5-cyclopropylpicolinamide derivative, preparation method therefor, and pharmaceutical composition comprising same for preventng or treating cancer

Abstract

The present invention relates to a 5-cyclopropylpicolinamide derivative represented by chemical formula I or II, and the like. The compound and the like according to the present invention have an inhibitory ability against HPK1, and thus can be effectively used in the prevention, amelioration, and / or treatment of diseases related thereto.

Description

5-cyclopropylpicolineamide derivative, method for preparing the same, and pharmaceutical composition for the prevention or treatment of cancer containing the same

[0001] The present invention relates to a novel 5-cyclopropylpicolineamide derivative, a method for producing the same, and uses thereof.

[0002] Cross-citation with related application(s)

[0003] This application claims the benefit of priority based on Korean Patent Application No. 10-2024-0140722 dated October 15, 2024, and all contents disclosed in the document of said Korean patent application are incorporated herein as part of this specification.

[0004] Immunotherapy for cancer is one of the treatment methods that has recently garnered significant attention in the field of cancer treatment. It exerts anticancer effects by activating the patient's immune system to induce an attack on cancer cells, and is reported to have fewer side effects than conventional treatments. In particular, immune checkpoint inhibitors (ICIs), which suppress immune checkpoints such as PD-1, PD-L1, and CTLA-4, enhance the anti-tumor immune response by inhibiting immune checkpoints that block the activation of immune cells. This allows for long-term sustained effects and can increase the likelihood of long-term survival for patients. However, there are limitations, as a significant number of patients do not respond to these immune checkpoint inhibitors or develop resistance over time, and the objective response rate is known to be only around 20-30% on average. Therefore, numerous studies are being conducted to overcome the limitations of low response rates associated with immunotherapies, including immune checkpoint inhibitors. Recently, attempts have been made to improve patient response rates by combining immune checkpoint inhibitors with other immune-activating agents. However, while treatment using immune checkpoint inhibitors has shown potential, it responds only to a portion of cancer patients, so there is a need for new treatments that can be used for a diverse range of patients.

[0005] Meanwhile, T cells are immune cells that play a crucial role in the cancer immune cycle, functioning as effector cells that recognize and kill tumor cells. In cancer patients, T cells continuously exposed to antigens enter a fatigued state within the tumor microenvironment and eventually lose their function. Furthermore, tumor-inhibitory signals such as PGE2, TGFβ, and adenosine interfere with T cell function. Therefore, therapies that enhance T cell function and restore the function of fatigued T cells can lead to improved tumor control.

[0006] Hematopoietic progenitor kinase 1 (HPK1), one of the various targets of immune activators, is a hematopoietic cell-specific Ste20-family serine / threonine kinase, also known as MAP4K1 (Mitogen-activated protein kinase kinase 1). HPK1 contains a kinase domain at its N-terminus that includes an ATP binding site. Additionally, the intermediate domain of HPK1 is a proline-rich motif that possesses binding sites for SH3-containing proteins such as Crkl, Grb2, and HIP-55, suggesting scaffolding functions such as recruiting and scaffolding. The C-terminus of HPK1 contains a citron homology domain, which acts as a regulatory domain in molecular interactions, including T cell adhesion. LCK and ZAP70, which are TCR signaling initiators, induce Tyr-379 phosphorylation and kinase activation of HPK1. As such, essential adapters for T cell (SLP76) and B cell (BLNK) signaling are known to bind to activated HPK1, which assists in blocking downstream signaling in both T cells and B cells. Therefore, small molecule kinase inhibitors targeting HPK1 can be used in cancer immunotherapy.

[0007] More specifically, HPK1 functions as a key negative regulator of the T cell receptor (TCR) signaling pathway; activated HPK1 acts as a brake on excessive T cell activation signals by inducing T cell proliferation, cytokine secretion, and the weakening of cytotoxic functions. HPK1 functions as a negative regulator of various subtypes of cell surface receptors on hematopoietic cells, including not only TCRs but also B cell receptors (BCRs), and is involved in regulating the function of dendritic cells, which are antigen-presenting cells (APCs). Therefore, the regulation of HPK1 is expected to achieve a dual effect, contributing to the long-term activation of T cells while also enhancing the antigen-presenting function of dendritic cells. This dual targeting can exert a synergistic effect in overcoming immunosuppression within the tumor microenvironment and suppressing tumors.

[0008] Furthermore, HPK1 inhibitors can be used alone or in combination with other therapeutic agents for cancer treatment. For example, HPK1 inhibitors can be used in combination with checkpoint blockers such as PD-L 1-axis or CTLA4 to increase the response rate to checkpoint blockade. Therefore, primary or secondary resistance to immune checkpoint blockades may be a potential indication for HPK1 inhibitors. In addition to immunotherapy, radiation, chemotherapy, surgery, tumor-targeting agents, or other immune-targeting agents may be used in combination with HPK1 inhibitors. Therefore, there is a need for the development of substances that can activate the immune system by inhibiting HPK1 and achieve excellent anticancer effects through combination with existing immunotherapy.

[0009] [Prior Art Literature]

[0010] (Non-patent literature 1) Liou et al., Immunity 2000; Sauer et al., JBC 2001

[0011] Under the background described above, the inventors of the present invention have investigated novel HPK1 inhibitors capable of fundamentally enhancing anti-tumor immune function and have confirmed that the novel 5-cyclopropylpicolineamide derivative according to the present invention has a strong inhibitory ability against HPK1 and can effectively inhibit tumor growth when used in combination with anticancer immunotherapy.

[0012] Accordingly, one example of the present invention is to provide a compound represented by the following formula I, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt:

[0013] [Chemical Formula I]

[0014]

[0015] (In the above chemical formula I,

[0016] X is C or N and;

[0017] Y1, Y2, Y3, and Y4 are each independently C, N, O, or S;

[0018] Z1 is absent, or H or C 1-4 It is alkyl;

[0019] Z2 and Z3 are each independently absent, or H, deuterium, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, 4-12-membered heterocyclil, hydroxyl, halogen, cyano, CO-H, CO-(C 1-4 Alkyl), CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), CO-N(C 1-4Alkyl)2, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, oxetanil, SO2-(C 1-4 alkyl), SO2-NH2, SO2-NH(C 1-4 alkyl), or SO2-N(C 1-4 Alkyl)2 and,

[0020] Here, the above C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 6-12 Aril, 4-12 won Heteroaryl, quaternary-12ary heterocyclils, tetrahydrofuranil, tetrahydropyranil, piperazinyl, piperidinyl, and oxetanil are halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 Substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2;

[0021] Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It is a haloalkyl.

[0022] Another example of the present invention is to provide a compound represented by the following formula II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt:

[0023] [Chemical Formula II]

[0024]

[0025] (In the above chemical formula II,

[0026] X is C or N and;

[0027] Y1, Y2, Y3, and Y4 are each independently C, N, O, or S;

[0028] Z1 is absent, or H or C 1-4 It is alkyl;

[0029] Cycle A is C3- 12 Cycloalkyl, C3- 12 Cycloalkenyl, C3- 12 Cycloalkinyl, C 6-12 It is an aryl, a 4-12-membered heterocycloalkyl, a 4-12-membered heterocycloalkenyl, a 4-12-membered cycloalkynyl, or a 4-12-membered heteroaryl, and

[0030] Here, the above Cycle A is deuterium, halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 Substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2;

[0031] Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It is a haloalkyl.

[0032] Another example of the present invention is to provide a pharmaceutical composition for the prevention, improvement, and / or treatment of cancer, comprising a compound of Formula I or II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt.

[0033] Another example of the present invention is to provide a pharmaceutical composition for the prevention, improvement, and / or treatment of cancer, comprising (a) a compound of formula I or II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt; and (b) an immune checkpoint inhibitor.

[0034] Another example of the present invention is to provide a composition for inhibiting hematopoietic progenitor kinase 1 (HPK1), comprising a compound of formula I or II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt.

[0035] Another example of the present invention is to provide a pharmaceutical composition for immunostimulating, comprising a compound of Formula I or II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt.

[0036] The present disclosure is summarized as follows:

[0037] 1. Compounds represented by the following chemical formula I, their enantiomers, diastereomers, tautomers, hydrates, solvates, or pharmaceutically acceptable salts:

[0038] [Chemical Formula I]

[0039]

[0040] In the above chemical formula I,

[0041] X is C or N and;

[0042] Y1, Y2, Y3, and Y4 are each independently C, N, O, or S;

[0043] Z1 is absent, or H or C 1-4 It is alkyl;

[0044] Z2 and Z3 are each independently absent, or H, deuterium, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, 4-12-membered heterocyclil, hydroxyl, halogen, cyano, CO-H, CO-(C 1-4 Alkyl), CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), CO-N(C 1-4 Alkyl)2, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, oxetanil, SO2-(C 1-4 alkyl), SO2-NH2, SO2-NH(C 1-4 alkyl), or SO2-N(C 1-4 Alkyl)2 and,

[0045] Here, the above C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 6-12 Aril, 4-12 won Heteroaryl, quaternary-12ary heterocyclils, tetrahydrofuranil, tetrahydropyranil, piperazinyl, piperidinyl, and oxetanil are halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 Substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2;

[0046] Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It is a haloalkyl.

[0047]

[0048] 2. Compounds represented by the following chemical formula II, their enantiomers, diastereomers, tautomers, hydrates, solvates, or pharmaceutically acceptable salts:

[0049] [Chemical Formula II]

[0050]

[0051] In the above chemical formula II,

[0052] X is C or N and;

[0053] Y1, Y2, Y3, and Y4 are each independently C, N, O, or S;

[0054] Z1 is absent, or H or C 1-4 It is alkyl;

[0055] Cycle A is C3- 12 Cycloalkyl, C3- 12 Cycloalkenyl, C3- 12 Cycloalkinyl, C 6-12 It is an aryl, a 4-12-membered heterocycloalkyl, a 4-12-membered heterocycloalkenyl, a 4-12-membered cycloalkynyl, or a 4-12-membered heteroaryl, and

[0056] Here, the above Cycle A is deuterium, halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 Substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2;

[0057] Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It is a haloalkyl.

[0058]

[0059] 3. In the above Paragraph 2,

[0060] The above Cycle A is cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptyl, cyclooctyl, azetidinyl, benzimidazolyl, benzofuranil, benzofurazanil, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranil, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazolin, isoxazoline, oxetanil, pyranil, pyrazinyl, Pyrazolyl, pyridazinyl, pyridopyridinyl, pyridyl, pyrimidyl, pyrrolyl, morpholino, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranil, tetrahydrothiopyranil, tetrahydroisoquinolinil, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, 1,4-dioxanyl, hexahydroazefinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholyl, thiomofolinyl, dihydrobenzoimidazolyl, dihydrobenzofuranil, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranil, Compounds, enantiomers, diastereomeric isomers, tautomeric isomers, hydrates, solvates, or pharmaceutically acceptable salts thereof, which are dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, or tetrahydrothienyl.

