoms", more preferably a 5-6-membered monoheteroaryl group having "heteroatoms selected from one or more of N, O and S, with 1-3 heteroatoms", or an 8-10-membered fused heteroaryl group having "heteroatoms selected from one or more of N, O and S, with 1-3 heteroatoms". The 5-6-membered monoheteroaryl group is preferably pyrazolyl, imidazolyl, thiazolyl, triazolyl, pyridazinyl, pyrimidinyl or pyrazinyl, for example For example The 8-10 membered fused heteroaryl is preferably indazolyl or pyrazolopyridinyl, for example

[0105] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, and further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, and further preferably a methyl group or an ethyl group.

[0106] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is a haloalkyl group, the haloalkyl group is preferably a C1-C8 haloalkyl group, more preferably a C1-C6 haloalkyl group, and further preferably a C1-C3 haloalkyl group, such as -CHF2 or CF3.

[0107] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, and further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, and further preferably a methoxy group or an ethoxy group.

[0108] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is a halogen, the halogen is preferably fluorine.

[0109] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is a cycloalkyl group, the cycloalkyl group is preferably a C3-C8 cycloalkyl group, more preferably a C3-C6 cycloalkyl group, for example

[0110] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0111] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an aryl group, the aryl group is preferably a 6-10 membered aryl group, more preferably a phenyl group.

[0112] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is a heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0113] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is an alkyl group, an amino group, a heterocyclic group, an aryl group or a heteroaryl group, and the alkyl group, the amino group, the heterocyclic group, the aryl group or the heteroaryl group is optionally further substituted by a halogen, the halogen is preferably fluorine.

[0114] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is an amino group, a heterocyclic group, an aryl group or a heteroaryl group, and the amino group, the heterocyclic group, the aryl group or the heteroaryl group is optionally further substituted by an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0115] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is an alkyl group, an amino group, a heterocyclic group, an aryl group or a heteroaryl group, and the alkyl group, the amino group, the heterocyclic group, the aryl group or the heteroaryl group is optionally further substituted by an alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0116] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, and further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, and further preferably a methyl group or an ethyl group.

[0117] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is an alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, and further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, and further preferably a methoxy group or an ethoxy group.

[0118] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is a halogen, the halogen is preferably fluorine, chlorine or bromine.

[0119] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a cycloalkyl group, the cycloalkyl group is preferably a C3-C8 cycloalkyl group, more preferably a C3-C6 cycloalkyl group, for example

[0120] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0121] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is an aryl group, the aryl group is preferably a 6-10 membered aryl group, more preferably a phenyl group.

[0122] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is a heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0123] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is -(CH2) n1 C(O)R cc When the -(CH2) n1 C(O)R cc Preferred

[0124] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is -(CH2) n1 SR aa When the -(CH2) n1 SR aa Preferred

[0125] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is -(CH2) n1 NR aa R bb When the -(CH2) n1 NR aa R bb Preferred

[0126] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkyl group, and the alkyl group is optionally further substituted by an unsubstituted alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0127] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkyl group, and the alkyl group is optionally further substituted by a substituted or unsubstituted heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0128] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkyl group, and the alkyl group is optionally further substituted by a substituted or unsubstituted heterocyclic group, the heterocyclic group is preferably substituted by an alkyl group, and the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0129] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkoxy group, and the alkoxy group is optionally further substituted by an unsubstituted alkoxy group, the unsubstituted alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0130] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkoxy group, and the alkoxy group is optionally further substituted by a substituted or unsubstituted heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0131] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkoxy group, and the alkoxy group is optionally further substituted by a substituted or unsubstituted heterocyclic group, the heterocyclic group is preferably substituted by an alkyl group, and the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0132] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkoxy group, and the alkoxy group is optionally further substituted by an unsubstituted heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0133] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an amino group, and the amino group is optionally further substituted by an unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0134] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heterocyclic group, and the heterocyclic group is optionally further substituted by an unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0135] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heterocyclic group, and the heterocyclic group is optionally further substituted by an unsubstituted alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0136] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heterocyclic group, and the heterocyclic group is optionally further substituted by a substituted or unsubstituted amino group, the amino group is preferably substituted by an alkyl group, and the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0137] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heteroaryl group, and the heteroaryl group is optionally further substituted by a substituted or unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0138] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heteroaryl group, and the heteroaryl group is optionally further substituted by a substituted or unsubstituted alkyl group, the alkyl group is preferably substituted by a halogen, and the halogen is preferably fluorine.

[0139] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heteroaryl group, and the heteroaryl group is optionally further substituted by an unsubstituted alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0140] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heteroaryl group, and the heteroaryl group is optionally further substituted by an unsubstituted cycloalkyl group, the cycloalkyl group is preferably a C3-C8 cycloalkyl group, more preferably a C3-C6 cycloalkyl group, for example

[0141] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): cc When it is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0142] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): cc When the heterocyclic group is optionally substituted by an unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0143] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group or an ethyl group.

[0144] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a hydroxyalkyl group, the alkyl group is preferably a C1-C8 hydroxyalkyl group, more preferably a C1-C6 hydroxyalkyl group, further preferably a C1-C3 hydroxyalkyl group, such as a hydroxymethyl group, a hydroxyethyl group, a hydroxypropyl group or a hydroxyisopropyl group, further preferably a hydroxymethyl group.

[0145] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a haloalkyl group, the haloalkyl group is preferably a C1-C8 haloalkyl group, more preferably a C1-C6 haloalkyl group, and further preferably a C1-C3 haloalkyl group, such as -CHF2 or CF3.

[0146] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0147] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a halogen, the halogen is preferably fluorine.

[0148] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a cycloalkyl group, the cycloalkyl group is preferably a C3-C8 cycloalkyl group, more preferably a C3-C6 cycloalkyl group, for example

[0149] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0150] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkyl group, the alkyl group is optionally further substituted by a halogen, and the halogen is preferably fluorine.

[0151] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkyl group, and the alkyl group is optionally further substituted by an unsubstituted alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0152] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkoxy group, and the alkoxy group is optionally further substituted by an unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0153] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a cycloalkyl group, the cycloalkyl group is preferably substituted by a hydroxyl group.

[0154] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a heterocyclic group, and the heterocyclic group is optionally further substituted by an unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0155] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): when the R3 is an alkyl group and the alkyl group is substituted by a halogen, the R3 is -CHF2 or CF3.

[0156] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkyl group, and the alkyl group is substituted by a hydroxyl group, the R3 is

[0157] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkyl group, and the alkyl group is substituted by an unsubstituted alkoxy group, the R3 is

[0158] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a cycloalkyl group, and the cycloalkyl group is optionally further substituted by a hydroxyl group, the R3 is

[0159] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a heterocyclic group, and the heterocyclic group is optionally further substituted by an unsubstituted alkyl group, the R3 is

[0160] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is -(CH2) n1 C(O)R aa When the -(CH2) n1 C(O)R aa Preferred

[0161] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is -(CH2) n1 C(O)NR aa R bb When the -(CH2) n1 C(O)NR aa R bb Preferred

[0162] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is -(CH2) n1 S(O) m1 R aa When the -(CH2) n1 S(O) m1 R aa Preferred

[0163] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is -(CH2) n1 S(O) m1 NR aa R bb When the -(CH2)n1 S(O) m1 NR aa R bb Preferred

[0164] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb When they are independently alkyl groups, the alkyl groups are preferably C1-C8 alkyl groups, more preferably C1-C6 alkyl groups, further preferably C1-C3 alkyl groups, such as methyl, ethyl, propyl or isopropyl groups, further preferably methyl groups.

[0165] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb When independently a heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0166] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb are independently alkyl groups, and when the alkyl group is optionally further substituted by a substituted or unsubstituted heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0167] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb are independently alkyl groups. When the alkyl group is optionally further substituted by a substituted or unsubstituted heterocyclic group, the heterocyclic group is preferably substituted by an alkyl group. The alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as methyl, ethyl, propyl or isopropyl group, further preferably a methyl group.

[0168] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb are independently alkyl groups, and when the alkyl group is optionally further substituted with an unsubstituted heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0169] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb When the amino group is independently amino and the amino group is optionally further substituted with an unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0170] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): -L1- preferably a bond, -CH2-, -(CH2)2-, -C(O)-, -C(O)CH2-, -CH2C(O)-, -C(O)CH2NH-, -C(O)CH2N(CH3)-, -C(O)CH2NHCH2-, -C(O)CH2NH(CH2)2-, -CH2C(O)N(CH3)-, -NH(CH2)2-, -S(O)2-, or -S(O)2NH-, more preferably a bond, -CH2-, -(CH2)2-, -C(O)-, -C(O)CH2-, -C(O)CH2NH-, -C(O)CH2N(CH3)-, -C(O)CH2NH(CH2)2-, -CH2C(O)N(CH3)-, or -S(O)2-; the left end of L1 is connected to ring B, and the right end of L1 is connected to R1.

[0171] In certain technical schemes of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L2 is preferably a bond, an oxygen atom, -CH2-, -CH(OH)-, -C(O)-, -NH-, -N(CH3)- or -S(O)2-, more preferably a bond, an oxygen atom, -NH-, or -N(CH3)-; the left end of L2 is connected to ring A, and the right end of L2 is connected to ring B.

[0172] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the L3 is preferably a bond, -NH- or -C(O)NH-, more preferably -NH-; the left end of L3 is connected to ring C, and the right end of L3 is connected to ring B.

[0173] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the ring A is preferably the following group,

[0174]

[0175]

[0176] More preferred

[0177] The left end of loop A is connected to L3, and the right end of loop A is connected to L2.

[0178] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the ring B is preferably the following group,

[0179] More preferred The upper end of ring B is connected to L1, and the lower end of ring B is connected to L2.

[0180] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the ring C is preferably the following group,

[0181]

[0182] More preferred

[0183] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): R1 is preferably a hydrogen atom, a methyl group, an ethyl group, a fluorine group, a methoxy group, an ethoxy group, a phenyl group, a cyano group, -CHF2, -CH2CH2CN, -CH2CH2F, -NHCH2CH2CN,

[0184] More preferably, a hydrogen atom, a methyl group, an ethyl group, a fluorine group, a cyano group, -CHF2, -CH2CH2CN, -CH2CH2F,

[0185]

[0186] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): R2 is preferably a hydrogen atom, fluorine, chlorine, bromine, amino, hydroxyl, cyano, methyl, methoxy, More preferably, a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a methyl atom, a methoxy atom,

[0187] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): R3 is preferably a hydrogen atom, a methyl group, an ethyl group, a fluorine group, a cyano group, -CHF2, CF3, More preferably, a hydrogen atom, a methyl group, an ethyl group, a fluorine group, a cyano group,

[0188] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): Structure -L1-R1 is preferably

[0189] More preferred

[0190]

[0191] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0192] L1 and R1 are defined as either of the following sets of definitions:

[0193] (1) L1 is an alkylene group, and R1 is a cycloalkyl group, a heterocyclic group, or a 5-membered heteroaryl group; wherein the cycloalkyl group or heterocyclic group is optionally further substituted by a cyano group; and the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0194] (2) L1 is a cycloalkyl group or a heterocyclic group, and R1 is a cyano group or an alkyl group; the alkyl group may be further substituted with a cyano group;

[0195] (3) L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is a heterocyclic group or a 5-membered heteroaryl group; the heterocyclic group or the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0196] (4) L1 is -C(O)(CH2) m1 NH(CH2) m2 -, R1 is a hydrogen atom, an alkoxy group, a cycloalkyl group, an aryl group or a heteroaryl group; the aryl group is optionally further substituted by an alkoxy group;

[0197] (5) L1 is -(CH2) n1 S(O) m1 -, R1 is a 5-membered heteroaryl group; the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0198] (6) L1 is -(CH2) n1 S(O) m1 NH-, R1 is an alkyl group; the alkyl group is optionally further substituted by a cyano group.

[0199] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0200] L1 and R1 are defined as either of the following sets of definitions:

[0201] (1) L1 is an alkylene group, and R1 is a cycloalkyl group, a heterocyclic group, or a 5-membered heteroaryl group; wherein the cycloalkyl group or heterocyclic group is optionally further substituted by a cyano group; and the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0202] (2) L1 is a cycloalkyl group or a heterocyclic group, and R1 is a cyano group or an alkyl group; the alkyl group is optionally further substituted with a cyano group;

[0203] (3) L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is a heterocyclic group or a 5-membered heteroaryl group; the heterocyclic group or the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0204] (4) L1 is -C(O)(CH2) m1 NH(CH2) m2-, R1 is a hydrogen atom, an alkoxy group, a cycloalkyl group, an aryl group, or a heteroaryl group; the aryl group is optionally further substituted by an alkoxy group;

[0205] (5) L1 is -(CH2) n1 S(O) m1 -, R1 is a 5-membered heteroaryl group; the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0206] (6) L1 is -(CH2) n1 S(O) m1 NH-, R1 is an alkyl group; the alkyl group is optionally further substituted by a cyano group;

[0207] L2 is -NR4-;

[0208] R4 is selected from a hydrogen atom or an alkyl group;

[0209] L3 is -NH-;

[0210] Ring A is a 6-14 membered fused heteroaryl group;

[0211] Ring B is selected from a 3-10 membered monoheterocyclic group or a 6-14 membered bridged heterocyclic group;

[0212] Ring C is a heteroaryl group;

[0213] R2 is selected from a hydrogen atom or an alkyl group;

[0214] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group.

[0215] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0216] L1 and R1 are defined as either of the following:

[0217] (1) L1 is an alkylene group, and R1 is a 5-membered heteroaryl group; wherein the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0218] (2) L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is a heterocyclic group or a 5-membered heteroaryl group; the heterocyclic group or the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0219] (3) L1 is -C(O)(CH2) m1 NH(CH2) m2 -, R1 is a hydrogen atom;

[0220] (4) L1 is -(CH2) n1 S(O) m1-, R1 is a 5-membered heteroaryl group; the 5-membered heteroaryl group is optionally further substituted by an alkyl group;

[0221] L2 is -NR4-;

[0222] R4 is selected from a hydrogen atom or an alkyl group;

[0223] L3 is -NH-;

[0224] Ring A is a 6-14 membered fused heteroaryl group;

[0225] Ring B is a 6-14 membered bridged heterocyclic group;

[0226] Ring C is a heteroaryl group;

[0227] R2 is selected from a hydrogen atom or an alkyl group;

[0228] R3 is selected from a hydrogen atom or an alkyl group.

[0229] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L1 is an alkylene group, R1 is a cycloalkyl group, a heterocyclic group or a 5-membered heteroaryl group; wherein the cycloalkyl group or heterocyclic group is optionally further substituted by a cyano group; and the 5-membered heteroaryl group is optionally further substituted by an alkyl group.

[0230] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L1 is a cycloalkyl group or a heterocyclic group, R1 is a cyano group or an alkyl group; the alkyl group is optionally further substituted by a cyano group.

[0231] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is a heterocyclic group or a 5-membered heteroaryl group; the heterocyclic group or the 5-membered heteroaryl group is optionally further substituted by an alkyl group.

[0232] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L1 is -C(O)(CH2) m1 NH(CH2) m2 -, R1 is a hydrogen atom, an alkoxy group, a cycloalkyl group, an aryl group or a heteroaryl group; the aryl group is optionally further substituted by an alkoxy group.

[0233] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L1 is -(CH2)n1 S(O) m1 -, R1 is a 5-membered heteroaryl group; the 5-membered heteroaryl group is optionally further substituted by an alkyl group.

[0234] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): L1 is -(CH2) n1 S(O) m1 NH-, R1 is an alkyl group; the alkyl group is optionally further substituted by a cyano group.

[0235] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0236]

[0237]

[0238] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0239] Ring B is selected from

[0240] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0241] Ring B is selected from

[0242] L1 is alkylene or -NH(CH2) n1 -;

[0243] L2 is selected from a bond, or -NH-;

[0244] L3 is NH;

[0245] Ring A is a 6-14 membered fused heteroaryl group;

[0246] Ring C is a heteroaryl group;

[0247] R1 is cyano;

[0248] R2 is a hydrogen atom;

[0249] R3 is selected from a hydrogen atom or an alkyl group;

[0250] n1 is 0, 1, or 2.

[0251] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0252] Ring B is

[0253] L1 is an alkylene group;

[0254] L2 is a key;

[0255] L3 is NH;

[0256] Ring A is a 6-14 membered fused heteroaryl group;

[0257] Ring C is a heteroaryl group;

[0258] R1 is cyano;

[0259] R2 is a hydrogen atom;

[0260] R3 is a hydrogen atom or an alkyl group.

[0261] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0262]

[0263] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0264] L2 is selected from a bond, -CHR aa -、-(CH2) n1 C(O)-, or -(CH2) n1 S(O)2-;R aa Selected from a hydrogen atom or a hydroxyl group;

[0265] n1 is 0, 1, or 2.

[0266] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0267] L2 is selected from a bond, -CHR aa -、-(CH2) n1 C(O)- or -(CH2) n1 S(O)2-;R aa selected from a hydrogen atom or a hydroxyl group;

[0268] n1 is 0, 1, or 2;

[0269] L1 is an alkylene group;

[0270] L3 is NH;

[0271] Ring A is a 6-14 membered fused heteroaryl group;

[0272] Ring B is a 6-14 membered bridged heterocyclic group;

[0273] Ring C is a heteroaryl group;

[0274] R1 is cyano;

[0275] R2 is selected from hydrogen atom, alkyl group, alkoxy group, or heterocyclic group;

[0276] R3 is selected from a hydrogen atom or an alkyl group.

[0277] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0278]

[0279] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0280]

[0281] Then, the right end of ring A is connected to L2.

[0282] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0283] Ring A is a 6-14 membered fused heteroaryl group, and Ring A is not Among them, the left end of ring A is connected to L3, and the right end of ring A is connected to L2;

[0284] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0285] L2 is selected from a bond, an oxygen atom, or -NR4-;

[0286] R4 is selected from a hydrogen atom or an alkyl group;

[0287] L3 is -NH-;

[0288] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group;

[0289] Ring C is a heteroaryl group;

[0290] R1 is selected from hydrogen, alkyl, alkoxy, cyano, cycloalkyl, heterocyclic, aryl, or heteroaryl; the heterocyclic or heteroaryl group is optionally further substituted with cyano or alkyl; the aryl group is optionally further substituted with alkoxy;

[0291] R2 is selected from hydrogen, alkyl, alkoxy, halogen, or heterocyclic group; the alkyl group is optionally further substituted by unsubstituted alkoxy, alkyl or unsubstituted heterocyclic group; the heterocyclic group is optionally further substituted by alkyl;

[0292] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group;

[0293] R aa is selected from a hydrogen atom or an alkyl group.

