Novel PD-L1 inhibitors

Abstract

The present invention relates to compounds useful for modulating the PD-1 / PD-L1 protein / protein interaction, which are useful for the treatment of various diseases associated with the overexpression of PD-1 / PD-L1, including infectious diseases and cancer. The invention also relates to compositions comprising such compounds and uses thereof.

Description

Technical Field

[0001] This invention relates to compounds for regulating PD-1 / PD-L1 protein / protein interactions, which can be used to treat various diseases associated with PD-1 / PD-L1 overexpression, including infectious diseases and cancer. The invention also relates to compositions comprising such compounds and their uses. Background Technology

[0002] Immune checkpoint molecules are inhibitory receptors expressed on immune cells that trigger immunosuppressive signaling pathways. These molecules are crucial for maintaining self-tolerance and regulating the length and intensity of effector immune responses in peripheral tissues in order to minimize collateral tissue damage.

[0003] Protein-protein interactions: PD1 / PD-L1 is an important immune checkpoint. PD-1 is expressed on all activated T cells and acts as a mechanism of immune tolerance, inhibiting the brake that alters T cell immune responses. PD-1 inhibits T cell function when it binds to its binding partner PD-L1 or PD-L2(1).

[0004] PD-L1 has been found to be overexpressed in various types of cancer cells. Upregulation of PD-1 on immune cells also occurs during acute and chronic infections (viral, bacterial, or fungal). Therefore, such immune checkpoints are believed to play a crucial role in suppressing antigen-specific T-cell responses in diseases such as cancer and infections.

[0005] Targeting the programmed cell death protein 1 / programmed cell death 1 ligand 1 (PD1 / PDL1) interaction has become an established strategy for cancer immunotherapy. Furthermore, the fact that pathogens also exploit these inhibitory pathways to evade immune defenses suggests that blocking measures can be used to prevent and treat infectious diseases, whether in the acute or chronic phase of infection (2)(3).

[0006] Most clinically used PD-1 / PD-L1 inhibitors are monoclonal antibodies, but their application is limited because they are PD-1 / PD-L1 inhibitors.

[0007] However, the development of small molecule immunomodulators for this pathway has lagged far behind, and currently only a limited number of candidate drugs have shown good PD-1 / PD-L1 blocking activity in cell-based assays (2). Therefore, it is necessary to identify the chemical components that contribute to this inhibition, particularly small molecule inhibitors. In particular, oral compounds that can help overcome the limitations of antibodies would be useful. Therefore, the identification and development of novel PD-1 / PD-L1 inhibitor compounds for the treatment of diseases or conditions associated with reversing T-cell exhaustion will open up new opportunities in the fields of cancer and infection therapy.

[0008] Non-patent literature

[0009] (1)MNWikes,SRLewin,Nat RevImmunol.2018,Vol.18(2),91–104

[0010] (2)C.Fang-Fang,L.Zheng et al.Oncoimmunology,2020,Vol.9no.1

[0011] (3)L.Chang,NPSeeram et al.Cancer Cell Int.2021,21-239 Summary of the Invention

[0012] This invention provides compounds of formula (I) or pharmaceutically acceptable salts or stereoisomers thereof.

[0013]

[0014] The substituents are as defined in this paper.

[0015] The present invention also relates to a pharmaceutical composition comprising a compound of the present invention or a pharmaceutically acceptable salt or stereoisomer thereof, and one or more pharmaceutically acceptable carriers or excipients.

[0016] The present invention also provides compounds and compositions for methods of treating diseases or conditions associated with reversing T-cell exhaustion, wherein such disease may be cancer or infection.

[0017] The present invention also provides a method for treating diseases or conditions associated with reversing T-cell exhaustion, wherein such disease may be cancer or infection. Detailed Implementation

[0018] definition

[0019] Unless otherwise specified, all scientific, chemical, and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. A dash (-) at the beginning or end of a chemical group is for convenience in indicating the attachment point. However, a chemical group may be represented with or without one or more dashes without losing its usual meaning. Unless otherwise specified, each linking substituent includes both the forward and reverse forms of the linking substituent. For example, -C 6-10 Aryl-C 1-4 Alkyl-including -C 6-10 Aryl-C 1-4 Alkyl- and -C 1-4 Alkyl-C 6-10 aryl-, and intends to disclose each of the forms individually, and may be attached to only one side (e.g., C 1-4 Alkyl or C 6-10 Aryl group (or attached to both sides).

[0020] The term "substituted" means that one atom or a group of atoms formally replaces hydrogen, becoming a "substituent" attached to another group. The phrase "optionally substituted" means unsubstituted or substituted. Unless otherwise stated, the term "substituted" refers to any degree of substitution, such as monosubstituted, disubstituted, trisubstituted, tetrasubstituted, or pentasubstituted, provided that such substitution is permissible. Substituents are chosen independently, and substitution can occur at any chemically accessible position. It should be understood that substitution at a given atom is limited by valence and molecular stability. In this disclosure, the letter X... n Y n R n It can be used to represent a hydrogen atom being substituent with one or more substituents (e.g., R). a R b R c R d R e R f Substituents are replaced by ) . Substituents are chosen independently, for example, if an R n Selected as an atom or a group of atoms (e.g., C) 1-6 Alkyl), then other R n It can be any other substituent from the list of possible substituents.

[0021] As used herein, the term "alkyl" refers to the general formula -C n H 2n+1 The saturated hydrocarbon group can be straight-chain or branched. Non-limiting examples of the alkyl moiety include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, etc. As used herein, the term "C" refers to... n-m "Alkyl" refers to an alkyl group having n to m carbon atoms. For example, the term "C1-6 "alkyl" is intended to individually disclose (but is not limited to) methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl and C6 alkyl.

[0022] As used herein, the term "alkynyl" refers to a straight-chain or branched hydrocarbon group corresponding to an alkyl group having one or more carbon-carbon triple bonds. The term "C n-m "Alynyl" refers to an alkynyl group having n to m carbon atoms. Non-limiting examples of alkynyl groups include ethynyl, propyn-1-yl, and propyn-2-yl.

[0023] As used herein, the term "alkoxy" refers to a group of the formula -O-alkyl, wherein the alkyl group is as defined above. The term "C" n-m "Alkoxy" refers to an alkoxy group whose alkyl group has n to m carbons. Non-limiting examples of alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), etc.

[0024] As used herein, the term "halogen" or "halogenated" refers to a halogen atom selected from fluorine (F), chlorine (Cl), or bromine (Br). In some preferred embodiments of the invention, the halogen group is Cl.

[0025] As used herein, the terms “nitrile” or “cyano” refer to the group of the formula -CN, also written as (-C≡N).

[0026] As used herein, the term "amino" refers to a group of the formula -NH2. Term C n -C m Alkyl-NHR n It refers to an amino group attached to an alkyl group as defined above, wherein another hydrogen atom is replaced by an atom or a group of atoms.

[0027] As used herein, the term "carbamoyl" refers to the formula -C(O)NH2, -NH2C(O), NHC(O)R n C(O)NHR n The group, also written as NHCOR n CONHR n .

[0028] As used herein, the term "carbonyl" refers to the -C(=O)- group, and can also be written as -C(O)- or -CO-.

[0029] The term "oxo" (=O) refers to an oxygen atom acting as a divalent substituent, forming a carbonyl group when attached to carbon, or a sulfoxide or sulfone group or N-oxide group when attached to a heteroatom. In some embodiments, the aryl or heterocyclic group may optionally be replaced by one or two oxo (=O) substituents.

[0030] As used herein, the term "aryl" refers to an aromatic hydrocarbon group, which can be monocyclic or polycyclic (e.g., having two fused rings). The term "C" n-m "Aryl" refers to an aryl group having n to m ring carbon atoms. Aryl groups include, for example, phenyl, naphthyl, indenyl, and indenyl.

[0031] As used herein, the term "heteroaryl" refers to a monocyclic or polycyclic aromatic heterocycle having at least one heteroatom ring member selected from sulfur, oxygen, and nitrogen. For example, the term 5-14 membered heteroaryl refers to an aromatic heterocycle having 5-14 ring atoms (including carbon atoms) and 1, 2, 3, or 4 independently selected heteroatom ring members (preferably nitrogen) from nitrogen, sulfur, and oxygen. Non-limiting examples of heteroaryl groups include pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrroleyl, pyrazolyl, azoleyl, imidazolyl, furanyl, quinolinyl, isoquinolinyl, naphthidyl, indoleyl, and benzofuranyl, etc.

[0032] As used herein, the term "cyclic hydrocarbon group" refers to a non-aromatic hydrocarbon ring system (monocyclic, bicyclic, or polycyclic), including cyclic alkyl and cyclic alkenyl groups. The term "C n-m A "cyclic hydrocarbon group" refers to a cyclic hydrocarbon group having n to m ring member carbon atoms. Cyclic hydrocarbon groups can include monocyclic or polycyclic groups (e.g., having 2, 3, or 4 fused rings). Non-limiting examples of cyclic hydrocarbon groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, and cycloheptanetrienyl.

[0033] As used herein, the term "heterocyclic hydrocarbon group" refers to a non-aromatic ring or ring system that may optionally contain one or more alkenyl groups as part of a ring structure, has at least one heteroatom ring member independently selected from nitrogen, sulfur, and oxygen, and may have, for example, 4-14 ring members, 4-10 ring members, 4-7 ring members, or 4-6 ring members. The term "heterocyclic hydrocarbon group" includes monocyclic 4-, 5-, 6-, and 7-membered heterocyclic hydrocarbon groups. Non-limiting examples of monocyclic heterocyclic hydrocarbon groups include piperidinyl, piperazinyl, pyrrolidinyl, azacyclic butyl, tetrahydropyranyl, and tetrahydrofuranyl, etc. Heterocyclic hydrocarbon groups may also include bicyclic or polycyclic (e.g., having two or three fused or bridged attachment rings) or spirocyclic systems.

[0034] For example, It should be considered as a heterocyclic hydrocarbon group substituted with oxo (=O) and R groups, respectively.

[0035] As used herein, the term "cyclic amide" refers to a cyclic compound containing an amide group –C(=O)N– in its ring. n -C m Cycloamides are cyclic amides that have n to m ring member carbon atoms (e.g., C3-C6).

[0036] The above terms can be used individually or in combination. For example, term C 6-10 Aryl-C 1-4 Alkyl-, 5-14-membered heteroaryl-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a Or C n -C m -Cyclic amide-C 1-4 Alkyl refers to aryl, 5-14 heteroaryl, amino, or C. n -C m - Cyclic amides combined with alkyl groups as defined above. For example, It should be considered to belong to the above C 6-10 Aryl-C 1-4 Alkyl- and C n -C m -Cyclic amide-C 1-4 Within the definition of alkyl-.

[0037] As used herein, the term “pharmaceutical acceptable” means compounds and materials that are generally safe, non-toxic and have no adverse effects on biology or otherwise, and includes compounds and materials suitable for veterinary use as well as for human pharmaceutical use.

[0038] The terms “subject” or “patient” or “recipient” are used interchangeably and refer to any mammal, preferably a mouse, rat, other rodent, rabbit, dog, cat, pig or primate, and most preferably a human.

[0039] The phrase “therapeutic effective amount” refers to the amount of an active compound or agent that elicits a biological or medical response in an tissue, system, animal, individual, or human.

[0040] As used herein, the term “treating” means suppressing the pathology or symptomology of a disease, condition, or symptom in an individual who is experiencing or exhibiting the disease, condition, or symptom; and / or improving the disease; for example, improving the disease, condition, or symptom in an individual who is experiencing or exhibiting the pathology or symptomology of the disease (i.e., reversing the pathology and / or symptomology), such as reducing the severity of the disease.

[0041] compound

[0042] This invention relates to compounds of formula (I) or pharmaceutically acceptable salts or stereoisomers thereof:

[0043]

[0044] in,

[0045] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[0046] R3 is H, methyl, halogen, or CN;

[0047] R4 and R5 can each be independently H, methyl, halogen or CN;

[0048] R7 represents H and C. 1-6 Alkyl, C 1-6 Alkoxy, halogen, or CN;

[0049] R1 is selected from H and C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a NHOR a C(O)R a , NHCOR a NHR a CONHR a NHSO2R a SO2NHR a and OCH2R a Or R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the C of R1 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R b Substituents;

[0050] R2 is selected from C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6-cycloamide-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a -NHOR a C(O)R a , NHCOR a CONHR a NHSO2R a SO2NHR a NHR a and OCH2R a The C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6-cyclic amide-C 1-4 Alkyl groups are each independently selected by 1, 2, 3 or 4 R groups. b Substituents;

[0051] R6 is selected from H and C. 1-6 Alkyl, C 2-6 Alkyne, halogens and OCH2R a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of 1, 2, 3, or 4 independently selected R groups. b Substituents;

[0052] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR c NHOR c , NHCOR c NHR c and OCH2R c , where R a The C mentioned in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. d Substituents;

[0053] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides C 1-4 Alkyl group, OH group, (=O group), NH2 group, NHOR group c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)NR c R c C(O)OR c OC(O)R c C 1-6 Alkyl-NHR c NHR c NR c R cS(O)2NR c R c , where R b The C mentioned 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. d Substituents;

[0054] Each R c Independently selected from H and C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides C 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides C 1-4Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0055] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides, C3-C6 cyclic amides 1-4 Alkyl-, CN, NH2, NHOR e C(O)R e C(O)NR e R e C(O)OR e OC(O)R e OC(O)NR e R e 、(=O),NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e S(O)2R e and S(O)2NR e R e , where R d The C mentioned 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides, C3-C6 cyclic amides 1-4 Alkyl groups, each optionally selected by one, two, or three independent R groups f Substituents;

[0056] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides 1-4 alkyl-, where R e The C mentioned 1-6 Alkyl, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides 1-4 Alkyl groups are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0057] Each R f Independently selected from H and C 1-4 Alkyl, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides, halogens, CN, COOH, OH, (=O).

[0058] In the compounds of formula (I) above,

[0059] Preferably,

[0060] X1-X6 are each independently C or N, provided that at least two and at most three of X1-X6 are N;

[0061] R3 and R5 are preferably each independently methyl or Cl. More preferably, both R3 and R5 are methyl. Alternatively, both R3 and R5 are Cl.

[0062] R4 is preferably H.

[0063] R7 is preferably H or C. 1-6 Alkoxy, more preferably H or OMe.

[0064] R1 is preferably selected from H and C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a , NHCOR a NHR a NHOR a C(O)R a CONHR a NHSO2R a SO2NHR a and OCH2R a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the C of R1 is... 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups, each optionally selected by one, two, or three independent R groups b Substituents;

[0065] R2 is preferably selected from C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a and NHR a The C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. b Substituents;

[0066] R6 is preferably selected from H and OCH2R. a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, which is optionally connected by 1, 2, 3, or 4 independently selected R groups. b Substituents;

[0067] Each R a Preferably selected independently from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0068] Each R b The substituents are preferably selected independently from C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)Rc,OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b The C mentioned1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each is R selected independently by 1, 2 or 3 people. d The substituent is substituted independently;

[0069] Each R c Preferably selected independently from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0070] Each R d Preferred to be independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R eNR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d The C mentioned 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0071] Each R e Preferably, the components are independently selected from H, OH, COOH, and C(O)R. f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e The C mentioned 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0072] Each R f Preferably selected independently from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0073] In the compounds of formula (I) above, the heteroaryl group You can choose from the following groups:

[0074]

[0075] In the compounds of formula (I) above, the heteroaryl group You can choose from the following groups:

[0076]

[0077] Preferably, the heteroaryl group Choose from the following groups:

[0078]

[0079] In the compounds of formula (I) above, R1 can be selected from the group consisting of: R b Replacement C 1-3 Alkoxy, NHC(O)R a 、Being R b Replacement C 6-10Aryl, R b Substituted 5-14 heteroaryl groups, NHR a CONHR a NHSO2R a and SO2NHR a R in equation (I) a R b Other variables are as defined in any of the implementations disclosed herein.

[0080] In the compounds of formula (I) above, R1 can be selected from the group consisting of:

[0081]

[0082] In this context, each subscript r is an independent integer of 0, 1, or 2; each subscript q is an independent integer of 0, 1, 2, or 3; Y1 and Y2 are each independent integers of C or N; and R b and R d As defined in any of the implementations disclosed herein.

[0083] Preferably, R1 is selected from the group consisting of the following:

[0084]

[0085] Among them, R c and R d As defined in any of the implementations disclosed herein.

[0086] In some embodiments, compounds of formula (I) above are provided herein, wherein R1 is selected from:

[0087]

[0088] Other variables in equation (I) are defined as in any of the embodiments disclosed herein.

[0089] In some embodiments, this document provides compounds of formula (I), wherein R3 is methyl, Cl or CN, R4 and R7 are H, R5 is H, methyl or Cl, and other variables of formula (I) are as defined in any of the embodiments disclosed herein.

[0090] In some embodiments, compounds of formula (I) are provided, wherein R3 is methyl, R4, R5 and R7 are H, and other variables of formula (I) are as defined in any of the embodiments disclosed herein.

[0091] In some embodiments, compounds of formula (I) are provided, wherein R3 and R5 are methyl groups, R4 and R7 are H groups, and other variables of formula (I) are as defined in any of the embodiments disclosed herein.

[0092] In some embodiments, compounds of formula (I) are provided, wherein R3 and R5 are Cl, R4 and R7 are H, and other variables of formula (I) are as defined in any of the embodiments disclosed herein.

[0093] In some embodiments, compounds having formula (II) are provided herein. The compounds of formula (II) of the present invention are preferred embodiments of compounds of formula (I) above, or pharmaceutically acceptable salts or stereoisomers thereof, specifically compounds represented by the following formula (II) or pharmaceutically acceptable salts or stereoisomers thereof:

[0094]

[0095] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the subscript n is 1, 2 or 3, preferably n is 1, and wherein X1-X3, X5 and X6, R1, R3-R7 and R b It has the same meaning as any implementation of formula (I) described herein.

[0096] In one embodiment, this disclosure provides a compound having formula (III): The preferred embodiment of the compound of formula (III) of the present invention is a compound of formula (I) above or a pharmaceutically acceptable salt or stereoisomer thereof, specifically a compound represented by the following formula (III) or a pharmaceutically acceptable salt or stereoisomer thereof:

[0097]

[0098] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the subscript m is 0, 1, 2 or 3, preferably m is 0 or 1, wherein X1-X3, X5 and X6, R1, R3-R7 and R b It has the same meaning as any implementation of formula (I) described herein.

[0099] In some embodiments, compounds having formula (IV) or (V) are provided herein. The compounds of formula (IV) or (V) of the present invention are preferred embodiments of compounds of formula (I) above, or pharmaceutically acceptable salts or stereoisomers thereof, specifically compounds represented by the following formula (IV) or (V), or pharmaceutically acceptable salts or stereoisomers thereof:

[0100]

[0101] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the subscript n in formula (IV) is 1, 2 or 3, preferably 1 or 2, wherein X1-X3, X5 and X6, R1, R3-R7 and R b It has the same meaning as any implementation of formula (I) described herein;

[0102] In equation (V), the subscript n is 1, 2, or 3, preferably 1 or 2, and X1-X4 and X6, R1, R3-R7 and R... b It has the same meaning as any implementation of formula (I) described herein.

[0103] In some embodiments, compounds having formula (VI) or (VII) are provided herein. The compounds of formula (VI) or (VII) of the present invention are preferred embodiments of compounds of formula (I) above, or pharmaceutically acceptable salts or stereoisomers thereof, specifically compounds represented by the following formula (VI) or (VII), or pharmaceutically acceptable salts or stereoisomers thereof:

[0104]

[0105] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the subscript p in Formula VI is 0 or 1, and wherein X1-X3, X5 and X6, R1, R3, R4-R7 and R a It has the same meaning as any implementation of formula (I) described herein.

[0106]

[0107] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the subscript p in formula VII is 0 or 1, and wherein X1-X4 and X6, R1, R3, R4-R7 and R a It has the same meaning as any implementation of formula (I) described herein.

[0108] In the compounds of formulas (II) to (VII) above,

[0109] Preferably, X1-X6 are each independently C or N, provided that at least two and at most three of X1-X6 are N;

[0110] R3 and R5 are preferably each independently methyl or Cl. More preferably, both R3 and R5 are methyl. Alternatively, both R3 and R5 are Cl.

[0111] R4 is preferably H.

[0112] R7 is preferably H or C. 1-6 Alkoxy, more preferably H or OMe.

[0113] R1 is preferably selected from H and C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a , NHCOR a NHR a NHOR a C(O)R a CONHR a NHSO2R a SO2NHR a and OCH2R a Or R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the C of R1 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups, each optionally selected by one, two, or three independent R groups b Substituent substitution;

[0114] R2 is preferably selected from C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a and NHR a The C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C1-4 Alkyl groups are each independently selected by one, two, or three R groups. b Substituents;

[0115] R6 is preferably selected from H and OCH2R. a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of 1, 2, 3, or 4 independently selected R groups. b Substituents;

[0116] Each R a Preferably selected independently from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a The C mentioned 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0117] Each R b The substituents are preferably selected independently from C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)Rc,OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each is R selected independently by 1, 2 or 3 people. d The substituent is substituted independently;

[0118] Each R c Preferably selected independently from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0119] Each R d Preferred to be independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)ORe OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0120] Each R e Preferably, the components are independently selected from H, OH, COOH, and C(O)R. f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0121] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0122] In the compounds of formula (II), (III), (IV) or (VI) above, the heteroaryl group You can choose from the following groups:

[0123]

[0124] The preferred option is:

[0125] In the compounds of formula (V) or (VII) above, the heteroaryl group Preferred options are:

[0126]

[0127] In the compounds of formulas (II)-(VII) above, R1 can be selected from the group consisting of: R b Replacement C 1-3 Alkyl groups, by R b Replacement C 6-10 Aryl, R b Substituted 5-14 heteroaryl groups, NHR a CONHR a NHSO2R aand SO2NHR a R a and R b As defined in any of the embodiments described herein. Other variables in equations (II)-(VII) are as defined in any of the embodiments disclosed herein.

[0128] In the compounds of formulas (II)-(VII) above, R1 can be selected from the group consisting of the following:

[0129]

[0130] In this context, each subscript r is an independent integer of 0, 1, or 2; each subscript q is an independent integer of 0, 1, 2, or 3; Y1 and Y2 are each independent integers of C or N; and R b and R d As defined in any of the embodiments disclosed herein. Other variables in equations (II)-(VII) are as defined in any of the embodiments disclosed herein.

[0131] In the compounds of formulas (II)-(VII) above, preferably, R1 is selected from the group consisting of:

[0132]

[0133] Among them, R c and R d As defined in any of the embodiments disclosed herein. Other variables in equations (II)-(VII) are as defined in any of the embodiments disclosed herein.

[0134] In some embodiments, compounds of formulas (II)-(VII) above are provided herein, wherein R1 is selected from:

[0135]

[0136] The other variables in equations (II)-(VII) are as defined in any of the embodiments disclosed herein.

[0137] In some embodiments, compounds of formula (I), (II), (III), (IV), (V), (VI), and (VII) are provided herein, wherein R3 is methyl, Cl, or CN, R4 and R7 are H, R5 is H, methyl, or Cl, and other variables are as defined in any embodiment of formula (I) disclosed herein.

[0138] In some embodiments, compounds of formulas (I), (II), (III), (IV), (V), (VI), and (VII) are provided, wherein R3 is methyl, R4, R5, and R7 are H, and other variables are as defined in any embodiment of formula (I) disclosed herein.

[0139] In some embodiments, compounds of formula (I), (II), (III), (IV), (V), (VI), and (VII) are provided herein, wherein R3 and R5 are methyl groups, R4 and R7 are H groups, and other variables are as defined in any embodiment of formula (I) disclosed herein.

[0140] In some embodiments, compounds of formula (I), (II), (III), (IV), (V), (VI), and (VII) are provided herein, wherein R3 and R5 are Cl, R4 and R7 are H, and other variables are as defined in any embodiment of formula (I) disclosed herein.

[0141] In some embodiments, a compound of formula (I) is provided, wherein R3 is methyl or Cl, R1, R4, R5, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e H is the variable. Other variables are defined as in any implementation of equation (I) disclosed herein.

[0142] In some embodiments, a compound of formula (I) is provided, wherein R3 and R5 are methyl or Cl, R1, R4, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e H is the variable. Other variables are defined as in any implementation of equation (I) disclosed herein.

[0143] In some embodiments, a compound of formula (II) is provided, wherein R3 and R5 are methyl or Cl, R1, R4, R6 and R7 are H, and R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e H is the variable. Other variables are defined as in any implementation of equation (II) disclosed herein.

[0144] In some embodiments, a compound of formula (II) is provided, wherein R3 is methyl or Cl, R1, R4, R5, R6 and R7 are H, and R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e H is the variable. Other variables are defined as in any implementation of equation (II) disclosed herein.

[0145] In some embodiments, compounds of formula (I) are provided herein, wherein R3 is methyl, R4, R5 and R7 are H, R1 and R6 are H or linked together to form a 4-10 membered heterocyclic hydrocarbon group, and R2 is a radical formed by R... b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For NHR c R c For 1 or 2 R d Replacement C 1-6 Alkyl, R d C(O)OR e S(O)2R e OR e And R e H or OH. Other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0146] In some embodiments, compounds of formula (II) are provided, wherein R3 is methyl, R4, R5 and R7 are H, R1 and R6 are H, or linked together to form a 4-10 membered heterocyclic hydrocarbon group, R b For NHR c R c For 1 or 2 R d Replacement C 1-6 Alkyl, R d C(O)OR e S(O)2R e OR e And R e H or OH. Other variables in equation (II) are as defined in any of the embodiments disclosed herein.

[0147] In some embodiments, a compound of formula (I) is provided, wherein R3 is methyl or Cl, R4, R5 and R7 are H, R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, and R2 is a radical formed by R... b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b For one or two Rd Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e OR e And R e For H. Other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0148] In some embodiments, a compound of formula (II) is provided, wherein R3 is methyl or Cl, R4, R5 and R7 are H, R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, R b For 1 or 2 R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e OR e And R e For H. Other variables in equation (II) are as defined in any of the embodiments disclosed herein.

[0149] In some embodiments, compounds of formula (I) are provided herein, wherein R3 is methyl, R4, R5 and R7 are H, R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, and R2 is a compound surrounded by three R groups. b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b1 For 1 or 2 R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e OR e And R e For H, R b2 and R b3 C 1-6 Alkoxy group. Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[0150] In some embodiments, a compound of formula (I) is provided, wherein R3 is CN, R1, R4, R5, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e For H. Other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0151] In some embodiments, a compound of formula (I) is provided, wherein R3 is a methyl group, R1, R4, R5, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 2-6 alkynyl group, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e For H. Other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0152] In some embodiments, compounds of formula (I) are provided, wherein R3 is methyl, R1, R4, R5, R6 and R7 are H, and R2 is a derivative of R. b Substituted 5-14 heteroaryl groups, R b C(O)NHR c R c For R d Replacement C 1-6 Alkyl, R d C(O)OR e And R e For H. Other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0153] In some embodiments, compounds of formula (III) are provided, wherein R3 is methyl, R1, R4, R5, R6 and R7 are H, m is O, and R b C(O)NHR c R c For R d Replacement C 1-6 Alkyl, R d C(O)OR e And Re is H. The other variables in equation (III) are as defined in any of the embodiments disclosed herein.

