Novel PD-L1 inhibitors

Abstract

The present invention relates to compounds for modulating PD-1 / PD-L1 protein / protein interactions that are useful in treating various diseases associated with PD-1 / PD-L1 overexpression, including infectious diseases and cancer. The present invention further relates to compositions comprising such compounds, and their uses.

Description

[Technical Field]

[0001] The present invention relates to compounds for modulating PD-1 / PD-L1 protein / protein interactions that are useful in treating various diseases associated with PD-1 / PD-L1 overexpression, including infectious diseases and cancer. The present invention further relates to compositions comprising such compounds, and their uses. [Background technology]

[0002] Immune checkpoint molecules are inhibitory receptors expressed in immune cells that activate immunosuppressive signaling pathways. These molecules are critically important for maintaining self-tolerance in peripheral tissues and regulating the length and magnitude of effector immune responses, with the aim of minimizing incidental tissue damage.

[0003] The protein-protein interaction PD1 / PD-L1 is a crucial immune checkpoint. PD-1 is expressed in all activated T cells and functions as an inhibitory brake to modify the T cell immune response as part of the immune tolerance mechanism. PD-1 inhibits T cell function when it binds to either its binding partner, PD-L1 or PD-L2. (1) .

[0004] PD-L1 is known to be overexpressed in various types of cancer cells. Upregulation of PD-1 in immune cells also occurs during acute and chronic viral infections, as well as bacterial and fungal infections. Therefore, this immune checkpoint is thought to play a critically important role in suppressing antigen-specific T cell responses in diseases such as cancer and infections.

[0005] Targeting programmed cell death protein 1 / programmed cell death ligand 1 (PD-1 / PDL1) interactions has become an established strategy for cancer immunotherapy. Furthermore, the fact that these inhibitory pathways are also utilized by pathogens to evade the immune response suggests that blockade may be used in the prevention and treatment of infectious diseases, either during the acute or chronic phase of infection. (2)(3) .

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

[0007] However, the development of small molecule immunomodulators targeting this pathway has lagged significantly, and currently, the number of drug candidates showing good PD-1 / PD-L1 blocking activity in cell-based assays is very limited. (2) Therefore, the identification of chemical moieties that promote this inhibition, particularly small molecule inhibitors, is necessary. In particular, obtaining orally administered compounds that can help overcome the limitations of antibodies would be useful. Thus, the identification and development of novel PD-1 / PD-L1 inhibitory compounds for treating diseases or conditions associated with the reversal of T cell exhaustion will open up new opportunities in the field of cancer and infectious disease treatment. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] MN Wikes, SR Lewin, Nat Rev Immunol. 2018, Vol. 18(2), 91~104 [Non-Patent Document 2] C. Fang-Fang, L. Zheng et al., Oncoimmunology, 2020, Vol. 9 no. 1 [Non-Patent Document 3] L. Chang, NP Seeram et al., Cancer Cell Int. 2021, 21~239 [Overview of the project] [Means for solving the problem]

[0009] The present invention provides a compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof.

[0010] [ka]

[0011] (The substituents are as defined herein.)

[0012] The present invention also relates to a pharmaceutical composition comprising the compound of the present invention, or a pharmaceutically acceptable salt or stereoisomer thereof, and one or more pharmaceutically acceptable carriers or excipients.

[0013] The present invention further provides compounds and compositions for use in methods for treating diseases or disorders related to the reversal of T-cell exhaustion, which may be cancer or infectious diseases.

[0014] The present invention further provides a method for treating diseases or disorders related to the reversal of T-cell exhaustion, which may be cancer or infectious diseases. [Modes for carrying out the invention]

[0015] definition Unless otherwise specified, all scientific terms, chemical names, and technical terms used herein have the same meaning as those commonly understood by those skilled in the art. Dashes (-) at the beginning or end of a chemical group are for convenience to indicate a bond point. However, a chemical group can be represented with or without one or more dashes without prejudice to its usual meaning. Unless otherwise specified, each linked substituent includes both forward and backward-facing forms of the linked substituent. For example, -C 6~10 Aryl-C 1~4 Alkyl- is -C 6~10 Aryl-C 1~4Alkyl- and -C 1~4 Alkyl-C 6~10 Both aryl- and, each of these forms is intended to be disclosed individually, and even if only one side (e.g., C 1~4 Alkyl or C 6~10 Aryl-) is bonded or both sides are bonded.

[0016] The term "substituted" means that an atom or group of atoms is formally replaced by a "substituent" bonded to another group. The phrase "may be substituted" means not substituted or substituted. Unless otherwise indicated, the term "substituted" means any level of substitution where such substitution is allowed, e.g., mono-substitution, di-substitution, tri-substitution, tetra-substitution, or penta-substitution. Substituents are independently selected and substitution can occur at any chemically available position. It should be understood that substitution at a given atom is limited by valence and molecular stability. In the present disclosure, one or more substituents (e.g., R a , R b , R c , R d , R e , R f ) can be used to indicate substitution of a hydrogen atom by, for example, X n , Y n , R n , etc. Substituents are each independently selected, e.g., if one R n is selected to be a particular atom or group of atoms (e.g., C 1~6 Alkyl), the other R n can be something else from the list of possible substituents.

[0017] As used herein, the term "alkyl" means a saturated hydrocarbon group of the general formula -C n H 2n+1 which can be linear or branched. Non-limiting examples of alkyl moieties include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, etc. As used herein, "Cn~m The term "alkyl" refers to an alkyl group having n to m carbon atoms. For example, "C 1~6 The term "alkyl" is intended to disclose (without limitation) methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl individually.

[0018] As used herein, the term "alkynyl" means a linear or branched hydrocarbon group corresponding to an alkyl group having one or more carbon-carbon triple bonds. n~m The term "alkynyl" refers to an alkynyl group having n to m carbon atoms. Non-restrictive examples of alkynyl groups include ethynyl, propyne-1-yl, and propyne-2-yl.

[0019] As used herein, the term "alkoxy" means a -O-alkyl group whose alkyl group is as defined above. n~m The term "alkoxy" refers to an alkoxy group whose alkyl group has n to m carbon atoms. Non-exclusive examples of alkoxy groups include methoxy, ethoxy, and propoxy (e.g., n-propoxy and isopropoxy).

[0020] As used herein, the terms "halogen" or "halo" refer to a halogen atom selected from fluoro(F), chloro(Cl), or bromo(Br). In some preferred embodiments of the present invention, the halogen group is Cl.

[0021] As used herein, the terms "nitrile" or "cyano" refer to the group of formula -CN (also written as (-C≡N)).

[0022] As used herein, the term "amino" refers to the group of formula -NH2. n ~C m Alkyl-NHR nThe term refers to an amino group linked to the alkyl group as defined above, wherein one more hydrogen atom is substituted by an atom or group of atoms.

[0023] As used herein, the term "carbamyl" refers to the formulas -C(O)NH2, -NH2C(O), and NHC(O)R n C(O)NHR n The basis of (NHCOR n CONHR n It means (also written as).

[0024] As used herein, the term "carbonyl" means a -C(=O)- group (which may also be written as -C(O)- or -CO-).

[0025] The term "oxo" (=O) refers to a divalent oxygen atom that forms a carbonyl group when bonded to a carbon atom, or a sulfoxide, sulfone, or N-oxide group when bonded to a heteroatom. In some embodiments, the aryl group or heterocyclic group may be substituted with one or two oxo (=O) substituents.

[0026] As used herein, the term "aryl" means an aromatic hydrocarbon group that may be monocyclic or polycyclic (for example, having two fused rings). n~m The term "aryl" refers to an aryl group having n to m ring carbon atoms. Examples of aryl groups include phenyl, naphthyl, indanyl, and indenyl.

[0027] As used herein, the term "heteroaryl" means 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 means an aromatic heterocycle having 5-14 ring atoms, including a carbon atom and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen, preferably nitrogen. Non-limiting examples of heteroaryl groups include pyridinyl, pyrimidinyl, pyrazinyl, pyridadinyl, pyrrolyl, pyrazolyl, azolyl, imidazolyl, furanyl, quinolinyl, isoquinolinyl, naphthilidinyl, indolyl, benzofuranyl, and the like.

[0028] As used herein, the term "cycloalkyl" means a non-aromatic hydrocarbon ring system (monocyclic, bicyclic, or polycyclic) containing a cycloalkyl group and an alkenyl group. n~m The term "cycloalkyl" refers to a cycloalkyl group having n to m ring-member carbon atoms. Cycloalkyl groups can include monocyclic or polycyclic (e.g., groups with two, three, or four fused rings) groups. Non-limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, and cycloheptatrienyl.

[0029] As used herein, the term "heterocycloalkyl" means a non-aromatic ring or non-aromatic ring system having at least one heteroatom ring member independently selected from nitrogen, sulfur, and oxygen, which may include one or more alkenylene groups as part of its ring structure, and which may have, for example, 4 to 14 ring members, 4 to 10 ring members, 4 to 7 ring members, or 4 to 6 ring members. Monocyclic 4-membered, 5-membered, 6-membered, and 7-membered heterocycloalkyl groups are included within the scope of the term "heterocycloalkyl". Non-limiting examples of monocyclic heterocycloalkyl groups include piperidinyl, piperazinyl, pyrrolidinyl, azetidinyl, tetrahydropyranil, and tetrahydrofuranil. Heterocycloalkyl groups may also include bicyclic or polycyclic (e.g., having two or three condensed or bridging rings) or spirocyclic systems.

[0030] for example,

[0031] [ka]

[0032] These should be considered heterocycloalkyl groups substituted with oxo groups (=O) and R groups, respectively.

[0033] As used herein, the term "cyclic amide" means a cyclic compound having an amide group -C(=O)N- in the ring. n ~C m A cyclic amide refers to a cyclic amide having n to m ring-member carbon atoms (e.g., C3 to C6).

[0034] The above terms may be used individually or in combination with each other. For example, C 6~10 Aryl-C 1~4 Alkyl-, 5-14 member heteroaryl-C 1~4 Alkyl-, C 1~6 Alkyl-NHR a , or C n ~C mThe term cyclic amide-C1~4 alkyl- refers to an aryl, a 5-14 membered heteroaryl, an amino group, or C n ~C m This refers to a combination of a cyclic amide and an alkyl group as defined above. For example,

[0035] [ka]

[0036] C 6~10 Aryl-C 1~4 Alkyl- and C n ~C m Cyclic amide-C 1~4 It should be considered to fall within the scope of the above definition regarding alkyl groups.

[0037] The term “pharmaceutically acceptable” as used herein is intended to mean compounds and materials that are generally safe, non-toxic, and not biologically or otherwise undesirable, and includes those that are acceptable for veterinary use and for pharmaceutically acceptable use in humans.

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

[0039] The term "therapeutic dose" refers to the amount of active compound or drug that elicits a biological or pharmacokinetic response in a tissue, system, animal, individual, or human.

[0040] As used herein, the terms “to treat” or “treatment” mean the inhibition of a disease, condition, or disorder in an individual experiencing or exhibiting the pathology or symptoms of a disease, condition, or disorder; and / or improvement of the disease; for example, improvement of a disease, condition, or disorder (i.e., reversal of the pathology and / or symptoms) in an individual experiencing or exhibiting the pathology or symptoms of a disease, condition, or disorder, for example, a reduction in the severity of the disease.

[0041] compound This invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof.

[0042] [ka]

[0043] (In the formula, Each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N; R3 is H, methyl, halogen, or CN; R4 and R5 are independently H, methyl, halogen, or CN; R7 H, C 1~6 Alkyl, C 1~6 It is an alkoxy, halogen, or CN; R1 is H, C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR a NHOR a , C(O)R a NHCORa , NHR a , CONHR a , NHSO₂R a , SO₂NHR a , and OCH₂R a selected from, or R¹ and R⁶ are linked together to form a 4- to 10-member heterocycloalkyl, and the C of R¹ 1~6 alkyl, C 2~6 alkynyl, C 1~6 alkoxy, C 6~10 aryl, 5- to 14-member heteroaryl, C 6~10 aryl-C 1~4 alkyl-, C 3~10 cycloalkyl-C 1~4 alkyl-, (5- to 14-member heteroaryl)-C 1~4 alkyl-, (4- to 10-member heterocycloalkyl)-C 1~4 alkyl- may each be substituted with one, two, three, or four independently selected R b substituents; R² is C 1~6 alkyl, C 2~6 alkynyl, C 1~6 alkoxy, C 6~10 aryl, 5- to 14-member heteroaryl, C 6~10 aryl-C 1~4 alkyl-, C 3~10 cycloalkyl-C 1~4 alkyl-, (5- to 14-member heteroaryl)-C 1~4 alkyl-, (4- to 10-member heterocycloalkyl)-C 1~4 alkyl-, C₃-C₆ cyclic amide-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 selected from, and the C of R² 1~6 ​​​​Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide-C 1~4 Each alkyl- is independently selected from 1, 2, 3, or 4 R b Substituting with a substituent; R6 H, C 1~6 Alkyl, C 2~6 Alkynyl, halogen, and OCH2R a R1 and R6 are selected from, or R1 and R6 are linked together, and one, two, three, or four independently selected R b Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR c NHOR c NHCOR c NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected from 1, 2, or 3 R d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide 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)NR c R c , C(O)OR c ,OC(O)R c、 C 1~6 Alkyl-NHR c NHR c、 NR c R c、 S(O)2NR c R c Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide C 1~4 Each alkyl- is independently selected from 1, 2, or 3 R d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 2~6 Alkenil, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. dSubstituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amides, C3-C6 cyclic amide C 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amides, C3-C6 cyclic amide C1~4 Each alkyl group consists of one, two, or three independently selected R groups. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Alkyl, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide C 1~4 Selected from alkyl-, R e C 1~6 Alkyl, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 Alkyl, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Selected from alkyl-, C3-C6 cyclic amides, halogens, CN, COOH, OH, (=O).

[0044] In the compound of formula (I) above, Preferably, Each of X1 to X6 is independently either C or N, provided that at least two and at most three of X1 to X6 are N; R3 and R5 are preferably independently methyl or Cl. More preferably, both R3 and R5 are methyl. Alternatively, both R3 and R5 are Cl.

[0045] R4 is preferably H.

[0046] R7 is preferably H or C 1~6 The material is an alkoxy, more preferably H or OMe.

[0047] R1 is preferably H, C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-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 Selected from, or R1 and R6 are linked together to form a 4-10 member heterocycloalkyl, and the C of R1 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. b Substitutions may also be present; R2 is preferably C 1~6Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR a , and NHR a Selected from, R2's C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected from 1, 2, or 3 R b Substituting with a substituent; R6 is preferably H and OCH2R a R1 and R6 are selected from, or R1 and R6 are linked together, and one, two, three, or four independently selected R b Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; Each R a Preferably, H and C are independently 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R d Substituting with a substituent; Each R b The substituents are preferably independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c Preferably, H and C are independently 1~6 Alkyl, C 1~6 Alkoxy, C 3~10Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d Preferably independently C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each Re Preferably, independently, H, OH, COOH, C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f Preferably, H and C are independently 1~4 The group is selected from alkyl, halogen, CN, COOH, OH, and (=O).

[0048] In the compound of formula (I) above, heteroaryl group

[0049] [ka]

[0050] teeth

[0051] [ka]

[0052] A selection can be made from the group consisting of the following:

[0053] In the compound of formula (I) above, heteroaryl group

[0054] [ka]

[0055] teeth

[0056] [ka]

[0057] A selection can be made from the group consisting of the following:

[0058] Preferably, heteroaryl group

[0059] [ka]

[0060] teeth

[0061] [ka]

[0062] It is selected from the group consisting of the following.

[0063] In the compound of formula (I) above, R1 is R b C replaced by 1~3 Alkoxy, NHC(O)R a , R b C replaced by 6~10 Ariel, R b Substituted 5-14 member heteroaryls, NHR a CONHR a NHSO2R a , and SO2NHR a The group consisting of can be selected. R in equation (I) a , R b , and other variable elements are as specified in any embodiment disclosed herein.

[0064] In the compound of formula (I) above, R1 is

[0065] [ka]

[0066] A group consisting of these can be selected. (In the formula, 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 C or N, R b and R d(This is as specified in any embodiment disclosed herein.)

[0067] Preferably, R1 is

[0068] [ka]

[0069] Selected from the group consisting of (In the formula, R c and R d (This is as specified in any embodiment disclosed herein.)

[0070] In some embodiments, R1

[0071] [ka]

[0072] Compounds of formula (I) described herein are provided, selected from the above, wherein the other variable elements of formula (I) are as defined in any embodiment disclosed herein.

[0073] In some embodiments, compounds of formula (I) are provided herein, wherein R3 is methyl, Cl, or CN, R4 and R7 are H, R5 is H, methyl, or Cl, and the other variable elements of formula (I) are as defined in any embodiment disclosed herein.

[0074] Compounds of formula (I) are provided herein, in some embodiments, where R3 is methyl, R4, R5, and R7 are H, and the other variable elements of formula (I) are as defined in any embodiment disclosed herein.

[0075] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are methyl, R4 and R7 are H, and the other variable elements of formula (I) are as defined in any embodiment disclosed herein.

[0076] In some embodiments, compounds of formula (I) are provided herein, wherein R3 and R5 are Cl, R4 and R7 are H, and the other variable elements of formula (I) are as defined in any embodiment disclosed herein.

[0077] In some embodiments, compounds having formula (II) are provided herein. The compounds of formula (II) of the present invention are preferred embodiments of the compounds of formula (I) above, or pharmaceutically acceptable salts or stereoisomers thereof, specifically those of formula (II) below:

[0078] [ka]

[0079] The compound represented by , or a pharmaceutically acceptable salt or stereoisomer thereof (wherein the formula, the subscript n is 1, 2, or 3, preferably the subscript n is 1, X1-X3, X5, and X6, R1, R3-R7, and R b (This has the same meaning as in any embodiment of formula (I) described herein).

[0080] In some embodiments, compounds having formula (III) are provided herein. The compounds of formula (III) of the present invention are preferred embodiments of the compounds of formula (I) above, or pharmaceutically acceptable salts or stereoisomers thereof, specifically those of formula (III):

[0081] [ka]

[0082] The compound represented by , or a pharmaceutically acceptable salt or stereoisomer thereof (wherein the formula is 0, 1, 2, or 3, preferably the subscript m is 0 or 1, and X1-X3, X5, and X6, R1, R3-R7, and R b (This has the same meaning as in any embodiment of formula (I) described herein).

[0083] 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 the compounds of formula (I) above, or pharmaceutically acceptable salts or stereoisomers thereof, specifically the following:

[0084] [ka]

[0085] The compound represented by formula (IV), or a pharmaceutically acceptable salt or stereoisomer thereof (wherein the subscript n is 1, 2, or 3, preferably the subscript n is 1 or 2, and X1-X3, X5, and X6, R1, R3-R7, and R b This has the same meaning as in any embodiment of formula (I) described herein; In formula (V), the subscript n is 1, 2, or 3, preferably 1 or 2, and X1 to X4, X6, R1, R3 to R7, and R b (This has the same meaning as in any embodiment of formula (I) described herein).

[0086] 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 the compounds of formula (I) above, or pharmaceutically acceptable salts or stereoisomers thereof, specifically those of formula (VI) or (VII):

[0087] [ka]

[0088] The compound represented by formula VI, or its pharmaceutically acceptable salt or stereoisomer (wherein the subscript p is 0 or 1, X1-X3, X5, and X6, R1, R3, R4-R7, and R a This has the same meaning as in any embodiment of formula (I) described herein;

[0089] [ka]

[0090] In formula VII, the subscript p is 0 or 1, and X1 to X4, and X6, R1, R3, R4 to R7, and R a (This has the same meaning as in any embodiment of formula (I) described herein).

[0091] In the compounds of the above formulas (II) to (VII), Preferably, X1 to X6 are each independently C or N, provided that at least two and at most three of X1 to X6 are N; R3 and R5 are preferably independently methyl or Cl. More preferably, both R3 and R5 are methyl. Alternatively, both R3 and R5 are Cl.

[0092] R4 is preferably H.

[0093] R7 is preferably H or C 1~6 The material is an alkoxy, more preferably H or OMe.

[0094] R1 is preferably H, C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-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 Selected from, or R1 and R6 are linked together to form a 4-10 member heterocycloalkyl, and the C of R1 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. b Substitutions may also be present; R2 is preferably C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR a , and NHR a Selected from, R2's C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected from 1, 2, or 3 R b Substituting with a substituent; R6 is preferably H, OCH2R a R1 and R6 are selected from, or R1 and R6 are linked together, and one, two, three, or four independently selected R b Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; Each R a Preferably, H and C are independently 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R d Substituting with a substituent; Each R b The substituents are preferably independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4Alkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c Preferably, H and C are independently 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d Preferably independently C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e Preferably, independently, H, OH, COOH, C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 The group is selected from alkyl, halogen, CN, COOH, OH, and (=O).

[0095] In the compounds of formula (II), (III), (IV), or formula (VI) above, heteroaryl group

[0096] [ka]

[0097] teeth

[0098] [ka]

[0099] A selection can be made from the group consisting of the following:

[0100] Preferably,

[0101] [ka]

[0102] That is the case.

[0103] In the compound of formula (V) or formula (VII) above, heteroaryl group

[0104] [ka]

[0105] Preferably

[0106] [ka]

[0107] That is the case.

[0108] In the compounds of formulas (II) to (VII) above, R1 is R b C replaced by 1~3 Alkoxy, R b C replaced by 6~10 Ariel, Rb Substituted 5-14 member heteroaryls, NHR a CONHR a NHSO2R a , and SO2NHR a A group consisting of R can be selected, a and R b The other variations of formulas (II) to (VII) are as specified in any embodiment disclosed herein.

[0109] In the compounds of formulas (II) to (VII) above, R1 is

[0110] [ka]

[0111] A group consisting of these can be selected. (In the formula, 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 C or N, R b and R d (These are as specified in any embodiment disclosed herein.) Other variations of formulas (II) to (VII) are as specified in any embodiment disclosed herein.

[0112] In the compounds of formulas (II) to (VII) above, preferably R1 is

[0113] [ka]

[0114] Selected from the group consisting of (In the formula, R c and R d (These are as specified in any embodiment disclosed herein.) Other variations of formulas (II) to (VII) are as specified in any embodiment disclosed herein.

[0115] In some embodiments, R1

[0116] [ka]

[0117] Compounds of formulas (II) to (VII) above are provided herein, selected from among, wherein the other variable elements of formulas (II) to (VII) are as defined in any embodiment disclosed herein.

[0118] Compounds of formulas (I), (II), (III), (IV), (V), (VI), and (VII) are provided herein, in some embodiments, where R3 is methyl, Cl, or CN, R4 and R7 are H, R5 is H, methyl, or Cl, and other variable elements are as defined in any embodiment of formula (I) disclosed herein.

[0119] Compounds of formulas (I), (II), (III), (IV), (V), (VI), and (VII) are provided herein, in some embodiments, where R3 is methyl, R4, R5, and R7 are H, and other variable elements are as defined in any embodiment of formula (I) disclosed herein.

[0120] Compounds of formulas (I), (II), (III), (IV), (V), (VI), and (VII) are provided herein, in some embodiments, where R3 and R5 are methyl, R4 and R7 are H, and other variable elements are as defined in any embodiment of formula (I) disclosed herein.

[0121] Compounds of formulas (I), (II), (III), (IV), (V), (VI), and (VII) are provided herein, in some embodiments, where R3 and R5 are Cl, R4 and R7 are H, and other variable elements are as defined in any embodiment of formula (I) disclosed herein.

[0122] In some embodiments, R3 is methyl or Cl, R1, R4, R5, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e Compounds of formula (I), wherein is H, are provided herein. Other variables are as specified in any embodiment of formula (I) disclosed herein.

[0123] In some embodiments, R3 and R5 are methyl or Cl, R1, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e Compounds of formula (I), wherein is H, are provided herein. Other variables are as specified in any embodiment of formula (I) disclosed herein.

[0124] In some embodiments, R3 and R5 are methyl or Cl, and R1, R4, R6, and R7 are H, b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e Compounds of formula (II), wherein is H, are provided herein. Other variable elements are as specified in any embodiment of formula (II) disclosed herein.