[0061]

[0062] 4. In the above Paragraph 1,

[0063] In the above chemical formula I

[0064] X is N and;

[0065] Y2 and Y3 are each N;

[0066] Z2 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12 heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinil, or oxetanil, and

[0067] Here, the above Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0068]

[0069] 5. In any one of the preceding paragraphs,

[0070] In the above chemical formula I

[0071] X is N and;

[0072] Y1 and Y2 are each N;

[0073] Z2 is absent, or H, C 1-10 Alkyl, C1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12 heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinil, or oxetanil, and

[0074] Here, the above Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0075]

[0076] 6. In any one of the preceding paragraphs,

[0077] In the above chemical formula I

[0078] X is N and;

[0079] Y1, Y2, and Y4 are each N;

[0080] Z2 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12 heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinil, or oxetanil, and

[0081] Here, the above Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0082]

[0083] 7. In any one of the preceding paragraphs,

[0084] In the above chemical formula I

[0085] X is N and;

[0086] Y1 and Y3 are each N;

[0087] Z3 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, 4-12-membered heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinil, oxetanil, and

[0088] Here, the above Z3 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0089]

[0090] 8. In any one of the preceding paragraphs,

[0091] In the above chemical formula II

[0092] X is N and;

[0093] Y1 is N and;

[0094] Cycle A is C 4-6 It is a cycloalkyl or a quaternary to hexavalent heterocycloalkyl, wherein Cycle A is C 4-6 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, wherein Y2 and Y3 are each C when the Cycle A is a cycloalkyl, and Y2 is N and Y3 is C, N, O, or S when the Cycle A is a quaternary to hexavalent heterocycloalkyl.

[0095]

[0096] 9. In any one of the preceding paragraphs,

[0097] The above chemical formula I is a compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is represented by any one of the following structures:

[0098] [Chemical Formula I-1]

[0099]

[0100] [Chemical Formula I-2]

[0101]

[0102] [Chemical Formula I-3]

[0103]

[0104] [Chemical Formula I-4]

[0105]

[0106] [Chemical Formula I-5]

[0107]

[0108]

[0109] 10. In any one of the preceding paragraphs,

[0110] The compound represented by the above chemical formula I is selected from the group consisting of the following compounds: a compound, its enantiomer, its diastereomer, its solvate, its tautomer, or its pharmaceutically acceptable salt:

[0111] 1) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0112] 2) 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0113] 3) 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0114] 4) 5-cyclopropyl-3-((1-ethyl-1H-1,2,4-triazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0115] 5) 5-cyclopropyl-3-((3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0116] 6) 5-cyclopropyl-3-((1-(1-hydroxy-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0117] 7) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)picolinamide,

[0118] 8) 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0119] 9) 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0120] 10) 5-cyclopropyl-3-((1,5-dimethyl-1H-imidazole-4-yl)amino)-6-(3-methyl-3H-imidazoo[4,5-c]pyridine-7-yl)picolinamide,

[0121] 11) 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0122] 12) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)picolinamide,

[0123] 13) 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0124] 14) 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide,

[0125] 15) 5-cyclopropyl-3-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0126] 16) 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0127] 17) 5-cyclopropyl-3-((3-fluoro-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0128] 18) 5-cyclopropyl-3-((3-(difluoromethyl)-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0129] 19) 5-cyclopropyl-3-((1-isopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide,

[0130] 20) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1-methylpiperidine-4-yl)-1H-pyrazole-4-yl)amino)picolinamide,

[0131] 21) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)picolinamide,

[0132] 22) 5-cyclopropyl-3-((1-ethyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0133] 23) 5-cyclopropyl-3-((1-(difluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0134] 24) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-4-yl)amino)picolinamide,

[0135] 25) 5-cyclopropyl-3-((1-cyclopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0136] 26) 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0137] 27) 5-cyclopropyl-3-((1-(difluoromethyl)-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0138] 28) 5-cyclopropyl-3-((1-isobutyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0139] 29) 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide,

[0140] 30) 5-cyclopropyl-3-((3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0141] 31) 5-cyclopropyl-3-((1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0142] 32) 5-cyclopropyl-3-((3-cyclopropyl-1-methyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0143] 33) 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0144] 34) 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0145] 35) 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0146] 36) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0147] 38) 5-cyclopropyl-3-((1-ethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0148] 39) 5-cyclopropyl-3-((1-isobutyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0149] 40) 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0150] 42) 3-((1-(tert-butyl)-3-methyl-1H-pyrazole-4-yl)amino)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0151] 43) 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0152] 44) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0153] 45) 5-cyclopropyl-3-((5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0154] 46) 5-cyclopropyl-3-((1-(2,2-difluoropropyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0155] 47) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-3-yl)amino)picolinamide,

[0156] 49) 5-cyclopropyl-3-((5-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0157] 50) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0158] 51) 5-cyclopropyl-3-((1-isopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0159] 52) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0160] 53) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0161] 54) 5-cyclopropyl-3-((3-fluoro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0162] 55) 5-cyclopropyl-3-((3-fluoro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0163] 56) 5-cyclopropyl-3-((1-cyclopropyl-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0164] 57) 5-cyclopropyl-3-((1-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0165] 58) 5-cyclopropyl-3-((1,5-dimethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0166] 59) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolineamide,

[0167] 60) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0168] 61) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-3-yl)amino)picolinamide,

[0169] 62) 5-cyclopropyl-3-((3-fluoro-1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0170] 63) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0171] 64) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0172] 65) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0173] 66) 5-cyclopropyl-3-((1-((1s,3s)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0174] 67) 5-cyclopropyl-3-((1-((1r,3r)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, or

[0175] 68) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((1s,3s)-3-(trifluoromethyl)cyclobutyl)-1H-pyrazole-3-yl)amino)picolinamide.

[0176]

[0177] 11. In any one of the preceding paragraphs,

[0178] The compound represented by the above chemical formula II is selected from the group consisting of the following compounds: a compound, its enantiomer, its diastereomer, its solvate, its tautomer, or its pharmaceutically acceptable salt:

[0179] 37) 5-cyclopropyl-3-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0180] 41) 5-cyclopropyl-3-((5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, and

[0181] 48) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-yl)amino)picolineamide.

[0182]

[0183] 12. A pharmaceutical composition for the prevention or treatment of cancer comprising the compound of any one of the preceding claims, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt.

[0184]

[0185] 13. In any one of the preceding paragraphs,

[0186] A pharmaceutical composition comprising, further comprising a pharmaceutically acceptable carrier, diluent, or excipient.

[0187]

[0188] 14. In any one of the preceding paragraphs,

[0189] The above cancers include blastoma, sarcoma, colorectal cancer, rectal cancer, colon cancer, colorectal cancer, thyroid cancer, oral cancer, pharyngeal cancer, laryngeal cancer, cervical cancer, brain cancer, brain tumor, glioblastoma, medulloblastoma, neuroblastoma, lung cancer, small cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous cell carcinoma, ovarian cancer, bladder cancer, kidney cancer, renal cell carcinoma, clear cell renal cell carcinoma, liver cancer, hepatocellular carcinoma, pancreatic cancer, prostate cancer, skin cancer, tongue cancer, breast cancer, uterine cancer, stomach cancer, bone cancer, lymphoma, blood cancer, peritoneal cancer, skin cancer, melanoma, cutaneous melanoma, ocular melanoma, rectal cancer, prostatic cancer, esophageal cancer, small intestine cancer, osteosarcoma, endocrine gland cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, gastric cancer, glioblastoma, ovarian cancer, endometrial cancer, salivary gland cancer, vulvar cancer, ependymoma. A pharmaceutical composition comprising one or more selected from the group consisting of Ewing's sarcoma, rhabdomyosarcoma, rhabdomyocarcinoma, renal cell tumor (Wilm's tumor), head and neck cancer, leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, lipoma, lipoblastoma, hibernation tumor, liposarcoma, leiomyoma, leiomyosarcoma, neurofibroma, and malignant Schwann tumor.

[0190]

[0191] 15. A composition for inhibiting hematopoietic progenitor kinase 1 (HPK1), comprising the compound of any one of the preceding claims, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt.

[0192]

[0193] 16. A pharmaceutical composition for immunostimulating, comprising the compound of any one of the preceding claims, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt.

[0194]

[0195] 17. A method for preparing a compound represented by the formula I of any one of the preceding claims, comprising the step of performing a Buchwald-Hartwig coupling of a compound represented by the following formula (i):

[0196] [Chemical formula (i)]

[0197]

[0198] In the above chemical formula (i),

[0199] X is C or N and;

[0200] W1 is an amine or a halo;

[0201] W2 is H, hydroxyl, C 1-4 alkyl, or C 1-4 It is an alkoxy.

[0202]

[0203] 18. A method for preparing a compound represented by Formula II of any one of the preceding claims, comprising the step of performing a Buchwald-Hartwig coupling reaction of a compound represented by the following formula (i):

[0204] [Chemical formula (i)]

[0205]

[0206] In the above chemical formula (i),

[0207] X is C or N and;

[0208] W1 is an amine or a halo;

[0209] W2 is H, hydroxyl, C 1-4 alkyl, or C 1-4It is an alkoxy.

[0210] However, the technical problems that the present invention aims to solve are not limited to those mentioned above, and other unmentioned problems will be clearly understood by those skilled in the art to which the present invention belongs from the description below.

[0211] The present specification relates to compounds of Formula I or II, enantiomers, diastereomers, tautomers, hydrates, solvates, or pharmaceutically acceptable salts thereof; methods for preparing the same; and uses thereof (e.g., uses for the prevention, improvement, and / or treatment of cancer; uses for inhibiting hematopoietic progenitor kinase 1 (HPK1); and uses for immune enhancement, etc.).

[0212] Through the experimental examples described below, it has been confirmed that the compound according to the present invention not only effectively inhibits HPK1 but also exhibits high specificity for HPK1 compared to GLK (Germinal Center Kinase-Like Kinase) and can regulate phosphorylated SLP-76, which is capable of blocking the TCR signaling pathway. In particular, when combined with immune checkpoint inhibitors, the compound according to the present invention can effectively inhibit tumor growth in animal models of cancer at a lower dose than that of previously known HPK1 inhibitors. Accordingly, the compound provided herein, its enantiomers, diastereomers, tautomers, hydrates, solvates, or pharmaceutically acceptable salts may be usefully employed for the prevention, improvement, and / or treatment of cancer, as well as for use in combination with anticancer immunotherapy or for immune enhancement.

[0213] Hereinafter, the compound of the present invention, the method of manufacturing the same, and the use thereof will be described in more detail.

[0214]

[0215] Definition of Terms

[0216] Unless otherwise defined, all technical terms used herein have the same meaning as generally understood by those skilled in the art to which the present invention pertains. Furthermore, although the present invention has been described in relation to specific methods and samples, analogs or equivalents thereof must be within the scope of the present invention. Additionally, numerical values ​​described herein are deemed to include the meaning of “about” unless explicitly stated otherwise. All publications and other references mentioned herein are incorporated herein by reference in their entirety.

[0217] Unless otherwise stated below, the “compound of Formula I” of the present invention includes all of the compound of Formula I, its enantiomer, diastereomer, tautomer, hydrate, solvate, and / or pharmaceutically acceptable salt, and the “compound of Formula II” includes all of the compound of Formula II, its enantiomer, diastereomer, tautomer, hydrate, solvate, and / or pharmaceutically acceptable salt, and all of these should be interpreted as being included within the scope of the present invention. Additionally, the compound of Formula I or II of the present invention may be referred to as the “compound of the present invention,” “5-cyclopropylpicolineamide derivative,” etc.