[0294] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0295] Ring A is a 6-14 membered fused heteroaryl group, and Ring A is not Among them, the left end of ring A is connected to L3, and the right end of ring A is connected to L2;

[0296] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0297] L2 is selected from an oxygen atom, or -NR4-;

[0298] R4 is selected from a hydrogen atom or an alkyl group;

[0299] L3 is -NH-;

[0300] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group;

[0301] Ring C is a heteroaryl group;

[0302] R1 is selected from hydrogen, alkyl, alkoxy, cyano, heterocyclic, or heteroaryl; the heterocyclic or heteroaryl group is optionally further substituted by cyano or alkyl;

[0303] R2 is selected from hydrogen, alkyl, alkoxy, halogen, or heterocyclic group; the alkyl group is optionally further substituted by an unsubstituted alkoxy group, an alkyl-substituted or unsubstituted heterocyclic group; the heterocyclic group is optionally further substituted by an alkyl group;

[0304] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group;

[0305] R aa is selected from a hydrogen atom or an alkyl group.

[0306] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring A is a 6-14 membered fused heteroaryl group, the 6-14 membered fused heteroaryl group is preferably a 6-14 membered fused heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 5- and 6-membered fused heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", or a 6- and 6-membered fused heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4". The 5- and 6-membered fused heteroaryl groups are preferably thienopyrimidinyl or pyrazolopyrimidinyl, benzopyrrole, pyrrolopyridinyl, imidazopyridinyl, triazolopyridinyl, imidazopyridazinyl, pyrrolopyrimidinyl, pyrazolopyrimidinyl, imidazopyrimidinyl, triazolopyrimidinyl, thienopyrimidinyl, thiazopyrimidinyl, pyrrolopyrazinyl, pyrazolopyrazinyl, imidazopyrazinyl, triazolopyrazinyl, pyrrolotriazinyl, imidazotriazinyl or imidazopyrazinone, and more preferably

[0307] The 6-membered fused heteroaryl is preferably isoquinolinyl, naphthyridinyl, pyridopyrazinyl, pyridopyrimidinyl, quinazolinyl, pteridinyl, quinoxalinyl, dihydropyranopyrimidinyl, dihydrodioxadienepyrimidinyl, More preferred

[0308]

[0309] Among them, the left end of ring A is connected to L3, and the right end of ring A is connected to L2.

[0310] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the ring A is preferably pyrrolopyrazinyl, pyrazolopyrazinyl, imidazopyrazinyl, triazolopyrazinyl, Pyridopyrazinyl, pteridinyl or quinoxalinyl, more preferably

[0311] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): The ring A is preferably pyrazolopyrimidinyl or pyrazolopyrazinyl, more preferably

[0312] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): The ring A is preferably imidazopyridinyl, imidazopyridazinyl, imidazopyrimidinyl, imidazopyrazinyl or imidazotriazinyl, more preferably

[0313] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): the ring A is preferably a thiazolyl pyrimidinyl group, more preferably

[0314] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above): The ring A is preferably a triazolopyridinyl, a triazolopyrimidinyl or a triazolopyrazinyl, more preferably

[0315] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0316]

[0317]

[0318]

[0319]

[0320]

[0321]

[0322] In certain technical solutions of the present invention, the compound represented by formula (I) is preferably a compound represented by formula (I-1),

[0323]

[0324] wherein ring D is a heterocycloalkenyl, aryl, or heteroaryl group;

[0325] X1, X2 and X3 are independently CH or N;

[0326] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0327] R1 is selected from halogen, cyano, alkyl, alkoxy, cycloalkyl, heterocyclic, or heteroaryl; the alkyl group is optionally further substituted with halogen or alkoxy; the heterocyclic group is optionally further substituted with cyano; the heteroaryl group is optionally further substituted with alkyl;

[0328] When L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is an alkyl group, a heterocyclic group, or a heteroaryl group; the alkyl group is optionally further substituted by a halogen; the heterocyclic group or heteroaryl group is optionally further substituted by an alkyl group;

[0329] L2, L3, R2, R3, Ring B, Ring C, x and y are as defined above.

[0330] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above):

[0331] Ring D is heterocycloalkenyl, aryl, or heteroaryl;

[0332] X1, X2 and X3 are independently CH or N;

[0333] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O)m1 -;

[0334] R1 is selected from halogen, cyano, alkyl, alkoxy, cycloalkyl, heterocyclic, or heteroaryl; the alkyl group is optionally further substituted with halogen or alkoxy; the heterocyclic group is optionally further substituted with cyano; the heteroaryl group is optionally further substituted with alkyl;

[0335] When L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is an alkyl group, a heterocyclic group, or a heteroaryl group; the alkyl group is optionally further substituted by a halogen; the heterocyclic group or heteroaryl group is optionally further substituted by an alkyl group;

[0336] L2 is selected from an oxygen atom, or -NR4-;

[0337] R4 is selected from a hydrogen atom or an alkyl group;

[0338] L3 is -NH-;

[0339] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered fused heterocyclic group, or a 6-14 membered bridged heterocyclic group;

[0340] Ring C is a heteroaryl group;

[0341] R2 is selected from hydrogen, alkyl, alkoxy, halogen, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 OR cc , or -(CH2) n1 NR aa R bb The alkyl group is optionally further substituted by an alkyl-substituted or unsubstituted heterocyclic group; the alkoxy group is optionally further substituted by an unsubstituted alkoxy group, an alkyl-substituted or unsubstituted heterocyclic group, or an unsubstituted heteroaryl group; the heterocyclic group is optionally further substituted by an unsubstituted alkyl group, an unsubstituted alkoxy group, or an alkyl-substituted amino group; the heteroaryl group is optionally further substituted by a halogen-substituted or unsubstituted alkyl group, an unsubstituted alkoxy group, or an unsubstituted cycloalkyl group;

[0342] R aa and R bb are the same or different and are each independently selected from a hydrogen atom or an alkyl group; the alkyl group is optionally further substituted by an alkyl-substituted or unsubstituted heterocyclic group, or an unsubstituted heteroaryl group;

[0343] R cc is a heterocyclic group; the heterocyclic group is optionally further substituted by an unsubstituted alkyl group;

[0344] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group.

[0345] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above):

[0346] Ring D is heterocycloalkenyl, aryl, or heteroaryl;

[0347] X1, X2 and X3 are independently CH or N;

[0348] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0349] R1 is selected from halogen, cyano, alkyl, heterocyclic, or heteroaryl; the alkyl group is optionally further substituted with halogen or alkoxy; the heterocyclic group is optionally further substituted with cyano; the heteroaryl group is optionally further substituted with alkyl;

[0350] When L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is an alkyl group, a heterocyclic group, or a heteroaryl group; the alkyl group is optionally further substituted by a halogen; the heterocyclic group or heteroaryl group is optionally further substituted by an alkyl group;

[0351] L2 is selected from an oxygen atom, or -NR4-;

[0352] R4 is selected from a hydrogen atom or an alkyl group;

[0353] L3 is -NH-;

[0354] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered fused heterocyclic group, or a 6-14 membered bridged heterocyclic group;

[0355] Ring C is a heteroaryl group;

[0356] R2 is selected from hydrogen, alkyl, alkoxy, halogen, cycloalkyl, heterocyclic, aryl, or heteroaryl; the heteroaryl is optionally further substituted with unsubstituted alkyl, unsubstituted alkoxy, or unsubstituted cycloalkyl;

[0357] R aa is selected from a hydrogen atom or an alkyl group;

[0358] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group.

[0359] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): Ring D is a heterocycloalkenyl group, an aryl group, or a heteroaryl group.

[0360] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): X1, X2 and X3 are independently CH or N.

[0361] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -.

[0362] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): R1 is selected from halogen, cyano, alkyl, heterocyclic group, or heteroaryl; the alkyl group is optionally further substituted by halogen or alkoxy; the heterocyclic group is optionally further substituted by cyano; the heteroaryl group is optionally further substituted by alkyl.

[0363] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): When L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is an alkyl group, a heterocyclic group, or a heteroaryl group; the alkyl group is optionally further substituted by a halogen; the heterocyclic group or heteroaryl group is optionally further substituted by an alkyl group.

[0364] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): L2 is selected from an oxygen atom, or -NR4-.

[0365] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): R4 is selected from a hydrogen atom or an alkyl group.

[0366] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): L3 is -NH-.

[0367] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered fused heterocyclic group, or a 6-14 membered bridged heterocyclic group.

[0368] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): Ring C is a heteroaryl group.

[0369] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): R2 is selected from a hydrogen atom, an alkyl group, an alkoxy group, a halogen, a cycloalkyl group, a heterocyclic group, an aryl group, or a heteroaryl group; the heteroaryl group is optionally further substituted by an unsubstituted alkyl group, an unsubstituted alkoxy group, or an unsubstituted cycloalkyl group.

[0370] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): R aa is selected from a hydrogen atom or an alkyl group.

[0371] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group.

[0372] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): When ring D is a heterocycloalkenyl group, the heterocycloalkenyl group is preferably a 3-8 membered heterocycloalkenyl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", and more preferably a 4-6 membered heterocycloalkenyl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0373] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): When ring D is an aromatic group, the aromatic group is preferably a 6-10 membered aromatic group, more preferably a phenyl group.

[0374] In certain technical solutions of the present invention, in the compound represented by the general formula (I-1), the definitions of certain groups are as follows (undefined groups are as shown above): When ring D is a heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0375] More preferred

[0376] In certain technical solutions of the present invention, the compound represented by formula (I) is preferably a compound represented by formula (I-2),

[0377]

[0378] Wherein, L1, L2, L3, R1, R2, R3, Ring B, Ring C, and y are as defined above;

[0379] x is 0, 1, or 2.

[0380] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above):

[0381] L1 is an alkylene group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0382] R aa is selected from a hydrogen atom or an alkyl group;

[0383] L2 is -NH-;

[0384] L3 is -NH-;

[0385] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group;

[0386] Ring C is a heteroaryl group;

[0387] R1 is an alkyl group, a cyano group, a heterocyclic group, or a heteroaryl group; the heterocyclic group is optionally further substituted by a cyano group;

[0388] R2 is selected from a hydrogen atom or an alkyl group;

[0389] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group;

[0390] x is 0, 1, or 2.

[0391] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above):

[0392] L1 is an alkylene group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -、-(CH2) n1 S(O) m1 -;

[0393] R aa is selected from a hydrogen atom or an alkyl group;

[0394] L2 is -NH-;

[0395] L3 is -NH-;

[0396] Ring B is selected from a 6-14 membered bridged heterocyclic group or a 6-14 membered fused heterocyclic group;

[0397] Ring C is a heteroaryl group;

[0398] R1 is an alkyl group, a cyano group, or a heterocyclic group;

[0399] R2 is selected from a hydrogen atom or an alkyl group;

[0400] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group;

[0401] x is 0, 1, or 2.

[0402] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above):

[0403] L1 is C1-C4 alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2)m2 -、-(CH2) n1 S(O) m1 -;

[0404] R aa A hydrogen atom or a C1-C3 alkyl group;

[0405] L2 is -NH-;

[0406] L3 is -NH-;

[0407] Ring B is selected from a 7-10 membered bridged heterocyclic group wherein "the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1-3" or a 7-10 membered fused heterocyclic group wherein "the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1-3";

[0408] Ring C is a 5-6 membered monoheteroaryl group having "one or more heteroatoms selected from N, O and S, with 1 to 3 heteroatoms";

[0409] R1 is a C1-C4 alkyl group, a cyano group, or a 4-6 membered monoheterocyclic group having one or more heteroatoms selected from N, O and S, with 1 to 3 heteroatoms;

[0410] R2 is selected from a hydrogen atom, or a C1-C3 alkyl group;

[0411] R3 is selected from a hydrogen atom, a C1-C3 alkyl group, or a C1-C3 hydroxyalkyl group;

[0412] x is 0, 1, or 2.

[0413] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When L1 is an alkylene group, the alkylene group is preferably a C1-C4 alkylene group, such as -CH2-, -(CH2)2-, -(CH2)3- or -(CH2)4-, more preferably -CH2-, or -(CH2)2-.

[0414] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 C(O)(CH2) m1 -, the -(CH2) n1 C(O)(CH2) m1 -Preferably -C(O)-, -C(O)CH2-, or -CH2C(O)-.

[0415] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, the -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -Preferably -C(O)CH2NH-, -C(O)CH2N(CH3)-, or -CH2C(O)N(CH3)-.

[0416] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 S(O) m1 -, the -(CH2) n1 S(O) m1 -Preferably -S(O)2-.

[0417] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): aa When it is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0418] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 3-10 membered monoheterocyclic group, the 3-10 membered monoheterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0419] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered bridged heterocyclic group, the 6-14 membered bridged heterocyclic group is preferably a 6-14 membered bridged heterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 7-10 membered bridged heterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0420] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered fused heterocyclic group, the 6-14 membered fused heterocyclic group is preferably a 6-14 membered fused heterocyclic group in which "the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 7-10 membered fused heterocyclic group in which "the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0421] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring C is a heteroaryl group, the heteroaryl group is preferably a 6-14-membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 5-6-membered single heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", or an 8-10-membered fused heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3". The 5-6-membered single heteroaryl group is preferably

[0422] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0423] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0424] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is a heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0425] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0426] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0427] In certain technical solutions of the present invention, in the compound represented by the general formula (I-2), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a hydroxyalkyl group, the alkyl group is preferably a C1-C8 hydroxyalkyl group, more preferably a C1-C6 hydroxyalkyl group, further preferably a C1-C3 hydroxyalkyl group, such as a hydroxymethyl group, a hydroxyethyl group, a hydroxypropyl group or a hydroxyisopropyl group, further preferably a hydroxymethyl group.

[0428] In certain technical solutions of the present invention, the compound represented by formula (I) is preferably a compound represented by formula (I-3),

[0429]

[0430] Wherein, L1, L2, L3, R1, R2, R3, Ring B, Ring C, and y are as defined above;

[0431] x is 0, 1, or 2.

[0432] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above):

[0433] L1 is an alkylene group, -(CH2)n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0434] L2 is an oxygen atom, or -NR4-;

[0435] R4 is selected from a hydrogen atom or an alkyl group;

[0436] L3 is -NH-;

[0437] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group;

[0438] Ring C is a heteroaryl group;

[0439] R1 is a hydrogen atom, an alkyl group, an alkoxy group, a cyano group, a cycloalkyl group, a heterocyclic group, an aryl group, or a heteroaryl group; the heterocyclic group or heteroaryl group is optionally further substituted with an unsubstituted alkyl group or a cyano group; the aryl group is optionally further substituted with an unsubstituted alkoxy group;

[0440] R2 is selected from hydrogen atom, alkyl group, heterocyclic group, or -(CH2) n1 SR aa The alkyl group is optionally further substituted by an unsubstituted alkoxy group, or an alkyl-substituted or unsubstituted heterocyclic group; the heterocyclic group is optionally further substituted by an alkyl group;

[0441] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group;

[0442] R aa is selected from a hydrogen atom or an alkyl group;

[0443] x is 0, 1, or 2.

[0444] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above):

[0445] L1 is an alkylene group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0446] L2 is an oxygen atom, or -NR4-;

[0447] R4 is selected from a hydrogen atom or an alkyl group;

[0448] L3 is -NH-;

[0449] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group;

[0450] Ring C is a heteroaryl group;

[0451] R1 is a hydrogen atom, an alkyl group, a cyano group, a heterocyclic group, or a heteroaryl group; the heterocyclic group or heteroaryl group is optionally further substituted by an unsubstituted alkyl group or a cyano group;

[0452] R2 is selected from a hydrogen atom or an alkyl group;

[0453] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group;

[0454] R aa is selected from a hydrogen atom or an alkyl group;

[0455] x is 0, 1, or 2.

[0456] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above):

[0457] L1 is C1-C4 alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0458] L2 is an oxygen atom, or -NR4-;

[0459] R4 is selected from a hydrogen atom or a C1-C3 alkyl group;

[0460] L3 is -NH-;

[0461] Ring B is selected from a 4-6 membered monoheterocyclic group wherein "the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1-3", a 7-10 membered bridged heterocyclic group wherein "the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1-3", or a 7-10 membered fused heterocyclic group wherein "the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1-3";

[0462] Ring C is a 5-6 membered monoheteroaryl group having "one or more heteroatoms selected from N, O and S, with 1 to 3 heteroatoms";

[0463] R1 is a hydrogen atom, a C1-C3 alkyl group, a cyano group, a 4-6 membered monoheterocyclic group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3", or a 5-6 membered heteroaryl group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3"; the monoheterocyclic group or heteroaryl group is optionally further substituted by a C1-C3 alkyl group or a cyano group;

[0464] R2 is selected from a hydrogen atom, or a C1-C3 alkyl group;

[0465] R3 is selected from a hydrogen atom, a C1-C3 alkyl group, or a C1-C3 hydroxyalkyl group;

[0466] R aa A hydrogen atom or a C1-C3 alkyl group;

[0467] x is 0, 1, or 2.

[0468] Preferred:

[0469] L1 is an alkylene group, -(CH2) n1 C(O)(CH2) m1 -, or -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -;

[0470] R1 is an alkyl group, a cyano group, a heterocyclic group or a heteroaryl group; the heterocyclic group is optionally further substituted by an alkyl group;

[0471] L2 is an oxygen atom, or -NR4-;

[0472] R4 is selected from a hydrogen atom or an alkyl group;

[0473] L3 is -NH-;

[0474] Ring B is a 6-14 membered bridged heterocyclic group;

[0475] Ring C is a heteroaryl group;

[0476] R2 is selected from a hydrogen atom or an alkyl group;

[0477] R3 is selected from a hydrogen atom or an alkyl group;

[0478] R aa is selected from a hydrogen atom or an alkyl group.

[0479] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is an alkylene group, the alkylene group is preferably a C1-C4 alkylene group, such as -CH2-, -(CH2)2-, -(CH2)3- or -(CH2)4-, more preferably -CH2-, or -(CH2)2-.

[0480] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 C(O)(CH2) m1 -, the -(CH2) n1 C(O)(CH2) m1 -Preferably -C(O)-, -C(O)CH2-, or -CH2C(O)-.

