Small molecule inhibitor targeting Epstein-Barr virus nuclear antigen protein, preparation method and application thereof

Abstract

The present invention provides a small molecule inhibitor targeting Epstein-Barr virus nuclear antigen protein, and / or a pharmaceutical composition comprising the same, which can be used to treat diseases caused by EBNA1 activity, such as, but not limited to, cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and / or rheumatoid arthritis. The present invention further provides a small molecule inhibitor targeting Epstein-Barr virus nuclear antigen protein, and / or a pharmaceutical composition comprising the same, which can be used to treat diseases caused by EBV infection in the lytic phase and / or latent phase.

Description

Technical Field

[0001] The present invention provides a small molecule inhibitor targeting Epstein-Barr virus nuclear antigen protein, a preparation method thereof, and an application thereof for treating and / or preventing diseases caused by EBNA1 activity. Background Art

[0002] Epstein-Barr virus (EBV) is a human herpesvirus (HHV-4) belonging to the gammaherpesvirinae subfamily. EBV is a B-lymphotropic virus that commonly infects humans. EBV initially infects oropharyngeal squamous epithelial cells and subsequently remains latent in B lymphocytes. Once activated, latent EBV can become a cause of many diseases, including tumors. Consequently, EBV was classified as a Group 1 human oncogenic virus by the International Association of Cancer Research (IARC) in 1997.

[0003] EBV invades the human body through epithelial cells and dormant immature B cells. The main gene products expressed by EBV-infected B lymphocytes include: EBV nuclear antigen family (EBNA1, EBNA2, EBNA3a, EBNA3b, EBNA3c and LP), latent membrane proteins (LMP-1, LMP-2A and LMP-2B) and EBV-encoded RNA (EBER-1, EBER-2). EBV has two forms of infection in B cells: (1) Proliferative infection: After EBV infects B cells, early gene products such as EA (early antigen) are synthesized first, followed by DNA replication, VCA (capsular protein) and MA (membrane antigen) synthesis, and finally the formation of complete virus particles and release, while the cell lyses and dies. (2) Non-proliferative infection: After EBV infects B cells, most viral genes are in a latent state, and the cell only synthesizes EBNA and LMP. EBV can be divided into four types based on its expression in different tumors: Type I latency leads to Burkitt lymphoma and gastric cancer; Type II latency causes Hodgkin lymphoma, nasopharyngeal carcinoma, and T / NK cell lymphoma; Type III causes infectious mononucleosis; and Type IV refers to healthy carriers. In all three types of pathogenic latency, the EBV nuclear antigen EBNA1 is a key protein that the virus must express.

[0004] Research has found that, in addition to causing Burkitt lymphoma, EBV is also implicated in Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, NK / T lymphocytic neoplasms, leiomyosarcoma, and malignant epithelial tumors of the stomach, breast, and lung. Studies have shown that EBNA1, a protein expressed by EBV, is involved in important pathological processes, including viral DNA replication, maintenance of viral latency, tumorigenesis through mutation, tumor cell migration, and immune escape. EBNA1 (viral nuclear antigen 1) has been detected in all of these tumor cells infected with EBV. Therefore, the development of EBNA1-based early screening for EBV infection and prevention of tumor development and progression has received significant attention in both academic and clinical research, and is particularly important for the early clinical diagnosis of nasopharyngeal carcinoma.

[0005] In recent years, research targeting EBNA1 to develop targeted chemotherapeutic agents for specific tumors has made significant progress. This has laid the foundation for target evaluation, structure-based drug design, and small molecule activity evaluation of the EBNA1 protein. For example, Messick TE et al. filed two international patents, WO2016183534A1 and WO2015073864A1, in 2015 and 2016, respectively, disclosing compounds with two aromatic rings linked by an alkyne conjugation. These compounds are designed to inhibit EBNA1 binding to DNA, blocking the replication of EBV-infected cells and exerting anti-tumor effects. In 2019, the group reported detailed research findings, demonstrating that their VK series of molecules exhibited robust EBNA1 inhibitory activity, demonstrating promising results in both cellular and mouse models of nasopharyngeal carcinoma. These molecules are currently in Phase I clinical trials [Sci. Transl. Med. 2019, 11, eaau5612]. This discovery demonstrates that the EBNA1 protein could serve as a novel drug target for the development of therapeutics for diseases associated with EBV infection, including tumors.

[0006] This invention aims to utilize a structure-based drug design approach to optimize the molecular structure by modifying the bridging functional groups of the two main segments of the molecule, targeting the complexation site where the EBNA1 protein interacts with DNA. The pharmaceutical small molecule compound of this invention exhibits low-level EBNA1 inhibitory activity, selectively inhibits the proliferation of EBV-positive tumor cell chains at the cellular level, and exhibits excellent ADMET activity, resulting in improved drugability. Summary of the Invention

[0007] The present invention provides compounds of the general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof as EBNA1 inhibitors:

[0008]

[0009] The present invention further provides a pharmaceutical composition comprising at least one compound of the present invention, or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof. The present invention further provides a pharmaceutical composition comprising at least one compound of the present invention, or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof and at least one pharmaceutically acceptable carrier, excipient or diluent. The present invention further provides a method for treating and / or preventing a disease or disorder caused by EBNA1 activity. The present invention further provides a method for preparing a drug for treating and / or preventing a disease or disorder caused by EBNA1 activity. The present invention further provides a method for treating and / or preventing a disease or disorder infected by Epstein-Barr virus (EBV) and / or associated with EBV infection. The present invention further provides a method for preparing a drug for treating and / or preventing a disease or disorder infected by Epstein-Barr virus (EBV) and / or associated with EBV infection. The present invention further provides a method for treating and / or preventing a disease infected by Epstein-Barr virus (EBV) and / or associated with EBV infection. The present invention further provides a method for treating and / or preventing an EBV infection in the lytic phase and / or latent phase. The present invention further provides a use of the compound for preparing a drug for treating and / or preventing diseases caused by EBV infection in the lytic and / or latent phases. The present invention further provides a method for preparing the compound of formula (I).

[0010] The present invention relates to compounds of general formula (I) or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof:

[0011]

[0012] in:

[0013] X 1 、X 2 、X 3 are identical or different and are independently selected from CR xa or nitrogen atoms;

[0014] R xa is selected from hydrogen and halogen; the halogen is selected from fluorine, chlorine, bromine and iodine;

[0015] R 1 Selected from -COOH, -C(=O)-OR 1a , -C(=O)-NH2, -C(=O)-NHR 1b 、-C(=O)-NR 1b R 1c 、-C(=O)-NH-S(=O)2-R 1b 、-C(=O)-NH-(CH2) q -R 1d 、 -S(=O)2OH, -B(OH)2, -S(=O)2-NH2, -S(=O)2-NHR 1b 、-S(=O)2-NR 1b R 1c ,

[0016] q is 0, 1, 2, or 3;

[0017] Among them, R 1a Independently selected from: Li;

[0018] or R 1a 、R 1b 、R 1c are the same or different and are independently selected from the group consisting of: hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl;

[0019] Preferably, R 1a 、R 1b 、R 1c are the same or different and are independently selected from: hydrogen, optionally substituted C1-C3 straight-chain alkyl, optionally substituted C1-C3 branched-chain alkyl, optionally substituted C1-C3 cycloalkyl;

[0020] More preferably R 1a 、R 1b 、R 1c are identical or different and independently selected from: hydrogen, methyl;

[0021] or R 1a 、R 1b 、R 1c are identical or different and are independently selected from: aryl, heterocyclyl, heteroaryl;

[0022] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0023] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0024] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0025] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0026] Preferably, the aryl group is selected from: phenyl;

[0027] The heteroaryl group is selected from: thienyl, furyl, imidazolyl;

[0028] More preferably, R 1a 、R 1b 、R 1c are identical or different and independently selected from: phenyl, thienyl, furyl;

[0029] or, R 1b With R 1c Together with the atoms to which they are attached, they form a cyclic group; the cyclic group is selected from: optionally substituted morpholinyl, optionally substituted pyrrolidinyl, optionally substituted piperazinyl;

[0030] R 1d Selected from: hydrogen, hydroxy, amino, cyano, -OC(=O)-R 17 、-OR 12 、-NR 9 R 10 , optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl;

[0031] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0032] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0033] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0034] Preferably, R 1d Selected from: hydrogen, hydroxy, amino, -OR 12 、-NR 9 R 10 , optionally substituted phenyl, optionally substituted thienyl, optionally substituted furanyl, optionally substituted imidazolyl;

[0035] More preferably, R 1dSelected from: hydrogen, hydroxy, methyl ether, amino, dimethylamino, piperazinyl, phenyl, thienyl, furyl;

[0036] R 2 Selected from the following groups:

[0037] hydrogen, amino, halogen, nitro, optionally substituted C1-C4 alkyl,

[0038] The dots Indicates the R 2 The point of attachment of the group to other groups of the compound molecule of general formula (I);

[0039] X 4 Selected from O, S, NR 2d ;

[0040] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0041] Hydrogen, halogen, amino, nitro, hydroxy, C1-C8 hydroxyalkyl, cyano, -(CH2) q -COOH, -(CH2) q -C(=O)-OR 8 、-(CH2) q -C(=O)-NH-R 8 、-N(H)C(=O)-R 8 、-N(H)S(=O)2-R 8 、-OR 8 、-NH-R 8 、-S(=O)2NH-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

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

[0043] or, R 2a Selected from aryl, heterocyclyl, heteroaryl:

[0044] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0045] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0046] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0047] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0048] Or, adjacent R 2a Together with the atoms to which they are attached, they form a ring structure, or adjacent R 2b The atoms to which they are connected form a ring structure, wherein the ring structure is selected from: phenyl, heteroaryl, and the heteroaryl is selected from: thienyl, furyl, pyrrolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the phenyl and heteroaryl are optionally substituted with R 4 one or more identical or different replacements;

[0049] R 2d Selected from hydrogen, optionally halogenated or non-halogenated C1-C3 straight-chain alkyl, isopropyl, cyclopropyl; preferably, the halogenated is selected from fluoro;

[0050] or, R 2d Selected from: -C(=O)-R 5 、-S(=O)2-R 5 ;

[0051] or, R 2d is selected from aryl, heterocyclyl, and heteroaryl;

[0052] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0053] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0054] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0055] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0056] L is selected from the following groups:

[0057]

[0058]

[0059] The dots represents the connection point where L is connected to the right fragment of the compound of general formula (I);

[0060] The asterisk * indicates L and R 3 connected junctions;

[0061] X 5 Selected from: O, NH, S;

[0062] Y 1 Selected from: O, NR L2 ;

[0063] The L is substituted by R L1 One or more substitutions are made at the same or different sites;

[0064] R L1 Selected from: hydrogen or fluorine atoms;

[0065] R L2 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl;

[0066] or, R L2 Selected from: -(CH2) q -R 7 、-C(=O)-N(H)-R 19、-C(=S)-N(H)-R 19 、-C(=O)-R 20 、-S(=O)2-R 20 ;

[0067] or, R L2 Selected from: aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0068] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0069] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0070] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0071] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0072] or R L2 and R 3 Together with the atoms to which they are attached, they are cyclized to form a 5-10 membered nitrogen and / or sulfur heterocyclic group, wherein the 5-10 membered nitrogen and / or sulfur heterocyclic group comprises a -C(=O)-, -S(=O)2- group;

[0073] R L3 、R L4 are identical or different and independently selected from: hydrogen or fluorine atoms;

[0074] or R L3 and R L4 Together with the atoms to which they are attached, they form carbonyl and thiocarbonyl groups;

[0075] or R L3 and R L4 Together with the atoms to which they are attached, they form a nitrogen and / or sulfur-containing heterocyclic group, wherein R L3 and R L4 The attached C atom is replaced by -S(=O)2-;

[0076] m, n are the same or different and are independently selected from: 1, 2 or 3 to form a ring system with different number of atoms;

[0077] q is 0, 1, 2, or 3;

[0078] R 3 Selected from the following groups:

[0079] C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl; the C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl are optionally substituted by R 6 one or more identical or different replacements;

[0080] or, R 3 Selected from the following groups:

[0081]

[0082]

[0083]

[0084] The dots represents the connection point to the right fragment of the compound of general formula (I);

[0085] X 6 Selected from O, S, NR 3g ;

[0086] X 7 Selected from O, S, NR 3g 、CHR 3a ;

[0087] Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced;

[0088] Z 1 Selected from O, S, NR 3h ;

[0089] where R 3aSelected from: hydrogen, halogen, nitro, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, hydroxyl, C1-C8 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2)q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C8 hydroxyalkyl group is a C1-C8 alkyl group substituted with a hydroxy group;

[0090] p and q are each independently 0, 1, 2 or 3;

[0091] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0092] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0093] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0094] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0095] or adjacent R 3a Together with the atoms to which they are attached, they form a ring structure, or R 3a and its adjacent R 3c and together with the atoms to which they are attached, form a ring structure, or R 3a and its adjacent R 3d and forming a ring structure together with the atoms to which they are attached, said ring structure including a saturated or aromatic ring structure selected from the group consisting of: cycloalkyl, aryl, heterocyclyl, heteroaryl;

[0096] Preferably, the cyclic structure is selected from: phenyl, pyridyl, pyrrolyl, thienyl, furyl, oxazolyl, thiazolyl, isoxazolyl, indazolyl, 5-7 membered nitrogen / oxygen saturated heterocyclic group, and the saturated heterocyclic group is selected from: tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0097] The cyclic structure is optionally substituted with a group R 18 one or more identical or different replacements;

[0098] R 3b Selected from:

[0099] hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, -C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 、-S(=O)2-R 20 ;

[0100] q is 0, 1, 2, or 3;

[0101] or, R 3b Selected from: aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0102] The aryl group is selected from the group consisting of: optionally substituted phenyl, naphthyl, anthracenyl;

[0103] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0104] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0105] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0106] R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0107] When L is selected from When R 3c and R 3dare the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 20 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0108] The aryl group is selected from the group consisting of: optionally substituted phenyl, naphthyl, anthracenyl;

[0109] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0110] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0111] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0112] or R 3c and R 3d and together with the atoms to which they are attached, form carbonyl, thiocarbonyl, and imine groups;

[0113] R 3e and R 3f are identical or different and are independently selected from:

[0114] hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, -C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 、-S(=O)2-R 20 ;

[0115] or, R 3e and R 3f and together with the atoms to which they are attached, form carbonyl and thiocarbonyl groups;

[0116] or, R3e and R 3f are identical or different and are independently selected from: aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0117] The aryl group is selected from the group consisting of: optionally substituted phenyl, naphthyl, anthracenyl;

[0118] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0119] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0120] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0121] R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl;

[0122] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0123] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0124] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0125] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18one or more identical or different replacements;

[0126] R 3h Selected from: hydrogen, nitro, cyano;

[0127] The R 4 Selected from: hydrogen, fluorine, chlorine, hydroxy, C1-C3 hydroxyalkyl, optionally substituted C1-C3 alkyl, optionally substituted halo C1-C3 alkyl, optionally substituted C1-C3 alkoxy, optionally substituted halo C1-C3 alkoxy, nitro, cyano, amino, acetyl, methylsulfonyl, acetamido, methylsulfonamido;

[0128] The R 5 Selected from: hydrogen, optionally substituted C1-C3 alkyl, optionally substituted halogenated C1-C3 alkyl;

[0129] The R 6 Selected from: hydroxyl, C1-C8 straight chain alkoxy, C3-C8 branched chain alkoxy, C3-C8 cycloalkoxy, -OC(=O)-R 20 , amino, -NH-C(=O)-R 20 、-NH-S(=O)2-R 20 、-NH-C(=O)-OR 20 、-NH-C(=O)-NH-R 20 、-NH-C(=S)-NH-R 20 ;

[0130] The R 7 Selected from: phenyl, naphthyl, heterocyclic group, heteroaryl, the heterocyclic group is selected from: 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the heteroaryl is selected from: thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl, the phenyl, naphthyl, heterocyclic group, heteroaryl are optionally substituted by R 18 one or more identical or different replacements;

[0131] The R 8 Selected from: optionally substituted C1-C3 alkyl, optionally substituted halogenated C1-C3 alkyl;

[0132] The R 9 、R 10are the same or different and are independently selected from: hydrogen, optionally substituted C1-C8 straight-chain alkyl or alkoxy, optionally substituted C3-C8 branched-chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy;

[0133] or, R 9 、R 10 are the same or different and are independently selected from: optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group;

[0134] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0135] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0136] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0137] Or the R 9 、R 10 and together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group, the nitrogen-containing heterocyclic group being selected from: azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, the nitrogen-containing heterocyclic group being substituted one or more times, identically or differently, with the following substituents: hydroxyl, C1-C8 hydroxyalkyl, C1-C8 straight-chain alkyl or alkoxy, C3-C8 branched-chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight-chain alkyl or alkoxy, halogenated C3-C8 branched-chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, amino, optionally substituted amide, optionally substituted sulfonamide;

[0138] The R 11 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy;

[0139] or, R 11Selected from: aryl, heterocyclic, heteroaromatic;

[0140] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0141] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0142] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0143] The aryl, heterocyclic group, and aromatic heteroyl group are substituted one or more times, identically or differently, with the following substituents: halogen, hydroxyl, C1-C8 hydroxyalkyl, C1-C8 straight-chain alkyl or alkoxy, C3-C8 branched-chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight-chain alkyl or alkoxy, halogenated C3-C8 branched-chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, amino, optionally substituted amide, optionally substituted sulfonamide, cyano, nitro, sulfonic acid, optionally substituted urea, and guanidino;

[0144] The R 12 Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl, aryl, heterocyclic group, aromatic hetero group; the C1-C8 alkyl group is substituted one or more times with the following substituents, the same or different: -OR 20 、-OH、-N(H)C(=O)-R 20 、-NR 9 R 10 ;

[0145] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0146] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0147] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0148] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0149] The R 13 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy;

[0150] Or, the R 13 Selected from: -(CH2) q -phenyl, -(CH2) q -halogenated phenyl, -(CH2) q -naphthyl, -(CH2) q -halonaphthyl, -(CH2) q -Anthracenyl, -(CH2) q -halogenated anthracenyl, -(CH2) q -heterocyclic group, -(CH2) q -halogenated heterocyclic group, -(CH2) q -heteroaryl, -(CH2) q -halogenated heteroaryl;

[0151] q is 0, 1, 2, or 3;

[0152] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0153] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0154] The phenyl, naphthyl, anthracenyl, heterocyclic group, heteroaryl group may be optionally substituted with R 18 one or more identical or different replacements;

[0155] The R 14 Selected from: heteroaryl, the heteroaryl is selected from: thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the heteroaryl is optionally substituted by R 18 one or more identical or different replacements;

[0156] The R 15 is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetane, tetrahydrofuran, tetrahydropyran, oxepane, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the saturated heterocyclic group is optionally substituted by R 18 one or more identical or different replacements;

[0157] The R 16 is selected from the group consisting of: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched or cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched or cycloalkyl, optionally substituted acyl, optionally substituted sulfonyl;

[0158] or, R 16 is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetane, tetrahydrofuran, tetrahydropyran, oxepane, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the saturated heterocyclic group is optionally substituted by R 18 one or more identical or different replacements;

[0159] or, R 16 Selected from: aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl group is selected from: phenyl, naphthyl, anthracenyl; the aromatic heteroaryl group is selected from: thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the aryl and heteroaryl groups are optionally substituted by R 18 one or more identical or different replacements;

[0160] q is 0, 1, 2, or 3;

[0161] The R 17Selected from: optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group;

[0162] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0163] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0164] The heteroaryl group is selected from the group consisting of thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; the R 18 Selected from: hydrogen, halogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C8 hydroxyalkyl, aryloxy, heterocyclyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl, aryl, heterocyclic group, heteroaromatic group;

[0165] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0166] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0167] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0168] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0169] The R 19 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl, heterocyclyl, heteroaryl;

[0170] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0171] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0172] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0173] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0174] The R 20 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl, heterocyclyl, heteroaryl;

[0175] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0176] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0177] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0178] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0179] wherein p and q are independently 0, 1, 2 or 3;

[0180] m, n are the same or different and are independently selected from: 1, 2 or 3 to form ring systems with different numbers of atoms.

[0181] The present invention further relates to a pharmaceutical composition comprising a compound of the above general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof.

[0182] The present invention further relates to a pharmaceutical composition comprising a compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives, and a pharmaceutically acceptable carrier, excipient or diluent.

[0183] The present invention further relates to a method for treating and / or preventing diseases or disorders caused by EBNA1 activity, comprising administering to a subject an effective amount of a compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives or pharmaceutical compositions thereof.

[0184] The present invention further relates to the use of the compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives or pharmaceutical compositions thereof for the preparation of drugs for treating and / or preventing diseases caused by EBNA1 activity.

[0185] The present invention further relates to a method for treating and / or preventing diseases or disorders caused by Epstein-Barr virus (EBV) infection and / or associated with EBV infection, which comprises administering to a subject an effective amount of a compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives or pharmaceutical compositions thereof.

[0186] The present invention further relates to the use of a compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotopically substituted derivatives, or pharmaceutical compositions thereof, for preparing a medicament for treating and / or preventing Epstein-Barr virus (EBV) infection and / or diseases associated with EBV infection. The present invention further relates to a method for treating and / or preventing EBV infection in the lytic and / or latent phase, the method comprising administering to a subject an effective amount of a compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotopically substituted derivatives, or pharmaceutical compositions thereof.

[0187] The present invention further relates to the use of the compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives or pharmaceutical compositions thereof for the preparation of drugs for treating and / or preventing diseases caused by EBV infection in the lytic and / or latent phases.

[0188] The compounds of the general formula (I) described herein, or their enantiomers, diastereomers, tautomers, salts, crystalline forms, solvates, and / or isotopically substituted derivatives, or pharmaceutical compositions thereof, as well as the aforementioned methods, can be used to treat and / or prevent the following diseases: diseases or disorders caused by EBNA1 activity. The present invention can further be used to treat and / or prevent EBV infection, and / or diseases or disorders associated with EBV infection, and diseases caused by EBV infection in the lytic and / or latent phases. The aforementioned diseases or disorders are selected from at least one of the following: cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. The cancers are particularly nasopharyngeal carcinoma, gastric cancer, non-Hodgkin's lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, hepatosplenic T-cell lymphoma, B-cell lymphoma, Burkitt's lymphoma, reticuloendothelioma, reticulocytosis, microglioma, diffuse large B-cell lymphoma, extranodal T / NK lymphoma / angiocentric lymphoma, follicular lymphoma, immunoblastic lymphadenoma, mucosal-associated lymphoma Tissue lymphoma, B-cell chronic lymphocytic leukemia, mantle cell lymphoma, mediastinal large B-cell lymphoma, lymphoplasmacytic lymphoma, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, lymphomatoid granuloma, angioimmunoblastic lymphadenopathy, leiomyosarcoma, X-linked lymphoproliferative disorder, post-transplant lymphoproliferative disorder, Hodgkin lymphoma and breast cancer, etc. Detailed Description of the Invention

[0189] In the detailed description of the present invention, many specific details are set forth for explanation purposes to enable those skilled in the art to understand the disclosed embodiments. However, it will be understood by those skilled in the art that the specific details of these embodiments do not constitute a limitation on the scope of the present invention. In addition, it will be readily understood by those skilled in the art that the specific order of the description and implementation of the present invention is merely illustrative and that the order may be changed while remaining within the spirit and scope of the embodiments disclosed herein.