[0218] That is, unless otherwise specified, the chemical formulas or names given in the specification and claims include not only tautomers but also all stereochemical, optical, and geometric isomers (e.g., enantiomers, diastereomers, E / Z isomers, etc.). Furthermore, the scope of the invention includes not only their racemates but also mixtures of distinct enantiomers in different proportions, mixtures of diastereomers, or any of the above forms of mixtures in which isomers and enantiomers are present, and further encompasses their pharmaceutically acceptable salts, solvates and hydrates of free compounds, or solvates of salts of said compounds.

[0219] As used herein, the term "alkyl" refers to an aliphatic hydrocarbon radical, meaning a linear and branched monovalent hydrocarbon having the indicated number of carbon atoms unless otherwise stated, and includes structural isomers. For example, C 1-7 Alkyl refers to an aliphatic hydrocarbon having 1 to 7 carbon atoms. In this specification, the term alkyl may be used as a concept encompassing both “saturated alkyl,” meaning not containing any alkene or alkyne groups, and “unsaturated alkyl,” meaning containing at least one alkene or alkyne group; however, it preferably refers to a saturated alkyl. In one embodiment of the present invention, the alkyl is C 1-20 , C 1-15 , C 1-12 , C 1-10 , C 1-8 , C 1-7 , C 1-6 , C 1-5 , C 1-4 , C 1-3 , or C 1-2 It may be an alkyl, but is not limited thereto.

[0220] In this specification, the term “heteroalkyl” refers to an alkyl group comprising at least one heteroatom (e.g., O, S, N, P, etc.) in addition to carbon and hydrogen. Like alkyls, heteroalkyls may also include branched or straight-chain forms and include structural isomers.

[0221] More specific examples of alkyls include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, n-heptyl, 1-methylhexyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethyl-propyl, 1,1-dimethyl-butyl, 2,2-dimethyl-butyl, 3,3-dimethyl-butyl, 1,1-dimethyl-propyl, isohexyl, Examples include 2-methylpentyl, 4-methylhexyl, 5-methylhexyl, etc., but the scope of the present invention is not limited thereto.

[0222] As used in this specification, the term "haloalkyl" refers to an alkyl group substituted with one or more halogen atoms, wherein "alkyl" is defined as above. "Halo" indicates a substituent of fluoro(-F), chloro(-Cl), bromo(-Br), or iodo(-I), and the term is used interchangeably with the term "halogen." The haloalkyl includes monohaloalkyl (where one hydrogen is substituted with a halogen), dihaloalkyl (where two hydrogens are substituted with a halogen), trihaloalkyl (where three hydrogens are substituted with a halogen), etc., and the substitution position may be present on any carbon atom of a straight-chain or branched alkyl. Specific examples of the haloalkyl include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, chloroethyl, bromopropyl, dichloropropyl, and trifluoroethyl.

[0223] As used herein, the term "alkenyl" refers to a group in which at least two carbon atoms are connected by at least one carbon-carbon double bond, and may be a straight chain or a branched chain. In one embodiment of the present invention, the alkenyl is C 2-20 , C 2-15 , C 2-12 , C 2-10, C 2-8 , C 2-7 , C 2-6 , C 2-5 , C 2-4 , or C 2-3 It may be an alkenyl, but is not limited to this.

[0224] More specific examples of alkenyls include ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, or 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propene, 1-ethyl-1-methyl-2-propene, 1-ethyl-2-methyl-1-propene, 1-ethyl-2-methyl-2-propene, 1-heptenyl, 2-heptenyl, 3-heptenyl, 1-octenyl, 2-octenyl, 3-octenyl, 4-octenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 4-nonenyl, 1-decenyl,Examples include 2-decenyl, 3-decenyl, 4-decenyl, and 5-decenyl, but the scope of the present invention is not limited thereto.

[0225] As used herein, the term "alkynyl" refers to a group in which at least two carbon atoms are connected by at least one carbon-carbon triple bond, and may be a straight chain or a branched chain. In the present invention, the alkynyl is C 2-20 , C 2-15 , C 2-12 , C 2-10 , C 2-8 , C 2-6 , C 2-5 , C 2-4 , or C 2-3 It may be an alkinyl, but is not limited to this.

[0226] As used herein, the term “hydroxyl (hydroxy)” refers to -OH, and “hydroxyalkyl” refers to a group in which one or more hydroxyls are bonded to any carbon atom within the alkyl group. Here, the alkyl group is defined as above, and the number of substituted hydroxyls may be one or more. The hydroxyalkyl group is C 1-20 , C 1-15 , C 1-12 , C 1-10 , C 1-8 , C 1-7 , C 1-6 , C 1-5 , C 1-4 , C 1-3 , or C 1-2 It may be a hydroxyl alkyl, but is not limited thereto.

[0227] As used herein, the term “cyano” refers to -CN, and “cyanoalkyl” refers to a group in which one or more cyanos are bonded to any carbon atom within the alkyl group. Here, the alkyl is defined as above, and the number of substituted cyanos may be one or more. The cyanoalkyl is C 1-20 , C 1-15 , C 1-12 , C 1-10 , C 1-8 , C1-7 , C 1-6 , C 1-5 , C 1-4 , C 1-3 , or C 1-2 It may be a cyanoalkyl, but is not limited thereto.

[0228] As used herein, the term “deuterium” refers to an isotope of hydrogen having a mass number of 2. The term “deuteride alkyl” means that at least one of any hydrogen atoms within an alkyl group is substituted with a deuterium atom, wherein alkyl is defined as above. The deuteride alkyl is deuteride C 1-20 , C 1-15 , C 1-12 , C 1-10 , C 1-8 , C 1-7 , C 1-6 , C 1-5 , C 1-4 , C 1-3 , or C 1-2 It may be an alkyl, but is not limited thereto.

[0229] As used herein, the term “alkoxy” refers to a substituent having a structure in which an alkyl group is connected through an oxygen atom, and may mean -O-alkyl or alkyl-O-. Here, alkyl is defined as above. For example, the alkoxy may be a straight chain, a branched chain, or a cyclic chain. In the present invention, the alkoxy is C 1-20 , C 1-15 , C 1-12 , C 1-10 , C 1-9 , C 1-8 , C 1-7 , C 1-6 , C 1-5 , C 1-4 , C 1-3 , or C 1-2It may be an alkoxy, but is not limited thereto. More specific examples of alkoxy include methoxy, ethoxy, n-propoxy, isopropoxy, i-propyloxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentyloxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutyloxy, 2-ethylbutyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, benzyloxy, p-methylbenzyloxy, or their monohalogenated and polyhalogenated variants, but the scope of the present invention is not limited thereto.

[0230] As used in this specification, the term “amide” refers to a functional group having a structure in which an amino is bonded to a carbonyl, and may be represented as -CO-NR2-. Here, the R may include the substituents described in this specification without limitation. If R has two hydrogens, it is called a primary amide; if one is substituted, it is called a secondary amide; and if both are substituted, it is called a tertiary amide.

[0231] The term “sulfonyl” as used in this specification refers to a substituent having a structure (-SO2-) in which a sulfur atom is double-bonded to two oxygen atoms, and the sulfur atom can be connected to another atom or group through two bonds.

[0232] The term “sulfonylamide” as used in this specification refers to a functional group having a structure in which a sulfonyl is bonded to an amino, and may be represented as -SO2-NR2-. Here, the R may include the substituents described in this specification without limitation. Depending on the degree of substitution of R, it is classified as a primary, secondary, or tertiary sulfonylamide.

[0233] As used herein, the terms “ring,” “cycle,” “cyclic,” and “cyclile” refer to cyclic hydrocarbon groups and encompass concepts including monocyclic, bicyclic, tricyclic, or polycyclic structures. Furthermore, the ring in this specification may be a saturated or partially unsaturated ring and encompasses concepts including both aromatic and non-aromatic rings. “Heteroring” or “heterocycle” refers to a ring containing one or more heteroatoms. In this case, the one or more heteroatoms may be of the same or different types. The term “membered,” used in conjunction with ring, refers to the number of skeletal atoms constituting the ring.

[0234] As used herein, the term "cycloalkyl" refers to a monovalent cyclic alkyl that may be substituted or unsubstituted. The cycloalkyl may comprise a saturated or partially unsaturated structure, but is preferably a saturated hydrocarbon ring structure. For example, C3- 20 Cycloalkyl may refer to a saturated hydrocarbon ring system having 3 to 20 carbon atoms. The cycloalkyl may be monovalent or polyvalent, and may be a monocyclic or polycyclic ring. The cycloalkyl is C 3-20 , C 3-15 , C 3-12 , C 3-10 , C 3-8 , C 3-6 , C 3-5 , C 3-4 , C 5-7 , C 5-6...or may be C3 cycloalkyl, but is not limited thereto. Specific examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, 3-methylcyclopentyl, 2,3-dimethylcyclopentyl, indanyl, cyclohexyl, cyclohexylene, 3-methylcyclohexyl, 4-methylcyclohexyl, 2,3-dimethylcyclohexyl, 3,4,5-trimethylcyclohexyl, 4-tert-butylcyclohexyl, cycloheptyl, and cyclooctyl, but the scope of the present invention is not limited thereto.

[0235] The cyclic hydrocarbon groups described in this specification may include, in addition to cycloalkyls of a saturated structure, partially unsaturated rings, such as cycloalkenyl and cycloalkynyl.

[0236] As used herein, the term “cycloalkenyl” refers to an unsaturated hydrocarbon ring substituent comprising one or more carbon-carbon double bonds within a ring structure. The cycloalkenyl may be monovalent or polyvalent and may be a monocyclic or polycyclic ring. The cycloalkenyl is C 3-20 , C 3-15 , C 3-12 , C 3-10 , C 3-8 , C 3-6 , C 3-5 , C 3-4 , C 5-7 , C 5-6 , or may be a C3 cycloalkenyl, but is not limited thereto. Specific examples of cycloalkenyls include cyclopentenyl, cyclohexenyl, etc., but are not limited thereto.

[0237] As used herein, the term “cycloalkynyl” refers to an unsaturated hydrocarbon ring substituent comprising one or more carbon-carbon triple bonds within a ring structure. The cycloalkynyl may be monovalent or polyvalent and may be a monocyclic or polycyclic ring. The cycloalkynyl is C 3-20 , C 3-15 , C 3-12 , C3-10 , C 3-8 , C 3-6 , C 3-5 , C 3-4 , C 5-7 , C 5-6 , or may be a C3 cycloalkynyl, but is not limited thereto.

[0238] As used herein, the term “aryl” refers to a monovalent or polyvalent ring that is polyunsaturated and typically includes an aromatic ring. The aryl may be a monocyclic or polycyclic ring. In the case of a polycyclic ring, it may include a saturated or partially unsaturated ring along with an aromatic ring. In the present invention, the aryl is C 6-20 , C 6-15 , C 6-12 , C 6-11 , C 6-10 , C 6-9 , C 6-8 , C 6-7 Or it may be a C6 aryl, but is not limited thereto. Specific examples of the above aryls include monocyclic aryls such as phenyl, biphenyl, terphenyl, toluyl, and quaternphenyl, and polycyclic aryls such as naphthyl, naphthalenyl, indenyl, anthracenyl, phenanthrenyl, pyrenyl, and benzopyrenyl, but the scope of the present invention is not limited thereto.