[0481] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, the -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -Preferably -C(O)CH2NH-, -C(O)CH2N(CH3)-, -C(O)CH2NHCH2-, -C(O)CH2NH(CH2)2-, or -CH2C(O)N(CH3)-.

[0482] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 S(O) m1 -, the -(CH2) n1 S(O) m1 -Preferably -S(O)2-.

[0483] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R4 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0484] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 3-10 membered monoheterocyclic group, the 3-10 membered monoheterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0485] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered bridged heterocyclic group, the 6-14 membered bridged heterocyclic group is preferably a 6-14 membered bridged heterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 7-10 membered bridged heterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0486] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered fused heterocyclic group, the 6-14 membered fused heterocyclic group is preferably a 6-14 membered fused heterocyclic group in which "the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 7-10 membered fused heterocyclic group in which "the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0487] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring C is a heteroaryl group, the heteroaryl group is preferably a 6-14-membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6-membered monoheteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0488] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, and further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, and further preferably a methyl group or an ethyl group.

[0489] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, and further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, and further preferably a methoxy group.

[0490] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is a cycloalkyl group, the cycloalkyl group is preferably a C3-C8 cycloalkyl group, more preferably a C3-C6 cycloalkyl group, for example

[0491] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0492] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an aromatic group, the aromatic group is preferably a 6-10 membered aromatic group, more preferably a phenyl group.

[0493] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is a heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0494] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the heterocyclic group or heteroaryl group is optionally further substituted by an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0495] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the aryl group is optionally further substituted by an alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0496] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, and further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, and further preferably a methyl group or an ethyl group.

[0497] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0498] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is -(CH2) n1 SR aa When the -(CH2) n1 SR aa Preferred

[0499] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkyl group, and the alkyl group is optionally further substituted by an unsubstituted unsubstituted alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0500] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkyl group, and the alkyl group is optionally further substituted by a substituted or unsubstituted heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0501] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the heterocyclic group is optionally further substituted by an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0502] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group or an ethyl group.

[0503] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a hydroxyalkyl group, the alkyl group is preferably a C1-C8 hydroxyalkyl group, more preferably a C1-C6 hydroxyalkyl group, further preferably a C1-C3 hydroxyalkyl group, such as a hydroxymethyl group, a hydroxyethyl group, a hydroxypropyl group or a hydroxyisopropyl group, further preferably a hydroxymethyl group.

[0504] In certain technical solutions of the present invention, in the compound represented by the general formula (I-3), the definitions of certain groups are as follows (undefined groups are as shown above): aa When it is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0505] In certain technical solutions of the present invention, the compound represented by the general formula (I) may be the compound represented by the following formula (I-4):

[0506]

[0507] Wherein, L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0508] R1 is selected from halogen, cyano, alkyl, alkoxy, heterocyclic group, or heteroaryl; the alkyl group is optionally further substituted with halogen or alkoxy; the heterocyclic group is optionally further substituted with cyano;

[0509] When L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is an alkyl group, a heterocyclic group, or a heteroaryl group; the alkyl group is optionally further substituted by a halogen; the heterocyclic group or heteroaryl group is optionally further substituted by an alkyl group;

[0510] L2, L3, R2, R3, Ring B, Ring C, x and y are as defined above.

[0511] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above):

[0512] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0513] R1 is selected from halogen, cyano, alkyl, alkoxy, heterocyclic group, or heteroaryl; the alkyl group is optionally further substituted with halogen or alkoxy; the heterocyclic group is optionally further substituted with cyano;

[0514] When L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is an alkyl group, a heterocyclic group, or a heteroaryl group; the alkyl group is optionally further substituted by a halogen; the heterocyclic group or heteroaryl group is optionally further substituted by an alkyl group;

[0515] L2 is -NR4-;

[0516] R4 is selected from a hydrogen atom or an alkyl group;

[0517] L3 is -NH-;

[0518] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group;

[0519] Ring C is a heteroaryl group;

[0520] R2 is selected from hydrogen, alkyl, alkoxy, halogen, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 OR cc , or -(CH2) n1 NR aa R bb The alkyl group is optionally further substituted by an alkyl-substituted or unsubstituted heterocyclic group; the alkoxy group is optionally further substituted by an unsubstituted alkoxy group, an alkyl-substituted or unsubstituted heterocyclic group, or an unsubstituted heteroaryl group; the heterocyclic group is optionally further substituted by an unsubstituted alkyl group, an unsubstituted alkoxy group, or an alkyl-substituted amino group; the heteroaryl group is optionally further substituted by a halogen-substituted or unsubstituted alkyl group, an unsubstituted alkoxy group, or an unsubstituted cycloalkyl group;

[0521] R aa and R bb are the same or different and are each independently selected from a hydrogen atom or an alkyl group; the alkyl group is optionally further substituted by an alkyl-substituted or unsubstituted heterocyclic group, or an unsubstituted heteroaryl group;

[0522] R cc is a heterocyclic group; the heterocyclic group is optionally further substituted by an unsubstituted alkyl group;

[0523] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group.

[0524] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above):

[0525] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0526] R1 is selected from halogen, cyano, alkyl, heterocyclic, or heteroaryl; the alkyl group is optionally further substituted with halogen or alkoxy; the heterocyclic group is optionally further substituted with cyano; the heteroaryl group is optionally further substituted with alkyl;

[0527] When L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is an alkyl group, a heterocyclic group, or a heteroaryl group; the alkyl group is optionally further substituted by a halogen; the heterocyclic group or heteroaryl group is optionally further substituted by an alkyl group;

[0528] L2 is -NR4-;

[0529] R4 is selected from a hydrogen atom or an alkyl group;

[0530] L3 is -NH-;

[0531] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group, or a 6-14 membered fused heterocyclic group;

[0532] Ring C is a heteroaryl group;

[0533] R2 is selected from hydrogen, alkyl, alkoxy, halogen, cycloalkyl, heterocyclic, aryl, or heteroaryl; the heteroaryl is optionally further substituted with unsubstituted alkyl, unsubstituted alkoxy, or unsubstituted cycloalkyl;

[0534] R3 is selected from a hydrogen atom, an alkyl group, or a hydroxyalkyl group.

[0535] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above):

[0536] L1 is selected from C1-C4 alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0537] R1 is selected from halogen, cyano, C1-C3 alkyl, a 4-6 membered monoheterocyclic group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3", or a 5-6 membered monoheteroaryl group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3"; the C1-C3 alkyl group is optionally further substituted with halogen or C1-C3 alkoxy; the heterocyclic group is optionally further substituted with cyano; the heteroaryl group is optionally further substituted with C1-C3 alkyl;

[0538] When L1 is -(CH2) n1 C(O)(CH2) m1 -, R1 is a C1-C3 alkyl group, a 4-6 membered monoheterocyclic group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3", or a 5-6 membered monoheteroaryl group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3"; the C1-C3 alkyl group is optionally further substituted with halogen; the heterocyclic group or heteroaryl group is optionally further substituted with a C1-C3 alkyl group;

[0539] L2 is -NR4-;

[0540] R4 is selected from a hydrogen atom or a C1-C3 alkyl group;

[0541] L3 is -NH-;

[0542] Ring B is selected from a 4-6 membered monoheterocyclic group wherein "the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1-3", a 7-10 membered bridged heterocyclic group wherein "the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1-3", or a 7-10 membered fused heterocyclic group wherein "the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1-3";

[0543] Ring C is a 5-6 membered monoheteroaryl group having "one or more heteroatoms selected from N, O and S, with 1 to 3 heteroatoms";

[0544] R2 is selected from a hydrogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group, a halogen, a cycloalkyl group, a 4-6 membered monoheterocyclic group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3", a 6-10 membered aryl group, or a 5-6 membered heteroaryl group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3"; the heteroaryl group is optionally further substituted by an unsubstituted C1-C3 alkyl group, an unsubstituted C1-C3 alkoxy group, or an unsubstituted 4-6 membered monoheterocyclic group "wherein the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3";

[0545] R3 is selected from a hydrogen atom, a C1-C3 alkyl group, or a C1-C3 hydroxyalkyl group.

[0546] L1 is an alkylene group, or -(CH2) n1 S(O) m1 -;

[0547] R1 is cyano or heterocyclic; the heterocyclic group is optionally further substituted by cyano;

[0548] L2 is -NH-;

[0549] L3 is -NH-;

[0550] R2 is selected from hydrogen atom, halogen, or alkoxy;

[0551] R3 is selected from a hydrogen atom or an alkyl group.

[0552] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is an alkylene group, the alkylene group is preferably a C1-C4 alkylene group, such as -CH2-, -(CH2)2-, -(CH2)3- or -(CH2)4-, more preferably -CH2-, or -(CH2)2-.

[0553] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 C(O)(CH2) m1 -, the -(CH2) n1 C(O)(CH2) m1 -Preferably -C(O)-, -C(O)CH2-, or -CH2C(O)-.

[0554] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, the -(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -Preferably -C(O)CH2NH- or -C(O)CH2N(CH3)-.

[0555] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the L1 is -(CH2) n1 S(O) m1 -, the -(CH2) n1 S(O) m1 -Preferably -S(O)2-.

[0556] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R4 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0557] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 3-10 membered monoheterocyclic group, the 3-10 membered monoheterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0558] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered bridged heterocyclic group, the 6-14 membered bridged heterocyclic group is preferably a 6-14 membered bridged heterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", more preferably a 7-10 membered bridged heterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0559] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring B is a 6-14 membered fused heterocyclic group, the 6-14 membered fused heterocyclic group is preferably a 6-14 membered fused heterocyclic group in which "the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 7-10 membered fused heterocyclic group in which "the heteroatoms are selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0560] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring C is a heteroaryl group, the heteroaryl group is preferably a 6-14-membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6-membered monoheteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0561] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is a halogen, the halogen is preferably fluorine.

[0562] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, and further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, and further preferably a methyl group or an ethyl group.

[0563] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is an alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, and further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, and further preferably a methoxy group or an ethoxy group.

[0564] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R1 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0565] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R1 is a heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0566] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, and further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, and further preferably a methyl group or an ethyl group.

[0567] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is an alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, and further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, and further preferably a methoxy group or an ethoxy group.

[0568] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is a halogen, the halogen is preferably fluorine, chlorine or bromine.

[0569] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is a heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0570] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is an aromatic group, the aromatic group is preferably a 6-10 membered aromatic group, more preferably a phenyl group.

[0571] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is a heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0572] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R2 is -(CH2) n1 NR aa R bb When the -(CH2) n1 NR aa R bb Preferred

[0573] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkyl group, and the alkyl group is optionally further substituted by a substituted or unsubstituted heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0574] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkoxy group, and the alkoxy group is optionally further substituted by an unsubstituted alkoxy group, the unsubstituted alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0575] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkoxy group, and the alkoxy group is optionally further substituted by an alkyl group or an unsubstituted heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0576] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkoxy group, and the alkoxy group is optionally further substituted by an alkyl group or an unsubstituted heterocyclic group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0577] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is an alkoxy group, and the alkoxy group is optionally further substituted by an unsubstituted heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0578] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heterocyclic group, and the heterocyclic group is optionally further substituted by an unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0579] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heterocyclic group, and the heterocyclic group is optionally further substituted by an unsubstituted alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0580] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heterocyclic group, and the heterocyclic group is optionally further substituted by an amino group substituted by an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0581] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heteroaryl group, and the heteroaryl group is optionally further substituted by a halogen or unsubstituted alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0582] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heteroaryl group, and the heteroaryl group is optionally further substituted by a halogen or an unsubstituted alkyl group, the halogen is preferably fluorine.

[0583] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heteroaryl group, and the heteroaryl group is optionally further substituted by an unsubstituted alkoxy group, the alkoxy group is preferably a C1-C8 alkoxy group, more preferably a C1-C6 alkoxy group, further preferably a C1-C3 alkoxy group, such as a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, further preferably a methoxy group.

[0584] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When R2 is a heteroaryl group, and the heteroaryl group is optionally further substituted by an unsubstituted cycloalkyl group, the cycloalkyl group is preferably a C3-C8 cycloalkyl group, more preferably a C3-C6 cycloalkyl group, for example

[0585] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb When they are independently alkyl groups, the alkyl groups are preferably C1-C8 alkyl groups, more preferably C1-C6 alkyl groups, further preferably C1-C3 alkyl groups, such as methyl, ethyl, propyl or isopropyl groups, further preferably methyl groups.

[0586] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bbare independently alkyl groups, and when the alkyl group is optionally further substituted by an alkyl group or an unsubstituted heterocyclic group, the heterocyclic group is preferably a 3-8 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 4-6 membered monoheterocyclic group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0587] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb When the alkyl group is independently substituted by an alkyl group or an unsubstituted heterocyclic group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group.

[0588] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): aa and R bb are independently alkyl groups, and when the alkyl group is optionally further substituted with an unsubstituted heteroaryl group, the heteroaryl group is preferably a 5-10 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6 membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3", for example

[0589] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is an alkyl group, the alkyl group is preferably a C1-C8 alkyl group, more preferably a C1-C6 alkyl group, further preferably a C1-C3 alkyl group, such as a methyl group, an ethyl group, a propyl group or an isopropyl group, further preferably a methyl group or an ethyl group.

[0590] In certain technical solutions of the present invention, in the compound represented by the general formula (I-4), the definitions of certain groups are as follows (undefined groups are as shown above): When the R3 is a hydroxyalkyl group, the alkyl group is preferably a C1-C8 hydroxyalkyl group, more preferably a C1-C6 hydroxyalkyl group, further preferably a C1-C3 hydroxyalkyl group, such as a hydroxymethyl group, a hydroxyethyl group, a hydroxypropyl group or a hydroxyisopropyl group, further preferably a hydroxymethyl group.

[0591] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0592]

[0593]

[0594]

[0595] In certain technical solutions of the present invention, the compound represented by the general formula (I) may be the compound represented by the following formula (I-5):

[0596]

[0597] in,

[0598] R 2a is a hydrogen atom, a cyano group, an alkyl group or an alkoxy group;

[0599] R 2b is a hydrogen atom or a cyano group;

[0600] R 2c is a hydrogen atom or a halogen;

[0601] R 2d is a hydrogen atom or a hydroxyl group;

[0602] n is 1 or 2;

[0603] L1, L2, L3, R1, R3, ring C, and y are as defined above.

[0604] In certain technical solutions of the present invention, the compound represented by formula (I-5) is preferably a compound represented by formula (I-5-1).

[0605]

[0606] Among them, n, R 2a 、R 2b 、R 2c and R 2d The definition of is the same as above.

[0607] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0608] In certain technical solutions of the present invention, in the compound represented by the general formula (I), the definitions of certain groups are as follows (undefined groups are as shown above):

[0609] L3 is selected from a bond, or -C(O)NR aa -;

[0610] R aais selected from a hydrogen atom or an alkyl group.

[0611] In certain technical solutions of the present invention, the compound represented by formula (I) is preferably a compound represented by formula (I-6),

[0612]

[0613] wherein L2 is selected from -NH-;

[0614] L3 is selected from a bond, or -C(O)NH-;

[0615] Ring A is selected from 6-14 membered fused heteroaryl groups;

[0616] Ring C is selected from heteroaryl;

[0617] y is 0, 1, 2, or 3;

[0618] n is 1 or 2.

[0619] In certain technical solutions of the present invention, the compound shown in formula (I) may have the following structure:

[0620]

[0621] In certain technical solutions of the present invention, the compound represented by the general formula (I) may be the compound represented by the following formula (I-7):

[0622]

[0623] Wherein, ring C is a heteroaryl group, and ring C is not

[0624] L1, L2, L3, R1, R2, R3, ring A, x and y are as defined above.

[0625] In certain technical solutions of the present invention, in the compound represented by the general formula (I-7), the definitions of certain groups are as follows (undefined groups are as shown above):

[0626] Ring C is heteroaryl, and Ring C is not

[0627] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -, or -(CH2) n1 S(O) m1 -;

[0628] L2 is selected from an oxygen atom, or -NR4-;

[0629] R4 is selected from a hydrogen atom or an alkyl group;

[0630] L3 is a hydrogen atom;

[0631] Ring A is a 6-14 membered fused heteroaryl group;

[0632] R1 is a hydrogen atom, a halogen, an alkyl group, a cyano group, or a heterocyclic group; the heterocyclic group is optionally further substituted by a cyano group;

[0633] R2 is a hydrogen atom;

[0634] R3 is selected from hydrogen atom, alkyl, hydroxyalkyl, cycloalkyl, -(CH2) n1 C(O)NR aa R bb , or -(CH2) n1 S(O) m1 NR aa R bb ;

[0635] R aa and R bb are independently selected from a hydrogen atom, or an alkyl group.

[0636] In certain technical solutions of the present invention, in the compound represented by the general formula (I-7), the definitions of certain groups are as follows (undefined groups are as shown above):

[0637] Ring C is heteroaryl, and Ring C is not

[0638] L1 is selected from alkylene, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -;

[0639] L2 is selected from an oxygen atom, or -NR4-;

[0640] R4 is selected from a hydrogen atom or an alkyl group;

[0641] L3 is a hydrogen atom;

[0642] Ring A is a 6-14 membered fused heteroaryl group;

[0643] R1 is a hydrogen atom, a halogen, an alkyl group, a cyano group, or a heterocyclic group;

[0644] R2 is a hydrogen atom;

[0645] R3 is selected from hydrogen atom, alkyl, hydroxyalkyl, -(CH2) n1 C(O)NR aa R bb ;

[0646] R aa and R bb are independently selected from a hydrogen atom, or an alkyl group.

[0647] In certain technical solutions of the present invention, in the compound represented by the general formula (I-7), the definitions of certain groups are as follows (undefined groups are as shown above): When the ring C is a heteroaryl group, the heteroaryl group is preferably a 6-14-membered heteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-4", and more preferably a 5-6-membered monoheteroaryl group with "heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1-3". The 5-6-membered monoheteroaryl group is preferably

[0648] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0649]

[0650]

[0651] In certain technical solutions of the present invention, the compound represented by the general formula (I) may be the compound represented by the following formula (I-8):

[0652]

[0653] Among them, R 3a and R 3b are independently hydrogen, halogen, hydroxy, cyano, alkyl, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclic or -(CH2) n1 C(O)NR aa R bb ; The alkyl, cycloalkyl or heterocyclic group is optionally further selected from halogen, hydroxyl, unsubstituted alkyl;

[0654] R aa and R bb are the same or different and are each independently selected from a hydrogen atom, or an alkyl group;

[0655] When R 3a When it is methyl, R 3b Not a hydrogen atom;

[0656] The definitions of R1, L1, L2 and L3 are the same as above;

[0657] n is 1 or 2.