[0190] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. When the definition of a term in an incorporated reference differs from the definition provided in the present specification, the definition provided in the present specification shall prevail.

[0191] Throughout the specification, the following terms take the meanings explicitly associated herein, unless the context clearly indicates otherwise.

[0192] As used herein, the phrase "in one embodiment" does not necessarily refer to the same embodiment, although it may. Additionally, as used herein, the phrase "in another embodiment" does not necessarily refer to a different embodiment, although it may. Thus, the various embodiments of the present invention may be readily combined without departing from the scope or spirit of the invention.

[0193] As used herein, the term "EBNA1 inhibitor" refers to a compound that inhibits EBNA1.

[0194] As used herein, the term "EBV" refers to Epstein-Barr virus.

[0195] As used herein, an "effective amount," "therapeutically effective amount," or "pharmaceutically effective amount" of a compound is an amount of the compound sufficient to provide a beneficial effect to the subject to which the compound is administered.

[0196] As used herein, the term "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, stabilizer, dispersant, suspending agent, diluent, excipient, thickener, solvent or encapsulating material, which is involved in carrying or delivering a compound useful for the present invention within a subject or to a subject so that it can perform its intended function.

[0197] As used herein, the term "alkyl" refers to a straight chain, branched chain, or cycloalkyl group having a specified number of carbon atoms (i.e., C1-8 refers to 1 to 8 carbon atoms). Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. Alkyl groups may be optionally substituted. Non-limiting examples of substituted alkyl groups include hydroxymethyl, chloromethyl, trifluoromethyl, aminomethyl, 1-chloroethyl, 2-hydroxyethyl, 1,2-difluoroethyl, 3-carboxypropyl, and the like.

[0198] As used herein, the term "alkoxy" refers to a group -O-alkyl, wherein the alkyl group is as defined above. The alkoxy group may be optionally substituted. The term C3-C8 cycloalkoxy refers to a ring comprising 3 to 8 carbon atoms and at least one oxygen atom (e.g., tetrahydrofuran, tetrahydro-2H-pyran). The C3-C8 cycloalkoxy group may be optionally substituted.

[0199] As used herein, the term "haloalkyl" refers to a straight and branched saturated aliphatic hydrocarbon group having a specified number of carbon atoms substituted with one or more halogens. Halogenated alkyl groups include perhalogenated alkyl groups in which all hydrogens of the alkyl group have been replaced with halogens (e.g., -CF3, CF2CF3). Halogenated alkyl groups may optionally be substituted with one or more substituents other than halogen. Examples of haloalkyl groups include, but are not limited to, fluoromethyl, dichloroethyl, trifluoromethyl, trichloromethyl, pentafluoroethyl, and pentachloroethyl groups.

[0200] As used herein, the term "halogen" refers to chlorine, bromine, fluorine, and iodine.

[0201] As used herein, the term "heterocyclyl" refers to a cyclic group wherein at least one ring member is a heteroatom selected from N, O, and S. Preferably, the number of heteroatoms is 1, 2, 3, or 4. Examples include 5-10 membered oxygen-containing heterocyclyls, 5-10 membered sulfur-containing heterocyclyls, and 5-10 membered nitrogen-containing heterocyclyls. Examples include 4-7 membered saturated heterocyclyls containing oxygen, nitrogen, and / or sulfur. Specific examples of such saturated heterocyclyls include, but are not limited to, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl, and the like.

[0202] As used herein, the term "heteroaryl" refers to a cyclic group wherein at least one ring member is a heteroatom selected from N, O, and S. Preferably, the number of heteroatoms is 1, 2, 3, or 4. Examples include 5-10 membered oxygen-containing heteroaryl, 5-10 membered sulfur-containing heteroaryl, and 5-10 membered nitrogen-containing heteroaryl. Specific examples include, but are not limited to, thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl.

[0203] As used herein, the term "optionally substituted" refers to substitution with any substituent that may be substituted, or non-substitution.

[0204] At various places in this specification, substituents of compounds are disclosed in groups or ranges. Specifically, this specification includes every individual subcombination of the members of such groups and ranges. For example, the term "C1-C8 alkyl" is specifically intended to disclose individually C1, C2, C3, C4, C5, C6, C7, C8, C1-C8, C1-C7, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C8, C2-C7, C2-C6, C2-C5, C2-C4, C2-C3, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4, C4-C8, C4-C7, C4-C6, C4-C5, C5-C8, C5-C7, C5-C6 alkyl. The term "C1-C6 alkyl" is specifically intended to disclose individually C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6 alkyl. The term "C1-C4 alkyl" is specifically intended to disclose individually C1, C2, C3, C4, C1-C4, C1-C3, C1-C2, C2-C4, C2-C3, and C3-C4 alkyl.

[0205] At various places in this specification, the term "aryl" refers to phenyl, naphthyl, anthracenyl; the term "heterocyclyl" refers to a 4-7 membered saturated heterocyclyl containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclyl is selected from the group consisting of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, and piperazinyl; the term "heteroaryl" refers to thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothiophenyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl.

[0206] The present invention relates to compounds of general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof:

[0207]

[0208] in:

[0209] X 1 、X 2 、X 3 are identical or different and are independently selected from CR xa or nitrogen atoms;

[0210] R xa is selected from hydrogen and halogen; the halogen is selected from fluorine, chlorine, bromine and iodine;

[0211] R 1 Selected from -COOH, -C(=O)-OR 1a , -C(=O)-NH2, -C(=O)-NHR 1b 、-C(=O)-NR 1b R 1c 、-C(=O)-NH-S(=O)2-R 1b 、-C(=O)-NH-(CH2) q -R 1d 、 -S(=O)2OH, -B(OH)2, -S(=O)2-NH2, -S(=O)2-NHR 1b 、-S(=O)2-NR 1b R 1c ,

[0212] q is 0, 1, 2, or 3;

[0213] Among them, R 1a Independently selected from: Li;

[0214] or R 1a 、R 1b 、R 1c are the same or different and are independently selected from the group consisting of: hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl;

[0215] Preferably, R 1a 、R 1b 、R 1care the same or different and are independently selected from: hydrogen, optionally substituted C1-C3 straight-chain alkyl, optionally substituted C3 branched-chain alkyl, optionally substituted C3 cycloalkyl;

[0216] More preferably, R 1a 、R 1b 、R 1c are identical or different and independently selected from: hydrogen, methyl;

[0217] or R 1a 、R 1b 、R 1c are identical or different and are independently selected from: aryl, heterocyclyl, heteroaryl;

[0218] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0219] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0220] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0221] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0222] Preferably, the aryl group is selected from: phenyl;

[0223] The heteroaryl group is selected from: thienyl, furyl, imidazolyl;

[0224] More preferably, R 1a 、R 1b 、R 1c are identical or different and independently selected from: phenyl, thienyl, furyl;

[0225] or, R 1b With R 1c Together with the atoms to which they are attached, they form a cyclic group; the cyclic group is selected from: optionally substituted morpholinyl, optionally substituted pyrrolidinyl, optionally substituted piperazinyl;

[0226] R 1d Selected from: hydrogen, hydroxy, amino, cyano, -OC(=O)-R 17 、-OR 12、-NR 9 R 10 , optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl;

[0227] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0228] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0229] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0230] Preferably, R 1d Selected from: hydrogen, hydroxy, amino, -OR 12 、-NR 9 R 10 , optionally substituted phenyl, optionally substituted thienyl, optionally substituted furanyl, optionally substituted imidazolyl;

[0231] More preferably, R 1d Selected from: hydrogen, hydroxy, methyl ether, amino, dimethylamino, piperazinyl, phenyl, thienyl, furyl;

[0232] R 2 Selected from the following groups:

[0233] hydrogen, amino, halogen, nitro, optionally substituted C1-C4 alkyl,

[0234] The dots Indicates the R 2 The point of attachment of the group to other groups of the compound molecule of general formula (I);

[0235] X 4 Selected from O, S, NR 2d ;

[0236] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0237] Hydrogen, halogen, amino, nitro, hydroxy, C1-C8 hydroxyalkyl, cyano, -(CH2) q-COOH, -(CH2) q -C(=O)-OR 8 、-(CH2) q -C(=O)-NH-R 8 、-N(H)C(=O)-R 8 、-N(H)S(=O)2-R 8 、-OR 8 、-NH-R 8 、-S(=O)2NH-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0238] q is 0, 1, 2, or 3;

[0239] or, R 2a Selected from aryl, heterocyclyl, heteroaryl:

[0240] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0241] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0242] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0243] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0244] Or, adjacent R 2a Together with the atoms to which they are attached, they form a ring structure, or adjacent R 2bThe atoms to which they are connected form a ring structure, wherein the ring structure is selected from: phenyl, heteroaryl, and the heteroaryl is selected from: thienyl, furyl, pyrrolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the phenyl and heteroaryl are optionally substituted with R 4 one or more identical or different replacements;

[0245] R 2d Selected from hydrogen, optionally halogenated or non-halogenated C1-C3 straight-chain alkyl, isopropyl, cyclopropyl; preferably, the halogenated is selected from fluoro;

[0246] or, R 2d Selected from: -C(=O)-R 5 、-S(=O)2-R 5 ;

[0247] or, R 2d is selected from aryl, heterocyclyl, and heteroaryl;

[0248] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0249] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0250] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0251] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0252] L is selected from the following groups:

[0253]

[0254] The dots represents the connection point where L is connected to the right fragment of the compound of general formula (I);

[0255] The asterisk * indicates L and R 3 connected junctions;

[0256] X 5Selected from: O, NH, S;

[0257] Y 1 Selected from: O, NR L2 ;

[0258] The L is substituted by R L1 One or more substitutions are made at the same or different sites;

[0259] R L1 Selected from: hydrogen or fluorine atoms;

[0260] R L2 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl;

[0261] or, R L2 Selected from: -(CH2) q -R 7 、-C(=O)-N(H)-R 19 、-C(=S)-N(H)-R 19 、-C(=O)-R 20 、-S(=O)2-R 20 ;

[0262] or, R L2 Selected from: aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0263] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0264] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0265] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0266] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0267] or R L2 and R 3 Together with the atoms to which they are attached, they are cyclized to form a 5-10 membered nitrogen and / or sulfur heterocyclic group, wherein the 5-10 membered nitrogen and / or sulfur heterocyclic group comprises a -C(=O)-, -S(=O)2- group;

[0268] R L3 、R L4 are identical or different and independently selected from: hydrogen or fluorine atoms;

[0269] or R L3 and R L4 Together with the atoms to which they are attached, they form carbonyl and thiocarbonyl groups;

[0270] or R L3 and R L4 Together with the atoms to which they are attached, they form a nitrogen and / or sulfur-containing heterocyclic group, wherein R L3 and R L4 The attached C atom is replaced by -S(=O)2-;

[0271] m, n are the same or different and are independently selected from: 1, 2 or 3 to form a ring system with different number of atoms;

[0272] q is 0, 1, 2, or 3;

[0273] R 3 Selected from the following groups:

[0274] C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl; the C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl are optionally substituted by R 6 one or more identical or different replacements;

[0275] or, R 3 Selected from the following groups:

[0276]

[0277]

[0278] The dots represents the connection point to the right fragment of the compound of general formula (I);

[0279] X 6 Selected from O, S, NR 3g ;

[0280] X7 Selected from O, S, NR 3g 、CHR 3a ;

[0281] Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced;

[0282] Z 1 Selected from O, S, NR 3h ;

[0283] where R 3a Selected from: hydrogen, halogen, nitro, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, hydroxyl, C1-C8 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C8 hydroxyalkyl group is a C1-C8 alkyl group substituted with a hydroxy group;

[0284] p and q are each independently 0, 1, 2 or 3;

[0285] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0286] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0287] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0288] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0289] or adjacent R 3a Together with the atoms to which they are attached, they form a ring structure, or R 3a and its adjacent R 3c and together with the atoms to which they are attached, form a ring structure, or R 3a and its adjacent R 3d and forming a ring structure together with the atoms to which they are attached, said ring structure including a saturated or aromatic ring structure selected from the group consisting of: cycloalkyl, aryl, heterocyclyl, heteroaryl;

[0290] Preferably, the cyclic structure is selected from: phenyl, pyridyl, pyrrolyl, thienyl, furyl, oxazolyl, thiazolyl, isoxazolyl, indazolyl, 5-7 membered nitrogen / oxygen saturated heterocyclic group, and the saturated heterocyclic group is selected from: tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0291] The cyclic structure is optionally substituted with a group R 18 one or more identical or different replacements;

[0292] R 3b Selected from:

[0293] hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, -C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 、-S(=O)2-R 20 ;

[0294] q is 0, 1, 2, or 3;

[0295] or, R 3b Selected from: aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0296] The aryl group is selected from the group consisting of: optionally substituted phenyl, naphthyl, anthracenyl;

[0297] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0298] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0299] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0300] R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0301] When L is selected from When R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 20 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0302] The aryl group is selected from the group consisting of: optionally substituted phenyl, naphthyl, anthracenyl;

[0303] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0304] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0305] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0306] or R 3c and R 3d and together with the atoms to which they are attached, form carbonyl, thiocarbonyl, and imine groups;

[0307] R 3e and R 3f are identical or different and are independently selected from:

[0308] hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, -C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 、-S(=O)2-R 20 ;

[0309] or, R 3e and R 3f and together with the atoms to which they are attached, form carbonyl and thiocarbonyl groups;

[0310] or, R 3e and R 3f are identical or different and are independently selected from: aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0311] The aryl group is selected from the group consisting of: optionally substituted phenyl, naphthyl, anthracenyl;

[0312] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0313] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0314] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0315] R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl;

[0316] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0317] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0318] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0319] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0320] R 3h Selected from: hydrogen, nitro, cyano;

[0321] The R 4 Selected from: hydrogen, fluorine, chlorine, hydroxy, C1-C3 hydroxyalkyl, optionally substituted C1-C3 alkyl, optionally substituted halo C1-C3 alkyl, optionally substituted C1-C3 alkoxy, optionally substituted halo C1-C3 alkoxy, nitro, cyano, amino, acetyl, methylsulfonyl, acetamido, methylsulfonamido;

[0322] The R 5 Selected from: hydrogen, optionally substituted C1-C3 alkyl, optionally substituted halogenated C1-C3 alkyl;

[0323] The R 6 Selected from: hydroxyl, C1-C8 straight chain alkoxy, C3-C8 branched chain alkoxy, C3-C8 cycloalkoxy, -OC(=O)-R 20 , amino, -NH-C(=O)-R 20 、-NH-S(=O)2-R 20 、-NH-C(=O)-OR 20 、-NH-C(=O)-NH-R 20 、-NH-C(=S)-NH-R 20 ;

[0324] The R 7Selected from: phenyl, naphthyl, heterocyclic group, heteroaryl, the heterocyclic group is selected from: 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the heteroaryl is selected from: thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl, the phenyl, naphthyl, heterocyclic group, heteroaryl are optionally substituted by R 18 one or more identical or different replacements;

[0325] The R 8 Selected from: optionally substituted C1-C3 alkyl, optionally substituted halogenated C1-C3 alkyl;

[0326] The R 9 、R 10 are the same or different and are independently selected from: hydrogen, optionally substituted C1-C8 straight-chain alkyl or alkoxy, optionally substituted C3-C8 branched-chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy;

[0327] or, R 9 、R 10 are the same or different and are independently selected from: optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group;

[0328] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0329] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0330] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0331] Or the R 9 、R 10and together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group, the nitrogen-containing heterocyclic group being selected from: azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, the nitrogen-containing heterocyclic group being substituted one or more times, identically or differently, with the following substituents: hydroxyl, C1-C8 hydroxyalkyl, C1-C8 straight-chain alkyl or alkoxy, C3-C8 branched-chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight-chain alkyl or alkoxy, halogenated C3-C8 branched-chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, amino, optionally substituted amide, optionally substituted sulfonamide;

[0332] The R 11 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy;

[0333] or, R 11 Selected from: aryl, heterocyclic, heteroaromatic;

[0334] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0335] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0336] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0337] The aryl, heterocyclic group, and aromatic heteroyl group are substituted one or more times, identically or differently, with the following substituents: halogen, hydroxyl, C1-C8 hydroxyalkyl, C1-C8 straight-chain alkyl or alkoxy, C3-C8 branched-chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight-chain alkyl or alkoxy, halogenated C3-C8 branched-chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, amino, optionally substituted amide, optionally substituted sulfonamide, cyano, nitro, sulfonic acid, optionally substituted urea, and guanidino;

[0338] The R 12Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl, aryl, heterocyclic group, aromatic hetero group; the C1-C8 alkyl group is substituted one or more times with the following substituents, the same or different: -OR 20 、-OH、-N(H)C(=O)-R 20 、-NR 9 R 10 ;

[0339] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0340] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0341] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0342] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0343] The R 13 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy;

[0344] Or, the R 13 Selected from: -(CH2) q -phenyl, -(CH2) q -halogenated phenyl, -(CH2) q -naphthyl, -(CH2) q -halonaphthyl, -(CH2) q -Anthracenyl, -(CH2) q -halogenated anthracenyl, -(CH2) q -heterocyclic group, -(CH2) q -halogenated heterocyclic group, -(CH2) q -heteroaryl, -(CH2) q -halogenated heteroaryl;

[0345] q is 0, 1, 2, or 3;

[0346] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0347] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0348] The phenyl, naphthyl, anthracenyl, heterocyclic group, heteroaryl group may be optionally substituted with R 18 one or more identical or different replacements;

[0349] The R 14 Selected from: heteroaryl, the heteroaryl is selected from: thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the heteroaryl is optionally substituted by R 18 one or more identical or different replacements;

[0350] The R 15 is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetane, tetrahydrofuran, tetrahydropyran, oxepane, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the saturated heterocyclic group is optionally substituted by R 18 one or more identical or different replacements;

[0351] The R 16 is selected from the group consisting of: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched or cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched or cycloalkyl, optionally substituted acyl, optionally substituted sulfonyl;

[0352] or, R 16 is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetane, tetrahydrofuran, tetrahydropyran, oxepane, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the saturated heterocyclic group is optionally substituted by R18 one or more identical or different replacements;

[0353] or, R 16 Selected from: aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl group is selected from: phenyl, naphthyl, anthracenyl; the aromatic heteroaryl group is selected from: thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the aryl and heteroaryl groups are optionally substituted by R 18 one or more identical or different replacements;

[0354] q is 0, 1, 2, or 3;

[0355] The R 17 Selected from: optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group;

[0356] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0357] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0358] The heteroaryl group is selected from the group consisting of thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; the R 18 Selected from: hydrogen, halogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C8 hydroxyalkyl, aryloxy, heterocyclyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20, optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl, aryl, heterocyclic group, heteroaromatic group;

[0359] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0360] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0361] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0362] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0363] The R 19 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl, heterocyclyl, heteroaryl;

[0364] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0365] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0366] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0367] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0368] The R 20Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl, heterocyclyl, heteroaryl;

[0369] The aryl group is selected from the group consisting of phenyl, naphthyl, and anthracenyl;

[0370] The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl;

[0371] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl;

[0372] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0373] wherein p and q are independently 0, 1, 2 or 3;

[0374] m, n are the same or different and are independently selected from: 1, 2 or 3 to form ring systems with different numbers of atoms.

[0375] In a preferred embodiment, the present invention relates to a compound of the above-mentioned general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof, wherein: at least one compound is selected from the following formulae:

[0376] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0377] R 2 Selected from the following groups:

[0378] Hydrogen, amino, nitro,

[0379] The dots Indicates the R 2 The point of attachment of the group to the other fragments of the compound of formula (I);

[0380] X 4 Selected from O, S, NR 2d ;

[0381] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0382] Hydrogen, halogen, amino, nitro, hydroxy, C1-C8 hydroxyalkyl, cyano, -(CH2) q -COOH, -(CH2) q -C(=O)-OR 8 、-(CH2) q -C(=O)-NH-R 8 、-N(H)C(=O)-R 8 、-N(H)S(=O)2-R 8 、-OR 8 、-NH-R 8 、-S(=O)2NH-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 , optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0383] Preferably, wherein R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0384] Hydrogen, halogen, cyano, -(CH2) q -COOH, -N(H)S(=O)2-R 8 、-OR 8 , C1-C8 straight chain alkyl or alkoxy, C3-C8 branched chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight chain alkyl or alkoxy, halogenated C3-C8 branched chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0385] More preferably, R 2a、R 2b 、R 2c are identical or different and are independently selected from:

[0386] Hydrogen, halogen, cyano, -(CH2) q -COOH, -N(H)S(=O)2-R 8 、-OR 8 , C1-C6 straight chain alkyl or alkoxy, C3-C6 branched chain alkyl or alkoxy, C3-C6 cycloalkyl or alkoxy, halogenated C1-C6 straight chain alkyl or alkoxy, halogenated C3-C6 branched chain alkyl or alkoxy, halogenated C3-C6 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0387] More preferably, R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0388] Hydrogen, halogen, cyano, -(CH2) q -COOH, -N(H)S(=O)2-R 8 、-OR 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0389] q is 0, 1, 2, or 3;

[0390] R 2d Selected from: hydrogen, optionally fluorinated or non-fluorinated C1-C3 straight chain alkyl, isopropyl, cyclopropyl, -C(=O)-R 5 、-S(=O)2-R 5 ;

[0391] Preferably, R 2d Selected from: hydrogen, fluorinated or non-fluorinated methyl, fluorinated or non-fluorinated ethyl, fluorinated or non-fluorinated propyl, isopropyl, cyclopropane, acetyl, methylsulfonyl, benzoyl, benzenesulfonyl.