[0239] As used herein, the term "heterocyclile(ril)" refers to a ring comprising, along with carbon atoms, one or more heteroatoms selected from non-carbon atoms, such as N, O, P, and S (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom) as ring constituents. Here, when the number of heteroatoms constituting a heterocyclile is 2 or more, the types of each heteroatom may be the same or different from one another. The heterocyclile may be monovalent or polyvalent, aromatic or non-aromatic, a monocyclic or polycyclic ring, and may have a saturated or partially unsaturated structure. Accordingly, the scope of the term heterocyclile includes heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, and heteroaryl, etc. Non-limiting examples of the above heterocyclils include thiophenyl, furanyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, pyridinyl, bipyridinyl, pyrimidinyl, triazinyl, triazolyl, pyridazinyl, pyrazinyl, pyridopyrimidyl, pyridopyrazinyl, pyrazinopyrazinyl, isooxazolyl, thiadiazolyl (e.g., 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl), dihydrothiopyraniyl, etc., but the scope of the present invention is not limited thereto.

[0240] As used herein, the term “heterocycloalkyl” refers to a cycloalkyl comprising one or more heteroatoms selected from N, O, P, and S (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom) as ring constituents. Herein, cycloalkyl is defined as above. That is, the heterocycloalkyl may be monovalent or polyvalent, and may be a monocyclic or polycyclic ring. The above heterocycloalkyl may be a 3 to 16-membered, 3 to 15-membered, 3 to 14-membered, 3 to 13-membered, 3 to 12-membered, 3 to 11-membered, 3 to 10-membered, 3 to 9-membered, 3 to 8-membered, 3 to 7-membered, 3 to 6-membered, 3 to 5-membered, 3 to 4-membered, 4 to 16-membered, 4 to 15-membered, 4 to 14-membered, 4 to 13-membered, 4 to 12-membered, 4 to 11-membered, 4 to 10-membered, 4 to 9-membered, 4 to 8-membered, 4 to 7-membered, 4 to 6-membered, 4 to 5-membered, 5 to 7-membered, or 5 to 6-membered heterocycloalkyl. However, it is not limited to this.

[0241] Specific examples of the above heterocycloalkyl include tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyrimidinyl, tetrahydropyridazinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyrazolopyridinyl, morpholino, oxetanyl, azetidinyl, diazetidinyl, triazetidinyl, diazcyclohexane derivatives, 1,4-dioxanyl, piperazinyl, piperazindianil, piperidinyl, pyrrolidinyl, morpholino, thiomopolinyl, thiomopolininid oxa-azaspiroheptyl, hexahydroazefinyl, hexahydropuropyrrolyl, oxa-azabicycloheptyl, imidazolidinyl, imidazolidinyl, 1,2-diazolidinyl. 1,4-Diazolidinyl, Triazolidinyl, Lactamyl, Tetrahydropyranil, Tetrahydrofuranil, Diazabicyclooctanil, Oxaindollyl, Benzoxazinonyl, Oxacyclobutanil, Azetidinyl, Azethiomophorinyl, Diazaspirooctanil, Tetrahydroisoquinolinyl, Dihydrobenzimidazolyl, Dihydropyranil, Dihydrotetrazollyl, Dihydrobenzofuranil, Dihydrobenzothiophenyl, Dihydrobenzoxazolyl, Dihydroindollyl, Dihydroazetidinyl, etc., but are not limited thereto.

[0242] As used herein, the term “heterocycloalkenyl” refers to a cycloalkenyl comprising one or more heteroatoms selected from N, O, P, and S (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom) as ring constituents. Herein, cycloalkenyl is defined as above. The above heterocycloalkenyl is 3 to 16, 3 to 15, 3 to 14, 3 to 13, 3 to 12, 3 to 11, 3 to 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6, 3 to 5, 3 to 4, 4 to 16, 4 to 15, 4 to 14, 4 to 13, 4 to 12, 4 to 11, 4 to 10, 4 to 9, 4 to 8, 4 to 7, 4 to 6, 4 to 5, 5 to 7, or 5 to 6. It may be a heterocycloalkenyl, but is not limited thereto.

[0243] Specific examples of the above heterocycloalkenyls include, but are not limited to, tetrahydropyridinyl, dihydropyranil, dihydroquinolinonil, oxazolinyl, isoxazolinyl, oxazolinyl, pyranyl, dihydrofuranil, dihydroimidazolyl, dihydrotetrazollyl, dihydroisothiazolyl, dihydrooxadiazollyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydrothiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, and dihydroquinolinyl.

[0244] As used in this specification, the term “heterocycloalkynyl” refers to a cycloalkynyl comprising one or more heteroatoms selected from N, O, P, and S (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom) as ring constituents. Herein, cycloalkynyl is defined as above. The above heterocycloalkinyl is 3 to 16, 3 to 15, 3 to 14, 3 to 13, 3 to 12, 3 to 11, 3 to 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6, 3 to 5, 3 to 4, 4 to 16, 4 to 15, 4 to 14, 4 to 13, 4 to 12, 4 to 11, 4 to 10, 4 to 9, 4 to 8, 4 to 7, 4 to 6, 4 to 5, 5 to 7, or 5 to 6. It may be heterocycloalkynyl, but is not limited thereto.

[0245] As used herein, the term “heteroaryl” means an aryl comprising one or more heteroatoms selected from N, O, P and S (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom) as ring constituents, wherein aryl is defined as above. For example, the heteroaryl may be in a saturated, partially saturated, or aromatic form that can optionally be fused with a benzo or cycloalkyl. Specific examples of the above heteroaryls include pyrrolyl, pyrazolyl, imidazolyl, benzimidazolyl, triazolyl, thienyl, tetrazolyl, oxazolyl, isooxazolyl, thiazolyl, thiadiazolyl, tetrazolyl, isothiazolyl, 1,2,4-oxazole, furyl, furanyl, thienyl, pyridinyl, pyridyl, pyridyl N-oxide, pyrazinyl, pyrimidinyl, pyridazinyl, indolinyl, indolyl, benzothiazolyl, triazinyl, isobenzofuranyl, benzisoxazolyl, benzoxazolyl, benzothiadiazolyl, benzothienyl, quinolinyl, quinazolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, isoquinolinyl, thiophenyl, acridyl, indazolyl, Indolazinyl, isoindolyl, pyridopyridinyl, puropyridinyl, carbazolyl, naphthpyridinyl, benzimidazolyl, benzocarbazolyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, pyridin-2-onyl, tetrazolopyridyl, methylenedioxybenzoyl, dibenzothiophenyl, pyrazolopyrimidyl, oxadiazolyl (e.g., 3,4-oxadiazolyl), or azaindolyl, etc., but the scope of the present invention is not limited thereto.

[0246] As used herein, the term “polycyclic ring” refers to a cyclic system of compounds in which two or more rings share atoms or bonds, or are connected without shared atoms, and may be fused, spiro, bridged, or linked. For example, a bicyclic system may be connected via 1,1-fusion (spiro), 1,2-fusion (fused), or 1,2-fusion (bridgehead). Each ring constituting the polycyclic ring may be a ring composed solely of carbon atoms, or it may include a heterocyclic ring comprising one or more hetero atoms selected from the group consisting of S, N, P, and O as ring constituents. Additionally, each ring of the polycyclic ring may be aromatic or non-aromatic, and the ring as a whole may be a saturated, unsaturated, or partially saturated structure.

[0247] Meanwhile, the substituents described in this specification may be connected to other atoms or groups through carbonyl, amide, sulfonyl, or sulfonylamide.

[0248] The term "independently" as used in this specification means that when more than one substituent is selected from a plurality of possible substituents, these substituents may be identical or different from each other.

[0249] As used herein, the terms “arbitrarily substituted” or “substituted” indicate the replacement of one or more hydrogen atoms with radicals of 1 or more valence. Such substitutions include monosubstitution, bisubstitution, tripsubstitution, quaternary substitution, or more. Where the substituted substituent comprises a straight-chain group, the substitution may occur within the chain (e.g., 2-hydroxypropyl, 2-aminobutyl, etc.) or at the chain ends (e.g., 2-hydroxyethyl, 3-cyanopropyl, etc.). The substituted substituent may be a straight-chain, branched-chain, or cyclic arrangement of covalently bonded carbons or heteroatoms. It is understood that the above definition is not intended to include unacceptable substitution patterns (e.g., methyl substituted with five fluorogroups, or halogen atoms substituted with other halogen atoms). Such unacceptable substitution patterns are known to those skilled in the art.

[0250] Meanwhile, in the chemical formulas described in this specification, if a substituent is not separately listed or mentioned, it may be considered that hydrogen is bonded, and in some cases, a substituent may be absent depending on the ring constituent elements forming the heterocycle.

[0251] In this specification, the statement that a substituent is “absent” means that the substituent does not exist. That is, the absence of a substituent means that, due to the valence characteristics of the atom indicated as being connected to the substituent in the structural formula, there is no chemical connection point at that position where the substituent can form a covalent bond, and thus the substituent is absent. For example, in the structural formula -XR, if X is CH3, since there is no longer a chemical connection point at X where R can form a covalent bond with C or H, R can be expressed as being absent.

[0252] The compound of the present invention may exist in the form of a "pharmaceutically acceptable salt." Alternatively, the compound of the present invention may be converted into its salt by conventional methods. As the salt, any salt commonly used in the art, such as an acid addition salt formed by a pharmaceutically acceptable free acid, may be used without limitation. The term "pharmaceutically acceptable salt" in the present invention means any organic or inorganic addition salt of said compound at a concentration having an active effect that is relatively non-toxic and harmless to the patient, such that the adverse effects attributable to said salt do not impair the beneficial efficacy of the compound of Formula I or II.

[0253] Acid addition salts are obtained from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromide, hydroiodide, nitrous acid, phosphoric acid, etc., aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates and alkandioates, aromatic acids, aliphatic and aromatic sulfonic acids, etc., non-toxic organic acids such as trifluoroacetic acid, acetate, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid, etc. These types of pharmaceutically non-toxic salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphate chloride, bromides, iodides, fluorides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caprates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, malieates, butyne 1,4-dioate, hexane-1,6-dioate, benzoates, chlorobenzoates, methyl benzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, and phthalates. Includes terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate, etc.

[0254] The acid addition salt according to the present invention can be prepared by conventional methods, for example, by dissolving a compound of formula I or II in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc., adding an organic acid or an inorganic acid to produce a precipitate, filtering and drying it, or by vacuum distilling the solvent and excess acid, drying it, and crystallizing it under an organic solvent.

[0255] In addition, pharmaceutically acceptable metal salts can be produced using a base. Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess amount of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. In this case, it is pharmaceutically suitable to produce sodium, potassium, or calcium salts as the metal salts. In addition, the corresponding salts are obtained by reacting the alkali metal or alkaline earth metal salt with a suitable base salt (e.g., silver nitrate).

[0256] In addition, a salt or solvate of a compound of formula I or II that is not pharmaceutically acceptable may be used as an intermediate in the preparation of a compound of formula I or II, a pharmaceutically acceptable salt or solvate thereof.

[0257] As used herein, the term “hydrate” refers to a compound of the present invention or a salt thereof containing stoichiometric or non-stoichiometric amounts of water bound by non-covalent intermolecular forces. A hydrate of a compound represented by Formula I or II of the present invention may contain stoichiometric or non-stoichiometric amounts of water bound by non-covalent intermolecular forces. The hydrate may contain at least one equivalent, preferably one to five equivalents of water. Such a hydrate may be prepared by crystallizing a compound represented by Formula I or II of the present invention, an isomer thereof, or a pharmaceutically acceptable salt thereof from water or a solvent containing water.