[0154] In some embodiments, compounds of formula (I) are provided, wherein R3 is methyl, R4, R5 and R7 are H, R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, and R2 is a radical formed by R... b Substituted 5-14 heteroaryl groups, R b C(O)NHR c R c For R d Replacement C 1-6 Alkyl, R d C(O)OR e And R e For H. Other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0155] In some embodiments, a compound of formula (III) is provided, wherein R3 is methyl, R4, R5 and R7 are H, R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, m is 0, and R b C(O)NHR c R c For R d Replacement C 1-6 Alkyl, R d C(O)OR e And R e For H. Other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0156] In some embodiments, compounds of formula (I) are provided herein, wherein R1 is selected from:

[0157]

[0158] Each subscript r is an independent integer of 0, 1, or 2; each subscript q is an independent integer of 0, 1, 2, or 3; and each of Y1 and Y2 is an independent C or N.

[0159] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[0160] R3 is methyl or Cl;

[0161] R5 is methyl or Cl;

[0162] R4 is H;

[0163] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0164] R2 is selected from C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a and NHR a C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. b Substituents;

[0165] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0166] Each R a Substituents are independently selected from H and C. 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0167] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where Rb C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0168] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0169] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)Re NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0170] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0171] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0172] In some embodiments, compounds of formula (I) are provided herein, wherein R1 is selected from:

[0173]

[0174] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[0175] R3 is a methyl group, or Cl;

[0176] R5 is methyl or Cl

[0177] R4 is H;

[0178] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0179] R2 is selected from C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a and NHR a C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. b Substituents;

[0180] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0181] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0182] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0183] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0184] Each R dSelected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0185] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0186] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0187] In some embodiments, compounds of formula (I) are provided herein, wherein R1 is selected from:

[0188]

[0189] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[0190] R3 is a methyl group, or Cl;

[0191] R5 is methyl or Cl

[0192] R4 is H;

[0193] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0194] R2 is selected from C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a and NHR a C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. b Substituents;

[0195] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0196] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0197] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each of the R options, which have 1, 2, or 3 independent choices, is replaced independently. d Substituents;

[0198] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0199] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0200] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0201] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0202] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e Let H be a variable, and let X1-X6 be independently either C or N, provided that at least two and at most five of X1-X6 are N, and R1 is selected from R. 1-aa R 1-bb R 1-cc R 1-dd R 1-bc R 1-bd R 1-dd R 1-de and R 1-ii ,

[0203] Among them, in R 1-aa R 1-bb R 1-cc R 1-dd R 1-bc R 1-bd R 1-dd R 1-de And R 1-ii In the table, each subscript r is an integer 0, 1, or 2, each subscript q is an integer 0, 1, 2, or 3, and Y1 and Y2 are each C or N.

[0204] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each of the R options, which have 1, 2, or 3 independent choices, is replaced independently. d Substituents;

[0205] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0206] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e ORe 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0207] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0208] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O). Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[0209] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e Let H be a variable, and let X1-X6 be independently either C or N, provided that at least two and at most five of X1-X6 are N, and R1 is selected from R. 1-a R 1-b R 1-c R 1-d R 1-e R 1-f R 1-g R 1-h and R 1-i ,

[0210] Among them, in R 1-a R 1-b R 1-c R1-d R 1-e R 1-f R 1-g R 1-h and R 1-i In the middle, each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0211] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups.f Substituents;

[0212] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0213] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O). Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[0214] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e Let H be a subset of R, and R1 be selected from R. 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R 1-6 R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14 The other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0215] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For NHR c R c For R d Replacement C 1-6 Alkyl, Rd OR e With or without C 1-4 Alkyl C3-C6 cyclic amides, R e For H or C 1-6 Alkyl groups, X1-X6, are each independently C or N, provided that at least two and at most five of X1-X6 are N, and R1 is selected from R 1-aa R 1-bb R 1-cc R 1-dd R 1-bc R 1-bd R 1-dd R 1-de and R 1-ii ,

[0216] Among them, R 1-aa R 1-bb R 1-cc R 1-dd R 1-bc R 1-bd R 1-dd R 1-de and R 1-ii In the table, each subscript r is an integer 0, 1, or 2, each subscript q is an integer 0, 1, 2, or 3, and Y1 and Y2 are each C or N.

[0217] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)Rc C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHRc is independently selected by 1, 2 or 3 R. d Substituents;

[0218] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0219] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0220] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0221] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O). Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[0222] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For NHR c R c For R d Replacement C 1-6 Alkyl, R d For whether or not C is present 1-4 Alkyl OR e Or C3-C6 cyclic amides, R e For H or C 1-6 Alkyl groups, X1-X6, are each independently C or N, provided that at least two and at most five of X1-X6 are N, and R1 is selected from R 1-a R 1-b R 1-c R 1-d R 1-e R 1-f R 1-g R 1-h and R 1-i ,

[0223] Among them, in R 1-a R 1-b R 1-c R 1-d R 1-e R 1-f R 1-g R1-h and R 1-i In the middle, each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d And R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0224] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0225] Each R eIndependently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0226] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O). Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[0227] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For NHR c R c For R d Replacement C 1-6 Alkyl, R d OR e With or without C 1-4 Alkyl C3-C6 cyclic amides, R e For H or C 1-6 Alkyl group, and R1 is selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14 The other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0228] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is C. 1-6 Alkyl-NHR a R a For R d Replacement C 1-6 Alkyl, R d OR e Or C3-C6 cyclic amides, Re For H or C 1-6 Alkyl groups, X1-X6, are each independently C or N, provided that at least two and at most five of X1-X6 are N, and R1 is selected from R 1-aa R 1-bb R 1-cc R 1-dd R 1-bc R 1-bd R 1-dd R 1-de and R 1-ii ,

[0229] Among them, R 1-aa R 1-bb R 1-cc R 1-dd R 1-bc R 1-bd R 1-dd R 1-de and R 1-ii In the table, each subscript r is an integer 0, 1, or 2, each subscript q is an integer 0, 1, 2, or 3, and Y1 and Y2 are each C or N.

[0230] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0231] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0232] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0233] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0234] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O). Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[0235] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are methyl or Cl, R4, R6 and R7 are H, and R2 is C. 1-6 Alkyl-NHR a R a For R d Replacement C 1-6 Alkyl, R d OR e Or C3-C6 cyclic amides, R e For H or C 1-6 Alkyl group, and R1 is selected from R 1-a R 1-b R 1-c R 1-d R 1-e R 1- f、R 1-g R 1-h and R 1-i ,

[0236] Among them, in R 1-a R 1-b R 1-c R 1-d R 1-e R 1-f R 1-g R 1-h and R 1-I In the middle, each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d And R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0237] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0238] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups.f Substituents;

[0239] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O). Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[0240] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is C. 1-6 Alkyl-NHR a R a For R d Replacement C 1-6 Alkyl, R d OR e Or C3-C6 cyclic amides, R e For H or C 1-6 Alkyl group, and R1 is selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14 The other variables in equation (I) are as defined in any of the embodiments disclosed herein.

[0241] In some embodiments, a compound having formula (II) is provided.

[0242]

[0243] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the subscript n is 1, 2 or 3;

[0244] X1-X3, X5 and X6 are each independently C or N, provided that at least two and at most five of X1-X3, X5 and X6 are N;

[0245] R3 is methyl or Cl;

[0246] R5 is methyl or Cl

[0247] R4 is H;

[0248] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0249] R1 is selected from:

[0250]

[0251] In R1, the subscripts r are each an integer 0, 1, or 2, the subscripts q are each an integer 0, 1, 2, or 3, and Y1 and Y2 are each an integer C or N.

[0252] Preferably, R1 is selected from R 1-a R 1-b R 1-c R 1-d R 1-e R 1-f R 1-g R 1-h and R 1-i More preferably selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14 ,

[0253] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0254] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0255] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0256] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R eand S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0257] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0258] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0259] In some embodiments, a compound having formula (III) is provided.

[0260]

[0261] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the subscript m is 0, 1, 2 or 3;

[0262] X1-X3, X5 and X6 are each independently C or N, provided that at least two and at most five of X1-X3, X5 and X6 are N;

[0263] R3 is a methyl group, or Cl;

[0264] R5 is methyl or Cl

[0265] R4 is H;

[0266] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0267] R1 is selected from:

[0268]

[0269] Each subscript r is an independent integer of 0, 1, or 2; each subscript q is an independent integer of 0, 1, 2, or 3; and each of Y1 and Y2 is an independent C or N.

[0270] Preferably, R1 is selected from R 1-a R 1-b R 1-c R 1-d R 1-e R 1-f R 1-g R 1-h and R 1-i More preferably selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14 ,

[0271] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0272] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0273] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0274] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0275] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0276] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0277] In some embodiments, compounds having formula (IV) or (V) are provided.

[0278]

[0279] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the subscript n in formula (IV) is 1, 2 or 3;

[0280] X1-X3, X5 and X6 are each independently C or N, provided that at least two and at most five of X1-X3, X5 and X6 are N;

[0281] R3 is methyl or Cl;

[0282] R5 is methyl or Cl

[0283] R4 is H;

[0284] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0285] R1 is selected from:

[0286]

[0287] In R1, the subscripts r are each an integer 0, 1, or 2, the subscripts q are each an integer 0, 1, 2, or 3, and Y1 and Y2 are each an integer C or N.

[0288] Preferably, R1 is selected from R 1-a R 1-b R 1-c R 1-d R 1-e R 1-fR 1-g R 1-h and R 1-i More preferably selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14

[0289] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0290] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0291] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0292] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0293] Each R e Independently selected from H, OH, COOH, C(O)R fC 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0294] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0295] In equation (V), the subscript m is 1, 2, or 3;

[0296] X1-X4 and X6 are each independently C or N, provided that at least two and at most five of X1-X4 and X6 are N;

[0297] R3 is methyl or Cl;

[0298] R5 is methyl or Cl

[0299] R4 is H;

[0300] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0301] R1 is selected from:

[0302]

[0303] In R1, the subscripts r are each an independent integer 0, 1, or 2, the subscripts q are each an independent integer 0, 1, 2, or 3, and Y1 and Y2 are each an independent C or N.

[0304] Preferably, R1 is selected from R 1-a R 1-b R 1-c R 1-d R 1-e R 1-f R 1-g R 1-h and R 1-i More preferably selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14

[0305] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0306] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0307] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0308] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0309] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0310] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0311] In some embodiments, a compound having formula (VI) is provided.

[0312]

[0313] Or its pharmaceutically acceptable salt or stereoisomer, wherein the subscript p is 0 or 1;

[0314] R1 is selected from:

[0315]

[0316] Each subscript r is an independent integer of 0, 1, or 2; each subscript q is an independent integer of 0, 1, 2, or 3; and each of Y1 and Y2 is an independent C or N.

[0317] X1-X3, X5 and X6 are each independently C or N, provided that at least two and at most five of X1-X3, X5 and X6 are N;

[0318] R3 is methyl or Cl;

[0319] R5 is methyl or Cl

[0320] R4 is H;

[0321] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0322] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0323] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups.d Substituents;

[0324] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0325] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0326] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0327] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0328] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0329] In some embodiments, a compound having formula (VI) is provided.

[0330]

[0331] Or its pharmaceutically acceptable salt or stereoisomer, wherein the subscript p is 0 or 1;

[0332] R1 is selected from:

[0333]

[0334] X1-X3, X5 and X6 are each independently C or N, provided that at least two and at most five of X1-X3, X5 and X6 are N;

[0335] R3 is methyl or Cl;

[0336] R5 is methyl or Cl

[0337] R4 is H;

[0338] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0339] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0340] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0341] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0342] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0343] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0344] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0345] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0346] In some embodiments, a compound having formula (VI) is provided.

[0347]

[0348] Or its pharmaceutically acceptable salt or stereoisomer, wherein the subscript p is 0 or 1;

[0349] R1 is selected from:

[0350]

[0351] X1-X3, X5 and X6 are each independently C or N, provided that at least two and at most five of X1-X3, X5 and X6 are N;

[0352] R3 is methyl or Cl;

[0353] R5 is methyl or Cl

[0354] R4 is H;

[0355] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0356] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0357] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0358] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHRc C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHRc is independently selected by 1, 2 or 3 R. d Substituents;

[0359] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0360] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)ORe NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0361] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0362] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0363] In some embodiments, a compound having formula (VII) is provided.

[0364]

[0365] Or its pharmaceutically acceptable salt or stereoisomer, wherein the subscript p is 0 or 1;

[0366] R1 is selected from:

[0367]

[0368] Each subscript r is an independent integer of 0, 1, or 2; each subscript q is an independent integer of 0, 1, 2, or 3; and each of Y1 and Y2 is an independent C or N.

[0369] X1-X4 and X6 are each independently C or N, provided that at least two and at most five of X1-X4 and X6 are N;

[0370] R3 is methyl or Cl;

[0371] R5 is methyl or Cl

[0372] R4 is H;

[0373] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0374] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0375] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0376] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHRc , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0377] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0378] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NRe C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0379] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0380] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0381] In some embodiments, a compound having formula (VII) is provided.

[0382]

[0383] Or its pharmaceutically acceptable salt or stereoisomer, wherein the subscript p is 0 or 1;

[0384] R1 is selected from:

[0385]

[0386] X1-X4 and X6 are each independently C or N, provided that at least two and at most five of X1-X4 and X6 are N;

[0387] R3 is methyl or Cl;

[0388] R5 is methyl or Cl

[0389] R4 is H;

[0390] R7 represents H and C. 1-6 Alkyl or C 1-6Alkoxy;

[0391] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0392] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0393] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHORc ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[0394] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0395] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e, where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0396] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0397] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0398] In some embodiments, a compound having formula (VII) is provided.

[0399]

[0400] Or its pharmaceutically acceptable salt or stereoisomer, wherein the subscript p is 0 or 1;

[0401] R1 is selected from:

[0402]

[0403] X1-X4 and X6 are each independently C or N, provided that at least two and at most five of X1-X4 and X6 are N;

[0404] R3 is methyl or Cl;

[0405] R5 is methyl or Cl

[0406] R4 is H;

[0407] R7 represents H and C. 1-6 Alkyl or C 1-6 Alkoxy;

[0408] R6 is selected from H and C. 1-6 Alkyl groups, halogens, and OCH2R a ;

[0409] Each R a Independently selected from H and C 1-6Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[0410] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR cNHR c Each of the R options, which have 1, 2, or 3 independent choices, is replaced independently. d Substituents;

[0411] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[0412] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups.f Substituents;

[0413] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0414] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[0415] This invention provides compounds of formula (VIII) or pharmaceutically acceptable salts or stereoisomers thereof.

[0416]

[0417] in,

[0418] X1-X4 can be C or N independently, provided that at least three of X1-X4 are N;

[0419] The subscript p is 1;

[0420] R3 and R5 are each independently methyl, Cl or CN;

[0421] R4 represents H and C. 1-6 Alkyl, halogen, or CN;

[0422] R6 represents H and C. 1-6 Alkyl or halogen;

[0423] R1 is:

[0424]

[0425] R aa For H, or R aa With R a Linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of one or two independently selected R groups. d Substituents;

[0426] R a Selected from C 1-6 Alkyl, C 1-6 Alkoxy and C 3-10 Cyclic hydrocarbon group, or R aa With R aLinked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of one or two independently selected R groups. d Substituents; where R a C 1-6 Alkyl, C 1-6 Alkoxy and C 3-10 Each of the cyclic hydrocarbon groups is independently selected by one or two independently chosen R groups. d Substituent substitution;

[0427] R cc For H, or R cc With R c Linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of one or two independently selected R groups. d Substituent substitution;

[0428] R c Selected from C 1-6 Alkyl, C 1-6 Alkoxy and C 3-10 Cyclic hydrocarbon group, or R cc and R c Linked together to form a 4-10 membered heterocyclic hydrocarbon group, said heterocyclic hydrocarbon group optionally being linked by one or two independently selected R groups. d Substituents; where R c C 1-6 Alkyl, C 1-6 Alkoxy and C 3-10 Each of the cyclic hydrocarbon groups is independently selected by one or two independently chosen R groups. d Substituents;

[0429] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[0430] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[0431] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH and (=O).

[0432] In the compound of formula (VIII) above,

[0433] Preferably,

[0434] X1-X4 can be C or N independently, provided that three of X1-X4 are N;

[0435] The subscript p is 1;

[0436] R3 and R5 are each independently methyl or Cl;

[0437] R4 and R6 are H;

[0438] R1 is:

[0439]

[0440] R aa For H, or R aa With R a Connected together to form an optional R d The 4-10 membered heterocyclic hydrocarbon groups substituted by the substituents;

[0441] R a Selected from C 1-6 Alkyl and C 3-10 Cyclic hydrocarbon group, or R aa With R a Linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally connected by one R d Substituent substitution; wherein, the C 1-6 Alkyl and C 3-10 Each cyclic hydrocarbon group is independently bounded by one Rd Substituent substitution;

[0442] R cc For H, or R cc With R c Connected together to form an optional R d Substituents: 4-10 membered heterocyclic hydrocarbon groups;

[0443] R c Selected from C 1-6 Alkyl and C 3-10 Cyclic hydrocarbon group, or R cc With R c Linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally connected by one R d Substituent substitution; wherein, the C 1-6 Alkyl and C 3-10 Each cyclic hydrocarbon group is independently bounded by one R d Substituent substitution;

[0444] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy and C3-C6 cyclic amides, C(O)OR e NHR e NR e C(O)R e OR e , where R d C 1-6 Alkyl, C 1-6 Alkoxy and C3-C6 cyclic amides are each optionally selected by one or two independently chosen R f Substituents;

[0445] Each R e Independently selected from H, OH, COOH and C(O)R f ;

[0446] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH and (=O).

[0447] Preferably, R f Independently selected from H, methyl, C 2-4 Alkyl groups, COOH, OH, and (=O)

[0448] Preferably, R aa and R a They link together to form cyclic amines that are substituted with CH2(OH) or C(O)OH.

[0449] Preferably, Rcc and R c They link together to form cyclic amines that are substituted with CH2(OH) or C(O)OH.

[0450] In the compounds of formula (VIII) above, the heteroaryl group You can choose from the following groups:

[0451]

[0452] Subscript p = 1, R in equation (VIII) aa and R a As defined in any of the implementations disclosed herein.

[0453] Preferably, heteroaryl yes In the compounds of formula (VIII) above, R1 can be selected from the group consisting of:

[0454]

[0455] The other variables in equation (VIII) are as defined in any of the embodiments disclosed herein.

[0456] In the compound of formula (VIII) above, R aa It can be H, and R a You can choose from:

[0457]

[0458] The other variables in equation (VIII) are as defined in any of the embodiments disclosed herein.

[0459] In the compound of formula (VIII) above,

[0460] R aa and R a They can be linked together to form compounds selected from the following:

[0461]

[0462] The other variables in equation (VIII) are as defined in any of the embodiments disclosed herein.

[0463] In the above-mentioned compound (VIII), it is preferred that both R3 and R5 are Cl; it is also preferred that both R3 and R5 are methyl.

[0464] In some embodiments, in the compound of formula (VIII) above, R3 and R5 are both Cl, X1-X4 are each independently C or N, provided that three of X1-X4 are N; the subscript p is 1; R4 and R6 are H; and other variables of formula (VIII) are as defined in any of the embodiments disclosed herein.

[0465] In some embodiments, in the compound of formula (VIII) above, R3 and R5 are both methyl, X1-X4 are each independently C or N, provided that three of X1-X4 are N; the subscript p is 1; R4 and R6 are H; and other variables of formula (VIII) are as defined in any of the embodiments disclosed herein.

[0466] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are Cl; R4 and R6 are H; p is 1; and R1 is R 1-j In R 1-j In the middle, R cc For H, R c For R d Replacement C 1-6 Alkyl, wherein R d OR e And R e For H, R aa For H, R a For R d Replacement C 1-6 Alkyl, wherein R d OR e And R e For H.

[0467] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are methyl groups; R4 and R6 are H, p is 1, and R1 is R 1-j In R 1-j In the middle, R cc For H, R c For R d Replacement C 1-6 Alkyl, wherein R d OR e And R e For H, R aa For H, R a For R d Replacement C 1-6 Alkyl, wherein R d OR e And R e For H.

[0468] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are Cl; R4 and R6 are H; p is 1; and R1 is R 1-j In R 1-j In the middle, R cc For H, R c For R d Replacement C 3-10 Cyclic hydrocarbon group, wherein R d OR e And R e For H, R aa For H, R a For R d Replacement C 3-10 Cyclic hydrocarbon group, wherein R d OR e And R e For H.

[0469] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are Cl; R4 and R6 are H; p is 1; and R1 is R 1-j In R 1-j In the middle, R cc For H, R c For R d Replacement C 1-6 Alkyl, wherein R d For NHR e And R e For C(O)R f R f C 1-4 Alkyl, R a For R d Replacement C 1-6 Alkyl, wherein R d For NHR e And R e For C(O)R f R f C 1-4 alkyl.

[0470] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are Cl; R4 and R6 are H; p is 1; and R1 is R 1-j In R 1-j In the middle, R cc and R c Connected together to form R d Substituted 4-10 membered heterocyclic hydrocarbon groups, wherein R d C(O)OH or C substituted with OH 1-6 Alkyl, R aa For H, Ra For R d Replacement C 1-6 Alkyl, wherein R d OR e R e For H.

[0471] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are Cl; R4 and R6 are H; p is 1; and R1 is R 1-j In R 1-j In the middle, R cc and R c Connected together to form R d Substituted 4-10 membered heterocyclic hydrocarbon groups, wherein R d C(O)OH or C substituted with OH 1-6 Alkyl, R aa and R a Connected together to form R d Substituted 4-10 membered heterocyclic hydrocarbon groups, wherein R d C(O)OH or C substituted with OH 1-6 alkyl.

[0472] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are both Cl or both are methyl; R4 and R6 are H, p is 1, and R1 is R 1-j In R 1-j In the middle, R cc For H, R c For R d Replacement C 1-6 Alkyl, wherein R d OR e And R e For H, R aa For H, R a For R d Replacement C 1-6 Alkyl, wherein R d It is a C3-C6 cyclic amide.

[0473] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are both Cl or both are methyl; R4 and R6 are H, p is 1, and R1 is R 1-j In R 1-j In the middle, R cc For H, R c For R d Replacement C 1-6 Alkyl, wherein R d It is a C3-C6 cyclic amide, R aa For H, Ra For R d Replacement C 1-6 Alkyl, wherein R d It is a C3-C6 cyclic amide.

[0474] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are both Cl or both are methyl; R4 and R6 are H, p is 1, and R1 is R 1-j In R 1-j In the middle, R cc For H, R c For R d Replacement C 1-6 Alkyl, wherein R d OR e And R e For H, R aa and R a Connected together to form R d Substituted 4-10 membered heterocyclic hydrocarbon groups, wherein R d C(O)OH or C substituted with OH 1-6 alkyl.

[0475] In each of the above implementation schemes, independently, C 1-6 The alkyl group is preferably methyl, ethyl, or C3 alkyl.

[0476] In some embodiments, compounds of formula (VIII) are provided herein, wherein R3 and R5 are both Cl or both are methyl; R4 and R6 are H, p is 1, and are heteroaryl. for:

[0477]

[0478] R aa Let H be the number of 'R', and R be the number of 'R'. a Selected from:

[0479]

[0480] R1 is selected from:

[0481]

[0482] Some embodiments of the present invention disclose a compound having Formula I, wherein the compound is selected from:

[0483] 2-(((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol;

[0484] 2-(((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)ethane-1-ol;

[0485] 2-(((2',2”-Dichloro-3”-(3-((((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol;

[0486] (S)-5-((((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)methyl)pyrrolidone-2-one;

[0487] (S)-5-((((2',2”-dimethyl-3”-(3-(((((S)-5-oxopyrrolid-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolid-2-one;

[0488] (R)-1-((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)pyrrolidine-3-carboxylic acid;

[0489] (S)-5-((((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)methyl)pyrrolidone;

[0490] (S)-5-((((2',2”-dimethyl-3”-(2-((((((S)-5-oxopyrrolid-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolid-2-one;

[0491] 2-(((2',2”-Dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol;

[0492] ((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-D-proline;

[0493] (S)-5-((((2',2”-dichloro-3”-(3-(((((S)-5-oxopyrrolid-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolid-2-one;

[0494] 2-(((2',2”-dichloro-3”-(2-(((1-hydroxy-2-methylpropane-2-yl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)-2-methylpropane-1-ol;

[0495] 2-(((2',2”-Dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)-2-methylpropane-1-ol;

[0496] ((7-(4”-(((S)-2-carboxypyrrolidone-1-yl)methyl)-2,2'-dichloro-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)-L-proline;

[0497] ((7-(4”-(((R)-2-carboxypyrrolidone-1-yl)methyl)-2,2'-dichloro-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)-D-proline;

[0498] N-(2-(((7-(4”-(((2-acetamidoethyl)amino)methyl)-2,2'-dichloro-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethyl)acetamide;

[0499] (S)-2-(((7-(2,2'-dichloro-4”-((2-(hydroxymethyl)pyrrolidin-1-yl)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol

[0500] (R)-2-(((7-(2,2'-dichloro-4”-((2-(hydroxymethyl)pyrrolidin-1-yl)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol;

[0501] 3-(((2',2”-Dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)propane-1-ol;

[0502] 3-(((2',2”-Dichloro-3”-(2-(((3-hydroxycyclobutyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)cyclobutane-1-ol;

[0503] 3-(((2',2”-Dichloro-3”-(2-((((3-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)propane-1-ol;

[0504] 2-(((7-(2,2'-dichloro-4”-(((2-hydroxyethyl)amino)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)-2-methylpropane-1-ol.

[0505] In one embodiment, the compound of formula (VIII) is:

[0506] 2-(((2',2”-Dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol.

[0507] Certain features of the invention described in individual embodiments may also be provided as a combination in a single embodiment. Therefore, it is contemplated that features of embodiments described as compounds of formula (I) may be combined in any suitable combination, and in combination with compounds of formulas (II)-(VII).

[0508] The compounds described and claimed herein may have one or more stereocenters and may be separated in enantiomeric pure form (optically active) or in mixtures of stereoisomers (e.g., racemic form). Methods for enantioselective synthesis and / or obtaining enantiomeric pure compounds from optically inactive starting materials are known in the art. The cis and trans geometric isomers of the compounds of the present invention may be separated as mixtures of isomers or as individual isomers.