[0125] In some embodiments, R3 is methyl or Cl, and R1, R4, R5, R6, and R7 are H, b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e Compounds of formula (II), wherein is H, are provided herein. Other variable elements are as specified in any embodiment of formula (II) disclosed herein.

[0126] In some embodiments, R3 is methyl, R4, R5, and R7 are H, R1 and R6 are H, or are linked together to form a 4-10 member heterocycloalkyl, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b NHR c And R c However, one or two R d C replaced by 1~6 It is alkyl, R d C(O)OR e S(O)2R e , or OR e And R e Compounds of formula (I), wherein the θ is H or OH, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0127] In some embodiments, R3 is methyl, R4, R5, and R7 are H, R1 and R6 are H, or are linked together to form a 4-10 member heterocycloalkyl group, R b NHR c And R c However, one or two R d C replaced by 1~6 It is alkyl, R d C(O)OR e S(O)2R e , or OR e And R eCompounds of formula (II), wherein the θ is H or OH, are provided herein. Other variations of formula (II) are as defined in any embodiment disclosed herein.

[0128] In some embodiments, R3 is methyl or Cl, R4, R5, and R7 are H, R1 and R6 are linked together to form a 4-10 member heterocycloalkyl group, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, one or two R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e OR e And R e Compounds of formula (I), wherein the compound is H, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0129] In some embodiments, R3 is methyl or Cl, R4, R5, and R7 are H, and R1 and R6 are linked together to form a 4-10 member heterocycloalkyl group, b However, one or two R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e OR e And R e Compounds of formula (II), wherein is H, are provided herein. Other variations of formula (II) are as defined in any embodiment disclosed herein.

[0130] In some embodiments, R3 is methyl, R4, R5, and R7 are H, R1 and R6 are linked together to form a 4-10 member heterocycloalkyl, and R2 is 3 R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b1 However, one or two R dA 4-10 member heterocycloalkyl substituted with R d C(O)OR e OR e And R e H is R b2 and R b3 C 1~6 Compounds of formula (I) that are alkoxys are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0131] In some embodiments, R3 is CN, R1, R4, R5, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e Compounds of formula (I), wherein the compound is H, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0132] In some embodiments, R3 is methyl, R1, R4, R5, R6, and R7 are H, and R2 is R b C replaced by 2~6 It is alkinyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e Compounds of formula (I), wherein the compound is H, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0133] In some embodiments, R3 is methyl, R1, R4, R5, R6, and R7 are H, and R2 is R b It is a 5-14 member heteroaryl substituted with R b C(O)NHRc And R c However, R d C replaced by 1~6 It is alkyl, R d C(O)OR e And R e Compounds of formula (I), wherein the compound is H, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0134] In some embodiments, R3 is methyl, R1, R4, R5, R6, and R7 are H, m is 0, R b C(O)NHR c And R c However, R d C replaced by 1~6 It is alkyl, R d C(O)OR e And R e Compounds of formula (III), wherein is H, are provided herein. Other variations of formula (III) are as defined in any embodiment disclosed herein.

[0135] In some embodiments, R3 is methyl, R4, R5, and R7 are H, R1 and R6 are linked together to form a 4-10 member heterocycloalkyl group, and R2 is R b It is a 5-14 member heteroaryl substituted with R b C(O)NHR c And R c However, R d C replaced by 1~6 It is alkyl, R d C(O)OR e And R e Compounds of formula (I), wherein the compound is H, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0136] In some embodiments, R3 is methyl, R4, R5, and R7 are H, R1 and R6 are linked together to form a 4-10 member heterocycloalkyl group, m is 0, R b C(O)NHR c And R c However, R d C replaced by 1~6 It is alkyl, R d C(O)OR e And R e Compounds of formula (III), wherein is H, are provided herein. Other variations of formula (I) are as specified in any embodiment disclosed herein.

[0137] In some embodiments, R1

[0138] [ka]

[0139] Selected from; 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 Y1 and Y2 are each independent integers of C or N; Each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 is H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R2 is C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C1~4 Alkyl-, C 1~6 Alkyl-NHR a , and NHR a Selected from, R2's C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 R is selected from one, two, or three alkyl groups, each independently. b Substituting with a substituent; R6 is H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a The substituents are independently H and C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 R is selected by independently choosing one or two alkyl- groups. d Substituting with a substituent; Each R b The substituents are independently C 1~6Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 R is selected independently of each other, either one, two, or three. d Substituting with a substituent; Each R c H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4Compounds of formula (I) selected from alkyl, halogen, CN, COOH, OH, (=O) are provided herein.

[0140] In some embodiments, R1 is

[0141]

Chemical formula

[0142] selected from; X1 to X6 are each independently C or N, provided that at least 2 and at most 5 of X1 to X6 are N; R3 is methyl or Cl; R5 is methyl or Cl; R4 is H; R7 is H, C 1~6 alkyl, or C 1~6 alkoxy; R2 is C 1~6 alkyl, C 2~6 alkynyl, C [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ R6 is H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 R is selected by independently choosing one or two alkyl- groups. d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C3~10 Cycloalkyl, 4- to 10-membered heterocycloalkyl, 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 is each independently substituted with one, two, or three independently selected R d substituents; Each R c is independently H, C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5- to 14-membered heteroaryl, 4- to 10-membered heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d , C(O)NHR d , and C(O)NR d R d selected from, R c of C 1~6 Alkyl, C / / 这里的“C Alkyl”表述似乎有误,推测可能是“C-Alkyl”,但按照要求保留原文翻译 1~6 Alkoxy, C 3~10 Cycloalkyl, 5- to 14-membered heteroaryl, 4- to 10-membered heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl is each independently substituted with one, two, or three independently selected R d substituents; Each R d is independently C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, C 3~10 Cycloalkyl, 5- to 14-membered heteroaryl, 4- to 10-membered heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds of formula (I), selected from alkyl, halogen, CN, COOH, OH, and (=O), are provided herein.

[0143] In some embodiments, R1

[0144] [ka]

[0145] Selected from; Each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 is H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R2 is C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR a , and NHR a Selected from, R2's C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 R is selected from one, two, or three alkyl groups, each independently. b Substituting with a substituent; R6 is H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 R is selected by independently choosing one or two alkyl- groups. d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 R is selected independently of each other, either one, two, or three. d Substituting with a substituent; Each R c H and C are independent. 1~6 Alkyl, C 1~6Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds of formula (I), selected from alkyl, halogen, CN, COOH, OH, and (=O), are provided herein.

[0146] In some embodiments, R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e H is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N, and R1 is 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 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-iiIn this case, the subscripts r are each independently integers 0, 1, or 2, the subscripts q are each independently integers 0, 1, 2, or 3, and Y1 and Y2 are each independently C or N; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 R is selected independently of each other, either one, two, or three. d Substituting with a substituent; Each R c H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHRd , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds of formula (I), selected from alkyl, halogen, CN, COOH, OH, and (=O), are provided herein. Other variations of formula (I) are as defined in any of the embodiments disclosed herein.

[0147] In some embodiments, R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e H is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N, and R1 is 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 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 Medium, each R c H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds of formula (I), selected from alkyl, halogen, CN, COOH, OH, and (=O), are provided herein. Other variations of formula (I) are as defined in any of the embodiments disclosed herein.

[0148] In some embodiments, R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e H is R1 is 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 Compounds of formula (I), selected from the above, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0149] In some embodiments, R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, Rb NHR c And R c However, R d C replaced by 1~6 It is alkyl, R d is OR e , or C 1~4 A C3-C6 cyclic amide with or without alkyl, R e is H or C 1~6 It is alkyl, and each of X1 to X6 is independently C or N, however, at least two and at most five of X1 to X6 are N, and R1 is 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 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 In this case, the subscripts r are each independently integers 0, 1, or 2, the subscripts q are each independently integers 0, 1, 2, or 3, and Y1 and Y2 are each independently C or N; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 R is selected independently of each other, either one, two, or three. d Substituting with a substituent; Each R c H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds of formula (I), selected from alkyl, halogen, CN, COOH, OH, and (=O), are provided herein. Other variations of formula (I) are as defined in any of the embodiments disclosed herein.

[0150] In some embodiments, R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b NHR c And R c However, R d C replaced by 1~6It is alkyl, R d is OR e , or C 1~4 A C3-C6 cyclic amide with or without alkyl, R e is H or C 1~6 It is alkyl, and each of X1 to X6 is independently C or N, however, at least two and at most five of X1 to X6 are N, and R1 is 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 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 Medium, each R c H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds of formula (I), selected from alkyl, halogen, CN, COOH, OH, and (=O), are provided herein. Other variations of formula (I) are as defined in any of the embodiments disclosed herein.

[0151] In some embodiments, R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is R b C replaced by6~10 Aryl-C 1~4 It is alkyl-, R b NHR c And R c However, R d C replaced by 1~6 It is alkyl, R d is OR e , or C 1~4 A C3-C6 cyclic amide with or without alkyl, R e is H or C 1~6 It is alkyl, and R1 is 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 Compounds of formula (I), selected from the above, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0152] In some embodiments, R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is C 1~6 Alkyl-NHR a And R a However, R d C replaced by 1~6 It is alkyl, R d is OR e Or it is a C3-C6 cyclic amide, R e is H or C 1~6 It is alkyl, and each of X1 to X6 is independently C or N, however, at least two and at most five of X1 to X6 are N, and R1 is 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 R1-ii 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 In this case, the subscripts r are each independently integers 0, 1, or 2, the subscripts q are each independently integers 0, 1, 2, or 3, and Y1 and Y2 are each independently C or N; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 R is selected independently of each other, either one, two, or three. d Substituting with a substituent; Each R c H and C are independent. 1~6Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides.f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds of formula (I), selected from alkyl, halogen, CN, COOH, OH, and (=O), are provided herein. Other variations of formula (I) are as defined in any of the embodiments disclosed herein.

[0153] In some embodiments, R3 and R5 are methyl or Cl, R4, R6, and R7 are H, and R2 is C 1~6 Alkyl-NHR a And R a However, R d C replaced by 1~6 It is alkyl, R d is OR e Or it is a C3-C6 cyclic amide, R e is H or C 1~6 It is alkyl, and R1 is 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 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 Medium, each R c H and C are independent. 1~6 Alkyl, C 1~6Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds of formula (I), selected from alkyl, halogen, CN, COOH, OH, and (=O), are provided herein. Other variations of formula (I) are as defined in any of the embodiments disclosed herein.

[0154] In some embodiments, R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is C 1~6 Alkyl-NHR a And R a However, R d C replaced by 1~6 It is alkyl, R d is OR e Or it is a C3-C6 cyclic amide, R e is H or C 1~6 It is alkyl, and R1 is 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 Compounds of formula (I), selected from the above, are provided herein. Other variations of formula (I) are as defined in any embodiment disclosed herein.

[0155] In some embodiments, formula (II)

[0156] [ka]

[0157] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript n is 1, 2, or 3; X1-X3, X5, and X6 are each independently either C or N, provided that at least two and at most five of X1-X3, X5, and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R1 is

[0158] [ka]

[0159] Selected from; In R1, 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 Y1 and Y2 are independently C or N; Preferably, R1 is 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 Selected from, more preferably, 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 , R1-13 , and R 1-14 Selected from; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0160] In some embodiments, formula (III)

[0161] [ka]

[0162] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript m is 0, 1, 2, or 3; X1-X3, X5, and X6 are each independently either C or N, provided that at least two and at most five of X1-X3, X5, and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R1 is

[0163] [ka]

[0164] Selected from; 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 Y1 and Y2 are independently C or N; Preferably, R1 is 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 Selected from, more preferably, 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 Selected from; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 of these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0165] In some embodiments, formula (IV) or (V)

[0166] [ka]

[0167] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript n is 1, 2, or 3; X1-X3, X5, and X6 are each independently either C or N, provided that at least two and at most five of X1-X3, X5, and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R1 is

[0168] [ka]

[0169] Selected from; In R1, 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 Y1 and Y2 are independently C or N; Preferably, R1 is 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 Selected from, more preferably, 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 Selected from; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, CN, NH2, C(O)OR e NHR e , NRe 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 Selected from alkyl, halogen, CN, COOH, OH, (=O); In equation (V), the subscript m is 1, 2, or 3; X1-X4 and X6 are each independently either C or N, provided that at least two and at most five of X1-X4 and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R1 is

[0170] [ka]

[0171] Selected from; In R1, 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 Y1 and Y2 are independently C or N. Preferably, R1 is 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 Selected from, more preferably, 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 Selected from; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, CN, NH2, C(O)OR e NHRe , 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0172] In some embodiments, formula (VI)

[0173] [ka]

[0174] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript p is 0 or 1; R1 is

[0175] [ka]

[0176] Selected from; 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 Y1 and Y2 are independently C or N; X1-X3, X5, and X6 are each independently either C or N, provided that at least two and at most five of X1-X3, X5, and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R fH and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0177] In some embodiments, formula (VI)

[0178] [ka]

[0179] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript p is 0 or 1; R1 is

[0180] [ka]

[0181] Selected from; X1-X3, X5, and X6 are each independently either C or N, provided that at least two and at most five of X1-X3, X5, and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c, and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0182] In some embodiments, formula (VI)

[0183] [ka]

[0184] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript p is 0 or 1; R1 is

[0185] [ka]

[0186] Selected from; X1-X3, X5, and X6 are each independently either C or N, provided that at least two and at most five of X1-X3, X5, and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C1~6 It is an alkoxy; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0187] In some embodiments, formula (VII)

[0188] [ka]

[0189] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript p is 0 or 1; R1 is

[0190] [ka]

[0191] Selected from; 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 Y1 and Y2 are independently C or N; X1-X4 and X6 are each independently either C or N, provided that at least two and at most five of X1-X4 and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R dSubstituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R cC 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each Rf H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0192] In some embodiments, formula (VII)

[0193] [ka]

[0194] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript p is 0 or 1; R1 is

[0195] [ka]

[0196] Selected from; X1-X4 and X6 are each independently either C or N, provided that at least two and at most five of X1-X4 and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6 It is an alkoxy; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHRc , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. dSubstituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0197] In some embodiments, formula (VII)

[0198] [ka]

[0199] Compounds having, or pharmaceutically acceptable salts or stereoisomers thereof, are provided herein (wherein the subscript p is 0 or 1; R1 is

[0200] [ka]

[0201] Selected from; X1-X4 and X6 are each independently either C or N, provided that at least two and at most five of X1-X4 and X6 are N; R3 is either methyl or Cl; R5 is either methyl or Cl; R4 is H; R7 H, C 1~6 Alkyl, or C 1~6It is an alkoxy; R6 H, C 1~6 Alkyl, halogen, and OCH2R a Selected from; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, CN, NH2, C(O)OR e NHRe , 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)).

[0202] The present invention provides a compound of formula (VIII), or a pharmaceutically acceptable salt or stereoisomer thereof.

[0203] [ka]

[0204] (In the formula, Each of X1 to X4 is independently either C or N, provided that at least three of X1 to X4 are N; The subscript p is 1; R3 and R5 are independently methyl, Cl, or CN; R4 is H, C 1~6 It is alkyl, halogen, or CN; R6 H, C 1~6 Alkyl or halogen; R1 is

[0205] [ka]

[0206] and; R aa is H, or R aa and R a These are linked together, and one or two independently selected R d Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; R a is C 1~6 Alkyl, C 1~6 Alkoxy, and C 3~10 Selected from cycloalkyl, or R aa and R a These are linked together, and one or two independently selected R d Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; R a C 1~6 Alkyl, C 1~6 Alkoxy, and C 3~10 Each cycloalkyl group is independently selected as one or two R groups. d Substituting with a substituent; R cc is H, or R cc and R c These are linked together, and one or two independently selected R d Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; R c is C 1~6 Alkyl, C 1~6 Alkoxy, and C 3~10 Selected from cycloalkyl, or Rcc and R c These are linked together, and one or two independently selected R d Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; R c C 1~6 Alkyl, C 1~6 Alkoxy, and C 3~10 Each cycloalkyl group is independently selected as one or two R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyls, 5-14 membered heteroaryls, 4-10 membered heterocycloalkyls, and C3-C6 cyclic amides are each selected as one, two, or three independently. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. fSubstitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, and (=O)).

[0207] In the compound of formula (VIII) above, Preferably, Each of X1 to X4 is independently either C or N, except that three of X1 to X4 are N; The subscript p is 1; R3 and R5 are independently methyl or Cl; R4 and R6 are H; R1 is

[0208] [ka]

[0209] and; R aa is H, or R aa and R a They are linked together, forming one R d Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; R a is C 1~6 Alkyl and C 3~10 Selected from cycloalkyl, or R aa and R a They are linked together, forming one R d Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; C 1~6 Alkyl and C 3~10 Each cycloalkyl group has one independent R d Substituting with a substituent; R cc is H, or R cc and R c They are linked together, forming one R d Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; R c is C1~6 Alkyl and C 3~10 Selected from cycloalkyl, or R cc and R c They are linked together, forming one R d Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; C 1~6 Alkyl and C 3~10 Each cycloalkyl group has one independent R d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C3-C6 cyclic amide, C(O)OR e NHR e , NR e C(O)R e , OR e Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy and C3-C6 cyclic amides are each selected as one or two independently. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f Selected from; Each R f H and C are independent of each other. 1~4 Selected from alkyl, halogen, CN, COOH, OH, and (=O).

[0210] Preferably, R f These are independently H, methyl, and C 2~4 Selected from alkyl, COOH, OH, and (=O).

[0211] Preferably, R aa and R a These are linked together to form a cyclic amine substituted with CH2(OH) or C(O)OH.

[0212] Preferably, R cc and R cThese are linked together to form a cyclic amine substituted with CH2(OH) or C(O)OH.

[0213] In the compound of formula (VIII) above, heteroaryl group

[0214] [ka]

[0215] teeth

[0216] [ka]

[0217] A group consisting of these can be selected, The subscript p=1, and R in equation (VIII) aa and R a This is as specified in any embodiment disclosed herein.

[0218] Preferably, heteroaryl group

[0219] [ka]

[0220] teeth

[0221] [ka]

[0222] That is the case.

[0223] In the compound of formula (VIII) above, R1 is

[0224] [ka]

[0225] A group consisting of these can be selected, Other variations of formula (VIII) are as specified in any embodiment disclosed herein.

[0226] In the compound of formula (VIII) above, R aa can be H, and R a teeth

[0227] [ka]

[0228] It can be selected from, Other variations of formula (VIII) are as specified in any embodiment disclosed herein.

[0229] In the compound of formula (VIII) above, R aa and R a They are linked together,

[0230] [ka]

[0231] A compound selected from these can be formed, Other variations of formula (VIII) are as specified in any embodiment disclosed herein.

[0232] In the compound of formula (VIII) above, preferably R3 and R5 are both Cl; preferably R3 and R5 are both methyl.

[0233] In some embodiments, in the compound of formula (VIII) above, R3 and R5 are both Cl, and X1 to X4 are independently C or N, except that three of X1 to X4 are N; the subscript p is 1; R4 and R6 are H; and other variable elements of formula (VIII) are as specified in any embodiment disclosed herein.

[0234] In some embodiments, in the compound of formula (VIII) above, R3 and R5 are both methyl, and X1 to X4 are independently C or N, except that three of X1 to X4 are N; the subscript p is 1; R4 and R6 are H; and other variable elements of formula (VIII) are as specified in any embodiment disclosed herein.

[0235] In some embodiments, R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 1~6 It is alkyl, R d is OR e And R e H is R aa H is R a However, R d C replaced by 1~6 It is alkyl, R d is OR e And R e Compounds of formula (VIII), wherein is H, are provided herein.

[0236] In some embodiments, R3 and R5 are methyl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 1~6 It is alkyl, R d is OR e And R e H is R aa H is R a However, R d C replaced by 1~6 It is alkyl, R d is OR e And R eCompounds of formula (VIII), wherein is H, are provided herein.

[0237] In some embodiments, R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 3~10 It is cycloalkyl, R d is OR e And R e H is R aa H is R a However, R d C replaced by 3~10 It is cycloalkyl, R d is OR e And R e Compounds of formula (VIII), wherein is H, are provided herein.

[0238] In some embodiments, R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 1~6 It is alkyl, R d NHR e And R e C(O)R f And R f C 1~4 It is alkyl, R a However, R d C replaced by 1~6 It is alkyl, R d NHR e And R e C(O)R f And R f C 1~4 Compounds of formula (VIII) that are alkyl are provided herein.

[0239] In some embodiments, R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc and R c They are linked together, R d Forms a 4-10 member heterocycloalkyl group substituted with R d C(O)OH, or C substituted with OH 1~6 It is alkyl, R aa H is R a However, R d C replaced by 1~6 It is alkyl, R d is OR e And R e Compounds of formula (VIII), wherein is H, are provided herein.

[0240] In some embodiments, R3 and R5 are Cl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc and R c They are linked together, R d Forms a 4-10 member heterocycloalkyl group substituted with R d C(O)OH, or C substituted with OH 1~6 It is alkyl, R aa and R a They are linked together, R d Forms a 4-10 member heterocycloalkyl group substituted with R d C(O)OH, or C substituted with OH 1~6 Compounds of formula (VIII) that are alkyl are provided herein.

[0241] In some embodiments, R3 and R5 are both Cl or both methyl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 1~6 It is alkyl, Rd is OR e And R e H is R aa H is R a However, R d C replaced by 1~6 It is alkyl, R d Compounds of formula (VIII), wherein is a C3-C6 cyclic amide, are provided herein.

[0242] In some embodiments, R3 and R5 are both Cl or both methyl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 1~6 It is alkyl, R d It is a C3-C6 cyclic amide, and R aa H is R a However, R d C replaced by 1~6 It is alkyl, R d Compounds of formula (VIII), wherein is a C3-C6 cyclic amide, are provided herein.

[0243] In some embodiments, R3 and R5 are both Cl or both methyl; R4 and R6 are H, p is 1, and R1 is R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 1~6 It is alkyl, R d is OR e And R e H is R aa and R a They are linked together, R d Forms a 4-10 member heterocycloalkyl group substituted with R d C(O)OH, or C substituted with OH 1~6 Compounds of formula (VIII) that are alkyl are provided herein.

[0244] In each of the above embodiments, independently, C 1~6 The alkyl group is preferably methyl, ethyl, or C3 alkyl.

[0245] In some embodiments, R3 and R5 are both Cl or both methyl; R4 and R6 are H, p is 1, and a heteroaryl group

[0246] [ka]

[0247] but

[0248] [ka]

[0249] and; R aa H is R a but

[0250] [ka]

[0251] Selected from; R1

[0252] [ka]

[0253] Selected from, Compounds of formula (VIII) are provided herein.

[0254] In some embodiments of the present invention, 2-(((7-(4''-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-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]pyridine-3-yl)methyl)amino)ethane-1-ol; 2-(((2',2''-Dichloro-3''-(3-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-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]pyridine-3-yl)methyl)amino)methyl)pyrrolidine-2-one; (S)-5-((((2',2''-dimethyl-3''-(3-(((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-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]pyridine-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]pyridine-2-yl)methyl)amino)methyl)pyrrolidin-2-one; (S)-5-((((2',2''-dimethyl-3''-(2-(((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one; 2-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-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]pyridine-3-yl)methyl)-D-proline; (S)-5-((((2',2''-Dichloro-3''-(3-(((((S)-5-Oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]Triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-Terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one; 2-(((2',2''-Dichloro-3''-(2-(((1-Hydroxy-2-methylpropan-2-yl)amino)methyl)-[1,2,4]Triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-Terphenyl]-4-yl)methyl)amino)-2-methylpropan-1-ol; 2-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)-2-methylpropan-1-ol; ((7-(4''-(((S)-2-carboxypyrrolidine-1-yl)methyl)-2,2'-dichloro-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)-L-proline; ((7-(4''-(((R)-2-carboxypyrrolidine-1-yl)methyl)-2,2'-dichloro-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-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]pyridine-2-yl)methyl)amino)ethyl)acetamide; (S)-2-(((7-(2,2'-Dichloro-4''-((2-(hydroxymethyl)pyrroridine-1-yl)methyl)-[1,1':3',1''-Terphenyl]-3-yl)-[1,2,4]Triazolo[1,5-a]pyridine-2-yl)methyl)amino)ethane-1-ol (R)-2-(((7-(2,2'-Dichloro-4''-((2-(hydroxymethyl)pyrroridine-1-yl)methyl)-[1,1':3',1''-Terphenyl]-3-yl)-[1,2,4]Triazolo[1,5-a]pyridine-2-yl)methyl)amino)ethane-1-ol; 3-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)propan-1-ol; 3-(((2',2''-Dichloro-3''-(2-(((3-hydroxycyclobutyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)cyclobutan-1-ol; 3-(((2',2''-Dichloro-3''-(2-(((3-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)propan-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]pyridine-2-yl)methyl)amino)-2-methylpropane-1-ol Compounds having formula I, selected from the above, are disclosed.