[0258] As used herein, the term “solvate” means a compound of the present invention or a salt thereof comprising stoichiometric or non-stoichiometric amounts of solvent bound by non-covalent intermolecular forces. Preferred solvents thereof include volatile, non-toxic, and / or solvents suitable for administration to humans.

[0259] The term "isomer" refers to a compound of the present invention or a salt thereof that has the same chemical formula or molecular formula but differs structurally or stereochemically. Such isomers include structural isomers such as tautomers, R or S isomers having an asymmetric carbon center, stereoisomers such as geometric isomers (trans, cis), and optical isomers (enantiomers). All of these isomers and mixtures thereof are also included within the scope of the present invention.

[0260] As used herein, the term “tautomer” refers to a type of structural isomer that has the same chemical or molecular formula but differs in the way its constituent atoms are connected, meaning that its structure changes by continuously switching back and forth between the two isomers, such as in a keto-eno structure.

[0261] As used herein, the terms “enantiomer” or “diastereomer” refer to isomers that have the same chemical formula or molecular formula but differ in the spatial arrangement of atoms within the molecule. The term “enantiomer” refers to an isomer that does not overlap with its mirror image, much like the relationship between a right hand and a left hand. Additionally, “diastereomer” refers to a stereoisomer that is not in a mirror image relationship, such as the trans form and the cis form; in this invention, this is limited to pharmaceutically acceptable diastereomers. All of these isomers and mixtures thereof are also included within the scope of this invention.

[0262] Additionally, the scope of the present invention may include compounds of Formula I or II, isotopic variants thereof, or polymorphs thereof.

[0263] As used herein, the term “isotope variant” refers to a compound containing isotopes in non-natural proportions in one or more atoms constituting the compound. Examples of isotopes that may be incorporated into the compounds of the present invention are isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, iodine, and chlorine, e.g., 2 H (deuterium), 3 H, 11 C, 13 C, 14 C, 18 F, 123 I, or 125 It includes I, etc., which may be naturally occurring or non-naturally occurring isotopes.

[0264] As used herein, the term “polymorph” refers to a solid form having the same chemical formula but different molecular arrangements and crystal structures. The polymorph has a specific crystal structure and can be characterized by methods such as X-ray diffraction (XRD), infrared spectroscopy (IR), and dissimilar scintigraphy (DSC).

[0265] Terms other than those described above may be interpreted in the sense commonly understood by those skilled in the art to which the present invention pertains.

[0266] In addition, unless otherwise indicated, the above definitions apply to terms used individually or as part of a larger group throughout this specification.

[0267]

[0268] Compound of chemical formula I

[0269] To solve the above-mentioned problem, the present invention provides a compound of the following formula I, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt:

[0270] [Chemical Formula I]

[0271]

[0272] (In the above chemical formula I,

[0273] X can be C or N;

[0274] Y1, Y2, Y3, and Y4 can each independently be C, N, O, or S;

[0275] Z1 is absent, or H or C 1-4 It can be alkyl;

[0276] Z2 and Z3 are each independently absent, or H, deuterium, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, 4-12-membered heterocyclil, hydroxyl, halogen, cyano, CO-H, CO-(C 1-4 Alkyl), CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), CO-N(C 1-4 Alkyl)2, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, oxetanil, SO2-(C 1-4 alkyl), SO2-NH2, SO2-NH(C 1-4 alkyl), or SO2-N(C 1-4 Can be alkyl)2;

[0277] Here, the above C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 6-12 Aril, 4-12 won Heteroaryl, quaternary-12ary heterocyclils, tetrahydrofuranil, tetrahydropyranil, piperazinyl, piperidinyl, and oxetanil are halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2;

[0278] Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It may be a haloalkyl.

[0279] In one example, the hydrogen can be replaced with deuterium.

[0280] In one example, the above X can be C or N. Here, 'C' which can be X conventionally refers to a carbon bonded with hydrogen (i.e., CH), but with the notation of hydrogen omitted. Therefore, in Chemical Formula I, if X is represented as C, X is understood to be CH, and if X is represented as N, it refers to a nitrogen atom within the ring.

[0281] In one example, Y1, Y2, Y3, and Y4 (hereinafter “Y n (which can be collectively referred to as ) can each independently be C, N, O, or S.

[0282] In the above chemical formula I, each Y according to the atomic types of Y1, Y2, Y3, and Y4 n Z1, Z2, Z3, and Z4 (hereinafter “Z”) indicated as being combined with n (which can be collectively referred to as ”) may be absent.

[0283] Here, “Z n "This is absent" means that, as explained in the definition of the terms above, each Z in Chemical Formula I n The valence of the bonded atom (indicated by Y1, Y2, Y3, or Y4) corresponds to that position due to its characteristics Z n Since there are no chemical connection points capable of forming covalent bonds, the corresponding Z n This means that it does not exist.

[0284] In one example, Z1 is absent (where Y1 can be N, O, or S), or H or C 1-4 It can be an alkyl.

[0285] In one example, Z2 is absent (where Y2 can be N, O, or S), H, deuterium, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 1-10haloalkyl (e.g., C 1-10 Monohaloalkyl, C 1-10 dihaloalkyl, or C 1-10 trihaloalkyl), C 6-10 Aril, 4-12 won Heteroaryl, 4-12-membered heterocyclil, hydroxyl, halogen, cyano, CO-H, CO-(C 1-4 Alkyl), CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), CO-N(C 1-4 Alkyl)2, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, oxetanil, SO2-(C 1-4 alkyl), SO2-NH2, SO2-NH(C 1-4 alkyl), or SO2-N(C 1-4 It can be alkyl)2. Here, if Z2 is present (i.e., if it is present as a specific group), Y2 can be N or C.

[0286] In one example, the heterocycle residue (e.g., heteroaryl or heterocyclil) may include one or more heteroatoms selected from N, O, P and S (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom) as ring constituents.

[0287] In one example, the 4-12-membered heterocyclile may be a 4-12-membered heterocycloalkyl, a 4-12-membered heterocycloalkenyl, or a 4-12-membered heterocycloalkynyl, but is not limited thereto. That is, the heterocyclile may be included without limitation as long as it is a ring containing one or more heteroatoms, may be a saturated or partially unsaturated ring, and may have a monocyclic or polycyclic structure.

[0288] In one example, Z2 is a halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl (e.g., monohaloalkyl, dihaloalkyl, or trihaloalkyl), hydroxylalkyl, cyano, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkyl, heterocycloalkynyl, heterocycloalkenyl, aryl, heteroaryl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0289] In one example, the above Z2 is a halo, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-10 Alkenyl, C 2-10 Alkinyl, C 1-10 Haloalkyl (e.g., monohaloalkyl, dihaloalkyl, or trihaloalkyl), C 1-10 Hydroxylalkyl, cyano, C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 Cycloalkynyl, 4-12-membered heterocycloalkyl, 4-12-membered heterocycloalkyl, 4-12-membered heterocycloalkynyl, 4-12-membered heterocycloalkenyl, C 6-10 Aryl, 4-12-membered heteroaryl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0290] In one example, the above Z2 is absent, or H, C 1-10 Alkyl, C 3-12 Cycloalkyl, C 1-10 Monohaloalkyl, C 1-10 Dihaloalkyl, C 1-10 Trihaloalkyl, C 1-10Alkoxy, quaternary to 12-membered heterocycloalkyl, piperidinyl, tetrahydropyranyl, or tetrahydrofuranyl, wherein Z2 is hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 1-10 Monohaloalkyl, C 1-10 Dihaloalkyl, C 1-10 Trihaloalkyl, C 3-12 It may be substituted or unsubstituted with one or more groups selected from the group consisting of cycloalkyl, quaternary-12ary heterocycloalkyl, and tetrahydropyranyl.

[0291] In one example, Z3 is absent (where Y3 can be N, O, or S), H, deuterium, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 1-10 haloalkyl (e.g., C 1-10 Monohaloalkyl, C 1-10 dihaloalkyl, or C 1-10 trihaloalkyl), C 6-10 Aril, 4-12 won Heteroaryl, 4-12-membered heterocyclil, hydroxyl, halogen, cyano, CO-H, CO-(C 1-4 Alkyl), CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), CO-N(C 1-4 Alkyl)2, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, oxetanil, SO2-(C 1-4 alkyl), SO2-NH2, SO2-NH(C 1-4 alkyl), or SO2-N(C 1-4 It can be alkyl)2. Here, if Z3 is present (i.e., if it is present as a specific group), Y3 can be N or C.

[0292] Here, the above-described details apply equally to the heterocyclic residue or heterocyclic.

[0293] In one example, the 4-12-membered heterocyclile may be a 4-12-membered heterocycloalkyl, a 4-12-membered heterocycloalkenyl, or a 4-12-membered heterocycloalkinyl.

[0294] In one example, the above Z3 is a halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl (e.g., monohaloalkyl, dihaloalkyl, or trihaloalkyl), hydroxylalkyl, cyano, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkyl, heterocycloalkynyl, heterocycloalkenyl, aryl, heteroaryl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0295] In one example, the above Z3 is a halo, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-10 Alkenyl, C 2-10 Alkinyl, C 1-10 Haloalkyl (e.g., monohaloalkyl, dihaloalkyl, or trihaloalkyl), C 1-10 Hydroxylalkyl, cyano, C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 Cycloalkynyl, 4-12-membered heterocycloalkyl, 4-12-membered heterocycloalkyl, 4-12-membered heterocycloalkynyl, 4-12-membered heterocycloalkenyl, C 6-10 Aryl, 4-12-membered heteroaryl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0296] In one example, the above Z3 is absent, or H, C 1-10 Alkyl, C 1-10 Monohaloalkyl, C 1-10 Dihaloalkyl, C 1-10 Trihaloalkyl, or C 3-12 It can be a cycloalkyl.

[0297] In one example, the above Z4 is absent (wherein Y4 may be N, O, or S), H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It can be a haloalkyl. Here, if Z4 is present (i.e., if it is present as a specific group), Y4 can be N or C.

[0298] In one example, the above Z4 is absent, or H, C 1-4 Alkyl, halo, C 1-10 Monohaloalkyl, C 1-10 dihaloalkyl, or C 1-10 It can be a trihaloalkyl.

[0299] In one example, the above Z4 may be absent or may be H, deuterium, halo, -CH3, -CD3, -CF3, or -CF2H.

[0300] In one example, X is N; Y2 and Y3 are each N; Z2 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12ary heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, or oxetanil, wherein Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2. Here, Y1 and Y4 may each be C. Here, Z1, Z3, and Z4 are as defined above.

[0301] Here, the above Z2 is a halo, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Haloalkyl, C 1-10 Hydroxylalkyl, cyano, C 3-12 Cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0302] Here, when the above Z2 exists (i.e., when it exists as a specific unit), Z3 may be absent.

[0303] Here, the above Z4 is absent or C 2-10 Alkyl, halo, or C 1-10 It may be a haloalkyl. Or, the above Z4 is absent, haloalkyl, or C 1-10 It may be a haloalkyl. Alternatively, the above Z4 may be characterized as not being methyl, but is not limited thereto.