[0509] In some embodiments, the compounds of the present invention have an (R)-configuration. In other embodiments, the compounds have an (S)-configuration. In compounds having more than one chiral center, each of the chiral centers may be independently (R) or (S).

[0510] As used herein, the term "compound" includes all geometric and stereoisomers of the structures shown. This invention also includes pharmaceutically acceptable salts of the compounds described herein. Pharmaceutically acceptable salts of this invention include salts of the parent compound that are generally regarded as safe (GRAS), such as salts formed from GRAS inorganic or organic acids.

[0511] All compounds and their pharmaceutically acceptable salts can exist either in their own form or with other substances, such as water and solvents. This, in turn, means that, in the solid state, the compounds and their salts described herein can exist in a variety of forms, for example, as solvates, including hydrates. Therefore, unless otherwise stated, the mention of compounds and their salts in this specification should be understood to cover any solid form of the compound (e.g., polymorphs or solvates).

[0512] The compounds of the present invention or their salts can be substantially or partially isolated / purified from the environment in which they are formed or detected. This can be accomplished by a purification process according to methods known in the art. The term substantially purified compound refers to a composition comprising at least 50 wt%, at least about 60 wt%, at least about 70 wt%, at least about 80 wt%, at least about 90 wt%, at least about 95 wt%, or at least about 99 wt% of the compounds of the present invention or their salts.

[0513] Medical use

[0514] For the sake of brevity, the uses and methods will be described simply with reference to "the compounds of the present invention". It should be understood that any of the disclosed compounds, including any embodiments thereof, may be used for the uses described herein.

[0515] The compounds of this invention can be used as pharmaceuticals.

[0516] The compounds of the present invention, or their pharmaceutically acceptable salts or stereoisomers, or the compositions of the present invention, may be used in methods for treating diseases or conditions associated with the inhibition of PD-1 / PD-L1 interaction, wherein the disease or condition is cancer or infection.

[0517] The compounds disclosed herein can inhibit the activity of PD-1 / PD-L1 protein / protein interactions, and therefore can be used to treat diseases and conditions associated with PD-1 / PD-L1 interaction activity. Therefore, the present invention provides compounds and compositions for methods of inhibiting PD-1 / PD-L1 interactions, said methods comprising administering to a patient in need of such treatment the compounds of the present invention or pharmaceutically acceptable salts or stereoisomers thereof.

[0518] The compounds of the present invention, or their pharmaceutically acceptable salts or stereoisomers, or the compositions of the present invention, can be further used to enhance, stimulate, and / or increase the immune response in patients with cancer or acute or chronic infections. The compounds disclosed herein can be used alone, in combination with other agents or therapies, or as adjuncts in the treatment of diseases or conditions, including cancer or infectious diseases.

[0519] The compounds of this invention induce the reversal of T cell exhaustion that may occur in cancer or infection. Experiments conducted by the applicant have demonstrated that the compounds of this invention inhibit PD-1 / PD-L1 interaction in vitro and / or in vivo, in cancer cells, and during infection. Blockade of PD-1 enhances the immune response in mammals (including humans) to cancer cells and infectious diseases.

[0520] In some embodiments, this document provides compounds and compositions used in methods for treating cancer.

[0521] In one embodiment, this disclosure provides compounds and compositions for a method of inhibiting tumor cell growth.

[0522] In some embodiments, this document provides a method for treating cancer, the method comprising administering the compounds and compositions of the present invention to a subject in need of such treatment.

[0523] In some embodiments provided herein, there is a method for inhibiting tumor cell growth, the method comprising administering the compounds and compositions of the present invention to a subject in need of such treatment.

[0524] The compounds of this invention can be used for all types of cancer with PD-L1 overexpression. Non-limiting examples of cancers that can be treated with the compounds of this invention include MSI-H / dMMR colorectal cancer, PM, pleural mesothelioma, TNBC, triple-negative breast cancer, CSCC, cutaneous squamous cell carcinoma, TMB-H, high tumor mutation burden, CRC, colorectal cancer, BCG-BC, BCG-Guérin bladder cancer, EC, endometrial cancer, ESCC, esophageal squamous cell carcinoma, SCLC, small cell lung cancer, RCC, renal cell carcinoma, MCC, Merkel cell carcinoma, HCC, hepatocellular carcinoma, PMBCL, primary mediastinal large B-cell lymphoma, CC, cervical cancer, GC, gastric cancer, MSI-H, high microsatellite instability, dMMR, mismatch repair deficiency, UC, urothelial carcinoma, cHL, classical Hodgkin lymphoma, HNSCC, head and neck squamous cell carcinoma, NSCLC, and non-small cell lung cancer.

[0525] Blocking the PD-1 pathway using the compounds of this disclosure can also be used to treat infections. Therefore, the compounds of this invention can be used in methods of treating infections. The compounds of this invention can be used to treat all types of infections with PD-1 / PD-L1 overexpression. These may be viral, bacterial, fungal, and parasitic infections. Non-limiting examples of infections that can be treated with the compounds of this invention are chronic hepatitis B, chronic hepatitis C, chronic hepatitis D, HIV and SIV, Covid and other coronaviruses, herpes simplex virus, cytomegalovirus, Kaposi's sarcoma-associated herpesvirus, varicella-zoster virus and other herpesviruses, influenza virus, lymphocytic choriomeningitis virus, Japanese encephalitis virus, Ebola virus, Hantavirus, Freund's retrovirus, respiratory syncytial virus, rabies virus, tuberculosis, malaria, Candida albicans, Helicobacter pylori, Staphylococcus aureus, Pseudomonas aeruginosa, Treponema pallidum, Borrelia burgdorferi, and sepsis.

[0526] In one embodiment, this disclosure provides compounds and compositions for a method of treating bacterial infections.

[0527] In one embodiment, this disclosure provides compounds and compositions used in a method for treating viral infections.

[0528] In one embodiment, this disclosure provides compounds and compositions for a method of treating chronic infections.

[0529] In one embodiment, this disclosure provides compounds and compositions for a method of treating acute infections.

[0530] In one embodiment, this disclosure provides a method for treating a viral infection, the method comprising administering a compound or composition of the invention to a subject in need of such treatment.

[0531] In one embodiment, this disclosure provides a method for treating a bacterial infection, the method comprising administering a compound or composition of the invention to a subject in need of such treatment.

[0532] In one embodiment, this disclosure provides a method for treating a chronic infection, the method comprising administering a compound or composition of the invention to a subject in need of such treatment.

[0533] In one embodiment, this disclosure provides a method for treating an acute infection, the method comprising administering a compound or composition of the invention to a subject in need of such treatment.

[0534] Preparation, dosage form and application

[0535] The present invention also relates to pharmaceutical compositions comprising the compounds disclosed herein or pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable carriers or excipients. In these compositions, the compounds of the present invention are used as the active ingredient.

[0536] Therefore, this disclosure provides a composition comprising a compound of formula (I) or any of the formulas described herein, or a pharmaceutically acceptable salt thereof or any embodiment thereof, and at least one pharmaceutically acceptable carrier or excipient.

[0537] These compositions can be prepared according to methods known in the art and can be administered via any route suitable for the condition to be treated. Suitable routes include, for example, topical, transdermal, parenteral, nasal, oral, and rectal administration. It should be understood that preferred routes may vary depending on, for example, the recipient's condition. Oral administration is particularly preferred and advantageous. The compounds according to the invention can be administered simply and safely via oral administration.

[0538] In preparing the compositions of the present invention, the active ingredients are typically mixed with excipients, diluted with excipients, or encapsulated in a carrier in the form of, for example, tablets, capsules, sachets, paper, or other containers (liquid, solid, spray).

[0539] Tablets, capsules, and other formulations suitable for oral administration are particularly preferred.

[0540] Examples of suitable excipients include microcrystalline cellulose, polyvinylpyrrolidone, cellulose, lactose, glucose, sucrose, alginate, gelatin, calcium silicate, water, sorbitol, mannitol, starch, gum arabic, calcium phosphate, syrup, and methylcellulose. Formulations may include emulsifiers and suspending agents; preservatives such as methylparaben and propylparaben; sweeteners; and flavoring agents. The composition may also include lubricants such as talc, magnesium stearate, and mineral oil; and wetting agents; the compositions of the present invention can be formulated using procedures known in the art.

[0541] General Synthesis. In another aspect, the present invention relates to methods for obtaining compounds according to the invention. Examples of general methods for obtaining the compounds of the invention and synthetic routes for preparing them and their intermediate compounds are explained below.

[0542]

[0543] General Solution 1

[0544]

[0545] In General Scheme 1, the following reaction conditions are typically applied: (Step 1) Synthesis via any metal cross-coupling reaction (such as the Suzuki coupling reaction); in the presence of a suitable catalyst (e.g., Pd(PPh3)4, Pd(dppf)Cl2) and a suitable base (e.g., Na2CO3, K2CO3, Cs2CO3), using a suitable solvent (1,4-dioxane, 1,2-dimethoxyethane), at a suitable temperature (e.g., 110°C); (Step 2) Conversion to the corresponding boron derivative (Int-A) using bis(pinacol)diboron and a base (e.g., KOAc) and a palladium catalyst (e.g., Pd(dppf)Cl2.DCM complex) in the presence of an inert solvent (e.g., dioxane, DMF, and THF, etc.), at a suitable temperature (e.g., 90 to 110°C). This compound is further used in another cross-metal coupling reaction using the above conditions.

[0546] General Solution 2

[0547]

[0548] In General Scheme 2, the following reaction conditions are typically applied: (Step 1) The corresponding bromine or iodine derivative is synthesized using a suitable halogenating agent (e.g., NBS or NIS); (Steps 2 and 3) In the presence of a suitable catalyst (e.g., Pd(PPh3)4, Pd(dppf)Cl2.DCM complex) and a suitable base (e.g., Na2CO3, K2CO3), in a suitable solvent (e.g., 1,4-dioxane, 1,2-dimethoxyethane), at a suitable temperature (e.g., 90 to 110 °C). (Step 4) Alkylation with a suitable base (e.g., K2CO3), or reductive amination with a suitable reducing agent (e.g., NaBH3CN, NaBH(OAc)3), or amide coupling with a suitable reagent (T3P, EDC, HOBt, HATU) in a suitable solvent (e.g., DCM, MeOH, DMF, or a mixture of solvents) at a suitable temperature (e.g., 25°C) to prepare compound (II) derivative; and other different reaction conditions depending on G1 to introduce R b .

[0549]

[0550] General Solution 3

[0551]

[0552] In general scheme 3, the following reaction conditions are typically applied: (Step 1) synthesis via copper-catalyzed coupling in a suitable solvent (e.g., acetonitrile) at a suitable temperature (e.g., 80°C) using a suitable reagent (e.g., CuI) and a suitable ligand (e.g., TEMDA) and a suitable base (e.g., Cs2CO3); (Step 2) synthesis in the presence of a suitable catalyst (e.g., Pd(dppf)Cl2) in a suitable solvent (e.g., 1,4-dioxane) using a suitable base (e.g., Na2CO3) at a suitable temperature (e.g., 110°C).

[0553]

[0554] General Solution 4

[0555]

[0556] In general scheme 4, the following reaction conditions are typically applied: Int-B is prepared from commercially available materials, according to the introduction of R... bThe coupling agent is used under different reaction conditions (e.g., alkylation with a suitable base, such as K2CO3, or reductive amination with a suitable reducing agent, such as NaBH3CN, NaBH(OAc)3, or amide coupling with a suitable reagent, such as T3P, EDC, HOBt, HATU, in a suitable solvent, such as DCM, MeOH, or DMF, at a suitable temperature). (Step 1) The amide is synthesized in the presence of a suitable catalyst (e.g., Pd(PPh3)4, Pd(dppf)Cl2, Pd(dppf)Cl2.DCM complex), in a suitable solvent (e.g., 1,4-dioxane, 1,2-dimethoxyethane), using a suitable base (e.g., Na2CO3, K2CO3, Cs2CO3) at a suitable temperature (e.g., 90°C or 110°C).

[0557]

[0558] General Solution 5

[0559]

[0560] In General Scheme 4, the following reaction conditions are typically applied: (Step 1) Synthesis from commercially available starting materials, using a suitable catalyst (e.g., Pd(dppf)Cl2) and a suitable base (e.g., Na2CO3), in a suitable solvent (e.g., 1,4-dioxane), at a suitable temperature (e.g., 90°C); (Step 2) Preparation of aldehydes using suitable reagents (e.g., OSO4, NaIO4), or preparation of alkyl halides using suitable reagents (e.g., OSO4, NaIO4, NaBH4, PBr3), and other different sets of reaction conditions introducing Rb. (Step 3) In the presence of a suitable catalyst (e.g., Pd(PPh3)4, Pd(dppf)Cl2, Pd(dppf)Cl2.DCM complex), in a suitable solvent (e.g., 1,4-dioxane, 1,2-dimethoxyethane), using a suitable base (e.g., Na2CO3, K2CO3, Cs2CO3) at a suitable temperature (e.g., 90°C or 110°C).

[0561] Example

[0562] The compounds of this invention can be prepared using known organic synthesis techniques. Those skilled in the art can readily select suitable solvents, temperatures, starting materials, and appropriate synthetic routes.

[0563] abbreviation:

[0564] ACN-acetonitrile

[0565] AcOH-acetic acid

[0566] BOC2O-Di-tert-butyl dicarbonate

[0567] t BuXphos-2-di-tert-butylphosphine-2',4',6'-triisopropylbiphenyl

[0568] B2Pin2-4,4,4',4,,5,5,5',5,-octamethyl-2,2'-bis-,3,2-dioxaborane

[0569] DCM-dichloromethane

[0570] DEAD-Diethyl azodicarbonate

[0571] Dess-martin-Diess-Martin-Periodine

[0572] DME-1,2-Dimethoxyethane

[0573] DMF-N,N'-dimethylformamide

[0574] Dialkylox-1,4-dioxane

[0575] EA-ethyl acetate

[0576] EtOH - Ethanol

[0577] Ex-example

[0578] FA-formic acid

[0579] h-hours

[0580] HPLC-High Performance Liquid Chromatography

[0581] KOAc-potassium acetate

[0582] LAH-Lithium Aluminum Hydrogen

[0583] LC-MS (Liquid Chromatography-Mass Spectrometry)

[0584] MeOH-methanol

[0585] MW Microwave Oven

[0586] MS-molecular sieve

[0587] NBS-N-bromosuccinimide

[0588] NIS-N-iodosuccinimide

[0589] NMR - Nuclear Magnetic Resonance

[0590] Pd2(dba)3-tris(dibenzylacetone)dipalladium(0)

[0591] Pd(PPh3)4-tetra(triphenylphosphine)palladium(0)

[0592] PdCl2(dppf)-[1,1'-bis(diphenylphosphine)ferrocene]palladium(II) chloride

[0593] PdCl2(dppf).dcm-[1,1'-bis(diphenylphosphine)ferrocene]palladium(II) chloride

[0594] dichloromethane complex

[0595] Preparative high-performance liquid chromatography (Prep-HPLC)

[0596] Py-pyridine

[0597] RT - room temperature

[0598] Sat. - saturated

[0599] SFC-Supercritical Fluid Chromatography

[0600] SM - Starting Materials

[0601] TEA-Triethylamine

[0602] TFA-trifluoroacetic acid

[0603] THF-Tetrahydrofuran

[0604] TLC (Thin Layer Chromatography)

[0605] TMEDA-Tetramethylethylenediamine

[0606] TPP-Triphenylphosphine

[0607] T3P-propanephosphonic anhydride

[0608] General considerations and analysis methods:

[0609] Unless otherwise specified, all compounds used in the reaction were commercially available. All compounds were characterized by NMR, HPLC, and LC-MS (ESI+APCI). NMR data were obtained on a Varian 400MHz spectrometer, and all chemical shifts are reported in parts per million (ppm) and measured relative to TMS. LC-MS (ESI+APCI) measurements were performed on a Shimadzu LCMS2020 equipped with an N-series mass spectrometer. The yields of compounds provided refer to the isolated compounds.

[0610] All compounds were purified or enantiomerized using one of the following methods.

[0611] Reversed-phase HPLC purification method:

[0612] 1. The crude compound was purified by reversed-phase HPLC using an Inertsil ODS 3V column (250x20) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O solution, B = 100% ACN.

[0613] 2. The crude compound was purified by reversed-phase HPLC using an Inertsil ODS column (250x20) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O solution, B = ACN:MeOH (1:1) 100%.

[0614] 3. The crude compound was purified by reversed-phase HPLC using the following method: X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O solution, B = 100% ACN.

[0615] 4. The crude compound was purified by reversed-phase HPLC as follows: X-Bridge C18 column (250x20) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O solution, B = ACN:MeOH (1:1) 100%.

[0616] 5. The crude compound was purified by reversed-phase HPLC as follows: Triart C18 column (250x21) mm, 5.0 μm; mobile phase (A:B), A = 10 mmol ABC in H2O solution, B = ACN:MeOH (1:1) 100%.

[0617] 6. The crude compound was purified by reversed-phase HPLC as follows: X-Bridge C18 column (250x20) mm, 5.0 μm; mobile phase (A:B), A = 10 mmol ABC in H2O solution, B = ACN:MeOH (1:1) 100%.

[0618] 7. The crude compound was purified by reversed-phase HPLC as follows: X-Bridge C18 column (250 x 20) mm, 5.0 μm; mobile phase (A:B), A = 10 mmol ABC in H2O solution, B = 100% ACN.

[0619] SFC purification method:

[0620] 1. Racemic compounds were chirally separated by SFC and dissolved in tetrahydrofuran:methanol (1:1). The chromatographic column was a chiral Pak IG (250 x 21) mm, 5.0 μm; the mobile phase was 55:45 (A:B). A = liquid CO2, B = acetonitrile:methanol (1:1), flow rate: 45 mL / min; wavelength: 233 nm.

[0621] 2. The racemic compound was chirally separated by SFC in a tetrahydrofuran:methanol (1:1) column. The column was a chiral Pak IC (250x21) mm, 5.0 μm; the mobile phase was 60:40 (A:B). A = liquid CO2, B = 0.2% triethylamine in methanol; flow rate: 40 mL / min; wavelength: 254 nm.

[0622] Chiral HPLC purification method:

[0623] 1. Racemic compounds were separated by chiral separation using normal-phase HPLC. The chromatographic column was a chiral Pak IG (250*21) mm, 5.0 μm; the mobile phase was 60:40 (A:B). A = 0.1% TFA in n-hexane solution, B = ethanol (1:1).

[0624] Example 1: 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzyl)piperidine-2-carboxylic acid

[0625]

[0626] The compound of Example 1 was synthesized via intermediate 4, as shown in the diagram below.

[0627]

[0628] Preparation of intermediate (4): 4,4,5,5-Tetramethyl-2-(2-methyl-[1,1'-biphenyl]-3-yl)-1,3,2-dioxaborane

[0629] Step 1: Synthesis of 3-bromo-2-methyl-1,1'-biphenyl

[0630] A solution of 1,4-dioxane (20 mL) of a mixture of 1-bromo-3-iodo-2-methylbenzene (4.0 g, 13.4 mmol), phenylboronic acid (1.72 g, 14.1 mmol), and an aqueous solution (4.0 mL) of Cs₂CO₃ (10.97 g, 33.6 mmol) and Pd(PPh₃)₄ (467 mg, 0.4 mmol) were added, and the mixture was degassed with N₂ for 30 min. The reaction mixture was then heated at 100 °C for 5 h. The reaction mixture was cooled to room temperature and diluted with EA (10 mL) and water (10 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine (20 mL), dried over Na₂SO₄, and concentrated under vacuum to give a crude product, which was purified by Biotage rapid column chromatography using a 0–10% ethyl acetate solution in hexane as the eluent to give the title compound (1.5 g, 45%) as a colorless liquid. LC-MS calculation showed C32H29N3O2(M+H)+: m / z = 487.6; measured value: 488.2.

[0631] Step 2: Synthesis of 4,4,5,5-Tetramethyl-2-(2-methyl-[1,1'-biphenyl]-3-yl)-1,3,2-dioxaborane

[0632] To a solution of 1,4-dioxane (15 mL) of a mixture of 3-bromo-2-methyl-1,1'-biphenyl (1.5 g, 6.0 mmol) and B2Pin2(pinacolyl)diborane (1.84 g, 7.2 mmol), KOAc (1.48 g, 15.1 mmol) and Pd(dppf)Cl2·DCM (247 mg, 0.3 mmol) were added, and the mixture was degassed with N2 for 30 min. The reaction mixture was then heated at 100 °C for 3 h. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with EA (3 x 25 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, and concentrated under vacuum to give a crude product. The crude product was purified by Biotage rapid column chromatography using a hexane solution of 0–10% ethyl acetate to give the title compound (1.0 g, 56%) as a grayish-white solid, which was used directly in the next step.

[0633] Preparation of Example 1: 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzyl)piperidine-2-carboxylic acid

[0634]

[0635] Step 1: Synthesis of 7-chloro-3-iodoimidazole[1,2-a]pyridine

[0636] NIS (7.74 g, 34.4 mmol) was added fractionally to a DMF (50 mL) solution of 7-chloroimidazolo[1,2-a]pyridine (5.0 g, 32.7 mmol) with stirring. The reaction mixture was stirred at room temperature for 16 hours. Under vigorous stirring, the reaction mixture was slowly poured into ice water. The precipitated solid was filtered off, washed with water, and dried under vacuum to give the title compound (8.8 g, 96%) as a pale yellow solid. The crude compound could be used in the next step without further purification.

[0637] Step 2: Synthesis of 4-(7-chloroimidazolo[1,2-a]pyridin-3-yl)benzaldehyde

[0638] 7-Chloro-3-iodoimidazole[1,2-a]pyridine (2.59 g, 9.8 mmol), (4-formylphenyl)boronic acid (1.67 g, 11.1 mmol), Na₂CO₃ (6.89 g, 6.51 mmol), Pd(PPh₃)₄ (538 mg, 0.04 mmol), water (65 mL), and DME (130 mL) were mixed and degassed with N₂ for 30 min. The reaction mixture was stirred at 80 °C for 16 h. The reaction mixture was cooled to room temperature and diluted with EA. The organic layer was separated, and the aqueous layer was extracted with EA (2 x 25 mL). The combined organic layers were washed with brine (50 mL), dried over Na₂SO₄, and concentrated under vacuum to give the crude product. The crude compound was purified by combined rapid column chromatography using a hexane solution of 10–50% ethyl acetate as the mobile phase to give the title compound (2.0 g, 84%) as a grayish-white solid.

[0639] Step 3: Synthesis of 4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzaldehyde

[0640] A solution of 1,4-dioxacyclopentane (10 mL) of 4-(7-chloroimidazolo[1,2-a]pyridin-3-yl)benzaldehyde (440 mg, 1.74 mmol) and 4,4,5,5-tetramethyl-2-(2-methyl-[1,1'-biphenyl]-3-yl)-1,3,2-dioxaborane (900 mg, 3.08 mmol) was stirred and added to water (2.5 mL) containing an aqueous solution of Na₂CO₃ (545 mg, 5.14 mmol) and Pd(dppf)Cl₂ (62 mg, 0.085 mmol). The mixture was degassed with N₂ for 30 min, and then the reaction mixture was heated at 110 °C for 16 h. After cooling to room temperature, EA (20 mL) and water (20 mL) were added to the mixture, and the mixture was separated. The aqueous layer was extracted with EA (3 × 20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The crude product was purified by Combiflash column chromatography using a hexane solution of (5-30%) ethyl acetate to give the title compound as a grayish-white solid (470 mg, 70%).

[0641] Step 4: Synthesis of 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzyl)piperidine-2-carboxylic acid

[0642] A mixture of 200 mg (0.51 mmol) of 4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzaldehyde, 51.2 mg (0.44 mmol) of piperidine-2-carboxylic acid, and one drop of AcOH in ethanol and DMF (1:1) (4.0 mL) was stirred at room temperature for 3 hours. NaBH3CN (97 mg, 1.54 mmol) was added to the reaction mixture, and stirring was continued at room temperature for 16 hours. The organic volatiles were removed under reduced pressure, the residue was dissolved in water, and extracted with DCM (3 x 20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and the solvent was evaporated under reduced pressure. The crude product was purified by reversed-phase HPLC (X-Bridge C18 column (250 x 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = ACN 100%) to give title compound 1 (20 mg, 8%) as a pale yellow solid.

[0643] 1H NMR(400MHz,DMSO-d6)δ:8.61(d,J=7.2Hz 1H), 7.82(s,1H), 7.66(t,J=8Hz,3H), 7.53(d,J=8Hz,2H), 7.47(t,J=7.6Hz,2H), 7.42-7.35(m,4H), 7.27(d,J=5.6Hz,1H), 7.04(d,J=7.2Hz,1H), 3.94(d,J=13.6Hz,1H), 3.57(d,J=13.6Hz,1H), 3.15-3.13(m,1H), 2.91(m,1H), 2.32(m,1H), 2.17(s,3H), 1.51(m,3H). LC-MS calculation: C33H31N3O2(M+H)+: m / z=501.63; Measured value: 502.25.

[0644] Racemic compound 1 was separated by chirality using normal-phase HPLC. The column was a chiral Pak IG (250*21) mm, 5.0 μm; the mobile phase was 60:40 (A:B). A was a hexane solution of 0.1% TFA, and B was ethanol (1:1), yielding peaks 1 and 2.

[0645] Peak 1: 1 H NMR(400MHz, DMSO-d6)δ:8.65(d,J=7.2Hz,1H),7.92(s,1H),7.76(d,J=7.2H z,2H),7.69(s,1H),7.59(d,J=7.2Hz,2H),7.49-7.34(m,7H),7.29(d,J=7.2H z,1H),7.12(d,J=6.8Hz,1H),4.22(m,1H),3.91(m,1H),2.67(s,1H),2.3(d, J=7.6Hz,1H),2.17(s,3H),2.0-1.98(m,2H),1.77(m,1H),1.62-1.47(m,4H).

[0646] LC-MS calculation yielded C33H31N3O2(M+H)+: m / z = 501.63; measured value: 502.2.

[0647] Peak 2: 1H NMR(400MHz,DMSO-d6)δ:8.65(d,J=7.2Hz,1H),7.92(s,1H),7.76(d,J=7.2Hz,2H ),7.69(s,1H),7.50-7.53(m,2H),7.81(t,J=7.6Hz,2H),7.42-7.34(m,5H),7.28 (d,J=7.2Hz,1H),7.13-7.08(m,1H),4.17(s,3H),3.78(d,J=12.8Hz,1H),3.11-3 .09(m,1H),2.63-2.58(m,1H),2.17-2.10(m,4H),1.90-1.73(m,3H),1.47(m,1H).

[0648] The LC-MS calculation result was C33H31N3O2(M+H)+: m / z = 501.63; the measured value was 502.2.

[0649] The following Examples 2 to 14 shown in Table 1 were prepared using a suitable amine according to a similar procedure as described in Example 1. Example 15 in Table 1 was prepared using a suitable amine according to a similar procedure as described in Example 52.