[0255] In one embodiment, the compound of formula (VIII) 2-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol That is the case.

[0256] Specific features of the present invention described in separate embodiments can also be realized by combining them in a single embodiment. Therefore, it is assumed that the features described as embodiments of the compound of formula (I) can be combined with any suitable combination of compounds of formulas (II) to (VII).

[0257] The compounds described and claimed herein may have one or more stereocenters and may be isolated as enantiopurines (optically active compounds) or as a mixture of stereoisomers, such as a racemate. Methods for obtaining enantiopurines by enantioselective synthesis and / or from optically inert starting materials are known in the art. The cis and trans geometric isomers of the compounds of the present invention may be isolated as a mixture of isomers or as separate isomers.

[0258] 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 two or more chiral centers, each chiral center may independently be (R) or (S).

[0259] As used herein, the term “compound” includes all geometric and stereoisomers of the illustrated structure. The present invention also includes pharmaceutically acceptable salts of the compounds described herein. The pharmaceutically acceptable salts of the present invention include GRAS salts of parent compounds formed, for example, from generally safe (GRAS) inorganic or organic acids.

[0260] All compounds and their pharmaceutically acceptable salts may exist in their pure form or in combination with other substances such as water and solvents. This means that, in the solid state, the compounds and salts described herein may exist in various forms, such as solvates including hydrates. Therefore, unless otherwise indicated, references to compounds and their salts herein should be understood to encompass all solid-state forms of such compounds (e.g., polymorphs or solvates).

[0261] The compounds or salts thereof of the present invention can be substantially or partially isolated / purified from the environment in which they are formed or detected. This can be done by purification processes known in the art. The term substantially purified compound means a composition comprising at least 50% by mass, at least about 60% by mass, at least about 70% by mass, at least about 80% by mass, at least about 90% by mass, at least about 95% by mass, or at least about 99% by mass of the compound or salt thereof of the present invention.

[0262] medical use For the sake of brevity, the uses and methods will be described only in relation to the "compounds of the present invention." It will be understood that any of the disclosed compounds (including any of their embodiments) can be used in relation to the uses described herein.

[0263] The compounds of this invention are intended for use as pharmaceuticals.

[0264] The compounds of the present invention, or their pharmaceutically acceptable salts or stereoisomers, or compositions of the present invention can be used in methods for treating diseases or disorders related to the inhibition of PD-1 / PD-L1 interaction, such as cancer or infectious diseases.

[0265] The compounds of this disclosure are capable of inhibiting the activity of PD-1 / PD-L1 protein / protein interactions and are therefore useful in treating diseases and disorders associated with the activity of PD-1 / PD-L1 interactions. Accordingly, the present invention provides compounds and compositions for use in a method of inhibiting PD-1 / PD-L1 interactions, comprising the step of administering the compounds of the present invention, or pharmaceutically acceptable salts or stereoisomers thereof, to a patient in need thereof.

[0266] Furthermore, the compounds of the present invention, or their pharmaceutically acceptable salts or stereoisomers, or compositions of the present invention can be used to enhance, stimulate, and / or increase the immune response in patients with cancer or acute or chronic infections. The compounds of the present disclosure can be used alone, in combination with other agents or therapeutic agents, or as adjuvants for the treatment of diseases or disorders, including cancer or infectious diseases.

[0267] The compounds of the present invention induce the reversal of T-cell exhaustion that may occur in cancer or infectious diseases. Experiments performed by the applicant have shown that the compounds of the present invention inhibit PD-1 / PD-L1 interactions in cancer cells and during infectious diseases in vitro and / or in vivo. Blocking PD-1 enhances the immune response to cancer cells and infectious diseases in mammals, including humans.

[0268] In some embodiments, compounds and compositions for use in methods for treating cancer are provided herein.

[0269] In one embodiment, the present disclosure provides compounds and compositions for use in methods for inhibiting the proliferation of tumor cells.

[0270] In some embodiments, methods for treating cancer are provided herein, comprising the step of administering the compounds and compositions of the present invention to a subject in need thereof.

[0271] In some embodiments, methods for inhibiting the proliferation of tumor cells are provided herein, comprising the step of administering the compounds and compositions of the present invention to a subject requiring such inhibition.

[0272] The compounds of the present invention can be used in all types of cancer in which PD-L1 overexpression is present. Non-limiting examples of cancers that can be treated with the compounds of the present 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, Calmette-Guérin bacillus 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, mediastinal primary B-cell large 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.

[0273] Blocking the PD-1 pathway with the compounds of this disclosure may also be useful for treating infectious diseases. Therefore, the compounds of the present invention can be used in methods for treating infectious diseases. The compounds of the present invention can be used in all types of infectious diseases in which PD-1 / PD-L1 overexpression is present. These may be viral infections, bacterial infections, fungal infections, and parasitic infections. Non-limiting examples of infectious diseases treatable with the compounds of the present invention include 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, frenetic retrovirus, respiratory syncytial virus, rabies virus, tuberculosis, malaria, Candida albicans, Helicobacter pylori, Staphylococcus aureus, Pseudomonas aeruginosa, Borrelia burgdorferi, and sepsis.

[0274] In one embodiment, the present disclosure provides compounds and compositions for use in methods for treating bacterial infections.

[0275] In one embodiment, the present disclosure provides compounds and compositions for use in methods for treating viral infections.

[0276] In one embodiment, the present disclosure provides compounds and compositions for use in methods for treating chronic infections.

[0277] In one embodiment, the present disclosure provides compounds and compositions for use in methods for treating acute infections.

[0278] In one embodiment, the present disclosure provides a method for treating a viral infection, comprising the step of administering a compound or composition of the present invention to a subject in need thereof.

[0279] In one embodiment, the present disclosure provides a method for treating a bacterial infection, comprising the step of administering a compound or composition of the present invention to a subject in need thereof.

[0280] In one embodiment, the present disclosure provides a method for treating a chronic infection, comprising the step of administering a compound or composition of the present invention to a subject in need thereof.

[0281] In one embodiment, the present disclosure provides a method for treating an acute infection, comprising the step of administering a compound or composition of the present invention to a subject in need thereof.

[0282] Formulation, dosage form, and administration The present invention also relates to pharmaceutical compositions comprising a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers or excipients. In these compositions, the compounds of the present invention are used as active ingredients.

[0283] Accordingly, this disclosure provides compositions 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.

[0284] These compositions can be prepared according to methods known in the art and administered via any route suitable for the condition to be treated. For example, preferred routes include topical, transdermal, parenteral, nasal, oral, and rectal administration. It will be recognized that the preferred route may vary, for example, depending on the recipient's condition. Oral administration is particularly preferred and advantageous. The compounds of the present invention can be administered easily and safely by oral administration.

[0285] When preparing the compositions of the present invention, the active ingredient is usually mixed with an excipient, diluted with an excipient, or encapsulated in a carrier in the form of, for example, a tablet, capsule, sachet, paper, or other container (liquid, solid, spray).

[0286] Tablets, capsules, and other formulations suitable for oral administration are particularly preferred.

[0287] Some 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. The formulation may contain emulsifiers and suspending agents; preservatives such as methyl and propyl hydroxybenzoates; sweeteners; and flavorings. The composition may also contain 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.

[0288] General Synthesis. In another aspect, the present invention relates to a method for obtaining the compounds of the present invention. Examples of general procedures for obtaining the compounds of the present invention, as well as examples of synthetic routes for preparing them and their intermediate compounds, are described below.

[0289] [ka]

[0290] General Scheme 1

[0291] [ka]

[0292] In general scheme 1, the following reaction conditions are typically applied: (Step 1) Synthesis is carried out at a suitable temperature (e.g., 110°C) using a suitable solvent (1,4-dioxane, 1,2-dimethoxyethane) in the presence of a suitable catalyst (e.g., Pd(PPh3)4, Pd(dppf)Cl2) and a suitable base (e.g., Na2CO3, K2CO3, Cs2CO3) by any metal cross-coupling reaction (e.g., Suzuki coupling reaction) at a suitable temperature (e.g., 110°C); (Step 2) The bis(pinacolato)diboron is converted to the corresponding boron derivative (Int-A) at a suitable temperature (e.g., 90-110°C) in the presence of an inert solvent such as dioxane, DMF, or THF, using a base (e.g., KOAc) and a palladium catalyst (e.g., Pd(dppf)Cl2.DCM complex). This compound is then used in another metal cross-coupling reaction using the conditions mentioned above.

[0293] General Scheme 2

[0294] [ka]

[0295] In general scheme 2, the following reaction conditions are usually applied: (Step 1) Prepare the corresponding bromo or iodine derivative by synthesis using a suitable halogenating reagent (e.g., NBS or NIS); (Steps 2 and 3) in a suitable solvent (e.g., 1,4-dioxane, 1,2-dimethoxyethane) at a suitable temperature (e.g., 90-110°C) 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); (Step 4) by alkylation using a suitable base (e.g., K2CO3) or reductive amination using a suitable reducing reagent (e.g., NaBH3CN, NaBH(OAc)3), or by amide coupling using a suitable reagent (T3P, EDC, HOBt, HATU) in a suitable solvent (e.g., DCM or MeOH or DMF or a solvent mixture) at a suitable temperature (e.g., 25°C); also, R bCompound (II) derivatives are prepared by various sets of reaction conditions corresponding to G1 for introducing the compound.

[0296] [ka]

[0297] General Scheme 3

[0298] [ka]

[0299] In general scheme 3, the following reaction conditions are usually applied: (Step 1) Synthesis in a suitable solvent (e.g., acetonitrile) at a suitable temperature (e.g., 80°C) by copper-catalyzed coupling using a suitable reagent (e.g., CuI), a suitable ligand (e.g., TEMDA), and a suitable base (e.g., Cs2CO3); (Step 2) in a suitable solvent such as 1,4-dioxane, in the presence of a suitable catalyst (e.g., Pd(dppf)Cl2) and a suitable base (e.g., Na2CO3) at a suitable temperature (e.g., 110°C).

[0300] [ka]

[0301] General Scheme 4

[0302] [ka]

[0303] In general scheme 4, the following reaction conditions are usually applied: From commercially available materials, R bInt-B is prepared in a suitable solvent such as DCM, MeOH, or DMF at a suitable temperature, depending on the reaction conditions of various sets used in accordance with the coupling reagents to introduce the compound (for example, by alkylation using a suitable base such as K2CO3, or by reductive amination using a suitable reducing reagent such as NaBH3CN, NaBH(OAc)3, or by amide coupling using a suitable reagent such as T3P, EDC, HOBt, HATU). (Step 1) Int-B is synthesized in a suitable solvent (e.g., 1,4-dioxane, 1,2-dimethoxyethane) in the presence of a suitable catalyst (e.g., Pd(PPh3)4, Pd(dppf)Cl2, Pd(dppf)Cl2.DCM complex) and a suitable base (e.g., Na2CO3, K2CO3, Cs2CO3) at a suitable temperature (e.g., 90 or 110°C).

[0304] [ka]

[0305] General Scheme 5

[0306] [ka]

[0307] In general scheme 5, the following reaction conditions are typically applied: (Step 1) Using commercially available starting materials and a suitable catalyst (e.g., Pd(dppf)Cl2), 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) Prepare the aldehyde using a suitable reagent (e.g., OSO4, NaIO4), or prepare the alkyl halide using a suitable reagent (e.g., OSO4, NaIO4, NaBH4, PBr3), and also prepare it using various other sets of reaction conditions for introducing Rb. (Step 3) The synthesis is carried out in a suitable solvent (e.g., 1,4-dioxane, 1,2-dimethoxyethane) in the presence of a suitable catalyst (e.g., Pd(PPh3)4, Pd(dppf)Cl2, Pd(dppf)Cl2.DCM complex) and a suitable base (e.g., Na2CO3, K2CO3, Cs2CO3) at a suitable temperature (e.g., 90 or 110°C). [Examples]

[0308] The compounds of the present invention can be prepared using known organic synthesis techniques. Those skilled in the art can easily select suitable solvents, temperatures, and starting materials, as well as suitable synthesis routes.

[0309] Abbreviation: ACN - Acetonitrile Acetic acid (ACOH) BOC2O - Di-tert-butyl dicarbonate t BuXphos-2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl B2Pin2- 4,4,4',4,,5,5,5',5,-Octamethyl-2,2'-B-,3,2-Dioxaborolane DCM - Dichloromethane DEAD - Diethyl azodicarboxylate Dess-martin - Dess-Martin Periodine DME-1,2-dimethoxyethane DMF - N,N'-dimethylformamide Dioxane - 1,4-dioxane EA - Ethyl acetate EtOH - Ethanol Example - FA - Formic Acid h - time HPLC - High-Performance Liquid Chromatography KOAc - Potassium acetate LAH - Lithium aluminum hydride LC-MS - Liquid Chromatography-Mass Spectrometry MeOH - methanol MW - Micro Oven MS - Molecular Sieve NBS - N-bromosuccinimide NIS - N-iodosuccinimide NMR - nuclear magnetic resonance Pd2(dba)3- Tris(dibenzylideneacetone)dipalladium(0) Pd(PPh3)4-Tetrakis(triphenylphosphine)palladium(0) PdCl2(dppf) - [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) PdCl2(dppf).dcm - [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex Prep-HPLC - Preparative High-Pressure Liquid Chromatography Py - Pyridine RT - room temperature Sat. - saturation SFC - Supercritical Fluid Chromatography SM - Departure materials TEA - Triethylamine TFA - Trifluoroacetic acid THF - Tetrahydrofuran TLC - Thin-Layer Chromatography TMEDA - Tetramethylethylenediamine TPP - Triphenylphosphine T3P - Propanephosphonic Acid Anhydride

[0310] General considerations and analytical methods: Unless otherwise specified, the compounds used in the reaction process were commercially available. All compounds were characterized by NMR, HPLC, and LC-MS (ESI+APCI). NMR data were acquired using a Varian 400 MHz spectrometer, and all chemical shifts were reported in parts per million (ppm), measured relative to TMS. LC-MS (ESI+APCI) measurements were performed on a Shimadzu LCMS 2020 with an N-Series mass spectrometer. The yields of the compounds shown refer to the isolated compounds.

[0311] All compounds were purified or their enantiomers were separated using one of the methods described below.

[0312] Reverse-phase HPLC purification method: 1. The crude compound was purified by reverse-phase HPLC using an Inertsil ODS 3V column (250 × 20 mm), 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN. 2. The crude compound was purified by reverse-phase HPLC using an Inertsil ODS column (250 × 20 mm, 5.0 μm); mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN:MeOH (1:1). 3. The crude compound was purified by reverse-phase HPLC using an X-Bridge C18 column (250 × 19 mm), 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN. 4. The crude compound was purified by reverse-phase HPLC using an X-Bridge C18 column (250 × 20 mm), 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN:MeOH (1:1). 5. The crude compound was purified by reverse-phase HPLC using a Triart C18 column (250 × 21 mm), 5.0 μm; mobile phase (A:B), A = 10 mmol ABC in H2O, B = 100% ACN:MeOH (1:1). 6. The crude compound was purified by reverse-phase HPLC using an X-Bridge C18 column (250 × 20 mm), 5.0 μm; mobile phase (A:B), A = 10 mmol ABC in H2O, B = 100% ACN:MeOH (1:1). 7. The crude compound was purified by reverse-phase HPLC using an X-Bridge C18 column (250 × 20 mm), 5.0 μm; mobile phase (A:B), A = 10 mmol ABC in H2O, B = 100% ACN.

[0313] SFC purification method: 1. Racemic compounds were dissolved in SFC {tetrahydrofuran:methanol (1:1)}, and subjected to chiral separation using a chiral Pak IG column (250×21) mm, 5.0 μm; mobile phase 55:45 (A:B); A = liquid CO2, B = acetonitrile:methanol (1:1), flow rate: 45 mL / min; at a wavelength of 233 nm. 2. Racemic compounds were subjected to chiral separation using SFC, {tetrahydrofuran:methanol (1:1)}, chiral Pak IC column (250×21) mm, 5.0 μm; mobile phase 60:40 (A:B); A = liquid CO2, B = 0.2% triethylamine methanol solution, flow rate 40 mL / min; wavelength 254 nm.

[0314] Chiral HPLC purification method: 1. Racemic compounds were subjected to chiral separation by normal-phase HPLC using a chiral Pak IG column (250*21) mm, 5.0 μm; mobile phase 60:40 (A:B). A = 0.1% TFA n-hexane solution, B = ethanol (1:1).

[0315] (Example 1) 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid

[0316] [ka]

[0317] The compound of Example 1 was synthesized via intermediate 4 and the route shown in the scheme below.

[0318] [ka]

[0319] Intermediate (4): Preparation of 4,4,5,5-tetramethyl-2-(2-methyl-[1,1'-biphenyl]-3-yl)-1,3,2-dioxaborolane

[0320] Step 1: Synthesis of 3-bromo-2-methyl-1,1'-biphenyl A mixture of 1-bromo-3-iodo-2-methylbenzene (4.0 g, 13.4 mmol) and phenylboronic acid (1.72 g, 14.1 mmol) in 1,4-dioxane (20 mL) was mixed with a solution of Cs2CO3 (10.97 g, 33.6 mmol) in water (4.0 mL) and Pd(PPh3)4 (467 mg, 0.4 mmol). The mixture was degassed with N2 for 30 minutes, and the reaction mixture was heated at 100 °C for 5 hours. 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 obtain the crude product. This was purified by Biotage flash column chromatography using 0-10% ethyl acetate hexane as the eluent to obtain the marked compound (1.5 g, 45%) as a colorless liquid. LC-MS: Calculated value of C32H29N3O2 (M+H)+: m / z = 487.6; measured value: 488.2.

[0321] Step 2: Synthesis of 4,4,5,5-tetramethyl-2-(2-methyl-[1,1'-biphenyl]-3-yl)-1,3,2-dioxaborolane A mixture of 3-bromo-2-methyl-1,1'-biphenyl (1.5 g, 6.0 mmol) and B2Pin2 (pinacolato)diborone (1.84 g, 7.2 mmol) in 1,4-dioxane (15 mL) was mixed with KOAc (1.48 g, 15.1 mmol) and Pd(dppf)Cl2.DCM (247 mg, 0.3 mmol). The mixture was degassed with N2 for approximately 30 minutes, and the reaction mixture was heated at 100 °C for 3 hours. The reaction mixture was cooled to room temperature, water was added to the reaction mixture, and it was extracted with EA (3 × 25 mL). The combined organic layer was washed with brine (20 mL), dried over Na2SO4, and concentrated under vacuum to obtain the crude product. The crude material was purified by Biotage flash column chromatography using a 0-10% ethyl acetate hexane solution to obtain the marked compound (1.0 g, 56%) as a yellowish-white solid, which was used directly in the next step.

[0322] Example 1: Preparation of 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid

[0323] [ka]

[0324] Step 1: Synthesis of 7-chloro-3-iodoimidazo[1,2-a]pyridine To a stirred solution of 7-chloroimidazo[1,2-a]pyridine (5.0 g, 32.7 mmol) in DMF (50 mL), NIS (7.74 g, 34.4 mmol) was added in several batches, and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was slowly poured into ice-cold water while vigorously stirring. The precipitated solid material was filtered off, washed with water, and dried under vacuum to obtain the marked compound (8.8 g, 96%) as a pale yellow solid. The crude compound was carried over to the next step without purification.

[0325] Step 2: Synthesis of 4-(7-chloroimidazo[1,2-a]pyridine-3-yl)benzaldehyde A mixture of 7-chloro-3-iodoimidazo[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) was degassed with N2 for 30 minutes, and the reaction mixture was stirred at 80°C for 16 hours. 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 × 25 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, and concentrated under vacuum to obtain the crude product. The crude compound was purified by combiflash column chromatography using a 10-50% ethyl acetate hexane solution as the mobile phase to obtain the marked compound (2.0 g, 84%) as a yellowish-white solid.

[0326] Step 3: Synthesis of 4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzaldehyde A mixture of 4-(7-chloroimidazo[1,2-a]pyridine-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-dioxaborolane (900 mg, 3.08 mmol) was stirred in 1,4-dioxane (10 mL). Na2CO3 (545 mg, 5.14 mmol) in aqueous solution (2.5 mL) and Pd(dppf)Cl2 (62 mg, 0.085 mmol) were added, and the mixture was degassed with N2 for about 30 minutes. The reaction mixture was then heated at 110 °C for 16 hours. Next, it was cooled to room temperature, and EA (20 mL) and water (20 mL) were added to the mixture to separate it. The aqueous layer was extracted with EA (3 × 20 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated. The resulting crude product was purified by combiflash column chromatography using a (5-30%) ethyl acetate hexane solution to obtain the labeled compound (470 mg, 70%) as a yellowish-white solid.

[0327] Step 4: Synthesis of 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid 4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzaldehyde (200 mg, 0.51 mmol), piperidine-2-carboxylic acid (51.2 mg, 0.44 mmol), and one drop of AcOH were mixed in ethanol and DMF (1:1) (4.0 mL) and 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. Organic volatiles were removed under reduced pressure, the residue was dissolved in water and extracted with DCM (3 × 20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and the solvent was evaporated under reduced pressure. The obtained crude material was purified by reverse-phase HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound 1 (20 mg, 8%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.61 (d, J =7.2 Hz 1H), 7.82 (s, 1H), 7.66 (t, J = 8Hz, 3H), 7.53 (d, J = 8 Hz, 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 = 13.6 Hz, 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 C33H31N3O2 (M+H)+ calculated value: m / z = 501.63; measured value: 502.25.

[0328] Racemic compound 1 was subjected to chiral separation using normal-phase HPLC with a chiral Pak IG column (250*21) mm, 5.0 μm; mobile phase 60:40 (A:B); A = 0.1% TFA n-hexane solution, B = ethanol (1:1), yielding peaks 1 and 2. Peak 1: 1 H NMR (400 MHz, DMSO-d6) δ: 8.65 (d, J = 7.2 Hz, 1H), 7.92 (s, 1H), 7.76 (d, J = 7.2 Hz, 2H), 7.69 (s, 1H), 7.59 (d, J = 7.2 Hz, 2H), 7.49-7.34 (m, 7H), 7.29 (d, J = 7.2 Hz, 1H), 7.12 (d, J = 6.8 Hz, 1H), 4.22 (m,1H), 3.91 (m, 1H), 2.67 (s, 1H), 2.3 (d, J = 7.6 Hz, 1H), 2.17 (s, 3H), 2.0-1.98 (m, 2H), 1.77 (m, 1H), 1.62-1.47 (m, 4H). Calculated value of LC-MS C33H31N3O2 (M+H)+: m / z = 501.63; Measured value: 502.2 Peak 2:1 H NMR (400 MHz, DMSO-d6) δ: 8.65(d, J = 7.2 Hz, 1H), 7.92 (s, 1H), 7.76 (d, J = 7.2 Hz, 2H), 7.69 (s, 1H), 7.50-7.53 (m, 2H), 7.81(t, J = 7.6 Hz, 2H), 7.42-7.34 (m, 5H), 7.28(d, J = 7.2 Hz, 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). Calculated value of LC-MS C33H31N3O2 (M+H)+: m / z = 501.63; Measured value: 502.2

[0329] Examples 2-14 shown in Table 1 were prepared using a suitable amine, following the same procedure as described for Example 1. Example 15 in Table 1 was prepared using a suitable amine, following the same procedure as described for Example 52.

[0330] [Table 1A]

[0331] [Table 1B]

[0332] [Table 1C]

[0333] [Table 1D]

[0334] (Example 20) 1-(2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid

[0335] [ka]

[0336] The compound of Example 20 was synthesized via the route shown in the scheme below.

[0337] [ka]

[0338] This was prepared in the same manner as described in Example 1 (Steps 1 and 2).