[0392] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0393] L is selected from the following groups:

[0394]

[0395] The dots represents the connection point where L is connected to the right fragment of the compound of general formula (I);

[0396] The asterisk * indicates L and R 3 connected junctions;

[0397] The L is substituted by R L1 One or more substitutions are made at the same or different sites;

[0398] R L1 Selected from: hydrogen or fluorine atoms;

[0399] R L2 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl;

[0400] Preferably, R L2 Selected from: hydrogen, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight chain alkyl, optionally substituted halogenated C3-C6 branched chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl;

[0401] More preferably, R L2 Selected from: hydrogen, optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched chain alkyl, optionally substituted C3-C4 cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched chain alkyl, optionally substituted halogenated C3-C4 cycloalkyl;

[0402] or, R L2 Selected from: -(CH2) q -R 7 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)-R 20 、-S(=O)2-R 20 ;

[0403] or R L2 and R 3 Together with the atoms to which they are attached, they are cyclized to form a 5-10 membered nitrogen and / or sulfur heterocyclic group, wherein the 5-10 membered nitrogen and / or sulfur heterocyclic group comprises a -C(=O)-, -S(=O)2- group;

[0404] q is 0, 1, 2, or 3;

[0405] The R 7 Selected from: phenyl, heterocyclic group, heteroaryl, the heterocyclic group is selected from: 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, the saturated heterocyclic group is selected from: oxetane, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl; the heteroaryl is selected from: thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl, the phenyl, heterocyclic group, heteroaryl are optionally substituted by R 18 one or more identical or different replacements;

[0406] Preferably, R 18 Selected from: hydrogen, F, Cl, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C8 hydroxyalkyl, phenyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl, aryl, heterocyclic group, heteroaromatic group; more preferably, the acyl group is an acyl group substituted by a C1-C4 alkyl group; the sulfonyl group is a sulfonyl group substituted by a C1-C4 alkyl group; further preferably, the acyl group is an acetyl group; the sulfonyl group is a methylsulfonyl group;

[0407] The aryl group is selected from: phenyl;

[0408] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0409] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0410] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0411] More preferably, the amino group is substituted with a C1-C4 alkyl group or a C1-C4 acyl group.

[0412] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0413] R 3 Selected from the following groups:

[0414]

[0415]

[0416] The dots represents the connection point to the right fragment of the compound of general formula (I);

[0417] X 6 Selected from O, S, NR 3g ;

[0418] X 7 Selected from O, S, NR 3g 、CHR 3a ;

[0419] Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced;

[0420] Z 1 Selected from O, S, NR 3h ;

[0421] where R 3a Selected from:

[0422] hydrogen, halogen, nitro, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2)q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0423] The aryl group is selected from: phenyl;

[0424] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0425] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0426] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0427] p and q are each independently 0, 1, 2 or 3;

[0428] Preferably, the R 11 Selected from: hydrogen, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy, optionally substituted halogenated C1-C6 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C6 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C6 cycloalkyl or alkoxy, aryl, heterocyclyl, heteroaryl;

[0429] The aryl group is selected from: phenyl;

[0430] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0431] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0432] Preferably, the R 17 is selected from the group consisting of: optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight chain alkyl, optionally substituted halogenated C3-C6 branched chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, phenyl, wherein the phenyl is optionally substituted with R 4 one or more identical or different replacements;

[0433] R 3b Selected from:

[0434] hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl, heteroaryl is optionally substituted by R 18 one or more identical or different replacements;

[0435] Preferably, the aryl group is selected from: phenyl;

[0436] The heteroaryl group is selected from: thienyl, pyridyl, pyrimidinyl, indolyl;

[0437] q is 0, 1, 2, or 3;

[0438] R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl;

[0439] When L is selected from When R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 20 Preferably, R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 8 ;

[0440] or R 3c and R 3d Together with the atoms to which they are attached, they form carbonyl, thiocarbonyl, and imino groups;

[0441] R 3e and R 3f are identical or different and are independently selected from:

[0442] Hydrogen, C1-C8 straight-chain alkyl, C3-C8 branched-chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight-chain alkyl, halogenated C3-C8 branched-chain alkyl, halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -;

[0443] The aryl and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0444] Preferably, the aryl group is selected from: phenyl;

[0445] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0446] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0447] or, R 3e and R 3f And together with the atoms to which they are attached, they form carbonyl and thiocarbonyl.

[0448] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or their enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives, wherein: R 1 Selected from -COOH, -C(=O)-OR 1a 、-C(=O)-NH-S(=O)2-R 1b 、-C(=O)-NH-(CH2) q -R 1d 、

[0449] Among them, R 1a Selected from: Li;

[0450] or R 1a 、R 1b 、R 1c are the same or different and are independently selected from: hydrogen, optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched or cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched or cycloalkyl;

[0451] More preferably, R 1a 、R 1b 、R 1c are the same or different and are independently selected from: methyl, ethyl, propyl;

[0452] R 1d Selected from hydroxyl, amino, cyano, -OR 12 、-NR 9 R 10 , aryl, heterocyclyl, heteroaryl;

[0453] Preferably, the aryl group is selected from: phenyl;

[0454] The heterocyclic group is selected from: azetidinyl, pyrrolidinyl;

[0455] The heteroaryl group is selected from: thienyl, furyl;

[0456] The R 9 、R 10The same or different and independently selected from: hydrogen, optionally substituted C1-C4 alkyl, optionally substituted halogenated C1-C4 alkyl, optionally substituted C1-C4 alkoxy, optionally substituted halogenated C1-C4 alkoxy;

[0457] or, R 9 、R 10 are the same or different and are independently selected from: optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group;

[0458] The aryl group is selected from: phenyl;

[0459] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0460] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0461] Or the R 9 、R 10 and together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group, wherein the nitrogen-containing heterocyclic group is selected from: azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl.

[0462] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or their enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives, wherein: R 2 is selected from hydrogen, amino, nitro, optionally substituted pyrrolyl, optionally substituted benzofuranyl, optionally substituted indolyl, optionally substituted benzothiophenyl, optionally substituted phenyl, optionally substituted benzothiadiazolyl, optionally substituted furanyl, optionally substituted pyrazolyl, optionally substituted indazolyl, optionally substituted benzothiazolyl, optionally substituted pyridinyl, optionally substituted imidazolyl, optionally substituted thienyl;

[0463] Preferably, the R 2 Optionally substituted one or more times with H, F, Cl, the same or different.

[0464] In a more preferred embodiment, the present invention relates to a compound of the above-mentioned general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof, wherein:

[0465] R 2Selected from hydrogen, amino, nitro, pyrrolyl, benzofuranyl, indolyl, benzo[b]thienyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C4 alkylphenyl, biphenyl, methylsulfonylaminophenyl, acetylphenyl, methylsulfonylphenyl, aminosulfonylphenyl, C1-C4 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl.

[0466] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0467] L is selected from:

[0468] R 2 Selected from: hydrogen, X 4 Selected from NR 2d ;

[0469] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0470] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0471] R 3 Selected from: where R 3a Selected from: hydrogen, halogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, -(CH2) q -OR 12 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2)q -; the aryl, heterocyclic, heteroaryl are optionally substituted with R 4 one or more identical or different replacements;

[0472] Preferably, R 3a Selected from: hydrogen, halogen, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight chain alkyl, optionally substituted halogenated C3-C6 branched chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, -(CH2) q -OR 12 ;

[0473] The R 12 Selected from: C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl; more preferably, selected from: methyl, ethyl, propyl, trifluoromethyl, trichloromethyl.

[0474] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0475] L is selected from:

[0476] R 2 Selected from: hydrogen,

[0477] X 4 Selected from NR 2d ;

[0478] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0479] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0480] R 3Selected from: in

[0481] R 3a Selected from: hydrogen, halogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, -(CH2) q -OR 12 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the phenyl, heterocyclic, heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0482] Preferably, R 3a Selected from: hydrogen, halogen, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight chain alkyl, optionally substituted halogenated C3-C6 branched chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, -(CH2) q -OR 12 ;

[0483] More preferably, R 3a Selected from: hydrogen, F, Cl, methyl, ethyl, propyl, trifluoromethyl, trichloromethyl, methoxy;

[0484] R 3c and R 3d are identical or different and are independently selected from: hydrogen, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 20 ;

[0485] R 3c and R 3d are identical or different and are independently selected from the group consisting of: hydrogen, hydroxy, C1-C4 hydroxyalkyl, -OC(=O)-R 20 ;

[0486] The R 12 Selected from: C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl; more preferably, selected from: methyl, ethyl, propyl, trifluoromethyl, trichloromethyl;

[0487] The R 20Selected from: C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl; more preferably, selected from: methyl, ethyl, propyl, trifluoromethyl, trichloromethyl.

[0488] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0489] L is selected from:

[0490] R 2 Selected from: hydrogen, X 4 Selected from NR 2d ;

[0491] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0492] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0493] R 3 Selected from: in

[0494] R 3a Selected from: hydrogen, halogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, -(CH2) q -OR 12 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the phenyl, heterocyclic, heteroaryl groups are optionally substituted with R 4one or more identical or different replacements;

[0495] Preferably, R 3a Selected from: hydrogen, halogen, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight chain alkyl, optionally substituted halogenated C3-C6 branched chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, -(CH2) q -OR 12 ;

[0496] More preferably, R 3a Selected from: hydrogen, F, Cl, methyl, ethyl, propyl, trifluoromethyl, trichloromethyl, methoxy;

[0497] R 3c and R 3d are identical or different and are independently selected from: hydrogen, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 20

[0498] R 3c and R 3d are identical or different and are independently selected from the group consisting of: hydrogen, hydroxy, C1-C4 hydroxyalkyl, -OC(=O)-R 20 ;

[0499] The R 12 Selected from: C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl; more preferably, selected from: methyl, ethyl, propyl, trifluoromethyl, trichloromethyl;

[0500] The R 20 Selected from: C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl; more preferably, selected from: methyl, ethyl, propyl, trifluoromethyl, trichloromethyl.

[0501] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0502] L is selected from:

[0503] R 2 Selected from: hydrogen, amino, nitro,

[0504] X 4 Selected from NR 2d ;

[0505] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0506] R 2 is selected from the group consisting of: hydrogen, amino, nitro, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times identically or differently by the following substituents, the substituents being selected from the group consisting of: fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy,

[0507] R 3 Selected from: in

[0508] R 3a Selected from: hydrogen, -(CH2) q -NR 9 R 10 , nitro, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, -(CH2) q -COOH, -C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NR 16 -S(=O)2-R 17 ;

[0509] Preferably, R 3a Selected from: hydrogen, -NH2, nitro, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, -(CH2) q -COOH, -C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NR 16 -S(=O)2-R 17 ;

[0510] The R 11is selected from: C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl; more preferably, R 11 Selected from: methyl, ethyl, propyl, trifluoromethyl;

[0511] The R 16 Selected from: hydrogen;

[0512] The R 17 is selected from the group consisting of: C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, C3-C4 cycloalkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl, halogenated C3-C4 cycloalkyl, and optionally substituted phenyl; more preferably, R 17 Selected from: methyl, ethyl, propyl, cyclopropyl, trifluoromethyl, trichloromethyl, methylphenyl;

[0513] The R 20 Selected from: C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl; more preferably, selected from: methyl, ethyl, propyl, trifluoromethyl, trichloromethyl.

[0514] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0515] L is selected from:

[0516] R 2 Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0517] X 4 Selected from O, S, NR 2d ;

[0518] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0519] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8, C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0520] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8 , C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0521] More preferably, R 2 Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0522] R 3 Selected from: in

[0523] R 3a Selected from:

[0524] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0525] The R 9 、R 10The same or different and independently selected from: hydrogen, optionally substituted C1-C4 alkyl, optionally substituted halogenated C1-C4 alkyl, optionally substituted C1-C4 alkoxy, optionally substituted halogenated C1-C4 alkoxy;

[0526] or, R 9 、R 10 are the same or different and are independently selected from: optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group;

[0527] The aryl group is selected from: phenyl;

[0528] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0529] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0530] Or the R 9 、R 10 and together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group selected from the group consisting of: azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl;

[0531] The R 11 Selected from: hydrogen, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy, optionally substituted halogenated C1-C6 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C6 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C6 cycloalkyl or alkoxy;

[0532] or, R 11 Selected from: aryl, heterocyclic, heteroaromatic;

[0533] The aryl group is selected from: phenyl;

[0534] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0535] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0536] The aryl, heterocyclic group, and aromatic heteroyl group are substituted one or more times, identically or differently, with the following substituents: halogen, hydroxyl, C1-C6 hydroxyalkyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl or alkoxy, amino, acetyl, acetamido, methylsulfonamido, methylbenzenesulfonamido, cyano, nitro, sulfonic acid, urea, and guanidino;

[0537] The R 12 Selected from: hydrogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl, heterocyclic group, aromatic hetero group; the C1-C6 alkyl is substituted one or more times with the following substituents, the same or different: -OR 20 、-OH、-N(H)C(=O)-R 20 、-NR 9 R 10 ;

[0538] The aryl group is selected from: phenyl;

[0539] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0540] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0541] The phenyl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0542] The R 13 is selected from the group consisting of: hydrogen, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy, optionally substituted halogenated C1-C6 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C6 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C6 cycloalkyl or alkoxy; or, said R 13 Selected from: -(CH2) q -phenyl, -(CH2) q -halogenated phenyl, -(CH2) q -heterocyclic group, -(CH2) q -halogenated heterocyclic group, -(CH2) q -heteroaryl, -(CH2) q -halogenated heteroaryl;

[0543] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0544] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0545] The phenyl, heterocyclic, and heteroaryl groups are optionally substituted one or more times with the following substituents: methyl, ethyl, Cl, F, and cyano;

[0546] The R 15 Selected from: 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic groups, wherein the saturated heterocyclic groups are selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0547] The R 17 Selected from: optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group;

[0548] The aryl group is selected from: phenyl;

[0549] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0550] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0551] More preferably, the R 17 Selected from: methyl, cyclopropane, phenyl, thienyl, indolyl; said phenyl, thienyl, indolyl is optionally substituted one or more times with the following substituents: methyl, ethyl, Cl, F, cyano;

[0552] The R 18Selected from: hydrogen, F, Cl, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy, optionally substituted halogenated C1-C6 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C6 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C6 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C6 hydroxyalkyl, phenyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl;

[0553] The R 20 Selected from: hydrogen, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, phenyl, morpholinyl; the phenyl group is substituted one or more times with the following substituents: methyl, ethyl, Cl, F, cyano;

[0554] More preferably, R 3aSelected from: hydrogen, fluorine, chlorine, amino, dimethylamino, nitro, cyano, methyl, isopropyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, -(CH2)q-COOH, phenylthio, acetyl, propionyl, isobutyryl, ethylcarbamoyl, (fluorophenyl)carbamoyl, phenylcarbamoyl, (chlorophenyl)carbamothioyl)oxy)methyl, (ethylcarbamothioyl)oxy)methyl, acetoxymethyl, (octanoyloxy)methyl, morpholinecarbonyl, acetylamino, acetylaminomethyl, thiophene-carboxamido, (cyclopentyl)carbamoyl propylureido)methyl, hexylureido, cyclohexylureido, (chlorophenyl)ureido, ((trifluoromethyl)phenyl)ureido, ((trifluoromethoxy)phenyl)ureido, (cyanophenyl)ureido, propylthioureido, (chlorophenyl)thioureido, ((trifluoromethyl)phenyl)thioureido, (methoxyphenyl)thioureido, (cyanophenyl)thioureido, cyclopropylsulfonyl, cyclopropylsulfonylmethyl, ((methylphenyl)sulfonylamino)methyl, N-(methylsulfonyl)methylsulfonylamino, (methylsulfonylamino)thiazolyl, morpholinylmethyl, ((chlorophenyl)thioureido, oxy)carbonyl)amino, (phenylamino)methyl, (benzylamino)methyl, methoxy, ethoxy, propoxy, butoxy, isopropoxy, ethoxymethyl, methoxyethoxy, trifluoromethoxy, acetamidoethoxy, phenoxy, fluorophenoxy, chlorophenoxy, (trifluoromethyl)phenoxy, cyanophenoxy, methoxyphenoxy, acetylphenoxy, (methylsulfonyl)phenoxy, phenoxymethyl, (fluorophenoxy)methyl, (chlorophenoxy)methyl, (trifluoromethyl)phenoxy)methyl, (tetrahydro-2H-pyranyl)oxy ), (tetrahydro-2H-pyranyl)oxy)methyl, (pyridinyloxy)methyl, ((fluoropyridinyl)oxy)methyl, (pyrimidinyloxy)methyl, (tetrahydrofuranyl)oxymethyl, (oxetanyloxy)methyl, (acetylpiperidinyl)oxymethyl), (hydroxyethoxy)methyl, (acetamidoethoxy)methyl), acetamidoethoxy, (methoxyethoxy)methyl, aminoethoxy, (methylamino)ethoxy, ((((tetrahydro-2H-pyran-4-yl)oxy)carbonyl)oxy)methyl, methoxyphenylureido;

[0555] p and q are each independently 0, 1, 2 or 3.

[0556] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0557] L is selected from:

[0558] R 2 Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0559] X 4 Selected from O, S, NR 2d ;

[0560] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0561] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0562] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8 , C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0563] More preferably, R 2Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0564] R 3 Selected from: where R 3a Selected from:

[0565] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0566] R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C6 alkyl;

[0567] or R 3c and R 3d and together with the atoms to which they are attached, form carbonyl, thiocarbonyl, and imine groups;

[0568] Preferably, R 3a Selected from: methoxy.

[0569] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0570] L is selected from:

[0571] R 2 Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0572] X 4 Selected from O, S, NR 2d ;

[0573] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0574] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R 8、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0575] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8 , C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0576] More preferably, R 2 Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0577] R 3 Selected from: in

[0578] X 6 Selected from O, S, NR 3g ,

[0579] Y 2 Selected from CH, CR 3a , N, and Y 2 A C atom at any position on the aromatic ring can be replaced,

[0580] R 3a Selected from:

[0581] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2)p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group; R 3g Selected from: hydrogen, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl are optionally substituted R 4 one or more identical or different replacements;

[0582] The aryl group is selected from: phenyl;

[0583] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0584] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0585] The sulfonyl group is selected from the group consisting of: methylsulfonyl, optionally substituted phenylsulfonyl;

[0586] The acyl group is selected from: acetyl, optionally substituted benzoyl;

[0587] The benzenesulfonyl group and the benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F;

[0588] Preferably, R 3a Selected from: hydrogen, tosyl.

[0589] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0590] L is selected from:

[0591] R 2Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0592] X 4 Selected from O, S, NR 2d ;

[0593] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0594] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0595] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8 , C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0596] More preferably, R 2Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0597] R 3 Selected from:

[0598] where Y 2 Selected from CH, CR 3a , N, and Y 2 A C atom at any position on the aromatic ring can be replaced,

[0599] R 3a Selected from:

[0600] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0601] Preferably, R 3a Selected from: hydrogen, fluorine, chlorine, tosyl.

[0602] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0603] L is selected from:

[0604] R 2 Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0605] X 4 Selected from O, S, NR 2d ;

[0606] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0607] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R 8 、-S(=O)2-R 8 、-C(=O)-R8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0608] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8 , C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0609] More preferably, R 2 Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0610] R 3 Selected from:

[0611] in

[0612] X 6 Selected from O, S, NR 3g ,

[0613] Y 2 Selected from CH, CR 3a , N, and Y 2 A C atom at any position on the aromatic ring can be replaced,

[0614] R 3a Selected from:

[0615] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p-R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0616] R 3g Selected from: hydrogen, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl are optionally substituted R 4 one or more identical or different replacements;

[0617] The aryl group is selected from: phenyl;

[0618] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0619] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0620] The sulfonyl group is selected from the group consisting of: methylsulfonyl, optionally substituted phenylsulfonyl;

[0621] The acyl group is selected from: acetyl, optionally substituted benzoyl;

[0622] The benzenesulfonyl group and the benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F;

[0623] R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C6 alkyl;

[0624] or R 3c and R 3d And together with the atoms to which they are attached, they form carbonyl, thiocarbonyl, and imine groups.

[0625] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0626] L is selected from:

[0627] R 2 Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0628] X 4 Selected from O, S, NR 2d ;

[0629] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0630] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0631] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8, C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0632] More preferably, R 2 Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0633] R 3 Selected from: in

[0634] Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced;

[0635] R 3a Selected from:

[0636] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0637] R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C6 alkyl;

[0638] or R 3c and R 3d And together with the atoms to which they are attached, they form carbonyl, thiocarbonyl, and imine groups.

[0639] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0640] L is selected from:

[0641] R 2 Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0642] X4 Selected from O, S, NR 2d ;

[0643] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0644] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0645] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8 , C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0646] More preferably, R 2 Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0647] R 3 Selected from: in

[0648] X 7 Selected from O, NR 3g ,

[0649] Z 1 Selected from O, S,

[0650] R 3b Selected from:

[0651] Optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl, heteroaryl is optionally substituted by R 18 one or more identical or different replacements;

[0652] Preferably, R 3b Selected from:

[0653] Optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl, heteroaryl is optionally substituted by R 18 one or more identical or different replacements;

[0654] The aryl group is selected from: phenyl;

[0655] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0656] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; the R 18Selected from: hydrogen, halogen, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy, optionally substituted halogenated C1-C6 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C6 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C6 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C6 hydroxyalkyl, aryloxy, heterocyclyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl, aryl, heterocyclic group, heteroaromatic group;

[0657] The aryl group is selected from: phenyl;

[0658] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0659] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0660] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 4 one or more identical or different replacements;

[0661] More preferably, the R 18 Selected from: halogen, C1-C6 straight chain alkyl or alkoxy, C3-C6 branched chain alkyl or alkoxy, C3-C6 cycloalkyl or alkoxy, halogenated C1-C6 straight chain alkyl or alkoxy, halogenated C3-C6 branched chain alkyl or alkoxy, halogenated C3-C6 cycloalkyl or alkoxy, morpholinyl, phenoxy;

[0662] More preferably, the R 18 Selected from: hydrogen, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, cyclopropyl, methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, trichloromethoxy, morpholinyl, phenoxy;

[0663] R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2)q -; the aryl, heterocyclic, heteroaryl are optionally substituted with R 4 one or more identical or different replacements;

[0664] The aryl group is selected from: phenyl;

[0665] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0666] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0667] R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C6 alkyl;

[0668] q is 0, 1, 2, or 3;

[0669] Preferably, R 3b Selected from: methyl, ethyl, cyclopropyl, cyclohexyl, phenyl;

[0670] More preferably, R 3 Selected from:

[0671] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0672] L is selected from:

[0673] R 2 Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0674] X 4 Selected from O, S, NR 2d ;

[0675] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0676] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0677] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8 , C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0678] More preferably, R 2 Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0679] R 3 Selected from: in

[0680] X 6 Selected from O, S, NR 3g ;

[0681] X 7 Selected from O, S, NR 3g ;

[0682] Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced;

[0683] R 3a Selected from:

[0684] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0685] Preferably, R 3b Selected from:

[0686] hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -、-C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 ; The aryl and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0687] Preferably, the R 18 Selected from: hydrogen, halogen, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy, optionally substituted halogenated C1-C6 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C6 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C6 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C6 hydroxyalkyl, aryloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl;

[0688] Preferably, R 3b Selected from:

[0689] Optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl, heteroaryl is optionally substituted by R 18 one or more identical or different replacements;

[0690] R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl are optionally substituted R 4 one or more identical or different replacements;

[0691] The aryl group is selected from: phenyl;

[0692] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0693] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0694] The sulfonyl group is selected from the group consisting of: methylsulfonyl, optionally substituted phenylsulfonyl;

[0695] The acyl group is selected from: acetyl, optionally substituted benzoyl;

[0696] The benzenesulfonyl group and the benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F;

[0697] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0698] L is selected from:

[0699] R 2 Selected from: hydrogen, amino, halogen, optionally substituted C1-C4 alkyl,

[0700] X 4 Selected from O, S, NR 2d ;

[0701] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from:

[0702] Hydrogen, halogen, cyano, -(CH2) q -COOH、-OR 8 、-N(H)S(=O)2-R 8 、-S(=O)2-R 8 、-C(=O)-R 8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl group is optionally substituted by R 4 one or more identical or different replacements;

[0703] Preferably, R 2 Selected from: hydrogen, amino, halogen, pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl; the pyrrolyl, benzofuranyl, indolyl, benzothiophenyl, phenyl, benzothiadiazolyl, furyl, pyrazolyl, indazolyl, benzothiazolyl, thiazolyl, imidazolyl, thienyl, oxazolyl, C1-C4 alkyl is optionally substituted one or more times with the following substituents, the substituents being the same or different, selected from: hydrogen, halogen, cyano, -(CH2) q -COOH, -OC(=O)-R 8 , C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, methylsulfonyl, acetyl, methylsulfonyl;

[0704] More preferably, R 2Selected from: hydrogen, amino, pyrrolyl, benzofuranyl, benzo[b]thienyl, indolyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C3 alkylphenyl, biphenyl, methylsulfonamidophenyl, C1-C3 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furyl, pyrazolyl, indazolyl, benzo[d]thiazolyl;

[0705] R 3 Selected from:

[0706] where R 3a Selected from:

[0707] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14-NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0708] X 7 Selected from O, NR 3g ,

[0709] R 3b Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -、-C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 ; The phenyl, aryl, heteroaryl are optionally substituted with R 18 one or more identical or different replacements;

[0710] R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl are optionally substituted R 4 one or more identical or different replacements;

[0711] The aryl group is selected from: phenyl;

[0712] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0713] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0714] The sulfonyl group is selected from the group consisting of: methylsulfonyl, optionally substituted phenylsulfonyl;

[0715] The acyl group is selected from: acetyl, optionally substituted benzoyl;

[0716] The benzenesulfonyl group and the benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F;

[0717] Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced;

[0718] R 3e and R 3f are identical or different and are independently selected from:

[0719] hydrogen, optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -、-C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=O)OR 19 、-S(=O)2-R 20 ;

[0720] or, R 3e and R 3f and together with the atoms to which they are attached, form a carbonyl group;

[0721] or, R 3e and R 3f are the same or different and are independently selected from: aryl, heterocyclyl, heteroaryl;

[0722] The aryl group is selected from: phenyl;

[0723] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0724] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0725] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 One or more substitutions, identical or different.