[0650] Table 1

[0651]

[0652]

[0653]

[0654] Example 20: 1-(2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzyl)piperidine-2-carboxylic acid

[0655]

[0656] The compound of Example 20 was synthesized via the route shown in the following scheme.

[0657]

[0658] Prepared in the same manner as described in Example 1 (steps 1 and 2).

[0659] Step 3: Synthesis of (2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzyl)proline

[0660] Proline 7 (51.2 mg, 0.44 mmol) and acetic acid (1 drop) were added to a stirred solution of 2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzaldehyde (150 mg, 0.44 mmol) in ethanol and DMF (1:1) (3.0 mL), and the mixture was stirred at room temperature for 3 hours. NaCNBH3 (83.8 mg, 1.33 mmol) was added to the reaction mixture, and stirring was continued at room temperature for 16 hours. The reaction was confirmed by TLC. The volatile organic compounds were evaporated under vacuum to obtain a crude residue, which was dissolved in water and extracted with DCM (3 × 10 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered, and evaporated. The crude substance was purified by preparative HPLC to give the title compound (30 mg, 15%) as a pale yellow solid.

[0661] 1 ¹H NMR (400MHz, DMSO-d⁶) δ: 8.7 (d, J = 6.8Hz, 1H), 7.94 (s, 1H), 7.66 (s, 1H), 7.27–7.49 (m, 8H), 7.08–7.04 (m, 3H), 4.3 (s, 2H), 3.93 (s, 6H), 3.79 (s, 1H), 3.45 (s, 1H), 2.98 (s, 3H), 2.27–2.32 (m, 1H), 2.18 (s, 3H), 1.95 (s, 2H), 1.76 (s, 1H). LC-MS calculated C₃₄H₃₃N₃O₄(M+H)⁺: m / z = 547.66; measured value: 548.5.

[0662] Chiral separation:

[0663] The racemic compounds were separated by chiral separation using normal-phase chromatography. The chromatographic column was a chiral Pak IG (250*21) mm, 5.0 μm column; the mobile phase was 60:40 (A:B). A = 0.1% TFA in n-hexane solution, B = ethanol (1:1), yielding peaks 1 and 2.

[0664] Peak 1: 1 H NMR (400MHz, DMSO-d6)8.7(d,J=6.8Hz,1H),7.94(s,1H),7.66(s,1H),7.27-7.49(m,8H),7.08-7.04(m,3H),4.3(s, 2H),3.93(s,6H),3.79(s,1H),3.45(s,1H),2.98(s,3H),2.27-2.32(m,1H),2.18(s,3H),1.95(s,2H),1.76(s,1H).

[0665] LC-MS calculation yielded C33H31N3O2(M+H)+: m / z = 547.66.63; measured value: 548.5.

[0666] Peak 2: 1 H NMR (400MHz, DMSO-d6) δ: 8.7 (d, J = 7.6Hz, 1H), 7.92 (s, 1H), 7.65 (s, 1H), 7.35-7.47 (m, 7H), 7.27 (d, J = 7.2Hz, 1H), 7.06 (d, J = 7. 26Hz,1H),7.01(s,2H),4.2(s,2H),3.92(s,6H),3.48(s,2H),2.83(s,1H),2.18(s,4H),1.97(s,1H),1.83(s,1H),1.67(s,1H).

[0667] LC-MS calculation yielded C34H33N3O4(M+H)+: m / z = 547.66; measured value: 548.4.

[0668] Following a similar procedure as described in Example 20, the following examples, as shown in Table 2, were prepared using appropriate amines:

[0669] Table 2

[0670]

[0671]

[0672] Example 23: (R)-(1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzyl)pyrrolidine-2-yl)methanol

[0673]

[0674] The compound of Example 23 was synthesized via the route shown in the following scheme.

[0675]

[0676] Under a nitrogen atmosphere, LAH (180 mg, 47.3 mmol) was added to a THF (20 mL) solution of (1 g, 23 mmol) of (4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)benzyl)-D-proline (23 mmol) at 0 °C. After stirring for 2 hours at room temperature, the reaction mixture was quenched with 1 N NaOH, filtered, washed with ethyl acetate, dried over Na2SO4, and concentrated to give the title compound (450 mg, 50%) as a yellow solid.

[0677] 1 H NMR(400MHz, DMSO-d6)δ:8.59(d,J=7.2Hz,1H),7.8(s,1H),7.64(d,J=8.0Hz,3H),7.51-7.45(m, 4H),7.42-7.34(m,5H),7.27(dd,J=6.8Hz,1H),7.04(dd,J=7.2Hz,1H),4.46(s,1H),4.13(d,J=13 0.2Hz, 1H), 3.49(d, J = 7.6Hz, 1H), 3.41(d, 2H), 2.83(t, J = 2.4Hz, 1H), 2.67-2.57(m, 2H), 2.2(s, 3H), 1.87(q, J = 8.4Hz, 1H), 1.64-1.56(m, 3H). LC-MS calculation: C32H31N3O(M+H)+: m / z = 473.62; measured value: 474.4

[0678] Following a similar procedure to that described in Example 23, the following examples, as shown in Table 3, were prepared using appropriate amines:

[0679] Table 3

[0680]

[0681]

[0682] Example 25: 1-(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzyl)azacyclobutane-3-carboxylic acid

[0683] The compound of Example 25 was synthesized via the route shown below.

[0684]

[0685] Step 1: Synthesis of 6-(3-bromo-2-methylphenyl)-2,3-dihydrobenzo[b][1,4]dioxin

[0686] The title compound was prepared in a manner similar to that in Example 1, yielding a viscous liquid of the title compound (5.2 g, 56%).

[0687] Step 2: Synthesis of 2-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane

[0688] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (5.2 g, 60%) of the title compound.

[0689] Step 3: Synthesis of 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzaldehyde

[0690] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (1.87 g, 90%). LC-MS calculations showed C29H22N2O3(M+H)+: m / z = 446.51; measured value: 447.25.

[0691] Step 4: Synthesis of 1-(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzyl)azacyclobutane-3-carboxylic acid

[0692] The title compound was prepared in a manner similar to that in Example 1. The crude product was purified by preparative HPLC to obtain the title compound (45 mg, 29%) as a white solid.

[0693] 1 H NMR (400MHz, DMSO-d6)δ:

[0694] 8.58 (d, J = 6.8 Hz, 1H), 7.80 (s, 1H), 7.63 (t, J = 7.6 Hz, 3H), 7.45 (d, J = 6.8 Hz, 2H), 7.33-7.31 (m, 2H), 7.24 (m, 1H), 7.03 (d, J = 6 Hz, 1H), 6.94-6.84 (m, 3H), 4.28 (s, 4H), 3.62 (s, 2H), 3.5 (m, 1H), 3.42 (s, 2H), 3.23 (s, 2H), 2.17 (s, 3H). LC-MS calculation: C33H28N3O4(M+H)+: m / z = 531.61; measured value: 532.2.

[0695] Following a similar procedure to that described in Example 25, the following examples, as shown in Table 4, were prepared using appropriate amines:

[0696] Table 4

[0697]

[0698]

[0699]

[0700]

[0701] Example 39: ((4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)-2,6-dimethoxybenzyl)-D-proline

[0702]

[0703] The compound of Example 39 was synthesized via the route shown in the following scheme.

[0704]

[0705] Step 1: Synthesis of 4-(7-chloroimidazolo[1,2-a]pyridin-3-yl)-2,6-dimethoxybenzaldehyde

[0706] The title compound (1.15 g, 37%) was prepared in the same manner as described in Example 1, yielding a white solid. LC-MS calculations yielded C16H13ClN2O3(M+H)+: m / z = 316.74; measured value: 317.25.

[0707] Step 2: Synthesis of 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)-2,6-dimethoxybenzaldehyde.

[0708] The title compound (1 g, 100%) was prepared in the same manner as described in Example 1, and a white solid was obtained. LC-MS calculation showed C31H26N2O5(M+H)+: m / z = 506.56; measured value: 507.25.

[0709] Step 3: Synthesis of tert-butyl(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)-2,6-dimethoxybenzyl)proline ester

[0710] The title compound was prepared in the same manner as described in Example 1, yielding a crude, brown, viscous substance (250 mg), which was used in the next step without purification. LC-MS calculation showed C40H43N3O6(M+H)+: m / z = 661.8; measured value: 662.5.

[0711] Step 4: Synthesis of (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)-2,6-dimethoxybenzyl)proline

[0712] At 0 °C, a solution of 4 M HCl in dioxane (5 mL) was added to a stirred solution of [250 mg, 377 mmol] of [4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl]imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxybenzyl]proline tert-butyl ester (2 mL) in DCM (5 mL). The reaction mixture was then stirred at room temperature for 16 hours. The volatile organic compounds were evaporated to give a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 x 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = ACN 100%) to give the title compound (55 mg, 24%) as a white solid.

[0713] 1 H NMR (400MHz, DMSO-d6) δ: 8.73 (d, J=6.8Hz, 1H), 7.93 (s, 1H), 7.64 (s, 1H), 7.32 (dd, J= 7.6Hz,2H),7.24(d,J=15.6Hz,1H),7.06-7.02(m,3H),6.94-6.84(m,3H),4.28(s,4H) ,4.23(s,2H),3.93(s,6H),3.56(d,J=5.2Hz,2H),2.87(d,J=6.8Hz,2H),2.18(s,3H),1.99-1.87(m,2H),1.67(s,1H). LC-MS calculation: C36H35N3O8(M+H)+:m / z=605.69; measured value: 606.4.

[0714] Following a similar procedure to that described in Example 39, suitable amines were used to prepare the following examples as shown in Table 5:

[0715] Table 5

[0716]

[0717]

[0718] Example 41: (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzoyl)glycine

[0719]

[0720] The compound of Example 41 was synthesized via the route shown in the following scheme.

[0721]

[0722] Step 1: Synthesis of methyl 4-(7-chloroimidazolo[1,2-a]pyridin-3-yl)benzoate

[0723] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (1.1 g, 35%). LC-MS calculations showed C15H11ClN2O2(M+H)+: m / z = 286.72; measured value: 287.2.

[0724] Step 2: Synthesis of methyl 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzoate

[0725] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (800 mg, 45%). LC-MS calculations showed C30H24N2O4(M+H)+: m / z = 476.53; measured value: 477.

[0726] Step 3: Synthesis of 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzoic acid

[0727] To a stirred solution of methyl 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzoate (800 mg, 1.67 mmol) in THF:MeOH (14 mL: 4 mL), 2 mL of an aqueous solution of LiOH·H₂O (121 mg, 5.042 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure, and the residue was dissolved in water, washed with diethyl ether (2 x 10 mL), and the aqueous layer was acidified with 1 N HCl and extracted with DCM (3 x 10 mL). The combined organic layers were dried over Na₂SO₄, filtered, evaporated under reduced pressure to give a crude product, washed with pentane, filtered, and dried under vacuum to give the title compound (600 mg, 77%) as a white solid. LC-MS calculation of C29H22N2O4(M+H)+: m / z = 462.51; measured value: 463.

[0728] Step 4: Synthesis of ethyl(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzoyl)glycine ester.

[0729] At 0 °C, T3P (193 mL, 0.64 mmol) was added to a stirred solution of 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzoic acid (200 mg, 0.43 mmol), glycine ethyl ester (71 mg, 0.51 mmol), and TEA (241 mL, 1.73 mmol) in DCM (10 mL), and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with water and DCM, and the organic layer was separated. The aqueous layer was extracted with DCM (3 x 10 mL), and the combined organic layers were dried over Na2SO4, filtered, and evaporated to give the title compound (190 mg, 80.23%) as a brown viscous substance, which could be used in the next step without purification. The LC-MS calculation result was C33H29N3O5(M)+: m / z = 547.61; the measured value was 547.2.

[0730] Step 5: Synthesis of (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzoyl)glycine

[0731] To a stirred solution of 190 mg (0.34 mmol) of ethyl (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)benzoyl)glycine ester in THF:MeOH (7.0 mL:2 mL), 43 mg (1.042 mmol) of LiOH·H₂O (1 mL) aqueous solution was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure, and the residue was dissolved in water, washed with diethyl ether (2 x 10 mL), and the aqueous layer was acidified with 1 N HCl and extracted with DCM (3 x 10 mL). The combined organic layers were dried over Na₂SO₄, filtered, evaporated under reduced pressure to give a crude product, washed with pentane, filtered, and dried under vacuum to give the title compound (8 mg, 15%) as a white solid.

[0732] 1 ¹H NMR (400MHz, DMSO-d⁶) δ: 8.70 (d, J = 7.2Hz, 1H), 8.05 (d, J = 8Hz, 2H), 7.95 (s, 1H), 7.85 (d, J = 8Hz, 2H), 7.65 (s, 1H), 7.33 (d, J = 7.6Hz, 2H), 7.24 (d, J = 7.2Hz, 1H), 7.08 (d, J = 6.8Hz, 1H), 6.94–6.84 (m, 3H), 4.28 (s, 4H), 3.91 (d, J = 4.4Hz, 2H), 2.18 (s, 3H). LC-MS calculated C₃¹H₂₅N₃O₅(M+H)⁺: m / z = 519.56; measured value: 518.2.

[0733] Following a similar procedure to that described in Example 41, the following examples, as shown in Table 6, were prepared using appropriate amines:

[0734] Table 6

[0735]

[0736] Example 44: N-(2-hydroxyethyl)-1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)-1H-pyrazole-3-carboxamide

[0737]

[0738] The compound of Example 44 was synthesized via the route shown in the following scheme.

[0739]

[0740] Step 1: Synthesis of ethyl 1-(7-chloroimidozop[1,2-a]pyridin-3-yl)-1H-pyrazole-3-carboxylate

[0741] TMEDA (0.08 mL, 0.53 mmol) was added to a solution of 7-chloro-3-iodoimidazolo[1,2-a]pyridine (500 mg, 1.79 mmol), ethyl 1H-pyrazole-3-carboxylate (189 mg, 1.34 mmol), CuI (52 mg, 0.26 mmol), and Cs₂CO₃ (880 mg, 2.69 mmol) in acetonitrile (5 mL). The mixture was refluxed for 16 hours. The filtrate was filtered through diatomaceous earth and concentrated by evaporation. The crude product was purified by Combiflash column chromatography using a hexane solution of 0-25% ethyl acetate to obtain the title compound (220 mg, 42%) as a grayish-white solid. LC-MS calculations showed C₁₃H₁₁ClN₄O₂(M+H)⁺: m / z = 290.71; measured value: 291.2.

[0742] Step 2: Synthesis of ethyl 1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)-1H-pyrazole-3-carboxylate

[0743] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (150 mg, 46%). LC-MS calculations showed C26H22N4O2(M+H)+: m / z = 422.49; measured value: 423.4.

[0744] Step 3: Synthesis of 1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)-1H-pyrazol-3-carboxylic acid

[0745] An aqueous solution (1 mL) of LiOH·H₂O (75 mg, 1.77 mmol) was added to a stirred solution of ethyl 1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)-1H-pyrazole-3-carboxylate (250 mg, 0.5924 mmol) in THF:MeOH (7.0 mL: 2 mL). The mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure, and the residue was dissolved in water, washed with diethyl ether (2 x 10 mL), and the aqueous layer was acidified with 1N HCl and extracted with DCM (3 x 10 mL). The combined organic layers were dried over Na₂SO₄, filtered, evaporated under reduced pressure to give a crude product, washed with pentane, filtered, and dried under vacuum to give the title compound (220 mg, 94%) as a grayish-white solid. The LC-MS calculation result was C24H18N4O2(M+H)+: m / z = 394.43; the measured value was 395.2.

[0746] Step 4: Synthesis of N-(2-hydroxyethyl)-1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)-1H-pyrazole-3-carboxamide:

[0747] The title compound was prepared in a manner similar to that in Example 41. The crude material was subjected to preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to give the title compound (29.6 mg, 27%) as a white solid.

[0748] 1 ¹H NMR (400MHz, DMSO-d⁶) δ: 8.42 (d, J = 7.2Hz, 1H), 8.34 (d, J = 5.6Hz, 2H), 7.98 (s, 1H), 7.69 (s, 1H), 7.33–7.49 (m, 7H), 7.28 (d, J = 7.2Hz, 1H), 7.13 (d, J = 6.8Hz, 1H), 6.98 (s, 1H), 4.74 (t, J = 5.2Hz, 1H), 3.5 (d, J = 6.0Hz, 2H), 3.32 (s, 2H), 2.14 (s, 3H). LC-MS calculated C₂₆H₂₃N₅O₂(M+H)⁺: m / z = 437.52; measured value: 438.4.

[0749] Following a similar procedure to that described in Example 44, the following examples, as shown in Table 7, were prepared using appropriate amines:

[0750] Table 7

[0751]

[0752] Example 48: (1-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)glycine

[0753]

[0754] The compound of Example 48 was synthesized via the route shown in the following scheme.

[0755]

[0756] Step 1: Ethyl 1-(7-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carboxylate

[0757] The title compound was prepared in a manner similar to that in Example 41, yielding a grayish-white solid (880 mg, 45%). LC-MS calculations showed C13H11ClN4O2(M+H)+: m / z = 290.71; measured value: 291.25.

[0758] Step 2: Synthesis of 1-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carboxylic acid

[0759] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (90 mg, 12%). LC-MS calculations showed C26H20N4O4(M+H)+: m / z = 452.47; measured value: 453.

[0760] Step 3: Synthesis of ethyl glycine ester of (1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)

[0761] The title compound was prepared in a manner similar to that in Example 41, yielding a brown, viscous solid (120 mg, crude). LC-MS calculations showed C30H27N5O5(M+H)+: m / z = 537.58; measured value: 538.

[0762] Step 4: Synthesis of (1-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)glycine

[0763] The title compound was prepared in a manner similar to that in Example 41, yielding a white solid (70 mg, 61%) of the title compound.

[0764] 1H NMR(400MHz, DMSO-d6)δ:12.6(s,1H),8.73(t,J=1.2Hz,1H),8.52(d,J=6.8Hz,1H),8.39(d,J =2.4Hz,1H),8.08(s,1H),7.72(s,1H),7.34(m,2H),7.26(d,J=7.2Hz,1H),7.18(d,J=6.8Hz,1 7.02 (d, J = 2.4 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 6.89 (s, 1H), 6.85 (d, J = 8.0 Hz, 1H), 4.28 (s, 4H), 3.93 (d, J = 6.0 Hz, 2H), 2.16 (s, 3H). LC-MS calculation: C28H23N5O5(M+H)+: m / z = 509.52; measured value: 510.3.

[0765] Example 49: (1-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)glycine

[0766]

[0767] The compound of Example 49 was synthesized via the route shown in the following scheme.

[0768]

[0769] Step 1: Ethyl 1-(7-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carboxylate

[0770] The title compound was prepared in a manner similar to that of Example 41, yielding a grayish-white solid (880 mg, 45%). LC-MS calculations showed C12H10ClN5O2(M+H)+: m / z = 291.7; measured value: 292.

[0771] Step 2: Synthesis of 1-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carboxylic acid

[0772] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (90 mg, 12%). LC-MS calculations showed C25H19N5O4(M+H)+: m / z = 453.46; measured value: 454.30 (M+1).

[0773] Step 3: Synthesis of ethyl glycine ester of (1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)

[0774] The title compound was prepared in a manner similar to that in Example 41, yielding a brown, viscous solid (120 mg, crude). LC-MS calculations showed C29H26N6O5(M+H)+: m / z = 538.56; measured value: 539.35 (M+1).

[0775] Step 4: Synthesis of (1-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)glycine

[0776] The title compound was prepared in a manner similar to that in Example 41, yielding a white solid (70 mg, 61%) of the title compound.

[0777] 1 H NMR(400MHz,DMSO-d6)δ:12.75(br s, 1H), 9.12(d, J = 7.2Hz, 1H), 8.94(s, 1H), 8.69(d, J = 2Hz, 1H), 7.86(s, 1H), 7.40-7.31(m, 2H), 7.28(d, J = 6.4Hz, 1H), 7.20(d, J = 7.2Hz, 1H), 7.07(d, J = 2Hz, 1H), 6.94(d, J = 8Hz, 1H), 6.90(s, 1H), 6.85(d, J = 8.4Hz, 1H), 4.29(s, 4H), 3.94(d, J = 5.2Hz, 2H), 2.18(s, 3H). LC-MS calculation: C27H22N6O5(M+H)+: m / z = 510.51; measured value: 511.35.

[0778] Example 50: (3-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)prop-2-yn-1-yl)-D-proline

[0779]

[0780] The compound of Example 50 was synthesized via the route shown in the following scheme.

[0781]

[0782] Step 1: Synthesis of 3-(7-chloroimidozopo[1,2-a]pyridin-3-yl)propyl-2-yn-1-ol

[0783] A mixture of 7-chloro-3-iodoimidazolo[1,2-a]pyridine (1.0 g, 3.59 mmol), propargyl alcohol (0.26 g, 4.3 mmol), TEA (1.25 mL, 8.9 mmol), CuI (40 mg, 0.18 mmol), Pd(PPh3)4 (200 mg, 0.18 mmol), and DMF (10 mL) was degassed with N2 for 30 min and stirred at room temperature for 2 h. The reaction mixture was diluted with water and extracted with ethyl acetate (3 x 15 mL). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered, and evaporated. The crude compound was purified by combiflash column chromatography using a hexane solution of 10-50% ethyl acetate as the mobile phase to give the title compound (720 mg, 97%) as a colorless liquid. The LC-MS calculation result was C10H7ClN2O(M+H)+: m / z = 206.63; the measured value was 207.20.

[0784] Step 2: Synthesis of 7-chloro-3-(3-iodopropyn-1-yl)imidazo[1,2-a]pyridine

[0785] In a DCM solution (10 mL) containing 3-(7-chloroimidazolo[1,2-a]pyridin-3-yl)propyl-2-yn-1-ol (620 mg, 3.09 mmol), TPP (1.2 g, 4.5 mmol), imidazole (300 mg, 4.5 mmol), and I2 (1.15 g, 4.5 mmol), the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with DCM (3 x 10 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated. The crude compound was purified by combined column chromatography using a hexane solution of 0-40% ethyl acetate as the mobile phase to give the title compound (500 mg, 52%) as a grayish-white solid. LC-MS calculation: C10H6ClIN2(M+H)+: m / z = 316.53; Found: 317.10.

[0786] Step 3: Synthesis of tert-butyl(3-(7-chloroimidazolo[1,2-a]pyridin-3-yl)propyl-2-yn-1-yl)-D-proline ester

[0787] A mixture of 7-chloro-3-(3-iodopropyn-1-yl)imidazo[1,2-a]pyridine (250 mg, 0.79 mmol), D-proline tert-butyl ester (200 mg, 0.95 mmol), and K₂CO₃ (330 mg, 2.37 mmol) in DMF (5 mL) was stirred at room temperature for 16 hours. The reaction mixture was diluted with water, extracted with ethyl acetate (3 x 10 mL), and the combined organic layers were washed with water and brine, dried over Na₂SO₄, filtered, and evaporated to give the title compound (310 mg). The crude product was used in the next step without further purification.

[0788] Step 4: Synthesis of tert-butyl(3-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)propyl-2-yn-1-yl)-D-proline ester

[0789] The reaction was carried out in a microwave reactor at 110°C for 1 hour in a manner similar to that in Example 1, yielding the title compound 30 (300 mg, 71%) as a white solid. LC-MS calculations showed C32H33N3O2(M+H)+: m / z = 491.64; measured value: 492.40.

[0790] Step 5: Synthesis of (3-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-3-yl)propyl-2-yn-1-yl)-D-proline:

[0791] The title compound was prepared in a manner similar to that of Example 39, yielding a white solid (20 mg, 8%). LC-MS calculations showed C28H25N3O2(M+H)+: m / z = 435.53; measured value: 436.35.

[0792] Following a similar procedure to that described in Example 50, suitable amines were used to prepare the following examples as shown in Table 8:

[0793] Table 8

[0794]

[0795] Example 52: 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)piperidine-2-carboxylic acid

[0796]

[0797] The compound of Example 52 was synthesized via the route shown in the following scheme.

[0798]

[0799] Step 1: Synthesis of 4-chloro-2-hydrazinopyridine

[0800] A mixture of 4-chloro-2-fluoropyridine (25 g, 190 mmol) and hydrazine monohydrate (67 mL, 209 mmol) was stirred at room temperature for 16 hours. The reaction was terminated by adding 4 M NaOH (63 mL) and water (125 mL), and the mixture was stirred for 15 minutes. The precipitated solid was filtered off, washed with water, and dried under vacuum to give the title compound (27 g, 98%) as a white solid.

[0801] The LC-MS calculation result was C5H6ClN3(M+H)+: m / z = 143.57; the measured value was 144.57.

[0802] Step 2: Synthesis of 7-chloro-[1,2,4]triazolo[4,3-a]pyridine

[0803] A mixture of 4-chloro-2-hydrazinopyridine (27 g, 188 mmol) and formic acid (27 mL, 10 vol) was refluxed for 16 hours. Volatile organic compounds were removed under reduced pressure, and the residue was dissolved in water and extracted with 5% methanol in DCM solution (3 x 200 mL). The combined organic layers were dried over Na₂SO₄, filtered, and evaporated to give the title compound (26 g, 90%) as a white solid. LC-MS calculations showed C₆H₄ClN₃(M+H)⁺: m / z = 153.57; measured value: 154.20.

[0804] Step 3: Synthesis of 3-bromo-7-chloro-[1,2,4]triazolo[4,3-a]pyridine

[0805] NBS (10.4 g, 58.6 mmol) was added in portions to a stirred solution of 7-chloro-[1,2,4]triazolo[4,3-a]pyridine (5 g, 32.5 mmol) in chloroform (250 mL). The reaction mixture was stirred at 0 °C for 16 hours at room temperature. A saturated NaHCO3 solution was added to the reaction mixture, and the mixture was extracted with DCM (2 x 50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered, and evaporated. The crude product was purified by combined rapid column chromatography using a 0-80% ethyl acetate solution in hexane to give the title compound (6.3 g, 83%) as a grayish-white solid. LC-MS calculations showed C6H3BrClN3(M+H)+: m / z = 232.47; measured value: 234.15.

[0806] Step 4: Synthesis of 4-(7-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzaldehyde

[0807] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (228 mg, 41%). LC-MS calculations showed C13H8ClN3O(M+H)+: m / z = 257.68; measured value: 257.95.

[0808] Step 5: Synthesis of 4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzaldehyde

[0809] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (95 mg, 27%). LC-MS calculations showed C26H19N3O(M+H)+: m / z = 389.46; measured value: 390.25.

[0810] Step 6: Synthesis of 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)piperidine-2-carboxylic acid

[0811] The title compound was prepared in a manner similar to that in Example 1 to obtain a crude product, which was purified by preparative HPLC to obtain a grayish-white solid of the title compound (7.6 mg, 7%).