[0339] Step 3: Synthesis of (2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)proline 2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzaldehyde (150 mg, 0.44 mmol) was stirred in ethanol and DMF (1:1) (3.0 mL). Proline 7 (51.2 mg, 0.44 mmol) and acetic acid (1 drop) were added, and the reaction mixture was stirred at room temperature for 3 hours. NaCNBH3 (83.8 mg, 1.33 mmol) was added to this reaction mixture, and stirring was continued at room temperature for 16 hours. Completion of the reaction was confirmed by TLC. Organic volatiles were evaporated under vacuum to obtain a crude residue. The residue 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 material was purified by preparative HPLC to obtain the labeled compound (30 mg, 15%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.7 (d, J = 6.8 Hz, 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 value for C34H33N3O4 (M+H)+: m / z = 547.66; Actual value: 548.5

[0340] Chiral separation: The racemic compound was subjected to chiral separation using normal-phase HPLC with a chiral Pak IG column (250*21) mm, 5.0 μm; mobile phase 60:40 (A:B); A = 0.1% TFA n-hexane solution, B = ethanol (1:1), to obtain peaks 1 and 2. Peak 1: 1 H NMR (400 MHz, DMSO-d6) 8.7 (d, J = 6.8 Hz, 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). Calculated value of LC-MS C33H31N3O2 (M+H)+: m / z = 547.66.63; Measured value: 548.5 Peak 2: 1H NMR (400 MHz, DMSO-d6) δ: 8.7 (d, J = 7.6 Hz, 1H), 7.92 (s, 1H), 7.65 (s, 1H), 7.35-7.47 (m, 7H), 7.27 (d, J = 7.2 Hz, 1H), 7.06 (d, J = 7.26 Hz, 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). Calculated value for LC-MS C34H33N3O4 (M+H)+: m / z = 547.66; Measured value: 548.4

[0341] The following examples shown in Table 2 were prepared using appropriate amines, following the same procedure as described for Example 20.

[0342] [Table 2]

[0343] (Example 23) (R)-(1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)pyrrolidine-2-yl)methanol

[0344] [ka]

[0345] The compound of Example 23 was synthesized by the route shown in the scheme below.

[0346] [ka]

[0347] (4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)-D-proline (1 g, 23 mmol) was dissolved in THF (20 mL) and LAH (180 mg, 47.3 mmol) was added under a nitrogen atmosphere at 0°C. After stirring at room temperature for 2 hours, the reaction mixture was stopped with 1N NaOH, filtered, washed with ethyl acetate, dried over Na2SO4, and concentrated to obtain the marked compound (450 mg, 50%) as a yellow solid. 1 H NMR (400 MHz, DMSO-d6) δ: 8.59 (d, J = 7.2 Hz, 1H), 7.8 (s, 1H), 7.64 (d, J = 8.0 Hz, 3H), 7.51-7.45 (m, 4H), 7.42-7.34 (m, 5H), 7.27 (dd, J = 6.8 Hz, 1H), 7.04 (dd, J = 7.2 Hz, 1H), 4.46 (s, 1H), 4.13 (d, J = 13.2 Hz, 1H), 3.49 (d, J = 7.6 Hz, 1H), 3.41 (d, 2H), 2.83 (t, J = 2.4 Hz, 1H), 2.67-2.57 (m, 2H), 2.2 (s, 3H), 1.87 (q, J = 8.4 Hz, 1H), 1.64-1.56 (m, 3H). Calculated value of LC-MS C32H31N3O (M+H)+: m / z = 473.62; Measured value: 474.4

[0348] The following examples shown in Table 3 were prepared using appropriate amines, following the same procedure as described for Example 23.

[0349] [Table 3]

[0350] (Example 25) 1-(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzyl)azetidine-3-carboxylic acid The compound of Example 25 was synthesized by the route shown in the scheme below.

[0351] [ka]

[0352] Step 1: Synthesis of 6-(3-bromo-2-methylphenyl)-2,3-dihydrobenzo[b][1,4]dioxin The labeled compound was prepared in the same manner as in Example 1 to obtain the labeled compound (5.2 g, 56%) as a viscous liquid.

[0353] 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-dioxaborolane The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (5.2 g, 60%) was obtained as a white solid.

[0354] Step 3: Synthesis of 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (1.87 g, 90%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ of C29H22N2O3: m / z = 446.51; measured value: 447.25.

[0355] Step 4: Synthesis of 1-(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzyl)azetidine-3-carboxylic acid The labeled compound was prepared in the same manner as in Example 1, and the crude material was purified by preparative HPLC to obtain the labeled compound (45 mg, 29%) as a white solid. 1 1H NMR (400 MHz, DMSO-d6) δ: 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 LC-MS Calculated value for C33H28N3O4 (M+H)+: m / z = 531.61; Measured value: 532.2

[0356] The following examples shown in Table 4 were prepared using appropriate amines, following the same procedure as described for Example 25.

[0357] [Table 4A]

[0358] [Table 4B]

[0359] [Table 4C]

[0360] [Table 4D]

[0361] (Example 39) ((4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)-2,6-dimethoxybenzyl)-D-proline

[0362] [ka]

[0363] The compound of Example 39 was synthesized by the route shown in the scheme below.

[0364] [ka]

[0365] Step 1: Synthesis of 4-(7-chloroimidazo[1,2-a]pyridine-3-yl)-2,6-dimethoxybenzaldehyde This was prepared in the same manner as described in Example 1 to obtain the marked compound (1.15 g, 37%) as a white solid. LC-MS: Calculated value (M+H)+ of C16H13ClN2O3: m / z = 316.74; Measured value: 317.25

[0366] Step 2: Synthesis of 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)-2,6-dimethoxybenzaldehyde This was prepared in the same manner as described in Example 1, and the marked compound (1 g, 100%) was obtained as a white solid. LC-MS: Calculated value of C31H26N2O5 (M+H)+: m / z = 506.56; measured value: 507.25.

[0367] Step 3: Synthesis of tert-butyl(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)-2,6-dimethoxybenzyl)proline This was prepared in the same manner as described in Example 1, and the labeled compound (250 mg) was obtained as a brown sticky mass as the crude product, which was used in the next step without purification. LC-MS: Calculated value (M+H)+ of C40H43N3O6: m / z = 661.8; Measured value: 662.5

[0368] Step 4: Synthesis of (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)-2,6-dimethoxybenzyl)proline A 4M HCl dioxane solution (5 mL) was added at 0°C to a stirred solution of tert-butyl(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)-2,6-dimethoxybenzyl) prolineate (250 mg, 377 mmol) in DCM (5 mL) and dioxane (2 mL). The reaction mixture was then stirred at room temperature for 16 hours. The organic volatiles were evaporated to obtain the crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the marked compound (55 mg, 24%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.73 (d, J = 6.8 Hz, 1H), 7.93 (s, 1H), 7.64 (s, 1H), 7.32 (dd, J = 7.6 Hz, 2H), 7.24 (d, J = 15.6 Hz, 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 = 5.2 Hz, 2H), 2.87 (d, J = 6.8 Hz, 2H), 2.18 (s, 3H), 1.99-1.87 (m, 2H), 1.67 (s, 1H). Calculated value of LC-MS C36H35N3O8 (M+H)+: m / z = 605.69; Measured value: 606.4.

[0369] The following examples shown in Table 5 were prepared using appropriate amines, following the same procedure as described for Example 39.

[0370] [Table 5]

[0371] (Example 41) (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzoyl)glycine

[0372] [ka]

[0373] The compound of Example 41 was synthesized by the route shown in the scheme below.

[0374] [ka]

[0375] Step 1: Synthesis of methyl 4-(7-chloroimidazo[1,2-a]pyridine-3-yl)benzoate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (1.1 g, 35%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C15H11ClN2O2: m / z = 286.72; Measured value: 287.2.

[0376] Step 2: Synthesis of methyl 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzoate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (800 mg, 45%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ of C30H24N2O4: m / z = 476.53; measured value: 477.

[0377] Step 3: Synthesis of 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzoic acid A mixture of methyl 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzoate (800 mg, 1.67 mmol) was stirred in THF:MeOH (14 mL:4 mL). A solution of LiOH.H2O (121 mg, 5.042 mmol) in water (2 mL) was added, and the reaction mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure, the residue was dissolved in water, washed with diethyl ether (2 × 10 mL), the aqueous layer was acidified with 1 N HCl, and extracted with DCM (3 × 10 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under reduced pressure to obtain the crude product. This was washed with pentane, filtered, and dried under vacuum to obtain the marked compound (600 mg, 77%) as a white solid. LC-MS: Calculated value (M+H)+ for C29H22N2O4: m / z = 462.51; Measured value: 463.

[0378] Step 4: Synthesis of ethyl (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzoyl)glycinate 4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzoic acid (200 mg, 0.43 mmol), ethyl glycinate (71 mg, 0.51 mmol), and TEA (241 mL, 1.73 mmol) were stirred in 10 mL of DCM. T3P (193 mL, 0.64 mmol) was added at 0°C, and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with water and DCM, and the organic layers were separated. The aqueous layer was extracted with 3 × 10 mL of DCM, and the combined organic layers were dried over Na₂SO₄, filtered, and evaporated to obtain the marked compound (190 mg, 80.23%) as a brown sticky mass, which was carried over to the next step without further purification. LC-MS: Calculated value (M)+ for C33H29N3O5: m / z = 547.61; Measured value: 547.2

[0379] Step 5: Synthesis of (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzoyl)glycine To a stirred solution of ethyl (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzoyl) glycinate (190 mg, 0.34 mmol) in THF:MeOH (7.0 mL:2 mL), a solution of LiOH.H2O (43 mg, 1.042 mmol) in water (1 mL) was added, and the reaction mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure, the residue was dissolved in water, washed with diethyl ether (2 × 10 mL), the aqueous layer was acidified with 1 N HCl, and extracted with DCM (3 × 10 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under vacuum to obtain the crude product, which was washed with pentane, filtered, and dried under reduced pressure to obtain the marked compound (8 mg, 15%) as a white solid. 1 H NMR (400 MHz, DMSO-d6) δ: 8.70 (d, J = 7.2 Hz, 1H), 8.05 (d, J = 8 Hz, 2H), 7.95 (s, 1H), 7.85 (d, J = 8 Hz, 2H), 7.65 (s, 1H), 7.33 (d, J = 7.6 Hz, 2H), 7.24 (d, J = 7.2 Hz, 1H), 7.08 (d, J = 6.8 Hz, 1H), 6.94-6.84 (m, 3H), 4.28 (s, 4H), 3.91 (d, J = 4.4 Hz, 2H), 2.18 (s, 3H).LC-MS C31H25N3O5 Calculated value of (M+H)+: m / z = 519.56; Measured value: 518.2.

[0380] The following examples shown in Table 6 were prepared using appropriate amines, following the same procedure as described for Example 41.

[0381] [Table 6]

[0382] (Example 44) N-(2-hydroxyethyl)-1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carboxamide

[0383] [ka]

[0384] The compound of Example 44 was synthesized by the route shown in the scheme below.

[0385] [ka]

[0386] Step 1: Synthesis of ethyl 1-(7-chloroimidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carboxylate 7-Chloro-3-iodoimidazo[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) were stirred in acetonitrile (5 mL). TMEDA (0.08 mL, 0.53 mmol) was added to the mixture, and the reaction mixture was refluxed for 16 hours. The reaction mixture was filtered through a Celite bed, and the filtrate was evaporated. The crude material was purified by combiflash column chromatography using a 0-25% ethyl acetate hexane solution to obtain the marked compound (220 mg, 42%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C13H11ClN4O2: m / z = 290.71; measured value: 291.2.

[0387] Step 2: Synthesis of ethyl 1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carboxylate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (150 mg, 46%) was obtained as a yellowish-white solid. LC-MS: Calculated value of C26H22N4O2 (M+H)+: m / z = 422.49; Measured value: 423.4.

[0388] Step 3: Synthesis of 1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carboxylic acid To a stirred solution of ethyl 1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carboxylate (250 mg, 0.5924 mmol) in THF:MeOH (7.0 mL:2 mL), a solution of LiOH.H2O (75 mg, 1.77 mmol) in water (1 mL) was added, and the reaction mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure, the residue was dissolved in water, washed with diethyl ether (2 × 10 mL), the aqueous layer was acidified with 1 N HCl, and extracted with DCM (3 × 10 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under reduced pressure to obtain the crude product, which was washed with pentane, filtered, and dried under vacuum to obtain the marked compound (220 mg, 94%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ for C24H18N4O2: m / z = 394.43; measured value: 395.2.

[0389] Step 4: Synthesis of N-(2-hydroxyethyl)-1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carboxamide: The labeled compound was prepared in the same manner as in Example 41, and the crude material was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (29.6 mg, 27%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.42 (d, J = 7.2 Hz, 1H), 8.34 (d, J = 5.6 Hz, 2H), 7.98 (s, 1H), 7.69 (s, 1H), 7.33-7.49 (m, 7H), 7.28 (d, J = 7.2 Hz, 1H), 7.13 (d, J = 6.8 Hz, 1H), 6.98 (s, 1H), 4.74 (t, J = 5.2 Hz, 1H), 3.5 (d, J = 6.0 Hz, 2H), 3.32 (s, 2H), 2.14 (s, 3H). Calculated value for LC-MS C26H23N5O2 (M+H)+: m / z = 437.52; Measured value: 438.4.

[0390] The following examples shown in Table 7 were prepared using appropriate amines, following the same procedure as described for Example 44.

[0391] [Table 7]

[0392] (Example 48) (1-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycine

[0393] [ka]

[0394] The compound of Example 48 was synthesized by the route shown in the scheme below.

[0395] [ka]

[0396] Step 1: Ethyl 1-(7-chloro-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carboxylate The labeled compound was prepared in the same manner as in Example 41, and the labeled compound (880 mg, 45%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C13H11ClN4O2: m / z = 290.71; Measured value: 291.25

[0397] 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]pyridine-3-yl)-1H-pyrazole-3-carboxylic acid The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (90 mg, 12%) was obtained as a white solid. LC-MS: Calculated value (M+H)+ of C26H20N4O4: m / z = 452.47; Measured value: 453.

[0398] Step 3: Synthesis of ethyl(1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycinate The labeled compound was prepared in the same manner as in Example 41, and the labeled compound (120 mg, crude product) was obtained as a brown sticky solid. LC-MS: Calculated value (M+H)+ of C30H27N5O5: m / z = 537.58; measured value: 538.

[0399] 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]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycine The labeled compound was prepared in the same manner as in Example 41, and the labeled compound (70 mg, 61%) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 12.6 (s, 1H), 8.73 (t, J = 1.2 Hz, 1H), 8.52 (d, J = 6.8 Hz, 1H), 8.39 (d, J = 2.4 Hz, 1H), 8.08 (s, 1H), 7.72 (s, 1H), 7.34 (m, 2H), 7.26 (d, J = 7.2 Hz, 1H), 7.18 (d, J = 6.8 Hz, 1H), 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). Calculated value of LC-MS C28H23N5O5 (M+H)+: m / z = 509.52; Measured value: 510.3

[0400] (Example 49) (1-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycine

[0401] [ka]

[0402] The compound of Example 49 was synthesized by the route shown in the scheme below.

[0403] [ka]

[0404] Step 1: Ethyl 1-(7-chloro-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carboxylate The labeled compound was prepared in the same manner as in Example 41, and the labeled compound (880 mg, 45%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C12H10ClN5O2: m / z = 291.7; Measured value: 292

[0405] 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]pyridine-3-yl)-1H-pyrazole-3-carboxylic acid The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (90 mg, 12%) was obtained as a white solid. LC-MS: Calculated value (M+H)+ of C25H19N5O4: m / z = 453.46; Measured value: 454.30 (M+1).

[0406] Step 3: Synthesis of ethyl(1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycinate The labeled compound was prepared in the same manner as in Example 41, and the labeled compound (120 mg, crude product) was obtained as a brown sticky solid. LC-MS: Calculated value of C29H26N6O5 (M+H)+: m / z = 538.56; Measured value: 539.35 (M+1)

[0407] 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]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycine The labeled compound was prepared in the same manner as in Example 41, and the labeled compound (70 mg, 61%) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ:12.75 (br s, 1H), 9.12 (d, J = 7.2 Hz, 1H), 8.94 (s, 1H), 8.69 (d, J = 2 Hz, 1H), 7.86 (s, 1H), 7.40-7.31 (m, 2H), 7.28 (d, J = 6.4 Hz, 1H), 7.20 (d, J = 7.2 Hz, 1H), 7.07 (d, J = 2 Hz, 1H), 6.94 (d, J = 8 Hz, 1H), 6.90 (s, 1H), 6.85 (d, J = 8.4 Hz, 1H), 4.29 (s, 4H), 3.94 (d, J = 5.2 Hz, 2H), 2.18 (s, 3H). Calculated value of LC-MS C27H22N6O5 (M+H)+: m / z = 510.51; Measured value: 511.35.

[0408] (Example 50) (3-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)propa-2-in-1-yl)-D-proline

[0409] [ka]

[0410] The compound of Example 50 was synthesized by the route shown in the scheme below.

[0411] [ka]

[0412] Step 1: Synthesis of 3-(7-chloroimidazo[1,2-a]pyridine-3-yl)propa-2-in-1-ol A mixture of 7-chloro-3-iodoimidazo[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 minutes and stirred at room temperature for 2 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (3 × 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 10-50% ethyl acetate hexane solution as the mobile phase to obtain the marked compound (720 mg, 97%) as a colorless liquid. LC-MS: Calculated value (M+H)+ of C10H7ClN2O: m / z = 206.63; Measured value: 207.20

[0413] Step 2: Synthesis of 7-chloro-3-(3-iodopropa-1-in-1-yl)imidazo[1,2-a]pyridine A mixture of 3-(7-chloroimidazo[1,2-a]pyridine-3-yl)propa-2-in-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) in DCM (10 mL) was stirred at room temperature for 1 hour. The reaction mixture was diluted with water, extracted with DCM (3 × 10 mL), and the combined organic layer was dried over Na2SO4, filtered, and evaporated. The crude compound was purified by combiflash column chromatography using 0-40% ethyl acetate hexane as the mobile phase to obtain the marked compound (500 mg, 52%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C10H6ClIN2: m / z = 316.53; Measured value: 317.10

[0414] Step 3: Synthesis of tert-butyl(3-(7-chloroimidazo[1,2-a]pyridine-3-yl)propa-2-in-1-yl)-D-proline A mixture of 7-chloro-3-(3-iodopropa-1-in-1-yl)imidazo[1,2-a]pyridine (250 mg, 0.79 mmol), tert-butyl D-prophosphate (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 × 10 mL), washed with water and brine, dried over Na2SO4, filtered, and evaporated to obtain the labeled compound (310 mg). The crude material was carried over to the next step without further purification.

[0415] Step 4: Synthesis of tert-butyl(3-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)propa-2-in-1-yl)-D-prolinate The labeled compound was prepared in the same manner as in Example 1 in a microwave reactor at 110°C for 1 hour to obtain labeled compound 30 (300 mg, 71%) as a white solid. LC-MS: Calculated value of C32H33N3O2 (M+H)+: m / z = 491.64; Measured value: 492.40.

[0416] Step 5: Synthesis of (3-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)propa-2-in-1-yl)-D-proline: The labeled compound was prepared in the same manner as in Example 39, and the labeled compound (20 mg, 8%) was obtained as a white solid. LC-MS: Calculated value of C28H25N3O2 (M+H)+: m / z = 435.53; Measured value: 436.35.

[0417] The following examples shown in Table 8 were prepared using appropriate amines, following the same procedure as described for Example 50.

[0418] [Table 8]

[0419] (Example 52) 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid

[0420] [ka]

[0421] The compound of Example 52 was synthesized by the route shown in the scheme below.

[0422] [ka]

[0423] Step 1: Synthesis of 4-chloro-2-hydrazinylpyridine 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 stopped by adding 4 M NaOH (63 mL) and water (125 mL), and the mixture was stirred for 15 minutes. The precipitated solid material was filtered off, washed with water, and dried in vacuum to obtain the marked compound (27 g, 98%) as a white solid. LC-MS: Calculated value (M+H)+ for C5H6ClN3: m / z = 143.57; Measured value: 144.57.

[0424] Step 2: Synthesis of 7-chloro-[1,2,4]triazolo[4,3-a]pyridine A mixture of 4-chloro-2-hydrazinylpyridine (27 g, 188 mmol) and formic acid (27 mL, 10 volumes) was refluxed for 16 hours. Organic volatiles were removed under reduced pressure, the residue was dissolved in water, extracted with 5% MeOH DCM solution (3 × 200 ml), and the combined organic layer was dried over Na₂SO₄, filtered, and evaporated to obtain the marked compound (26 g, 90%) as a white solid. LC-MS: Calculated value (M+H)+ of C₆H₄ClN₃: m / z = 153.57; measured value: 154.20.

[0425] Step 3: Synthesis of 3-bromo-7-chloro-[1,2,4]triazolo[4,3-a]pyridine 7-Chloro-[1,2,4]triazolo[4,3-a]pyridine (5 g, 32.5 mmol) was stirred in chloroform (250 mL) and NBS (10.4 g, 58.6 mmol) was added in several batches at 0°C. The reaction mixture was stirred at room temperature for 16 hours. Saturated NaHCO3 solution was added to the reaction mixture and extracted with DCM (2 × 50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered, and evaporated. The crude material was purified by combiflash column chromatography using 0-80% ethyl acetate hexane solution to obtain the marked compound (6.3 g, 83%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C6H3BrClN3: m / z = 232.47; measured value: 234.15.

[0426] Step 4: Synthesis of 4-(7-chloro-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (228 mg, 41%) was obtained as a yellowish-white solid. LC-MS: Calculated value of C13H8ClN3O (M+H)+: m / z = 257.68; Measured value: 257.95.

[0427] Step 5: Synthesis of 4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (95 mg, 27%) was obtained as a yellowish-white solid. LC-MS: Calculated value of C26H19N3O (M+H)+: m / z = 389.46; Measured value: 390.25.

[0428] Step 6: Synthesis of 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid The labeled compound was prepared in the same manner as in Example 1 to obtain a crude product, which was purified by preparative HPLC to obtain the labeled compound (7.6 mg, 7%) as a yellowish-white solid. 1 H NMR (400 MHz, DMSO-d6) δ:8.62 (d, J = 6.8 Hz, 1H), 7.91 (d, J = 8.0 Hz, 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 = 6.4 Hz, 1H), 3.95 (d, J = 13.2 Hz, 1H), 3.58 (d, J = 14 Hz, 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). Calculated value of LC-MS C32H30N4O2 (M+H)+: m / z = 502.62; Measured value: 503.45.

[0429] The following examples shown in Table 9 were prepared using appropriate amines, following the same procedure as described for Example 52.

[0430] [Table 9A]

[0431] [Table 9B]

[0432] [Table 9C]

[0433] (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]pyridine-3-yl)benzyl)-D-proline

[0434] [ka]

[0435] The compound of Example 62 was synthesized by the route shown in the scheme below.

[0436] [ka]

[0437] Step 1: Synthesis of 3''-bromo-2',2''-dimethyl-[1,1':3',1''-terphenyl]-4-carboaldehyde The marked compound was prepared in the same manner as in Example 1, and the marked compound (1.76 g, 57%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C21H17BrO: m / z = 365.27; Measured value: 366.

[0438] Step 2: Synthesis of 2',2''-dimethyl-3''-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde

[0439] The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (1.54 g, 79%) was obtained as a light brown solid. LC-MS: Calculated value (M+H)+ of C27H29BO3: m / z = 412.34; Measured value: 413.

[0440] Step 3: Synthesis of tert-butyl(4-(7-(4''-formyl-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (278 mg, 86%) was obtained as a light brown solid. LC-MS: Calculated value (M+H)+ of C43H42N4O3: m / z = 662.83; Measured value: 663.

[0441] Step 4: Synthesis of tert-butyl(4-(7-(4''-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline To a stirred 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]pyridine-3-yl)benzyl)-D-prolinate (270 mg, 0.40 mmol) in ethanol (10.0 mL), ethanolamine (0.04 mL, 0.61 mmol) and acetic acid (0.05 mL, 0.816 mmol) were added, and the reaction mixture was stirred at 80°C for 16 hours. The reaction mixture was cooled to room temperature, NaBH3CN (77 mg, 1.22 mmol) was added, and stirring was continued at room temperature for another 16 hours. Organic volatiles were evaporated under vacuum, water was added to the residue, and the mixture was stirred for 30 minutes. The mixture was filtered and dried under vacuum to obtain the marked compound (224 mg, 77%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ for C45H49N5O3: m / z = 707.92; Measured value: 708.40.