[0658] In certain technical solutions of the present invention, in the compound represented by the general formula (I-8), the definitions of certain groups are as follows (undefined groups are as shown above):

[0659] R 3a and R 3b are independently hydrogen, halogen, hydroxy, cyano, alkyl, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclic or -(CH2) n1 C(O)NR aa R bb ; The alkyl, cycloalkyl or heterocyclic group is optionally further selected from halogen, hydroxyl, unsubstituted alkyl;

[0660] R aa and R bb are the same or different and are each independently selected from a hydrogen atom, or an alkyl group;

[0661] When R 3a When it is methyl, R 3b Not a hydrogen atom;

[0662] L1 is selected from alkylene, or -(CH2) n1 S(O) m1 -;

[0663] L2 is -NR4-;

[0664] L3 is -NH-;

[0665] R1 is selected from cyano or heterocyclic; the heterocyclic group is optionally further substituted by cyano;

[0666] n is 1 or 2.

[0667] In certain technical solutions of the present invention, in the compound represented by the general formula (I-8), the definitions of certain groups are as follows (undefined groups are as shown above):

[0668] R 3a and R 3b are independently hydrogen, halogen, alkyl, hydroxyalkyl, or cycloalkyl;

[0669] When R 3a When it is methyl, R 3b Not a hydrogen atom;

[0670] L1 is selected from alkylene;

[0671] L2 is -NH-;

[0672] L3 is -NH-;

[0673] R1 is cyano;

[0674] n is 1 or 2.

[0675] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0676]

[0677] In certain technical solutions of the present invention, among the compounds represented by the general formula (I), the compounds represented by the general formula (I) may be compounds represented by the following formula (I-9), and the definitions of certain groups are as follows (undefined groups are as shown above):

[0678]

[0679] wherein Ring B is selected from a 3-10 membered monoheterocyclic group or a 6-14 membered fused heterocyclic group;

[0680] R1, R3, L1, L2, L3 and y are defined as above.

[0681] In certain technical solutions of the present invention, in the compound represented by the general formula (I-8), the definitions of certain groups are as follows (undefined groups are as shown above):

[0682] Ring B is selected from a 3-10 membered monoheterocyclic group or a 6-14 membered fused heterocyclic group;

[0683] L1 is selected from alkylene, or -(CH2) n1 S(O) m1 -;

[0684] L2 is -NH-;

[0685] L3 is -NH-;

[0686] R1 is selected from cyano or heterocyclic; the heterocyclic group is optionally further substituted by cyano;

[0687] R3 is selected from a hydrogen atom or an alkyl group;

[0688] y is 0, 1, or 2.

[0689] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0690] In certain technical solutions of the present invention, among the compounds represented by the general formula (I), the compounds represented by the general formula (I) may be compounds represented by the following formula (I-10), and the definitions of certain groups are as follows (undefined groups are as shown above):

[0691]

[0692] Wherein, L2 is selected from an oxygen atom, or -NR4-;

[0693] R4 is an alkyl group;

[0694] R1, R3, L1, L3 and y are defined as above.

[0695] In certain technical solutions of the present invention, in the compound represented by the general formula (I-10), the definitions of certain groups are as follows (undefined groups are as shown above):

[0696] L2 is selected from an oxygen atom, or -NR4-;

[0697] R4 is an alkyl group;

[0698] L1 is selected from alkylene, or -(CH2) n1 S(O) m1 -;

[0699] L3 is -NH-;

[0700] R1 is selected from cyano or heterocyclic; the heterocyclic group is optionally further substituted by cyano;

[0701] R3 is selected from a hydrogen atom or an alkyl group;

[0702] y is 0, 1, or 2.

[0703] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0704]

[0705] In certain technical solutions of the present invention, the compound represented by formula (I) may be any of the following structures:

[0706]

[0707]

[0708]

[0709]

[0710]

[0711]

[0712]

[0713]

[0714]

[0715]

[0716]

[0717]

[0718] The object of the present invention is to provide a compound represented by general formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound represented by general formula (I) has the following structure:

[0719]

[0720] in:

[0721] L1 is selected from a bond, an alkylene group, an alkenylene group, an alkynyl group, a cycloalkyl group, a heterocyclic group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -、-NR aa (CH2) n1 -、-(CH2) n1 S(O) m1 -or-(CH2) n1 S(O) m1 NR aa -;

[0722] L2 is selected from a bond, an oxygen atom, a sulfur atom, -CR aa R bb -、-(CH2) n1 C(O)-, -NR4- or -(CH2) n1 S(O) m1 -;

[0723] L3 is selected from a bond, -NR aa -or-C(O)NR aa -;

[0724] Ring A is selected from 6-14 membered heteroaryl, wherein the 6-14 membered heteroaryl is selected from 6-14 membered fused heteroaryl; preferably 5-membered fused heteroaryl, 5-membered fused heteroaryl or 6-membered fused heteroaryl;

[0725] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered bridged heterocyclic group or a 6-14 membered fused heterocyclic group;

[0726] Ring C is selected from heteroaryl;

[0727] R1 is selected from hydrogen, deuterium, oxo, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxyl, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 -、-(CH2)n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 NR cc C(O)R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0728] R2 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 O(CH2) m1 R aa 、-(CH2) n1 OR aa 、-(CH2) n1 NR aa (CH2) m1 R aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 S-, -(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc Rdd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0729] R3 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aaS(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0730] R4 is selected from the group consisting of hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, and alkynyl;

[0731] R aa 、R bb 、Rcc and R dd are the same or different and are each independently selected from the group consisting of hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, halogen, cyano, nitro, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl, wherein the alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

[0732] x is an integer of 0, 1, 2 or 3;

[0733] y is an integer of 0, 1, 2, 3, 4 or 5;

[0734] m1 is an integer of 0, 1 or 2;

[0735] m2 is an integer of 0, 1 or 2; and

[0736] n1 is an integer of 0, 1, 2, 3, 4 or 5.

[0737] The present invention also relates to a preferred embodiment, wherein the above-mentioned general formula (I), its stereoisomers or pharmaceutically acceptable salts thereof are characterized in that:

[0738] in:

[0739] L1 is selected from a bond, an alkylene group, an alkenylene group, an alkynyl group, a cycloalkyl group, a heterocyclic group, -NR aa (CH2) n1 -、-(CH2) n1 S(O) m1 -or-(CH2) n1 S(O) m1 NR aa -;

[0740] L2 is selected from a bond, an oxygen atom, a sulfur atom, -CR aa R bb -、-(CH2) n1 C(O)-, -NR4- or -(CH2) n1 S(O) m1 -;

[0741] L3 is selected from a bond, -NR aa -or-C(O)NRaa -;

[0742] Ring A is selected from 6-14 membered heteroaryl, wherein the 6-14 membered heteroaryl is selected from 6-14 membered fused heteroaryl; preferably 5-membered fused heteroaryl, 5-membered fused heteroaryl or 6-membered fused heteroaryl;

[0743] Ring B is selected from a 6-14 membered bridged heterocyclic group or a 6-14 membered fused heterocyclic group;

[0744] Ring C is selected from heteroaryl;

[0745] R1 is selected from hydrogen, deuterium, oxo, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bbwherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxyl, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 NR cc C(O)R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0746] R2 is a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, an oxo group, a haloalkyl group, an alkoxy group, a hydroxyalkyl group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, or an alkynyl group;

[0747] R3 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2)n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc Rdd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0748] R4 is a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a haloalkyl group, an alkoxy group, a hydroxyalkyl group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, or an alkynyl group;

[0749] R aa 、R bb 、R cc and R dd are the same or different and are each independently selected from the group consisting of hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, halogen, cyano, nitro, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl, wherein the alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

[0750] x is an integer of 0, 1, 2 or 3;

[0751] y is an integer of 0, 1, 2, 3, 4 or 5;

[0752] m1 is an integer of 0, 1 or 2;

[0753] m2 is an integer of 0, 1 or 2; and

[0754] n1 is an integer of 0, 1, 2, 3, 4 or 5.

[0755] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomers or pharmaceutically acceptable salts thereof are compounds represented by general formula (II) and general formula (IIA), their stereoisomers or pharmaceutically acceptable salts thereof:

[0756]

[0757] in:

[0758] W is selected from a nitrogen atom or an alkylene group; and

[0759] n is an integer of 0, 1, 2 or 3;

[0760] L1, L2, L3, Ring A, Ring C, R1 to R3, x and y are as described in the general formula (I).

[0761] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (IIIA), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0762]

[0763] in:

[0764] R5 is selected from hydrogen, halogen, cyano, alkyl, alkoxy, hydroxyalkyl, haloalkyl, -(CH2) n1 OR aa 、-(CH2) n1 C(O)NR aa R bb , cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the alkyl, alkoxy, hydroxyalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxyl, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted, unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0765] R6 is selected from hydrogen, halogen, cyano, alkyl, alkoxy, hydroxyalkyl, haloalkyl, cycloalkyl, heterocyclic or -(CH2) n1 C(O)NR aa R bb ;

[0766] L1, L2, L3, Ring A, Ring B, R1, R2 and x are as described in the general formula (I).

[0767] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (III), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0768]

[0769] in:

[0770] R 10 and R 11 The same or different, each independently selected from hydrogen atom, halogen, cyano, alkyl, alkoxy, hydroxyalkyl, haloalkyl, -(CH2) n1 OR aa 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 S(O) m1 NRaa R bb -, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the alkyl, alkoxy, hydroxyalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxyl, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0771] L1, L2, L3, Ring A, Ring B, R1, R2 and x are as described in the general formula (I).

[0772] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (IV), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0773]

[0774] in:

[0775] Ring D is selected from heterocyclyl, aryl or heteroaryl; preferably 5-6 membered heterocyclyl, 6-10 membered aryl or 5-6 membered heteroaryl;

[0776] E1, E2 and E3 are the same or different and are independently selected from nitrogen atoms or -CR aa -;

[0777] R4 is selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl or alkoxy;

[0778] R7 is selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, oxo or thio; and

[0779] z is an integer of 0, 1, 2 or 3;

[0780] L1, L3, Ring C, R1, R3, R aa , y and n are as described in the general formula (I).

[0781] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (V), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0782]

[0783] in:

[0784] Ring G is selected from heterocyclyl, aryl or heteroaryl; preferably 5-6 membered heterocyclyl, 6-10 membered aryl or 5-6 membered heteroaryl;

[0785] R8 is selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, oxo or thio; and

[0786] p is an integer of 0, 1, 2 or 3;

[0787] R5 and R6 are as defined herein;

[0788] L1, E1, E2, E3, R4 and n are as described in the general formula (IV).

[0789] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (VI), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0790]

[0791] in:

[0792] Ring K is selected from heterocyclic group, aryl group or heteroaryl group; preferably 5-6 membered heterocyclic group, 6-10 membered aryl group, 5-6 membered heteroaryl group;

[0793] R9 is selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, oxo or thio; and

[0794] q is an integer of 0, 1, 2 or 3;

[0795] R5 and R6 are as defined herein;

[0796] E1, E2, E3 and R4 are as described in the general formula (IV).

[0797] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (VII), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0798]

[0799] in:

[0800] n is an integer of 0, 1 or 2;

[0801] L2, Ring A, R2, R5, R6 and x are as described in the general formula (IIIA).

[0802] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (III), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (VIII), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0803]

[0804] in:

[0805] M1 is selected from nitrogen atom or -CR aa -;

[0806] R 12 is selected from a hydrogen atom, a cyano group, a halogen group, an alkyl group or an alkoxy group; and

[0807] z is an integer of 0, 1 or 2;

[0808] L1, L2, Ring C, R1, R3, R7, R aa and y are as described in general formula (IV).

[0809] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (IX), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0810]

[0811] in:

[0812] Ring C, R3, R 12 , R7, y and z are as described in the general formula (VII).

[0813] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (X), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0814]

[0815] in:

[0816] R5 to R6 are as described in the general formula (IIIA);

[0817] R 12 , R7 and z are as described in the general formula (VII).

[0818] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (XI), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0819]

[0820] in:

[0821] L1, L2, Ring B, Ring C, R3 and R 12 As described in general formula (I)

[0822] R7, y and z are as described in the general formula (IX).

[0823] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (XII), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0824]

[0825] in:

[0826] L1 is selected from a bond, an alkylene group, an alkenylene group, an alkynyl group, a cycloalkyl group, a heterocyclic group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -、-(CH2) n1 S(O) m1 -or-(CH2) n1 S(O) m1 NR aa -;

[0827] Ring B is selected from a 3-10 membered monoheterocyclic group, a 6-14 membered spiroheterocyclic group, a 6-14 membered bridged heterocyclic group or a 6-14 membered fused heterocyclic group;

[0828] Ring T is selected from aryl or heteroaryl;

[0829] R1 is selected from hydrogen, deuterium, oxo, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NRaa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxyl, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 NR cc C(O)R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0830] R3 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR ccR dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0831] R4 is a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a haloalkyl group, an alkoxy group, a hydroxyalkyl group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, or an alkynyl group;

[0832] R 13 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 O(CH2) m1 R aa 、-(CH2) n1 OR aa 、-(CH2) n1 NR aa (CH2) m1 R aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NRaa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 S-, -(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 Rdd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0833] R aa 、R bb 、R cc and R dd are the same or different and are each independently selected from the group consisting of hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, halogen, cyano, nitro, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl, wherein the alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

[0834] y is an integer of 0, 1, 2, 3, 4 or 5;

[0835] q is an integer of 0, 1, 2, 3, 4 or 5;

[0836] m1 is an integer of 0, 1 or 2;

[0837] m2 is an integer of 0, 1 or 2; and

[0838] n1 is an integer of 0, 1, 2, 3, 4 or 5.

[0839] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (XIII), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0840]

[0841] in:

[0842] R5 is selected from a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, an alkynyl group, a cycloalkyl group, a hydroxyalkyl group, a heterocyclic group, an oxoheterocyclic group, a thioheterocyclic group, an aryl group, or a heteroaryl group;

[0843] R6 is selected from a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, an alkynyl group, a cycloalkyl group, a hydroxyalkyl group, a heterocyclic group, an oxoheterocyclic group, a thioheterocyclic group, an aryl group or a heteroaryl group;

[0844] n is an integer of 0, 1 or 2;

[0845] L1, Ring T, R1, R3, R4, R 13 and q are as described in the general formula (XII).

[0846] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (XIV), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0847]

[0848] in:

[0849] L1, R1, R4~R6, R 13 , q and n are as described in the general formula (XIII).

[0850] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (XV), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0851]

[0852] in:

[0853] L1 is selected from a bond, an alkylene group, an alkenylene group, an alkynyl group, a cycloalkyl group, a heterocyclic group, -(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -、-(CH2) n1 S(O) m1 -or-(CH2) n1 S(O) m1 NR aa -;

[0854] J1, J2 and J3 are the same or different, and are independently selected from nitrogen atoms, sulfur atoms, oxygen atoms, NR aa or CR 14 ;

[0855] R1 is selected from hydrogen, deuterium, oxo, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxyl, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 NR cc C(O)R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0856] R4 is a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a haloalkyl group, an alkoxy group, a hydroxyalkyl group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, or an alkynyl group;

[0857] R5 is selected from a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, an alkynyl group, a cycloalkyl group, a hydroxyalkyl group, a heterocyclic group, an oxoheterocyclic group, a thioheterocyclic group, an aryl group, or a heteroaryl group;

[0858] R6 is selected from a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, an alkynyl group, a cycloalkyl group, a hydroxyalkyl group, a heterocyclic group, an oxoheterocyclic group, a thioheterocyclic group, an aryl group or a heteroaryl group;

[0859] R 14 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 O(CH2) m1 R aa 、-(CH2) n1 OR aa 、-(CH2) n1 NR aa (CH2) m1 R aa 、-NR aaC(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 S-, -(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0860] R aa 、R bb 、R cc and R dd are the same or different and are each independently selected from the group consisting of hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, halogen, cyano, nitro, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl, wherein the alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

[0861] n is an integer of 0, 1 or 2;

[0862] m1 is an integer of 0, 1 or 2;

[0863] m2 is an integer of 0, 1 or 2; and

[0864] n1 is an integer of 0, 1, 2, 3, 4 or 5.

[0865] The present invention also relates to a preferred embodiment, wherein the compound represented by the general formula (I), its stereoisomer or its pharmaceutically acceptable salt is a compound represented by the general formula (XVI), its stereoisomer or its pharmaceutically acceptable salt.

[0866] Acceptable salt:

[0867]

[0868] in:

[0869] R 15 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 O(CH2) m1 R aa 、-

[0870] (CH2) n1 OR aa 、-(CH2) n1 NR aa (CH2) m1 R aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-

[0871] (CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、

[0872] -(CH2) n1 S-, -(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-

[0873] (CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、

[0874] -(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-

[0875] (CH2) n1 NRcc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0876] L1, R1, R5~R6, R aa ~R dd and n are as described in general formula (XIV).

[0877] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (XVII), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0878]

[0879] in:

[0880] R 16 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 O(CH2) m1 R aa 、-(CH2) n1 OR aa 、-(CH2) n1 NR aa (CH2) m1 R aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NRaa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 S-, -(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 Rdd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0881] r is an integer of 0, 1 or 2; and

[0882] L1, R1, R4~R6, R aa ~R dd , n, n1, m1 and m2 are as described in the general formula (XV).