[0812] 1 H NMR(400MHz, DMSO-d6)δ:8.62(d,J=6.8Hz,1H),7.91(d,J=8.0Hz,2H),7.84(s,1H),7.60(d,J=8 Hz,3H),7.5-7.46(m,2H),7.46-7.34(m,4H),7.34-7.28(m,1H),7.10(d,J=6.4Hz,1H),3.95(d,J =13.2Hz,1H), 3.58(d,J=14Hz,1H), 3.2-3.15(m,1H), 2.95-2.85(m,1H), 2.3-2.1(m,1H), 2.17(s,3H), 1.9-1.3(m,2H), 1.6-1.45(m,4H). LC-MS calculation: C32H30N4O2(M+H)+: m / z = 502.62; measured value: 503.45.

[0813] Following a similar procedure to that described in Example 52, suitable amines were used to prepare the following examples as shown in Table 9:

[0814] Table 9

[0815]

[0816]

[0817] Example 62: (4-(7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline

[0818]

[0819] The compound of Example 62 was synthesized via the route shown in the following scheme.

[0820]

[0821] Step 1: Synthesis of 3”-bromo-2',2”-dimethyl-[1,1':3',1”-terphenyl]-4-carboxaldehyde

[0822] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (1.76 g, 57%). LC-MS calculations showed C21H17BrO(M+H)+: m / z = 365.27; measured value: 366.

[0823] Step 2: Synthesis of 2',2”-dimethyl-3”-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde.

[0824] The title compound was prepared in a manner similar to that in Example 1, yielding a light brown solid (1.54 g, 79%). LC-MS calculations showed C27H29BO3(M+H)+: m / z = 412.34; measured value: 413.

[0825] Step 3: Synthesis of (4-(7-(4”-formyl-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline tert-butyl ester

[0826] The title compound was prepared in a manner similar to that in Example 1, yielding a light brown solid (278 mg, 86%). LC-MS calculations showed C43H42N4O3(M+H)+: m / z = 662.83; measured value: 663.

[0827] Step 4: Synthesis of (4-(7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline tert-butyl ester

[0828] Ethanolamine (0.04 mL, 0.61 mmol) and acetic acid (0.05 mL, 0.816 mmol) were added to a 10.0 mL ethanol solution of tert-butyl(4-(7-(4”-formyl-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline ester (270 mg, 0.40 mmol), and the mixture was stirred at 80 °C for 16 h. The reaction mixture was cooled to room temperature, and NaBH3CN (77 mg, 1.22 mmol) was added. The mixture was stirred at room temperature for another 16 h. The volatile organic compounds were evaporated under vacuum, and water was added to the residue. The mixture was stirred for 30 min, filtered, and dried under vacuum to give the title compound (224 mg, 77%) as a grayish-white solid. The LC-MS calculation result was C45H49N5O3(M+H)+:m / z = 707.92; the measured value was 708.40.

[0829] Step 5: Synthesis of (4-(7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline

[0830] TFA (0.75 mL) was added to a stirred solution of (4-(7-(4”-((((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline tert-butyl ester (147 mg, 0.207 mmol) in DCM (3.0 mL) at 0 °C. The reaction mixture was then stirred at room temperature for 16 hours. The organic volatiles were evaporated, and water was added to the residue. The aqueous layer was extracted with DCM (3 x 15 mL), and the combined organic layers were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. The crude substance was subjected to preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to give the title compound (25 mg, 19%) as a white solid.

[0831] 1H NMR(400MHz, DMSO-d6)δ:8.60(d,J=7.6Hz,1H),7.92(d,J=6.8Hz,2H),7.85(s,1H),7.63(d,J=7.6Hz,2H),7.41-7.35(m,4H ),7.33(d,J=7.2Hz,2H),7.24(d,J=8.8Hz,2H),7.16(d,J=7.6Hz,1H),7.09(d,J=6.8Hz,1H),4.5(s,1H),4.14(d,J=13.2Hz ,1H), 3.77-3.72(m,3H), 3.49(t,J=5.6Hz,2H), 3.49-3.33(m,3H), 3.05-3.48(m,1H), 2.61(t,J=5.6Hz,2H), 2.14-2.07(m,1H), 2.03(s,3H), 1.95(s,3H), 1.9-1.88(m,1H), 1.78-1.65(m,2H). LC-MS calculation: C41H41N5O3(M+H)+: m / z=651.81; measured value: 652.7.

[0832] Following a similar procedure as described in Example 62, the following examples, as shown in Table 10, were prepared using appropriate amines:

[0833] Table 10

[0834]

[0835]

[0836] Example 66: 2-(((2',2”-dichloro-3”-(3-(4-((((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[0837]

[0838] The compound of Example 66 was synthesized via the route shown in the following scheme.

[0839]

[0840] 2,2'-(2-chloro-1,3-phenyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborane)

[0841] To a stirred solution of 1,3-dibromo-2-chlorobenzene (5 g, 20.08 mmol), 2,2'-(2-chloro-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxane) (2.4 g, 40.8 mmol) in 1,4-dioxane (75 mL), KOAc (11.78 g, 120 mmol) and Pd(dppf)Cl2 (1.02 g, 0.14 mmol) were added, and the mixture was degassed for 30 min. The reaction mixture was heated in a microwave oven at 140 °C for 2 h. After cooling to room temperature, the mixture was diluted with water and extracted with ethyl acetate (3 x 25 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and evaporated. The crude product was purified by Biotage rapid column chromatography using a 0–10% ethyl acetate solution in hexane to give the title compound (3.0 g, 48%) as a white solid. LC-MS calculation: C18H27B2ClO4(M+H)+: m / z = 364.48; Measured value: 365.

[0842] Example 66: 2-(((2',2”-dichloro-3”-(3-(4-((((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[0843]

[0844] Step 1: Synthesis of 3'-bromo-2'-chloro-[1,1'-biphenyl]-4-carboxaldehyde

[0845] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (1.7 g, 43%) of the title compound.

[0846] Step 2: 2',2”-Dichloro-3”-(4,4,5,5-Tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde

[0847] To a stirred solution of 3'-bromo-2'-chloro-[1,1'-biphenyl]-4-carboxaldehyde (500 mg, 1.65 mmol), 2,2'-(2-chloro-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxane) (470 mg, 1.86 mmol, reference) in 1,4-dioxane (3.5 mL), KOAc (498 mg, 5.07 mmol) and Pd(dppf)Cl2 (138 mg, 0.16 mmol) were added. The mixture was degassed for 30 minutes, and then the reaction mixture was heated in a microwave oven at 140 °C for 2 hours. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate (3 × 25 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and evaporated. The crude substance was purified by Biotage rapid column chromatography using a hexane solution of 0-10% ethyl acetate to give the title compound as a white solid (460 mg, 60%).

[0848] Step 3: 2',2”-Dichloro-3”-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde:

[0849] A 1,4-dioxane solution (4 mL) of a mixture of 2',2”-dichloro-3”-(4,4,5,5-tetramethyl-1,3,2-dioxaborphane-2-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde (120 mg, 26.48 mmol) and 4-(7-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzaldehyde (68 mg, 26.48 mmol) was added to an aqueous solution (0.4 mL) of K2CO3 (109 mg, 79.4 mmol) and Pd(PPh3)4 (15.2 mg, 1.3 mmol), and then dissolved in N2. The mixture was degassed for 30 minutes, and then the reaction mixture was heated in MW at 140 °C for 2 hours. The reaction mixture was diluted with ethyl acetate (10 mL) and water (10 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 × 30 mL). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The crude substance was purified by Biotage rapid column chromatography using a DCM solution of (0–10%) methanol to give the title compound (64.6 g, 44%) as a grayish-white solid. LC-MS calculations: C₃₂H₁₉Cl₂N₃O₂(M+H)⁺: m / z = 548.42; Found: 548.30.

[0850] Step 4: Synthesis of 2-(((2',2”-dichloro-3”-(3-(4-((((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethanol-1-ol

[0851] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (7.1 mg, 10%).

[0852] 1 ¹H NMR (400MHz, DMSO-d⁶): δ: 8.62 (d, J = 6.8Hz, 1H), 7.96 (s, 1H), 7.89 (d, J = 7.6Hz, 2H), 7.65-7.58 (m, 4H), 7.53 (t, J = 4Hz, 2H), 7.51-7.42 (m, 6H), 7.14-7.12 (m, 1H), 4.49 (q, J = 5.6Hz, 2H), 3.83 (s, 2H), 3.76 (s, 2H), 3.5 (q, J = 5.2Hz, 4H), 2.6 (q, J = 6Hz, 4H). LC-MS calculation: C₃₆H₃₃Cl₂N₅O₂(M+H)⁺: m / z = 638.59; measured value: 639.

[0853] Example 67: (4-(7-(2,2'-dichloro-4”-(((2-hydroxyethyl)amino)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline

[0854]

[0855] The compound of Example 67 was synthesized via the route shown in the following scheme.

[0856]

[0857] Step 1: Synthesis of (4-(7-(2,2'-dichloro-4”-formyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline tert-butyl ester

[0858] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (348 mg, 80%). LC-MS calculations showed C41H36Cl2N4O3(M+H)+: m / z = 703.66; measured value: 703.45.

[0859] Step 2: Synthesis of (4-(7-(2,2'-dichloro-4”-(((2-hydroxyethyl)amino)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline tert-butyl ester

[0860] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (188 mg, 72%). LC-MS calculations showed C43H43Cl2N5O3(M+H)+: m / z = 748.75; measured value: 749.45.

[0861] Step 3: Synthesis of (4-(7-(2,2'-dichloro-4”-(((2-hydroxyethyl)amino)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline

[0862] The title compound was prepared in a manner similar to that of Example 39, yielding a grayish-white solid (35 mg, 20%).

[0863] 1 ¹H NMR (400MHz, DMSO-d⁶) δ: 8.64 (d, J = 7.2Hz 1H), 8.19 (s, 1H), 4.5 (s, 2H), 4.15 (d, J = 13.6Hz, 1H), 3.81 (s, 2H), 3.75 (d, J = 13.6Hz, 1H), 3.51 (d, J = 5.6Hz, 2H), 3.1–3.0 (m, 2H), 2.2–2.09 (m, 2H), 2.0–1.85 (m, 2H), 1.85–1.7 (m, 2H). LC-MS calculated C₃₉H₃₅Cl₂N₅O₃(M+H)⁺: m / z = 692.64; measured value: 693.

[0864] Example 68: (4-(7-(3'-(5-((((2-hydroxyethyl)amino)methyl)pyridinamido)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline

[0865]

[0866] The compound of Example 68 was synthesized via the route shown in the following scheme.

[0867]

[0868] Step 1: Synthesis of methyl 6-((3-bromo-2-methylphenyl)carbamoyl)nicotinic acid ester

[0869] At 0 °C, DIPEA (2.35 mL, 1.38 mmol) and HATU (3.14 g, 8.2 mmol) were added to a stirred solution of 5-(methoxycarbonyl)pyridinecarboxylic acid (1 g, 5.52 mmol) and 3-bromo-2-methylaniline (1.027 g, 5.52 mmol) in DMF (10 mL). The reaction mixture was stirred at room temperature for 16 hours, diluted with water, and extracted with ethyl acetate (2 × 50 mL). The organic layer was washed with sodium bicarbonate solution (1 × 50 mL), water, and brine. The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude residue was purified by combi flash NextGen 300+ elution with 0–30% EtOAc / n-hexane to give the title compound (1.76 g, 92%) as a grayish-white solid. The LC-MS calculation result was C15H13BrN2O3(M+H)+: m / z = 349.18; the measured value was 350.45.

[0870] Step 2: Synthesis of N-(3-bromo-2-methylphenyl)-5-(hydroxymethyl)pyridine amide

[0871] Sodium borohydride (381 mg, 0.01 mmol) was added to a THF:MeOH (7 mL: 1 mL) solution of methyl 6-((3-bromo-2-methylphenyl)carbamoyl)nicotinic acid (1.76 g, 0.005 mmol) and the reaction mixture was stirred at 0 °C for approximately 16 hours. Ammonium chloride solution was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate (3 x 25 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and the solvent was evaporated under reduced pressure. The crude product was purified by Biotage rapid column chromatography using a 0-30% ethyl acetate solution in hexane to give the title compound (0.979 g, 60%) as a white solid. LC-MS calculations showed C₁₄H₁₃BrN₂O₂(M+H)⁺: m / z = 321.17; the measured value was 322.45.

[0872] Step 3: Synthesis of N-(3-bromo-2-methylphenyl)-5-formylpyridine amide

[0873] DMP (381 mg, 898 mmol) was added at 0 °C to a solution of N-(3-bromo-2-methylphenyl)-5-(hydroxymethyl)pyridine amide (500 mg, 1.5568 mmol) and sodium bicarbonate (326.9 mg, 3891 mmol) in DCM (12.5 mL), and stirred at room temperature for about 2 hours. The reaction mixture was filtered through diatomaceous earth, washed with DCM (20 mL), and the solvent was evaporated under reduced pressure. The crude product was purified by Biotage rapid column chromatography using a 0-20% ethyl acetate solution in hexane to give the title compound xx (530 mg, 60%) as a white solid. LC-MS calculations showed C14H11BrN2O2(M+H)+: m / z = 319.16; measured value: 320.2.

[0874] Step 4: Synthesis of N-(3-bromo-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)pyridine amide

[0875] The title compound was prepared in a microwave environment in a manner similar to that in Example 1, yielding a grayish-white solid (648 mg, 60%). LC-MS calculations showed C16H18BrN3O2(M+H)+: m / z = 364.24; measured value: 365.

[0876] Step 5: Synthesis of (4-(7-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborphane-2-yl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline tert-butyl ester

[0877] The title compound was prepared in a manner similar to that in Example 1, yielding a brown solid (2.2 g, 53.6%). LC-MS calculations showed C35H43BN4O4(M+H)+: m / z = 594.56; measured value: 595.

[0878] Step 6: Synthesis of (4-(7-(3'-(5-((((2-hydroxyethyl)amino)methyl)pyridinamido)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline tert-butyl ester

[0879] The title compound was prepared in a microwave environment in a manner similar to that in Example 1, yielding a colorless liquid (1.5 g, 45%). LC-MS calculations showed C45H49N7O4(M+H)+: m / z = 751.93; measured value: 752.

[0880] Step 7: Synthesis of (4-(7-(3'-(5-((((2-hydroxyethyl)amino)methyl)pyridinamido)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline

[0881] The title compound was prepared in a manner similar to that in Example 39, yielding a crude title compound (2.2 g, 53.6%). The crude substance was subjected to preparative HPLC (X-Bridge C18 column (250 x 19) mm, 5.0 μm; mobile phase (A: B), A = 0.1% FA aqueous solution, B = 100% ACN) to give a white solid title compound (25 mg, 17%).

[0882] 1 H NMR(400MHz, DMSO-d6)δ:10.36(s,1H),8.69(s,1H),8.61(d,J=7.2Hz,1H),8.15(d,J=8Hz,1H),8.04(d,J=8Hz,1H),7.93(d,J =7.6Hz,2H),7.87(d,J=8Hz,2H),7.63(d,J=8Hz,2H),7.4(t,J=6.4Hz,2H),7.34(t,J=8Hz,1H),7.22(d,J=4.4Hz,1H),7.08(dd ,J=7.2Hz,2H),4.14(d,J=12.4Hz,1H),3.92(s,2H),3.77(d,J=13.2Hz,1H),3.50(s,2H),2.65(d,J=12.4Hz,1H),2.59-2.54(m,2H),2.16-2.11(m,1H),2.07(s,3H),1.9(m,2H),1.80-1.74(m,2H),LC-MS calculated as C41H41N7O4(M+H)+:m / z=695.82; measured value: 694.4.

[0883] Following a similar procedure as described in Example 68, suitable amines were used to prepare the following examples as shown in Table 11:

[0884] Table 11

[0885]

[0886] Example 70: 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(3-(4-(((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridineamide

[0887]

[0888] The compound of Example 70 was synthesized via the route shown in the following scheme.

[0889]

[0890] Step 1: Synthesis of N-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)-[1,1'-biphenyl]-3-yl)-5-carboxypyridine amide.

[0891] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (550 mg, 36%). LC-MS calculations showed C27H29BN2O4(M+H)+: m / z = 456.35; measured value: 457.35.

[0892] Step 2: Synthesis of 5-formyl-N-(3'-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridineamide

[0893] The title compound was prepared in a manner similar to that in Example 1, yielding a colorless, viscous substance (85 mg, 70%). LC-MS calculations showed C34H25N5O3(M+H)+: m / z = 551.61; measured value: 552.15.

[0894] Step 3: Synthesis of 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(3-(4-((((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridineamide

[0895] The title compound was prepared in a manner similar to that in Example 1. The crude product obtained was purified by preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain the title compound (15 mg, 15%) as a white solid.

[0896] 1H NMR(400MHz, DMSO-d6)δ:10.84(s,1H),8.68(s,1H),8.59(d,J=6.8Hz,1H),8.17(s,2H),8.14(d,J=8Hz,1H), 8.02(d,J=8Hz,1H),7.85-7.92(m,4H),7.62(d,J=8Hz,2H),7.32-7.44(m,3H),7.22(d,J=5.2Hz,1H),7.08(d d,J=6Hz,2H), 4.61(s,2H), 3.90(d,J=13.2Hz,4H), 3.53(t,J=5.6Hz,2H), 3.48(t,J=6Hz,2H), 2.69(t,J=6Hz,2H), 2.6(t,J=5.6Hz,2H), 2.07(s,3H), 2.01(s,3H), LC-MS calculated as C38H39N7O3(M+H)+:m / z=641.78; measured value: 642.5.

[0897] Following a similar procedure to that described in Example 70, the following examples, as shown in Table 12, were prepared using appropriate amines:

[0898] Table 12

[0899]

[0900] Example 73: (2'R)-((((2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis([1,2,4]triazolo[4,3-a]pyridine-7,3-diyl))bis(4,1-phenylene))bis(methylene))di-D-proline

[0901]

[0902] The compound of Example 73 was synthesized via the route shown in the following scheme.

[0903]

[0904] Step 1: Synthesis of 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenol

[0905] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (825 mg, 76%).

[0906] Step 2: Synthesis of 2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diol

[0907] Under a nitrogen atmosphere, K3PO4 (335.4 mg, 3.42 mmol) was added to a stirred solution of 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)phenol (369.1 mg, 1.71 mmol) and 3-bromo-2-methylphenol (400.0 mg, 1.71 mmol) in 1,4-dioxane (5 mL) and water (1.25 mL). The mixture was purged with nitrogen for 30 min, and then Pd(dppf)Cl2 (62.5 mg, 0.09 mmol) was added. The reaction mixture was heated in a microwave oven at 120 °C for 2 h. After cooling to room temperature, the mixture was diluted with water and extracted with ethyl acetate (2 x 50 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was adsorbed onto silica gel and purified by combined rapid column chromatography using ethyl acetate in hexane (0-25%) to give the title compound as a grayish-white solid (181 mg, 49.4%).

[0908] Step 3: Synthesis of 2,2'-dimethyl-[1,1'-biphenyl]-3,3'-dimethylbis(trifluoromethanesulfonate)

[0909] At 0 °C, trifluoromethanesulfonic anhydride (0.798 mL, 4.74 mmol) was added via syringe to a stirred mixture of 2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diol (1.00 g, 3.16 mmol) and DIPEA (1.38 mL, 7.90 mmol) in 10 mL of dichloromethane. After 30 minutes, ethanol (0.5 mL) was added. The reaction was stirred at 0 °C for 30 minutes. The reaction mixture was concentrated under reduced pressure. The residue was purified by combined rapid column chromatography using ethyl acetate (0-10%) in hexane to give the title compound (130 mg, 22%) as a brown solid.

[0910] Step 4: Synthesis of 2,2'-(2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborane)

[0911] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (130 mg, 65%).

[0912] Step 5: Synthesis of ((((2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis([1,2,4]triazolo[4,3-a]pyridine-7,3-diyl))bis(4,1-phenylene))bis(methylene))(R)-di-D-proline di-tert-butyl ester

[0913] The title compound was prepared in a manner similar to that in Example 1, yielding a crude compound as a brown semi-solid (506 mg). LC-MS calculations showed C58H62N8O4(M+H)+: m / z = 935.19; measured value: 936.50.

[0914] Step 6: Synthesis of (2'R)-((((2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis([1,2,4]triazolo[4,3-a]pyridine-7,3-diyl))bis(4,1-phenylene))bis(methylene))di-D-proline

[0915] The title compound was prepared in a manner similar to that of Example 62, yielding a grayish-white solid (35 mg, 14%).

[0916] 1 H NMR(400MHz,DMSO-d6)δ:8.60(d,J=7.2Hz,2H),7.92(d,J=8Hz,4H),7.86(s,2H),7 .63(d,J=8Hz,4H),7.43-7.41(m,4H),7.28(d,J=6.8Hz,2H),7.10(d,J=7.2Hz,2H), 4.14 (d, J = 13.6 Hz, 2H), 3.76 (d, J = 13.6 Hz, 2H), 3.05 (s, 2H), 2.6 (s, 2H), 2.13-2.06 (m, 8H), 1.92-1.76 (m, 8H), LC-MS calculated as C50H46N8O4(M+H)+: m / z = 822.97; measured value: 821.6.

[0917] Example 74: Synthesis of (S)-5-((((2',2”-dimethyl-3”-(3-(4-(((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one

[0918]

[0919] The compound of Example 74 was synthesized via the route shown in the following scheme.

[0920]

[0921] Step 1: Synthesis of 3”-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2',2”-dimethyl-[1,1':3',1”-terphenyl]-4-carboxaldehyde

[0922] The title compound was prepared in a manner similar to that in Example 1, yielding a brown semi-solid title compound (170 mg, 70%). LC-MS calculations showed C34H25N3O2(M+H)+: m / z = 507.59; measured value: 508.20.

[0923] Step 2: Synthesis of (S)-5-((((2',2”-dimethyl-3”-(3-(4-((((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one

[0924] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (20 mg, 20%).

[0925] 1 ¹H NMR (400MHz, DMSO-d⁶) δ: 8.59 (d, J = 7.2Hz, 1H), 7.709 (s, 1H), 7.314-7.412 (m, 7H), 7.235 (t, J = 5.6Hz, 2H), 7.15 (d, J = 7.6Hz, 1H), 4.48-4.52 (m, 2H), 4.29 (s, 2H), 3.76 (s, 2H), 3.44-3.49 (m, 4H), 2.609 (t, J = 5.2Hz, 4H), 2.007 (s, 3H), 1.945 (s, 3H). LC-MS calculated as C₄₄H₄₅N₇O₂(M+H)⁺: m / z = 703.89. Measured value: 704.6.

[0926] Following a similar procedure to that described in Example 74, suitable amines were used to prepare the following examples as shown in Table 13:

[0927] Table 13

[0928]

[0929] Example 77: 2-((4-(7-(3'-(5-((((2-hydroxyethyl)amino)methyl)-6-methoxypyridin-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)amino)ethane-1-ol

[0930]

[0931] The compound of Example 77 was synthesized via the route shown in the following scheme.

[0932]

[0933] Step 1: Synthesis of 6-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-[1,1'-biphenyl]-3-yl)-2-methoxynicotinaldehyde

[0934] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (125 mg, 24%). LC-MS calculations showed C27H30BNO4(M+H)+: m / z = 443.35; measured value: 444.15.

[0935] Step 2: Synthesis of 6-(3'-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-2-methoxynicotinaldehyde

[0936] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (107 mg, 74%). LC-MS calculations showed C34H26N4O3(M+H)+: m / z = 538.61; measured value: 539.25.

[0937] Step 3: Synthesis of 2-((4-(7-(3'-(5-((((2-hydroxyethyl)amino)methyl)-6-methoxypyridin-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)amino)ethane-1-ol

[0938] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (19 mg, 16%).

[0939] 1H NMR(400MHz,DMSO-d6)δ:8.59(d,J=7.2Hz,1H),8.2(s,2H),7.91(d,J=8Hz,2H),7.85(s,1 H),7.80(d,J=7.2Hz,1H),7.62(d,J=8Hz,2H),7.45-7.35(m,4H),7.23(q,J=6.8Hz,2H),7. 15 (d, J = 7.2 Hz, 1H), 7.09 (d, J = 7.2 Hz, 1H), 3.9 (s, 5H), 3.7 (s, 2H), 3.5 (q, J = 5.2 Hz, 4H), 2.69 (t, J = 5.2 Hz, 4H), 2.08 (s, 3H). LC-MS calculation: C38H40N6O3(M+H)+: m / z = 628.78; Measured value: 629.6.

[0940] Following a similar procedure as described in Example 77, suitable amines were used to prepare the following examples as shown in Table 14:

[0941] Table 14

[0942]

[0943]

[0944] Example 79: (S)-5-(((4-(7-(3'-((3-((((R)-3-hydroxypyrrolidine-1-yl)methyl)-1,7-naphthidin-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)amino)methyl)pyrrolidine-2-one

[0945]

[0946] The compound of Example 79 was synthesized via the route shown in the following scheme.

[0947]

[0948] Step 1: Synthesis of 5-bromo-3-methylpyridine amide

[0949] At room temperature, thionyl chloride (4.05 mL, 55.5 mmol) was added to a stirred mixture of 5-bromo-3-methylpyridinecarboxylic acid (10 g, 46.2 mmol) in toluene (100 mL) and DMF (0.025 mL). The reaction mixture was heated to 0 °C and maintained for 2 hours. After cooling to room temperature, ammonium hydroxide solution (60 mL) was added to the reaction mixture, the solid product was separated, filtered, washed with water, and dried under vacuum to give the title compound (9 g, 90%) as a grayish-white solid.

[0950] Steps 2 and 3: Synthesis of 3-bromo-1,7-naphthidium-8(7H)-one

[0951] At room temperature, DMF-DMA (7.2 mL, 54.4 mmol) was added to a stirred mixture of 5-bromo-3-methylpyridineamide (9 g, 41.8 mmol) and toluene (80 mL). The reaction mixture was heated at 110 °C for 24 hours, then cooled to room temperature and added dropwise to a stirred solution of tBuOK (7.04 g, 62.7 mmol) and toluene (80 mL). The reaction mixture was heated again to 110 °C and held for 3 hours. Volatile organic compounds were removed under reduced pressure, and the pH of the reaction mixture was adjusted to 7 with 1 N HCl solution to give a solid. The solid was filtered, washed with water, and dried under vacuum to give the title compound (4.5 g, 48%) as a brown solid. LC-MS calculation: C8H5BrN2O(M+H)+: m / z = 225.05; Measured value: 224.95.

[0952] Step 4: Synthesis of 3-bromo-8-chloro-1,7-naphthidine

[0953] At room temperature, phosphorus oxychloride (3.05 mL, 33.3 mmol) was added to a stirred mixture of 3-bromo-1,7-naphthidium-8(7H)-one (2.5 g, 11.1 mmol) and toluene (100 mL), followed by N,N-diethylaniline (5.2 mL, 33 mmol). The reaction mixture was heated at 110 °C for 2 hours. Volatile organic compounds were removed under reduced pressure, and the residue was diluted with cold water. The mixture was stirred at room temperature for 1 hour, the solid was separated, filtered, washed with water, and dried under vacuum to give the title compound (2.3 g, 85%) as a brown solid. LC-MS calculation of C8H4BrClN2(M+H)+: m / z = 243.49; Found: 244.90.