[0442] 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]pyridine-3-yl)benzyl)-D-proline A 147 mg, 0.207 mmol tert-butyl(4-(7-(4''-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-prolineate solution (147 mg, 0.207 mmol) was stirred in 3.0 mL of DCM, to which 0.75 mL of TFA was added at 0°C. The reaction mixture was then stirred at room temperature for 16 hours. Organic volatiles were evaporated, and water was added to the residue. The aqueous layer was extracted with 3 × 15 mL of DCM, and the combined organic layers were dried over Na₂SO₄, filtered, and the solvent was removed under reduced pressure. The crude material was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the marked compound (25 mg, 19%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.60 (d, J = 7.6 Hz, 1H), 7.92 (d, J = 6.8 Hz, 2H), 7.85 (s, 1H), 7.63 (d, J = 7.6 Hz, 2H), 7.41-7.35 (m, 4H), 7.33 (d, J = 7.2 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 7.6 Hz, 1H), 7.09 (d, J = 6.8 Hz, 1H), 4.5 (s, 1H), 4.14 (d, J = 13.2 Hz, 1H), 3.77-3.72 (m, 3H), 3.49 (t, J = 5.6 Hz, 2H),3.49-3.33 (m, 3H), 3.05-3.48 (m, 1H), 2.61 (t, J = 5.6 Hz, 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 Calculated value for C41H41N5O3 (M+H)+: m / z = 651.81; Actual value: 652.7.

[0443] The following examples shown in Table 10 were prepared using appropriate amines, following the same procedure as described for Example 62.

[0444] [Table 10]

[0445] (Example 66) 2-(((2',2''-Dichloro-3''-(3-(4-(((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]Triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-Terphenyl]-4-yl)methyl)amino)ethane-1-ol

[0446] [ka]

[0447] The compound of Example 66 was synthesized by the route shown in the scheme below.

[0448] [ka]

[0449] 2,2'-(2-chloro-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) 1,3-dibromo-2-chlorobenzene (5 g, 20.08 mmol) and 2,2'-(2-chloro-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (2.4 g, 40.8 mmol) were stirred 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 minutes. The reaction mixture was then heated in a microwave 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 material was purified by Biotage flash column chromatography using a 0-10% ethyl acetate hexane solution to obtain the marked compound (3.0 g, 48%) as a white solid. LC-MS: Calculated value (M+H)+ for C18H27B2ClO4: m / z = 364.48; Measured value: 365.

[0450] (Example 66) 2-(((2',2''-Dichloro-3''-(3-(4-(((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]Triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-Terphenyl]-4-yl)methyl)amino)ethane-1-ol

[0451] [ka]

[0452] Step 1: Synthesis of 3'-bromo-2'-chloro-[1,1'-biphenyl]-4-carboaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (1.7 g, 43%) was obtained as a yellowish-white solid.

[0453] Step 2: 2',2''-Dichloro-3''-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde 3'-Bromo-2'-chloro-[1,1'-biphenyl]-4-carboaldehyde (500 mg, 1.65 mmol) and 2,2'-(2-chloro-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (470 mg, 1.86 mmol, standard) were stirred in 1,4-dioxane (3.5 mL). KOAc (498 mg, 5.07 mmol) and Pd(dppf)Cl2 (138 mg, 0.16 mmol) were added, and the mixture was degassed for 30 minutes. The reaction mixture was then heated in a microwave 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 material was purified by Biotage flash column chromatography using a 0-10% ethyl acetate hexane solution to obtain the labeled compound (460 mg, 60%) as a white solid.

[0454] Step 3: 2',2''-Dichloro-3''-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde A mixture of 2',2''-dichloro-3''-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde (120 mg, 26.48 mmol) and 4-(7-chloro-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzaldehyde (68 mg, 26.48 mmol) in 1,4-dioxane (4 mL) was mixed with K2CO3 (109 mg, 79.4 mmol) in water (0.4 mL) and Pd(PPh3)4 (15.2 mg, 1.3 mmol). The mixture was degassed with N2 for 30 minutes, and the reaction mixture was heated in a 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 dried over Na₂SO₄, filtered, and evaporated. The crude material was purified by Biotage flash column chromatography using a (0-10%) methanol DCM solution to obtain the marked compound (64.6 g, 44%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C₃₂H₁₇Cl₂N₃O₂: m / z = 548.42; measured value: 548.30.

[0455] Step 4: Synthesis of 2-(((2',2''-dichloro-3''-(3-(4-(((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (7.1 mg, 10%) was obtained as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6): δ: 8.62 (d, J= 6.8 Hz, 1H), 7.96 (s, 1H), 7.89 (d, J = 7.6 Hz, 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 = 5.6 Hz, 2H), 3.83 (s, 2H), 3.76 (s, 2H), 3.5 ( q, J = 5.2 Hz, 4H), 2.6 (q, J = 6 Hz, 4H). LC-MS C36H33Cl2N5O2 Calculated value of (M+H)+: m / z = 638.59; Measured value: 639.

[0456] (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]pyridine-3-yl)benzyl)-D-proline

[0457] [ka]

[0458] The compound of Example 67 was synthesized by the route shown in the scheme below.

[0459] [ka]

[0460] Step 1: Synthesis of tert-butyl(4-(7-(2,2'-dichloro-4''-formyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (348 mg, 80%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C41H36Cl2N4O3: m / z = 703.66; Measured value: 703.45.

[0461] Step 2: Synthesis of tert-butyl(4-(7-(2,2'-dichloro-4''-(((2-hydroxyethyl)amino)methyl)-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (188 mg, 72%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C43H43Cl2N5O3: m / z = 748.75; Measured value: 749.45

[0462] 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]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 39, and the labeled compound (35 mg, 20%) was obtained as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6) δ:8.64 (d, J =7.2 Hz 1H), 8.19 (s, 1H), 4.5 (s, 2H), 4.15 (d, J = 13.6 Hz, 1H), 3.81(s, 2H), 3.75(d, J = 13.6 Hz, 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 C39H35Cl2N5O3 Calculated value of (M+H)+: m / z = 692.64; Actual value: 693.

[0463] (Example 68) (4-(7-(3'-(5-(((2-hydroxyethyl)amino)methyl)picolinamide)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline

[0464] [ka]

[0465] The compound of Example 68 was synthesized by the route shown in the scheme below.

[0466] [ka]

[0467] Step 1: Synthesis of methyl 6-((3-bromo-2-methylphenyl)carbamoyl)nicotinate 5-(methoxycarbonyl)picolinic acid (1 g, 5.52 mmol) and 3-bromo-2-methylaniline (1.027 g, 5.52 mmol) were stirred in DMF (10 mL), to which DIPEA (2.35 mL, 1.38 mmol) and HATU (3.14 g, 8.2 mmol) were added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was 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 Na₂SO₄, filtered, and evaporated. The crude residue was purified with CombiFlash NextGen 300+ eluting with 0-30% Ân-hexane solution to obtain the marked compound (1.76 g, 92%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ for C15H13BrN2O3: m / z = 349.18; Measured value: 350.45.

[0468] Step 2: Synthesis of N-(3-bromo-2-methylphenyl)-5-(hydroxymethyl)picolinamide To a stirred solution of methyl 6-((3-bromo-2-methylphenyl)carbamoyl)nicotinate (1.76 g, 0.005 mmol) in THF:MeOH (7 mL:1 mL), sodium borohydride (381 mg, 0.01 mmol) was added at 0°C, and the reaction mixture was stirred at room temperature for approximately 16 hours. Ammonium chloride solution was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate (3 × 25 mL). The combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and the solvent was evaporated under reduced pressure. The crude material was purified by Biotage flash column chromatography using a 0-30% ethyl acetate hexane solution to obtain the marked compound (0.979 g, 60%) as a white solid. LC-MS: Calculated value of C14H13BrN₂O₂ (M+H)+: m / z = 321.17; measured value: 322.45.

[0469] Step 3: Synthesis of N-(3-bromo-2-methylphenyl)-5-formylpicolinamide N-(3-bromo-2-methylphenyl)-5-(hydroxymethyl)picolinamide (500 mg, 1.5568 mmol) and sodium bicarbonate (326.9 mg, 3891 mmol) were stirred in DCM (12.5 mL). DMP (381 mg, 898 mmol) was added at 0°C, and the reaction mixture was stirred at room temperature for approximately 2 hours. The reaction mixture was filtered on a Celite bed, washed with DCM (20 mL), and the solvent was evaporated under reduced pressure. The crude material was purified by Biotage flash column chromatography using a 0-20% ethyl acetate hexane solution to obtain the labeled compound xx (530 mg, 60%) as a white solid. LC-MS: Calculated value (M+H)+ of C14H11BrN2O2: m / z = 319.16; measured value: 320.2.

[0470] Step 4: Synthesis of N-(3-bromo-2-methylphenyl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide The labeled compound was prepared in microwaves in the same manner as in Example 1, and the labeled compound (648 mg, 60%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C16H18BrN3O2: m / z = 364.24; Measured value: 365.

[0471] Step 5: Synthesis of tert-butyl(4-(7-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (2.2 g, 53.6%) was obtained as a brown solid. LC-MS: Calculated value (M+H)+ of C35H43BN4O4: m / z = 594.56; measured value: 595.

[0472] Step 6: Synthesis of tert-butyl(4-(7-(3'-(5-(((2-hydroxyethyl)amino)methyl)picolinamide)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in microwaves in the same manner as in Example 1, and the labeled compound (1.5 g, 45%) was obtained as a colorless liquid. LC-MS: Calculated value (M+H)+ of C45H49N7O4: m / z = 751.93; Measured value: 752.

[0473] Step 7: Synthesis of (4-(7-(3'-(5-(((2-hydroxyethyl)amino)methyl)picolinamide)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 39, and the labeled compound (2.2 g, 53.6%) was obtained as the crude product. The crude material was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (25 mg, 17%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ:10.36 (s, 1H), 8.69 (s, 1H), 8.61 (d, J = 7.2Hz, 1H), 8.15 (d, J = 8 Hz, 1H), 8.04(d, J = 8Hz, 1H), 7.93(d, J = 7.6 Hz, 2H), 7.87 (d, J = 8 Hz, 2H), 7.63 (d, J = 8 Hz, 2H), 7.4 (t, J = 6.4 Hz, 2H), 7.34(t, J = 8Hz, 1H), 7.22 (d, J = 4.4 Hz, 1H), 7.08 (dd, J = 7.2Hz, 2H), 4.14 (d, J = 12.4 Hz, 1H), 3.92 (s, 2H), 3.77(d,J = 13.2Hz,, 1H), 3.50 (s, 2H), 2.65 (d, J =12.4 Hz, 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 value of C41H41N7O4 (M+H)+: m / z = 695.82; Actual value: 694.4.

[0474] The following examples shown in Table 11 were prepared using appropriate amines, following the same procedure as described for Example 68.

[0475] [Table 11]

[0476] (Example 70) 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(3-(4-(((2-hydroxyethyl)amino)methyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide

[0477] [ka]

[0478] The compound of Example 70 was synthesized by the route shown in the scheme below.

[0479] [ka]

[0480] Step 1: Synthesis of N-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-3-yl)-5-formylpicolinamide

[0481] The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (550 mg, 36%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ of C27H29BN2O4: m / z = 456.35; Measured value: 457.35.

[0482] Step 2: Synthesis of 5-formyl-N-(3'-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (85 mg, 70%) was obtained as a colorless sticky mass. LC-MS: Calculated value (M+H)+ of C34H25N5O3: m / z = 551.61; Measured value: 552.15.

[0483] 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]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide The labeled compound was prepared in the same manner as in Example 1, and the resulting crude material was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (15 mg, 15%) as a white solid. 1H NMR (400 MHz, 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 = 8 Hz, 1H), 7.85-7.92 ( m, 4H), 7.62 (d, J = 8 Hz, 2H), 7.32-7.44 (m, 3H), 7.22(d, J = 5.2Hz, 1H), 7.08 (dd, J = 6 Hz, 2H), 4.61 (s, 2H), 3.90 (d, J = 13.2 Hz, 4H), 3.53 LC-MS Calculated value for C38H39N7O3 (M+H)+: m / z = 641.78; Actual value: 642.5.

[0484] The following examples shown in Table 12 were prepared using appropriate amines, following the same procedure as described for Example 70.

[0485] [Table 12]

[0486] (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

[0487] [ka]

[0488] The compound of Example 73 was synthesized by the route shown in the scheme below.

[0489] [ka]

[0490] Step 1: Synthesis of 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (825 mg, 76%) was obtained as a yellowish-white solid.

[0491] Step 2: Synthesis of 2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diol 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (369.1 mg, 1.71 mmol) and 3-bromo-2-methylphenol (400.0 mg, 1.71 mmol) were stirred in 1,4-dioxane (5 ml) and water (1.25 ml), to which K3PO4 (335.4 mg, 3.42 mmol) was added under an N2 atmosphere. The mixture was purged with N2 for 30 minutes, and Pd(dppf)Cl2 (62.5 mg, 0.09 mmol) was added. The reaction mixture was heated in a MW at 120°C for 2 hours. After cooling to room temperature, it was diluted with water and extracted with ethyl acetate (2 × 50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was adsorbed onto silica gel and purified by combiflash column chromatography using a (0-25%) ethyl acetate-hexane solution to obtain the labeled compound (181 mg, 49.4%) as a yellowish-white solid.

[0492] Step 3: Synthesis of 2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyrbis(trifluoromethanesulfonate) 2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diol (1.00 g, 3.16 mmol) and DIPEA (1.38 mL, 7.90 mmol) were stirred in dichloromethane (10 mL), to which trifluoromethanesulfonic anhydride (0.798 mL, 4.74 mmol) was added by syringe at 0°C. After 30 minutes, ethanol (0.5 mL) was added. The reaction mixture was stirred at 0°C for 30 minutes. The reaction mixture was concentrated under reduced pressure. The residue was purified by combiflash column chromatography using a (0-10%) ethyl acetate hexane solution to obtain the marked compound (130 mg, 22%) as a brown solid.

[0493] Step 4: Synthesis of 2,2'-(2,2'-dimethyl-[1,1'-biphenyl]-3,3'-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (130 mg, 65%) was obtained as a white solid.

[0494] Step 5: Synthesis of di-tert-butyl((((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 The indicated compound was prepared in the same manner as in Example 1, and the crude compound (506 mg) was obtained as a brown semi-solid. LC-MS: Calculated value (M+H)+ of C58H62N8O4: m / z = 935.19; measured value: 936.50.

[0495] 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 The labeled compound was prepared in the same manner as in Example 62, and the labeled compound (35 mg, 14%) was obtained as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.60 (d, J=7.2 Hz, 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 = 6.8 Hz, 2H), 7.10 (d, J = 7.2 Hz, 2H), 4.14 (d, J = 13.6 Hz, 2H), 3.76(d, J = 13.6Hz, 2H), 3.05 (s, 2H), 2.6 (s, 2H), 2.13-2.06 (m, 8H), 1.92-1.76 (m, Calculated value for LC-MS C50H46N8O4 (M+H)+ (8H): m / z = 822.97; Measured value: 821.6.

[0496] (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]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one

[0497] [ka]

[0498] The compound of Example 74 was synthesized by the route shown in the scheme below.

[0499] [ka]

[0500] Step 1: Synthesis of 3''-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2',2''-dimethyl-[1,1':3',1''-terphenyl]-4-carboaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (170 mg, 70%) was obtained as a light brown solid. LC-MS: Calculated value (M+H)+ of C34H25N3O2: m / z = 507.59; measured value: 508.20.

[0501] 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]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (20 mg, 20%) was obtained as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.59 (d, J = 7.2 Hz, 1H), 7.709 (s, 1H), 7.314-7.412 (m, 7H), 7.235 (t, J = 5.6Hz, 2H), 7.15(d, J = 7.6 Hz, 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 = 5.2 Hz, 4H), 2.007 (s, 3H), 1.945 (s, 3H), LC-MS C44H45N7O2 Calculated value of (M+H)+: m / z = 703.89. Measured value: 704.6.

[0502] The following examples shown in Table 13 were prepared using appropriate amines, following the same procedure as described for Example 74.

[0503] [Table 13]

[0504] (Example 77) 2-((4-(7-(3'-(5-(((2-hydroxyethyl)amino)methyl)-6-methoxypyridine-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)amino)ethane-1-ol

[0505] [ka]

[0506] The compound of Example 77 was synthesized by the route shown in the scheme below.

[0507] [ka]

[0508] Step 1: Synthesis of 6-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-3-yl)-2-methoxynicotinaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (125 mg, 24%) was obtained as a white solid. LC-MS: Calculated value (M+H)+ of C27H30BNO4: m / z = 443.35; Measured value: 444.15.

[0509] Step 2: Synthesis of 6-(3'-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-2-methoxynicotinaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (107 mg, 74%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C34H26N4O3: m / z = 538.61; Measured value: 539.25.

[0510] Step 3: Synthesis of 2-((4-(7-(3'-(5-(((2-hydroxyethyl)amino)methyl)-6-methoxypyridine-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)amino)ethane-1-ol The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (19 mg, 16%) was obtained as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.59 (d, J = 7.2 Hz, 1H), 8.2 (s, 2H), 7.91 (d, J = 8 Hz, 2H), 7.85(s, 1H), 7.80 (d, J = 7.2 Hz, 1H), 7.62 ( d, J = 8 Hz, 2H), 7.45-7.35 (m, 4H), 7.23 (q, J = 6.8 Hz, 2H), 7.15(d, J = 7.2Hz, 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 = 5.2Hz, 4H), 2.08 (s, 3H), Calculated value of LC-MS C38H40N6O3 (M+H)+: m / z = 628.78; Measured value: 629.6.

[0511] The following examples shown in Table 14 were prepared using appropriate amines, following the same procedure as described for Example 77.

[0512] [Table 14]

[0513] (Example 79) (S)-5-(((4-(7-(3'-((3-(((R)-3-hydroxypyrrolidine-1-yl)methyl)-1,7-naphthyridine-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)amino)methyl)pyrrolidine-2-one

[0514] [ka]

[0515] The compound of Example 79 was synthesized via the route shown in the scheme below.

[0516] [ka]

[0517] Step 1: Synthesis of 5-bromo-3-methylpicorinamide 5-bromo-3-methylpicolinic acid (10 g, 46.2 mmol) was stirred in toluene (100 mL) and DMF (0.025 mL), to which thionyl chloride (4.05 mL, 55.5 mmol) was added at room temperature. The reaction mixture was heated at 0°C for 2 hours. The reaction mixture was cooled 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 obtain the marked compound (9 g, 90%) as a yellowish-white solid.

[0518] Steps 2 and 3: Synthesis of 3-bromo-1,7-naphthyridine-8(7H)-one DMF-DMA (7.2 mL, 54.4 mmol) was added at room temperature to a stirred mixture of 5-bromo-3-methylpicolinamide (9 g, 41.8 mmol) in toluene (80 mL). The reaction mixture was heated at 110 °C for 24 hours. The reaction mixture was cooled to room temperature and added dropwise to a stirred solution of tBuOK (7.04 g, 62.7 mmol) in toluene (80 mL). The reaction mixture was heated again at 110 °C for 3 hours. Organic volatiles were removed under vacuum, and the reaction mixture was adjusted to pH 7 by adding a 1N HCl solution to obtain a solid. This solid was filtered, washed with water, and dried under reduced pressure to obtain the marked compound (4.5 g, 48%) as a brown solid. LC-MS: Calculated value of C8H5BrN2O (M+H)+: m / z = 225.05. Measured value: 224.95.

[0519] Step 4: Synthesis of 3-bromo-8-chloro-1,7-naphthyridine To a stirred mixture of 3-bromo-1,7-naphthyrizine-8(7H)-one (2.5 g, 11.1 mmol) in toluene (100 mL), phosphorus oxychloride (3.05 mL, 33.3 mmol) was added, followed by N,N-diethylaniline (5.2 mL, 33 mmol) at room temperature. The reaction mixture was heated at 110 °C for 2 hours. Organic volatiles 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 obtain the marked compound (2.3 g, 85%) as a brown solid. LC-MS: Calculated value of C8H4BrClN2 (M+H)+: m / z = 243.49. Measured value: 244.90.

[0520] Step 5: Synthesis of 8-chloro-3-vinyl-1,7-naphthyridine A mixture of 3-bromo-8-chloro-1,7-naphthyridine (1.7 g, 6.9 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (860 mg, 5.5 mmol) in 1,4-dioxane (20 mL) was mixed with Na2CO3 (1.47 g, 13.8 mmol) in water (5 mL) and Pd(dppf)Cl2 (260 mg, 0.3 mmol). The mixture was degassed with N2 for 30 minutes, and the reaction mixture was heated at 90°C for 16 hours. The reaction mixture was diluted with ethyl acetate, filtered through a Celite tub, washed with ethyl acetate, and the filtrate was evaporated. The crude material was purified by Biotage flash column chromatography using a (0-30%) ethyl acetate-hexane solution to obtain the marked compound (700 mg, 60%) as a brown, rubbery mass. LC-MS: Calculated value (M+H)+ for C10H7ClN2: m / z = 190.63. Measured value: 191.0.

[0521] Step 6: Synthesis of N-(3-bromo-2-methylphenyl)-3-vinyl-1,7-naphthyridine-8-amine 8-chloro-3-vinyl-1,7-naphthyridine (200 mg, 0.1 mmol) and 3-bromo-2-methylaniline (195 mg, 0.1 mmol) were dissolved in IPA (10 mL), to which methanesulfonic acid (105 mg, 0.1 mmol) was added at ambient temperature. The resulting reaction mixture was heated to 60 °C and stirred at 60 °C for 7 hours. After cooling to room temperature, the pH was adjusted to 8-9 with 20% sodium hydroxide (NaOH) aqueous solution. The neutralization reaction mixture was stirred at ambient temperature for 30 minutes, and the solid was collected by filtration. The wet cake was then purified at room temperature for 2 hours by reslurrying in a mixture of MTBE (20 mL) and water (10 mL). The solid was collected by filtration and dried under vacuum to obtain the marked compound (300 mg, 85%) as a yellow solid, which was used in the subsequent reaction without further purification. LC-MS: Calculated value (M+H)+ for C17H14BrN3: m / z = 340.22. Measured value: 340.20.

[0522] Step 7: Synthesis of 8-((3-bromo-2-methylphenyl)amino)-1,7-naphthyrizine-3-carbaldehyde OsO4 (300 mg, 1.18 mmol) was added at room temperature to a stirred solution of N-(3-bromo-2-methylphenyl)-3-vinyl-1,7-naphthyridine-8-amine (260 mg, 0.7 mmol) and 2,6-dimethylpyridine (184 mg, 1.4 mmol) in THF (20 mL) and water (6 mL). The mixture was stirred at room temperature for 1 hour, after which NaIO4 (330 mg, 1.5 mmol) was added. The resulting reaction mixture was then heated to 30-35°C and stirred at that 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 then concentrated under reduced pressure. The solid was filtered off, and the residue was suspended in water (20.0 mL). The suspension was heated to 50°C and stirred at 50°C for 1 hour. The solid was then filtered off, and the wet cake was further purified by reslurrying in MTBE (6.2 mL). The suspension was heated at 50°C for 1 hour and then filtered. The collected solid was dried under vacuum to obtain the labeled compound (300 mg) as the crude product, which was carried over to the next step without purification. LC-MS: Calculated value (M+H)+ of C16H12BrN3O: m / z = 342.20. Measured value: 343.95.