[0726] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0727] L is selected from:

[0728] R 2 Selected from: hydrogen,

[0729] X 4 Selected from NR 2d ;

[0730] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0731] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0732] R 3Selected from: optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl;

[0733] Preferably, R 3 Selected from: optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl;

[0734] More preferably, R 3 Selected from: optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched chain alkyl, optionally substituted C3-C4 cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched chain alkyl, optionally substituted halogenated C3-C4 cycloalkyl.

[0735] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0736] L is selected from:

[0737] R 2 Selected from: hydrogen,

[0738] X 4 Selected from NR 2d ;

[0739] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0740] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0741] R 3 Selected from

[0742] R 3a Selected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched chain alkyl, optionally substituted C3-C4 cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched chain alkyl, optionally substituted halogenated C3-C4 cycloalkyl, -C(=O)-NHR 13 ;

[0743] The R 13 Selected from: hydrogen, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight chain alkyl, optionally substituted halogenated C3-C6 branched chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl;

[0744] Or, the R 13 Selected from: -(CH2) q -phenyl, -(CH2) q -halogenated phenyl group;

[0745] Preferably, R 13 Selected from: hydrogen, optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched chain alkyl, optionally substituted C3-C4 cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched chain alkyl, optionally substituted halogenated C3-C4 cycloalkyl;

[0746] Or, preferably, the R 13 Selected from: -(CH2) q -phenyl, -(CH2) q -halogenated phenyl; the halogenated phenyl is selected from the group consisting of fluoro and chloro;

[0747] More preferably, R 3 Selected from: (benzylcarbamoyl)phenyl.

[0748] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0749] L is selected from:

[0750] R L1 Selected from: hydrogen, F,

[0751] R L2 Selected from: hydrogen,

[0752] R 2 Selected from: hydrogen,

[0753] X 4 Selected from NR 2d ;

[0754] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0755] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0756] R 3 Selected from: C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl; the C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl are optionally substituted by R 6 one or more identical or different replacements;

[0757] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0758] L is selected from:

[0759] R L1 Selected from: hydrogen, F,

[0760] R L2 Selected from: hydrogen,

[0761] R 2 Selected from: hydrogen,

[0762] X4 Selected from NR 2d ;

[0763] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0764] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0765] R 3 Selected from: in

[0766] X 7 Selected from: NR 3g ,

[0767] Z 1 Selected from: O, S,

[0768] q is 0, 1, 2, or 3;

[0769] R 3b Selected from:

[0770] Optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0771] The aryl group is selected from: phenyl;

[0772] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0773] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0774] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0775] Preferably, R 3b Selected from:

[0776] Optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, aryl-(CH2) q -; the aryl group is selected from: phenyl;

[0777] The phenyl group is optionally substituted by R 18 are substituted one or more times identically or differently, said R 18 is selected from the group consisting of: F, Cl, nitro, C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenoxy; preferably, R 18 Selected from: F, Cl, methyl, ethyl, propyl, isopropyl, cyclopropyl, methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, trichloromethoxy, phenoxy;

[0778] More preferably, R 3b Selected from:

[0779] Optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched chain alkyl, optionally substituted C3-C4 cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched chain alkyl, optionally substituted halogenated C3-C4 cycloalkyl, aryl-(CH2) q -; the aryl group is selected from: phenyl;

[0780] More preferably, R 3b Selected from:

[0781] Methyl, ethyl, propyl, isopropyl, cyclopropyl, trifluoromethyl, trichloromethyl

[0782] R 3g Selected from: hydrogen.

[0783] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0784] L is selected from:

[0785] R L1 Selected from: hydrogen, F,

[0786] R L2 Selected from: hydrogen,

[0787] R 2 Selected from: hydrogen,

[0788] X 4 Selected from NR 2d ;

[0789] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0790] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0791] R 3 Selected from:

[0792] where R 3b Selected from:

[0793] Optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl, heteroaryl is optionally substituted by R 18 one or more identical or different replacements;

[0794] The aryl group is selected from: phenyl;

[0795] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0796] Preferably, the R 18 Selected from: F, Cl, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl;

[0797] More preferably, R 3b Selected from:

[0798] Optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, aryl-(CH2) q -; the aryl group is optionally substituted with R 18 one or more identical or different replacements;

[0799] The aryl group is selected from: phenyl;

[0800] The R 18 is selected from the group consisting of: F, Cl, C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, C3-C4 cycloalkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl, halogenated C3-C4 cycloalkyl; further preferably, the R 18 Selected from: methyl, ethyl, propyl, isopropyl, cyclopropyl, trifluoromethyl, trichloromethyl;

[0801] More preferably, R 3b Selected from:

[0802] methyl, ethyl, propyl, isopropyl, cyclopropyl, trifluoromethyl, trichloromethyl;

[0803] R 3g Selected from: hydrogen, aryl-(CH2) q -; the aryl group is optionally substituted with R 18 One or more times the same or different substitution; the aryl group is selected from: phenyl; preferably, R 3g Selected from: hydrogen, phenylmethyl.

[0804] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0805] L is selected from:

[0806] R L1 Selected from: hydrogen, F,

[0807] R L2 Selected from: hydrogen,

[0808] R 2 Selected from: hydrogen,

[0809] X 4 Selected from NR 2d ;

[0810] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0811] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0812] R 3 Selected from: in

[0813] R 3a Selected from:

[0814] hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, hydroxy, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q-O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 、-C(=O)-R 20 、-C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 )2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 , aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl group is a C1-C6 alkyl group substituted with a hydroxy group;

[0815] The aryl group is selected from: phenyl;

[0816] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0817] The aryl and heteroaryl groups are optionally substituted with R 18 One or more identical or different substitutions; R 3c and R 3d Together with the atom to which they are attached, they form a carbonyl group.

[0818] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0819] L is selected from:

[0820] R L1 is hydrogen, R L2 is aryl-(CH2) q -; the aryl group is selected from: phenyl;

[0821] R 2 Selected from: hydrogen, X 4 Selected from NR 2d ;

[0822] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0823] Preferably, R 2 Selected from: hydrogen, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0824] R 3 Selected from: in

[0825] R 3b Selected from:

[0826] Optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -;

[0827] The aryl group is selected from: phenyl;

[0828] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0829] The aryl and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0830] Preferably, R 3b Selected from: aryl-(CH2) q -; the aryl group is optionally substituted with R 18 one or more identical or different replacements;

[0831] The aryl group is selected from: phenyl;

[0832] The R 18 Selected from: F, Cl, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl.

[0833] Preferably, the R 18 Selected from: F, Cl, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, C3-C6 cycloalkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, halogenated C3-C6 cycloalkyl;

[0834] More preferably, the R 18 Selected from: F, Cl, C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, C3-C4 cycloalkyl, halogenated C1-C4 straight chain alkyl, halogenated C3-C4 branched chain alkyl, halogenated C3-C4 cycloalkyl;

[0835] More preferably, the R 18 Selected from: methyl, ethyl, propyl, isopropyl, cyclopropyl, trifluoromethyl, trichloromethyl.

[0836] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0837] L is selected from:

[0838] R L2 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl;

[0839] Preferably, R L2 Selected from: hydrogen, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight chain alkyl, optionally substituted halogenated C3-C6 branched chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl;

[0840] Preferably, R L2 Selected from: hydrogen, optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched chain alkyl, optionally substituted C3-C4 cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched chain alkyl, optionally substituted halogenated C3-C4 cycloalkyl;

[0841] More preferably, R L2 Selected from: methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl;

[0842] R 2 Selected from:

[0843] X 4 Selected from NR 2d ;

[0844] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0845] Preferably, R 2Selected from: pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0846] More preferably, R 2 Selected from: pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is substituted one or more times with the following substituents: fluorine, chlorine, methoxy;

[0847] R 3 Selected from: in

[0848] R 3b Selected from:

[0849] Optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -;

[0850] The aryl group is selected from: phenyl;

[0851] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0852] The aryl and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0853] The R 18 Selected from: F, Cl, nitro, C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenoxy;

[0854] More preferably, the R 18 Selected from: methyl, ethyl, propyl, isopropyl, cyclopropyl, methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, trichloromethoxy, phenoxy.

[0855] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0856] L is selected from:

[0857] R L2 Selected from: aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -,

[0858] The aryl-(CH2) q - is selected from: phenyl-CH2-;

[0859] The heterocyclic group -(CH2) q -selected from: piperidinyl-CH2-;

[0860] The heteroaryl-(CH2) q - is selected from: indolyl-CH2-, thienyl-CH2-, benzothienyl-CH2-, furyl-CH2-, benzofuranyl-CH2-, pyridyl-CH2-,

[0861] Wherein phenyl, indolyl, thienyl, benzothienyl, furyl, benzofuranyl, pyridyl, piperidyl is substituted one or more times by the following substituents selected from: halogen, cyano, -NR 9 R 10 , hydroxy, C1-C8 hydroxyalkyl, C1-C8 straight-chain alkyl or alkoxy, C3-C8 branched-chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight-chain alkyl or alkoxy, halogenated C3-C8 branched-chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, optionally substituted amide, optionally substituted sulfonamide;

[0862] Preferably, the substituent is selected from: fluorine, chlorine, cyano, -NR 9 R 10 , hydroxy, C1-C6 hydroxyalkyl, C1-C6 straight-chain alkyl or alkoxy, C3-C6 branched-chain alkyl or alkoxy, C3-C6 cycloalkyl or alkoxy, halogenated C1-C6 straight-chain alkyl or alkoxy, halogenated C3-C6 branched-chain alkyl or alkoxy, halogenated C3-C6 cycloalkyl or alkoxy, optionally substituted amide, optionally substituted sulfonamide;

[0863] The sulfonamide group is selected from: methylsulfonamide, optionally substituted benzenesulfonamide;

[0864] The amide group is selected from: acetamide, optionally substituted benzamide;

[0865] The benzenesulfonylamino group and the benzylamino group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F;

[0866] More preferably, the substituent is selected from: fluorine, chlorine, cyano, -NR 9 R 10 , hydroxy, C1-C4 hydroxyalkyl, C1-C4 straight-chain alkyl or alkoxy, C3-C4 branched-chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight-chain alkyl or alkoxy, halogenated C3-C4 branched-chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, optionally substituted amide, optionally substituted sulfonamide;

[0867] Further preferably, the substituent is selected from the group consisting of: hydrogen, fluorine, chlorine, cyano, -NH2, hydroxyl, hydroxymethyl, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0868] R 2 Selected from:

[0869] X 4 Selected from NR 2d ;

[0870] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0871] Preferably, R 2 Selected from: pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0872] More preferably, R 2 Selected from: pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is substituted one or more times with the following substituents: fluorine, chlorine, methoxy;

[0873] R 3 Selected from: in

[0874] R 3b Selected from: optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight chain alkyl, optionally substituted halogenated C3-C8 branched chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -;

[0875] The aryl group is selected from: phenyl;

[0876] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0877] The aryl and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0878] Preferably, the R 18 Selected from: hydrogen, halogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, optionally substituted halogenated C1-C8 straight chain alkyl or alkoxy, optionally substituted halogenated C3-C8 branched chain alkyl or alkoxy, optionally substituted halogenated C3-C8 cycloalkyl or alkoxy, aryl, heteroaryl, heterocyclyl; the aryl group is selected from: phenyl;

[0879] Preferably, R 3b Selected from: optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight chain alkyl, optionally substituted halogenated C3-C6 branched chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -;

[0880] The R 18 Selected from: F, Cl, C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenoxy;

[0881] More preferably, the R 18Selected from: methyl, ethyl, propyl, isopropyl, cyclopropyl, methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, trichloromethoxy, phenoxy;

[0882] More preferably, R 3b Selected from: methyl, ethyl, propyl, cyclopropyl, isopropyl, isobutyl, tert-butyl.

[0883] In another preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0884] L is selected from:

[0885] R 2 Selected from:

[0886] X 4 Selected from NR 2d ;

[0887] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0888] Preferably, R 2 Selected from: pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0889] More preferably, R 2 Selected from: pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is substituted one or more times with the following substituents: fluorine, chlorine, methoxy;

[0890] R L2 and R 3 Together with the atoms to which they are attached, they are cyclized to form a 5-10 membered nitrogen and / or sulfur heterocyclic group, wherein the 5-10 membered nitrogen and / or sulfur heterocyclic group comprises a -C(=O)-, -S(=O)2- group;

[0891] Preferably, the 5-10 membered nitrogen-containing heterocyclic group is selected from: 1,1-dioxadibenzo[d]isothiazol-2(3H)-yl.

[0892] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0893] L is selected from:

[0894] R L1 Selected from: hydrogen, fluorine;

[0895] R 2 Selected from: hydrogen, halogen, amino,

[0896] X 4 Selected from NR 2d ;

[0897] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0898] Preferably, R 2 Selected from: hydrogen, halogen, amino, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0899] More preferably, R 2 Selected from: hydrogen, halogen, amino, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is substituted one or more times with the following substituents: fluorine, chlorine, methoxy;

[0900] R 3 Selected from:

[0901] R 3aSelected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C4 straight-chain alkyl, optionally substituted C3-C4 branched-chain alkyl, optionally substituted C3-C4 cycloalkyl, optionally substituted halogenated C1-C4 straight-chain alkyl, optionally substituted halogenated C3-C4 branched-chain alkyl, optionally substituted halogenated C3-C4 cycloalkyl.

[0902] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0903] L is selected from: in

[0904] R L1 Selected from: hydrogen, fluorine;

[0905] R 2 Selected from: hydrogen, halogen, amino, X 4 Selected from NR 2d ;

[0906] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0907] Preferably, R 2 Selected from: hydrogen, halogen, amino, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0908] More preferably, R 2 Selected from: hydrogen, halogen, amino, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is substituted one or more times with the following substituents: fluorine, chlorine, methoxy;

[0909] R 3 Selected from: in

[0910] X 7 Selected from: O, NR 3g ;

[0911] Z1 Selected from: O;

[0912] R 3b Selected from:

[0913] Optionally substituted C1-C8 straight-chain alkyl, optionally substituted C3-C8 branched-chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted halogenated C1-C8 straight-chain alkyl, optionally substituted halogenated C3-C8 branched-chain alkyl, optionally substituted halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -;

[0914] q is 0, 1, 2, or 3;

[0915] The aryl group is selected from: phenyl;

[0916] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0917] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0918] The aryl, heterocyclic and heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0919] Preferably, R 3b Selected from:

[0920] Optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched chain alkyl, optionally substituted C3-C4 cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched chain alkyl, optionally substituted halogenated C3-C4 cycloalkyl, aryl-(CH2) q -; the aryl group is optionally substituted with R 18 one or more identical or different replacements;

[0921] q is 0, 1, 2, or 3;

[0922] The aryl group is selected from: phenyl;

[0923] The R 18Selected from: F, Cl, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, C3-C6 cycloalkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, halogenated C3-C6 cycloalkyl, morpholinyl, phenoxy;

[0924] More preferably, R 3b Selected from: methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl;

[0925] R 3g Selected from: hydrogen, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, aryl-(CH2) q -, heterocyclic group-(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl are optionally substituted R 4 one or more identical or different replacements;

[0926] The aryl group is selected from: phenyl;

[0927] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0928] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0929] The sulfonyl group is selected from the group consisting of: methylsulfonyl, optionally substituted phenylsulfonyl;

[0930] The acyl group is selected from: acetyl, optionally substituted benzoyl;

[0931] The benzenesulfonyl and benzoyl groups are optionally substituted one or more times with the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy groups are optionally substituted one or more times with the following substituents: Cl, F.

[0932] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0933] L is selected from:

[0934] R L1 Selected from: hydrogen, fluorine;

[0935] R 2 Selected from: hydrogen, halogen, amino, X 4 Selected from O, S, NR 2d ;

[0936] where R 2a 、R 2b 、R 2c are identical or different and are independently selected from the group consisting of hydrogen, fluorine, optionally substituted C1-C4 straight-chain alkyl or alkoxy, optionally substituted C3-C4 branched-chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy, optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 branched-chain alkyl or alkoxy, optionally substituted halogenated C3-C4 cycloalkyl or alkoxy;

[0937] Preferably, R 2 Selected from: hydrogen, halogen, amino, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is optionally substituted one or more times with the following substituents, which are the same or different, and the substituents are selected from: hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy, trifluoromethoxy;

[0938] More preferably, R 2 Selected from: hydrogen, halogen, amino, pyrrolyl, indolyl, phenyl, wherein the pyrrolyl, indolyl, phenyl is substituted one or more times with the following substituents: fluorine, chlorine, methoxy;

[0939] R 3 Selected from:

[0940] R 3a Selected from: hydrogen, halogen, nitro, cyano, hydroxy, C1-C6 hydroxyalkyl, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl;

[0941] Preferably, R 3a Selected from: hydrogen, F, Cl, nitro, cyano, hydroxy, C1-C6 hydroxyalkyl, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl;

[0942] More preferably, R 3aSelected from: hydrogen, F, Cl, hydroxy, C1-C4 hydroxyalkyl, methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl, cyclohexyl.

[0943] In a more preferred embodiment, the present invention relates to compounds of the above-mentioned general formula (I), or their enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives, wherein: the acyl group is selected from acetyl and the sulfonyl group is selected from methylsulfonyl.

[0944] In a more preferred embodiment, the present invention relates to a compound of the above-mentioned general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof, wherein:

[0945] The aryl-(CH2) q - is selected from: aryl-(CH2)3-, aryl-(CH2)2-, aryl-CH2-, aryl-;

[0946] The heterocyclic group -(CH2) q - is selected from: heterocyclyl-(CH2)3-, heterocyclyl-(CH2)2-, heterocyclyl-CH2-, heterocyclyl-;

[0947] The heteroaryl-(CH2) q - is selected from the group consisting of: heteroaryl-(CH2)3-, heteroaryl-(CH2)2-, heteroaryl-CH2-, heteroaryl-.

[0948] In a more preferred embodiment, the present invention relates to a compound of the above-mentioned general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof, wherein:

[0949] The halogenated group is selected from the group consisting of fluoro and chloro;

[0950] Or, halogen is selected from: fluorine, chlorine, bromine, iodine; preferably, halogen is selected from: fluorine, chlorine.

[0951] In a more preferred embodiment, the present invention relates to a compound of the above-mentioned general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof, wherein:

[0952] R 3a Selected from: -(CH2) q -NR 16 -S(=O)2-R 17 , the R 16 Preferably selected from: hydrogen.

[0953] In a more preferred embodiment, the present invention relates to a compound of the above-mentioned general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof, wherein:

[0954] R 3a Selected from: -(CH2) q -S-(CH2) p -R 11 , the R 11 Preferably selected from: benzene.

[0955] In a more preferred embodiment, the present invention relates to a compound of the above-mentioned general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof, wherein:

[0956] C1-C4 straight chain alkyl, C3-C4 branched chain alkyl, C3-C4 cycloalkyl is selected from the group consisting of methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, isopropyl, isobutyl, and tert-butyl;

[0957] or C1-C4 alkyl is selected from the group consisting of methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, isopropyl, isobutyl, and tert-butyl;

[0958] Or C1-C3 alkyl is selected from: methyl, ethyl, propyl, isopropyl, cyclopropyl.

[0959] In each of the above embodiments, the present invention relates to a compound of the above general formula (I), or an enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotope-substituted derivative thereof, wherein:

[0960] p and q are each independently 0, 1, 2 or 3;

[0961] m, n are the same or different and are independently selected from: 1, 2 or 3 to form ring systems with different numbers of atoms.