[0954] Step 5: Synthesis of 8-chloro-3-vinyl-1,7-naphthidine

[0955] To a 1,4-dioxane solution (20 mL) of a mixture of 3-bromo-8-chloro-1,7-naphthidine (1.7 g, 6.9 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborane (860 mg, 5.5 mmol), 5 mL of an aqueous solution of Na₂CO₃ (1.47 g, 13.8 mmol) and Pd(dppf)Cl₂ (260 mg, 0.3 mmol) was added, the mixture was degassed with N₂ for 30 min, and then heated at 90 °C for 16 h. The reaction mixture was diluted with ethyl acetate, filtered through diatomaceous earth, washed with ethyl acetate, and the filtrate was evaporated. The crude substance was purified by Biotage rapid column chromatography using (0-30%) ethyl acetate in hexane to give the title compound (700 mg, 60%) as a brown, viscous substance. LC-MS calculation: C10H7ClN2(M+H)+: m / z = 190.63; measured value: 191.0.

[0956] Step 6: Synthesis of N-(3-bromo-2-methylphenyl)-3-vinyl-1,7-naphthidine-8-amine

[0957] Methanesulfonic acid (105 mg, 0.1 mmol) was added to a solution of 8-chloro-3-vinyl-1,7-naphthidine (200 mg, 0.1 mmol) and 3-bromo-2-methylaniline (195 mg, 0.1 mmol) in IPA (10 mL) at ambient temperature. The resulting reaction mixture was heated to 60 °C and stirred at 60 °C for 7 hours. The mixture was cooled to room temperature, and the pH was adjusted to 8–9 with a 20% aqueous sodium hydroxide (NaOH) solution. The neutralized reaction mixture was stirred at ambient temperature for 30 minutes, and the solid was collected by filtration. The wet filter cake was added to a mixture of MTBE (20 mL) and water (10 mL) at room temperature and stirred for 2 hours to resuspend the cake, thus purifying it. The solid was collected by filtration and dried under vacuum to give the title compound (300 mg, 85%) as a yellow solid, which could be used for subsequent reactions without further purification. The LC-MS calculation is C17H14BrN3(M+H)+: m / z 340.22 = measured value: 340.20.

[0958] Step 7: Synthesis of 8-((3-bromo-2-methylphenyl)amino)-1,7-naphthidine-3-carboxaldehyde

[0959] OsO4 (300 mg, 1.18 mmol) was added to a stirred solution of N-(3-bromo-2-methylphenyl)-3-vinyl-1,7-naphthidium-8-amine (260 mg, 0.7 mmol) and 2,6-dimethylpyridine (184 mg, 1.4 mmol) in THF (20 mL) and water (6 mL) at room temperature. The mixture was stirred at room temperature for 1 hour, and then NaIO4 (330 mg, 1.5 mmol) was added. The resulting reaction mixture was heated to 30–35 °C and stirred at this temperature for 15 hours. Water (14.0 mL) was added to the reaction mixture. The resulting mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. The solids were collected by filtration, and the residue was resuspended in water (20.0 mL). The suspension was heated to 50 °C and stirred at 50 °C for 1 hour. The solids were then collected by filtration, and the wet cake was re-slurried in MTBE (6.2 mL) for further purification. The suspension was heated at 50 °C for 1 hour and then filtered. The collected solid was dried under vacuum to obtain a crude product of the title compound (300 mg), which could be used in the next step without purification. LC-MS calculation: C16H12BrN3O(M+H)+: m / z = 342.20; Measured value: 343.95.

[0960] Step 8: Synthesis of (R)-1-((8-((3-bromo-2-methylphenyl)amino)-1,7-naphthid-3-yl)methyl)pyrrolidine-3-ol

[0961] A DCM solution (15 mL) of 8-((3-bromo-2-methylphenyl)amino)-1,7-naphthyl-3-carboxaldehyde (220 mg, 0.6 mmol), (A)-pyrrolidine-3-ol hydrochloride (140 mg, 1.13 mmol), and triethylamine (0.150 mL, 1.13 mol) was stirred at room temperature for 2 hours. Sodium triacetoxyborohydride (280 mg, 1.2 mmol) was added to the mixture in portions over 30 minutes at room temperature. The reaction mixture was stirred at 25–30 °C for 1 hour. The reaction mixture was cooled to 0–5 °C and the reaction was terminated with 10% sodium bicarbonate aqueous solution (10 mL). The reaction mixture was then gradually heated to room temperature and stirred overnight at room temperature. The resulting solid was collected by filtration and washed with dichloromethane (10 mL), water (5 mL), and heptane (5 mL). The wet solid was dried under vacuum to give a crude title compound (300 mg, 115%) as a pale yellow solid, which could be used in the next step without purification. LC-MS calculation showed C20H21BrN4O(M+H)+: m / z = 413.32, measured value: 413.05.

[0962] Step 9: Synthesis of (R)-1-((8-((2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-[1,1'-biphenyl]-3-yl)amino)-1,7-naphthid-3-yl)methyl)pyrrolidine-3-ol (209)

[0963] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (130 mg, 35%). LC-MS calculation: C33H39BN4O3(M+H)+: m / z = 550.51; Measured value: 551.25.

[0964] Step 10: Synthesis of (R)-4-(7-(3'-((3-((3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthidin-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzaldehyde

[0965] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (90 mg, 60%). LC-MS calculation: C40H35N7O2(M+H)+: m / z = 645.77; Measured: 642.20.

[0966] Step 11: Synthesis of (S)-5-(((4-(7-(3'-((3-(((R)-3-hydroxypyrrolidine-1-yl)methyl)-1,7-naphthidin-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)amino)methyl)pyrrolidine-2-one

[0967] The title compound was prepared in a manner similar to that in Example 1, and the crude title compound was obtained. It was then purified by preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = ACN 100%), to obtain the title compound (25 mg, 48%) as a pale yellow solid.

[0968] 1H NMR(400MHz,DMSO-d6)δ:9.321(s,1H),8.86(s,1H),8.59(d,J=6.8Hz,1H), 8.44(d,J=7.6Hz,1H),8.18(s,1H),8.05(d,J=6Hz,1H),7.9(d,J=7.6Hz,2H) ,7.86(s,1H),7.68(s,1H),7.60(d,J=8.4Hz,2H),7.4(t,J=6.8Hz,2H),7.33 9(t,J=8Hz,1H),7.24(d,J=6.8Hz,1H),7.175(d,J=5.6Hz,1H),7.095(d,J=6 0.8Hz, 1H), 6.94(d, J = 7.6Hz, 1H), 4.720(d, J = 4.4Hz, 1H), 4.220(s, 1H), 3.8-3.86(m, 4H), 3.64(s, 1H), 2.72-2.76(m, 1H), 2.66(d, J = 8Hz, 2H), 2.63(s, 1H), 2.38(dd, J = 9.6Hz, J = 9.6Hz, 2H), 2.125(d, J = 13.2Hz, 6H) 2.04(s, 3H), 1.709(d, J = 4.8Hz, 1H), LC-MS calculated as C45H45N9O2(M+H)+: m / z = 743.92; measured value: 744.3.

[0969] Following a similar procedure to that described in Example 79, the following examples, as shown in Table 15, were prepared using appropriate amines:

[0970] Table 15

[0971]

[0972] Example 82: (4-(7-(3'-(5-(((2-hydroxyethyl)carbamoyl)-6-methoxypyridin-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline tert-butyl ester

[0973]

[0974] The compound of Example 82 was synthesized via the route shown in the following scheme.

[0975]

[0976] Step 1: Synthesis of 6-chloro-N-(2-hydroxyethyl)-2-methoxynicotinamide

[0977] The title compound was prepared in a manner similar to that of Example 68, yielding a grayish-white solid (446 mg, 80%). LC-MS calculation: C9H11ClN2O3(M+H)+: m / z = 230.65; Measured: 231.

[0978] Step 2: Synthesis of tert-butyl(4-(7-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline ester

[0979] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (56 mg, 76%). LC-MS calculations showed C42H49BN4O4(M+H)+: m / z = 684.69; measured value: 685.30.

[0980] Step 3: Synthesis of tert-butyl(4-(7-(3'-(5-(((2-hydroxyethyl)carbamoyl)-6-methoxypyridin-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline ester

[0981] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (56 mg, 76%). LC-MS calculations showed C45H48N63O5(M+H)+: m / z = 752.92; measured value: 753.65.

[0982] Step 4: Synthesis of (4-(7-(3'-(5-(((2-hydroxyethyl)carbamoyl)-6-methoxypyridin-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)-D-proline

[0983] The title compound was prepared in a manner similar to that of Example 39, yielding a white solid (25 mg, 10%) of the title compound.

[0984] 1H NMR(400MHz,DMSO-d6)δ:8.61(d,J=7.2Hz 1H),8.34-8.28(m,2H),7.92(d,J=8Hz,2H),7.86(s,1H),7.6(d,J=8Hz,2H),7.49(d,J=7.2Hz,1H), 7.44-7.39(m,3H),7.33(d,J=8.1Hz,1H),7.26(d,J=4.4Hz,,2H),7.1(d,J=7.2Hz,1H),4.8(s,1H), 4.14 (d, J = 13.2 Hz, 1H), 4.02 (s, 3H), 3.79 (d, J = 12.8 Hz, 1H), 3.53 (s, 3H), 3.42-.32 (m, 2H), 3.05 (s, 1H), 2.4-2.55 (m, 2H), 2.16-1.75 (m, 10H). LC-MS calculation: C41H40N6O5(M+H)+: m / z = 696.81; measured value: 697.5.

[0985] Example 83: (1-(7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)glycine ethyl ester

[0986]

[0987] The compound of Example 83 was synthesized via the route shown in the following scheme.

[0988]

[0989] Step 1: Synthesis of 7-bromo-3-iodo-[1,2,4]triazolo[4,3-a]pyridine

[0990] The title compound was prepared in a manner similar to that in Example 1, yielding a brown solid (5 g, 55.5%) of the title compound.

[0991] Step 2: Synthesis of ethyl 1-(7-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carboxylate

[0992] The title compound was prepared in a manner similar to that in Example 1, yielding a yellow solid (1.2 g, 57.6%).

[0993] Step 3: Synthesis of 1-(7-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carboxylic acid

[0994] The title compound was prepared in a manner similar to that in Example 41, yielding a yellow viscous liquid containing the title compound (260 mg, 43.6%).

[0995] Step 4: Synthesis of ethyl glycine (1-(7-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)glycine

[0996] The title compound was prepared in a manner similar to that of Example 68, yielding a yellow, viscous solid (250 mg, 75.1%).

[0997] Step 5: Synthesis of (1-(7-(4”-formyl-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)glycine

[0998] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (250 mg, 61.5%) of the title compound.

[0999] Step 6: Synthesis of (1-(7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazole-3-carbonyl)glycine

[1000] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (16 mg, 5.9%) of the title compound.

[1001] 1 H NMR(400MHz,DMSO-d6)δ:9.03(d,J=7.2Hz,1H),8.76-8.76(m,1H),8.68(s,1H),7.89 (s,1H),7.46-7.42(m,4H),7.40-7.32(m,3H),7.27-7.16(m,4H),7.06(d,J=2.4Hz,1 H) 5.15-4.51(br.s,2H), 3.87-3.84(m,4H), 3.54(t,J=5.8Hz,2H), 2.71(t,J=5.8Hz,2H), 2.03(s,3H), 1.94(s,3H), LC-MS calculated as C35H33N7O4(M+H)+:m / z=615.6; measured value: 616.3.

[1002] Example 84: 2-((4-(7-(3'-((3-((((2-hydroxyethyl)amino)methyl)-1,7-naphthidin-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)amino)ethane-1-ol

[1003]

[1004] The compound of Example 84 was synthesized via the route shown in the following scheme.

[1005]

[1006] Step 1: Synthesis of 4-(7-(2,2'-dimethyl-3'-((3-vinyl-1,7-naphthid-8-yl)amino)-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzaldehyde

[1007] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (60 mg, 50%). LC-MS calculations showed C37H28N6O(M+H)+: m / z = 572.67, while the measured value was 573.40.

[1008] Step 2: Synthesis of 8-((3'-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)amino)-1,7-naphthyl-3-carboxaldehyde

[1009] The title compound was prepared in a manner similar to that of Example 79, yielding a pale yellow solid (10 mg, 12%). LC-MS calculations showed C36H26N6O2(M+H)+: m / z = 574.64, with a measured value of 575.35.

[1010] Step 3: Synthesis of 2-((4-(7-(3'-((3-((((2-hydroxyethyl)amino)methyl)-1,7-naphthidin-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)benzyl)amino)ethane-1-ol

[1011] The title compound was prepared in a manner similar to that in Example 1, and the crude product was purified by preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain the title compound as a yellow solid (60 mg, 12.6%).

[1012] 1 H NMR(400MHz, DMSO-d6)δ:9.32(s,1H),8.90(s,1H),8.59(d,J=6.8Hz,1H),8.46(d,J=8Hz,1H),8.2(s,1H),8.0 5(d,J=5.6Hz,1H),7.9(d,J=8Hz,2H),7.86(s,1H),7.6(d,J=7.6Hz,2H),7.32-7.42(m,3H),7.24(d,J=6.8Hz, 1H), 7.16(d,J=6Hz,1H), 7.1(d,J=7.2Hz,1H), 6.94(d,J=7.6Hz,1H), 4.51(s,2H), 3.96(s,2H), 3.86(s,2H), 3.5(s,4H), 2.5-2.69(m,4H), 2.14(s,3H), 2.04(s,3H). LC-MS calculation: C40H40N8O2(M+H)+: m / z=664.81; measured value: 665.4.

[1013] Example 85: 2-(((3”-(3-(((2-hydroxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2',2”-dimethyl-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethanol-1-ol

[1014]

[1015] The compound of Example 85 was synthesized via the route shown in the following scheme.

[1016]

[1017] Step 1: Synthesis of 7-bromo-3-chloro-[1,2,4]triazolo[4,3-a]pyridine

[1018] NCS (509 mg, 3.82 mmol) was added to a stirred solution (10 mL) of 7-bromo-[1,2,4]triazolo[4,3-a]pyridine (500 mg, 2.55 mmol) in DMF. The resulting solution was stirred at 50 °C for 2 hours. The reaction mixture was cooled to room temperature, diluted with water (20 mL), and extracted with ethyl acetate (2 x 10 mL). The combined organic layers were washed with water (2 x 10 mL) and brine (10 mL), dried over anhydrous Na₂SO₄, filtered, and evaporated under reduced pressure to give the title compound (520 mg, 88%) as a pale yellow solid. LC-MS calculation: C₄₀H₄₀N₈O₂(M+H)⁺: m / z = 232.4; Found: 234.1.

[1019] Step 2: Synthesis of 7-bromo-N-(2-methoxyethyl)-[1,2,4]triazolo[4,3-a]pyridine-3-amine

[1020] A mixture of 7-bromo-3-chloro-[1,2,4]triazolo[4,3-a]pyridine (500 mg, 2.15 mmol) and 2-methoxyethyl-1-amine (1.0 mL) was stirred in a sealed container at 140 °C for 3 hours. The reaction mixture was cooled to room temperature, diluted with DCM (10 mL), adsorbed onto silica gel, and purified by combined rapid column chromatography using ethyl acetate (50-60%) in hexane to give the title compound (130 mg, 22%) as a grayish-white compound. LC-MS calculations: C9H11BrN4O(M+H)+: m / z = 271.12; Found: 271.3.

[1021] Step 3: Synthesis of 3”-(3-((2-methoxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2',2”-dimethyl-[1,1':3',1”-terphenyl]-4-carboxaldehyde

[1022] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (100 mg, 44%). LC-MS calculations showed C30H28N4O2(M+H)+: m / z = 476.5; measured value: 477.2.

[1023] Step 4: Synthesis of 2-(((3”-(3-(((2-methoxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2',2”-dimethyl-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[1024] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (100 mg, 60%). LC-MS calculations showed C32H35N5O2(M+H)+: m / z = 521.6; measured value: 522.5.

[1025] Step 5: Synthesis of 2-(((3”-(3-(((2-hydroxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2',2”-dimethyl-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[1026] BBr3 (0.036 mL, 0.383 mmol) was added at 0 °C to a mixture of 2-(((3”-(3-((2-methoxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2',2”-dimethyl-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol (100 mg, 0.191 mmol) in 10 mL of DCM solution, and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with NaHCO3 (10 mL), extracted with DCM (10 mL x 2), the combined organic layers were washed with brine, dried with Na2SO4, filtered, and the solvent was concentrated under reduced pressure to obtain the title compound (90 mg, crude). The crude substance was analyzed by preparative HPLC (X-Bridge). A C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN. ) yielded the title compound as a grayish-white solid (7.0 mg, 7.5%).

[1027] 1 H NMR(400MHz, DMSO-d6)δ:8.60(d,J=7.2Hz,1H),7.40-7.30(m,8H),7.21(d,J=7.2Hz,2H),7.14( d,J=7.2Hz,1H),6.90(dd,J=6.8Hz,1.9Hz,1H),6.43-6.41(m,1H),4.63(t,J=5.4Hz,1H),4.44(t ,J=5.4Hz,1H),3.75(s,2H),3.56(q,6.0Hz,2H),3.48(q,6.0Hz,2H),3.34-3.29(m,2H),2.61(t,J=5.8Hz,2H),1.98(s,3H),1.93(s,3H). LC-MS calculation: C31H33N5O2(M+H)+:m / z=507.64; measured value: 508.5.

[1028] Example 86: (S)-5-((((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)methyl)pyrrolidone-2-one

[1029]

[1030] The compound of Example 86 was synthesized via the route shown in the following scheme.

[1031]

[1032] Step 1: Synthesis of ethyl 7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylate

[1033] A mixture of 4-bromo-2-hydrazinopyridine (6 g, 31.9 mmol) and diethyl oxalate (7.0 mL, 51.3 mmol) was stirred in a sealed tube at 150 °C for 1 hour. The reaction mixture was cooled to room temperature, diluted with water (50 mL), and stirred at room temperature for 30 minutes. The resulting solid was filtered and dried under vacuum to give the title compound (4.0 g, 45.9%) as a yellow solid. LC-MS calculations showed C9H8BrN3O2(M+H)+: m / z = 270.09; the measured value was 271.9.

[1034] Step 2: Synthesis of (7-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methanol

[1035] The title compound was prepared in a manner similar to that in Example 68, yielding a yellow solid (2.5 g, 74.1%).

[1036] Step 3: Synthesis of 7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carboxaldehyde

[1037] The title compound was prepared in a manner similar to that in Example 68, yielding a yellow solid (1.5 g, 61%). LC-MS calculations showed C7H4BrN3O(M)+: m / z = 226.03; measured value: 226.15.

[1038] Step 4: Synthesis of (S)-5-((((7-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)methyl)pyrrolidone-2-one

[1039] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (950 mg, 68%). LC-MS calculations showed C12H14BrN5O(M+H)+: m / z = 323.04; measured value: 324.

[1040] Step 5: Synthesis of (S)-((7-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)((5-oxopyrrolidone-2-yl)methyl)tert-butyl carbamate

[1041] At room temperature, triethylamine (900 mg, 8.9 mmol) was added to a stirred solution of (S)-5-((((7-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)methyl)pyrrolidone-2-one (950 mg, 2.93 mmol) in MeOH:DCM (5%) (30 mL), followed by di-tert-butyl dicarbonate (0.826 mg, 3.8 mmol) under N2 atmosphere at room temperature, and the mixture was stirred for 16 hours. The reaction mixture was diluted with water (30 mL) and extracted with DCM (3 x 30 mL). The combined organic layers were washed with water (20 mL) and brine (10 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by combined rapid column chromatography using (0–5%) MeOH:DCM to give the title compound (290.0 mg, 23.3%) as a pale yellow viscous solid. The LC-MS calculation result was C17H22BrN5O3(M+H)+: m / z = 424.3; the measured value was 424.2.

[1042] Step 6: Synthesis of (S)-((7-(4”-formyl-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)tert-butyl carbamate

[1043] The title compound was prepared in a manner similar to that in Example 1, yielding a yellow viscous liquid (90 mg, 43.4%). LC-MS calculations showed C38H39BrN5O4(M+H)+: m / z = 629.76; measured value: 630.2.

[1044] Step 7: Synthesis of (S)-((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)tert-butyl carbamate

[1045] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (90 mg, 93.3%). LC-MS calculations showed C40H46N6O4(M+H)+: m / z = 674.85; measured value: 675.4.

[1046] Step 8: Synthesis of (S)-5-((((7-(4”-((((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)methyl)pyrrolidone-2-one

[1047] The title compound was prepared in a manner similar to that in Example 39, and a crude product was obtained. This crude product was then passed through a preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain a white solid title compound (22 mg, 28.7%).

[1048] 1 H NMR (400MHz, DMSO-d6) δ: 8.58 (d, J = 7.2Hz, 1H), 7.71 (s, 1H), 7.64 (s, 1H), 7.41-7.31 (m, 7H), 7.25-7. 21(m,2H),7.15(d,J=7.6Hz,1H),7.05(d,J=6.4Hz,1H),4.48(t,J=5.4Hz,1H),4.29(s,2H),3.76(s,2H ), 3.60-3.58(m,1H), 3.49(q,J=5.6Hz,2H), 2.61(t,J=5.8Hz,2H), 2.56-2.50(m,2H), 2.11-2.03(m,6H), 2.00(s,3H), 1.94(s,3H), 1.64-1.63(m,1H). LC-MS calculation: C35H38N6O2(M+H)+: m / z=574.73; measured value: 575.3.

[1049] Example 87: (R)-1-((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)pyrrolidine-3-carboxylic acid

[1050]

[1051] The compound of Example 87 was synthesized via the route shown in the following scheme.

[1052]

[1053] Step 1: Synthesis of methyl (R)-1-((7-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)pyrrolidine-3-carboxylate

[1054] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (76 mg, 17%). LC-MS calculations showed C44H45N7O2(M+H)+: m / z = 574.64, while the measured value was 575.35.

[1055] Step 2: Synthesis of (R)-1-((7-(4”-formyl-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)pyrrolidine-3-carboxylate methyl ester

[1056] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow semi-solid (96.4 mg, 73%). LC-MS calculations showed C34H32N4O3(M+H)+: m / z = 544.66; measured value: 545.30.

[1057] Step 3: Synthesis of methyl (R)-1-((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)pyrrolidine-3-carboxylate

[1058] The title compound was prepared in a manner similar to that in Example 1 to obtain a crude title compound (140 mg), which could be used in the next step without purification.

[1059] Step 4: Synthesis of (R)-1-((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)pyrrolidine-3-carboxylic acid

[1060] The crude title compound was prepared in a manner similar to that in Example 41 and passed through a preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = ACN 100%) to obtain a grayish-white solid (35 mg, 37%).

[1061] 1H NMR(400MHz,DMSO-d6)δ:8.528(d,J=7.2Hz,1H),7.726(s,1H),7.318-7.421(m,7H),7.2 35(t,J=6.4Hz,2H),7.15(d,J=7.6Hz,1H),7.063(d,J=7.2Hz,1H),4.5(s,br,1H),4.18( s,2H), 3.77(s,2H), 3.5(t,J=5.2Hz,2H), 2.9-2.95(m,1H), 2.8(t,J=9.2Hz,1H), 2.502-2.722(m,6H), 1.944-2.0(m,7H), LC-MS calculated as C35H37N5O3(M+H)+:m / z=575.71; measured value: 576.7.

[1062] Following a similar procedure to that described in Example 87, suitable amines were used to prepare the following examples as shown in Table 16:

[1063] Table 16

[1064]

[1065] Example 89: 2,2'-((((2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis([1,2,4]triazolo[4,3-a]pyridine-7,3-diyl))bis(methylene))bis(azanediyl))bis(ethane-1-ol)

[1066]

[1067] The compound of Example 89 was synthesized via the route shown in the following scheme.

[1068]

[1069] Step 1: Synthesis of 7,7'-(2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis([1,2,4]triazolo[4,3-a]pyridine-3-carboxaldehyde)

[1070] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (55 mg, 34%). LC-MS calculations showed C28H20N6O2(M+H)+: m / z = 472.51; measured value: 473.5.

[1071] Step 2: Synthesis of 2,2'-((((2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis([1,2,4]triazolo[4,3-a]pyridine-7,3-diyl))bis(methylene))bis(azanediyl))bis(ethane-1-ol)

[1072] The crude title compound was prepared in a manner similar to that in Example 1 and subjected to preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain a grayish-white solid (1.4 mg, 2.5%).

[1073] 1 H NMR(400MHz,DMSO-d6)δ:8.58(d,J=6.8Hz,1H),7.71-7.64(m,3H),7.42-7.31(m,7H), 7.23(t,J=6.8Hz,2H),7.15(d,J=7.2Hz,1H),7.05(d,J=6.4Hz,1H),4.29(s,2H),3.76 -3.75(m,2H), 3.62-3.59(m,2H), 2.54-2.50(m,2H), 2.13-2.05(m,7H), 2.00(s,3H), 1.94(s,3H), 1.70-1.63(m,3H). LC-MS calculation: C32H34N8O2(M+H)+: m / z = 562.68; measured value: 563.3.

[1074] Example 90: (S)-5-((((2',2”-dimethyl-3”-(3-((((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one

[1075]

[1076] The compound of Example 90 was synthesized via the route shown in the following scheme.

[1077]

[1078] Step 1: Synthesis of 7-(4”-formyl-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-carboxaldehyde

[1079] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (110 mg, 42%). LC-MS calculations showed C28H21N3O2(M+H)+: m / z = 431.51; measured value: 432.30.

[1080] Step 2: Synthesis of (S)-5-((((2',2”-dimethyl-3”-(3-((((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one

[1081] The crude title compound was prepared in a manner similar to that in Example 1 and subjected to preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain a grayish-white solid (3 mg, 3.7%).

[1082] 1 H NMR(400MHz,DMSO-d6)δ:8.58(d,J=6.8Hz,1H),7.71-7.64(m,3H),7.42-7.31(m,7H), 7.23(t,J=6.8Hz,2H),7.15(d,J=7.2Hz,1H),7.05(d,J=6.4Hz,1H),4.29(s,2H),3.76 -3.75(m,2H), 3.62-3.59(m,2H), 2.54-2.50(m,2H), 2.13-2.05(m,7H), 2.00(s,3H), 1.94(s,3H), 1.70-1.63(m,3H). LC-MS calculation: C38H41N7O2(M+H)+: m / z = 627.79; measured value: 628.3.