[0523] Step 8: Synthesis of (R)-1-((8-((3-bromo-2-methylphenyl)amino)-1,7-naphthyridine-3-yl)methyl)pyrrolidine-3-ol A mixture of 8-((3-bromo-2-methylphenyl)amino)-1,7-naphthyrizine-3-carboaldehyde (220 mg, 0.6 mmol), (A)-pyrrolidine-3-ol hydrochloride (140 mg, 1.13 mmol), and triethylamine (0.150 mL, 1.13 mol) in DCM (15 mL) was stirred at room temperature for 2 hours. Sodium triacetoxyborohydride (280 mg, 1.2 mmol) was added dropwise to the mixture at room temperature over 30 minutes. 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 stopped 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 filtered and washed with dichloromethane (10 mL), water (5 mL), and heptane (5 mL). The wet solid was dried under vacuum to obtain the labeled compound (300 mg, 115%) as a pale yellow solid, which was carried over to the next step without purification. LC-MS: Calculated value (M+H)+ of C20H21BrN4O: m / z = 413.32, measured value: 413.05.

[0524] Step 9: Synthesis of (R)-1-((8-((2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-3-yl)amino)-1,7-naphthyridine-3-yl)methyl)pyrrolidine-3-ol (209) The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (130 mg, 35%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ of C33H39BN4O3: m / z = 550.51. Measured value: 551.25.

[0525] Step 10: Synthesis of (R)-4-(7-(3'-((3-((3-hydroxypyrrolidine-1-yl)methyl)-1,7-naphthyridine-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (90 mg, 60%) was obtained as a pale yellow solid. LC-MS: Calculated value of C40H35N7O2 (M+H)+: m / z = 645.77. Measured value: 642.20.

[0526] Step 11: Synthesis of (S)-5-(((4-(7-(3'-((3-(((R)-3-hydroxypyrrolidine-1-yl)methyl)-1,7-naphthyridine-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)amino)methyl)pyrrolidine-2-one The labeled compound was prepared in the same manner as in Example 1 to obtain the labeled compound as a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (25 mg, 48%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ:9.321 (s, 1H), 8.86 (s, 1H), 8.59 (d, J = 6.8Hz, 1H), 8.44 (d, J = 7.6 Hz, 1H), 8.18 (s, 1H), 8.05 (d, J = 6 Hz, 1H), 7.9 (d, J = 7.6 Hz, 2H), 7.86 (s, 1H), 7.68 (s, 1H), 7.60 (d, J = 8.4Hz, 2H), 7.4 (t, J = 6.8 Hz, 2H), 7.339 (t, J = 8Hz, 1H), 7.24 (d, J = 6.8 Hz, 1H), 7.175 (d, J = 5.6 Hz, 1H), 7.095 (d ,J = 6.8Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 4.720 (d, J =4.4 Hz, 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 = 8 Hz, 2H), 2.63 (s, 1H), 2.38 (dd, J = 9.6 Hz, J =9.6 Hz, 2H), 2.125 (d, J = 13.2 Hz, 6H) 2.04 (s, 3H), 1.709 (d, J = 4.8 Hz, 1H), Calculated value of LC-MS C45H45N9O2 (M+H)+: m / z = 743.92; Measured value: 744.3.

[0527] The following examples shown in Table 15 were prepared using appropriate amines, following the same procedure as described for Example 79.

[0528] [Table 15]

[0529] (Example 82) tert-butyl(4-(7-(3'-(5-((2-hydroxyethyl)carbamoyl)-6-methoxypyridine-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-prolinate

[0530] [ka]

[0531] The compound of Example 82 was synthesized by the route shown in the scheme below.

[0532] [ka]

[0533] Step 1: Synthesis of 6-chloro-N-(2-hydroxyethyl)-2-methoxynicotinamide The labeled compound was prepared in the same manner as in Example 68, and the labeled compound (446 mg, 80%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C9H11ClN2O3: m / z = 230.65. Measured value: 231.

[0534] Step 2: Synthesis of tert-butyl(4-(7-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (56 mg, 76%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C42H49BN4O4: m / z = 684.69; measured value: 685.30.

[0535] Step 3: Synthesis of tert-butyl(4-(7-(3'-(5-((2-hydroxyethyl)carbamoyl)-6-methoxypyridine-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (56 mg, 76%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C45H48N63O5: m / z = 752.92; Measured value: 753.65.

[0536] Step 4: Synthesis of (4-(7-(3'-(5-((2-hydroxyethyl)carbamoyl)-6-methoxypyridine-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)-D-proline The labeled compound was prepared in the same manner as in Example 39, and the labeled compound (25 mg, 10%) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ:8.61 (d, J =7.2 Hz 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 = 7.2 Hz, 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 = 7.2 Hz, 1H), 4.8 (s, 1H), 4.14(d, J = 13.2Hz, 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, 10 H). LC-MS Calculated value for C41H40N6O5 (M+H)+: m / z = 696.81; Actual value: 697.5.

[0537] (Example 83) Ethyl (1-(7-(4''-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycinate

[0538] [ka]

[0539] The compound of Example 83 was synthesized by the route shown in the scheme below.

[0540] [ka]

[0541] Step 1: Synthesis of 7-bromo-3-iodo-[1,2,4]triazolo[4,3-a]pyridine The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (5 g, 55.5%) was obtained as a brown solid.

[0542] Step 2: Synthesis of ethyl 1-(7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carboxylate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (1.2 g, 57.6%) was obtained as a yellow solid.

[0543] Step 3: Synthesis of 1-(7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carboxylic acid The labeled compound was prepared in the same manner as in Example 41, and the labeled compound (260 mg, 43.6%) was obtained as a yellow, rubbery liquid.

[0544] Step 4: Synthesis of ethyl (1-(7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycinate The labeled compound was prepared in the same manner as in Example 68, and the labeled compound (250 mg, 75.1%) was obtained as a yellow, rubbery solid.

[0545] 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]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycine The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (250 mg, 61.5%) was obtained as a white solid.

[0546] 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]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycine The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (16 mg, 5.9%) was obtained as a white solid. 1 H NMR (400 MHz, DMSO-d6) δ: 9.03 (d, J = 7.2 Hz, 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= 2.4 Hz, 1H) 5.15-4.51 (br.s, 2H), 3.87-3.84 (m, 4H), 3.54 (t, J= 5.8 Hz, 2H), 2.71 (t, J= 5.8Hz, 2H), 2.03 (s, 3H), Calculated value for LC-MS C35H33N7O4 (M+H)+ at 1.94 (s, 3H): m / z = 615.6; Measured value: 616.3.

[0547] (Example 84) 2-((4-(7-(3'-((3-(((2-hydroxyethyl)amino)methyl)-1,7-naphthyridine-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)amino)ethane-1-ol

[0548] [ka]

[0549] The compound of Example 84 was synthesized by the route shown in the scheme below.

[0550] [ka]

[0551] Step 1: Synthesis of 4-(7-(2,2'-dimethyl-3'-((3-vinyl-1,7-naphthyridine-8-yl)amino)-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (60 mg, 50%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ of C37H28N6O: m / z = 572.67, measured value: 573.40.

[0552] Step 2: Synthesis of 8-((3'-(3-(4-formylphenyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)amino)-1,7-naphthyridine-3-carbaldehyde The labeled compound was prepared in the same manner as in Example 79, and the labeled compound (10 mg, 12%) was obtained as a pale yellow solid. LC-MS: Calculated value of C36H26N6O2 (M+H)+: m / z = 574.64, measured value: 575.35.

[0553] Step 3: Synthesis of 2-((4-(7-(3'-((3-(((2-hydroxyethyl)amino)methyl)-1,7-naphthyridine-8-yl)amino)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)amino)ethane-1-ol The labeled compound was prepared in the same manner as in Example 1 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (60 mg, 12.6%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ:9.32 (s, 1H), 8.90 (s, 1H), 8.59 (d, J = 6.8Hz, 1H), 8.46 (d, J = 8 Hz, 1H), 8.2(s, 1H), 8.05(d, J = 5.6 Hz, 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 = 6.8 Hz, 1H), 7.16(d, J = 6 Hz, 1H), 7.1 (d, J = 7.2 Hz, 1H), 6.94(d, J = 7.6 Hz, 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 Calculated for C40H40N8O2 (M+H)+: m / z = 664.81; Actual: 665.4.

[0554] (Example 85) 2-(((3''-(3-((2-hydroxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2',2''-dimethyl-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[0555] [ka]

[0556] The compound of Example 85 was synthesized by the route shown in the scheme below.

[0557] [ka]

[0558] Step 1: Synthesis of 7-bromo-3-chloro-[1,2,4]triazolo[4,3-a]pyridine 7-Bromo-[1,2,4]triazolo[4,3-a]pyridine (500 mg, 2.55 mmol) was stirred in DMF (10 mL), to which NCS (509 mg, 3.82 mmol) was added at room temperature under a N2 atmosphere. 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 × 10 mL). The combined organic layers were washed with water (2 × 10 mL) and brine solution (10 mL), dried over anhydrous Na₂SO₄, filtered, and evaporated under reduced pressure to obtain the marked compound (520 mg, 88%) as a pale yellow solid. LC-MS: Calculated value of C₄₀H₄₀N₄O₂ (M+H)₁: m / z = 232.4; Measured value: 234.1.

[0559] Step 2: Synthesis of 7-bromo-N-(2-methoxyethyl)-[1,2,4]triazolo[4,3-a]pyridine-3-amine A mixture of 7-bromo-3-chloro-[1,2,4]triazolo[4,3-a]pyridine (500 mg, 2.15 mmol) and 2-methoxyethane-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 combiflash column chromatography using (50-60%) ethyl acetate-hexane solution to obtain the marked compound (130 mg, 22%) as a yellowish-white substance. LC-MS: Calculated value of C9H11BrN4O (M+H)+: m / z = 271.12; measured value: 271.3.

[0560] Step 3: Synthesis of 3''-(3-((2-methoxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2',2''-dimethyl-[1,1':3',1''-terphenyl]-4-carboaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (100 mg, 44%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ of C30H28N4O2: m / z = 476.5; Measured value: 477.2.

[0561] Step 4: Synthesis of 2-(((3''-(3-((2-methoxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2',2''-dimethyl-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (100 mg, 60%) was obtained as a white solid. LC-MS: Calculated value of C32H35N5O2 (M+H)+: m / z = 521.6; Measured value: 522.5.

[0562] Step 5: Synthesis of 2-(((3''-(3-((2-hydroxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2',2''-dimethyl-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol 2-(((3''-(3-((2-methoxyethyl)amino)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2',2''-dimethyl-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol (100 mg, 0.191 mmol) was mixed in DCM (10 ml) with BBr3 (0.036 mL, 0.383 mmol) at 0°C, and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was stopped with NaHCO3 (10 mL), extracted with DCM (10 mL x 2), washed with brine, dried over Na2SO4, filtered, and the solvent was concentrated under reduced pressure to obtain the labeled compound (90 mg, crude product). The crude material was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the marked compound (7.0 mg, 7.5%) as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.60 (d, J= 7.2 Hz, 1H), 7.40- 7.30 (m, 8 H), 7.21 (d, J= 7.2 Hz, 2H), 7.14 (d, J= 7.2 Hz, 1H), 6.90 (dd, J=6.8 Hz, 1.9 Hz, 1H), 6.43-6.41 (m, 1H), 4.63 (t, J= 5.4 Hz, 1H), 4.44 (t, J= 5.4 Hz, 1H), 3.75 (s, 2H), 3.56 (q, 6.0 Hz, 2H), 3.48 (q, 6.0 Hz, 2H), 3.34-3.29 (m, 2H), 2.61 (t, J= 5.8 Hz, 2H), 1.98 (s, 3H), 1.93 (s, 3H). Calculated value for LC-MS C31H33N5O2 (M+H)+: m / z = 507.64; Actual value: 508.5.

[0563] (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]pyridine-3-yl)methyl)amino)methyl)pyrrolidine-2-one

[0564] [ka]

[0565] The compound of Example 86 was synthesized by the route shown in the scheme below.

[0566] [ka]

[0567] Step 1: Synthesis of ethyl 7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylate A mixture of 4-bromo-2-hydrazinylpyridine (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 obtain the marked compound (4.0 g, 45.9%) as a yellow solid. LC-MS: Calculated value of C9H8BrN3O2 (M+H)+: m / z = 270.09; measured value: 271.9.

[0568] Step 2: Synthesis of (7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methanol The labeled compound was prepared in the same manner as in Example 68, and the labeled compound (2.5 g, 74.1%) was obtained as a yellow solid.

[0569] Step 3: Synthesis of 7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carbaldehyde The labeled compound was prepared in the same manner as in Example 68, and the labeled compound (1.5 g, 61%) was obtained as a yellow solid. LC-MS: Calculated value (M)+ of C7H4BrN3O: m / z = 226.03; Measured value: 226.15.

[0570] Step 4: Synthesis of (S)-5-((((7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)amino)methyl)pyrrolidine-2-one The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (950 mg, 68%) was obtained as a white solid. LC-MS: Calculated value (M+H)+ of C12H14BrN5O: m / z = 323.04; Measured value: 324.

[0571] Step 5: Synthesis of tert-butyl(S)-((7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate (S)-5-((((7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)amino)methyl)pyrrolidine-2-one (950 mg, 2.93 mmol) was stirred in 30 ml of 5% MeOH:DCM. Triethylamine (900 mg, 8.9 mmol) was added at room temperature, and then di-tert-butyl dicarbonate (0.826 mg, 3.8 mmol) was added at room temperature under an N2 atmosphere, and the mixture was stirred for 16 hours. The reaction mixture was diluted with water (30 ml) and extracted using DCM (3 × 30 ml). The combined organic layers were washed with water (20 ml) and brine solution (10 ml), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by combiflash column chromatography using (0-5%) MeOH:DCM to obtain the marked compound (290.0 mg, 23.3%) as a pale yellow rubbery solid. LC-MS: Calculated value (M+H)+ for C17H22BrN5O3: m / z = 424.3; Measured value: 424.2.

[0572] Step 6: Synthesis of tert-butyl(S)-((7-(4''-formyl-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (90 mg, 43.4%) was obtained as a yellow, rubbery liquid. LC-MS: Calculated value (M+H)+ of C38H39BrN5O4: m / z = 629.76; Measured value: 630.2.

[0573] Step 7: Synthesis of tert-butyl(S)-((7-(4''-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The marked compound was prepared in the same manner as in Example 1, and the marked compound (90 mg, 93.3%) was obtained as a white solid. LC-MS: Calculated value (M+H)+ of C40H46N6O4: m / z = 674.85; Measured value: 675.4

[0574] 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]pyridine-3-yl)methyl)amino)methyl)pyrrolidine-2-one The labeled compound was prepared in the same manner as in Example 39 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (22 mg, 28.7%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.58 (d, J= 7.2 Hz, 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= 7.6 Hz, 1H), 7.05 (d, J= 6.4 Hz, 1H), 4.48 (t, J= 5.4 Hz, 1H), 4.29 (s, 2H), 3.76 (s, 2H), 3.60- 3.58 (m, 1H), 3.49 (q, J= 5.6 Hz, 2H), 2.61 (t, J= 5.8 Hz, 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). Calculated value of LC-MS C35H38N6O2 (M+H)+: m / z = 574.73; Actual value: 575.3.

[0575] (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]pyridine-3-yl)methyl)pyrrolidine-3-carboxylic acid

[0576] [ka]

[0577] The compound of Example 87 was synthesized by the route shown in the scheme below.

[0578] [ka]

[0579] Step 1: Synthesis of methyl(R)-1-((7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)pyrrolidine-3-carboxylate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (76 mg, 17%) was obtained as a white solid. LC-MS: Calculated value of C44H45N7O2 (M+H)+: m / z = 574.64, measured value: 575.35.

[0580] Step 2: Synthesis of methyl(R)-1-((7-(4''-formyl-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)pyrrolidine-3-carboxylate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (96.4 mg, 73%) was obtained as a pale yellow semi-solid. LC-MS: Calculated value (M+H)+ of C34H32N4O3: m / z = 544.66; Measured value: 545.30.

[0581] 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]pyridine-3-yl)methyl)pyrrolidine-3-carboxylate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (140 mg) was obtained as a crude product, which was carried over to the next step without purification.

[0582] 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]pyridine-3-yl)methyl)pyrrolidine-3-carboxylic acid The labeled compound was prepared in the same manner as in Example 41 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (35 mg, 37%) as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.528 (d, J= 7.2 Hz, 1H), 7.726 (s, 1H), 7.318-7.421 (m, 7H), 7.235 (t, J = 6.4 Hz, 2H), 7.15 (d, J = 7.6 Hz, 1H), 7.063 (d, J= 7.2 Hz, 1H), 4.5 (s, br, 1H), 4.18 (s, 2H), 3.77 (s, 2H), 3.5 (t, J = 5.2 Hz, 2H), 2.9- 2.95 (m, 1H), 2.8 (t, J= 9.2Hz, 1H), Calculated values ​​for LC-MS C35H37N5O3 (M+H)+: m / z = 575.71; measured value: 576.7. (2.502-2.722 (m, 6H), 1.944-2.0 (m, 7H); Measured value: 576.7.

[0583] The following examples shown in Table 16 were prepared using appropriate amines, following the same procedure as described for Example 87.

[0584] [Table 16]

[0585] (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(azandiyl))bis(ethane-1-ol)

[0586] [ka]

[0587] The compound of Example 89 was synthesized by the route shown in the scheme below.

[0588] [ka]

[0589] 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-carbaldehyde) The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (55 mg, 34%) was obtained as a white solid. LC-MS: Calculated value of C28H20N6O2 (M+H)+: m / z = 472.51; measured value: 473.5.

[0590] 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(azandiyl))bis(ethane-1-ol) The labeled compound was prepared in the same manner as in Example 1 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (1.4 mg, 2.5%) as a yellowish-white solid. 1 H NMR (400 MHz, DMSO-d6) δ: 8.58 (d, J= 6.8 Hz, 1H), 7.71-7.64 (m, 3H), 7.42-7.31 (m, 7H), 7.23 (t, J= 6.8 Hz, 2H), 7.15 (d, J= 7.2 Hz, 1H), 7.05 (d, J= 6.4 Hz, 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). Calculated value of LC-MS C32H34N8O2 (M+H)+: m / z = 562.68; Measured value: 563.3.

[0591] (Example 90) (S)-5-((((2',2''-dimethyl-3''-(3-(((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one

[0592] [ka]

[0593] The compound of Example 90 was synthesized by the route shown in the scheme below.

[0594] [ka]

[0595] 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-carbaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (110 mg, 42%) was obtained as a yellowish-white solid. LC-MS: Calculated value of C28H21N3O2 (M+H)+: m / z = 431.51; Measured value: 432.30.

[0596] 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]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one The labeled compound was prepared in the same manner as in Example 1 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (3 mg, 3.7%) as a yellowish-white solid. 1 H NMR (400 MHz, DMSO-d6) δ: 8.58 (d, J= 6.8 Hz, 1H), 7.71-7.64 (m, 3H), 7.42-7.31 (m, 7H), 7.23 (t, J= 6.8 Hz, 2H), 7.15 (d, J= 7.2 Hz, 1H), 7.05 (d, J= 6.4 Hz, 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). Calculated value of LC-MS C38H41N7O2 (M+H)+: m / z = 627.79; Measured value: 628.3.

[0597] The following examples shown in Table 17 were prepared using appropriate amines, following the same procedure as described for Example 90.

[0598] [Table 17]

[0599] (Example 92) 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(3-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide

[0600] [ka]

[0601] The compound of Example 92 was synthesized via the route shown in the scheme below.

[0602] [ka]

[0603] Step 1: Synthesis of 5-formyl-N-(3'-(3-formyl-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (60 mg, 57%) was obtained as a white solid. LC-MS: Calculated value (M+H)+ of C28H21N5O3: m / z = 475.51; Measured value: 476.35 (M+1).

[0604] Step 2: Synthesis of 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(3-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (15 mg, 16%) was obtained as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6) 10.34 (s, 1H), 8.67 (d, J = 5.2 Hz, 2H), 8.59 (d, J = 7.2 Hz, 1H), 8.13 (d, J = 7.6 Hz, 1H), 8.01 (d, J = 8 Hz, 1H), 7.89 (d, J = 8 Hz, 1H), 7.71 (s, 1H), 7.49-7.39 (m, 3H), 7.2 (d, J = 7.2 Hz, 1H), 7.05 (d, J =6.4 Hz, 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 = 7.6 Hz, 3H), 1.98 (s, 3H). Calculated value of LC-MS C33H36N6O3 (M+H)+: m / z = 564.69; Measured value: 565.5

[0605] The following examples shown in Table 18 were prepared using appropriate amines, following the same procedure as described for Example 92.

[0606] [Table 18]

[0607] (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]pyridine-6-yl)-[1,1'-biphenyl]-3-yl)-3-methoxypyrazine-2-yl)methyl)amino)methyl)pyrrolidine-2-one

[0608] [ka]

[0609] The compound of Example 94 was synthesized by the route shown in the scheme below.

[0610] [ka]

[0611] Step 1: Synthesis of 5-(2,2'-dimethyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-3-yl)-3-methoxypyrazine-2-carboaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (210 mg, 43%) was obtained as a yellow, rubbery liquid. LC-MS: Calculated value (M+H)+ of C26H29BN2O4: m / z = 444.34; measured value: 445.35.

[0612] Step 2: Synthesis of 6-(3'-(5-formyl-6-methoxypyrazine-2-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-carbaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (150 mg, 69%) was obtained as a yellow solid. LC-MS: Calculated value of C27H21N5O3 (M+H)+: m / z = 463.5; Measured value: 464.35.

[0613] 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]pyridine-6-yl)-[1,1'-biphenyl]-3-yl)-3-methoxypyrazine-2-yl)methyl)amino)methyl)pyrrolidine-2-one The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (27 mg, 12.6%) was obtained as a yellow solid. 1H NMR (400 MHz, 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= 6.8 Hz, 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). Calculated value for LC-MS C37H41N9O3 (M+H)+: m / z = 659.8; Measured value: 660.4.

[0614] (Example 95) (S)-N-(2,2'-dimethyl-3'-(3-((((5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-[1,1'-biphenyl]-3-yl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide

[0615] [ka]

[0616] The compound of Example 95 was synthesized by the route shown in the scheme below.

[0617] [ka]

[0618] Step 1: Synthesis of tert-butyl(S)-((7-(3'-(5-formylpicolinamide)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (90 mg, 41%) was obtained as a pale yellow, rubbery solid. LC-MS: Calculated value (MH) for C38H39N7O5: m / z = 673.77; Measured value: 672.4.

[0619] Step 2: Synthesis of tert-butyl(S)-((7-(3'-(5-(((2-hydroxyethyl)amino)methyl)picolinamide)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (850 mg, 91.3%) was obtained as a white solid. LC-MS: Calculated value (M+H)+ of C40H46N8O5: m / z = 718.86; Measured value: 719.2.

[0620] Step 3: Synthesis of (S)-N-(2,2'-dimethyl-3'-(3-((((5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-[1,1'-biphenyl]-3-yl)-5-(((2-hydroxyethyl)amino)methyl)picolinamide The labeled compound was prepared in the same manner as in Example 39 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (21 mg, 28.7%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ:10.34 (s, 1H), 8.67 (s, 1H), 8.59 (d, J= 6.8 Hz, 1H), 8.13 (d, J= 7.6 Hz, 1H), 8.01 (d, J= 8.0 Hz, 1H), 7.88 (d, J= 8.4 Hz, 1H), 7.72 (s, 1H), 7.64 (s, 1H), 7.40-7.31 (m, 3H), 7.20 (d, J= 7.2 Hz, 1H), 7.05 (t, J= 6.2 Hz, 2H), 4.49 (t, J= 5.0 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 2H), 3.60-3.58 (m, 1H), 3.47 (q, J= 5.4 Hz, 2H), 2.57-2.50 (m, 4H), 2.09-2.01 (m, 6H), 1.98 (s, 3H), 1.64-1.62 (m, 1H). Calculated value for LC-MS C35H38N8O3 (M+H)+: m / z = 618.74; Measured value: 619.2

[0621] (Example 96) 2-(((2',2''-Dichloro-3''-(3-(((2-hydroxyethyl)amino)methyl)-[1,2,4]Triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-Terphenyl]-4-yl)methyl)amino)ethane-1-ol

[0622] [ka]

[0623] The compound of Example 96 was synthesized by the route shown in the scheme below.