[0962] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0963] L is selected from:

[0964] 1,3-substituted-bicyclo[1.1.1]pentanyl, 2,6-substituted-diazacyclo[3.3]heptanyl, oxy-azetidinyl, 3-amino-azetidin-1-yl, 3-amino(benzyl)-azetidin-1-yl, aminoethynyl, 1,2-substituted cyclopropane, 3-alkenylazetidin-1-yl, 3-sulfanyl-azetidin-1-yl, 3-sulfinylazetidin-1-yl, 3-sulfonylazetidin-1-yl, 1H-1,2,3-triazol-4-yl;

[0965] Wherein, the oxy-azetidinyl group is selected from: 3-oxy-azetidin-1-yl, azetidinyl-3-oxyl;

[0966] The aminoethynyl group is selected from:

[0967] aminoethynyl, amino(alkyl)ethynyl, amino(aryl-CH2-)ethynyl, amino(heterocyclyl-CH2-)ethynyl, amino(heteroaryl-CH2-)ethynyl, amino(sulfonyl)ethynyl;

[0968] The alkyl group is selected from the group consisting of an optionally substituted C1-C8 straight-chain alkyl group, an optionally substituted C3-C8 branched-chain alkyl group, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted halogenated C1-C8 straight-chain alkyl group, an optionally substituted halogenated C3-C8 branched-chain alkyl group, and an optionally substituted halogenated C3-C8 cycloalkyl group;

[0969] Preferably, the alkyl group is selected from: optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted halogenated C1-C6 straight-chain alkyl, optionally substituted halogenated C3-C6 branched-chain alkyl, optionally substituted halogenated C3-C6 cycloalkyl;

[0970] The aryl, heterocyclic, heteroaryl groups are optionally substituted with R 18 one or more identical or different replacements;

[0971] The aryl group is selected from: phenyl, naphthyl; preferably phenyl

[0972] The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl;

[0973] The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolinyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl;

[0974] The sulfonyl group is selected from the group consisting of: methylsulfonyl, optionally substituted phenylsulfonyl;

[0975] The acyl group is selected from: acetyl, optionally substituted benzoyl;

[0976] The benzenesulfonyl group and the benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F;

[0977] More preferably, amino(alkyl)ethynyl is selected from: amino(methyl)ethynyl;

[0978] The amino(aryl-CH2-)ethynyl group is selected from the group consisting of amino(benzyl)ethynyl, amino(4-fluorobenzyl)ethynyl, amino(4-methylbenzyl)ethynyl, amino(4-trifluoromethylbenzyl)ethynyl, amino(methoxybenzyl)ethynyl, amino(2-fluorobenzyl)ethynyl, and amino(4-(hydroxymethyl)benzyl)ethynyl;

[0979] The amino(heterocyclyl-CH2-)ethynyl group is selected from the group consisting of amino((1-methylpiperidin-4-yl)methyl)ethynyl;

[0980] The amino(heteroaryl-CH2-)ethynyl group is selected from the group consisting of amino(pyridin-3-ylmethyl)ethynyl, amino(furan-2-ylmethyl)ethynyl, amino(1-methyl-1H-indol-5-yl)methylethynyl, and amino(thiophen-2-ylmethyl)ethynyl.

[0981] The amino(sulfonyl)ethynyl group is selected from the group consisting of: amino(methylsulfonyl)ethynyl, amino(cyclopropylsulfonyl)ethynyl, amino(phenylsulfonyl)ethynyl, amino((4-methylphenyl)sulfonyl)ethynyl, amino(benzo[b]thiophene-3-sulfonyl)ethynyl, amino(thiophene-2-sulfonyl)ethynyl, and amino(benzofuran-5-sulfonyl)ethynyl.

[0982] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0983] R 3 Selected from:

[0984]

[0985]

[0986]

[0987]

[0988] In a preferred embodiment, the present invention relates to compounds of the above general formula (I), or enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives thereof, wherein:

[0989] The compound is selected from the group consisting of: 3-(3-(acetoxy(4-methoxyphenyl)methyl)bicyclo[1.1.1]pentan-1-yl)benzoic acid, 3-(3-(acetoxy(6-(trifluoromethyl)pyridin-3-yl)methyl)bicyclo[1.1.1]pentan-1-yl)benzoic acid, 3-(3-(hydroxy(6-(trifluoromethyl)pyridin-3-yl)methyl)bicyclo[1.1.1]pentan-1-yl)benzoic acid, 3-(3-phenylbicyclo[1.1.1]pentan-1-yl)benzoic acid, methyl 3-(3-phenylbicyclo[1.1.1]pentan-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-phenylbicyclo[1.1.1]pentan-1-yl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid, methyl 3-(3-(4-methoxyphenyl)bicyclo[1.1.1]pentan-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-methoxyphenyl)bicyclo[1.1.1]pentan-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 2-amino-3-(6-phenyl-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, methyl 2-amino-3-(6-phenyl-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, 3-(6-phenyl-2,6-diazaspiro[3.3]heptane-2-yl)benzoate-2-(1H-pyrrol-1-yl)benzoate, 2-amino-3-(6-phenyl-2,6-diazaspiro[3.3]heptane-2-yl)benzoate benzoic acid, methyl 2-amino-3-(6-(4-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, methyl 2-amino-3-(6-(4-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, methyl 2-amino-3-(6-(3-(methoxycarbonyl)phenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, methyl 2-amino-3-(6-(3-(methoxycarbonyl)phenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, methyl 2-amino-3-(6-(3-carboxyphenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, .3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(6-(3-carboxyphenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(6-(2-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(6-(2-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(6-(2-nitrophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(6-(2-nitrophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(6-(4-(methoxycarbonyl)phenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(6-(4-carboxyphenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(6-(3-nitrophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-nitrobenzoate, methyl 3-(6-(3-nitrophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-nitrobenzoate )-2-nitrobenzoic acid, methyl 3-(6-(3-(methylsulfonylamino)phenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-nitrobenzoate, 3-(6-(3-(methylsulfonylamino)phenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-nitrobenzoic acid, methyl 3-(6-(3-acetylaminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-aminobenzoate, methyl 3-(6-(3-acetylaminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)-2-aminobenzoate, 2-amino-3-(6-(3-(cyclopropanesulfonylamino)phenyl)-2,6-diazaspiro[3.3] benzoic acid, methyl 2-amino-3-(6-(3-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, methyl 2-amino-3-(6-(3-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, methyl 2-amino-3-(6-(3-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoate, 3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid, 2-amino-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid, 3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid benzoic acid, methyl 3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-indol-6-yl)benzoate, methyl 3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-indol-6-yl)benzoate, methyl 6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylate, methyl 6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylate,Methyl 2-(Benzo[b]thiophen-6-yl)-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)benzoate, 2-(Benzo[b]thiophen-6-yl)-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid, Methyl 2-(Benzo[c][1,2,5]thiadiazol-5-yl)-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)benzoate, 2-(Benzo[c][1,2,5]thiadiazol-5-yl)-3-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)benzoate, 2-(Furan-2-yl)-3-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)benzoate Methyl benzoate, 2-(furan-3-yl)-3-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid, 2-(furan-3-yl)-3-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid, 3'-fluoro-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, 3'-fluoro-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, 2-(benzofuran-6-yl)-3-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid, 3'-chloro-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid 3'-Chloro-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, 3'-cyano-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, 6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2,3'-dicarboxylic acid, 4'-chloro-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, 4'-chloro-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, )phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, 3'-(trifluoromethyl)-6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid methyl ester, 3'-(trifluoromethyl)-6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, 3',5'-difluoro-6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid methyl ester, 3',5'-difluoro-6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid,6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1':4',1"-terphenyl]-2-carboxylic acid methyl ester, 6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1':4',1"-terphenyl]-2-carboxylic acid, 3'-(methylsulfonamido)-6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid methyl ester, 3'-methoxy-6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid methyl ester, 3'-methoxy-6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid methyl ester, benzoic acid, 3-((1-(3-(benzylcarbamoyl)phenyl)azetidin-3-yl)oxy)benzoic acid, 3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrazol-1-yl)benzoic acid methyl ester, 3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrazol-1-yl)benzoic acid methyl ester, 3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrazol-1-yl)benzoic acid, 3-((1-(3-(benzylcarbamoyl)phenyl)azetidin-3-yl)oxy)benzoic acid, 3-(3-(3-carboxyphenoxy)azetidin-1-yl)-2-aminobenzyl acid, 3-(3-(3-carboxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(acetoxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-((octanoyloxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(acetamidomethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(acetamidomethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate )benzoic acid, methyl 3-(3-(4-(cyclopropylsulfonamidomethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-methoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-methoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(4-(trifluoromethyl)phenoxy)azetidin-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(4-(trifluoromethyl)phenoxy)azetidin-1-yl)benzoate,2-(1H-pyrrol-1-yl)-3-(3-(4-(trifluoromethoxy)phenoxy)azetidin-1-yl)benzoic acid methyl ester, 2-(1H-pyrrol-1-yl)-3-(3-(4-(trifluoromethoxy)phenoxy)azetidin-1-yl)benzoic acid, 3-(3-((6-chloropyridin-3-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-((6-chloropyridin-3-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-acetylphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, -(3-(4-acetylphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(1-hydroxyethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(1-hydroxyethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(1-hydroxyethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((2,6-dichloropyridin-4-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, acid, methyl 3-(3-(4-cyanophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-cyanophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-chlorophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-chlorophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(dimethylamino)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-ethoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-ethoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-phenoxyazetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-phenoxyazetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-phenoxyazetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(3-((1H-indol-6-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-propoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-propoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-propoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-butoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-butoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid, methyl 3-(3-(4-isopropoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(4-(((tetrahydro-2H-pyran-4-yl)oxy)methyl)phenoxy)azetidin-1-yl)benzoate, methyl 3-(3-(4-(phenoxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate )azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(phenoxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-nitrophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(3-propylthioureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 2-(1H-pyrrol-1-yl)-3-(3-(4-(3-(4-(trifluoromethyl)phenyl)thioureido)phenoxy)azetidin-1-yl)benzoic acid methyl ester, 3-(3-(4-(3-propylthioureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, -(2-methoxyphenyl)thioureayl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-acetamidophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-acetamidophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 2-(1H-pyrrol-1-yl)-3-(3-(4-(thiophene-2-carboxamido)phenoxy)azetidin-1-yl)benzoic acid methyl ester, 2-(1H-pyrrol-1-yl)-3-(3-(4-(thiophene-2-carboxamido)phenoxy)azetidin-1-yl)benzoic acid,3-(3-(4-(N-(methylsulfonyl)methylsulfonamido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(methylsulfonamido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(cyclopropanesulfonamido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(cyclopropanesulfonamido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(cyclopropanesulfonamido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(3-(4-chlorophenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(3-cyclohexylureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(3-cyclohexylureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(3-hexylureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(3-chlorophenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, benzoic acid, methyl 3-(3-(4-(3-(3-chlorophenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(3-(2-chlorophenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(3-(2-chlorophenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(3-(2-chlorophenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid, methyl 3-(3-(4-(3-(3-cyanophenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((4-methoxybenzyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(thiazol-4-yl)methoxy)azetidin-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(thiazol-4-yl)methoxy)azetidin-1-yl)benzoate, methyl 3-(3-(pyrazin-2-yl)methoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(3-(pyrazin-2-yl)methoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(2-oxo-2-(phenylamino)ethoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(2-oxo-2-(phenylamino)ethoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(((2,4-dimethoxyphenyl)carbamoyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(((4-chlorophenyl)carbamothioyl)oxy)azetidin-1-yl )-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(((4-chlorophenyl)carbamothioyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-((cyclohexylcarbamoyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-((cyclohexylcarbamoyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(((3-fluoro-4-(morpholin-2-yl)phenyl)carbamoyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(((4 1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(((4-(trifluoromethoxy)phenyl)carbamoyl)oxy)azetidin-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(((4-(trifluoromethyl)benzyl)carbamoyl)oxy)azetidin-1-yl)benzoate, methyl 3-(3-((cyclopropylcarbamoyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((cyclopropylcarbamoyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(((4-bromophenyl)carbamothioyl)oxy)azetidin-1-yl)benzoate benzoic acid, methyl 3-(3-(((4-bromophenyl)carbamothioyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(((4-methoxyphenyl)carbamothioyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(((4-methoxyphenyl)carbamothioyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(((4-methoxyphenyl)carbamothioyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((ethylcarbamothioyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(3-((ethylaminothiocarbonyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(((2,4-dichlorophenyl)aminothiocarbonyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-(((2,4-dichlorophenyl)aminothiocarbonyl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-cyclopropylureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-(4-phenoxyphenyl)ureido)azetidin-1-yl)-2- Methyl (1H-pyrrol-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(3-(4-(trifluoromethoxy)phenyl)ureido)azetidin-1-yl)benzoate, 3-(3-(3-(4-phenoxyphenyl)ureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 2-(1H-pyrrol-1-yl)-3-(3-(3-(4-(trifluoromethoxy)phenyl)ureido)azetidin-1-yl)benzoic acid, 3-(3-(3-cyclopropylureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(3-(3,5-dimethoxyphenyl)ureido)azetidin-1-yl) benzoic acid, methyl 3-(3-(3-(3,5-dimethoxyphenyl)ureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-ethylthioureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-ethylthioureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-ethylthioureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-ethylthioureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-(4-chlorophenyl)thioureido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid, methyl 3-(3-((4-methylphenyl)sulfonamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((4-methylphenyl)sulfonamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((4-methylphenyl)sulfonamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-benzamidoazetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-benzamidoazetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(2-nitrobenzamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(3-(2-nitrobenzamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(cyclopropanesulfonamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(cyclopropanesulfonamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((N-benzyl-4-methylphenyl)sulfonamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((N-benzyl-4-methylphenyl)sulfonamido)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid, methyl 3-(3-(4-hydroxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-hydroxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(2-(tert-butyloxy)-2-oxovinyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(p-tolylsulfanyl)azetidin-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(p-tolylsulfanyl)azetidin-1-yl)benzoate, benzoic acid, methyl 2-(1H-pyrrol-1-yl)-3-(3-(p-tolylsulfonyl)azetidin-1-yl)benzoate, methyl 2-(1H-pyrrol-1-yl)-3-(3-(p-tolylsulfinyl)azetidin-1-yl)benzoate, methyl 3-(3-(4-(4-chlorophenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(4-chlorophenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(4-chlorophenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(4-chlorophenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(4-chlorophenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, ) benzoic acid, methyl 3-(3-(4-(3-methoxyphenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-chloro-4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-chloro-4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-chloro-4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-fluoro-4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(3-(4-(4-fluorophenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(4-fluorophenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(3,5-difluoro-4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(3,5-difluoro-4-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(4-acetylphenoxy)phenoxy)azetidin-1-yl)-2-(1H -pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(4-acetylphenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(phenylthio)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(phenylthio)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(phenylthio)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(4-cyanophenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(4-(methylsulfonyl)phenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(4-(methylsulfonyl)phenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(4-(methylsulfonyl)phenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-propionylphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-propionylphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid, methyl 3-(3-(4-isobutyrylphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-methoxy-4-(2-methoxyethoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-methoxy-4-(2-methoxyethoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(2-acetamidoethoxy)-3-methoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(3-(4-(2-acetamidoethoxy)-3-methoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(3-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-phenoxyphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, -pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(3-(4-chlorophenyl)thioureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(3-(3-chlorophenyl)thioureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(3-(3-cyanophenyl)thioureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate Methyl benzoate, 3-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, N-(thiophen-2-ylmethyl)-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzamide, ethyl 3-(3-(4-(ethoxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-(4-(ethoxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-(4-(ethoxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(((((tetrahydro- 2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(morpholinylmethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-(4-((((4-chlorophenyl)carbamothioyl)oxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-((((4-chlorophenyl)carbamothioyl)oxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester,3-(3-(4-(((ethylaminothiocarboxamido)oxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(((ethylaminothiocarboxamido)oxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-((4-chlorophenoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-((4-chlorophenoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-((4-chlorophenoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, benzoic acid, methyl 3-(3-(4-((pyridin-3-yloxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-((pyridin-3-yloxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-((pyridin-3-yloxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-((4-fluorophenoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate Acid, methyl 3-(3-(4-((3-fluorophenoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-((3-fluorophenoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-((3-(trifluoromethyl)phenoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-((3-(trifluoromethyl)phenoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid, methyl 3-(3-(4-(hydroxymethyl)-3-methylphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-aminophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-aminophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-aminophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(2-aminophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(2-aminophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-((3-phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-((3-phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(pyridin-3-yloxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(pyridin-3-yloxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(2-(methylsulfonamido)thiazol-4-yl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(2-(methylsulfonamido)thiazol-4-yl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid 4-(phenylcarbamoyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(phenylcarbamoyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(ethylcarbamoyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(morpholine-4-carbonyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(morpholine-4-carbonyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid methyl ester, 3-(((N-benzyl-4-methylphenyl)sulfonamido)acetyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(1-(4-(hydroxymethyl)phenyl)-1H-1,2,3-triazol-4-yl)-2-(1H-indol-6-yl)benzoate, methyl 3-(1,1-dioxadibenzo[d]isothiazol-2(3H)-yl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((N-benzyl-4-methylphenyl)sulfonamido)acetyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(2 -phenylcyclopropane)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(hydroxy(4-methoxyphenyl)methyl)bicyclo[1.1.1]pentan-1-yl)benzoic acid, 3-(6-phenyl-2,6-diazaspiro[3.3]heptane-2-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 2-amino-3-(6-(2-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-yl)benzoic acid methyl ester, 2-(furan-2-yl)-3-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid, 2-(benzofuran-6-yl)-3-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)benzoic acid methyl ester,3'-Cyano-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, 3'-carboxy-6-(3-(4-hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid methyl ester, 6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-3'-(methylsulfonamido)-[1,1'-biphenyl]-2-carboxylic acid, 3'-cyano-4'-fluoro-6-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-[1,1'-biphenyl]-2-carboxylic acid, methyl 2-amino-3-(3-(3-carboxyphenoxy)azetidin-1-yl)benzoate, 3-(3-(4 -(((4-methylphenyl)sulfonamido)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((2,6-difluoropyridin-4-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-((2,6-difluoropyridin-4-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-nitrophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((N-(pyridin-3-ylmethyl)-N-(4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1 -yl)benzoic acid lithium salt, 3-(3-(3-(2-(methylsulfonamido)thiazol-4-yl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(3-(2-methoxyphenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(3-hexylureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(4-(trifluoromethyl)phenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(4-(trifluoromethyl)phenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(3-acetylphenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(3-acetylphenoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-(4-(trifluoromethoxy)phenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-(4-(trifluoromethoxy)phenyl)ureido)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(3-(3-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(3-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(hydroxymethyl)-2-methylphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(hydroxymethyl)-2-methylphenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-nitrophenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(phenylamino)benzoic acid benzoic acid, methyl 3-(3-(4-(ethylcarbamoyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((1-toluenesulfonyl-1H-indol-5-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((1-toluenesulfonyl-1H-indol-5-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-((1-toluenesulfonyl-1H-indol-5-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-((1-toluenesulfonyl-1H-indol-5-yl)oxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 1-yl)benzoic acid methyl ester, 3-(3-(3,4-bis(2-methoxyethoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-((tetrahydro-2H-pyran-2-yl)oxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(2-(methylamino)ethoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(4-(2-aminoethoxy)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, -1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(((N-(furan-2-ylmethyl)-4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium 3-(((N-(furan-2-ylmethyl)-4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate,Methyl 3-(((4-methyl-N-((1-methyl-1H-indol-5-yl)methyl)phenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium 3-(((4-methyl-N-((1-methyl-1H-indol-5-yl)methyl)phenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((4-methyl-N-((1-methylpiperidin-4-yl)methyl)phenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, 3-(((4-methyl-N-((1-methylpiperidin-4-yl)methyl)phenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid Lithium, methyl 3-((N-benzylbenzo[b]thiophene-3-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium 3-((N-benzylbenzo[b]thiophene-3-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-benzylthiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium 3-((N-benzylthiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-benzylthiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium 3-((N-(2-fluorobenzyl)thiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate benzoate, methyl 3-((N-(4-fluorobenzyl)thiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-(4-fluorobenzyl)thiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-(4-fluorobenzyl)thiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((4-methyl-N-(thiophen-2-ylmethyl)phenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((4-methyl-N-(thiophen-2-ylmethyl)phenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium 3-((N-(4-fluorobenzyl)thiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate benzo[b]thiophene-3-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((N-(4-(hydroxymethyl)benzyl)-4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((N-(4-(hydroxymethyl)benzyl)-4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium 3-(((N-(4-(hydroxymethyl)benzyl)-4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-((1-methyl-1H-indol-5-yl)methyl)benzo[b]thiophene-3-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate,Lithium 3-((N-((1-methyl-1H-indol-5-yl)methyl)benzo[b]thiophene-3-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-(4-(trifluoromethyl)benzyl)thiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium 3-((N-(4-(trifluoromethyl)benzyl)thiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-(4-(trifluoromethyl)benzyl)thiophene-2-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-((1-methyl-1H-indol-5-yl)methyl)benzofuran-5-sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, benzoic acid, methyl 3-((N-benzyl-N-benzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-((N-benzyl-N-benzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((N-(4-methylbenzyl)-N-(4-methylbenzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(((N-(4-methylbenzyl)-N-(4-methylbenzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium salt of 3-(((N-(4-methylbenzyl)-N-(4-methylbenzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, Methyl N-(4-fluorobenzyl)-4-methylbenzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, 3-(((N-(4-fluorobenzyl)-4-methylbenzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium salt of 3-(((N-(4-(trifluoromethyl)benzyl)-N-(4-methylbenzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium salt of 3-(((N-(4-(trifluoromethyl)benzyl)-(4-methylbenzenesulfonyl)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium salt of 3-(3-((4-isopropylphenyl)thio)azetidin-1-yl)-2-(1H- 1-yl)benzoic acid methyl ester, 3-(3-((4-chlorophenyl)sulfanyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(cyclohexylsulfanyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-(phenylsulfanyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-((4-(hydroxymethyl)phenyl)sulfanyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(3-((4-isopropylphenyl)sulfonyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester,Methyl 3-(3-((4-chlorophenyl)sulfonyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, Methyl 3-(3-(cyclohexylsulfonyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, Methyl 3-(3-(phenylsulfonyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, Methyl 3-(3-((4-(hydroxymethyl)phenyl)sulfonyl)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, Methyl 3-(3-(4-(((5-fluoropyridin-3-yl)oxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate , 3-(3-(4-(((5-fluoropyridin-3-yl)oxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-((pyrimidin-5-yloxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-(4-((pyrimidin-5-yloxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-((pyrimidin-5-yloxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(phenylamino)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(benzylamino)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(benzylamino)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(benzylamino)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(3-(2-methoxyethoxy)-4-((2-methoxyethoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, N-(2-cyanoethyl)-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzamide, N-methylsulfonyl-(3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl))benzamide, methyl 3-(3-(4-(2-methoxyethoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, 3-(3-(4-(2-methoxyethoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate,3-(3-(4-(2-hydroxyethoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(3-(4-(2-hydroxyethoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-(2-acetamidoethoxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(tetrahydrofuran-3-yl)oxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(tetrahydrofuran-3-yl)oxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, )-2-(1H-pyrrol-1-yl)benzoic acid, methyl 3-(3-(4-((oxetane-3-oxy)methyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(3-(4-(1-acetylpiperidin-4-yl)oxymethyl)phenoxy(azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzoate, methyl 3-(1,1-dioxadibenzo[d]isothiazol-2(3H)-yl)ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-(((N-benzyl-4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid, 3-((N-benzylmethylsulfonamido)ethynyl)-2-( 1H-pyrrol-1-yl) benzoic acid methyl ester, 3-((N-benzylmethylsulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid lithium salt, 3-(((N-methyl-4-methylphenylsulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(((N-methyl-4-methylphenylsulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(((N-(4-methoxybenzyl)-4-methylphenylsulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid methyl ester, 3-(((N-(4-methoxybenzyl)-4-methylphenylsulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoic acid lithium salt, 3-( Methyl ((N-(pyridin-3-ylmethyl)-N-(4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, N-(furan-2-ylmethyl)-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzamide, methyl 3-(((N-(pyridin-4-ylmethyl)-N-(4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, lithium salt of 3-(((N-(pyridin-4-ylmethyl)-N-(4-methylphenyl)sulfonamido)ethynyl)-2-(1H-pyrrol-1-yl)benzoate, methyl 2-amino-3-(2-phenylcyclopropane)benzoate,2-Amino-3-(2-phenylcyclopropane)benzoic acid, 3-(2-phenylcyclopropane)-2-(1H-pyrrol-1-yl)benzoic acid, 2-(1H-pyrrol-1-yl)-3-(3-(4-(((tetrahydro-2H-pyran-4-yl)oxy)methyl)phenoxy)azetidin-1-yl)benzoic acid, methyl 2-(benzo[b]thiophen-2-yl)-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)benzoate, N-(2-dimethylamino)ethyl)-3-(3-(4-(hydroxymethyl)phenoxy)azetidin-1-yl)-2-(1H-pyrrol-1-yl)benzamide.