[0883] The present invention also relates to a preferred embodiment, wherein any of the general formulas, stereoisomers or pharmaceutically acceptable salts thereof are characterized in that:

[0884] Ring A is selected from the following groups:

[0885]

[0886]

[0887] Ring B is selected from the following groups:

[0888]

[0889] Ring C is selected from the following groups:

[0890]

[0891] The present invention also relates to a preferred embodiment, wherein any of the general formulas, stereoisomers or pharmaceutically acceptable salts thereof are characterized in that:

[0892] L1 is C 3-8 Cycloalkyl, C 3-8 Heterocycloalkyl, -(CH2) n1 -、-(CH2) n1 C(O)(CH2) m1 -、-(CH2) n1 C(O)(CH2) m1 NR aa (CH2) m2 -、-NR aa (CH2) n1 -、-(CH2) n1 S(O) m1 -or-(CH2) n1 S(O)m1 NR aa -;

[0893] L2 is selected from a bond, an oxygen atom, -CR aa R bb -、-(CH2) n1 C(O)-, -NR4- or -(CH2) n1 S(O) m1 -;

[0894] L3 is selected from a bond, -NR aa -or-C(O)NR aa -;

[0895] R1 is selected from cyano, -(CH2) n1 R aa 、-(CH2) n1 C(O)R aa 、C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl, wherein the C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups are optionally further selected from hydrogen atoms, cyano groups, C 1-6 Alkyl, C 1-6 substituted by one or more substituents in the alkoxy group;

[0896] R2 hydrogen atom, halogen, cyano, hydroxyl, oxo, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-12 Aryl, 5-10 membered heteroaryl, -(CH2) n1 R aa 、-O(CH2) n1 R aa 、-S(CH2) n1 R aa or -NR aa (CH2) n1 R bb , wherein the C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl and 5-10 membered heteroaryl groups are optionally further selected from hydrogen atoms, cyano groups, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl or -NR cc R dd is substituted by one or more substituents in;

[0897] R3 is selected from hydrogen, cyano, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, -(CH2) n1 OR aa 、-C(O)NR aa R bb or -(CH2) n1 S(O) m1 R aa wherein the cycloalkyl and heterocyclic groups are optionally further selected from hydrogen atoms, C 1-6 substituted by one or more substituents in the alkyl or hydroxy groups;

[0898] R4 is selected from a hydrogen atom or a methyl group;

[0899] R aa 、R bb 、R cc and R dd are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl, C 1-6 Haloalkyl, cyano, hydroxy, amino, C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 Aryl or 5-10 membered heteroaryl; wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, amino, C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl and 5-10 membered heteroaryl groups are optionally further substituted by hydrogen atoms, cyano groups, hydroxyl groups, amino groups, aminoalkyl groups, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, C 6-10 The aryl group or the 5-10 membered heteroaryl group is substituted by one or more substituents.

[0900] The object of the present invention is to provide a compound represented by general formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound represented by general formula (I) has the following structure:

[0901]

[0902] in:

[0903] L1 is selected from a bond, an alkylene group, an alkenylene group, an alkynyl group, a cycloalkyl group, a heterocyclic group, -NR aa (CH2) n1 -、-(CH2) n1 S(O)m1 -or-(CH2) n1 S(O) m1 NR aa -;

[0904] L2 is selected from a bond, an oxygen atom, a sulfur atom, -CR aa R bb -、-(CH2) n1 C(O)-, -NR4- or -(CH2) n1 S(O) m1 -;

[0905] L3 is selected from a bond, -NR aa -or-C(O)NR aa -;

[0906] Ring A is selected from 6-14 membered heteroaryl, wherein the 6-14 membered heteroaryl is selected from 6-14 membered fused heteroaryl; preferably 5-membered fused heteroaryl, 5-membered fused heteroaryl or 6-membered fused heteroaryl;

[0907] Ring B is selected from a 6-14 membered bridged heterocyclic group or a 6-14 membered fused heterocyclic group;

[0908] Ring C is selected from heteroaryl;

[0909] R1 is selected from hydrogen, deuterium, oxo, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1 OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aaR bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, alkyl, haloalkyl, halogen, amino, oxo, nitro, cyano, hydroxyl, alkenyl, alkynyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 NR cc C(O)R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0910] R2 is a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, an oxo group, a haloalkyl group, an alkoxy group, a hydroxyalkyl group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, or an alkynyl group;

[0911] R3 is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, heterocyclic, oxoheterocyclic, thioheterocyclic, aryl, heteroaryl, -(CH2) n1 R aa 、-(CH2) n1OR aa 、-NR aa C(O)(CH2) n1 OR aa 、-NR aa C(=S)(CH2) n1 OR bb 、-(CH2) n1 SR aa 、-(CH2) n1 C(O)R aa 、-(CH2) n1 C(O)OR aa 、-(CH2) n1 S(O) m1 R aa 、-(CH2) n1 S(O) m1 NR aa R bb 、-(CH2) n1 P(O) m2 R aa R bb 、-(CH2) n1 NR aa R bb 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 NR aa C(O)R bb or -(CH2) n1 NR aa S(O) m1 R bb wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl groups are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2)n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0912] R4 is a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a haloalkyl group, an alkoxy group, a hydroxyalkyl group, a haloalkoxy group, a halogen, an amino group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, or an alkynyl group;

[0913] R aa 、R bb 、R cc and R dd are the same or different and are each independently selected from the group consisting of hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, halogen, cyano, nitro, hydroxy, amino, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl, wherein the alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxyalkyl, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted alkyl, halogen, hydroxy, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

[0914] x is an integer of 0, 1, 2 or 3;

[0915] y is an integer of 0, 1, 2, 3, 4 or 5;

[0916] m1 is an integer of 0, 1 or 2;

[0917] m2 is an integer of 0, 1 or 2; and

[0918] n1 is an integer of 0, 1, 2, 3, 4 or 5.

[0919] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomers or pharmaceutically acceptable salts thereof are compounds represented by general formula (II) and general formula (IIA), their stereoisomers or pharmaceutically acceptable salts thereof:

[0920]

[0921] in:

[0922] W is selected from a nitrogen atom or an alkylene group; and

[0923] n is an integer of 0, 1, 2 or 3;

[0924] L1, L2, L3, Ring A, Ring C, R1 to R3, x and y are as described in the general formula (I).

[0925] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (IIIA), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0926]

[0927] in:

[0928] R5 is selected from hydrogen, halogen, cyano, alkyl, alkoxy, hydroxyalkyl, haloalkyl, -(CH2) n1 OR aa 、-(CH2) n1 C(O)NR aa R bb , cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the alkyl, alkoxy, hydroxyalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxyl, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted, unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 Rcc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 R dd is substituted by one or more substituents in;

[0929] R6 is selected from hydrogen, halogen, cyano, alkyl, alkoxy, hydroxyalkyl, haloalkyl, cycloalkyl, heterocyclic or -(CH2) n1 C(O)NR aa R bb ;

[0930] L1, L2, L3, Ring A, Ring B, R1, R2 and x are as described in the general formula (I).

[0931] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (III), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0932]

[0933] in:

[0934] R 10 and R 11The same or different, each independently selected from hydrogen atom, halogen, cyano, alkyl, alkoxy, hydroxyalkyl, haloalkyl, -(CH2) n1 OR aa 、-(CH2) n1 C(O)NR aa R bb 、-(CH2) n1 S(O) m1 NR aa R bb -, cycloalkyl, heterocyclic, aryl or heteroaryl, wherein the alkyl, alkoxy, hydroxyalkyl, haloalkyl, cycloalkyl, heterocyclic, aryl and heteroaryl are optionally further selected from hydrogen atoms, deuterium atoms, substituted or unsubstituted alkyl, halogen, hydroxyl, substituted or unsubstituted amino, oxo, nitro, cyano, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, -(CH2) n1 -、-(CH2) n1 R cc 、-(CH2) n1 OR cc 、-(CH2) n1 SR cc 、-(CH2) n1 C(O)R cc 、-(CH2) n1 C(O)OR cc 、-(CH2) n1 S(O) m1 R cc 、-(CH2) n1 S(O) m1 NR cc R dd 、-(CH2) n1 NR cc R dd 、-(CH2) n1 C(O)NR cc R dd 、-(CH2) n1 C(O)NR cc S(O) m1 R dd 、-(CH2) n1 NR cc S(O) m1 R dd or -(CH2) n1 NR cc S(O) m1 Rdd is substituted by one or more substituents in;

[0935] L1, L2, L3, Ring A, Ring B, R1, R2 and x are as described in the general formula (I).

[0936] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (IV), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0937]

[0938] in:

[0939] Ring D is selected from heterocyclyl, aryl or heteroaryl; preferably 5-6 membered heterocyclyl, 6-10 membered aryl or 5-6 membered heteroaryl;

[0940] E1, E2 and E3 are the same or different and are independently selected from nitrogen atoms or -CR aa -;

[0941] R4 is selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl or alkoxy;

[0942] R7 is selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, oxo or thio; and

[0943] z is an integer of 0, 1, 2 or 3;

[0944] L1, L3, Ring C, R1, R3, R aa , y and n are as described in the general formula (I).

[0945] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (V), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0946]

[0947] in:

[0948] Ring G is selected from heterocyclyl, aryl or heteroaryl; preferably 5-6 membered heterocyclyl, 6-10 membered aryl or 5-6 membered heteroaryl;

[0949] R8 is selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, oxo or thio; and

[0950] p is an integer of 0, 1, 2 or 3;

[0951] R5 and R6 are as defined herein;

[0952] L1, E1, E2, E3, R4 and n are as described in the general formula (IV).

[0953] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (VI), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0954]

[0955] in:

[0956] Ring K is selected from heterocyclic group, aryl group or heteroaryl group; preferably 5-6 membered heterocyclic group, 6-10 membered aryl group, 5-6 membered heteroaryl group;

[0957] R9 is selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, oxo or thio; and

[0958] q is an integer of 0, 1, 2 or 3;

[0959] R5 and R6 are as defined herein;

[0960] E1, E2, E3 and R4 are as described in the general formula (IV).

[0961] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (VII), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0962]

[0963] in:

[0964] n is an integer of 0, 1 or 2;

[0965] L2, Ring A, R2, R5, R6 and x are as described in the general formula (IIIA).

[0966] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (III), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (VIII), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0967]

[0968] in:

[0969] M1 is selected from nitrogen atom or -CR aa -;

[0970] R 12is selected from a hydrogen atom, a cyano group, a halogen group, an alkyl group or an alkoxy group; and

[0971] z is an integer of 0, 1 or 2;

[0972] L1, L2, Ring C, R1, R3, R7, R aa and y are as described in general formula (IV).

[0973] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (IX), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0974]

[0975] in:

[0976] Ring C, R3, R 12 , R7, y and z are as described in the general formula (VII).

[0977] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (X), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0978]

[0979] in:

[0980] R5 to R6 are as described in the general formula (IIIA);

[0981] R 12 , R7 and z are as described in the general formula (VII).

[0982] The present invention also relates to a preferred embodiment, wherein the compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof is a compound represented by general formula (XI), its stereoisomer or a pharmaceutically acceptable salt thereof:

[0983]

[0984] in:

[0985] L1, L2, Ring B, Ring C, R3 and R 12 As described in general formula (I)

[0986] R7, y and z are as described in the general formula (IX).

[0987] The present invention also relates to a preferred embodiment, wherein any of the general formulas, stereoisomers or pharmaceutically acceptable salts thereof are characterized in that:

[0988] Ring A is selected from the following groups:

[0989]

[0990]

[0991] Ring B is selected from the following groups:

[0992]

[0993] Ring C is selected from the following groups:

[0994]

[0995] The present invention also relates to a preferred embodiment, wherein any of the general formulas, stereoisomers or pharmaceutically acceptable salts thereof are characterized in that:

[0996] L1 is C 3-8 Cycloalkyl, C 3-8 Heterocycloalkyl, -(CH2) n1 -、-NR aa (CH2) n1 -、-(CH2) n1 S(O) m1 -or-(CH2) n1 S(O) m1 NR aa -;

[0997] L2 is selected from a bond, an oxygen atom, -CR aa R bb -、-(CH2) n1 C(O)-, -NR4- or -(CH2) n1 S(O) m1 -;

[0998] L3 is selected from a bond, -NR aa -or-C(O)NR aa -;

[0999] R1 is selected from cyano, -(CH2) n1 R aa 、C 3-8 Cycloalkyl or 3-10 membered heterocyclic group, wherein the cycloalkyl and heterocyclic group are optionally further substituted by one or more substituents selected from hydrogen atom or cyano group;

[1000] R2 hydrogen atom, halogen, cyano, hydroxyl, oxo, C 1-6 Alkyl, C 1-6 Alkoxy or 3-10 membered heterocyclic group; preferably hydrogen atom, halogen, cyano, hydroxyl, oxo, C 1-3 Alkoxy, C1-3 an alkyl group or a 3-8 membered heterocyclic group; more preferably a hydrogen atom, a fluorine group, a cyano group, a hydroxyl group, an oxo group, a methoxy group, a methyl group or a morpholinyl group;

[1001] R3 is selected from hydrogen, cyano, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic group, -(CH2) n1 OR aa 、-C(O)NR aa R bb or -(CH2) n1 S(O) m1 R aa wherein the cycloalkyl and heterocyclic groups are optionally further selected from hydrogen atoms, C 1-6 substituted by one or more substituents in the alkyl or hydroxy groups;

[1002] R4 is selected from a hydrogen atom or a methyl group;

[1003] R aa 、R bb 、R cc and R dd are the same or different and are each independently selected from hydrogen atom, C 1-6 Alkyl, cyano, hydroxy, amino or 3-10 membered heterocyclic group; wherein the C 1-6 The alkyl group, amino group and 3-10 membered heterocyclic group are optionally further substituted by one or more substituents selected from hydrogen atom, cyano group, hydroxyl group and 5-10 membered heteroaryl group.

[1004] The present invention further relates to the use of any compound of the general formula (I), its stereoisomers or pharmaceutically acceptable salts, or the pharmaceutical composition in the preparation of JAK kinase inhibitor drugs.

[1005] The present invention also relates to a method for treating, preventing and / or treating a condition mediated by a JAK kinase inhibitor, which comprises administering to a patient a therapeutically effective dose of a compound represented by general formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[1006] The present invention also relates to a pharmaceutical composition comprising a therapeutically effective dose of a compound represented by general formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.

[1007] The present invention also relates to the use of the compound of general formula (I), its stereoisomers or pharmaceutically acceptable salts, or the pharmaceutical composition in the preparation of drugs for treating inflammatory diseases and tumor diseases.

[1008] The present invention also relates to a method for treating an inflammatory disease and a method for treating a tumor disease, which comprises administering a therapeutically effective dose of a pharmaceutical composition to a patient, wherein the inflammatory disease is selected from rheumatoid arthritis, dermatitis, psoriasis, and inflammatory bowel disease; wherein the gastrointestinal inflammatory disease is a chronic intestinal inflammatory disease, and more preferably ulcerative colitis and Crohn's disease.

[1009] The present invention also relates to a method for treating a tumor disease, comprising administering a therapeutically effective dose of the pharmaceutical composition to a patient, wherein the tumor disease is selected from myelofibrosis, polycythemia vera and essential thrombocythemia, myelocytic leukemia (AML), acute lymphoblastic leukemia (ALL), breast ductal carcinoma and non-small cell lung cancer (NSCLC).

[1010] The present invention also relates to a pharmaceutical composition comprising a compound represented by the above-mentioned general formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers, diluents or excipients, wherein the compound represented by the general formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof can be a therapeutically effective amount.

[1011] The present invention further relates to the use of any compound of the general formula (I), its stereoisomers or pharmaceutically acceptable salts, or the above-mentioned pharmaceutical composition in the preparation of JAK kinase inhibitors.

[1012] The present invention also relates to the use of the compound of general formula (I), its stereoisomers or pharmaceutically acceptable salts, or the pharmaceutical composition described above, in the preparation of a medicament for preventing and / or treating diseases associated with JAK kinases. The JAK kinase-related diseases are preferably inflammatory diseases and / or tumor diseases; the inflammatory diseases are preferably selected from rheumatoid arthritis, dermatitis, psoriasis, and inflammatory bowel disease; gastrointestinal inflammatory diseases are preferably chronic intestinal inflammatory diseases, and more preferably ulcerative colitis and Crohn's disease. The tumor diseases are preferably selected from myelofibrosis, polycythemia vera, essential thrombocythemia, myeloid leukemia, acute lymphocytic leukemia, breast ductal carcinoma, and non-small cell lung cancer.

[1013] The present invention also relates to the use of the compound of general formula (I), its stereoisomers or pharmaceutically acceptable salts, or the pharmaceutical composition in the preparation of a medicament, wherein the medicament is preferably a medicament for treating inflammatory diseases and / or tumor diseases. The inflammatory disease is preferably selected from rheumatoid arthritis, dermatitis, psoriasis, and inflammatory bowel disease; wherein the gastrointestinal inflammatory disease is a chronic intestinal inflammatory disease, further preferably ulcerative colitis and Crohn's disease. The tumor disease is preferably selected from myelofibrosis, polycythemia vera and essential thrombocythemia, myeloid leukemia, acute lymphocytic leukemia, breast ductal carcinoma, and non-small cell lung cancer.

[1014] The present invention also relates to a method for treating inflammatory diseases, comprising administering to a patient a therapeutically effective dose of the compound represented by the above-mentioned general formula (I), its stereoisomers or pharmaceutically acceptable salts, or the above-mentioned pharmaceutical composition, wherein the inflammatory disease is selected from rheumatoid arthritis, dermatitis, psoriasis, and inflammatory bowel disease; wherein the gastrointestinal inflammatory disease is a chronic intestinal inflammatory disease, and more preferably ulcerative colitis and Crohn's disease.

[1015] The present invention also relates to a method for treating tumor diseases, which comprises administering to a patient a therapeutically effective dose of the compound represented by the above-mentioned general formula (I), its stereoisomers or pharmaceutically acceptable salts, or the above-mentioned pharmaceutical composition, wherein the tumor disease is selected from myelofibrosis, polycythemia vera and essential thrombocythemia, myelocytic leukemia, acute lymphocytic leukemia, breast ductal carcinoma and non-small cell lung cancer.

[1016] The present invention also relates to a method for preventing and / or treating a condition mediated by JAK kinase, comprising administering to a patient a therapeutically effective dose of the compound represented by the general formula (I), its stereoisomers or pharmaceutically acceptable salts, or the pharmaceutical composition described above. The JAK kinase-mediated condition is preferably an inflammatory disease and / or a tumor disease; the inflammatory disease is preferably selected from rheumatoid arthritis, dermatitis, psoriasis, and inflammatory bowel disease; wherein the gastrointestinal inflammatory disease is preferably a chronic intestinal inflammatory disease, and further preferably ulcerative colitis and Crohn's disease. The tumor disease is preferably selected from myelofibrosis, polycythemia vera and essential thrombocythemia, myelocytic leukemia, acute lymphocytic leukemia, breast ductal carcinoma, and non-small cell lung cancer.