[0304] In one example, X is N; Y2 and Y3 are each N; Y1 and Y4 are each C; and Z2 is C 1-10 Alkyl, C 1-10 Haloalkyl, C 1-10 Alkoxy, C 3-12 cycloalkyl, quaternary-12-membered heterocycloalkyl, tetrahydropyranyl, or piperidinyl, wherein Z2 is a hydroxyl, halo, C 1-10 Haloalkyl, C 1-10 Alkoxy, and C 3-12 It may be substituted or unsubstituted with one or more groups selected from the group consisting of cycloalkyls; said Z3 is absent; and Z1 and Z4 are each independently absent, or H, C 1-10 Alkyl, halo, or C 1-10 It can be a haloalkyl.

[0305] In another example, X is N; Y1 and Y2 are each N; Z2 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12ary heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, or oxetanil, wherein Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2. Here, Y3 and Y4 may each be C. Here, Z1, Z3, and Z4 are as defined above.

[0306] Here, the above Z2 is a halo, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Haloalkyl, C 1-10 Hydroxylalkyl, cyano, C 3-12 Cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0307] Here, when Z2 exists (i.e., when it exists as a specific unit), Z1 may be absent. Also, when Z1 exists, Z2 may be absent.

[0308] In one example, X is N; Y1 and Y2 are each N; Y3 and Y4 are each C; and Z2 is C 1-10 Alkyl, C 1-10 Haloalkyl, C 1-10 Alkoxy, C 3-12 cycloalkyl, quaternary-12-membered heterocycloalkyl, tetrahydropyranyl, or tetrahydrofuranyl, wherein Z2 is a halo, C 1-10 Haloalkyl, C 1-10 Alkoxy, C 3-12 It may be substituted or unsubstituted with one or more groups selected from the group consisting of cycloalkyl, quaternary-12ary heterocycloalkyl, and tetrahydropyranyl; said Z1 is absent; said Z3 and Z4 are each independently absent, or H or C 1-10 It can be an alkyl.

[0309] In one example, X is N, Y1 and Y2 are each N; Y3 and Y4 are each C; and Z1 is C 1-10 It is alkyl; said Z2 is absent; said Z3 and Z4 are each independently absent, or H, C 1-10 Alkyl, C 1-10haloalkyl, or C 3-12 It can be a cycloalkyl.

[0310] In another example, X is N; Y1, Y2, and Y4 are each N; Z2 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12ary heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, or oxetanil, wherein Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2. Here, Y3 may be C. Here, Z1, Z3, and Z4 are as defined above.

[0311] Here, the above Z2 is a halo, hydroxyl, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Haloalkyl, C 1-10 Hydroxylalkyl, cyano, C 3-12 Cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0312] Here, when the above Z2 exists (i.e., when it exists as a specific unit), the above Z1 and Z4 may each be absent.

[0313] In one example, X is N; Y1, Y2, and Y4 are each N; Y3 is C; and Z2 is C 1-10 It is alkyl; Z1 and Z4 are absent; and Z3 may be H.

[0314] In another example, X is N; Y1 and Y3 are each N; Z3 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12ary heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, oxetanil, where Z3 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2. Here, Y2 and Y4 may each be C. Here, Z1, Z2, and Z4 are as defined above.

[0315] Here, when the above Z3 exists (i.e., when it exists as a specific machine), the above Z1 may be absent.

[0316] In one example, X is N; Y1 and Y3 are each N; Y2 and Y4 are each; and Z3 is C 1-10 It is alkyl; Z1 is absent; and Z2 and Z4 are each independently H or C 1-10 It can be an alkyl.

[0317] In one example, the above chemical formula I may be represented by any one of the following structures, but is not limited thereto:

[0318] [Chemical Formula I-1]

[0319]

[0320] [Chemical Formula I-2]

[0321]

[0322] [Chemical Formula I-3]

[0323]

[0324] [Chemical Formula I-4]

[0325]

[0326] [Chemical Formula I-5]

[0327]

[0328] (Here, X, Z1, Z2, Z3, and / or Z4 indicated in each structural formula are as defined above.)

[0329] In one example, the Z4 of the above formula I-1 is absent, halo, or C 1-10 It may be a haloalkyl. In one example, the Z4 of the above formula I-1 may be characterized as not being methyl, but is not limited thereto.

[0330] In one example, the compound represented by the above chemical formula I may be represented by any one of the structural formulas selected from Table 1 of the present specification.

[0331] In one example, the compound represented by the above chemical formula I may be selected from the group consisting of the following:

[0332] 1) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0333] 2) 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0334] 3) 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0335] 4) 5-cyclopropyl-3-((1-ethyl-1H-1,2,4-triazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0336] 5) 5-cyclopropyl-3-((3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0337] 6) 5-cyclopropyl-3-((1-(1-hydroxy-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0338] 7) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)picolinamide,

[0339] 8) 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0340] 9) 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0341] 10) 5-cyclopropyl-3-((1,5-dimethyl-1H-imidazole-4-yl)amino)-6-(3-methyl-3H-imidazoo[4,5-c]pyridine-7-yl)picolinamide,

[0342] 11) 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0343] 12) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)picolinamide,

[0344] 13) 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0345] 14) 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide,

[0346] 15) 5-cyclopropyl-3-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0347] 16) 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0348] 17) 5-cyclopropyl-3-((3-fluoro-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0349] 18) 5-cyclopropyl-3-((3-(difluoromethyl)-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0350] 19) 5-cyclopropyl-3-((1-isopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide,

[0351] 20) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1-methylpiperidine-4-yl)-1H-pyrazole-4-yl)amino)picolinamide,

[0352] 21) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)picolinamide,

[0353] 22) 5-cyclopropyl-3-((1-ethyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0354] 23) 5-cyclopropyl-3-((1-(difluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0355] 24) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-4-yl)amino)picolinamide,

[0356] 25) 5-cyclopropyl-3-((1-cyclopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0357] 26) 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0358] 27) 5-cyclopropyl-3-((1-(difluoromethyl)-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0359] 28) 5-cyclopropyl-3-((1-isobutyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0360] 29) 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide,

[0361] 30) 5-cyclopropyl-3-((3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0362] 31) 5-cyclopropyl-3-((1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0363] 32) 5-cyclopropyl-3-((3-cyclopropyl-1-methyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0364] 33) 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0365] 34) 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0366] 35) 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0367] 36) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0368] 38) 5-cyclopropyl-3-((1-ethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0369] 39) 5-cyclopropyl-3-((1-isobutyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0370] 40) 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0371] 42) 3-((1-(tert-butyl)-3-methyl-1H-pyrazole-4-yl)amino)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0372] 43) 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0373] 44) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0374] 45) 5-cyclopropyl-3-((5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0375] 46) 5-cyclopropyl-3-((1-(2,2-difluoropropyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0376] 47) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-3-yl)amino)picolinamide,

[0377] 49) 5-cyclopropyl-3-((5-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0378] 50) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0379] 51) 5-cyclopropyl-3-((1-isopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0380] 52) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0381] 53) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0382] 54) 5-cyclopropyl-3-((3-fluoro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0383] 55) 5-cyclopropyl-3-((3-fluoro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0384] 56) 5-cyclopropyl-3-((1-cyclopropyl-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0385] 57) 5-cyclopropyl-3-((1-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0386] 58) 5-cyclopropyl-3-((1,5-dimethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0387] 59) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolineamide,

[0388] 60) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0389] 61) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-3-yl)amino)picolinamide,

[0390] 62) 5-cyclopropyl-3-((3-fluoro-1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0391] 63) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0392] 64) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0393] 65) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide,

[0394] 66) 5-cyclopropyl-3-((1-((1s,3s)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0395] 67) 5-cyclopropyl-3-((1-((1r,3r)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, or

[0396] 68) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((1s,3s)-3-(trifluoromethyl)cyclobutyl)-1H-pyrazole-3-yl)amino)picolinamide.

[0397]

[0398] Compound of Chemical Formula II

[0399] To solve the above-mentioned problem, the present invention provides a compound of the following formula II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt:

[0400] [Chemical Formula II]

[0401]

[0402] (In the above chemical formula II,

[0403] X can be C or N;

[0404] Y1, Y2, Y3, and Y4 can each independently be C, N, O, or S;

[0405] Z1 is absent, or H or C 1-4 It can be alkyl;

[0406] Cycle A is C3- 12 Cycloalkyl, C3- 12 Cycloalkenyl, C3- 12 Cycloalkinyl, C 6-12 It may be an aryl, a 4-12-membered heterocycloalkyl, a 4-12-membered heterocycloalkenyl, a 4-12-membered cycloalkinyl, or a 4-12-membered heteroaryl;

[0407] Here, the above Cycle A is deuterium, halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2;

[0408] Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It may be a haloalkyl.

[0409] In one example, the hydrogen can be replaced with deuterium.

[0410] In one example, the above X can be C or N. Here, 'C' which can be X conventionally refers to a carbon bonded to hydrogen (i.e., CH), but with the hydrogen notation omitted. Therefore, in Chemical Formula I, if X is represented as C, it is understood that X is CH, and if X is represented as N, it refers to a nitrogen atom within the ring.

[0411] In one example, Y1, Y2, Y3, and Y4 (hereinafter “Y n(which can be collectively referred to as ) can each independently be C, N, O, or S.

[0412] In the above chemical formula II, depending on the atomic types of Y1, Y2, Y3, and Y4, Z1 indicated as bonded to Y1 and Z4 indicated as bonded to Y4 may be absent (hereinafter Z1 and / or Z4 are “Z n It can be collectively referred to as ”).

[0413] Here, “Z n "This is absent" means that, as explained in the definition of the terms above, each Z in Chemical Formula II n The valence of the bonded atom (indicated by Y1 or Y4) corresponds to that position due to its characteristics Z n Since there are no chemical connection points capable of forming covalent bonds, the corresponding Z n This means that it does not exist.

[0414] In the above chemical formula II, Y2 and Y3 can each independently be C, N, O, or S. Here, 'C' which can be Y2 and / or Y3 may refer to a carbon atom C alone, or to a carbon from which the hydrogen is conventionally omitted (i.e., CH).

[0415] In one example, Z1 is absent (where Y1 can be N, O, or S), or H or C 1-4 It can be an alkyl.

[0416] In one example, the above Cycle A is C3- 12 Cycloalkyl, C3- 12 Cycloalkenyl, C3- 12 Cycloalkinyl, C 6-12 It may be an aryl, a 4-12-membered heterocycloalkyl, a 4-12-membered heterocycloalkenyl, a 4-12-membered cycloalkinyl, or a 4-12-membered heteroaryl.

[0417] Here, the Cycle A may be a monocyclic or polycyclic (bicyclic, tricyclic, or more) ring structure, and when the Cycle A is a polycyclic ring, each ring may independently be a saturated or partially unsaturated ring, and may be an aromatic or non-aromatic ring. Additionally, when the Cycle A is a polycyclic ring, the polycyclic rings may be fused, spiro, bridged, or linked.

[0418] Here, if the above Cycle A has a ring structure in which the skeletal atoms consist only of carbon (C) (e.g., if the above Cycle A is cycloalkyl, cycloalkenyl, cycloalkynyl, or aryl), then Y2 and Y3 are C (C or CH).

[0419] Here, the heterocyclic structure that can be Cycle A (e.g., heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, heteroaryl) may include one or more heteroatoms selected from N, O, P, and S (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom) as ring constituents.