[0624] [ka]

[0625] 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-carbaldehyde A mixture of 2',2''-dichloro-3''-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde (200 mg, 0.44 mmol) and 7-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carboaldehyde (99.74 mg, 0.44 mmol) in 1,4-dioxane (8 mL) was mixed with K2CO3 (182.9 mg, 1.32 mmol) in water (0.8 mL) and Pd(dppf)Cl2 (17 mg, 0.022 mmol). The mixture was degassed with N2 for 30 minutes, and the reaction solution was heated in a 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 layer was washed with brine, dried over Na₂SO₄, filtered, and evaporated. The crude material was purified by Biotage flash column chromatography using a (0-10%) methanol DCM solution to obtain the marked compound (45 mg, 22%) as a pale yellow solid. LC-MS: Calculated value (M+H)+ of C₂₆H₁₅Cl₂N₃O₂: m / z = 472.33; measured value: 472.20.

[0626] Step 2: Synthesis of 2-(((2',2''-dichloro-3''-(3-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (8 mg, 16%) was obtained as a yellowish-white solid. The crude material was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (20 mg, 42%) as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6): δ: 8.62 (d, J = 7.6 Hz, 1H), 8.2 (s, 1H), 7.81 (s, 1H), 7.68-7.4 ( m, 10H), 7.08 ( d, J = 7.2 Hz, 1H), 4.50 ( s, 2H), 4.3 (s, 2H), 3.84 ( s, 2H), 3.52 (t, J= 5.6Hz, 2H), 3.45 (t, j = 6 Hz, 2H), 2.67-(t, J = 5.6 Hz, 2H), 2.6 (t, J = 6 Hz, 2H). LC-MS C30H29Cl2N5O2 Calculated value of (M+H)+: m / z = 562.5; Measured value: 564.

[0627] The following examples shown in Table 19 were prepared using appropriate amines, following the same procedure as described for Example 96.

[0628] [Table 19]

[0629] (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]pyridine-2-yl)methyl)amino)ethane-1-ol

[0630] [ka]

[0631] The compound of Example 98 was synthesized by the route shown in the scheme below.

[0632] [ka]

[0633] Step 1: Synthesis of ethyl N-[(4-chloropyridine-2-yl)carbamate]carbamate A mixture of 4-chloropyridine-2-amine (2 g, 11.5 mmol) and O-ethylcarbonoisothiocyanate (1.4 mL, 11.5 mmol) in dioxane (40 mL) was stirred at room temperature for 4 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (3 × 10 mL). The combined organic layer was washed with brine, dried over Na₂SO₄, filtered, and the solvent was evaporated under reduced pressure to obtain the marked compound (3.2 g, 92%), which was carried over to the next step without purification. LC-MS: Calculated value of C₁₀H₂S (M+H)₁: m / z = 259.71; measured value: 260.20.

[0634] Step 2: Synthesis of 7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-amine 0.85 g, 0.0121 mmol of hydroxylamine HCl (0.85 g, 0.0121 mmol) was stirred in EtOH (20 mL) and DIPEA (1.3 mL, 0.0072 mmol), to which 7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-amine (0.74 g, 0.0024 mmol) was added at room temperature. 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 obtain a solid. This solid was filtered, washed with water, and dried under vacuum to obtain the marked compound (0.35 g, 67%). The crude material was carried over to the next step without further purification. LC-MS: Calculated value (M+H)+ of C6H5ClN4: m / z = 168.58; measured value: 169.

[0635] Step 3: Synthesis of 7-bromo-2-iodo-[1,2,4]triazolo[1,5-a]pyridine A solution of 2-bromo-7-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.2 g, 0.0011 mmol) in 48% HBr aqueous solution (2 mL) was stirred, and a solution of NaNO2 (0.13 g, 0.0017 mmol) in aqueous solution (0.5 mL) was added at 0°C. The reaction mixture was stirred at 0°C for 5 hours. Next, a solution of copper(I) bromide (0.21 g, 0.0014 mmol) in 48% HBr aqueous solution (0.5 mL) was added. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into ice-cold water, the solid was separated, filtered, washed with water, and dried under vacuum to obtain the marked compound (0.27 g, 51%). The crude material was carried over to the next step without further purification. LC-MS: Calculated value (M+H)+ for C6H3BClN3: m / z = 232.47; measured value: 233.9.

[0636] Step 4: Synthesis of 7-chloro-2-vinyl-[1,2,4]triazolo[1,5-a]pyridine A mixture of 2-bromo-7-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.3 g, 9 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.1 g, 6 mmol) in 1,4-dioxane (7 mL) was added to a solution of Na2CO3 (0.2 g, 1.8 mmol) in water (3.0 mL) and Pd(dppf)Cl2 (35 mg, 0.04 mmol). The mixture was degassed with N2 for 30 minutes, and the reaction mixture was heated at 110 °C for 16 hours. The reaction mixture was then cooled to room temperature and diluted with ethyl acetate (50 mL) and water (50 mL). The organic layers were separated, and the aqueous layer was extracted with ethyl acetate (3 × 30 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated. The crude material was purified by Biotage flash column chromatography using a (0-10%) methanol DCM solution to obtain the marked compound (0.3 g, 45%) as a colorless liquid. LC-MS: Calculated value (M+H)+ of C8H6ClN3: m / z = 179.61; Measured value: 180.05.

[0637] Step 5: Synthesis of 2',2''-dimethyl-3''-(2-vinyl-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (300 mg, 45%) was obtained as a colorless liquid. LC-MS: Calculated value (M+H)+ of C29H23N3O: m / z = 429.52; Measured value: 430.15.

[0638] Step 6: Synthesis of 2',2''-dimethyl-3''-(2-vinyl-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde 2',2''-dimethyl-3''-(2-vinyl-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde (100 mg, 23.3 mmol) and 2,6-lutidine (0.05 mL, 41.95 mmol) were stirred in THF (8 mL) and water (2 mL) to which OsO4 (0.55 mL, 8.72 mmol) was added. After 10 minutes, NaIO4 (90 mg, 41.95 mmol) was added, and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered and washed with a 10% MeOH DCM mixture. The filtrate was concentrated under reduced pressure to obtain the crude product. The crude material was purified by Biotage flash column chromatography using (0-10%) ethyl acetate hexane solution to obtain the marked compound (90 mg, 99%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ for C28H21N3O2: m / z = 431.5; Measured value: 432.15.

[0639] 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]pyridine-2-yl)methyl)amino)ethane-1-ol The labeled compound was prepared in the same manner as in Example 1 to obtain the crude product. The crude material was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (10 mg, 3%) as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6): δ: 8.59 (d, J= 7.2 Hz, 1H), 7.7 (s, 1H), 7.41-7.31 (m, 7H), 7.24 (t, J = 5.6 Hz, 2H), 7.15 9d, J = 7.2 Hz, 1H), 7.05 (d, J = 7.2 Hz, 1H), 4.51 (d, J = 4.4 Hz, 2H), 4.29 (s, 2H), 3.77 9s, 2H), 3.32-3.49(m, 4H), 2.59-2.63 9m, 4H), 2.00 9s, 3H), 1.94 (s, 3H). Calculated value of LC-MS C32H35N5O2 (M+H)+: m / z = 521.67; Measured value: 522.25.

[0640] The following examples shown in Table 20 were prepared using appropriate amines, following the same procedure as described for Example 98.

[0641] [Table 20]

[0642] (Example 100) 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide

[0643] [ka]

[0644] The compound of Example 100 was synthesized by the route shown in the scheme below.

[0645] [ka]

[0646] Step 1: Synthesis of 7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-carbaldehyde The labeled compound was prepared in the same manner as in Example 79, and the labeled compound (40 mg, 42%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ of C7H4ClN3O: m / z = 181.58, measured value: 182.10.

[0647] Step 2: Synthesis of 5-formyl-N-(3'-(2-formyl-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (55 mg, 58%) was obtained as a pale yellow sticky mass. LC-MS: Calculated value (M+H)+ of C28H21N5O3: m / z = 475.51, measured value: 476.10.

[0648] Step 3: Synthesis of 5-(((2-hydroxyethyl)amino)methyl)-N-(3'-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)picolinamide The labeled compound was prepared in the same manner as in Example 1 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (5 mg, 10%) as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6): 8.929 (d, J = 6.8 Hz, 1H), 8.678 (s, 1H), 8.205 (s, 1H), 8.13 (d, J = 7.6 Hz, 1H), 8.02 (d, J = 8 Hz, 1H), 7.88 (d, J = 7.6 Hz, 1H), 7.76 (s, 1H), 7.31-7.41 (m, 3H), 7.21 (d, J =6.8 Hz, 2H), 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), LC-MS Calculated value of C32H35N7O3 (M+H)+: m / z = 565.2; Actual value: 565.5

[0649] The following examples shown in Table 21 were prepared using appropriate amines, following the same procedure as described for Example 100.

[0650] [Table 21]

[0651] (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]pyridine-2-yl)methyl)amino)methyl)pyrrolidine-2-one

[0652] [ka]

[0653] The compound of Example 102 was synthesized by the route shown in the scheme below.

[0654] [ka]

[0655] Step 1: Synthesis of tert-butyl((7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (400 mg, 42%) was obtained as a pale yellow sticky mass. LC-MS: Calculated value (M+H)+ for C17H22ClN5O3: m / z = 379.85, measured value: 380.10.

[0656] Step 2: Synthesis of tert-butyl(S)-((7-(4''-formyl-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (230 mg, 100%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ for C38H39N5O4: m / z = 629.76, measured value: 630.25.

[0657] Step 3: Synthesis of tert-butyl(S)-((7-(4''-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (140 mg, 99%) was obtained as a pale yellow solid. LC-MS: Calculated value (M+H)+ for C40H46N6O4: m / z = 674.85, measured value: 675.35.

[0658] 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]pyridine-2-yl)methyl)amino)methyl)pyrrolidine-2-one The labeled compound was prepared in the same manner as in Example 39 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (55 mg, 42%) as a yellowish-white solid. 1H NMR (400 MHz, DMSO-d6) δ:8.92 (d, J =7.2 Hz 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 = 20 Hz, 6H) ,1.69 (s,1H), LC-MS calculated value for C35H38N6O2 (M+H)+: m / z = 574.73; measured value: 575.7.

[0659] (Example 103) (S)-N-(2,2'-dimethyl-3'-(2-((((5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1'-biphenyl]-3-yl)-4-(((2-hydroxyethyl)amino)methyl)benzamide

[0660] [ka]

[0661] The compound of Example 103 was synthesized by the route shown in the scheme below.

[0662] [ka]

[0663] Step 1: Synthesis of 5-((((7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)amino)methyl)pyrrolidine-2-one The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (850 mg, 90%) was obtained as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C12H14ClN5O: m / z = 279.73, measured value: 280.05.

[0664] Step 2: tert-butyl((7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate 5-((((7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)amino)methyl)pyrrolidine-2-one (850 mg, 30 mmol) and TEA (1.3 mL, 91 mmol) were stirred in methanol (1 mL) and DCM (9 mL) to which anhydrous Boc (860 mg, 39 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 5 hours. Organic volatiles 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 obtain the crude product. The crude compound was purified by combiflash column chromatography using a 0-30% ethyl acetate hexane solution as the mobile phase to obtain the labeled compound 3 (850 mg, 74%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ for C17H22ClN5O3: m / z = 379.85, measured value: 380.10.

[0665] Step 3: Synthesis of tert-butyl(S)-((7-(3'-(4-formylbenzamide)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (200 mg, 79%) was obtained as a yellowish-white solid. LC-MS: Calculated value of C39H40N6O5 (M+H)+: m / z = 672.79. Measured value: 673.30.

[0666] Step 4: Synthesis of tert-butyl(S)-((7-(3'-(4-(((2-hydroxyethyl)amino)methyl)benzamide)-2,2'-dimethyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)((5-oxopyrrolidine-2-yl)methyl)carbamate The labeled compound was prepared in the same manner as in Example 1, and the labeled compound (100 mg, 79.4%) was obtained as a yellowish-white solid. LC-MS: Calculated value (MH)+ of C41H47N7O5: m / z = 717.87. Measured value: 716.25.

[0667] Step 5: Synthesis of (S)-N-(2,2'-dimethyl-3'-(2-((((5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1'-biphenyl]-3-yl)-4-(((2-hydroxyethyl)amino)methyl)benzamide The labeled compound was prepared in the same manner as in Example 39 to obtain a crude product, which was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (25 mg, 17%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ:8.92 (d, J =6.8 Hz 1H), 8.19 (s, 2H), 7.97 (d, J = 7.6Hz, 2H), 7.76 (s, 1H), 7.65(s, 1H), 7.52 (d, J = 7.6 Hz, 2H), 7.297-7.29 (m, 4H), 7.212 (s, 2H), 7.09 (d , J = 7.2 Hz,, 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). Calculated value of LC-MS C36H39N7O3 (M+H)+: m / z = 617.75; Measured value: 618.3.

[0668] (Example 104) 2-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol

[0669] [ka]

[0670] The compound of Example 104 was synthesized by the route shown in the scheme below.

[0671] [ka]

[0672] Step 1: Synthesis of 2-(((2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)ethane-1-ol The labeled compound was prepared in the same manner as in Example 1 to obtain the crude product. The crude material was purified by preparative HPLC (X-Bridge C18 column (250 × 19) mm, 5.0 μm; mobile phase (A:B), A = 0.1% FA in H2O, B = 100% ACN) to obtain the labeled compound (10 mg, 32%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ: 8.96 (d, J= 7.2 Hz, 1H), 8.189 (s, 1H), 7.856 (s, 1H), 7.447-7.611 (m, 9H), 7.25 (d, J = 6.8 Hz, 1H), 4.5 (s, br, 2H), 3.957 (s, 2H), 3.83 (s, 2H), 3.504 (t, J = 6 Hz, 4H), 2.67 (d, J = 4.8 Hz, 4H), LC-MS Calculated value of C30H29Cl2N5O2 (M+H)+: m / z = 562.5; Actual value: 563.2.

[0673] The following examples shown in Table 22 (Tables 22 and 23) were prepared using appropriate amines, following the same procedure as described for Example 104.

[0674] [Table 22]

[0675] [Table 23A]

[0676] [Table 23B]

[0677] (Example 112) 2-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]Triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-Terphenyl]-4-yl)methyl)amino)-2-methylpropane-1-ol

[0678] [ka]

[0679] The compound of Example 112 was synthesized by the route shown in the scheme below.

[0680] [ka]

[0681] Step 1: Synthesis of 2-(((7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)amino)ethane-1-ol 7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-carbaldehyde (500 mg, 2.75 mmol) and ethanolamine (0.16 mL, 2.75 mmol) were stirred in methanol (10 mL) and zinc chloride (561 mg, 4.12 mmol) was added. Sodium cyanoborohydride (250 mg, 4.12 mmol) was added to the resulting mixture, and the reaction mixture was heated at 80 °C for 16 hours. Organic volatiles were removed under reduced pressure, and the resulting crude material was purified by flash column chromatography using a (5-10%) methanol-dichloromethane solution to obtain the marked compound 2-(((7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)amino)ethane-1-ol (320 mg, 51%) as a yellowish-white solid. LC-MS: Calculated value (M+H)+ of C9H11ClN4O: m / z = 226.06; Measured value: 227.10

[0682] Step 2: Synthesis of 2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde Step 2: 2-(((7-chloro-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)amino)ethane-1-ol (100 mg, 0.44 mmol) and 2',2''-dichloro-3''-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde (200 mg, 0.44 mmol) were mixed in 1,4-dioxane (10 mL) and water (1 mL), to which K2CO3 (182 mg, 1.32 mmol) was added. The resulting reaction mixture was degassed with N2 for 20 minutes. Pd(dppf)Cl2.DCM (36 mg, 0.044 mmol) was added to this reaction mixture, and the reaction solution was 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 material was purified by flash column chromatography using methanol and dichloromethane as the mobile phase (0-10%) to obtain the marked compound 2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde (250 mg, 43%) as a brown solid. LC-MS: Calculated value (M+H)+ of C28H22Cl2N4O2: m / z = 516.11; measured value: 517.05

[0683] Step 3: Synthesis of 2-(((2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)-2-methylpropan-1-ol 2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-carboaldehyde (100 mg, 0.19 mmol) and 2-amino-2-methyl-1-propanol (0.02 mL, 0.19 mmol) were stirred in methanol (2 mL) to which zinc chloride (39 mg, 0.28 mmol) and sodium borohydride cyanohydride (18 mg, 0.28 mmol) were added. The resulting mixture was stirred at 80°C for 16 hours. Organic volatiles were removed under reduced pressure, and the resulting crude product was purified by preparative HPLC (INT ODS 3V-C18 (4.6*250) mm, 5 μm; mobile phase (A:B), A = 0.1% formic acid aqueous solution, B = acetonitrile) to obtain the marked compound 2-(((2',2''-dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)-2-methylpropan-1-ol (15 mg, 13%) as a yellowish-white solid. LC-MS Calculated value for C32H33Cl2N5O2 (M+H)+: m / z = 590.55; Actual value: 590.10 1H NMR (400 MHz, DMSO-d6): 8.98 (d, 1H, J=7.2 Hz, 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=5.6 Hz), 2.69-2.67 (m, 2H), 2.54 (s, 2H), 1.24 (s, 2H), 1.09 (s, 6H).

[0684] The following examples shown in Table 23 (Table 24) were prepared using appropriate amines, following the same procedure as described for Example 112.

[0685] [Table 24]

[0686] PD1-PDL1 HTRF assay Using CisBio HTRF assay kits purchased exclusively from CisBio, we performed IC of compounds. 50 The values ​​were confirmed. The PD1-PDL1 HTRF assay measures the interaction between two proteins, PD1 and PDL1. This interaction is detected using anti-Tag1 labeled with europium (HTRF donor) that binds to PDL1, and anti-Tag2 labeled with XL665 (HTRF acceptor) that binds to PD1. When these two antibodies are in close proximity, excitation of the donor fluorophore causes FRET emission from the acceptor fluorophore. The presence of an inhibitor of this interaction results in a decrease in the HTRF signal.

[0687] The assay was performed in a 96-well white assay plate. Following the manufacturer's protocol, all reagents, including Tag1-PDL1, Tag2-PD1, anti-Tag1-PDL1, and anti-Tag2-PD1, were thawed and diluted in PPI europium detection buffer to achieve the desired concentrations. A 1000 μM stock solution of the test inhibitor in DMSO was prepared. Eight concentrations (1000–0.001 μM) were prepared by diluting the stock solution in DMSO. Furthermore, eight diluted standard stock solutions (100–0.0001 μM) were prepared by diluting these stock solutions in PPI europium detection buffer. 2 μL of the diluted standard stock solution of the test inhibitor, followed by 4 μL of Tag1-PDL1 (5 nM) and 4 μL of Tag2-PD1 (50 nM), were added to the 96-well plate. The plate was incubated at room temperature for 15 minutes. Subsequently, 10 μL of the pre-mixed anti-Tag1-PDL1 and anti-Tag2-PD1 solutions were added. The plates were sealed and incubated at room temperature for 1 hour. HTRF signals were read using a Perkin Elmer Envision plate reader with excitation wavelengths of 320 nm and emission wavelengths of 620 nm and 665 nm. The results were calculated by multiplying the ratio of the acceptor signal at 665 nm to the donor signal at 620 nm by 10⁴. IC 50 The values ​​were determined using the Hill formula with GraphPad's Prism software.

[0688] The compounds of the present invention exemplified in the examples are ICs within the following range. 50 The value was shown. +: IC 50 ≤10nM; ++: 10nM <IC 50 ≤100nM; +++: 100nM <IC 50 <1000nM

[0689] The data obtained for the example compounds described in Examples 1 to 105 using the PD-1 / PD-L1 homogeneous time-resolved fluorescence (HTRF) binding assay are shown in Table 24 (Table 25).

[0690] [Table 25A]

[0691] [Table 25B]

[0692] [Table 25C]

[0693] Embodiment (Ea) E1a Compounds of formula (I), or pharmaceutically acceptable salts or stereoisomers thereof.

[0694] [ka]

[0695] (In the formula, Each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N; R3 is H, methyl, halogen, or CN; R4 and R5 are independently H, methyl, halogen, or CN; R7 H, C 1~6 Alkyl, C 1~6 It is an alkoxy, halogen, or CN; R1 is H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR aNHCOR a NHR a NHOR a , C(O)R a CONHR a NHSO2R a SO2NHR a , and OCH2R a Selected from, or R1 and R6 are linked together to form a 4-10 member heterocycloalkyl, and the C of R1 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. b Substitutions may also be present; R2 is C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR a , and NHR a Selected from, R2's C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4Each alkyl- is independently selected from 1, 2, or 3 R b Substituting with a substituent; R6 H, C 1~6 Alkyl, halo, and OCH2R a R1 and R6 are selected from, or R1 and R6 are linked together, and one, two, three, or four independently selected R b Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected as one or two R d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, OH, (=O), NH2, NHOR c NHC(O)R c , OR c , C(O)R cC(O)NHR c , C(O)OR c , C 1~6 Alkyl-NHR c NHR c Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halo, CN, COOH, OH, (=O)).

[0696] E2a Formula (II)

[0697] [ka]

[0698] The compound described in E1a, or a pharmaceutically acceptable salt or stereoisomer thereof (wherein X1-X3, X5, and X6, R1, R3, R4-R7, and R b (This has the same meaning as in E1a, where the subscript n is 1, 2, or 3).

[0699] E3a The compound described in E2a, where n is 1.

[0700] E4a Formula (III)

[0701] [ka]

[0702] The compound described in E1a, or a pharmaceutically acceptable salt or stereoisomer thereof (wherein X1-X3, X5, and X6, R1, R3, R4-R7, and R b (This has the same meaning as in E1a, where the subscript m is 0, 1, 2, or 3).

[0703] E5a Formula (IV) or (V)

[0704] [ka]

[0705] A compound described in E1a having, or a pharmaceutically acceptable salt or stereoisomer thereof (wherein X1-X6, R1, R3, R4-R7, and R b (This has the same meaning as in E1a, where the subscript n is 1, 2, or 3).

[0706] E6a Equation (VI) or (VII)

[0707] [ka]

[0708] A compound described in E1a, or a pharmaceutically acceptable salt or stereoisomer thereof (wherein X1-X6, R1, R3, R4-R7, and Ra have the same meanings as in E1a, and the subscript p is 0 or 1).

[0709] E7a heteroaryl group

[0710] [ka]

[0711] but

[0712] [ka]

[0713] A compound selected from the group consisting of E1a to E6a, or a pharmaceutically acceptable salt or stereoisomer thereof.

[0714] E8a A compound according to any one of E1a to E7a, wherein R3 is methyl, Cl, or CN, R4 and R7 are H, and R5 is H, methyl, or Cl.

[0715] E9a A compound described in any one of E1a to E7a, wherein R3 is methyl and R4, R5, and R7 are H.

[0716] E10a A compound described in any one of E1a to E7a, wherein R3 and R5 are methyl and R4 and R7 are H.

[0717] E11a A compound described in any one of E1a to E7a, wherein R3 and R5 are Cl and R4 and R7 are H.

[0718] E12a R3 and R5 are methyl or Cl, R1, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e The compound described in E1a, wherein is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N.

[0719] E13a R3 is methyl or Cl, R1, R4, R5, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e The compound described in E1a, wherein is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N.

[0720] E14a R3 is methyl, R4, R5, and R7 are H, R1 and R6 are H, or linked together to form a 4-10 member heterocycloalkyl, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b NHR c And R c However, one or two R d C replaced by 1~6 It is alkyl, R d C(O)OR e S(O)2R e , or OR e And Re The compound described in E1a, wherein is H or OH, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N.

[0721] E15a R3 is methyl or Cl, R4, R5, and R7 are H, R1 and R6 are linked together to form a 4-10 member heterocycloalkyl group, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, one or two R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e OR e And R e The compound described in E1a, wherein is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N.

[0722] E16a R3 is methyl, R4, R5, and R7 are H, R1 and R6 are linked together to form a 4-10 member heterocycloalkyl, and R2 is one of three R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b1 However, one or two R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e OR e And R e H is R b2 and R b3 C 1~6 The compound described in E1a, which is an alkoxy, wherein each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N.

[0723] E17a R3 is CN, R1, R4, R5, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e The compound described in E1a, wherein is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N.

[0724] E18a R3 is methyl, R1, R4, R5, R6, and R7 are H, and R2 is R b C replaced by 2~6 It is alkinyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e The compound described in E1a, wherein is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N.