[0990] In another embodiment, the present invention also relates to a pharmaceutical composition comprising one or more compounds of the above-mentioned general formula (I) according to the present invention, or their enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives.

[0991] In another embodiment, the present invention also relates to a pharmaceutical composition comprising one or more compounds of the above-mentioned general formula (I) according to the present invention, or their enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives, and a pharmaceutically acceptable carrier, excipient or diluent.

[0992] In another embodiment, the present invention also relates to a method for treating and / or preventing diseases or disorders caused by EBNA1 activity, which comprises administering to a subject an effective amount of a compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives.

[0993] In another embodiment, the present invention also relates to the use of one or more compounds of the above-mentioned general formula (I) according to the present invention, or their enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives for the preparation of a medicament for treating and / or preventing diseases caused by EBNA1 activity, comprising administering to a subject an effective amount of at least one compound according to the present invention, or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives.

[0994] In another embodiment, the present invention also relates to a method for treating and / or preventing diseases or disorders caused by EBNA1 activity, comprising administering to a subject an effective amount of at least one pharmaceutical composition according to the present invention.

[0995] In another embodiment, the present invention also relates to the use of one or more pharmaceutical compositions according to the present invention for preparing a medicament for treating and / or preventing diseases caused by EBNA1 activity, comprising administering to a subject an effective amount of at least one pharmaceutical composition according to the present invention.

[0996] In preferred embodiments, the disease or disorder is cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis.

[0997] In a more preferred embodiment, the cancer is nasopharyngeal carcinoma, gastric cancer, non-Hodgkin's lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, hepatosplenic T-cell lymphoma, B-cell lymphoma, Burkitt's lymphoma, reticuloendothelioma, reticulocytosis, microglioma, diffuse large B-cell lymphoma, extranodal T / NK lymphoma / angiocentric lymphoma, follicular lymphoma, immunoblastic lymphoma, mucosal Related lymphoid tissue lymphoma, B-cell chronic lymphocytic leukemia, mantle cell lymphoma, mediastinal large B-cell lymphoma, lymphoplasmacytic lymphoma, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, lymphomatoid granuloma, angioimmunoblastic lymphadenopathy, leiomyosarcoma, X-linked lymphoproliferative disorder, post-transplant lymphoproliferative disorder, Hodgkin lymphoma, or breast cancer.

[0998] In another embodiment, the present invention also relates to a method for treating and / or preventing diseases or disorders caused by Epstein-Barr virus (EBV) infection and / or associated with EBV infection, which method comprises administering to a subject an effective amount of at least one compound according to the present invention, or its enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotopically substituted derivative or a pharmaceutical composition thereof.

[0999] In another embodiment, the present invention also relates to the use of the compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives or pharmaceutical compositions thereof for the preparation of drugs for treating and / or preventing Epstein-Barr virus (EBV) infection and / or diseases associated with EBV infection, comprising administering to a subject an effective amount of at least one compound or pharmaceutical composition according to the present invention.

[1000] In another embodiment, the present invention also relates to a method for treating and / or preventing EBV infection in the lytic and / or latent phase, which comprises administering to a subject an effective amount of at least one compound according to the present invention, or its enantiomer, diastereomer, tautomer, salt, crystal form, solvate and / or isotopically substituted derivative or a pharmaceutical composition thereof.

[1001] In another embodiment, the present invention also relates to the use of the compound of the above general formula (I), or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives or pharmaceutical compositions thereof, for the preparation of drugs for treating and / or preventing diseases caused by EBV infection in the lytic and / or latent phases, comprising administering to a subject an effective amount of at least one compound according to the present invention, or its enantiomers, diastereomers, tautomers, salts, crystal forms, solvates and / or isotope-substituted derivatives or pharmaceutical compositions thereof.

[1002] The examples and preparations provided herein further illustrate and illustrate the compounds of the present invention and their preparation methods. It should be understood that the scope of the following preparations and examples does not limit the scope of the present invention in any way.

[1003] The following synthetic routes describe methods for preparing derivatives of formula (I) of the present invention. The starting materials, reagents, catalysts, solvents, etc. used in the following synthetic schemes can be prepared by methods well known to those skilled in the art of organic chemistry or are commercially available. All final derivatives of the present invention can be prepared by the methods described in the schemes or similar methods, which are well known to those skilled in the art of organic chemistry. All variables used in these schemes are defined below.

[1004] Preparation method

[1005] Unless otherwise noted, all reagents were purchased from reagent companies and used without purification. Most reactions were performed under anhydrous conditions under nitrogen. Reagent and solvent purification was performed according to Purification of Laboratory Chemicals (WLF Armarego, Christina Li Lin Chai, Elsevier Inc. 2009). Unless otherwise noted, solvents were redistilled before use. Tetrahydrofuran (THF) was treated with a sodium-benzophenone system, dichloromethane and N,N'-dimethylformamide (DMF) were treated with calcium hydride, and methanol was treated with magnesium shavings and redistilled. Triethylamine, diisopropylethylamine (DIPEA), and pyridine were treated with calcium hydride and redistilled. Reactions were monitored by thin-layer chromatography (TLC) using GF254 (60-F250, 0.2 mm) silica gel plates. Color development was performed using UV light (wavelength 254 nm) or iodine, or by soaking in phosphomolybdic acid or ninhydrin solution and then heating for color development. Flash column chromatography was performed using silica gel 60 (230-400 mesh ASTM), typically using ethyl acetate and n-hexane or dichloromethane and methanol as eluents. 1H NMR was measured using a DRX-300, Brüker Avance-400, or Brüker Avance-500 NMR spectrometer, with chemical shifts localized using residual peaks of deuterated solvents. High-resolution mass spectra were measured using an ABI Q-star Elite mass spectrometer or a Thermo Scientific Q Exactive Focus mass spectrometer. The liquid chromatography mass spectrometer was an Agilent 6125.

[1006] General experimental operation 1:

[1007]

[1008] In a round-bottom flask, m-bromobenzyl alcohol G1 (1 equivalent) was dissolved in anhydrous dichloromethane. Imidazole (2 equivalents) was added, and tert-butyldiphenylsilyl chloride (TBDPSCl) (1.5 equivalents) was added under ice. The reaction system was allowed to warm naturally and monitored by thin-layer chromatography. After the reaction, the dichloromethane was removed under reduced pressure, and the residue was dissolved in a large amount of ethyl acetate and washed with saturated ammonium chloride, saturated sodium bicarbonate, and saturated brine. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and then separated by silica gel column chromatography to obtain G2 (yield 99%). Compound G2 (1 equivalent) was dissolved in anhydrous diethyl ether and set aside. Magnesium metal turnings (2 equivalents, ground before use) were placed in two round-bottom flasks. Anhydrous diethyl ether was introduced under nitrogen. Elemental iodine and 1,2-dibromoethane were added sequentially and gently heated to initiate the Grignard reaction. After initiation, slowly add the ether solution of compound G2, continue to keep the reaction at a low boiling reflux state for 2 hours after the addition is complete, and slowly stir at room temperature for 12 hours to obtain the ether solution of Grignard reagent G3. The concentration of Grignard reagent G7 is about 1.17 mmol / ml. After standing, filter it with a filter membrane, seal it, and store it at low temperature for later use. Take Grignard reagent G7 (1.2 equivalents) in a round-bottom flask, cool it in an ice bath, and inject tricyclic [1.1.1.0 1.3 ]Ether / diethoxymethane solution of pentane G4 (1 equivalent). Warm to room temperature and stir in the dark overnight to obtain a solution of new Grignard reagent G12. Take an appropriate volume of Grignard reagent G5, add aromatic aldehyde G6 (2 equivalents) under ice bath cooling, warm to room temperature and continue stirring for 20-30 minutes, then add water to quench. The reaction solution is diluted with a large amount of ethyl acetate and washed with saturated ammonium chloride, saturated sodium bicarbonate and saturated brine respectively. The organic phase is dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography to obtain a yellow oil G7 (total yield 30-50%).

[1009] Compound G7 (1.0 equivalent) was dissolved in anhydrous dichloromethane, and triethylamine (10.0 equivalent), DMAP (0.5 equivalent), and acetic anhydride (4.0 equivalent) were added respectively. After reacting at room temperature for 0.5 hour, saturated ammonium chloride was added to quench the reaction. The reaction solution was diluted with a large amount of ethyl acetate and washed with saturated ammonium chloride, saturated sodium bicarbonate, and saturated brine. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was directly dissolved in anhydrous tetrahydrofuran without purification. Tetrabutylammonium fluoride (TBAF) solution (1.5 equivalent, 0.5 mol / L tetrahydrofuran solution) was added, and the reaction was carried out at room temperature for 0.5-1 hour. Saturated ammonium chloride was added to quench the reaction. The reaction solution was diluted with a large amount of ethyl acetate and washed with saturated ammonium chloride, saturated sodium bicarbonate, and saturated brine. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and dried. The crude product obtained was dissolved in anhydrous dichloromethane without purification, and anhydrous sodium bicarbonate (2.0 equivalents) and Dess-Martin reagent (1.5 equivalents) were added. The reaction was allowed to react at room temperature for 3-4 hours. The reaction was monitored for completion by thin-layer chromatography and quenched with saturated ammonium chloride. The reaction solution was diluted with a large amount of ethyl acetate and washed with saturated ammonium chloride, saturated sodium bicarbonate, and saturated aqueous sodium chloride solution, respectively. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the benzaldehyde intermediate. The intermediate was dissolved in tert-butyl alcohol without separation, and 2-methyl-2-butene (20.0 equivalents) was added. Sodium chlorite (10 equivalents) and sodium dihydrogen phosphate buffer (0.5 mol / L, pH 6.0) were added under ice cooling, and the reaction was continued at room temperature for 2-3 hours. The reaction was monitored for completion by thin-layer chromatography, and the reaction solution was diluted with a large amount of ethyl acetate and washed with saturated ammonium chloride, saturated sodium bicarbonate, and saturated brine, respectively. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography to obtain carboxylic acid G8 (yield see Example).

[1010] Compound G8 (1 equivalent) was dissolved in anhydrous methanol, and potassium tert-butoxide (2.0 equivalents, 0.05 mol / L methanol solution) was added. The mixture was stirred at room temperature overnight. Water was added for dilution, and the pH was adjusted to 3-4 with dilute hydrochloric acid (0.5 mol / L). The mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and separated using analytical silica gel chromatography to obtain compound G9 (yield see Example).

[1011] General experimental operation 2:

[1012]

[1013] The procedure for preparing the Grignard reagent from the aromatic halide ArX G9 is omitted. The Grignard reagent reacts with G4 to produce a new Grignard reagent G11. Freshly prepared anhydrous zinc chloride (1.1 equivalents, in tetrahydrofuran) is added to the unseparated reaction solution and stirred at room temperature for 2 hours to obtain zinc reagent G12 for use. Methyl m-bromobenzoate G13 (1.1 equivalents) and Pd(dppf)Cl2 (0.01 equivalents) are added to a round-bottom flask equipped with a magnetic stirrer. After stirring at room temperature for 5 minutes, the zinc reagent G12 prepared above is added and the reaction is allowed to react at 50°C overnight under nitrogen protection. The reaction is quenched by adding saturated aqueous ammonium chloride solution and extracted with a large amount of ethyl acetate. The organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated to dryness, and passed through a silica gel column (n-hexane:ethyl acetate = 30:1) to obtain crude compound G14. The crude compound was separated by HPLC (instrument brand, column brand, solvent composition, flow rate, detector, wavelength) to obtain pure compound G14 (yield see Example). The hydrolysis of G14 was carried out under standard conditions as before to obtain carboxylic acid G15.

[1014] General experimental operation three:

[1015]

[1016] Compound G17 (1.0 equivalent), palladium tetratriphenylphosphine (0.1 equivalent), and cesium carbonate (5.0 equivalent) were added to a round-bottom flask. Dry N,N-dimethylformamide was injected under nitrogen. G23 (5.0 equivalent) was added with stirring. The temperature was raised to 100°C and allowed to react overnight under nitrogen. The reaction mixture was cooled to room temperature, diluted with a large amount of ethyl acetate, and washed with saturated sodium bicarbonate and saturated brine, respectively. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography to yield compound G18.

[1017] Compound G18 (1.0 equivalent) was dissolved in anhydrous dichloromethane, anhydrous trifluoroacetic acid was added under an ice bath, stirring was continued at room temperature for more than 30 minutes, and thin layer chromatography was used to monitor the reaction until the end. The solvent was removed by rotary evaporation under reduced pressure, and an appropriate amount of dichloromethane was added and then concentrated under reduced pressure. The operation was repeated twice. The residue was dried with an oil pump to obtain intermediate G19. Fluorinated compound G20 (2.0 equivalents) and potassium carbonate (5.0 equivalents) were added to the reaction flask without purification. N,N-dimethylformamide was then injected under nitrogen protection. Stir at room temperature under nitrogen protection for 1-5 hours and thin layer chromatography was used to monitor the reaction until the end. The reaction solution was diluted with ethyl acetate and washed with saturated sodium bicarbonate and saturated brine respectively. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and then separated by column chromatography to obtain compound G21 (yield see Example).

[1018] For aromatic rings containing electron-withdrawing substituents, the first step of coupling can also be achieved through aromatic substitution reaction (SN Ar The coupling of G22 and G17 occurred smoothly under alkaline conditions, and after derivatization and removal of Boc, it reacted with G20 to obtain G25.

[1019]

[1020] Nitro group reduction procedure: Dissolve the nitro-substituted compound to be reduced (1.0 equivalent) in ethanol, add an equal volume of saturated aqueous ammonium chloride solution, add reduced iron powder / zinc powder (20.0 equivalents), heat to reflux and stir under nitrogen for more than 2 hours, and monitor the reaction by thin-layer chromatography until completion. After cooling the reaction solution to room temperature, dilute it with a large amount of ethyl acetate and wash it with saturated aqueous sodium bicarbonate solution. The organic phase is dried over anhydrous sodium sulfate, and the aqueous phase is extracted twice with ethyl acetate. The organic phases are combined, dried over anhydrous sodium sulfate, filtered, and concentrated, and then separated by column chromatography to obtain the compound.

[1021] Hydrolysis operation: Same as above, alkaline hydrolysis of methyl ester to carboxylic acid.

[1022] Synthesis of pyrrole:

[1023]

[1024] Compound G26 (1.0 equivalent) was dissolved in anhydrous chloroform. Appropriate amounts of dry silica gel, compound G27 (5 equivalents), and anhydrous acetic acid (50 equivalents) were added. The mixture was then refluxed under nitrogen for at least 2 hours and monitored by thin-layer chromatography until completion. The mixture was cooled to room temperature, filtered to remove the solid, and the filter cake was washed with dichloromethane. The organic phase was concentrated under reduced pressure and separated using preparative thin-layer chromatography to yield the target compound G28 containing the pyrrole heterocycle.

[1025] General experimental operation four:

[1026]

[1027] N-Boc-3-hydroxyazetidine G29 (1 equivalent) was dissolved in dichloromethane and cooled under a nitrogen atmosphere. Triethylamine (1.5 equivalents) was added under ice-bath cooling, followed by the slow dropwise addition of methylsulfonyl chloride (1.5 equivalents). The reaction mixture was allowed to warm to room temperature for 2 hours. The solvent was removed by rotary evaporation under reduced pressure, and the mixture was diluted with a large amount of ethyl acetate and washed once with water. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to afford intermediate compound G30 as a pale yellow oil. Without further purification, G30 was dissolved in N,N-dimethylformamide, 4-hydroxybenzaldehyde G31 (1.2 equivalents) and cesium carbonate (2.2 equivalents) were added, and the mixture was heated to 100°C under nitrogen for overnight reaction. After cooling to room temperature, the reaction mixture was diluted with a large amount of ethyl acetate and washed twice with a saturated aqueous solution of ammonium chloride and once with a saturated aqueous solution of sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and isolated by silica gel column chromatography to afford compound G32 (54%).

[1028] Compound G32 (1 equivalent) was dissolved in a solvent, and sodium borohydride (3.0 equivalents) was added under nitrogen protection and ice-bath cooling. A small amount of methanol was then added and the reaction was allowed to react at room temperature for 2 hours. The reaction was quenched with saturated aqueous ammonium chloride, the solvent was removed by rotary evaporation under reduced pressure, and the mixture was extracted with a large amount of ethyl acetate. The organic phase was washed three times with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain compound G33. Compound G33 was dissolved in an appropriate amount of dichloromethane and treated with excess trifluoroacetic acid to remove the Boc protection and obtain compound G34.

[1029] Route 1: Compound G33 (1 equivalent) and imidazole (2.0 equivalents) were dissolved in dichloromethane. Under nitrogen protection and ice-bath cooling, tert-butyldiphenylsilyl chloride (TBDPSCl) (1.5 equivalents) was added and the mixture was allowed to react at room temperature overnight. After quenching the reaction with water, the solvent was removed by rotary evaporation under reduced pressure and extracted with a large amount of ethyl acetate. The organic phase was washed three times with pure water, dried over anhydrous sodium sulfate, filtered, concentrated, and then isolated by silica gel column chromatography to obtain the protected product (88%). The protected product (1.0 equivalent) was dissolved in dichloromethane, and diisopropylethylamine (5.0 equivalents) was added under ice-bath cooling, followed by the dropwise addition of trimethylsilyl trifluoromethanesulfonate (TMSOTf) (4.0 equivalents). The reaction was allowed to react at room temperature for 2 hours. The reaction was quenched with saturated aqueous ammonium chloride and extracted with a large amount of ethyl acetate. The organic phase was washed twice with saturated sodium bicarbonate solution and once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then separated by silica gel column chromatography to obtain the Boc-free secondary amine intermediate (yield 100%). The secondary amine intermediate (1.0 equivalent), substituted halobenzoic acid methyl ester G35 (1.0 equivalent), tetrakis(triphenylphosphine)palladium (0.05 equivalent), cesium carbonate (2.0 equivalent), and triphenylphosphine (0.15 equivalent) were dissolved in N,N-dimethylformamide and reacted at 110°C overnight under nitrogen. After cooling to room temperature, the mixture was diluted with a large amount of ethyl acetate and washed twice with saturated ammonium chloride solution and once with saturated sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and separated by preparative thin-layer chromatography to obtain the coupled compound (65%). The coupling compound (1.0 equivalent) was dissolved in tetrahydrofuran, and tetrabutylammonium fluoride (2.0 equivalent, 1 mol / L tetrahydrofuran solution) was added. The reaction was allowed to react at room temperature for 3 hours. The reaction was quenched with saturated aqueous ammonium chloride, the solvent was removed by rotary evaporation under reduced pressure, and then extracted with a large amount of ethyl acetate. The organic phase was washed twice with saturated aqueous ammonium chloride and once with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, concentrated, and isolated by silica gel column chromatography to obtain compound G36 (yield see Example). The hydrolysis reaction to obtain G37 was the same as above (omitted).

[1030] Route 2: Intermediate G34 (1.0 equivalent), methyl 3-fluoro-2-nitrobenzoate G38 (1.0 equivalent), and cesium carbonate (2.0 equivalent) were dissolved in N,N-dimethylformamide and heated to 50°C under nitrogen for 2 hours. The reaction solution was cooled to room temperature, diluted with a large amount of ethyl acetate, and washed three times with a saturated aqueous solution of ammonium chloride. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated, and isolated by silica gel column chromatography to obtain compound G39 (74%). The nitro group reduction, pyrrole synthesis, and hydrolysis steps to obtain G40-G42 were the same as above (omitted).

[1031] Route 3: Compound G40 (1 equivalent) was dissolved in 1,4-dioxane-water. Concentrated hydrochloric acid was added under ice-cooling. Stirring was continued for 10 minutes, followed by the slow addition of an aqueous solution of sodium nitrite (1.1 equivalent). After 1 hour of reaction, an aqueous solution of potassium iodide (1.5 equivalents) was added under ice-cooling, and the mixture was slowly warmed to room temperature and reacted for 16 hours. Saturated sodium bicarbonate solution was added to adjust the pH to 7. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and separated by silica gel column chromatography to afford the iodinated intermediate (yield 20-50%). The iodinated intermediate and aromatic boronic acid (ArB(OH)2) (1.5 equivalents) were dissolved in tetrahydrofuran-water. Catalysts Pd(dppf)Cl2 (0.1 equivalent) and K2CO3 (3 equivalents) were added, and the mixture was heated to 90°C and reacted for 16 hours. After completion of the reaction, the residue was dissolved in ethyl acetate, washed twice with saturated brine, dried over anhydrous sodium sulfate, and separated by chromatographic analysis to afford compound G43. The reaction steps for preparing G44 by hydrolysis are the same as before (omitted).

[1032] General experimental operation five:

[1033]

[1034] The above synthetic routes are all achieved by using the reaction route shown in "General Experimental Operation 4" by changing the substituent form of G45. The experimental operations are omitted.

[1035] General experimental operation six:

[1036]

[1037] Compound G57 (1 equivalent) and phenol compound G58 (1.2 equivalents) were dissolved in dichloromethane. Triphenylphosphine (2.2 equivalents) and diethyl azodicarboxylate (DEAD) (2.0 equivalents) were added under nitrogen protection and ice-bath cooling. The reaction was allowed to react overnight at room temperature. After quenching the reaction with water, the solvent was removed by rotary evaporation under reduced pressure, and the mixture was extracted with a large amount of ethyl acetate. The organic phase was washed three times with pure water, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography or thin-layer preparative chromatography to obtain intermediate G59.

[1038] The esterification reaction of compound G57 was carried out in the same manner as before (omitted).

[1039] The procedure for obtaining the amino intermediate G62 by azidation-reduction of compound G57 and the subsequent reaction with an electrophilic reagent are the same as above (omitted).