[1083] Following a similar procedure to that described in Example 90, suitable amines were used to prepare the following examples as shown in Table 17:

[1084] Table 17

[1085]

[1086] Example 92: 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(3-((((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridineamide

[1087]

[1088] The compound of Example 92 was synthesized via the route shown in the following scheme.

[1089]

[1090] Step 1: Synthesis of 5-formyl-N-(3'-(3-formyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridine amide

[1091] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (60 mg, 57%). LC-MS calculations showed C28H21N5O3(M+H)+: m / z = 475.51; measured value: 476.35 (M+1).

[1092] Step 2: Synthesis of 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(3-((((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridineamide

[1093] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (15 mg, 16%).

[1094] 1 H NMR (400MHz, DMSO-d6)10.34(s,1H),8.67(d,J=5.2Hz,2H),8.59(d,J=7.2Hz,1H),8.13(d,J=7.6Hz ,1H),8.01(d,J=8Hz,1H),7.89(d,J=8Hz,1H),7.71(s,1H),7.49-7.39(m,3H),7.2(d,J=7.2Hz,1H) ,7.05(d,J=6.4Hz,2H),4.52-4.47(m,2H),4.39(s,2H),3.85(s,2H),3.49-3.44(m,4H),2.62-2.58(m,4H),2.07(d,J=7.6Hz,3H),1.98(s,3H). LC-MS calculation: C33H36N6O3(M+H)+:m / z=564.69; measured value: 565.5.

[1095] Following a similar procedure to that described in Example 92, suitable amines were used to prepare the following examples as shown in Table 18:

[1096] Table 18

[1097]

[1098] Example 94: (S)-5-((((5-(2,2'-dimethyl-3'-(3-(((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-[1,1'-biphenyl]-3-yl)-3-methoxypyrazin-2-yl)methyl)amino)methyl)pyrrolidine-2-one

[1099]

[1100] The compound of Example 94 was synthesized via the route shown in the following scheme.

[1101]

[1102] Step 1: Synthesis of 5-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborphane-2-yl)-[1,1'-biphenyl]-3-yl)-3-methoxypyrazine-2-carboxaldehyde

[1103] The title compound was prepared in a manner similar to that in Example 1, yielding a yellow viscous liquid (210 mg, 43%). LC-MS calculations showed C26H29BN2O4(M+H)+: m / z = 444.34; measured value: 445.35.

[1104] Step 2: Synthesis of 6-(3'-(5-formyl-6-methoxypyrazin-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-carboxaldehyde

[1105] The title compound was prepared in a manner similar to that in Example 1, yielding a yellow solid (150 mg, 69%). LC-MS calculations showed C27H21N5O3(M+H)+: m / z = 463.5; measured value: 464.35.

[1106] Step 3: Synthesis of (S)-5-((((5-(2,2'-dimethyl-3'-(3-(((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-[1,1'-biphenyl]-3-yl)-3-methoxypyrazin-2-yl)methyl)amino)methyl)pyrrolidine-2-one

[1107] The title compound was prepared in a manner similar to that in Example 1, yielding a yellow solid (27 mg, 12.6%).

[1108] 1 H NMR(400MHz,DMSO-d6)δ:8.60-8.28(m,1H),8.34(s,1H),8.16(m,1H),7.72-7.64(m,3H),7.51 -7.49(m,1H),7.43-7.38(m,3H),7.28-7.24(m,2H),7.06-7.04(d,J=6.8Hz,1H),4.29(s,2H), 3.96 (s, 3H), 3.89 (s, 2H), 3.62-3.59 (m, 2H), 2.66-2.60 (m, 2H), 2.59-2.50 (m, 2H), 2.13-2.04 (m, 9H), 2.00 (s, 3H), 1.70-1.63 (m, 2H). LC-MS calculation: C37H41N9O3(M+H)+: m / z = 659.8; measured value: 660.4.

[1109] Example 95: (S)-N-(2,2'-dimethyl-3'-(3-((((5-oxopyrrolidone-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-5-(((2-hydroxyethyl)amino)methyl)pyridineamide

[1110]

[1111] The compound of Example 95 was synthesized via the route shown in the following scheme.

[1112]

[1113] Step 1: Synthesis of tertiary carbamate (S)-((7-(3'-(5-formylpyridinamido)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate

[1114] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow viscous solid (90 mg, 41%).

[1115] LC-MS calculated C38H39N7O5(MH): m / z = 673.77; measured value: 672.4.

[1116] Step 2: Synthesis of (S)-((7-(3'-(5-((((2-hydroxyethyl)amino)methyl)pyridinamido)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)tert-butyl carbamate

[1117] The title compound was prepared in a manner similar to that in Example 1, yielding a white solid (850 mg, 91.3%). LC-MS calculations showed C40H46N8O5(M+H)+: m / z = 718.86; measured value: 719.2.

[1118] Step 3: Synthesis of (S)-N-(2,2'-dimethyl-3'-(3-((((5-oxopyrrolidone-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-5-(((2-hydroxyethyl)amino)methyl)pyridine amide

[1119] The title compound was prepared in a manner similar to that in Example 39, and a crude product was obtained. This crude product was purified by preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain the title compound as a white solid (21 mg, 28.7%).

[1120] 1 H NMR(400MHz, DMSO-d6)δ:10.34(s,1H),8.67(s,1H),8.59(d,J=6.8Hz,1H),8.13(d,J=7.6Hz,1H), 8.01(d,J=8.0Hz,1H),7.88(d,J=8.4Hz,1H),7.72(s,1H),7.64(s,1H),7.40-7.31(m,3H),7.20(d, J=7.2Hz,1H),7.05(t,J=6.2Hz,2H),4.49(t,J=5.0Hz,1H),4.29(s,2H),3.85(s,2H),3.60-3.58(m ,1H),3.47(q,J=5.4Hz,2H),2.57-2.50(m,4H),2.09-2.01(m,6H),1.98(s,3H),1.64-1.62(m,1H).

[1121] The LC-MS calculation result is C35H38N8O3(M+H)+:m / z = 618.74; the measured value is 619.2.

[1122] Example 96: 2-(((2',2”-dichloro-3”-(3-((((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethanol-1-ol

[1123]

[1124] The compound of Example 96 was synthesized via the route shown in the following scheme.

[1125]

[1126] Step 1: Synthesis of 7-(2,2'-dichloro-4”-formyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-carboxaldehyde

[1127] Add 0.8 mL of an aqueous solution of K₂CO₃ (182.9 mg, 1.32 mmol) and Pd(dppf)Cl₂ (17 mg, 0.022 mmol) to a 1,4-dioxane solution (8 mL) of a mixture of 2',2”-dichloro-3”-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde (200 mg, 0.44 mmol), 7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carboxaldehyde (99.74 mg, 0.44 mmol) and Pd(dppf)Cl₂ (17 mg, 0.022 mmol) to a solution of 1,4-dioxane. The mixture was then treated with N₂. The mixture was degassed for 30 minutes, and then the reaction was heated in MW at 140 °C for 2 hours. The reaction mixture was diluted with ethyl acetate (10 mL) and water (10 mL), the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and evaporated. The crude substance was purified by Biotage rapid column chromatography using a (0–10%) methanol-DCM solution to give the title compound (45 mg, 22%) as a pale yellow solid. LC-MS calculations: C₂₆H₁₅Cl₂N₃O₂(M+H)⁺: m / z = 472.33; Found: 472.20.

[1128] Step 2: Synthesis of 2-(((2',2”-dichloro-3”-(3-((((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[1129] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (8 mg, 16%). The crude product was subjected to preparative HPLC (X-Bridge C18 column (250 x 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to yield a grayish-white solid (20 mg, 42%).

[1130] 1 ¹H NMR (400MHz, DMSO-d⁶): δ: 8.62 (d, J = 7.6Hz, 1H), 8.2 (s, 1H), 7.81 (s, 1H), 7.68–7.4 (m, 10H), 7.08 (d, J = 7.2Hz, 1H), 4.50 (s, 2H), 4.3 (s, 2H), 3.84 (s, 2H), 3.52 (t, J = 5.6Hz, 2H), 3.45 (t, J = 6Hz, 2H), 2.67–(t, J = 5.6Hz, 2H), 2.6 (t, J = 6Hz, 2H). LC-MS calculation: C₃₀H₂₉Cl₂N₅O₂(M+H)⁺: m / z = 562.5; measured value: 564.

[1131] Following a similar procedure to that described in Example 96, suitable amines were used to prepare the following examples as shown in Table 19:

[1132] Table 19

[1133]

[1134] Example 98: 2-(((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol

[1135] The compound of Example 98 was synthesized via the route shown in the following scheme.

[1136]

[1137] Step 1: Synthesis of N-[(4-chloropyridin-2-yl)aminothioyl]carbamate ethyl ester

[1138] A dioxane solution (40 mL) of a mixture of 4-chloropyridin-2-amine (2 g, 11.5 mmol) and O-ethyl isothiocyanate (1.4 mL, 11.5 mmol) was stirred at room temperature for 4 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and the solvent was evaporated under reduced pressure to give the title compound (3.2 g, 92%), which could be used in the next step without further purification. LC-MS calculations: C₁₀H₁₀ClN₃O₂S(M+H)⁺: m / z = 259.71; Found: 260.20.

[1139] Step 2: Synthesis of 7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-amine

[1140] At room temperature, 7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-amine (0.74 g, 0.0024 mmol) was added to a stirred solution of hydroxylamine HCl (0.85 g, 0.0121 mmol) in EtOH (20 mL) and DIPEA (1.3 mL, 0.0072 mmol). The reaction mixture was heated at 90 °C for 16 hours. Organic volatiles were removed under reduced pressure, and the residue was dissolved in water to give a solid. The solid was filtered, washed with water, and dried under vacuum to give the title compound (0.35 g, 67%). The crude substance was used in the next step without further purification. LC-MS calculations showed C6H5ClN4(M+H)+: m / z = 168.58; measured value: 169.

[1141] Step 3: Synthesis of 7-bromo-2-iodo-[1,2,4]triazolo[1,5-a]pyridine

[1142] At 0 °C, 0.5 mL of an aqueous solution of NaNO2 (0.13 g, 0.0017 mmol) was added to a stirred solution of 2 mL of 48% HBr aqueous solution of 2-bromo-7-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.2 g, 0.0011 mmol). The reaction mixture was stirred at 0 °C for 5 hours, and then 0.5 mL of 48% HBr aqueous solution of copper bromide (I) (0.21 g, 0.0014 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours, and the reaction mixture was poured into ice water. The solid was separated, filtered, washed with water, and dried under vacuum to give the title compound (0.27 g, 51%). The crude substance could be used in the next step without further purification. LC-MS calculation: C6H3BClN3(M+H)+: m / z = 232.47; Measured value: 233.9.

[1143] Step 4: Synthesis of 7-chloro-2-vinyl-[1,2,4]triazolo[1,5-a]pyridine

[1144] A 1,4-dioxane solution (7 mL) of a mixture of 2-bromo-7-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.3 g, 9 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborane (0.1 g, 6 mmol) was added to an aqueous solution (3.0 mL) of Na₂CO₃ (0.2 g, 1.8 mmol) and Pd(dppf)Cl₂ (35 mg, 0.04 mmol). The mixture was degassed with N₂ for 30 min, and then heated at 110 °C for 16 h. The reaction was then cooled to room temperature and diluted with ethyl acetate (50 mL) and water (50 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 × 30 mL). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The crude substance was purified by Biotage rapid column chromatography using (0-10%) methanol in DCM to give the title compound (0.3 g, 45%) as a colorless liquid. LC-MS calculation: C8H6ClN3(M+H)+: m / z = 179.61; Measured value: 180.05.

[1145] Step 5: Synthesis of 2',2”-dimethyl-3”-(2-vinyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde

[1146] The title compound was prepared in a manner similar to that in Example 1, yielding a colorless liquid containing the title compound (300 mg, 45%). LC-MS calculations showed C29H23N3O(M+H)+: m / z = 429.52; measured value: 430.15.

[1147] Step 6: Synthesis of 2',2”-dimethyl-3”-(2-vinyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde

[1148] OsO4 (0.55 mL, 8.72 mmol) was added to a mixture of 2',2”-dimethyl-3”-(2-vinyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde (100 mg, 23.3 mmol), 2,6-dimethylpyridine (0.05 mL, 41.95 mmol) in THF (8 mL) and water (2 mL) under stirring. After 10 minutes, NaIO4 (90 mg, 41.95 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered and diluted with 10%... Washed with a mixture of MeOH / DCM. The filtrate was concentrated under reduced pressure to give the crude product. The crude product was purified by Biotage rapid column chromatography using (0-10%) ethyl acetate in hexane to give the title compound (90 mg, 99%) as a grayish-white solid. LC-MS calculation: C28H21N3O2(M+H)+: m / z = 431.5; Found: 432.15.

[1149] Step 7: Synthesis of 2-(((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol

[1150] The title compound was prepared in a manner similar to that in Example 1 to obtain a crude product. The crude product was subjected to preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain a grayish-white solid of the title compound (10 mg, 3%).

[1151] 1 H NMR (400MHz, DMSO-d6): δ: 8.59 (d, J = 7.2Hz, 1H), 7.7 (s, 1H), 7.41-7.31 (m, 7H), 7.24 (t, J = 5.6Hz, 2H), 7.15 9d,J=7.2Hz,1H),7.05(d,J=7.2Hz,1H),4.51(d,J=4.4Hz,2H),4.29(s,2H),3.779s,2H),3.32-3.49(m,4H),2.59-2.63 9m,4H),2.00 9s,3H),1.94(s,3H).

[1152] The LC-MS calculation result was C32H35N5O2(M+H)+: m / z = 521.67; the measured value was 522.25.

[1153] Following a similar procedure as described in Example 98, the following examples, as shown in Table 20, were prepared using appropriate amines:

[1154] Table 20

[1155]

[1156] Example 100: 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridineamide

[1157]

[1158] The compound of Example 100 was synthesized via the route shown in the following scheme.

[1159]

[1160] Step 1: Synthesis of 7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-carboxaldehyde

[1161] The title compound was prepared in a manner similar to that of Example 79, yielding a pale yellow solid (40 mg, 42%). LC-MS calculations showed C7H4ClN3O(M+H)+: m / z = 181.58, with a measured value of 182.10.

[1162] Step 2: Synthesis of 5-formyl-N-(3'-(2-formyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridineamide

[1163] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow viscous substance (55 mg, 58%). LC-MS calculations showed C28H21N5O3(M+H)+: m / z = 475.51, while the measured value was 476.10.

[1164] Step 3: Synthesis of 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)pyridineamide

[1165] The title compound was prepared in a manner similar to that in Example 1, and a crude product was obtained. This crude product was then purified by preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain the title compound (5 mg, 10%) as a grayish-white solid.

[1166] 1H NMR(400MHz,DMSO-d6):8.929(d,J=6.8Hz,1H),8.678(s,1H),8.205(s,1H),8.13(d,J=7.6Hz,1H ),8.02(d,J=8Hz,1H),7.88(d,J=7.6Hz,1H),7.76(s,1H),7.31-7.41(m,3H),7.21(d,J=6.8Hz,2 The wavelengths were: 7.04 (d, J = 6.8 Hz, 1H), 4.57 (s, 2H), 3.95 (s, 2H), 3.86 (s, 2H), 3.48 (s, 4H), 2.68 (d, J = 7.6 Hz, 2H), 2.59 (s, 2H), 2.06 (s, 3H), 1.97 (s, 3H). The LC-MS calculation was C32H35N7O3(M+H)+: m / z = 565.2; the measured value was 565.5.

[1167] Following a similar procedure to that described in Example 100, and using appropriate amines, the following examples, as shown in Table 21, were prepared:

[1168] Table 21

[1169]

[1170] Example 102: (S)-5-((((7-(4”-((((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)methyl)pyrrolidone-2-one

[1171]

[1172] The compound of Example 102 was synthesized via the route shown in the following scheme.

[1173]

[1174] Step 1: Synthesis of tert-butyl carbamate ((7-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)((5-oxopyrrolidone-2-yl)methyl)carbamate

[1175] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow viscous substance (400 mg, 42%).

[1176] The LC-MS calculation result was C17H22ClN5O3(M+H)+: m / z = 379.85, while the measured value was 380.10.

[1177] Step 2: Synthesis of (S)-((7-(4”-formyl-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)tert-butyl carbamate

[1178] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (230 mg, 100%).

[1179] The LC-MS calculation result is C38H39N5O4(M+H)+:m / z = 629.76, while the measured value is 630.25.

[1180] Step 3: Synthesis of (S)-((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)tert-butyl carbamate

[1181] The title compound was prepared in a manner similar to that in Example 1, yielding a pale yellow solid (140 mg, 99%).

[1182] The LC-MS calculation result is C40H46N6O4(M+H)+:m / z=674.85, and the measured value is 675.35.

[1183] Step 4: Synthesis of (S)-5-((((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)methyl)pyrrolidone

[1184] The title compound was prepared in a manner similar to that in Example 39, yielding a crude product, which was then purified by preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain a grayish-white solid (55 mg, 42%).

[1185] 1 H NMR(400MHz,DMSO-d6)δ:8.92(d,J=7.2Hz 1H), 8.21(s,2H), 7.75(s,1H), 7.66(s,1H), 7.46(d,J=7.6Hz,2H), 7.32-7.4(m,5H), 7.16-7.25(m,4H), 3.916-3.989(m,4H), 3.619(s,1H), 3.559(s,2H), 2.74(s,2H), 2.61-2.67(s,2H), 2.09(s,3H), 1.97(d,J=20Hz,6H), 1.69(s,1H), LC-MS calculated as C35H38N6O2(M+H)+:m / z=574.73; measured value: 575.7.

[1186] Example 103: (S)-N-(2,2'-dimethyl-3'-(2-((((5-oxopyrrolidone-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-4-(((2-hydroxyethyl)amino)methyl)benzamide

[1187]

[1188] The compound of Example 103 was synthesized via the route shown in the following scheme.

[1189]

[1190] Step 1: Synthesis of 5-((((7-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)methyl)pyrrolidone

[1191] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (850 mg, 90%). LC-MS calculations showed C12H14ClN5O(M+H)+: m / z = 279.73, while the measured value was 280.05.

[1192] Step 2: ((7-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)((5-oxopyrrolidone-2-yl)methyl)tert-butyl carbamate

[1193] At 0 °C, Boc anhydride (860 mg, 39 mmol) was added to a stirred mixture of 5-((((7-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)methyl)pyrrolidone-2-one (850 mg, 30 mmol), TEA (1.3 mL, 91 mmol) in methanol (1 mL), and DCM (9 mL). The reaction was stirred at room temperature for 5 hours, and the volatile organic compounds were removed under reduced pressure. The residue was dissolved in water and extracted with DCM (3 × 10 mL). The combined organic layers were dried over Na2SO4, filtered, and the solvent was evaporated under reduced pressure to give the crude product. The crude compound was purified by combined rapid column chromatography using a 0-30% ethyl acetate solution in hexane as the mobile phase to give the title compound 3 (850 mg, 74%) as a grayish-white solid. The LC-MS calculation result was C17H22ClN5O3(M+H)+: m / z = 379.85, while the measured value was 380.10.

[1194] Step 3: Synthesis of (S)-((7-(3'-(4-formylbenzamido)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)tert-butyl carbamate

[1195] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (200 mg, 79%). LC-MS calculation: C39H40N6O5(M+H)+: m / z = 672.79; Measured: 673.30.

[1196] Step 4: Synthesis of (S)-((7-(3'-(4-((((2-hydroxyethyl)amino)methyl)benzamido)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)tert-butyl carbamate

[1197] The title compound was prepared in a manner similar to that in Example 1, yielding a grayish-white solid (100 mg, 79.4%). LC-MS calculation: C41H47N7O5(MH)+: m / z = 717.87; Measured: 716.25.

[1198] Step 5: Synthesis of (S)-N-(2,2'-dimethyl-3'-(2-((((5-oxopyrrolidone-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1'-biphenyl]-3-yl)-4-(((2-hydroxyethyl)amino)methyl)benzamide

[1199] The title compound was prepared in a manner similar to that in Example 39, yielding a crude product, which was then passed through a preparative HPLC system (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain a white solid (25 mg, 17%). 1H NMR(400MHz, DMSO-d6)δ:8.92(d,J=6.8Hz1H),8.19(s,2H),7.97(d,J=7.6Hz,2H),7.76(s,1H),7.65(s,1H),7.52(d,J =7.6Hz,2H),7.297-7.29(m,4H),7.212(s,2H),7.09(d,J=7.2Hz,,1H),3.91-3.99(m,4H),3.62(s,1H),3.53(s,2H),3 .53 (s, 2H), 2.68 (s, 2H), 1.977 (d, J = 4.8 Hz, 6H), 1.69 (s, 1H). LC-MS calculated as C36H39N7O3(M+H)+: m / z = 617.75; measured value: 618.3. Example 104: 2-(((2',2”-dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[1200]

[1201] The compound of Example 104 was synthesized via the route shown in the following scheme.

[1202]

[1203] Step 1: Synthesis of 2-(((2',2”-dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[1204] The title compound was prepared in a manner similar to that in Example 1 to obtain a crude product. The crude product was subjected to preparative HPLC (X-Bridge C18 column (250x19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA aqueous solution, B = 100% ACN) to obtain the title compound (10 mg, 32%) as a white solid.

[1205] ¹H NMR (400MHz, DMSO-d⁶): δ: 8.96 (d, J = 7.2Hz, ¹H), 8.189 (s, ¹H), 7.856 (s, ¹H), 7.447–7.611 (m, 9H), 7.25 (d, J = 6.8Hz, ¹H), 4.5 (s, br, 2H), 3.957 (s, 2H), 3.83 (s, 2H), 3.504 (t, J = 6Hz, 4H), 2.67 (d, J = 4.8Hz, 4H). LC-MS calculation: C₃₀H₂₉Cl₂N₅O₂(M+H)⁺: m / z = 562.5; Measured value: 563.2.

[1206] Following a similar procedure as described in Example 104, the following examples shown in Table 22 were prepared using appropriate amines:

[1207] Table 22

[1208]

[1209]

[1210] Table 22 (continued):

[1211] Example 112: 2-(((2',2”-dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)-2-methylpropane-1-ol

[1212]

[1213] The compound of Example 112 was synthesized via the route shown in the following scheme.

[1214]

[1215] Step 1: Synthesis of 2-(((7-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol

[1216] Zinc chloride (561 mg, 4.12 mmol) was added to a stirred solution (10 mL) of 7-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-carboxaldehyde (500 mg, 2.75 mmol) and ethanolamine (0.16 mL, 2.75 mmol). Sodium cyanoborohydride (250 mg, 4.12 mmol) was added to the mixture, and the reaction mixture was heated at 80 °C for 16 hours. The volatile organic compounds were removed under reduced pressure, and the crude product was purified by rapid column chromatography using a (5-10%) methanol solution in dichloromethane to give the title compound 2-(((7-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol (320 mg, 51%) as a grayish-white solid. LC-MS calculation: C9H11ClN4O(M+H)+: m / z = 226.06; Measured value: 227.10

[1217] Step 2: Synthesis of 2',2”-dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde

[1218] A mixture of 2-(((7-chloro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol (100 mg, 0.44 mmol) and a solution of 2',2”-dichloro-3”-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde (200 mg, 0.44 mmol) in 1,4-dioxane (10 mL), water (1 mL), and K2CO3 (182 mg, 1.32 mmol) were added. The resulting reaction mixture was degassed with N2 for 20 min. Pd(dppf)Cl2·DCM (36 mg, 0.044 mmol) was added to the reaction mixture. The reaction mixture was then microwaved at 85 °C for 1 hour. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, and the aqueous layer was washed with ethyl acetate (3 × 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and evaporated on a rotary evaporator. The resulting crude product was purified by rapid column chromatography using methanol and dichloromethane as the mobile phase (0–10%) to give the title compound 2',2”-dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde (250 mg, 43%) as a brown solid. LC-MS calculation: C28H22Cl2N4O2(M+H)+: m / z = 516.11; Found: 517.05

[1219] Step 3: Synthesis of 2-(((2',2”-dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)-2-methylpropane-1-ol

[1220] A stirred solution (2 mL) of a methanol solution of 2',2”-dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-carboxaldehyde (100 mg, 0.19 mmol) and 2-amino-2-methyl-1-propanol (0.02 mL, 0.19 mmol) was added to zinc chloride (39 mg, 0.28 mmol) and sodium cyanoborohydride (18 mg, 0.28 mmol). The resulting mixture was stirred at 80 °C for 16 hours. Volatile organic compounds were removed under reduced pressure, and the crude product was passed through a preparative column (INT ODS). 3V-C18 (4.6*250) mm, 5 μm; mobile phase (A:B), A = 0.1% formic acid aqueous solution, B = acetonitrile), yielded the title compound 2-(((2',2”-dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)-2-methylpropane-1-ol (15 mg, 13%). LC-MS calculated C32H33Cl2N5O2(M+H)+: m / z=590.55; measured values: 590.101H NMR (400MHz, DMSO-d6): 8.98(d,1H,J=7.2Hz,8.21(s,2H),7.86(s,1H),7.64-7.43(m,8H),7.27-7.25(m,1H),4.6(bs,2H),3.96(s,2H),3.81(s,2H),3.49(t,2H,J=5.6Hz),2.69-2.67(m,2H),2.54(s,2H),1.24(s,2H),1.09(s,6H).

[1221] Following a similar procedure as described in Example 112, the following examples shown in Table 23 were prepared using appropriate amines:

[1222] Table 23

[1223]

[1224] PD1-PDL1 HTRF Measurement

[1225] The CisBio HTRF assay kit, purchased exclusively from CisBio, is used to determine the IC50 of compounds. 50The PD1-PDL1 HTRF assay measures the interaction between two proteins, PD1 and PDL1. The interaction is detected using anti-Tag1, labeled with europium (HTRF donor), which binds to PDL1, and anti-Tag2, labeled with XL665 (HTRF receptor), which binds to PD1. When the two antibodies are brought close together, excitation of the donor fluorophore leads to FRET emission of the receptor fluorophore. The presence of an inhibitor of this interaction results in attenuation of the HTRF signal.

[1226] The assay was performed in a 96-well white assay plate. All reagents, including Tag1-PDL1, Tag2-PD1, anti-Tag1-PDL1, and anti-Tag2-PD1, were thawed and diluted with PPI europium detection buffer to the desired concentrations according to the manufacturer's protocol. A 1000 μM stock solution of the test inhibitor was prepared in DMSO. The stock solution was diluted in DMSO to prepare eight concentrations (1000–0.001 μM). These stock solutions were further diluted in PPI europium detection buffer to prepare eight working stock solutions (100–0.0001 μM). 2 μL of the working stock solution of the test inhibitor was added to the 96-well plate, followed by 4 μL of Tag1-PDL1 (5 nM) and 4 μL of Tag2-PD1 (50 nM). After incubating at room temperature for 15 minutes, 10 μL of the pre-mixed anti-Tag1-PDL1 and anti-Tag2-PD1 solutions were added. The plate was sealed and incubated at room temperature for 1 hour. HTRF signals were read using a Perkin Elmer Envision microplate reader with an excitation wavelength of 320 nm and emission wavelengths of 620 nm and 665 nm. The results were obtained by multiplying the ratio of the receptor signal at 665 nm to the donor signal at 620 nm by 10⁴. The IC₀ was determined using the Hill equation with GraphPad Prism software. 50 value.