[1017] Detailed Description of the Invention

[1018] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[1019] The term "alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 8 carbon atoms, more preferably an alkyl group containing 1 to 6 carbon atoms, and most preferably an alkyl group containing 1 to 3 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2, 3-Dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched-chain isomers thereof. More preferred are lower alkyl groups containing 1 to 6 carbon atoms, non-limiting examples of which include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, and the like. The alkyl group may be substituted or unsubstituted. When substituted, the substituent may be substituted at any available point of attachment. The substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate groups. Methyl, ethyl, isopropyl, tert-butyl, haloalkyl, deuterated alkyl, alkoxy-substituted alkyl and hydroxy-substituted alkyl are preferred.

[1020] The term "alkylene" refers to an alkyl group in which one hydrogen atom is further substituted, for example: "methylene" refers to -CH2-, "ethylene" refers to -(CH2)2-, "propylene" refers to -(CH2)3-, "butylene" refers to -(CH2)4-, etc. The term "alkenyl" refers to an alkyl group as defined above consisting of at least two carbon atoms and at least one carbon-carbon double bond, for example, ethenyl, 1-propenyl, 2-propenyl, 1-, 2- or 3-butenyl, etc. The alkenyl group may be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, and heterocycloalkylthio.

[1021] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent, wherein the cycloalkyl ring contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, more preferably 3 to 8 carbon atoms, and most preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, and the like; polycyclic cycloalkyls include spirocyclic, fused, and bridged cycloalkyls, preferably cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, and cycloheptyl, and more preferably cyclopropyl, cyclobutyl, and cyclopentyl.

[1022] The term "spiroalkyl" refers to a polycyclic group having a carbon atom (called a spiro atom) shared between 5 to 20 monocyclic rings, which may contain one or more double bonds, but no ring has a completely conjugated π electron system. Preferably, it is 6 to 14 yuan, more preferably 7 to 10 yuan. According to the number of spiro atoms shared between the rings, the spiroalkyl group is divided into a single spiroalkyl group, a double spiroalkyl group or a multi-spiroalkyl group, preferably a single spiroalkyl group and a double spiroalkyl group. More preferably, it is a 4 yuan / 4 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 5 yuan or 5 yuan / 6 yuan single spiroalkyl group. Non-limiting examples of spiroalkyl groups include:

[1023]

[1024] It also includes spirocycloalkyl groups that share a spiro atom with a heterocycloalkyl group. Non-limiting examples include:

[1025]

[1026]

[1027] The term "fused cycloalkyl" refers to a 5 to 20-membered, all-carbon polycyclic group in which each ring in the system shares a pair of adjacent carbon atoms with the other rings in the system, wherein one or more rings may contain one or more double bonds, but no ring has a completely conjugated π electron system. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused cycloalkyl, preferably bicyclic or tricyclic, more preferably 4-membered / 4-membered, 5-membered / 5-membered or 5-membered / 6-membered bicyclic alkyl. Non-limiting examples of fused cycloalkyl include:

[1028]

[1029] The term "bridged cycloalkyl" refers to a 5-20 membered, all-carbon polycyclic group in which any two rings share two carbon atoms that are not directly connected, which may contain one or more double bonds, but no ring has a completely conjugated π electron system. Preferably, it is 6-14 members, more preferably 7-10 members. Depending on the number of constituent rings, it can be classified as a bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyl group, preferably a bicyclic, tricyclic or tetracyclic group, more preferably a bicyclic or tricyclic group. Non-limiting examples of bridged cycloalkyl groups include:

[1030]

[1031] The cycloalkyl ring may be fused to an aryl, heteroaryl or heterocycloalkyl ring, wherein the ring attached to the parent structure is a cycloalkyl, non-limiting examples of which include indanyl, tetrahydronaphthyl, benzocycloheptanyl, etc. The cycloalkyl group may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[1032] The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing 3 to 20 ring atoms, one or more of which is selected from nitrogen, oxygen, boron, phosphorus, S(O), m (where m is an integer from 0 to 2) or P(O) n(wherein n is an integer from 0 to 2) heteroatoms, but excluding the ring portion of -OO-, -OS- or -SS-, the remaining ring atoms are carbon. Preferably, it contains 3 to 12 ring atoms, of which 1 to 4 are heteroatoms; more preferably, it contains 3 to 10 ring atoms; and most preferably, it contains 3 to 8 ring atoms. Non-limiting examples of monocyclic heterocyclic groups include oxetanyl, azetidinyl, pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, pyranyl, and the like, preferably oxetanyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, pyrazolidinyl, morpholinyl, piperidinyl, piperazinyl, and pyranyl. More preferred are azetidinyl, oxetanyl, pyrrolidinyl, tetrahydropyranyl, morpholinyl, piperidinyl and piperazinyl. Polycyclic heterocyclic groups include spirocyclic, condensed ring and bridged heterocyclic groups; wherein the spirocyclic, condensed ring and bridged heterocyclic groups are optionally connected to other groups through single bonds, or further connected to other cycloalkyl, heterocyclic, aryl and heteroaryl groups through any two or more atoms on the ring.

[1033] The term "spiroheterocyclyl" refers to a polycyclic heterocyclic group in which the monocyclic rings of 3 to 20 members share one atom (called a spiro atom), wherein one or more of the ring atoms is nitrogen, oxygen, boron, phosphorus, S(O), m (where m is an integer from 0 to 2) or P(O) n (wherein n is an integer 0 to 2) heteroatoms, and the remaining ring atoms are carbon. It may contain one or more double bonds, but no ring has a completely conjugated π electron system. It is preferably 6 to 14 members, more preferably 7 to 10 members. According to the number of shared spiral atoms between the rings, the spiro heterocyclic group is divided into a single spiral heterocyclic group, a double spiral heterocyclic group or a multi-spiro heterocyclic group, preferably a single spiral heterocyclic group and a double spiral heterocyclic group. More preferably 3 yuan / 5 yuan, 4 yuan / 5 yuan, 4 yuan / 6 yuan, 5 yuan / 5 yuan or 5 yuan / 6 yuan single spiral heterocyclic group. Non-limiting examples of spiro heterocyclic groups include:

[1034]

[1035] wait.

[1036] The term "fused heterocyclyl" refers to a polycyclic heterocyclic group of 5 to 20 members, wherein each ring in the system shares a pair of adjacent atoms with other rings in the system, one or more rings may contain one or more double bonds, but no ring has a completely conjugated π electron system, wherein one or more ring atoms are selected from nitrogen, oxygen or S(O) m(wherein m is an integer from 0 to 2) heteroatoms, the remaining ring atoms being carbon. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused heterocyclic groups, preferably bicyclic or tricyclic, more preferably 3-membered / 5-membered, 4-membered / 5-membered or 5-membered / 6-membered bicyclic fused heterocyclic groups. Non-limiting examples of fused heterocyclic groups include:

[1037]

[1038] wait.

[1039] The term "bridged heterocyclyl" refers to a 5- to 14-membered polycyclic heterocyclic group in which any two rings share two atoms that are not directly connected, which may contain one or more double bonds but no ring has a completely conjugated π electron system, wherein one or more ring atoms are selected from nitrogen, oxygen or S(O) m (wherein m is an integer from 0 to 2) heteroatoms, the remaining ring atoms being carbon. Preferably, it is 6 to 14 members, more preferably 7 to 10 members. Depending on the number of constituent rings, it can be classified as a bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocyclic group, preferably a bicyclic, tricyclic or tetracyclic group, more preferably a bicyclic or tricyclic group. Non-limiting examples of bridged heterocyclic groups include:

[1040]

[1041] The heterocyclyl ring may be fused to an aryl, heteroaryl or cycloalkyl ring, wherein the ring attached to the parent structure is a heterocyclyl, non-limiting examples of which include:

[1042]

[1043] wait.

[1044] The heterocyclyl group may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[1045] The term "aryl" refers to a 6- to 14-membered all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of carbon atoms) group having a conjugated π electron system, preferably 6- to 10-membered, such as phenyl and naphthyl. More preferably, phenyl. The aryl ring may be fused to a heteroaryl, heterocyclyl, or cycloalkyl ring, wherein the ring attached to the parent structure is the aryl ring, non-limiting examples of which include:

[1046]

[1047] wait.

[1048] The aryl group may be substituted or unsubstituted. When substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[1049] The term "heteroaryl" refers to a heteroaromatic system containing 1 to 4 heteroatoms and 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur and nitrogen. The heteroaryl group is preferably 5-10-membered, more preferably 5-membered or 6-membered, such as imidazolyl, furyl, thienyl, thiazolyl, pyrazolyl, oxazolyl, pyrrolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, thiadiazole, oxadiazole, pyrazinyl and pyridazinyl, and is preferably pyrazinyl, pyridazinyl, oxazolyl, oxadiazole, tetrazolyl, triazolyl, thienyl, imidazolyl, pyridyl, pyrimidinyl, pyrazolyl, thiazolyl, thiadiazole, pyrazolyl and pyrimidinyl; more preferably pyrazinyl, pyridyl, pyridazinyl, pyrimidinyl, imidazolyl, triazolyl, pyrazolyl and thiazolyl.

[1050] The term "fused heteroaryl" refers to a heteroaromatic system containing 1 to 6 heteroatoms and 4 to 20 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur and nitrogen. The fused heteroaryl is preferably 6 to 14-membered, more preferably 6 or 10-membered. The fused heteroaryl ring refers to a heteroaryl group fused to an aryl, heterocyclyl or cycloalkyl ring, non-limiting examples of which include:

[1051]

[1052]

[1053] The heteroaryl or fused heteroaryl may be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[1054] The term "alkoxy" refers to-O-(alkyl) and-O-(unsubstituted cycloalkyl), wherein the definition of alkyl is as described above. The limiting examples of alkoxy include: methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy. Alkoxy can be optionally substituted or unsubstituted, and when substituted, substituents are preferably one or more following groups, which are independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[1055] "Haloalkyl" refers to an alkyl group substituted with one or more halogens, wherein alkyl is as defined above.

[1056] "Haloalkoxy" refers to an alkoxy group substituted with one or more halogens, wherein alkoxy is as defined above.

[1057] "Hydroxyalkyl" refers to an alkyl group substituted with a hydroxy group, wherein alkyl is as defined above.

[1058] "Alkenyl" refers to a chain alkenyl group, also known as an alkene group, wherein the alkenyl group can be further substituted with other related groups, for example: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[1059] "Alkynyl" refers to (CH≡C- or -C≡C-), wherein the alkynyl can be further substituted by other related groups, such as: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[1060] "Hydroxy" refers to an -OH group.

[1061] "Halogen" refers to fluorine, chlorine, bromine or iodine.

[1062] "Amino" refers to -NH2.

[1063] "Cyano" refers to -CN.

[1064] "Nitro" refers to -NO2.

[1065] "Carboxyl" refers to -C(O)OH.

[1066] "THF" refers to tetrahydrofuran.

[1067] "EtOAc" refers to ethyl acetate.

[1068] "MeOH" refers to methanol.

[1069] "DMF" refers to N,N-dimethylformamide.

[1070] "DIPEA" refers to diisopropylethylamine.

[1071] "AN" refers to acrylonitrile.

[1072] "TFA" refers to trifluoroacetic acid.

[1073] "MeCN" refers to acetylene glycol.

[1074] "DMA" refers to N,N-dimethylacetamide.

[1075] "Et2O" refers to diethyl ether.

[1076] "DCE" refers to 1,2-dichloroethane.

[1077] "DIPEA" refers to N,N-diisopropylethylamine.

[1078] "NBS" refers to N-bromosuccinimide.

[1079] "NIS" refers to N-iodosuccinimide.

[1080] "Cbz-Cl" refers to benzyl chloroformate.

[1081] "Pd2(dba)3" refers to tris(dibenzylideneacetone)dipalladium.

[1082] "Dppf" refers to 1,1'-bis(diphenylphosphino)ferrocene.

[1083] "HATU" refers to 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[1084] "KHMDS" refers to potassium hexamethyldisilazide.

[1085] "LiHMDS" refers to lithium bis(trimethylsilylamide).

[1086] "MeLi" refers to methyllithium.

[1087] "n-BuLi" refers to n-butyllithium.

[1088] "NaBH(OAc)3" refers to sodium triacetoxyborohydride.

[1089] Different expressions such as “X is selected from A, B, or C”, “X is selected from A, B and C”, “X is A, B or C”, and “X is A, B and C” all express the same meaning, that is, X can be any one or more of A, B, and C.

[1090] The hydrogen atoms described in the present invention can all be replaced by their isotope deuterium, and any hydrogen atom in the example compounds of the present invention can also be replaced by a deuterium atom.

[1091] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, "a heterocyclic group optionally substituted with an alkyl group" means that the alkyl group may but need not be present, and that the description includes instances where the heterocyclic group is substituted with an alkyl group and instances where the heterocyclic group is not substituted with an alkyl group.

[1092] "Substituted" means that one or more hydrogen atoms, preferably up to 5, more preferably 1 to 3 hydrogen atoms, in a group are replaced independently of one another by a corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and a person skilled in the art can determine (by experiment or theory) which substitutions are possible or impossible without undue effort. For example, an amino or hydroxyl group with free hydrogen may be unstable when combined with a carbon atom with an unsaturated (e.g., olefinic) bond.

[1093] A "pharmaceutical composition" refers to a mixture containing one or more compounds described herein, or their physiologically / pharmaceutically acceptable salts or prodrugs, together with other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitating absorption of the active ingredient and thereby exerting its biological activity.

[1094] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present invention that are safe and effective when used in mammals and have the desired biological activity. DETAILED DESCRIPTION

[1095] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[1096] Example

[1097] The structures of the compounds of the present invention are determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer, using deuterated dimethyl sulfoxide (DMSO-d6), deuterated methanol (CD3OD), and deuterated chloroform (CDCl3) as the solvents, with tetramethylsilane (TMS) as the internal standard.

[1098] Liquid chromatography-mass spectrometry (LC-MS) was performed using an Agilent 1200 Infinity Series mass spectrometer. HPLC was performed using an Agilent 1200DAD high-pressure liquid chromatograph (Sunfire C18 150×4.6 mm column) and a Waters 2695-2996 high-pressure liquid chromatograph (Gi min i C18 150×4.6 mm column).

[1099] Thin layer chromatography silica gel plates use Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The specifications used for TLC are 0.15mm-0.20mm, and the specifications used for thin layer chromatography separation and purification products are 0.4mm-0.5mm. Column chromatography generally uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier.

[1100] The starting materials in the examples of the present invention are known and can be purchased commercially, or can be synthesized using or according to methods known in the art.

[1101] Unless otherwise specified, all reactions of the present invention are carried out under continuous magnetic stirring in a dry nitrogen or argon atmosphere, with dry solvents and reaction temperatures in degrees Celsius.

[1102] Example 1

[1103] 3-((3-exo)-3-((7-((5-methylthiooxazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1104]

[1105] Step 1: tert-Butyl (3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate

[1106]

[1107] The compound 5,7-dichloro-1,6-naphthyridine (100 mg, 0.502 mmol), tert-butyl (3-exo)-3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate (119 mg, 0.527 mmol), and diisopropylethylamine (195 mg, 1.51 mmol) were dissolved in dimethyl sulfoxide (4 mL). The reaction mixture was heated to 110°C and stirred for 22 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with saturated sodium chloride solution. The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound as an off-white solid (173 mg, 92%).

[1108] 1 H NMR (400MHz, DMSO-d6) δ8.89(dd,J=4.2,1.3Hz,1H),8.72(d,J=8.3Hz,1H),7.74(d,J=7.5Hz,1H),7.48(dd,J=8 .4,4.3Hz,1H),6.96(s,1H),4.70-4.56(m,1H),4.16(s,2H),2.05-1.87(m,4H),1.81-1.57(m,4H),1.44(s,9H).

[1109] MS m / z(ESI):389.2[M+H] + .

[1110] Step 2: Preparation of 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octane-8-yl)propionitrile

[1111]

[1112] Tert-butyl (3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate (100 mg, 0.257 mmol) was dissolved in dichloromethane (1 mL). Trifluoroacetic acid (0.5 mL) was added with stirring at room temperature. The resulting reaction mixture was stirred at room temperature for 30 minutes, concentrated under reduced pressure to remove the solvent, and anhydrous methanol was added for dissolution. Diisopropylethylamine (332 mg, 2.57 mmol) and acrylonitrile (16 mg, 0.31 mmol) were then added in sequence. The reaction mixture was stirred at room temperature for 26.5 hours. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a white powder (81 mg, 92%).

[1113] 1H NMR (400MHz, DMSO-d6) δ8.90-8.87(m,1H),8.72(d,J=8.3Hz,1H),7.76(d,J=7.7Hz,1H),7.47(dd,J=8.4,4.3H z,1H),6.94(s,1H),4.51-4.35(m,1H),3.34(s,2H),2.69-2.58(m,4H),1.98-1.88(m,2H),1.84-1.62(m,6H).

[1114] MS m / z(ESI):342.1[M+H] + .

[1115] Step 3: Preparation of 3-((3-exo)-3-((7-((5-methylthiooxazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octane-8-yl)propionitrile

[1116]

[1117] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (50 mg, 0.146 mmol), 5-methylthiooxazol-2-amine (25 mg, 0.219 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (7 mg, 0.009 mmol) and cesium carbonate (86 mg, 0.263 mmol) were added to ultra-dry 1,4-dioxane (5 mL). The reaction mixture was saturated with dry nitrogen and then sealed and heated to 110°C with stirring for 24 hours. The reaction mixture was then cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure. The title compound was separated by preparative TLC to obtain a yellow-green solid (14 mg, 23%).

[1118] 1 H NMR (400MHz, DMSO-d6) δ10.77(s,1H),8.71-8.63(m,1H),8.55(d,J=8.3Hz,1H),7.47(d,J=8.6Hz,1H),7.10(dd,J=8.3,4. 3Hz,1H),7.02(d,J=1.1Hz,1H),6.46(s,1H),4.96-4.77(m,1H),3.36(s,2H),2.65(s,4H),2.32(s,3H),2.04-1.72(m,8H).

[1119] MS m / z(ESI):420.2[M+H] + .