[1040] The hydrolysis reaction is carried out in the same manner as above (omitted). Note that some thiourea compounds G69 are unstable and will partially decompose into urea structures during the hydrolysis process.

[1041] General experimental operation seven:

[1042]

[1043] Compound G71 (1 equivalent) and compound G38 (1 equivalent) were dissolved in DMF. Potassium carbonate (4 equivalents) was added and the mixture was heated to 60°C for 3 hours. After the reaction, the mixture was quenched with water and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography to obtain G72 (yield 89%). G72 was dissolved in dichloromethane, imidazole (2 equivalents) and TBSCl (1.5 equivalents) were added, stirred at room temperature for 1 hour, quenched with water, and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography to obtain a silyl ether intermediate (yield 90%). The silyl ether intermediate was dissolved in ethanol, reduced iron powder (7.5 equivalents) was added, and then a saturated ammonium chloride solution was added. The mixture was refluxed at 75°C for 1 hour. After the reaction, the solid was removed by filtration and extracted with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated, and the residue was separated by silica gel column chromatography to give G73 (yield 71%).

[1044] The synthesis of pyrrole was the same as above (omitted). The intermediate forming the pyrrole ring was dissolved in dichloromethane, and tetra-tert-butylammonium fluoride (TBAF, 1.2 equivalents) was added under ice-cooling. After reacting at room temperature for 1 hour, the mixture was diluted with a large amount of dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was separated by silica gel column chromatography to obtain G74 (yield 90%).

[1045] Compound G74 (1 equivalent) was dissolved in toluene, and cuprous iodide (0.15 equivalent), the ligand 3,4,7,8-tetramethyl-1,10-phenanthroline (0.3 equivalent), and cesium carbonate (2 equivalents) were added. The displacement system was an inert nitrogen atmosphere. Iodide G75 (1 equivalent) was added, and the reaction was stirred at 110°C for 12 hours. After completion of the reaction, the solvent was evaporated and G76 was isolated by thin-layer preparative chromatography (yield see Example).

[1046] The steps for hydrolysis to obtain G77 are the same as above (omitted).

[1047] General experimental operation eight:

[1048]

[1049] The synthesis of compound G74 was the same as above (omitted).

[1050] Compound G74 (1 equivalent), boronic acid compound G78 (3 equivalents), anhydrous copper acetate (0.3 equivalent), and 40-60 mesh 4A molecular sieves were dissolved in dichloromethane. The oxygen atmosphere was replaced, and triethylamine was added to react with stirring at 35°C for 12 hours. After filtration and concentration, the residue was separated by thin-layer preparative chromatography to obtain product G76 (yield see Example).

[1051] The steps for hydrolysis to obtain G77 are the same as above (omitted).

[1052] General experimental operation nine:

[1053]

[1054] The synthesis of compound G74 was the same as above (omitted).

[1055] Compound G74 (1 equivalent), fluorinated compound G79 (2 equivalents), and anhydrous cesium carbonate (2 equivalents) were dissolved in DMF and heated to 100°C for 12 hours. After the reaction, the mixture was filtered and concentrated, and the residue was separated by thin-layer preparative chromatography to obtain product G80 (yield see Example).

[1056] The steps for hydrolysis to obtain G81 are the same as above (omitted).

[1057] General experimental operation 10:

[1058]

[1059] The nitro reduction reaction operation is the same as before (omitted).

[1060] The reaction operation of coupling with electrophilic reagent to form amide is the same as before (omitted).

[1061] The hydrolysis reaction is carried out in the same manner as above (omitted). Note that some thiourea compounds are unstable and will decompose into urea structures during the hydrolysis process.

[1062] General experimental operation 11:

[1063]

[1064] Compound G74 (1 equivalent) was dissolved in dry tetrahydrofuran and sodium hydride (1.5 equivalents) was added under ice-cooling, followed by compound G92 (1.2 equivalents) and a catalytic amount of tetrabutylammonium iodide (0.2 equivalents). After reacting at room temperature for 1 hour, the mixture was quenched with ice water and extracted with ethyl acetate. The organic phase was washed with saturated aqueous ammonium chloride, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography to yield compound G93 (yield see Example). The hydrolysis reaction to obtain compound G94 was performed in the same manner as above (omitted).

[1065] The reaction procedure of compound G74 with electrophi...

Claims

1. A compound of general formula (I), or a salt and / or isotope-substituted derivative thereof: in: X 1 , X 2 , X 3 are the same or different and are independently selected from CR xa ; R xa is selected from hydrogen and halogen; the halogen is selected from fluorine, chlorine, bromine and iodine; R 1 Selected from -COOH, -C(=O)-OR 1a 、-C(=O)-NR 1b R 1c 、-C(=O)-NH-S(=O)2-R 1b 、-S(=O)2OH、- S(=O)2-NR 1b R 1c , Among them, R 1a Independently selected from: Li; or R 1a , R 1b , R 1c are the same or different and are independently selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl; or R 1a , R 1b , R 1c are identical or different and are independently selected from: aryl, heterocyclyl, heteroaryl; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 4 Replace once or more times the same or differently; or, R 1b With R 1c Together with the atoms to which they are attached, they form a cyclic group; the cyclic group is selected from: optionally substituted morpholinyl, optionally substituted pyrrolidinyl, optionally substituted piperazinyl; R 2 Selected from the following groups: Amino, nitro, The dots Indicates the R 2 The point of attachment of the group to other groups of the compound molecule of the general formula (I); X 4 Selected from O, S, NR 2d ; Where R 2a , R 2b , R 2c are identical or different and are independently selected from: Hydrogen, halogen, amino, nitro, hydroxy, C1-C8 hydroxyalkyl, cyano, -(CH2) q -COOH, -(CH2) q -C(=O)-OR 8 、-(CH2) q -C(=O)-NH-R 8 、-N(H)C(=O)-R 8 、-N(H)S(=O)2-R 8 、-OR 8 、-NH-R 8 、- S(=O)2NH-R 8 、-S(=O)2-R 8 , -C(=O)-R 8 、-OC(=O)-R 8 , optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, phenyl, the phenyl being optionally substituted by R 4 Replace once or more times the same or differently; q is 0, 1, 2, or 3; or, R 2a Selected from aryl, heterocyclic, heteroaryl: The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 4 Replace once or more times the same or differently; Or, adjacent R 2a Together with the atoms to which they are attached, they form a ring structure, or adjacent R 2b The atoms connected to them form a ring structure, wherein the ring structure is selected from: phenyl, heteroaryl, and the heteroaryl is selected from: thienyl, furyl, pyrrolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the phenyl and heteroaryl are optionally substituted by R 4 Replace once or more times the same or differently; R 2d Selected from hydrogen, optionally halogenated or non-halogenated C1-C3 straight chain alkyl, isopropyl, cyclopropyl; or, R 2d Selected from: -C(=O)-R 5 、-S(=O)2-R 5 ; or, R 2d is selected from aryl, heterocyclyl, heteroaryl; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 4 Replace once or more times the same or differently; L is selected from the following groups: The dots represents the connection point where L is connected to the right fragment of the compound of general formula (I); The asterisk * indicates L and R 3 connected connection points; The L is substituted by R L1 Substitution is performed once or multiple times at the same or different sites; R L1 Selected from: hydrogen or fluorine atoms; R L2 is selected from the group consisting of: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl; or, R L2 Selected from: -(CH2) q -R 7 、-C(=O)-N(H)-R 19 , -C(=S)-N(H)-R 19 , -C(=O)-R 20 、-S(=O)2-R 20 ; or, R L2 Selected from: aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; or R L2 and R 3 Together with the atoms to which they are attached, they are cyclized to form a 5-10 membered nitrogen- and / or sulfur-containing heterocyclic group, wherein the 5-10 membered nitrogen- and / or sulfur-containing heterocyclic group comprises a -C(=O)-, -S(=O)2- group; R 3 Selected from the following groups: C3-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl; the C3-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl are optionally substituted by R 6 Replace once or more times the same or differently; or, R 3 Selected from the following groups: The dots represents the connection point to the right fragment of the compound of general formula (I); X 6 Selected from O, S, NR 3g ; X 7 Selected from O, S, NR 3g , CHR 3a ; Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced; Z 1 Selected from O, S, NR 3h ; Where R 3a is selected from the group consisting of: hydrogen, halogen, nitro, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, hydroxyl, C1-C8 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C8 hydroxyalkyl is a C1-C8 alkyl substituted with a hydroxyl group; p and q are independently 0, 1, 2 or 3; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; or adjacent R 3a Together with the atoms to which they are attached, they form a ring structure, or R 3a and its adjacent R 3c and together with the atoms to which they are attached form a ring structure, or R 3a and its adjacent R 3d and forming a ring structure together with the atoms to which they are attached, the ring structure comprising a saturated or aromatic ring structure selected from the group consisting of: cycloalkanes, aryls, heterocyclyls, heteroaryls; Or, the ring structure is selected from: phenyl, pyridyl, pyrrolyl, thienyl, furanyl, oxazolyl, thiazolyl, isoxazolyl, indazolyl, 5-7 membered nitrogen / oxygen saturated heterocyclic group, and the saturated heterocyclic group is selected from: tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The cyclic structure is optionally substituted by a group R 18 Replace once or more times the same or differently; R 3b Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, -C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 、-S(=O)2-R 20 ; or, R 3b Selected from: aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; q is 0, 1, 2, or 3; The aryl group is selected from: optionally substituted phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; When L is selected from When R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 20 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; The aryl group is selected from: optionally substituted phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; or R 3c and R 3d and together with the atoms to which they are attached, form carbonyl, thiocarbonyl, and imine groups; R 3e and R 3f are identical or different and are independently selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, -C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 、-S(=O)2-R 20 ; or, R 3e and R 3f and together with the atoms to which they are attached, form carbonyl and thiocarbonyl groups; or, R 3e and R 3f are identical or different and are independently selected from: aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; The aryl group is selected from: optionally substituted phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; R 3h Selected from: hydrogen, nitro, cyano; or, R 3 Selected from: When L is selected from When R 3 Selected from: The R 4 is selected from the group consisting of: hydrogen, fluorine, chlorine, hydroxy, C1-C3 hydroxyalkyl, optionally substituted C1-C3 alkyl, optionally substituted C1-C3 alkoxy, nitro, cyano, amino, acetyl, methylsulfonyl, acetamido, methylsulfonamido; The R 5 is selected from: hydrogen, optionally substituted C1-C3 alkyl; The R 6 Selected from: hydroxyl, C1-C8 straight chain alkoxy, C3-C8 branched chain alkoxy, C3-C8 cycloalkoxy, -OC(=O)-R 20 , amino, -NH-C(=O)-R 20 、-NH-S(=O)2-R 20 、-NH-C(=O)-OR 20 、-NH-C(=O)-NH-R 20 、-NH-C(=S)-NH-R 20 ; The R 7 is selected from: phenyl, naphthyl, heterocyclic group, heteroaryl, the heterocyclic group is selected from: 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the heteroaryl is selected from: thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl, the phenyl, naphthyl, heterocyclic group, heteroaryl are optionally substituted by R 18 Replace once or more times the same or differently; The R 8 Selected from: optionally substituted C1-C3 alkyl; The R 9 , R 10 The same or different and independently selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy; or, R 9 , R 10 are the same or different and are independently selected from: optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; Or the R 9 , R 10 and together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group, the nitrogen-containing heterocyclic group is selected from: azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, the nitrogen-containing heterocyclic group is substituted one or more times, identically or differently, with the following substituents: hydroxyl, C1-C8 hydroxyalkyl, C1-C8 straight-chain alkyl or alkoxy, C3-C8 branched-chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight-chain alkyl or alkoxy, halogenated C3-C8 branched-chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, amino, optionally substituted amide, optionally substituted sulfonamide; The R 11 is selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy; or, R 11 Selected from: aryl, heterocyclic, heteroaromatic; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic group, and aromatic hetero group are substituted one or more times, identically or differently, with the following substituents: halogen, hydroxyl, C1-C8 hydroxyalkyl, C1-C8 straight-chain alkyl or alkoxy, C3-C8 branched-chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight-chain alkyl or alkoxy, halogenated C3-C8 branched-chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, amino, optionally substituted amide, optionally substituted sulfonamide, cyano, nitro, sulfonic acid, optionally substituted urea, and guanidinyl; The R 12 Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl, aryl, heterocyclic group, aromatic hetero group; the C1-C8 alkyl group is substituted one or more times with the following substituents, the same or different: -OR 20 、-OH、-N(H)C(=O)-R 20 、-NR 9 R 10 ; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; The R 13 is selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy; Or, the R 13 Selected from: -(CH2) q -phenyl, -(CH2) q -halophenyl, -(CH2) q -Naphthyl, -(CH2) q -halonaphthyl, -(CH2) q -Anthracene, -(CH2) q -halogenated anthracene, -(CH2) q -heterocyclic group, -(CH2) q -halogenated heterocyclic group, -(CH2) q -heteroaryl, -(CH2) q - halogenated heteroaryl; q is 0, 1, 2, or 3; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The phenyl, naphthyl, anthracenyl, heterocyclic group, heteroaryl group may be optionally substituted by R 18 Replace once or more times the same or differently; The R 14 Selected from: heteroaryl, the heteroaryl is selected from: thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the heteroaryl is optionally substituted by R 18 Replace once or more times the same or differently; The R 15 is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the saturated heterocyclic group is optionally substituted by R 18 Replace once or more times the same or differently; The R 16 is selected from the group consisting of: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched or cycloalkyl, optionally substituted acyl, optionally substituted sulfonyl; or, R 16 is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; the saturated heterocyclic group is optionally substituted by R 18 Replace once or more times the same or differently; or, R 16 Selected from: aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl group is selected from: phenyl, naphthyl, anthracenyl; the aromatic heteroyl group is selected from: thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, benzothiazolyl; the aryl and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; q is 0, 1, 2, or 3; The R 17 Selected from: optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted heterocyclic group, optionally substituted heteroaromatic group; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The R 18 is selected from the group consisting of: hydrogen, halogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C8 hydroxyalkyl, aryloxy, heterocyclyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl, aryl, heterocyclic group, heteroaromatic group; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 4 Replace once or more times the same or differently; The R 19 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl, heterocyclic group, aromatic hetero group; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; The R 20 Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl, heterocyclic group, aromatic hetero group; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; wherein p and q are independently 0, 1, 2 or 3.

2. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, which is at least one compound selected from the following formulae:

3. The compound according to claim 1, or its salt and / or isotope-substituted derivative, wherein: R 2 Selected from the following groups: Amino, nitro, The dots Indicates the R 2 The point of attachment of the group to other fragments of the compound of formula (I); X 4 Selected from O, S, NR 2d ; Where R 2a , R 2b , R 2c are identical or different and are independently selected from: Hydrogen, halogen, amino, nitro, hydroxy, C1-C8 hydroxyalkyl, cyano, -(CH2) q -COOH, -(CH2) q -C(=O)-OR 8 、-(CH2) q -C(=O)-NH-R 8 、-N(H)C(=O)-R 8 、-N(H)S(=O)2-R 8 、-OR 8 、-NH-R 8 、-S(=O)2NH-R 8 、-S(=O)2-R 8 , -C(=O)-R 8 , optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, phenyl, the phenyl being optionally substituted by R 4 Replace once or more times the same or differently; q is 0, 1, 2, or 3; R 2d Selected from: hydrogen, optionally fluorinated or non-fluorinated C1-C3 straight chain alkyl, isopropyl, cyclopropyl, -C(=O)- R 5 、-S(=O)2-R 5 。 4. The compound according to claim 1, or its salt and / or isotope-substituted derivative, wherein: L is selected from the following groups: The dots represents the connection point where L is connected to the right fragment of the compound of general formula (I); The asterisk * indicates L and R 3 connected connection points; The L is substituted by R L1 Substitution is performed once or multiple times at the same or different sites; R L1 Selected from: hydrogen or fluorine atoms; R L2 is selected from the group consisting of: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl; or, R L2 Selected from: -(CH2) q -R 7 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 , -C(=O)-R 20 、-S(=O)2-R 20 ; or R L2 and R 3 Together with the atoms to which they are attached, they are cyclized to form a 5-10 membered nitrogen- and / or sulfur-containing heterocyclic group, wherein the 5-10 membered nitrogen- and / or sulfur-containing heterocyclic group comprises a -C(=O)-, -S(=O)2- group; q is 0, 1, 2, or 3; The R 7 is selected from: phenyl, heterocyclic group, heteroaryl, the heterocyclic group is selected from: 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl; the heteroaryl is selected from: thienyl, furanyl, pyrrolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl, the phenyl, heterocyclic group, heteroaryl are optionally substituted by R 18 Replace once or more times the same or differently; R 18 is selected from the group consisting of: hydrogen, F, Cl, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C8 hydroxyalkyl, phenyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl, aryl, heterocyclic group, heteroaromatic group; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 4 One or more substitutions may be identical or different.

5. The compound according to claim 1, or its salt and / or isotope-substituted derivative, wherein: R 3 Selected from the following groups: The dots represents the connection point to the right fragment of the compound of general formula (I); X 6 Selected from O, S, NR 3g ; X 7 Selected from O, S, NR 3g , CHR 3a ; Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced; Z 1 Selected from O, S, NR 3h ; Where R 3a Selected from: hydrogen, halogen, nitro, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl is a C1-C6 alkyl substituted with a hydroxyl group; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; p and q are independently 0, 1, 2 or 3; R 3b Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl or heteroaryl may be optionally substituted with R 18 Replace once or more times the same or differently; q is 0, 1, 2, or 3; R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl; When L is selected from When R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 20 ; or R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C8 alkyl, hydroxy, C1-C8 hydroxyalkyl, -OC(=O)-R 8 ; or R 3c and R 3d Together with the atoms to which they are attached, they form carbonyl, thiocarbonyl, and imino groups; R 3e and R 3f are identical or different and are independently selected from: Hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; The aryl and heteroaryl groups are optionally substituted with R 18 one or more times identically or differently substituted, or, R 3e and R 3f and together with the atoms to which they are attached, form carbonyl and thiocarbonyl groups; or, R 3 Selected from: When L is selected from When R 3 Selected from:

6. The compound according to claim 1, or its salt and / or isotope-substituted derivative, wherein: R 1 Also selected from: -C(=O)-NH-(CH2) q -R 1d , q is 0, 1, 2, or 3; R 1d Selected from: hydrogen, hydroxyl, cyano, -NR 9 R 10 , optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl; The aryl group is selected from: phenyl, naphthyl, anthracenyl; The heterocyclic group is selected from: a 4-7 membered saturated heterocyclic group containing oxygen, nitrogen, and / or sulfur, and the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, thiazolyl, pyridinyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, indazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzotriazolyl, and benzothiazolyl.

7. The compound according to claim 1, or its salt and / or isotope-substituted derivative, wherein: R 1 Selected from -COOH, -C(=O)-OR 1a 、-C(=O)-NH-S(=O)2-R 1b 、-C(=O)-NH-(CH2) q -R 1d , Among them, R 1a Selected from: Li; or R 1a , R 1b , R 1c are the same or different and are independently selected from: hydrogen, optionally substituted C1-C4 straight chain alkyl, optionally substituted C3-C4 branched or cycloalkyl, optionally substituted halogenated C1-C4 straight chain alkyl, optionally substituted halogenated C3-C4 branched or cycloalkyl; or R 1a , R 1b , R 1c are the same or different and are independently selected from: phenyl, thienyl, furanyl, imidazolyl; R 1d Selected from hydroxyl, cyano, -NR 9 R 10 , aryl, heterocyclyl, heteroaryl; The aryl group is selected from: phenyl; The heterocyclic group is selected from: azetidinyl, pyrrolidinyl; The heteroaryl group is selected from: thienyl, furyl; The R 9 , R 10 are the same or different and are independently selected from: hydrogen, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 alkoxy; or, R 9 , R 10 are the same or different and are independently selected from: optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; Or the R 9 , R 10 and together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group, wherein the nitrogen-containing heterocyclic group is selected from: azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl; q is 0, 1, 2, or 3.

8. The compound according to claim 1, or its salt and / or isotope-substituted derivative, wherein: R 2 Selected from: amino, nitro, optionally substituted pyrrolyl, optionally substituted benzofuranyl, optionally substituted indolyl, optionally substituted benzothiophenyl, optionally substituted phenyl, optionally substituted benzothiadiazolyl, optionally substituted furanyl, optionally substituted pyrazolyl, optionally substituted indazolyl, optionally substituted benzothiazolyl, optionally substituted pyridinyl, optionally substituted imidazolyl, optionally substituted thienyl.

9. The compound according to claim 7, or its salt and / or isotope-substituted derivative, wherein: R 2 Selected from: amino, nitro, pyrrolyl, benzofuranyl, indolyl, benzo[b]thienyl, phenyl, halophenyl, cyanophenyl, cyanohalophenyl, carboxyphenyl, halo-substituted C1-C4 alkylphenyl, biphenyl, methylsulfonylaminophenyl, acetylphenyl, methylsulfonylphenyl, aminosulfonylphenyl, C1-C4 alkoxyphenyl, benzo[c][1,2,5]thiadiazolyl, furanyl, pyrazolyl, indazolyl, benzo[d]thiazolyl.

10. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, wherein: L is selected from: R 2 Selected from: amino, nitro, X 4 Selected from NR 2d ; Where R 2a , R 2b , R 2c are the same or different and are independently selected from: hydrogen, fluorine, optionally substituted C1-C4 straight chain alkyl or alkoxy, optionally substituted C3-C4 branched chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy; R 3 Selected from: in, R 3a Selected from: hydrogen, -(CH2) q -NR 9 R 10 , nitro, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, -(CH2) q -COOH, -C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NR 16 -S(=O)2-R 17 .

11. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, wherein: L is selected from: R 2 Selected from: amino, X 4 Selected from O, S, NR 2d ; Where R 2a , R 2b , R 2c are identical or different and are independently selected from: Hydrogen, halogen, cyano, -(CH2) q -COOH, -OR 8 、-N(H)S(=O)2-R 8 、-S(=O)2-R 8 , -C(=O)-R 8 、-OC(=O)-R 8 , C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenyl, the phenyl is optionally substituted by R 4 Replace once or more times the same or differently; R 3 Selected from: in R 3a Selected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl is a C1-C6 alkyl substituted with a hydroxyl group; The R 9 , R 10 are the same or different and are independently selected from: hydrogen, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 alkoxy; or, R 9 , R 10 are the same or different and are independently selected from: optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaromatic group; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; Or the R 9 , R 10 and together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group, wherein the nitrogen-containing heterocyclic group is selected from: azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl; The R 11 is selected from: hydrogen, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy; or, R 11 Selected from: aryl, heterocyclic, heteroaromatic; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl, heterocyclic group, and aromatic hetero group are substituted one or more times, identically or differently, with the following substituents: halogen, hydroxyl, C1-C6 hydroxyalkyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl or alkoxy, amino, acetyl, acetamido, methylsulfonamido, methylbenzenesulfonamido, cyano, nitro, sulfonic acid, urea, and guanidinyl; The R 12 Selected from: hydrogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl, heterocyclic group, aromatic hetero group; the C1-C6 alkyl is substituted one or more times by the following substituents, the same or different: -OR 20 、-OH、-N(H)C(=O)-R 20 、-NR 9 R 10 ; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The phenyl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; The R 13 is selected from: hydrogen, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy; or, said R 13 Selected from: -(CH2) q -phenyl, -(CH2) q -halophenyl, -(CH2) q -heterocyclic group, -(CH2) q -halogenated heterocyclic group, -(CH2) q -heteroaryl, -(CH2) q - halogenated heteroaryl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The phenyl, heterocyclic, heteroaryl groups are optionally substituted one or more times by the following substituents: methyl, ethyl, Cl, F, cyano; The R 15 Selected from: 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic groups, wherein the saturated heterocyclic groups are selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The R 17 Selected from: optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted aryl, optionally substituted heterocyclic group, optionally substituted aromatic hetero group; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; or the R 17 Selected from: methyl, cyclopropane, phenyl, thienyl, indolyl; the phenyl, thienyl, indolyl are optionally substituted one or more times with the following substituents: methyl, ethyl, Cl, F, cyano; The R 18 is selected from: hydrogen, F, Cl, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C6 hydroxyalkyl, phenyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl; The R 20 Selected from: hydrogen, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched alkyl, optionally substituted C3-C6 cycloalkyl, phenyl, morpholinyl; the phenyl is substituted one or more times by the following substituents: methyl, ethyl, Cl, F, cyano; p and q are independently 0, 1, 2 or 3; or, R 3 Selected from or, R 3 Selected from: in X 6 Selected from O, S, NR 3g , Y 2 Selected from CH, CR 3a , N, and Y 2 A C atom at any position on the aromatic ring can be replaced, R 3a Selected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl is a C1-C6 alkyl substituted with a hydroxyl group; R 3g Selected from: hydrogen, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl group are optionally substituted R 4 Replace once or more times the same or differently; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The sulfonyl group is selected from: methylsulfonyl, optionally substituted benzenesulfonyl; The acyl group is selected from: acetyl, optionally substituted benzoyl; The benzenesulfonyl group and benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F; or, R 3 Selected from: where Y 2 Selected from CH, CR 3a , N, and Y 2 A C atom at any position on the aromatic ring can be replaced, R 3a Selected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl is a C1-C6 alkyl substituted with a hydroxyl group; or, R 3 Selected from: in X 6 Selected from O, S, NR 3g , Y 2 Selected from CH, CR 3a , N, and Y 2 A C atom at any position on the aromatic ring can be replaced, R 3a Selected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl is a C1-C6 alkyl substituted with a hydroxyl group; R 3g Selected from: hydrogen, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl group are optionally substituted R 4 Replace once or more times the same or differently; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The sulfonyl group is selected from: methylsulfonyl, optionally substituted benzenesulfonyl; The acyl group is selected from: acetyl, optionally substituted benzoyl; The benzenesulfonyl group and benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F; R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C6 alkyl; or R 3c and R 3d and together with the atoms to which they are attached, form carbonyl, thiocarbonyl, and imine groups; or, R 3 Selected from: in Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced; R 3a Selected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl is a C1-C6 alkyl substituted with a hydroxyl group; R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C6 alkyl; or R 3c and R 3d and together with the atoms to which they are attached, form carbonyl, thiocarbonyl, and imine groups; or, R 3 Selected from: in X 7 Selected from O, NR 3g , Z 1 Selected from O, S, R 3b Selected from: Optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl or heteroaryl may be optionally substituted with R 18 Replace once or more times the same or differently; The R 18 is selected from the group consisting of: hydrogen, halogen, optionally substituted C1-C6 straight chain alkyl or alkoxy, optionally substituted C3-C6 branched chain alkyl or alkoxy, optionally substituted C3-C6 cycloalkyl or alkoxy, nitro, optionally substituted amino, hydroxy, C1-C6 hydroxyalkyl, aryloxy, heterocyclyloxy, heteroaryloxy, -(CH2) q -COOH, -OC(=O)-R 20 , optionally substituted amide, cyano, sulfonic acid, optionally substituted sulfonamide, optionally substituted acyl, optionally substituted sulfonyl, aryl, heterocyclic group, heteroaromatic group; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 4 Replace once or more times the same or differently; q is 0, 1, 2, or 3; R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the aryl, heterocyclic group, heteroaryl group is optionally substituted by R 4 Replace once or more times the same or differently; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; R 3c and R 3d are the same or different and are independently selected from: hydrogen, fluorine, C1-C6 alkyl; or, R 3 Selected from: in X 6 Selected from O, S, NR 3g ; X 7 Selected from O, S, NR 3g ; Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced; R 3a Selected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl is a C1-C6 alkyl substituted with a hydroxyl group; R 3b Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -、-C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 ; The aryl and heteroaryl groups are optionally substituted with R 18 Replace once or more times the same or differently; R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl group are optionally substituted R 4 Replace once or more times the same or differently; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The sulfonyl group is selected from: methylsulfonyl, optionally substituted benzenesulfonyl; The acyl group is selected from: acetyl, optionally substituted benzoyl; The benzenesulfonyl group and benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F; or, R 3 Selected from: X 7 Selected from O, NR 3g , Y 2 Selected from CH, CR 3a , N, and Y 2 The C atom at any position on the aromatic ring can be replaced; wherein R 3a Selected from: hydrogen, halogen, nitro, cyano, optionally substituted C1-C6 straight chain alkyl, optionally substituted C3-C6 branched chain alkyl, optionally substituted C3-C6 cycloalkyl, hydroxyl, C1-C6 hydroxyalkyl, -(CH2) q -COOH, -(CH2) q -OR 12 、-(CH2) q -O-(CH2) p -R 11 、-(CH2) q -NH-(CH2) p -R 11 、-(CH2) q -S-(CH2) p -R 11 , -C(=O)-R 20 , -C(=O)-NHR 13 、-(CH2) q -OC(=S)-NHR 13 、-(CH2) q -OC(=O)-R 13 、-C(=O)-OR 20 、-(CH2) q -NH-C(=O)-R 11 、-(CH2) q -NH-C(=O)-NH-R 17 、-NH-C(=S)-NH-R 17 、-(CH2) q -NR 16 -S(=O)2-R 17 、-N(SO2R 17 2. -R 14 -NH-S(=O)2-R 20 、-(CH2) q -R 15 、-NH-C(=O)-OR 13 、-(CH2) q -C(=O)NR 9 R 10 、-(CH2) q -NR 9 R 10 、-(CH2) q -S(=O)2-(CH2) p -R 11 、Aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; the C1-C6 hydroxyalkyl is a C1-C6 alkyl substituted with a hydroxyl group; R 3b Selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -、-C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=S)N(H)-R 19 、-C(=O)OR 19 ; The phenyl, aryl, heteroaryl are optionally substituted by R 18 Replace once or more times the same or differently; R 3g Selected from: hydrogen, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl group are optionally substituted R 4 Replace once or more times the same or differently; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The sulfonyl group is selected from: methylsulfonyl, optionally substituted benzenesulfonyl; The acyl group is selected from: acetyl, optionally substituted benzoyl; The benzenesulfonyl group and benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F; R 3e and R 3f are identical or different and are independently selected from: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -、-C(=O)-R 20 、-C(=O)N(H)-R 19 、-C(=O)OR 19 、-S(=O)2-R 20 ; or, R 3e and R 3f and together with the atoms to which they are attached, form a carbonyl group; or, R 3e and R 3f are the same or different and are independently selected from: aryl, heterocyclic, heteroaromatic; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 One or more substitutions may be identical or different.

12. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, wherein: L is selected from: R L1 Selected from: hydrogen, F, R L2 Selected from: hydrogen, R 2 Selected from: X 4 Selected from NR 2d ; Where R 2a , R 2b , R 2c are the same or different and are independently selected from: hydrogen, fluorine, optionally substituted C1-C4 straight chain alkyl or alkoxy, optionally substituted C3-C4 branched chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy; R 3 Selected from: C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl; the C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl are optionally substituted by R 6 Replace once or more times the same or differently; or, R 3 Selected from: in X 7 Selected from: NR 3g , Z 1 Selected from: O, S, q is 0, 1, 2, or 3; R 3b Selected from: Optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; R 3g Selected from: hydrogen; or, R 3 Selected from: Where R 3b Selected from: Optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; the aryl or heteroaryl may be optionally substituted with R 18 Replace once or more times the same or differently; The aryl group is selected from: phenyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The R 18 Selected from: F, Cl, C1-C8 straight chain alkyl, C3-C8 branched chain alkyl, C3-C8 cycloalkyl, halogenated C1-C8 straight chain alkyl, halogenated C3-C8 branched chain alkyl, halogenated C3-C8 cycloalkyl; or, R 3 Selected from: or L is selected from: R L1 is hydrogen, R L2 For aryl-(CH2) q -; the aryl group is selected from: phenyl; R 2 Selected from: X 4 Selected from NR 2d ; Where R 2a , R 2b , R 2c are the same or different and are independently selected from: hydrogen, fluorine, optionally substituted C1-C4 straight chain alkyl or alkoxy, optionally substituted C3-C4 branched chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy; R 3 Selected from: in R 3b Selected from: Optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; The aryl group is selected from: phenyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl and heteroaryl groups are optionally substituted with R 18 One or more substitutions may be identical or different.

13. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, wherein: L is selected from: R L2 is selected from the group consisting of: hydrogen, optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl; R 2 Selected from: X 4 Selected from NR 2d ; Where R 2a , R 2b , R 2c are the same or different and are independently selected from: hydrogen, fluorine, optionally substituted C1-C4 straight chain alkyl or alkoxy, optionally substituted C3-C4 branched chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy; R 3 Selected from: in R 3b Selected from: Optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; The aryl group is selected from: phenyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl and heteroaryl groups are optionally substituted with R 18 Replace once or more times the same or differently; The R 18 Selected from: F, Cl, nitro, C1-C4 straight chain alkyl or alkoxy, C3-C4 branched chain alkyl or alkoxy, C3-C4 cycloalkyl or alkoxy, halogenated C1-C4 straight chain alkyl or alkoxy, halogenated C3-C4 branched chain alkyl or alkoxy, halogenated C3-C4 cycloalkyl or alkoxy, phenoxy; Or, L is selected from: R L2 Selected from: aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -, the aryl-(CH2) q - is selected from: phenyl-CH2-; the heterocyclic group-(CH2) q - is selected from: piperidinyl-CH2-; said heteroaryl-(CH2) q - is selected from: indolyl-CH2-, thienyl-CH2-, benzothienyl-CH2-, furyl-CH2-, benzofuranyl-CH2-, pyridinyl-CH2-, wherein phenyl, indolyl, thienyl, benzothienyl, furanyl, benzofuranyl, pyridinyl-, piperidinyl- is substituted one or more times by the following substituents selected from: halogen, cyano, -NR 9 R 10 , hydroxy, C1-C8 hydroxyalkyl, C1-C8 straight-chain alkyl or alkoxy, C3-C8 branched-chain alkyl or alkoxy, C3-C8 cycloalkyl or alkoxy, halogenated C1-C8 straight-chain alkyl or alkoxy, halogenated C3-C8 branched-chain alkyl or alkoxy, halogenated C3-C8 cycloalkyl or alkoxy, optionally substituted amide, optionally substituted sulfonamide; R 2 Selected from: X 4 Selected from NR 2d ; Where R 2a , R 2b , R 2c are the same or different and are independently selected from: hydrogen, fluorine, optionally substituted C1-C4 straight chain alkyl or alkoxy, optionally substituted C3-C4 branched chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy; R 3 Selected from: in R 3b Selected from: optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heteroaryl-(CH2) q -; The aryl group is selected from: phenyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl and heteroaryl groups are optionally substituted with R 18 Replace once or more times the same or differently; The R 18 is selected from: hydrogen, halogen, optionally substituted C1-C8 straight chain alkyl or alkoxy, optionally substituted C3-C8 branched chain alkyl or alkoxy, optionally substituted C3-C8 cycloalkyl or alkoxy, aryl, heteroaryl, heterocyclic group; the aryl group is selected from: phenyl; Or, L is selected from: R 2 Selected from: X 4 Selected from NR 2d ; Where R 2a , R 2b , R 2c are the same or different and are independently selected from: hydrogen, fluorine, optionally substituted C1-C4 straight chain alkyl or alkoxy, optionally substituted C3-C4 branched chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy; R L2 and R 3 Together with the atoms to which they are attached, they are cyclized to form a 5-10 membered nitrogen and / or sulfur heterocyclic group, wherein the 5-10 membered nitrogen and / or sulfur heterocyclic group includes a -C(=O)-, -S(=O)2- group.

14. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, wherein: L is selected from: in R L1 Selected from: hydrogen, fluorine; R 2 Selected from: amino, X 4 Selected from NR 2d ; Where R 2a , R 2b , R 2c are the same or different and are independently selected from: hydrogen, fluorine, optionally substituted C1-C4 straight chain alkyl or alkoxy, optionally substituted C3-C4 branched chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy; R 3 Selected from: in X 7 Selected from: O, NR 3g ; Z 1 Selected from: O; R 3b Selected from: Optionally substituted C1-C8 straight chain alkyl, optionally substituted C3-C8 branched chain alkyl, optionally substituted C3-C8 cycloalkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -; q is 0, 1, 2, or 3; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; R 3g Selected from: hydrogen, C1-C6 straight chain alkyl, C3-C6 branched chain alkyl, halogenated C1-C6 straight chain alkyl, halogenated C3-C6 branched chain alkyl, aryl-(CH2) q -, heterocyclic group -(CH2) q -, heteroaryl-(CH2) q -, optionally substituted sulfonyl, optionally substituted acyl; the aryl, heterocyclic group, heteroaryl group are optionally substituted R 4 Replace once or more times the same or differently; The aryl group is selected from: phenyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The sulfonyl group is selected from: methylsulfonyl, optionally substituted benzenesulfonyl; The acyl group is selected from: acetyl, optionally substituted benzoyl; The benzenesulfonyl group and benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F.

15. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, wherein: L is selected from: R L1 Selected from: hydrogen, fluorine; R 2 Selected from: amino, X 4 Selected from O, S, NR 2d ; Where R 2a , R 2b , R 2c are the same or different and are independently selected from: hydrogen, fluorine, optionally substituted C1-C4 straight chain alkyl or alkoxy, optionally substituted C3-C4 branched chain alkyl or alkoxy, optionally substituted C3-C4 cycloalkyl or alkoxy; R 3 Selected from: R 3a Selected from: hydrogen, halogen, nitro, cyano, hydroxyl, C1-C6 hydroxyalkyl, optionally substituted C1-C6 straight-chain alkyl, optionally substituted C3-C6 branched-chain alkyl, optionally substituted C3-C6 cycloalkyl; or, R 3 Selected from:

16. The compound according to any one of claims 1 to 9, or a salt and / or an isotope-substituted derivative thereof, wherein: L is selected from: Oxy-azetidin-1-yl, 3-amino-azetidin-1-yl, 3-amino(benzyl)-azetidin-1-yl, aminoethynyl, 3-alkenylazetidin-1-yl, 3-sulfanyl-azetidin-1-yl, 3-sulfinylazetidin-1-yl, 3-sulfonylazetidin-1-yl, 1H-1,2,3-triazol-4-yl; Wherein, the oxy-azetidinyl group is selected from: 3-oxy-azetidin-1-yl; The aminoethynyl group is selected from: aminoethynyl, amino(alkyl)ethynyl, amino(aryl-CH2-)ethynyl, amino(heterocyclyl-CH2-)ethynyl, amino(heteroaryl-CH2-)ethynyl, amino(sulfonyl)ethynyl; The alkyl group is selected from: an optionally substituted C1-C8 straight chain alkyl group, an optionally substituted C3-C8 branched chain alkyl group, and an optionally substituted C3-C8 cycloalkyl group; The aryl, heterocyclic and heteroaryl groups are optionally substituted by R 18 Replace once or more times the same or differently; The aryl group is selected from: phenyl, naphthyl; The heterocyclic group is selected from: a 4-7 membered oxygen- and nitrogen-containing saturated heterocyclic group, wherein the saturated heterocyclic group is selected from: oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, and piperazinyl; The heteroaryl group is selected from the group consisting of thienyl, furanyl, pyrrolyl, pyridyl, pyrimidinyl, indolyl, quinolyl, quinazolinyl, benzofuranyl, benzothienyl, benzoxazolyl, and benzothiazolyl; The sulfonyl group is selected from: methylsulfonyl, optionally substituted benzenesulfonyl; The acyl group is selected from: acetyl, optionally substituted benzoyl; The benzenesulfonyl group and benzoyl group are optionally substituted one or more times by the following substituents: methyl, ethyl, methoxy, Cl, F, cyano; the methyl, ethyl, methoxy group are optionally substituted one or more times by the following substituents: Cl, F.

17. The compound according to claim 16, or a salt and / or isotope-substituted derivative thereof, wherein: The amino(alkyl)ethynyl group is selected from: amino(methyl)ethynyl group; The amino(aryl-CH2-)ethynyl group is selected from the group consisting of amino(benzyl)ethynyl, amino(4-fluorobenzyl)ethynyl, amino(4-methylbenzyl)ethynyl, amino(4-trifluoromethylbenzyl)ethynyl, amino(methoxybenzyl)ethynyl, amino(2-fluorobenzyl)ethynyl, and amino(4-(hydroxymethyl)benzyl)ethynyl; The amino(heterocyclyl-CH2-)ethynyl group is selected from: amino((1-methylpiperidin-4-yl)methyl)ethynyl; The amino(heteroaryl-CH2-)ethynyl group is selected from the group consisting of amino(pyridin-3-ylmethyl)ethynyl, amino(furan-2-ylmethyl)ethynyl, amino(1-methyl-1H-indol-5-yl)methylethynyl, and amino(thiophen-2-ylmethyl)ethynyl; The amino(sulfonyl)ethynyl group is selected from the group consisting of amino(methylsulfonyl)ethynyl, amino(cyclopropylsulfonyl)ethynyl, amino(benzenesulfonyl)ethynyl, amino((4-methylphenyl)sulfonyl)ethynyl, amino(benzo[b]thiophene-3-sulfonyl)ethynyl, amino(thiophene-2-sulfonyl)ethynyl and amino(benzofuran-5-sulfonyl)ethynyl.

18. The compound according to any one of claims 1, 4, 5, 11-14, or a salt and / or an isotope-substituted derivative thereof, wherein: The optionally substituted C1-C8 straight-chain alkyl group is: an optionally substituted halogenated C1-C8 straight-chain alkyl group; Or, the optionally substituted C3-C8 branched alkyl group is: an optionally substituted halogenated C3-C8 branched alkyl group; Or, the optionally substituted C3-C8 cycloalkyl group is: optionally substituted halogenated C3-C8 cycloalkyl group.

19. The compound according to any one of claims 1, 3, 4, and 13, or a salt and / or an isotope-substituted derivative thereof, wherein: The optionally substituted C1-C8 straight-chain alkyl or alkoxy group is: an optionally substituted halogenated C1-C8 straight-chain alkyl or alkoxy group; Or, the optionally substituted C3-C8 branched alkyl or alkoxy group is: an optionally substituted halogenated C3-C8 branched alkyl or alkoxy group; Or, the optionally substituted C3-C8 cycloalkyl or alkoxy group is: an optionally substituted halogenated C3-C8 cycloalkyl or alkoxy group.

20. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, wherein: The optionally substituted C1-C3 alkyl group is: an optionally substituted halogenated C1-C3 alkyl group; Or, the optionally substituted C1-C3 alkoxy group is: an optionally substituted halogenated C1-C3 alkoxy group.

21. The compound according to any one of claims 5, 11, and 15, or a salt and / or an isotope-substituted derivative thereof, wherein: The optionally substituted C1-C6 straight-chain alkyl group is: an optionally substituted halogenated C1-C6 straight-chain alkyl group; Or, the optionally substituted C3-C6 branched alkyl group is: an optionally substituted halogenated C3-C6 branched alkyl group; Or, the optionally substituted C3-C6 cycloalkyl group is: optionally substituted halogenated C3-C6 cycloalkyl group.

22. The compound according to claim 11, or a salt and / or isotope-substituted derivative thereof, wherein: The optionally substituted C1-C6 straight-chain alkyl or alkoxy group is: an optionally substituted halogenated C1-C6 straight-chain alkyl or alkoxy group; Or, the optionally substituted C3-C6 branched alkyl or alkoxy group is: an optionally substituted halogenated C3-C6 branched alkyl or alkoxy group; Or, the optionally substituted C3-C6 cycloalkyl or alkoxy group is: an optionally substituted halogenated C3-C6 cycloalkyl or alkoxy group.

23. The compound according to any one of claims 7 and 11, or a salt and / or an isotope-substituted derivative thereof, wherein: The optionally substituted C1-C4 alkyl group is: an optionally substituted halogenated C1-C4 alkyl group; Or, the optionally substituted C1-C4 alkoxy group is: an optionally substituted halogenated C1-C4 alkoxy group.

24. The compound according to any one of claims 10, 12-15, or a salt and / or an isotope-substituted derivative thereof, wherein: The optionally substituted C1-C4 straight-chain alkyl or alkoxy group is: an optionally substituted halogenated C1-C4 straight-chain alkyl or alkoxy group; Or, the optionally substituted C3-C4 branched alkyl or alkoxy group is: an optionally substituted halogenated C3-C4 branched alkyl or alkoxy group; Or, the optionally substituted C3-C4 cycloalkyl or alkoxy group is: an optionally substituted halogenated C3-C4 cycloalkyl or alkoxy group.

25. The compound according to claim 1, or a salt and / or isotope-substituted derivative thereof, wherein: The optionally substituted C3-C8 branched or cycloalkyl group is: an optionally substituted halogenated C3-C8 branched or cycloalkyl group.

26. The compound according to any one of claims 1-4, 6-9, 17, or a salt and / or an isotope-substituted derivative thereof, wherein: R 3 Selected from:

27. A compound, or a salt and / or isotope-substituted derivative thereof, wherein the compound is selected from:

28. A pharmaceutical composition comprising a compound according to any one of claims 1 to 27, or a salt and / or an isotopically substituted derivative thereof.

29. A pharmaceutical composition comprising a compound according to any one of claims 1 to 27, or a salt and / or isotopically substituted derivative thereof, and a pharmaceutically acceptable carrier, excipient or diluent.

30. Use of a compound according to any one of claims 1 to 27, or a salt and / or isotope-substituted derivative thereof, in the preparation of a medicament for treating and / or preventing nasopharyngeal carcinoma.

31. Use of the pharmaceutical composition according to any one of claims 28 to 29 in the preparation of a medicament for treating and / or preventing nasopharyngeal carcinoma.

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