[1227] The compounds of the present invention, as exemplified in the embodiments, exhibit IC values ​​within the following ranges. 50 Value: +: IC 50 ≤10nM; ++: 10nM <IC 50 ≤100nM; +++: 100nM <IC 50 <1000nM

[1228] Table 23 provides data obtained using PD-1 / PD-L1 homogeneous time-resolved fluorescence (HTRF) binding analysis for the compounds of the examples described in Examples 1 to 105.

[1229] Table 24 shows the results of the PD-1 / PD-L1 homogeneous time-resolved fluorescence (HTRF) binding assays of the compounds of this invention.

[1230]

[1231]

[1232] Table 24 (continued)

[1233]

[1234]

[1235] Implementation Plan (Ea)

[1236] E1a. A compound of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof.

[1237]

[1238] in,

[1239] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[1240] R3 is H, methyl, halogen, or CN;

[1241] R4 and R5 can each be independently H, methyl, halogen or CN;

[1242] R7 represents H and C. 1-6 Alkyl, C 1-6 Alkoxy, halogen, or CN;

[1243] R1 is selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a , NHCOR a NHR a NHOR a C(O)R a CONHR a NHSO2R a SO2NHR a and OCH2R aAlternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the C of R1 is... 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 aryl, C6-10 aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups, each optionally selected by one, two, or three independent R groups b Substituents;

[1244] R2 is selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a and NHR a C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. b Substituents;

[1245] R6 is selected from H and C. 1-6 Alkyl, halogen and OCH2R a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, optionally by 1, 2, 3, or 4 independently selected R groups. b Substituents;

[1246] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[1247] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR cEach independently represents one, two, or three independently selected R. d Substituents;

[1248] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[1249] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[1250] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[1251] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[1252] E2a. The compound according to E1a has formula (II).

[1253]

[1254] Or its pharmaceutically acceptable salts or stereoisomers, wherein X1-X3, X5 and X6, R1, R3, R4-R7 and R b It has the same meaning as in E1a, with the subscript n being 1, 2, or 3.

[1255] E3a. The compound described in E2a, where n is 1.

[1256] E4a. The compound according to E1a has formula (III).

[1257]

[1258] Or its pharmaceutically acceptable salts or stereoisomers, wherein X1-X3, X5 and X6, R1, R3, R4-R7 and R b It has the same meaning as in E1a, with the subscript m being 0, 1, 2, or 3.

[1259] E5a. Compounds based on E1a that have formula (IV) or (V)

[1260]

[1261] Or its pharmaceutically acceptable salts or stereoisomers, wherein X1-X6, R1, R3, R4-R7 and R b It has the same meaning as in E1a, with the subscript n being 1, 2, or 3.

[1262] E6a. Compounds according to E1a, having formula (VI) or (VII).

[1263]

[1264] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein X1-X6, R1, R3, R4-R7 and Ra have the same meaning as in E1a, and the subscript p is 0 or 1.

[1265] E7a. The compound according to any one of E1a-E6a, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the heteroaryl group Selected from the following groups:

[1266]

[1267] E8a. The compound according to any one of E1a-E7a, wherein R3 is methyl, Cl or CN, R4 and R7 are H, and R5 is H, methyl or Cl.

[1268] E9a. The compound according to any one of E1a-E7a, wherein R3 is methyl and R4, R5 and R7 are H.

[1269] E10a. The compound according to any one of E1a-E7a, wherein R3 and R5 are methyl groups and R4 and R7 are H groups.

[1270] E11a. The compound according to any one of E1a-E7a, wherein R3 and R5 are Cl, and R4 and R7 are H.

[1271] E12a. The compound according to E1a, wherein R3 and R5 are methyl or Cl, R1, R4, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e R e Let H be a variable, and let X1-X6 be C or N independently, provided that at least two and at most five of X1-X6 are N.

[1272] E13a. The compound according to E1a, wherein R3 is a methyl group or Cl, R1, R4, R5, R6 and R7 are H, and R2 is a derivative of R... b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b It was R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d It is C(O)OR e R eH is a variable, and X1-X6 are each independently either C or N, provided that at least two and at most five of X1-X6 are N.

[1273] E14a. A compound according to E1a, wherein R3 is a methyl group, R4, R5 and R7 are H, R1 and R6 are H, or are linked together to form a 4-10 membered heterocyclic hydrocarbon group, and R2 is a methyl group. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b It is NHR c R c Is it by 1 or 2 Rs? d Replacement C 1-6 Alkyl, R d It is C(O)OR e S(O)2R e OR e R e It is H or OH, where X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N.

[1274] E15a. The compound according to E1a, wherein R3 is methyl or Cl, R4, R5 and R7 are H, R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, and R2 is a methyl group. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b Is it by 1 or 2 Rs? d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d It is C(O)OR e OR e R e Let H be an array of elements, where X1-X6 are each independently either C or N, provided that at least two and at most five of X1-X6 are N.

[1275] E16a. The compound according to E1a, wherein R3 is a methyl group, R4, R5 and R7 are H, R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, and R2 is a group consisting of 3 R groups. b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b1 Is it by 1 or 2 Rs? d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d It is C(O)OR e OR e And R e It is H, R b2 and R b3 It is C 1-6Alkoxy groups, wherein each of X1-X6 is independently C or N, provided that at least two and at most five of X1-X6 are N.

[1276] E17a. The compound according to E1a, wherein R3 is CN, R1, R4, R5, R6 and R7 are H, and R2 is a precipitate. b Replacement C 6-10 Aryl-C 1-4 Alkyl, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e R e Let H be the number of elements, where X1-X6 are each independently either C or N, provided that at least two and at most five of X1-X6 are N.

[1277] E18a. The compound according to E1a, wherein R3 is a methyl group, R1, R4, R5, R6 and R7 are H, and R2 is a derivative of R. b Replacement C 2-6 alkynyl group, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e Let H be a subset of X1-X6, where each of X1-X6 is independently either C or N, provided that at least two and at most five of X1-X6 are N.

[1278] E19a. The compound according to E1a, wherein R3 is a methyl group, R1, R4, R5, R6 and R7 are H, and R2 is a derivative of R... b Substituted 5-14 heteroaryl groups, R b It is C(O)NHR c R c It was R d Replacement C 1-6 Alkyl, R d It is C(O)OR e R e Let H be an integer, where X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N.

[1279] E20a. The compound according to E1a, wherein R3 is methyl, R4, R5 and R7 are H, R1 and R6 are linked together to form a 4-10 membered heterocyclic hydrocarbon group, and R2 is a radical formed by R... b Substituted 5-14 heteroaryl groups, R b C(O)NHR c R c For R d Replacement C1-6 Alkyl, R d C(O)OR e R e Let H be the number of elements, where X1-X6 are each independently either C or N, provided that at least two and at most five of X1-X6 are N.

[1280] Implementation Plan (Eb)

[1281] E1b. Compounds of formula (I) or their pharmaceutically acceptable salts or stereoisomers.

[1282]

[1283] in,

[1284] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[1285] R2 is R b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e For H;

[1286] R3 and R5 are each independently methyl or Cl;

[1287] R7 represents H and C. 1-6 Alkyl, C 1-6 Alkoxy, halogen, or CN;

[1288] R4 and R6 are H

[1289] And R1 is selected from R 1-aa R 1-bb R 1-cc R 1-dd R 1-bc R 1-bd R 1-dd R 1-de and R 1-ii ,

[1290] Among them, R 1-aa R 1-bb R 1-cc R 1-dd R 1-bc R 1-bd R 1-dd R 1-de And R 1-iiIn the table, each subscript r is an integer 0, 1, or 2, each subscript q is an integer 0, 1, 2, or 3, and Y1 and Y2 are each C or N.

[1291] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each independently represents one, two, or three independently selected R. d Substituents;

[1292] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[1293] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[1294] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[1295] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O). Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[1296] E2b. The compound according to E1b, wherein R1 is selected from R 1-a R 1-b R 1-c R 1-d R 1-e R 1-f R 1-g R 1-h and R 1-i ,

[1297] Among them, R 1-a R 1-b R1 -c R 1-d R 1-e R 1-f R 1-g R 1-h In the middle, each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c And R b C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each R is independently selected by 1, 2, or 3 independent selections. d Substituents;

[1298] Each R c Independently selected from H and C 1-6Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[1299] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[1300] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein Re C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[1301] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O). Other variables in formula (I) are as defined in any of the embodiments disclosed herein.

[1302] E3b. The compound according to E1b, wherein R1 is selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14 .

[1303] E4b. The compound according to any one of E1b-E3b, wherein R3 and R5 are both Cl.

[1304] E5b. The compound according to any one of E1b-E3b, wherein R3 and R5 are both methyl groups.

[1305] E6b. A compound of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is a derivative of R... b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b For NHR c R c For R d Replacement C 1-6 Alkyl, R d OR e R e For H or C 1-6 Alkyl group, wherein each of X1-X6 is independently C or N, provided that at least two and at most five of X1-X6 are N, wherein R1 is as defined in E1b.

[1306] E7b. The compound according to E6b, wherein R1 is selected from R as defined in E2b. 1-a R 1-b R 1-cR 1-d R 1-e R 1-f R 1-g R 1-h and R 1-I .

[1307] E8b. The compound according to E6b, wherein R1 is selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14 .

[1308] E9b. The compound according to any one of E6b-E8b, wherein R3 and R5 are both Cl.

[1309] E10b. The compound according to any one of E6b-E8b, wherein R3 and R5 are both methyl groups.

[1310] E11b. A compound of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is C. 1-6 Alkyl-NHR a R a For R d Replacement C 1-6 Alkyl, R d OR e Or C3-C6 cyclic amides, R e For H or C 1-6 Alkyl group, wherein each of X1-X6 is independently C or N, provided that at least two and at most five of X1-X6 are N, wherein R1 is as defined in E1b.

[1311] E12b. The compound according to E11b, wherein R1 is selected from R as defined in E2b. 1-a R 1-b R1 -c R 1-d R 1-e R 1-f R 1-g R 1-h and R 1-I .

[1312] E13b. The compound according to E11b, wherein R1 is selected from R 1-1 R 1-2 R 1-3 R 1-4 R 1-5 R-6, R 1-7 R 1-8 R 1-9 R 1-10 R 1-11 R 1-12 R 1-13 and R 1-14 .

[1313] E14b. The compound according to any one of E11b-E13b, wherein R3 and R5 are both Cl.

[1314] E15b. The compound according to any one of E11b-E13b, wherein R3 and R5 are both methyl groups.

[1315] E16b. A compound of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is C. 1-6 Alkyl-NHR a R a For R d Replacement C 1-6 Alkyl, R d OR e Or C3-C6 cyclic amides, R e For H or C 1-6 Alkyl group, wherein each of X1-X6 is independently C or N, provided that at least two and at most five of X1-X6 are N, wherein R1 is selected from:

[1316] C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, NHOR a C(O)R a , NHCOR a NHR a CONHR a NHSO2R a and SO2NHR a C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl group with 1 or 2 R b Substituents;

[1317] In R1:

[1318] Each R a Selected independently from C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl and (5-14-membered heteroaryl)-C 1-4 Alkyl groups, each independently of R d replace;

[1319] Each R b Substituents are independently selected from C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, NHC(O)R c C(O)NHR c NHR c And OMe, where C 6-10 Aryl and C 6-10 Aryl-C 1-4 Alkyl groups are each independently controlled by R d Replaced;

[1320] Each R c Selected independently from C 1-6 Alkyl groups, C groups substituted with OH 1-6 Alkyl, 4-10 membered heterocyclic hydrocarbon groups and (4-10 membered heterocyclic hydrocarbon groups)-C 1-4 alkyl-, where C 1-6 Alkyl, 4-10 membered heterocyclic hydrocarbon groups and (4-10 membered heterocyclic hydrocarbon groups)-C 1-4 Alkyl groups are each independently replaced by (=O), (OH) or COOH;

[1321] Each R d Independently selected from NHR e 4-10 membered heterocyclic hydrocarbon groups and (4-10 membered heterocyclic hydrocarbon groups)-C 1-4 Alkyl-, wherein 4-10 membered heterocyclic hydrocarbon groups and (4-10 membered heterocyclic hydrocarbon groups)-C 1-4 Alkyl groups are each independently replaced by (=O), (OH) or COOH;

[1322] Each R e Independently selected from C substituted with OH 1-6 Alkyl, 4-10 membered heterocyclic hydrocarbon groups and (4-10 membered heterocyclic hydrocarbon groups)-C 1-4 Alkyl-, wherein 4-10 membered heterocyclic hydrocarbon groups and (4-10 membered heterocyclic hydrocarbon groups)-C1-4 Alkyl groups are each independently replaced by (=O), (OH) or COOH;

[1323] E17b. A compound of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein;

[1324] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[1325] R2 is R b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b For R d Substituted 4-10 membered heterocyclic hydrocarbon groups, R d C(O)OR e And R e For H;

[1326] R3 and R5 are each independently methyl or Cl;

[1327] R7 represents H and C. 1-6 Alkyl, C 1-6 Alkoxy, halogen, or CN;

[1328] R4 and R6 are H; where R1 is as defined in E16b.

[1329] E18b. A compound of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R3 and R5 are each independently methyl or Cl, R4, R6 and R7 are H, and R2 is a derivative of R... b Replacement C 6-10 Aryl-C 1-4 Alkyl-, R b For NHR c R c For R d Replacement C 1-6 Alkyl, R d OR e R e For H or C 1-6 Alkyl group, wherein each of X1-X6 is independently C or N, provided that at least two and at most five of X1-X6 are N, wherein R1 is as defined in E16b.

[1330] Implementation Plan (Ec)

[1331] Ec1. Compounds of formula (I) or their pharmaceutically acceptable salts or stereoisomers.

[1332]

[1333] in,

[1334] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[1335] R3 is H, methyl, halogen, or CN;

[1336] R4 and R5 can each be independently H, methyl, halogen or CN;

[1337] R7 represents H and C. 1-6 Alkyl, C 1-6 Alkoxy, halogen, or CN;

[1338] R1 is selected from H and C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a NHOR a C(O)R a , NHCOR a NHR a CONHR a NHSO2R a SO2NHR a and OCH2R a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the C of R1 is... 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R b Substituents;

[1339] R2 is selected from C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6-cycloamide-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a -NHOR a C(O)R a , NHCOR a CONHR a NHSO2R a SO2NHR a NHR a and OCH2R a C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6-cyclic amide-C 1-4 Alkyl groups are each independently selected by 1, 2, 3 or 4 R groups. b Substituents;

[1340] R6 is selected from H and C. 1-6 Alkyl, C 2-6 Alkyne, halogens and OCH2R a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of 1, 2, 3, or 4 independently selected R groups. b Substituents;

[1341] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR c NHOR c , NHCOR c NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. d Substituents;

[1342] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides C 1-4 Alkyl group, OH group, (=O group), NH2 group, NHOR group c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)NR c R c C(O)OR c OC(O)R c C 1-6 Alkyl-NHR c NHR c NR c Rc S(O)2NR c R c , where R b C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides C 1-4 Alkyl groups are each independently selected by one, two, or three R groups. d Substituents;

[1343] Each R c Independently selected from H and C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides C 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides C 1-4Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[1344] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides, C3-C6 cyclic amides 1-4 Alkyl-, CN, NH2, NHOR e C(O)R e C(O)NR e R e C(O)OR e OC(O)R e OC(O)NR e R e 、(=O),NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides, C3-C6 cyclic amides 1-4 Alkyl groups, each optionally selected by one, two, or three independent R groups f Substituents;

[1345] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides 1-4 alkyl-, where R e C 1-6 Alkyl, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides 1-4 Alkyl groups are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[1346] Each R f Independently selected from H and C 1-4 Alkyl, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C3-C6 cyclic amides, halogens, CN, COOH, OH, (=O).

[1347] Ec2. The compound according to Ec1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:

[1348] X1-X6 are each independently C or N, provided that at least two and at most five of X1-X6 are N;

[1349] R3 is H, methyl, halogen, or CN;

[1350] R4 and R5 can each be independently H, methyl, halogen or CN;

[1351] R7 represents H and C. 1-6 Alkyl, C 1-6 Alkoxy, halogen, or CN;

[1352] R1 is selected from H and C. 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a , NHCOR a NHR a NHOR a C(O)R a CONHR a NHSO2R a SO2NHR a and OCH2R a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the C of R1 is... 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups, each optionally selected by one, two, or three independent R groups b Substituents;

[1353] R2 is selected from C 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, C 1-6 Alkyl-NHR a and NHR a C of R2 1-6 Alkyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 heteroaryl, C 6-10 Aryl-C 1-4 Alkyl-, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C1-4 Alkyl groups are each independently selected by one, two, or three R groups. b Substituents;

[1354] R6 is selected from H and C. 1-6 Alkyl, halogen and OCH2R a Alternatively, R1 and R6 can be linked together to form a 4-10 membered heterocyclic hydrocarbon group, optionally by 1, 2, 3, or 4 independently selected R groups. b Substituents;

[1355] Each R a Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl-, NHR c and OCH2R c , where R a C in 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, 5-14 membered heteroaryl, 4-10 membered heterocyclic hydrocarbon group, C 6-10 Aryl-C 1-4 Alkyl, (5-14-membered heteroaryl)-C 1-4 Alkyl-, (4-10 membered heterocyclic hydrocarbon group)-C 1-4 Alkyl groups are each independently selected by one or two independent R groups. d Substituents;

[1356] Each R b Substituents are independently selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c , where R b C1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, OH, (=O), NH2, NHOR c ,NHC(O)R c OR c C(O)R c C(O)NHR c C(O)OR c C 1-6 Alkyl-NHR c NHR c Each of the R options, which have 1, 2, or 3 independent choices, is replaced independently. d Substituents;

[1357] Each R c Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Alkyl, C(O)R d C(O)NHR d and C(O)NR d R d , where R c C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C 6-10 Aryl-C 1-4 Alkyl, C3-C6 cyclic amides 1-4 Each alkyl group is independently selected by one, two, or three independently chosen R groups. d Substituents;

[1358] Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R eNR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents;

[1359] Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e C 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents;

[1360] Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH, (=O).

[1361] Ec3. The compound according to Ec1 or Ec2, having formula (II).

[1362]

[1363] Or its pharmaceutically acceptable salts or stereoisomers, wherein X1-X3, X5 and X6, R1, R3, R4-R7 and R b It has the same meaning as in Ecs1 or Ecs2, with the subscript n being 1, 2, or 3.

[1364] Ec4. The compound according to Ec3, where n is 1.

[1365] Ec5. Compounds according to Eb1 or Eb2, having formula (IV) or (V).

[1366]

[1367] Or a pharmaceutically acceptable salt or stereoisomer thereof, wherein X1-X3, X5 and X6, R1, R3, R4-R7 and R... b It has the same meaning as in Ecs1 or Ecs2, with the subscript n being 1, 2 or 3;

[1368] In equation (V), X1-X4 and X6, R1, R3, R4-R7 and R b It has the same meaning as in Ecs1 or Ecs2, and the subscript n is 1, 2 or 3.

[1369] Ec6. Compounds according to Ec1 or Ec2, having form...

Claims

1. A compound of formula (VIII) or a pharmaceutically acceptable salt or stereoisomer thereof. in, X1-X4 can be C or N independently, provided that at least three of X1-X4 are N; The subscript p is 1; R3 and R5 are each independently methyl, Cl or CN; R4 represents H and C. 1-6 Alkyl, halogen, or CN; R6 represents H and C. 1-6 Alkyl or halogen; R1 is: R aa For H, or R aa With R a Linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of one or two independently selected R groups. d Substituents; R a Selected from C 1-6 Alkyl, C 1-6 Alkoxy and C 3-10 Cyclic hydrocarbon group, or R aa With R a Linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of one or two independently selected R groups. d Substituents; where R a The C mentioned 1-6 Alkyl, C 1-6 Alkoxy and C 3-10 Each of the cyclic hydrocarbon groups is independently selected by one or two independently chosen R groups. d Substituent substitution; R cc For H, or R cc With R c Linked together to form a 4-10 membered heterocyclic hydrocarbon group, wherein the heterocyclic hydrocarbon group is optionally composed of one or two independently selected R groups. d Substituent substitution; R c Selected from C 1-6 Alkyl, C 1-6 Alkoxy and C 3-10 Cyclic hydrocarbon group, or R cc and R c Linked together to form a 4-10 membered heterocyclic hydrocarbon group, said heterocyclic hydrocarbon group optionally being linked by one or two independently selected R groups. d Substituents; where R c The C mentioned 1-6 Alkyl, C 1-6 Alkoxy and C 3-10 Each of the cyclic hydrocarbon groups is independently selected by one or two independently chosen R groups. d Substituents; Each R d Selected independently from C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cyclic hydrocarbon groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic hydrocarbon groups, C3-C6 cyclic amides, CN, NH2, C(O)OR e NHR e NR e R e NR e C(O)R e NR e C(O)OR e OR e 、(=O),S(O)2R e and S(O)2NR e R e , where R d The C mentioned 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 3-10 Cycloalkyl groups, 5-14 membered heteroaryl groups, 4-10 membered heterocyclic alkyl groups, and C3-C6 cyclic amides are each optionally represented by one, two, or three independently selected R groups. f Substituents; Each R e Independently selected from H, OH, COOH, C(O)R f C 1-6 Alkyl groups and 5-14 heteroaryl groups, wherein R e The C mentioned 1-6 The alkyl group and the 5-14 heteroaryl group are each optionally surrounded by one, two, or three independently selected R groups. f Substituents; Each R f Independently selected from H and C 1-4 Alkyl, halogen, CN, COOH, OH and (=O).

2. The compound of claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the heteroaryl group Selected from the following groups: R aa and R a As defined in claim 1.

3. The compound according to any one of claims 1 or 2, wherein R3 and R5 are Cl; R4 and R6 are H and p is 1.

4. The compound according to any one of claims 1-3, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R3 and R5 are Cl; R4 and R6 are H, p is 1, and wherein the heteroaryl group is... for: R aa and R a As defined in claim 1.

5. The compound according to any one of claims 1-4, wherein, R1 is selected from:

6. The compound according to any one of claims 1-5, wherein R aa It is H and R a Selected from:

7. The compound according to any one of claims 1-5, wherein R aa and R a They are linked together to form compounds selected from the following:

8. The compound according to claim 1, wherein R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j , where R 1-j In the middle, R cc For H, R c For R d Replacement C 1-6 Alkyl, wherein R d OR e And R e For H, R aa For H, R a For R d Replacement C 1-6 Alkyl, wherein R d OR e And R e For H.

9. The compound according to claim 1, wherein R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j , where R 1-j In the middle, R cc For H, R c For R d Replacement C 3-10 Cyclic hydrocarbon group, wherein R d OR e And R e For H, R aa For H, R a For R d Replacement C 3-10 Cyclic hydrocarbon group, wherein R d OR e And R e For H.

10. The compound according to claim 1, wherein R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j , where R 1-j In the middle, R cc For H, R c For R d Replacement C 1-6 Alkyl, wherein R d For NHR e And R e For C(O)R f R f C 1-4 Alkyl, R a For R d Replacement C 1-6 Alkyl, wherein R d For NHR e And R e For C(O)R f R f C 1-4 alkyl.

11. The compound according to claim 1, wherein R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j , where R 1-j In the middle, R cc and R c Connected together to form R d Substituted 4-10 membered heterocyclic hydrocarbon groups, wherein R d C replaced by OH 1-6 Alkyl, R aa For H, R a For R d Replacement C 1-6 Alkyl, wherein R d OR e R e For H.

12. The compound according to claim 1, wherein R3 and R5 are Cl; R4 and R6 are H, p is 1, and the heteroaryl group for: R aa Let H be the number of 'R', and R be the number of 'R'. a Selected from: R1 is selected from:

13. The compound according to claim 1, wherein the compound is selected from: 2-(((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol; 2-(((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)ethane-1-ol; 2-(((2',2”-Dichloro-3”-(3-((((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol; (S)-5-((((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)methyl)pyrrolidone-2-one; (S)-5-((((2',2”-dimethyl-3”-(3-(((((S)-5-oxopyrrolid-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolid-2-one; (R)-1-((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)pyrrolidine-3-carboxylic acid; (S)-5-((((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)methyl)pyrrolidone; (S)-5-((((2',2”-dimethyl-3”-(2-((((((S)-5-oxopyrrolid-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolid-2-one; 2-(((2',2”-Dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)ethane-1-ol; ((7-(4”-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-D-proline; (S)-5-((((2',2”-dichloro-3”-(3-(((((S)-5-oxopyrrolid-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)methyl)pyrrolid-2-one; 2-(((2',2”-dichloro-3”-(2-(((1-hydroxy-2-methylpropane-2-yl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)-2-methylpropane-1-ol; 2-(((2',2”-Dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)-2-methylpropane-1-ol; ((7-(4”-(((S)-2-carboxypyrrolidone-1-yl)methyl)-2,2'-dichloro-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)-L-proline; ((7-(4”-(((R)-2-carboxypyrrolidone-1-yl)methyl)-2,2'-dichloro-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)-D-proline; N-(2-(((7-(4”-(((2-acetamidoethyl)amino)methyl)-2,2'-dichloro-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethyl)acetamide; (S)-2-(((7-(2,2'-dichloro-4”-((2-(hydroxymethyl)pyrrolidin-1-yl)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol (R)-2-(((7-(2,2'-dichloro-4”-((2-(hydroxymethyl)pyrrolidin-1-yl)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)ethane-1-ol; 3-(((2',2”-Dichloro-3”-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)propane-1-ol; 3-(((2',2”-Dichloro-3”-(2-(((3-hydroxycyclobutyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)cyclobutane-1-ol; 3-(((2',2”-Dichloro-3”-(2-((((3-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-[1,1':3',1”-terphenyl]-4-yl)methyl)amino)propane-1-ol; 2-(((7-(2,2'-dichloro-4”-(((2-hydroxyethyl)amino)methyl)-[1,1':3',1”-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methyl)amino)-2-methylpropane-1-ol.

14. A pharmaceutical composition comprising a compound according to any one of claims 1-13 or a pharmaceutically acceptable salt or stereoisomer thereof, and one or more pharmaceutically acceptable excipients or carriers.

15. A compound according to any one of claims 1-13 or a pharmaceutically acceptable salt or stereoisomer thereof, or a composition according to claim 14, used in a method for treating cancer.

16. A compound according to any one of claims 1-13 or a pharmaceutically acceptable salt or stereoisomer thereof, or a composition according to claim 14, in a method for treating an infection, preferably wherein the infection is a viral, bacterial, or fungal infection.

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