[1120] Example 2

[1121] 3-(3-exo)-3-((7-((5-(hydroxymethyl)thiazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1122]

[1123] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (50 mg, 0.146 mmol), (2-aminothiazol-5-yl)methanol (38 mg, 0.292 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)] )] Palladium (II) (58 mg, 0.073 mmol) and cesium carbonate (143 mg, 0.438 mmol) were added to ultra-dry 1,4-dioxane (5 mL), and the reaction mixture was saturated with dry nitrogen to deoxygenate. The mixture was then heated to 140°C using a microwave reactor and stirred for 2.5 hours, then cooled to room temperature. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The title compound (8.6 mg, 14%) was separated and purified by silica gel column chromatography and reverse-phase HPLC.

[1124] 1 H NMR (400MHz, DMSO-d6) δ10.85(s,1H),8.70-8.65(m,1H),8.60-8.53(m,1H),7.47(d,J=8.6Hz,1H),7.18(s,1H),7.11(dd,J=8.3,4.3Hz,1H),6.50(s ,1H),5.16(t,J=5.2Hz,1H),4.86(dd,J=16.7,8.2Hz,1H),4.56(d,J=5.2H z,2H),3.33(s,2H),2.65(s,4H),1.99-1.86(m,4H),1.81(d,J=7.4Hz,4H).

[1125] MS m / z(ESI):436.1[M+H] + .

[1126] Example 3

[1127] 3-((3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1128]

[1129] Step 1: Preparation of 2,4-dichloro-5-tosyl-7-hydrogen-pyrrolo[2,3-d]pyrimidine

[1130]

[1131] To a solution of 2,4-dichloropyrrolo[3,2-d]pyrimidine (200 mg, 1.06 mmol) in dichloromethane (5 mL) were added TsCl (242 mg, 1.27 mmol) and DIPEA (273 mg, 2.12 mmol) in sequence, followed by stirring at room temperature overnight. Upon completion of the reaction, the reaction mixture was extracted with DCM (15 mL x 3) and washed with saturated sodium chloride (15 mL x 3). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the solvent was concentrated under reduced pressure. The resulting product was purified by silica gel column chromatography (PE:DCM from 0 to 70:30) to afford the title compound as a white solid (360 mg, 99%).

[1132] MS m / z(ESI):343.0[M+H] + .

[1133] Step 2: Preparation of 2-chloro-N-(5-methyl-1H-pyrazol-3-yl)-7-toluenesulfonyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

[1134]

[1135] To a solution of 2,4-dichloro-5-tosyl-7-hydro-pyrrolo[2,3-d]pyrimidine (171 mg, 0.5 mmol) in MeCN (10 mL) were added 3-amino-5-methylpyrazole (53 mg, 0.55 mmol) and DIPEA (129 mg, 1 mmol), followed by stirring at 100°C under microwave conditions for 2 hours. Upon completion of the reaction, the reaction solution was extracted with EA (15 mL x 3) and washed with saturated sodium chloride (15 mL x 3). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting product was purified by silica gel column chromatography (DCM:MeOH from 0 to 95:5) to afford the title compound as a pale yellow solid (185 mg, 92%).

[1136] MS m / z(ESI):402.1[M+H]+ .

[1137] Step 3: Preparation of tert-butyl-(3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylic acid

[1138]

[1139] To a solution of 2-chloro-N-(5-methyl-1H-pyrazol-3-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (100 mg, 0.25 mmol) in n-BuOH (5 mL) were added N-Boc-exo-3-aminotropane (85 mg, 0.375 mmol) and DIPEA (64.5 mg, 0.5 mmol) in sequence, followed by stirring at 150°C under microwave conditions for 12 hours. Upon completion of the reaction, the reaction mixture was extracted with EA (15 mL x 3) and washed with saturated aqueous sodium chloride (15 mL x 3). The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the organic solvent was concentrated under reduced pressure to afford the title compound as a pale yellow solid (100 mg, 68%).

[1140] MS m / z(ESI):593.1[M+H] + .

[1141] Step 4: Preparation of 3-((3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-8-azabicyclo[3.2.1]octane-8-yl)propionitrile

[1142]

[1143] Tert-butyl-(3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylic acid (100 mg, 0.17 mmol) was dissolved in 4.0 N hydrochloric acid and ethyl acetate solution (2 mL). The mixture was stirred at room temperature for 30 minutes and then spun down to dryness. MeOH (10 mL) was then added to dissolve the mixture. DIPEA (88 mg, 0.68 mmol) was slowly added dropwise and stirred at room temperature for 10 minutes. Acrylonitrile (14 mg, 0.26 mmol) was added and stirring continued for 2 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (DCM:MeOH = 10:1) to afford the title compound as a yellow solid (52.6 mg, 57%).

[1144] MS m / z(ESI):546.1[M+H] + .

[1145] Step 5: Preparation of 3-((3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-8-azabicyclo[3.2.1]octane-8-yl)propionitrile

[1146]

[1147] To a mixed solution of 3-((3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (50 mg, 0.09 mmol) in 1,4-dioxane (10 mL) and methanol (5 mL) was added an aqueous solution (0.2 mL) of sodium hydroxide (36 mg, 0.9 mmol), followed by heating and stirring at 55°C overnight. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and analyzed by prep-HPLC to yield the title compound as a white solid (10 mg, 29%).

[1148] 1 H NMR(400MHz,DMSO)δ11.85(s,1H),10.72(s,1H),9.38(s,1H),6.67(s,3H),5.92(s,1H ),4.11(s,1H),3.29(s,2H),2.62(s,4H),2.20(s,3H),1.90(s,2H),1.82-1.47(m,6H).

[1149] MS m / z(ESI):392.2[M+H] + .

[1150] Example 4

[1151] 3-((3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)amino)-8-azabicyclo

[1152] [3.2.1]octan-8-yl)propionitrile

[1153]

[1154] Step 1: Preparation of 2-chloro-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine

[1155]

[1156] 2,4-Dichloroquinazoline (199 mg, 1.0 mmol), 5-methyl-1H-pyrazol-3-amine (99 mg, 1.02 mmol), and triethylamine (213 mg, 2.1 mmol) were added to anhydrous ethanol (5 mL) and stirred at room temperature for 18 hours. The reaction solution was concentrated under reduced pressure, and the resulting solid was suspended in water-ethanol (v / v = 9:1, 20 mL). The resulting solid was filtered, washed with petroleum ether, and dried to obtain the title compound (240 mg, 92%).

[1157] MS m / z(ESI):260.1,262.1[M+H] + .

[1158] Step 2: tert-Butyl (3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate

[1159]

[1160] 2-Chloro-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (40 mg, 0.154 mmol) and tert-butyl (3-exo)-3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate (70 mg, 0.308 mmol) were added to n-butanol (3 mL). The mixture was stirred at room temperature and then microwaved at 150°C for 4 hours. The solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the crude title compound (120 mg), which was used directly in the next reaction.

[1161] MS m / z(ESI):450.2[M+H] + .

[1162] Step 3: Preparation of 3-((3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)amino)-8-azabicyclo[3.2.1]octane-8-yl)propionitrile

[1163]

[1164] The crude product of tert-butyl (3-exo)-3-((4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate (120 mg, 0.154 mmol) was dissolved in methanol (3 mL) and added to a 4M HCl solution in 1,4-dioxane (10 mL) with stirring at room temperature. The reaction mixture was stirred at room temperature for 30 minutes, and the solvent was removed by concentration under reduced pressure. The residue was dissolved in anhydrous methanol (10 mL), and diisopropylethylamine (0.51 mL, 3.08 mmol) and acrylonitrile (10 mg, 0.154 mmol) were added sequentially with stirring at room temperature. The reaction mixture was stirred at room temperature for another 2.5 hours, and the solvent was removed by concentration under reduced pressure. The residue was separated and purified by silica gel column chromatography and reverse phase HPLC to obtain the title compound (6.0 mg, 10%).

[1165] 1 H NMR (400MHz, CD3OD) δ8.04(d,J=8.1Hz,1H),7.58(t,J=7.5Hz,1H),7.39(s,1H),7.16(t,J=7.5Hz,1H),6.62(s,1H),4.35( s,1H),3.37(s,2H),2.76(t,J=6.9Hz,2H),2.62(t,J=6.9Hz,2H),2.31(s,3H),2.16-1.74(m,6H),1.67(t,J=11.7Hz,2H).

[1166] MS m / z(ESI):403.2[M+H] + .

[1167] Example 5

[1168] 3-(cis-5-((7-((5-methyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)propionitrile

[1169]

[1170] Step 1: Preparation of tert-butyl (3aR, 5r, 6aS)-5-((7-chloro-1,6-naphthyridin-5-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

[1171]

[1172] Tert-butyl cis-5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (100 mg, 0.442 mmol), 5,7-dichloro-1,6-naphthyridine (83 mg, 0.42 mmol) and diisopropylethylamine (0.208 mL, 1.26 mmol) were dissolved in DMSO (2 mL), heated to 110°C and stirred for 15 hours. The reaction solution was diluted with ethyl acetate, and the ethyl acetate layer was washed with saturated aqueous sodium chloride solution. The organic phase was collected and dried over anhydrous sodium sulfate. After filtration, the organic solvent was concentrated under reduced pressure. The resulting product was separated and purified by silica gel column chromatography to obtain the title compound (142 mg, 87%).

[1173] MS m / z(ESI):389.4[M+H] + .

[1174] Step 2: Preparation of 3-(cis-5-((7-chloro-1,6-naphthyridin-5-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)propionitrile

[1175]

[1176] Tert-butyl cis-5-((7-chloro-1,6-naphthyridin-5-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (142 mg, 0.365 mmol) was dissolved in methanol (2 mL). 4 M HCl in 1,4-dioxane (10 mL) was added with stirring at room temperature. The mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure. The residue was redissolved in anhydrous methanol (10 mL). Diisopropylethylamine (1.2 mL, 7.3 mmol) and acrylonitrile (0.03 mL, 0.438 mmol) were added sequentially. The resulting reaction mixture was stirred at room temperature for another 2 hours, then concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography to obtain the title compound (123 mg, 98%).

[1177] MS m / z(ESI):342.1[M+H] + .

[1178] Step 3: Preparation of 3-(cis-5-((7-((5-methyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)propionitrile

[1179]

[1180] 3-(cis-5-((7-chloro-1,6-naphthyridin-5-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)propionitrile (50 mg, 0.146 mmol), tert-butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate (44 mg, 0.219 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (7 mg, 0.009 mmol) and cesium carbonate (86 mg, 0.263 mmol) were added to ultra-dry 1,4-dioxane (5 mL). The reaction mixture was saturated with dry nitrogen and then sealed and heated to 100°C with stirring for 17 hours. After that, it was cooled to room temperature and filtered, and the filtrate was concentrated under reduced pressure. The product was redissolved in 4M HCl in 1,4-dioxane (10 mL), stirred at room temperature for 30 minutes, and the solvent was concentrated under reduced pressure. The residue was separated by prep-HPLC to obtain the title compound (2.6 mg, 4%).

[1181] 1 H NMR (400MHz, CD3OD) δ8.54(dd,J=9.0,5.7Hz,1H),8.43-8.24(m,1H),7.06(d,J=5.8Hz,1H),6.66(d,J=5. 2Hz,1H),6.12(s,1H),4.63-4.48(m,1H),3.06-2.56(m,8H),2.55-2.34(m,4H),2.28(s,3H),1.57(s,2H).

[1182] MS m / z(ESI):403.2[M+H] + .

[1183] Example 6

[1184] 3-((3-exo)-3-((7-((1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1185]

[1186] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (50 mg, 0.146 mmol), tert-butyl 3-(l2-azanyl)-1H-pyrazole-1-carboxylate (40 mg, 0.219 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (7 mg, 0.009 mmol) and cesium carbonate (86 mg, 0.263 mmol) were added to ultra-dry 1,4-dioxane (5 mL). The reaction mixture was saturated with dry nitrogen to deoxygenate, sealed in a tube, heated to 110°C, stirred for 16 hours, cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure. The product was redissolved in dichloromethane (2 mL), trifluoroacetic acid (1 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The product was concentrated under reduced pressure, and the residue was separated by prep-HPLC to obtain the title compound (17 mg, 31%).

[1187] 1 H NMR (400MHz, DMSO-d6) δ12.07(s,1H),8.81(s,1H),8.58(d,J=3.3Hz,1H),8.42(d,J=8.6Hz,1H),7.58(s,1H),7.14(dd,J=6.2,2.8Hz,1H),6.97(dd ,J=7.9,4.2Hz,1H),6.75(s,1H),6.34(s,1H),4.59-4.42(m,1H),3.33(s, 2H),2.63(s,4H),1.97-1.86(m,2H),1.78(ddt,J=24.7,23.4,7.2Hz,6H).

[1188] MS m / z(ESI):389.2[M+H] + .

[1189] Example 7

[1190] 3-((3-exo)-3-((7-((5-(difluoromethyl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1191]

[1192] The preparation of 3-((3-exo)-3-((7-((5-(difluoromethyl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 1.

[1193] MS m / z(ESI):439.2[M+H] + .

[1194] Example 8

[1195] 3-((3-exo)-3-((7-((5-(trifluoromethyl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1196]

[1197] The preparation of 3-((3-exo)-3-((7-((5-(trifluoromethyl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 1.

[1198] MS m / z(ESI):457.2[M+H] + .

[1199] Example 9

[1200] 3-((3-exo)-3-((7-((5-fluoro-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1201]

[1202] The preparation of 3-((3-exo)-3-((7-((5-fluoro-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 1.

[1203] 1 H NMR (400MHz, DMSO-d6) δ11.61(d,J=1.5Hz,1H),9.35(s,1H),8.65(dd,J=4.3,1.2Hz,1H),8.49(d,J=8.8Hz,1H),7.40(d,J=7.8Hz,1H),7.07(dd,J=8. 4,4.3Hz,1H),6.25(s,1H),5.77(dd,J=6.0,2.1Hz,1H),4.47-4.39(m,1H) ,3.32(s,2H),2.62(t,J=4.2Hz,4H),1.95-1.86(m,2H),1.83-1.70(m,6H).

[1204] MS m / z(ESI):407.2[M+H] + .

[1205] Example 10

[1206] 3-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)-1H-pyrazole-5-carbonitrile

[1207]

[1208] The preparation of 3-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)-1H-pyrazole-5-carbonitrile was carried out according to Example 1.

[1209] MS m / z(ESI):414.2[M+H] + .

[1210] Example 11

[1211] 3-((3-exo)-3-((7-((5-ethyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1212]

[1213] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (100 mg, 0.292 mmol), 5-ethyl-1H-pyrazol-3-amine (65 mg, 0.584 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (115 mg, 0.146 mmol) and cesium carbonate (286 mg, 0.876 mmol) were added to ultra-dried 1,4-epoxyhexacyclopropane (10 mL). The reaction solution was saturated with dry nitrogen and heated to 150°C in a microwave synthesizer for 8 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and separated by silica gel column chromatography and reverse phase HPLC to obtain the title compound (2.2 mg, 2%).

[1214] 1H NMR (400MHz, DMSO-d6) δ11.77(s,1H),8.71(s,1H),8.57(dd,J=4.1,1.4Hz,1H),8. 40(d,J=7.1Hz,1H),7.12(d,J=8.4Hz,1H),6.95(dd,J=8.1,4.4Hz,1H),6.68(s,1H ),6.16(s,1H),4.53(dd,J=12.8,5.6Hz,1H),3.33(s,2H),2.63(ddd,J=24.2,9.2, 4.8Hz, 6H), 1.92 (dd, J=8.1, 4.4Hz, 2H), 1.85-1.66 (m, 6H), 1.20 (t, J=7.6Hz, 3H).

[1215] MS m / z(ESI):417.2[M+H] + .

[1216] Example 12

[1217] 3-((3-exo)-3-((7-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1218]

[1219] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (100 mg, 0.292 mmol), 5-cyclopropyl-1H-pyrazol-3-amine (72 mg, 0.585 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1 ,1'-biphenyl)] palladium(II) (115 mg, 0.146 mmol) and cesium carbonate (285 mg, 0.876 mmol) were added to ultra-dry 1,4-dioxane (5 mL), and the reaction mixture was saturated with dry nitrogen and heated to 150°C with stirring in a microwave oven for 3 hours, then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography and reverse phase HPLC to give the title compound (20 mg, 16%).

[1220] 1H NMR (400MHz, DMSO-d6) δ11.75(s,1H),8.67(s,1H),8.57(d,J=3.2Hz,1H),8.44-8.36(m,1H),7.12(ddd,J=12.4,9.6,3.9Hz,1H),6.96(dd,J=8.0,3. 9Hz,1H),6.70(s,1H),6.06(s,1H),4.53(d,J=4.9Hz,1H),3.33(s,2H),2. 63(s,4H),2.01-1.63(m,9H),0.91(d,J=7.5Hz,2H),0.70(d,J=4.3Hz,2H).

[1221] MS m / z(ESI):429.2[M+H] + .

[1222] Example 13

[1223] 3-((3-exo)-3-((7-((5-(oxetan-3-yl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1224]

[1225] The preparation of 3-((3-exo)-3-((7-((5-(oxetan-3-yl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 12.

[1226] MS m / z(ESI):445.2[M+H] + .

[1227] Example 14

[1228] 3-((3-exo)-3-((7-((5-(1-methylazetidin-3-yl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1229]

[1230] The preparation of 3-((3-exo)-3-((7-((5-(1-methylazetidin-3-yl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 12.

[1231] MS m / z(ESI):458.3[M+H] + .

[1232] Example 15

[1233] 3-((3-exo)-3-((7-((4,5-dimethyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-

[1234] Azabicyclo[3.2.1]octan-8-yl)propionitrile

[1235]

[1236] The preparation of 3-((3-exo)-3-((7-((4,5-dimethyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 12.

[1237] 1 H NMR (400MHz, DMSO-d6) δ8.76 (dd, J=4.2, 1.3Hz, 1H), 8.60 (d, J=8.2Hz, 1H), 7. 44(d,J=8.4Hz,1H),7.24(dd,J=8.3,4.4Hz,1H),7.10(s,1H),4.97(s,2H),4. 52(dd,J=16.9,8.1Hz,1H),3.33(s,2H),2.66(dd,J=10.4,2.9Hz,7H),1.92(d dd,J=5.9,3.4,1.8Hz,2H),1.85(s,3H),1.72(ddd,J=20.9,11.4,4.3Hz,6H).

[1238] MS m / z(ESI):417.1[M+H] + .