[0725] E19a R3 is methyl, R1, R4, R5, R6, and R7 are H, and R2 is R b It is a 5-14 member heteroaryl substituted with R b C(O)NHR c And R c However, R d C replaced by 1~6 It is alkyl, R d C(O)OR e And R e The compound described in E1a, wherein is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N.

[0726] E20a R3 is methyl, R4, R5, and R7 are H, R1 and R6 are linked together to form a 4-10 member heterocycloalkyl group, and R2 is R b It is a 5-14 member heteroaryl substituted with R b C(O)NHR c And R c However, R d C replaced by 1~6 It is alkyl, R d C(O)OR e And R e The compound described in E1a, wherein is H, and X1 to X6 are each independently C or N, provided that at least two and at most five of X1 to X6 are N.

[0727] Embodiment (Eb) E1b Compounds of formula (I), or pharmaceutically acceptable salts or stereoisomers thereof.

[0728] [ka]

[0729] (In the formula, Each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N; R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b R d A 4-10 member heterocycloalkyl substituted with R d is C(O)OR e And R e is H; R3 and R5 are independently methyl or Cl; R7 H, C 1~6 Alkyl, C 1~6 It is an alkoxy, halogen, or CN; R4 and R6 are H. R1 is R 1-aa , R1-bb , R 1-cc , R 1-dd , R 1-bc , R 1-bd , R 1-dd , R 1-de , and R 1-ii 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 In this case, 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 Y1 and Y2 are independently C or N; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 of these is independently selected as one, two, or three R elements. d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides are each independently selected as 1, 2, or 3 R f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 (Selected from alkyl, halogen, CN, COOH, OH, (=O)). Other variations of formula (I) are as specified in any embodiment disclosed herein.

[0730] E2b R1 is 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 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 Medium, each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, OH, (=O), NH2, NHOR c NHC(O)R c , ORc , C(O)R c C(O)NHR c , C(O)OR c , C 1~6 Alkyl-NHR c NHR c Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 R is selected independently of each other, either one, two, or three. d Substituting with a substituent; Each R c H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 A compound as described in E1b, selected from alkyl, halogen, CN, COOH, OH, (=O). Other variations of formula (I) are as specified in any embodiment disclosed herein.

[0731] E3b R1 is R 1-1 , R 1-2 , R1-3 , 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 A compound selected from those listed in E1b.

[0732] E4b A compound described in any one of E1b to E3b, wherein both R3 and R5 are Cl.

[0733] E5b A compound described in any one of E1b to E3b, wherein both R3 and R5 are methyl.

[0734] E6b A compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof (wherein R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b is NHR c And R c R d C replaced by 1~6 It is alkyl, R d is OR e And R e is H or C 1~6 It is an alkyl group, where X1 to X6 are each independently either C or N, provided that at least two and at most five of X1 to X6 are N, and R1 is as defined in E1b).

[0735] E7b R1 is R as defined in E2b 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 A compound selected from the compounds listed in E6b.

[0736] E8b R1 is 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 A compound selected from the compounds listed in E6b.

[0737] E9b A compound described in any one of E6b to E8b, wherein both R3 and R5 are Cl.

[0738] E10b A compound described in any one of E6b to E8b, wherein both R3 and R5 are methyl.

[0739] E11b A compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof (wherein R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is C 1~6 Alkyl-NHR a And R a R d C replaced by 1~6 It is alkyl, R d is OR e Or it is a C3-C6 cyclic amide, R e is H or C 1~6 It is an alkyl group, where X1 to X6 are each independently either C or N, provided that at least two and at most five of X1 to X6 are N, and R1 is as defined in E1b).

[0740] E12b R1 is R as defined in E2b 1-a , R1-b , R 1-c , R 1-d , R 1-e , R 1-f , R 1-g , R 1-h , and R 1-I A compound selected from those listed in E11b.

[0741] E13b R1 is 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 A compound selected from those listed in E11b.

[0742] E14b A compound described in any one of E11b to E13b, wherein both R3 and R5 are Cl.

[0743] E15b A compound described in any one of E11b to E13b, wherein both R3 and R5 are methyl.

[0744] E16b A compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof (wherein R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is C 1~6 Alkyl-NHR a And R a R d C replaced by 1~6 It is alkyl, R d is OR e Or it is a C3-C6 cyclic amide, R e is H or C 1~6It is an alkyl group, and each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N, and R1 is C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, NHOR a , C(O)R a NHCOR a NHR a CONHR a NHSO2R a , and SO2NHR a Selected from, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl- is one or two R b Substituting with a substituent; During R1, Each R a R is independent of R d C, which was substituted independently in each case. 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl and (5-14 member heteroaryl)-C 1~4 Selected from alkyl-; Each R b The substituents are independently C 6~10 Ariel, C 6~10 Aryl-C 1~4 Alkyl, NHC(O)R c C(O)NHR c NHR c Selected from , and OMe, C 6~10 Aryl and C 6~10 Aryl-C 1~4 Each alkyl group is independently R d It has been replaced with; Each R c C is independent 1~6 C substituted with alkyl and OH groups1~6 Alkyl, 4-10 member heterocycloalkyl, and (4-10 member heterocycloalkyl)-C 1~4 Selected from alkyl-, C 1~6 Alkyl, 4-10 member heterocycloalkyl, and (4-10 member heterocycloalkyl)-C 1~4 Each alkyl group is independently substituted with (=O), (OH), or COOH; Each R d It is independently NHR e , 4-10 member heterocycloalkyl, and (4-10 member heterocycloalkyl)-C 1~4 Selected from alkyl-, including 4-10 member heterocycloalkyl and (4-10 member heterocycloalkyl)-C 1~4 Each alkyl group is independently substituted with (=O), (OH), or COOH; Each R e These are independently substituted C with OH. 1~6 Alkyl, 4-10 member heterocycloalkyl, and (4-10 member heterocycloalkyl)-C 1~4 Selected from alkyl-, including 4-10 member heterocycloalkyl and (4-10 member heterocycloalkyl)-C 1~4 Each alkyl group is independently substituted with (=O), (OH), or COOH.

[0745] E17b A compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof (wherein, Each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N; R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b R d A 4-10 member heterocycloalkyl substituted with R d is C(O)OR e And R e is H; R3 and R5 are independently methyl or Cl; R7 H, C 1~6 Alkyl, C 1~6 It is an alkoxy, halogen, or CN; R4 and R6 are H; R1 is as specified in E16b).

[0746] E18b A compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof (wherein R3 and R5 are independently methyl or Cl, R4, R6, and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b is NHR c And R c R d C replaced by 1~6 It is alkyl, R d is OR e And R e is H or C 1~6 It is an alkyl group, where X1 to X6 are each independently either C or N, provided that at least two and at most five of X1 to X6 are N, and R1 is as specified in E16b).

[0747] Embodiment (Ec) Ec1 Compounds of formula (I), or pharmaceutically acceptable salts or stereoisomers thereof.

[0748] [ka]

[0749] (In the formula, Each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N; R3 is H, methyl, halogen, or CN; R4 and R5 are independently H, methyl, halogen, or CN; R7 H, C 1~6 Alkyl, C 1~6It is an alkoxy, halogen, or CN; R1 is H, C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-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 Selected from, or R1 and R6 are linked together to form a 4-10 member heterocycloalkyl, and the C of R1 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl group consists of one, two, three, or four independently selected R groups. b Substitutions may also be present; R2 is C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide-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 Selected from, R2's C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide-C 1~4 Each alkyl- is independently selected from 1, 2, 3, or 4 R b Substituting with a substituent; R6 H, C 1~6 Alkyl, C 2~6 Alkynyl, halogen, and OCH2R a R1 and R6 are selected from, or R1 and R6 are linked together, and one, two, three, or four independently selected R b Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; Each R a H and C are independent of each other. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR c NHOR c NHCOR c NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Each alkyl- is independently selected from 1, 2, or 3 R d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide 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)NR c R c , C(O)OR c ,OC(O)R c、 C 1~6 Alkyl-NHR c NHR c、 NR c R c、 S(O)2NR c R c Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide C 1~4 Each alkyl- is independently selected from 1, 2, or 3 R d Substituting with a substituent; Each R c H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C1~6 Alkyl, C 2~6 Alkenil, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. d Substituting with a substituent; Each R d C is independent 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amides, C3-C6 cyclic amide C 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)2Re , and S(O)2NR e R e Selected from, R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C3-C6 cyclic amides, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1~6 Alkyl, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide C 1~4 Selected from alkyl-, R e C 1~6 Alkyl, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide C 1~4 Each alkyl group consists of one, two, or three independently selected R groups. f Substitutions may also be present; Each R f H and C are independent of each other. 1~4 Alkyl, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Selected from alkyl-, C3-C6 cyclic amides, halogens, CN, COOH, OH, (=O).

[0750] Ec2 Each of X1 to X6 is independently either C or N, provided that at least two and at most five of X1 to X6 are N; R3 is H, methyl, halogen, or CN; R4 and R5 are independently H, methyl, halogen, or CN; R7 is H, C 1~6 Alkyl, C 1~6 It is an alkoxy, halogen, or CN; R1 is H, C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-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 Selected from, or R1 and R6 are linked together to form a 4-10 member heterocycloalkyl, and the C of R1 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4Alkyl-, C 3~10 Cycloalkyl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 R is selected independently, with each alkyl group consisting of one, two, or three alkyl groups. b Substitutions may also be present; R2 is C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, C 1~6 Alkyl-NHR a , and NHR a Selected from, R2's C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, C 6~10 Aryl-C 1~4 Alkyl-, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 R is selected from one, two, or three alkyl groups, each independently. b Substituting with a substituent; R6 is H, C 1~6 Alkyl, halogen, and OCH2R a Selected from, or R1 and R6 are linked together, resulting in 1, 2, 3, or 4 independently selected R b Forms a 4-10 member heterocycloalkyl group which may be substituted with substituents; Each R a H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 Alkyl-, NHR c , and OCH2R c Selected from, R a C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Aryl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, (5-14 member heteroaryl)-C 1~4 Alkyl-, (4-10 member heterocycloalkyl)-C 1~4 R is selected by independently choosing one or two alkyl- groups. d Substituting with a substituent; Each R b The substituents are independently C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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 Selected from, R b C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 4-10 member heterocycloalkyl, 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)ORc , C 1~6 Alkyl-NHR c NHR c R is selected independently of each other, either one, two, or three. d Substituting with a substituent; Each R c H and C are independent. 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 Alkyl, C(O)R d C(O)NHR d , and C(O)NR d R d Selected from, R c C 1~6 Alkyl, C 1~6 Alkoxy, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 6~10 Aryl-C 1~4 Alkyl, C3-C6 cyclic amide C 1~4 R is selected by independently selecting one, two, or three alkyl groups. d Substituting with a substituent; Each R d C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C3-C6 cyclic amide, 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 Selected from, Rd C 1~6 Alkyl, C 1~6 Alkoxy, C 6~10 Ariel, C 3~10 R is selected from one, two, or three independently selected cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C3-C6 cyclic amides. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R. f , C 1~6 Selected from alkyl and 5-14 member heteroaryls, R e C 1~6 R is selected to consist of one, two, or three independently selected alkyl and 5-14 membered heteroaryl groups. f Substitutions may also be present; Each R f H and C are independent. 1~4 Compounds listed in Ec1, selected from alkyl, halogen, CN, COOH, OH, (=O), or pharmaceutically acceptable salts or stereoisomers thereof.

[0751] Ec3 Formula (II)

[0752] [ka]

[0753] A compound described in Ec1 or Ec2 having, or a pharmaceutically acceptable salt or stereoisomer thereof (wherein X1-X3, X5, and X6, R1, R3, R4-R7, and R b (This has the same meaning as in Ec1 or 2, where the subscript n is 1, 2, or 3).

[0754] Ec4 The compound described in Ec3, where n is 1.

[0755] Ec5 Formula (IV) or (V)

[0756] [ka]

[0757] A compound described in Eb1 or 2 having, or a pharmaceutically acceptable salt or stereoisomer thereof (in formula (IV), X1-X3, X5, and X6, R1, R3, R4-R7, and R b It has the same meaning as in Ec1 or 2, and the subscript n is 1, 2, or 3; In equation (V), X1 to X4, and X6, R1, R3, R4 to R7, and R b (This has the same meaning as in Ec1 or 2, where the subscript n is 1, 2, or 3).

[0758] Ec6 Equation (VI) or (VII)

[0759] [ka]

[0760] A compound described in Ec1 or 2 having, or a pharmaceutically acceptable salt or stereoisomer thereof (in formula (VI), X1-X3, X5, and X6, R1, R3, R4-R7, and R a has the same meaning as in Ec1 or 2, and the subscript p is 0 or 1; in equation (VII), X1 to X4, and X6, R1, R3, R4 to R7, and R a (This has the same meaning as in Ec1 or 2, where the subscript p is 0 or 1).

[0761] Ec7 A compound as described in any one of Ec1 to 6, wherein R3 is methyl, Cl, or CN, R4 and R7 are H, and R5 is H, methyl, or Cl, or R3 is methyl, and R4, R5, and R7 are H, or R3 and R5 are methyl, and R4 and R7 are H, or R3 and R5 are Cl, and R4 and R7 are H.

[0762] Ec8 R1

[0763] [ka]

[0764] A compound selected from any one of Ec1-7. (In the formula, 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 C or N, R b and R d (This is as specified in any one of the preceding embodiments.)

[0765] Ec9 R3 and R5 are methyl or Cl, R4, R6 and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b However, R d A 4-10 member heterocycloalkyl substituted with R d C(O)OR e And R e H is and R1 is

[0766] [ka]

[0767] A compound selected from either Ec1 or Ec2.

[0768] Ec10 R3 and R5 are methyl or Cl, R4, R6 and R7 are H, and R2 is R b C replaced by 6~10 Aryl-C 1~4 It is alkyl-, R b NHR c And R c However, R d C replaced by 1~6It is alkyl, R d is OR e And R e is H or C 1~6 It is alkyl, and R1 is 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 , R 1-14 , and R 1-15 A compound selected from the group consisting of, whichever is Ec1 or 2 described above.

[0769] Ec11 R3 and R5 are methyl or Cl, R4, R6, and R7 are H, and R2 is C 1~6 Alkyl-NHR a And R a However, R d C replaced by 1~6 It is alkyl, R d is OR e Or it is a C3-C6 cyclic amide, R e is H or C 1~6 It is alkyl, and R1 is 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 , R 1-14 , and R 1-15 A compound selected from the group consisting of, whichever is Ec1 or 2 described above.

[0770] Ec12 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid; (4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)proline; 3-((4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)amino)oxetane-3-carboxylic acid; (2S,4R)-4-hydroxy-1-(4(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)pyrrolidine-2-carboxylic acid; 1-((4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)amino)cyclobutane-1-carboxylic acid; 4-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)morpholine-3-carboxylic acid; 1-(2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid; 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)azetidine-3-carboxylic acid; N-(2-hydroxyethyl)-1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carboxamide; 1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid; 1-(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzyl)piperidine-2-carboxylic acid; (4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzyl)proline; 3-((4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)amino)propan-1-ol; (2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)proline; (2,6-dimethoxy-4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)proline; (4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)valine; (4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)-L-proline; (4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)-D-proline; (4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)glycine; (S)-1-(4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)azetidine-2-carboxylic acid; (4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)proline; 3-Hydroxy-4-((4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)benzyl)amino)butanoic acid; (1-(7-(2-methyl-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridine-3-yl)-1H-pyrazole-3-carbonyl)glycine; 4-(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzyl)morpholine-3-carboxylic acid; 2-((4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)benzyl)amino)ethane-1-ol; (3S,5R)-1-(4-(7-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-yl)benzyl)-5-hydroxypyrrolidine-3-carboxylic acid; 3-((4-(7-(2-methyl-[1,1'-biphenyl]-3-yl)-[1,2,4]triazolo[4,3-a]pyridine-3-yl)b...

Claims

1. Compounds of formula (VIII), or pharmaceutically acceptable salts or stereoisomers thereof. 【Chemistry 1】 (In the formula, X 1 ~X 4 Each is independently C or N, however X 1 ~X 4 At least three of them are N; The subscript p is 1; R 3 and R 5 Each of these is independently methyl, Cl, or CN; R 4 H, C 1～6 It is alkyl, halogen, or CN; R 6 is H, C 1～6 alkyl, or halogen; R 1 teeth 【Chemistry 2】 and; R aa is H, or R aa and R a These are linked together, and one or two independently selected R d Forms a 4- to 10-membered heterocycloalkyl group which may be substituted with substituents; R a is C 1～6 Alkyl, C 1～6 Alkoxy, and C 3～10 Selected from cycloalkyl, or R aa and R a These are linked together, and one or two independently selected R d Forms a 4- to 10-membered heterocycloalkyl group which may be substituted with substituents; R a C 1～6 Alkyl, C 1～6 Alkoxy, and C 3～10 Each cycloalkyl group is independently selected as one or two R groups. d Substituting with a substituent; R cc is H, or R cc and R c These are linked together, and one or two independently selected R d Forms a 4- to 10-membered heterocycloalkyl group which may be substituted with substituents; R c is C 1～6 Alkyl, C 1～6 Alkoxy, and C 3～10 Selected from cycloalkyl, or R cc and R c These are linked together, and one or two independently selected R d Forms a 4- to 10-membered heterocycloalkyl group which may be substituted with substituents; R c C 1～6 Alkyl, C 1～6 Alkoxy, and C 3～10 Each cycloalkyl group is independently selected as one or two R groups. d Substituting with a substituent; Each R d C is independent 1～6 Alkyl, C 1～6 Alkoxy, C 6～10 Ariel, C 3～10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, C 3 ~C 6 Cyclic amides, CN, NH 2 , 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) 2 R e , and S(O) 2 NR e R e Selected from, R d C 1～6 Alkyl, C 1～6 Alkoxy, C 6～10 Ariel, C 3～10 Cycloalkyl, 5-14 member heteroaryl, 4-10 member heterocycloalkyl, and C 3 ~C 6 Each cyclic amide is selected from 1, 2, or 3 independently. f Substitutions may also be present; Each R e These are independently H, OH, COOH, and C(O)R f , C 1～6 Selected from alkyl and 5-14 member heteroaryls, R e C 1～6 Alkyl and 5-14 membered heteroaryls are each independently selected in groups of 1, 2, or 3. f Substitutions may also be present; Each R f H and C are independent of each other. 1～4 (Selected from alkyl, halogen, CN, COOH, OH, and (=O)).

2. heteroaryl group 【Transformation 3】 but 【Chemistry 4】 Selected from the group consisting of, R aa and R a This is as defined in claim 1. The compound described in claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof.

3. R 3 and R 5 Cl is; R 4 and R 6 The compound according to claim 1 or 2, wherein is H and p is 1.

4. R 3 and R 5 is Cl; R 4 and R 6 is H, p is 1, and the heteroaryl group 【Transformation 5】 but 【Transformation 6】 And, R aa and R a This is as defined in claim 1. A compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt or stereoisomer thereof.

5. R 1 but 【Transformation 7】 A compound selected from any one of claims 1 to 4.

6. R aa H is R a but 【Transformation 8】 A compound selected from any one of claims 1 to 5.

7. R aa and R a are connected together to 【Chemistry 9】 A compound according to any one of claims 1 to 5, which forms a compound selected from the above.

8. R 3 and R 5 Cl is; R 4 and R 6 H is, p is 1, R 1 R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 1～6 It is alkyl, R d is OR e And R e H is R aa H is R a However, R d C replaced by 1～6 It is alkyl, R d is OR e And R e The compound according to claim 1, wherein is H.

9. R 3 and R 5 Cl is; R 4 and R 6 H is, p is 1, R 1 R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 3～10 It is cycloalkyl, R d is OR e And R e H is R aa H is R a However, R d C replaced by 3～10 It is cycloalkyl, R d is OR e And R e The compound according to claim 1, wherein is H.

10. R 3 and R 5 Cl is; R 4 and R 6 H is, p is 1, R 1 R 1-j And R 1-j Medium, R cc H is R c However, R d C replaced by 1～6 It is alkyl, R d NHR e And R e C(O)R f And R f C 1～4 It is alkyl, R a However, R d C replaced by 1～6 It is alkyl, R d NHR e And R e C(O)R f And R f C 1～4 The compound according to claim 1, wherein it is alkyl.

11. R 3 and R 5 Cl is; R 4 and R 6 H is, p is 1, R 1 R 1-j And R 1-j Medium, R cc and R c They are linked together, R d Forms a 4- to 10-membered heterocycloalkyl group substituted with R d However, C substituted with OH 1～6 It is alkyl, R aa H is R a However, R d C replaced by 1～6 It is alkyl, R d is OR e And R e The compound according to claim 1, wherein is H.

12. R 3 and R 5 Cl is; R 4 and R 6 H is present, p is 1, and it is a heteroaryl group 【Chemistry 10】 but 【Chemistry 11】 And, R aa H is R a but 【Chemistry 12】 Selected from, R 1 but 【Chemistry 13】 A compound according to claim 1, selected from the following.

13. 2-(((7-(4''-(((2-hydroxyethyl)amino)methyl)-2,2'-dimethyl-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-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]pyridine-3-yl)methyl)amino)ethane-1-ol; 2-(((2',2''-Dichloro-3''-(3-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-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]pyridine-3-yl)methyl)amino)methyl)pyrrolidine-2-one; (S)-5-((((2',2''-dimethyl-3''-(3-(((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-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]pyridine-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]pyridine-2-yl)methyl)amino)methyl)pyrrolidin-2-one; (S)-5-((((2',2''-dimethyl-3''-(2-(((((S)-5-oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one; 2-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-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]pyridine-3-yl)methyl)-D-proline; (S)-5-((((2',2''-Dichloro-3''-(3-(((((S)-5-Oxopyrrolidine-2-yl)methyl)amino)methyl)-[1,2,4]Triazolo[4,3-a]pyridine-7-yl)-[1,1':3',1''-Terphenyl]-4-yl)methyl)amino)methyl)pyrrolidine-2-one; 2-(((2',2''-Dichloro-3''-(2-(((1-Hydroxy-2-methylpropan-2-yl)amino)methyl)-[1,2,4]Triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-Terphenyl]-4-yl)methyl)amino)-2-methylpropan-1-ol; 2-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)-2-methylpropan-1-ol; ((7-(4''-(((S)-2-carboxypyrrolidine-1-yl)methyl)-2,2'-dichloro-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl)methyl)-L-proline; ((7-(4''-(((R)-2-carboxypyrrolidine-1-yl)methyl)-2,2'-dichloro-[1,1':3',1''-terphenyl]-3-yl)-[1,2,4]triazolo[1,5-a]pyridine-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]pyridine-2-yl)methyl)amino)ethyl)acetamide; (S)-2-(((7-(2,2'-Dichloro-4''-((2-(hydroxymethyl)pyrroridine-1-yl)methyl)-[1,1':3',1''-Terphenyl]-3-yl)-[1,2,4]Triazolo[1,5-a]pyridine-2-yl)methyl)amino)ethane-1-ol (R)-2-(((7-(2,2'-Dichloro-4''-((2-(hydroxymethyl)pyrroridine-1-yl)methyl)-[1,1':3',1''-Terphenyl]-3-yl)-[1,2,4]Triazolo[1,5-a]pyridine-2-yl)methyl)amino)ethane-1-ol; 3-(((2',2''-Dichloro-3''-(2-(((2-hydroxyethyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)propan-1-ol; 3-(((2',2''-Dichloro-3''-(2-(((3-hydroxycyclobutyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)cyclobutan-1-ol; 3-(((2',2''-Dichloro-3''-(2-(((3-hydroxypropyl)amino)methyl)-[1,2,4]triazolo[1,5-a]pyridine-7-yl)-[1,1':3',1''-terphenyl]-4-yl)methyl)amino)propan-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]pyridine-2-yl)methyl)amino)-2-methylpropane-1-ol A compound according to claim 1, selected from the following.

14. A pharmaceutical composition comprising a compound according to any one of claims 1 to 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 to 13, or a pharmaceutically acceptable salt or stereoisomer thereof, or a composition according to claim 14, for use in a method of treating cancer.

16. A compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt or stereoisomer thereof, or a composition according to claim 14, for use in a method of treating an infection, preferably a viral, bacterial, or fungal infection.

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