[0420] Here, if the Cycle A is heterocyclic, one or more of Y2 and Y3 may be N, O, or S, and the Cycle A may further include one or more heteroatoms selected from N, O, P, and S in addition to Y2 and Y3. In one example, when the Cycle A is heterocyclic, Y2 may be N and Y3 may be C (C or CH), and the Cycle A may or may not include one or more heteroatoms in addition to Y2.

[0421] In one example, the above Cycle A may be a heterocyclic containing one or more N atoms, but is not limited thereto.

[0422] In one example, the above Cycle A is C3- 12 It may be a cycloalkyl or a quaternary-12-membered heterocycloalkyl, and specifically, C 4-6 It may be a cycloalkyl or a quaternary to hexavalent heterocycloalkyl.

[0423] Here, if the above Cycle A is a quaternary-12-membered heterocycloalkyl, Y2 may be N, O, or S, and Y3 may be C. In this case, the above Cycle A may or may not include one or more heteroatoms (e.g., N, O, P, and / or S) in addition to Y2.

[0424] In one example, the above Cycle A is cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptyl, cyclooctyl, azetidinyl, benzimidazolyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazolin, isoxazoline, oxetanil, pyranyl, Pyrazinyl, Pyrazolyl, Pyridazinyl, Pyridopyridinyl, Pyridyl, Pyrimidyl, Pyrrolyl, Morpolino, Quinazolinyl, Quinolyl, Quinoxalinyl, Tetrahydropyranil, Tetrahydrothiopyranil, Tetrahydroisoquinolinyl, Tetrazolyl, Tetrazolopyridyl, Thiadiazolyl, Thiazolyl, Thienyl, Triazolyl, 1,4-Dioxanyl, Hexahydroazefinyl, Piperazinyl, Piperidinyl, Pyridin-2-onyl, Pyrrolidinyl, Mopolinyl, Thiomopolinyl, Dihydrobenzoimidazolyl, Dihydrobenzofuranyl, Dihydrobenzothiophenyl, Dihydrobenzoxazolyl, It may be dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiazolyl, dihydrothiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, or tetrahydrothienyl, but is not limited thereto.

[0425] In one example, Cycle A of the above formula II is deuterium, halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl (e.g., monohaloalkyl, dihaloalkyl, or trihaloalkyl), hydroxylalkyl, cyano, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl(2). That is, each skeletal atom (C or heteroatom) constituting Cycle A may be independently substituted or unsubstituted with any one or more of the aforementioned substituents. Here, “substitution” means that one or more hydrogen atoms bonded to the skeletal atom constituting Cycle A are replaced with any one of the aforementioned substituents, as described in the definition of the terms above.

[0426] In one example, the above Cycle A is deuterium, halo, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkinyl, C 1-10 Haloalkyl, C 1-10 Hydroxylalkyl, cyano, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 It may be substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

[0427] In one example, the above Z4 is absent (wherein Y4 may be N, O, or S), H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It may be a haloalkyl (e.g., monohaloalkyl, dihaloalkyl, or trihaloalkyl).

[0428] In one example, the above Z4 may be absent or may be H, deuterium, halo, -CH3, -CD3, -CF3, or -CF2H.

[0429] In one example, X is N; Y1 is N; and Cycle A is as defined above, wherein Cycle A is C3- 12 Cycloalkyl, C3- 12 Cycloalkenyl, C3- 12 Cycloalkynyl, or C 6-12 In the case of an aryl, Y2 and Y3 are each C (C or CH), and in the case where Cycle A is a quaternary-12-membered heterocycloalkyl, quaternary-12-membered heterocycloalkenyl, quaternary-12-membered cycloalkynyl, or quaternaryl, Y2 is N and Y3 may be C, N, O, or S, but is not limited thereto. Here, Z1 is absent; Z4 is absent or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It may be a haloalkyl. Here, the Cycle A may or may not include one or more heteroatoms in addition to Y2 and Y3 (where Y3 is N, O, or S).

[0430] In one example, X is N; Y1 is N; and Cycle A is a substituted or unsubstituted C 4-6 It is a cycloalkyl or a quaternary to hexavalent heterocycloalkyl, wherein Cycle A is C 4-6 When it is a cycloalkyl, Y2 and Y3 are each C (C or CH), and when Cycle A is a tetrocycloalkyl, Y2 is N and Y3 may be C, N, O, or S, but is not limited thereto. Here, Z1 is absent; Z4 is absent or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It may be a haloalkyl. Here, the Cycle A may or may not include one or more heteroatoms in addition to Y2 and Y3 (where Y3 is N, O, or S).

[0431] In one example, X is N; Y1 and Y2 are N; Y3 and Y4 are C; and Cycle A may be a substituted or unsubstituted quaternary to hexavalent heterocycloalkyl, but is not limited thereto. Here, Z1 is absent; Z4 is absent or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It can be a haloalkyl.

[0432] In one example, the above chemical formula II may be represented by the following structure, but is not limited thereto:

[0433] [Chemical Formula II-1]

[0434]

[0435] (In the above chemical formula II-1,

[0436] X is C or N and;

[0437] Cycle A is a quaternary-12-membered heterocycloalkyl, quaternary-12-membered heterocycloalkenyl, quaternary-12-membered cycloalkynyl, or quaternary-12-membered heteroaryl, and

[0438] Here, the above Cycle A is deuterium, halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 Substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2;

[0439] Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It is a haloalkyl.

[0440] Here, the above Cycle A may have only one heteroatom, which is a skeletal atom, or two or more.

[0441] In one example, the compound represented by the above chemical formula II may be represented by any one of the structural formulas selected from Table 1 of the present specification.

[0442] In one example, the compound represented by the above chemical formula II may be selected from the group consisting of the following:

[0443] 37) 5-cyclopropyl-3-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide,

[0444] 41) 5-cyclopropyl-3-((5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, and

[0445] 48) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-yl)amino)picolineamide.

[0446]

[0447] Method for preparing a compound of chemical formula I or II

[0448] The present invention provides a method for preparing a compound of formula I or II as described above.

[0449] One example of the present invention relates to a method for preparing a compound of formula I or II, comprising the step of performing a Buchwald-Hartwig coupling of a compound represented by the following formula (i):

[0450] [Chemical formula (i)]

[0451]

[0452] (In the above chemical formula (i),

[0453] X can be C (specifically CH) or N;

[0454] W1 can be an amine (e.g., a primary amine, a secondary amine, or a tertiary amine) or a halo;

[0455] W2 is H, hydroxyl, C 1-4 alkyl, or C 1-4 It may be an alkoxy.

[0456] Herein, where W1 is an amine, the manufacturing method may further include the step of performing Birchwald-Hartwick coupling using a compound represented by chemical formula (i); or, prior to performing Birchwald-Hartwick coupling, reacting the compound of chemical formula (i) with tert-butyl nitrite (tBuNO2) and cupric bromide (CuBr2) to produce a compound of chemical formula (i)-1:

[0457] [Chemical formula (i)-1]

[0458]

[0459] (In the above chemical formula (i),

[0460] X can be C (specifically CH) or N;

[0461] W2 is H, hydroxyl, C 1-4 alkyl, or C 1-4 It may be an alkoxy.

[0462] Here, the solvent used in the step of preparing the compound of formula (i)-1 may be acetonitrile, but is not limited thereto.

[0463] In one example, the compound coupled to the Birchwald-Hartwick compound represented by the above chemical formula (i) may be represented by the following chemical formula (m) or (n), but is not limited thereto:

[0464] [Chemical formula (m)]

[0465]

[0466] (In the above chemical formula (m),

[0467] R is an amine or a halo;

[0468] Y 1-4 and Z 1-4 is Y defined in the aforementioned chemical formula I. 1-4 and Z 1-4 It is the same as.)

[0469] That is, Y of the above chemical formula (m). 1-4 and Z 1-4 In this, Y of the aforementioned chemical formula I 1-4 and Z 1-4 The same specific explanation applies to .

[0470] [Chemical formula (n)]

[0471]

[0472] (In the above chemical formula (n),

[0473] R is an amine or a halo;

[0474] Y 1-4 , Z 1-4 , and Cycle A is Y as defined in the aforementioned chemical formula II. 1-4 , Z 1-4 , and is identical to Cycle A.)

[0475] That is, Y of the above chemical formula (n) 1-4 , Z 1-4 , and in Cycle A, Y of the aforementioned Chemical Formula II 1-4 , Z 1-4 The same specific explanation applies to , and Cycle A.

[0476] In one example, the compound represented by the above chemical formula (i) can be prepared by a manufacturing method comprising the step of Suzuki coupling the compound represented by the following chemical formula (ii) with the compound represented by the following chemical formula (iii):

[0477] [Chemical formula (ii)]

[0478]

[0479] (In the above chemical formula (ii),

[0480] W1 is an amine or a halo;

[0481] The above W2 is H, hydroxyl, C 1-4 alkyl, or C 1-4 It is an alkoxy;

[0482] The above W3 is a halo.)

[0483] In one example, the above W2 may be O-methyl, O-ethyl, or O-propyl.

[0484] [Chemical Formula (iii)]

[0485]

[0486] (In the above chemical formula (iii),

[0487] X is C (specifically CH) or N, and

[0488] Q1 and Q1 are each independently H or C 1-6 It is an alkyl; or Q1 and Q1 together form a 5- to 6-membered heterocycloalkyl, and

[0489] The above heterocycloalkyl is C 1-4 It is substituted or unsubstituted with alkyl groups.)

[0490] Here, the statement that Q1 and Q1 together form a pentagonal to hexagonal heterocycloalkyl means that the boron atom (B) and two oxygen atoms indicated as being connected to Q1 and Q1 in formula (iii) form a pentagonal to hexagonal heterocycloalkyl together with Q1 and Q1. That is, the heterocycloalkyl includes the boron atom, two oxygen atoms, Q1, and Q1 of formula (iii) as skeletal atoms.

[0491] In one example, the heterocycloalkyl group comprises 1 to 4, 1 to 3, 1 to 2, or 1 C 1-4 It can be substituted with alkyl.

[0492] In one example, the above chemical formula (iii) can be represented by the following chemical formula (iv).

[0493] [Chemical Formula (iv)]

[0494]

[0495] (In the above chemical formula (iv),

[0496] X is C (specifically CH) or N, and

[0497] Q 3-6 Each independently H or C 1-4 It is an alkyl.

[0498] Here, the palladium catalyst used in the Suzuki reaction of the compound represented by chemical formula (ii) and the compound represented by chemical formula (iii) may be selected from Pd(dppf)Cl2, Pd(PPh3)4, PD2(dba)3, and PD(OAc)2, but is not limited thereto, and any palladium catalyst commonly used in the Suzuki reaction may be used without limitation.

[0499] Here, the base used in the Suzuki reaction may be selected from cesium carbonate, calcium carbonate, tripotassium phosphate, potassium carbonate, sodium carbonate, sodium hydroxide, and potassium hydroxide, but is not limited thereto, and any base commonly used in the Suzuki reaction may be used.

[0500] Here, the solvent used in the above Suzuki reaction may be 1,4-dioxane, but is not limited thereto.

[0501] Hereinafter, the method for preparing Formula I or II of the present invention is explained in more detail through the following Reaction Scheme 1.

[0502] One example of the present invention relates to a method for preparing a compound of Formula I or II represented by the following reaction scheme 1:

[0503] [Reaction Equation 1]

[0504]

[0505] The following reaction schemes 1-1 to 1-3 are continuous processes and represent the above reaction scheme 1 as a whole.