[1239] Example 16

[1240] 3-((3-exo)-3-((7-((4-fluoro-5-methyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1241]

[1242] The preparation of 3-((3-exo)-3-((7-((4-fluoro-5-methyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 12.

[1243] MS m / z(ESI):421.2[M+H] + .

[1244] Example 17

[1245] 3-((3-exo)-3-((7-((5-methoxy-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1246]

[1247] The preparation of 3-((3-exo)-3-((7-((5-methoxy-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 12.

[1248] MS m / z(ESI):419.2[M+H] + .

[1249] Example 18

[1250] 3-((3-exo)-3-((7-((5-(methoxymethyl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1251]

[1252] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (72 mg, 0.21 mmol), 2-(2-aminothiazol-5-yl)propan-2-ol (54 mg, 0.42 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (83 mg, 0.105 mmol) and cesium carbonate (205 mg, 0.63 mmol) were added to ultra-dried 1,4-epoxyhexacyclopropane (10 mL). The reaction mixture was saturated with dry nitrogen and heated to 150°C in a microwave synthesizer with stirring for 7 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and separated by prep-HPLC to obtain the title compound (22.4 mg, 25%).

[1253] 1 H NMR (400MHz, DMSO-d6) δ8.57(d,J=3.5Hz,1H),8.50(d,J=8.6Hz,1H),7.07(dd,J=8.0,4.7Hz,1H),6.74(s,1H),6.35(s,1H ),4.63(td,J=10.8,6.1Hz,1H),4.43(s,2H),3.71-3.48(m,2H),3.35(s,3H),2.93(s,2H),2.75(s,2H),2.23-1.75(m,8H).

[1254] MS m / z(ESI):433.2[M+H] + .

[1255] Example 19

[1256] 3-((3-exo)-3-((7-((5-(hydroxymethyl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1257]

[1258] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (100 mg, 0.292 mmol), (3-amino-1H-pyrazol-5-yl)methanol (66 mg, 0.584 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (115 mg, 0.146 mmol) and cesium carbonate (286 mg, 0.877 mmol) were added to ultra-dried 1,4-epoxyhexacyclopropane (15 mL). The reaction mixture was saturated with dry nitrogen and heated to 150°C in a microwave synthesizer with stirring for 6 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and separated by prep-HPLC to give the title compound (15.7 mg, 13%).

[1259] 1 H NMR (400MHz, DMSO-d6) δ11.94(s,1H),8.77(s,1H),8.58(d,J=3.3Hz,1H),8.41(d, J=8.1Hz,1H),7.13(s,1H),6.97(dd,J=7.9,4.4Hz,1H),6.72(s,1H),6.24(s,1H),5 .20(d,J=1.8Hz,1H),4.53(dd,J=6.8,4.2Hz,1H),4.45(d,J=5.2Hz,2H),3.33(s,2H ),2.63(s,4H),1.95-1.87(m,2H),1.80(dd,J=13.3,7.7Hz,4H),1.75-1.67(m,2H).

[1260] MS m / z(ESI):419.2[M+H] + .

[1261] Example 20

[1262] 3-((3-exo)-3-((7-((5-(2-hydroxypropan-2-yl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1263]

[1264] The preparation of 3-((3-exo)-3-((7-((5-(2-hydroxypropan-2-yl)-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 2.

[1265] MS m / z(ESI):447.3[M+H] + .

[1266] Example 21

[1267] 3-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)-1H-pyrazole-5-carboxamide

[1268]

[1269] The preparation of 3-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)-1H-pyrazole-5-carboxamide was carried out according to Example 2.

[1270] MS m / z(ESI):432.2[M+H] + .

[1271] Example 22

[1272] 3-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)-N-methyl-1H-pyrazole-5-carboxamide

[1273]

[1274] The preparation of 3-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)-N-methyl-1H-pyrazole-5-carboxamide was carried out according to Example 2.

[1275] MS m / z(ESI):446.2[M+H] + .

[1276] Example 23

[1277] 3-((3-exo)-3-((7-((2-methyl-1H-imidazol-4-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1278]

[1279] The preparation of 3-((3-exo)-3-((7-((2-methyl-1H-imidazol-4-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 6.

[1280] MS m / z(ESI):403.2[M+H] + .

[1281] Example 24

[1282] 3-((3-exo)-3-((7-((5-methyl-1H-1,2,4-triazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1283]

[1284] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (100 mg, 0.292 mmol), 5-methyl-4H-1,2,4-triazol-3-amine hydrochloride (47.2 mg, 0.351 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (115 mg, 0.146 mmol) and cesium carbonate (171 mg, 0.526 mmol) were added to ultra-dried 1,4-epoxyhexacyclopropane (10 mL). The reaction solution was saturated with dry nitrogen and heated to 150°C in a microwave synthesizer with stirring for 4 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and separated by silica gel column chromatography and reverse phase HPLC to give the title compound (12.4 mg, 10.5%).

[1285] 1 H NMR (400MHz, DMSO-d6) δ12.73(s,1H),9.19(s,1H),8.68-8.62(m,1H),8.47(d,J=8.3Hz,1H),7.23(dt,J=39.0,8.1Hz,2H),7.08(dd,J=8.2, 4.2Hz,1H),4.48(td,J=12.0,6.7Hz,1H),3.31-3.30(m,2H),2.63(t,J=3.0Hz,4H),2.28(s,3H),1.92-1.80(m,6H),1.69(t,J=11.8Hz,2H).

[1286] MS m / z(ESI):404.2[M+H]+ .

[1287] Example 25

[1288] 3-((3-exo)-3-((7-((1-methyl-1H-imidazol-4-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1289]

[1290] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (100 mg, 0.292 mmol), 1-methyl-1H-imidazole-4-amine hydrochloric acid (78 mg, 0.585 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino- To ultra-dry 1,4-dioxane (5 mL) was added palladium (II) (115 mg, 0.146 mmol) and cesium carbonate (477 mg, 1.46 mmol). The reaction mixture was saturated with dry nitrogen and heated to 140°C with stirring for 4 hours in a microwave oven, then cooled to room temperature. The filtrate was filtered and concentrated under reduced pressure. The title compound (4.4 mg, 4%) was separated and purified by silica gel column chromatography and reverse-phase HPLC.

[1291] 1 H NMR (400MHz, DMSO-d6) δ8.77(s,1H),8.55(dd,J=4.2,1.3Hz,1H),8.40(d,J=8.4Hz,1H),7.36(s,1H),7.17(d,J=7.5Hz,2H),6.92( dd,J=8.3,4.3Hz,1H),6.32(s,1H),4.56(ddd,J=17.5,12.0,6.1Hz,1H),3.64(s,3H),3.34(s,2H),2.64(s,4H),2.06-1.65(m,8H).

[1292] MS m / z(ESI):403.2[M+H] + .

[1293] Example 26

[1294] 3-((3-exo)-3-((7-((1-methyl-1H-1,2,4-triazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1295]

[1296] The preparation of 3-((3-exo)-3-((7-((1-methyl-1H-1,2,4-triazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 25.

[1297] MS m / z(ESI):404.2[M+H] + .

[1298] Example 27

[1299] 3-((3-exo)-3-((7-((1H-indazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo

[1300] [3.2.1]octan-8-yl)propionitrile

[1301]

[1302] The preparation of 3-((3-exo)-3-((7-((1H-indazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 6.

[1303] MS m / z(ESI):439.2[M+H] + .

[1304] Example 28

[1305] 3-((3-exo)-3-((7-((1H-pyrazolo[3,4-c]pyridin-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1306]

[1307] The preparation of 3-((3-exo)-3-((7-((1H-pyrazolo[3,4-c]pyridin-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 6.

[1308] MS m / z(ESI):440.2[M+H] + .

[1309] Example 29

[1310] 3-((3-exo)-3-((7-(pyrazin-2-ylamino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1311]

[1312] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (50 mg, 0.146 mmol), pyrazin-2-amine (21 mg, 0.219 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (7 mg, 0.009 mmol) and cesium carbonate (86 mg, 0.263 mmol) were added to ultra-dry 1,4-dioxane (5 mL). The reaction mixture was saturated with dry nitrogen, sealed and heated to 110°C with stirring for 23 hours, then cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure. The title compound (30.2 mg, 52%) was separated by prep-HPLC.

[1313] 1 H NMR (400MHz, DMSO-d6) δ9.65 (s, 1H), 9.28 (d, J = 0.4Hz, 1H), 8.70 (d, J = 3.1H z,1H),8.55(d,J=8.3Hz,1H),8.33-8.20(m,3H),8.07(d,J=2.5Hz,1H),7.40 (d,J=8.0Hz,1H),7.15(dd,J=8.3,4.3Hz,1H),7.04(s,1H),4.54(ddd,J=16 .1,11.1,6.6Hz,1H),3.34(d,J=0.9Hz,2H),2.64(s,4H),2.00-1.69(m,8H).

[1314] MS m / z(ESI):401.3[M+H] + .

[1315] Example 30

[1316] 3-((3-exo)-3-((7-(pyrimidin-2-ylamino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1317]

[1318] The preparation of 3-((3-exo)-3-((7-(pyrimidin-2-ylamino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 29.

[1319] MS m / z(ESI):401.2[M+H] + .

[1320] Example 31

[1321] 3-((3-exo)-3-((7-((5-(2-hydroxypropan-2-yl)thiazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1322]

[1323] Step 1: Preparation of 2-(2-aminothiazol-5-yl)propan-2-ol

[1324]

[1325] Ethyl 2-aminothiazole-5-carboxylate (345 mg, 2.0 mmol) was dissolved in dry tetrahydrofuran (10 mL) and cooled to 0°C. Methylmagnesium bromide (3 M in ether, 4 mL, 12 mmol) was added dropwise to the reaction mixture under nitrogen. The reaction mixture was stirred at 0°C for 17 hours. The reaction was quenched by adding water and extracted with ethyl acetate. The ethyl acetate layer was washed sequentially with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (237 mg, 75%).

[1326] MS m / z(ESI):159.2[M+H] + .

[1327] Second step reaction: Preparation of 3-((3-exo)-3-((7-((5-(2-hydroxypropane-2-yl)thiazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1328]

[1329] 3-((3-exo)-3-((7-chloro-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile (50 mg, 0.146 mmol), 2-(2-aminothiazol-5-yl)propan-2-ol (46 mg, 0.292 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (57 mg, 0.073 mmol) and cesium carbonate (143 mg, 0.438 mmol) were added to ultra-dried 1,4-epoxyhexacyclopropane (5 mL). The reaction mixture was saturated with dry nitrogen and heated to 90°C with stirring for 4 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and separated by prep-HPLC to obtain the title compound (29.8 mg, 44%).

[1330] 1 H NMR (400MHz, DMSO-d6) δ10.71(s,1H),8.67(dd,J=4.2,1.2Hz,1H),8.56(d,J=8.3Hz,1H),7.40(d,J=8.5Hz,1H),7.13-7.07(m,2H),6.49(s,1H ),5.25(s,1H),4.83(dd,J=17.2,8.5Hz,1H),3.35(s,2H),2.65(s,4H),1.93(dt,J=12.9,9.8Hz,4H),1.80(dd,J=8.5,1.5Hz,4H),1.52(s,6H).

[1331] MS m / z(ESI):464.2[M+H] + .

[1332] Example 32

[1333] 3-((3-exo)-3-((7-((5-(1-hydroxycyclopropyl)thiazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1334]

[1335] The preparation of 3-((3-exo)-3-((7-((5-(1-hydroxycyclopropyl)thiazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 31.

[1336] MS m / z(ESI):462.2[M+H] + .

[1337] Example 33

[1338] 3-((3-exo)-3-((7-((5-(hydroxymethyl)-4-methylthiooxazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1339]

[1340] The preparation of 3-((3-exo)-3-((7-((5-(hydroxymethyl)-4-methylthiooxazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile was carried out according to Example 31.

[1341] MS m / z(ESI):450.2[M+H] + .

[1342] Example 34

[1343] 2-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)thiazole-5-sulfonamide

[1344]

[1345] The preparation of 2-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)thiazole-5-sulfonamide was carried out according to Example 2.

[1346] MS m / z(ESI):485.1[M+H] + .

[1347] Example 35

[1348] 2-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)thiazole-5-carboxamide

[1349]

[1350] Step 1: Preparation of tert-butyl (3-exo)-3-((7-((5-carbamoylthiazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate

[1351]

[1352] Dissolve tert-butyl (3-exo)-3-((7-((5-cyanothiazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate (72 mg, 0.15 mmol) in DMSO (5 mL). Add lithium hydroxide monohydrate (19 mg, 0.45 mmol) and 30% aqueous hydrogen peroxide (0.18 mL, 0.45 mmol) sequentially with stirring at room temperature. Stirring is continued at room temperature for 21 hours. The reaction mixture is diluted with ethyl acetate, and the organic phase is washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and filtered. The crude product is used directly in the next reaction.

[1353] MS m / z(ESI):496.1[M+H] + .

[1354] Second step reaction: Preparation of 2-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)thiazole-5-carboxamide

[1355]

[1356] Tert-butyl (3-exo)-3-((7-((5-carbamoylthiazol-2-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate was dissolved in 4M HCl in 1,4-dioxane (10 mL) and stirred at room temperature for 15 minutes. The mixture was concentrated under reduced pressure, and the residue was redissolved in anhydrous methanol (10 mL). DIPEA (0.74 mL, 4.5 mmol) and acrylonitrile (0.2 mL, 3.0 mmol) were added sequentially. The resulting reaction mixture was stirred at room temperature for another 70 minutes. The solvent was removed by concentration under reduced pressure, and the residue was separated by prep-HPLC to yield the title compound (6.1 mg, 9%).

[1357] 1H NMR (400MHz, DMSO-d6) δ11.23 (s, 1H), 8.71 (dd, J=4.2, 1.3Hz, 1H), 8.61 (d, J= 7.9Hz,1H),7.95(s,1H),7.70(s,1H),7.49(d,J=8.6Hz,1H),7.16(dd,J=8.4,4 .3Hz,1H),7.10(s,1H),6.55(s,1H),4.82(dd,J=17.6,9.3Hz,1H),3.32-3.27( m,2H),2.65(t,J=3.1Hz,4H),2.00(dd,J=14.0,6.3Hz,2H),1.91-1.74(m,6H).

[1358] Example 36

[1359] 6-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)pyridazine-3-carboxamide

[1360]

[1361] The preparation of 6-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)pyridazine-3-carboxamide was carried out according to Example 2.

[1362] MS m / z(ESI):444.2[M+H] + .

[1363] Example 37

[1364] 6-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)-N-methylpyridazine-3-carboxamide

[1365]

[1366] The preparation of 6-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)-N-methylpyridazine-3-carboxamide was carried out according to Example 2.

[1367] MS m / z(ESI):458.2[M+H] + .

[1368] Example 38

[1369] 5-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)pyrazine-2-carboxamide

[1370]

[1371] The preparation of 5-((5-(((3-exo)-8-(2-cyanoethyl)-8-azabicyclo[3.2.1]octan-3-yl)amino)-1,6-naphthyridin-7-yl)amino)pyrazine-2-carboxamide was carried out according to Example 2.

[1372] MS m / z(ESI):444.2[M+H] + .

[1373] Example 39

[1374] 3-((3-exo)-3-((2-((5-methyl-1H-pyrazol-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propionitrile

[1375]

[1376] Step 1: Preparation of tert-butyl-(3-exo)-3-((2-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate

[1377]

[1378] To a solution of 2,4-dichloro-7-tosyl-7-hydro-pyrrolo[2,3-d]pyrimidine (171 mg, 0.5 mmol) in ethanol (10 mL) were added tert-butyl-(3-exo)-3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate (136 mg, 0.6 mmol) and DIPEA (129 mg, 1 mmol), followed by stirring at 8...

Claims

1. A compound represented by the general formula (I-4) or a pharmaceutically acceptable salt thereof: in, L1 is selected from C1-C4 alkylene or -S(O)2-; L2 is -NR4-; R4 is a hydrogen atom; L3 is -NH-; Ring B is selected from Ring C is selected from R1 is selected from cyano or a 4-membered monoheterocyclic group "wherein the heteroatom is selected from one or more of N and O, and the number of heteroatoms is 1-3"; the monoheterocyclic group is further substituted by cyano; R2 is selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy, halogen, cyclopropyl, 4-6 membered monoheterocyclic group "heteroatoms selected from one or more of N and O, with 1-3 heteroatoms", phenyl or 5-6 membered heteroaryl "heteroatoms selected from N, with 1-3 heteroatoms"; the heteroaryl may be further substituted by one or more of C1-C3 alkyl or C1-C3 alkoxy; R3 is selected from a hydrogen atom or a C1-C3 alkyl group; x is selected from 0 or 1; y is selected from 0 or 1.

2. The compound represented by the general formula (I-4) according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that: Ring C is 3. The compound represented by the general formula (I-4) according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that: The 4-membered monoheterocyclic group in R1 is 4. The compound represented by the general formula (I-4) according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that: When R2 is a 4-6 membered monoheterocyclic group with "a heteroatom selected from one or more of N and O, and 1 to 3 heteroatoms", the monoheterocyclic group is 5. The compound represented by the general formula (I-4) according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that: When R2 is a 5-6 membered heteroaryl group with a heteroatom selected from N and 1 to 3 heteroatoms, the heteroaryl group is selected from 6. A compound as described below or a pharmaceutically acceptable salt thereof:

7. A pharmaceutical composition comprising a therapeutically effective dose of a compound represented by the general formula (I-4) as described in any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers, diluents or excipients.

8. Use of the compound represented by the general formula (I-4) according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition according to claim 7 in the preparation of a JAK inhibitor drug.

9. Use of the compound represented by the general formula (I-4) according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition according to claim 7 in the preparation of drugs for treating inflammatory diseases and tumor diseases, wherein the inflammatory disease is selected from rheumatoid arthritis, dermatitis, psoriasis, inflammatory bowel disease, and the tumor disease is selected from myelofibrosis, polycythemia vera and essential thrombocythemia, acute myeloid leukemia, acute lymphocytic leukemia, breast ductal carcinoma and non-small cell lung cancer, and the inflammatory bowel disease is a chronic intestinal inflammatory disease.

10. The use according to claim 9, characterized in that The chronic intestinal inflammatory disease is selected from ulcerative colitis and Crohn's disease.

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