[0506] [Reaction Equation 1-1]

[0507] Steps 1 to 5 of the above reaction scheme 1 are shown.

[0508]

[0509] [Reaction Equation 1-2]

[0510] Steps 6 to 8 of the above reaction scheme 1 are shown.

[0511]

[0512] [Reaction Equation 1-3]

[0513] Represents Step 9 of the above reaction scheme 1.

[0514]

[0515] In the above reaction equation, X, Y 1-4 , Z 1-4 The definitions of , and Cycle A are as previously defined in Chemical Formula I or II.

[0516] Each step of the above reaction equation 1 will be explained in detail below.

[0517] Step 1 above is a step of preparing a compound corresponding to Formula 2 by reacting a compound represented by Formula 1 with di-tert-butyl dicarbonate and 4-dimethylaminopyridine. In one example, acetonitrile may be used as the solvent in Step 1, but is not limited thereto.

[0518] Step 2 above is a step of preparing a compound represented by Chemical Formula 4 by introducing a cyclopropyl group into the compound represented by Chemical Formula 2 through a Suzuki coupling reaction. In one example, the palladium catalyst in Step 2 above may be selected from Pd(dppf)Cl2, Pd(PPh3)4, PD2(dba)3, and PD(OAc)2, but is not limited thereto. In one example, 1,4-dioxane may be used as the solvent in Step 2 above, but is not limited thereto.

[0519] Step 3 above is a step of deprotecting the compound represented by Chemical Formula 4 using trifluoroacetic acid. Through the deprotection step, the protecting group of the compound represented by Chemical Formula 4 is removed and converted into a compound represented by Chemical Formula 5. In one example, dichloromethane may be used as the solvent for the deprotection process of Step 3, but is not limited thereto.

[0520] Step 4 above is a step of preparing a compound represented by Chemical Formula 6 by reacting the compound represented by Chemical Formula 5 with N-bromosuccinimide. Through the reaction with N-bromosuccinimide, a bromo group is introduced into the compound represented by Chemical Formula 5. In one example, acetonitrile may be used as the solvent in Step 4, but is not limited thereto.

[0521] Step 5 above is a step of preparing a compound represented by compound 7a by performing a Suzuki reaction of the compound represented by Chemical Formula 6 in the presence of a palladium catalyst and a base. In one example, the compound of Chemical Formula (iii) described above may be used as the compound performing the Suzuki reaction with the compound represented by Chemical Formula 6. In one example, the compound represented by Chemical Formula 6-1 below may be used as the compound performing the Suzuki reaction with the compound represented by Chemical Formula 6.

[0522] [Chemical Formula 6-1]

[0523]

[0524] In one example, the palladium catalyst used in the Suzuki reaction of step 5 above may be selected from Pd(dppf)Cl2, Pd(PPh3)4, PD2(dba)3, and PD(OAc)2, but is not limited thereto.

[0525] In one example, the base used in the Suzuki reaction of step 5 above may be selected from cesium carbonate, calcium carbonate, tripotassium phosphate, potassium carbonate, sodium carbonate, sodium hydroxide, and potassium hydroxide, but is not limited thereto.

[0526] In one example, the solvent used in the Suzuki reaction of step 5 above may be 1,4-dioxane, but is not limited thereto.

[0527] Step 6 above is a step of preparing a compound represented by Chemical Formula 7b by reacting the compound represented by Chemical Formula 7a with tert-butyl nitrite (tBuNO2) and cupric bromide (CuBr2). In one example, acetonitrile may be used as the solvent in Step 6, but is not limited thereto.

[0528] Steps 7a and 7b above are steps of performing a Birchwald-Hartwick coupling of a compound represented by chemical formula 7a or 7b to produce a compound represented by chemical formula 8a or 8b; or a compound represented by chemical formula 9a or 9b. Theoretically, when performing the Birchwald-Hartwick coupling, a compound represented by chemical formula 9a or 9b may be produced, but a compound represented by chemical formula 8a or 8b may also be produced. If a compound represented by chemical formula 8a or 8b is produced through this step, the compound can be converted into a compound represented by chemical formula 9a or 9b through step 8 described below.

[0529] Step 8 above is a step of preparing a compound represented by Formula 9a or 9b by performing Fischer esterification of a compound represented by Formula 8a or 8b. In one example, sulfuric acid may be used as the acid catalyst for the Fischer esterification of the compound, but is not limited thereto. In one example, methanol may be used as the solvent for the Fischer esterification reaction, but is not limited thereto.

[0530] Step 9 above is a step of preparing a compound of Formula 10a or 10b by reacting a compound represented by Formula 9a or 9b with an ammonia solution in methanol. In one example, the concentration of ammonia dissolved in the methanol may be 1 to 10 M, 3 to 10 M, 5 to 10 M, 5 to 9 M, 5 to 8 M, 5 to 7.5 M, 6 to 7.5 M, 6.5 to 7.5 M, or 7 M, but is not limited thereto. In one example, methanol may be used as the solvent in Step 9, but is not limited thereto.

[0531]

[0532] Uses of compounds of chemical formula I or II

[0533] The compound according to the present invention has inhibitory ability against hematopoietic progenitor kinase 1 (HPK1) and can be used for the prevention, improvement, and / or treatment of HPK1-related diseases or disorders.

[0534] The above-mentioned hematopoietic progenitor kinase 1 (HPK1) is a protein of the serine / threonine Ste20-associated protein kinase family that is specifically expressed in blood cells, and is also referred to as MAP4K1 (Mitogen-activated protein kinase kinase kinase 1). HPK1 functions as a negative regulator of T cell receptors (TCRs), B cell receptors (BCRs), and dendritic cells. HPK1 is a known protein, and its function and sequence information are known; for example, specific information can be retrieved from the protein database Uniprot (Uniprot reference number: Q92918).

[0535] Specifically, one example of the present invention relates to a composition for the prevention, improvement, and / or treatment of HPK1-related diseases or disorders, comprising a compound of Formula I or II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt (hereinafter abbreviated as “compound of Formula I or II, etc.”). Herein, the compound of Formula I or II, etc. may be included as an active ingredient in the composition. Herein, the composition may be a pharmaceutical composition.

[0536] Another example of the present invention relates to a method for preventing, improving, and / or treating HPK1-related diseases or disorders, comprising the step of administering a compound of Formula I or II, etc., to a subject requiring prevention, improvement, and / or treatment of an HPK1-related disease or disorder. Herein, the method may further comprise the step of identifying a subject requiring prevention, improvement, and / or treatment of an HPK1-related disease or disorder prior to the step of administration. Herein, the compound of Formula I or II, etc., may be administered in a pharmaceutically effective amount.

[0537] Another example of the present invention relates to the use of compounds of Formula I or II, etc., for the prevention, improvement, and / or treatment of HPK1-related diseases or disorders.

[0538] Another example of the present invention relates to the use of compounds of Formula I or II, etc., for the manufacture of pharmaceutical agents for the prevention, improvement, and / or treatment of HPK1-related diseases or disorders.

[0539] Another example of the present invention relates to a kit for the prevention, improvement, and / or treatment of HPK1-related diseases or disorders, comprising a compound of formula I or II, etc.

[0540] The above HPK1-related disease or disorder refers to a disease that can be directly or indirectly induced by abnormal HPK1 or dysregulation of HPK1. For example, the above HPK1-related disease or disorder may be a disease that can be directly or indirectly induced by overexpression and / or overactivation of HPK1.

[0541] In one example, the HPK1-related disease or disorder may be an immune-related disease or disorder.

[0542] The above immune-related diseases or disorders encompass all diseases caused by impairment and / or insufficient activity of the immune system, and may be, for example, one or more selected from the group consisting of cancer, cancer metastasis, infectious diseases, autoimmune diseases, inflammatory diseases, etc., but are not limited thereto. The above inflammation may be inflammation (e.g., chronic or acute inflammation) and may include inflammation caused by infection (e.g., local inflammation, systemic inflammation, etc.), but is not limited thereto.

[0543] For the treatment of one or more of the diseases listed above, another example of the present invention may provide a combination therapy in which a compound of Formula I or II as a first active ingredient and a second active ingredient are administered simultaneously, sequentially, or in combination. Herein, the combination may be further combined with one or more additional active ingredients.

[0544] Meanwhile, the compound according to the present invention can achieve an anticancer effect by activating an antitumor immune response through the inhibition of HPK1, and can more effectively inhibit tumor growth when used in combination with anticancer immunotherapy such as immune checkpoint inhibitors.

[0545] Accordingly, compounds of Formula I or II of the present invention, enantiomers, diastereomers, tautomers, hydrates, solvates, or pharmaceutically acceptable salts thereof may be used for the prevention, improvement, and / or treatment of cancer.

[0546] Specifically, one example of the present invention relates to a composition for the prevention, improvement, and / or treatment of cancer comprising a compound of Formula I or II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt (hereinafter abbreviated as “compound of Formula I or II, etc.”). Herein, the compound of Formula I or II, etc. may be included as an active ingredient in the composition. Herein, the composition may be a pharmaceutical composition. Herein, the composition may be intended for use in combination with other anticancer immunotherapy.

[0547] Another example of the present invention relates to a method for preventing, improving, and / or treating cancer, comprising the step of administering a compound of Formula I or II, etc., to a subject requiring prevention, improvement, and / or treatment of cancer. Herein, the method may further comprise the step of identifying a subject requiring prevention, improvement, and / or treatment of cancer prior to the step of administration. Herein, the compound of Formula I or II, etc., may be administered in a pharmaceutically effective amount.

[0548] Another example of the present invention relates to the use of compounds of Formula I or II, etc., for the prevention, improvement, and / or treatment of cancer.

[0549] Another example of the present invention relates to the use of compounds of Formula I or II, etc., for the manufacture of drugs for the prevention, improvement, and / or treatment of cancer.

[0550] Another example of the present invention relates to a kit for the prevention, improvement, and / or treatment of cancer using a compound of formula I or II, etc.

[0551] In one example, the cancer may be a solid tumor or a blood cancer.

[0552] In one example, the cancer may be selected from, but is not limited to, carcinoma, sarcoma, leukemia, lymphoma, central nervous system tumor, multiple myeloma, melanoma, germ cell tumor, and / or other cancers.

[0553] In one example, the cancer is a blastoma, sarcoma, colorectal cancer (e.g., colon cancer, rectal cancer, colorectal cancer, etc.), thyroid cancer, oral cancer, pharyngeal cancer, laryngeal cancer, cervical cancer, brain cancer, brain tumor, glioblastoma, medulloblastoma, neuroblastoma, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous cell carcinoma of the lung, etc.), ovarian cancer, bladder cancer, kidney cancer (e.g., renal cell carcinoma, clear cell renal cell carcinoma, etc.), liver cancer, hepatocellular carcinoma, pancreatic cancer, prostate cancer, skin cancer, tongue cancer, breast cancer, uterine cancer, stomach cancer, bone cancer, lymphoma, blood cancer, peritoneal cancer, skin cancer, melanoma, cutaneous melanoma, ocular melanoma, rectal cancer, prostatic cancer, esophageal cancer, small intestine cancer, osteosarcoma, endocrine gland cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, gastric cancer, glioblastoma, It may include one or more selected from the group consisting of ovarian cancer, endometrial cancer, salivary gland cancer, vulvar cancer, ependymoma, Ewing's sarcoma, rhabdomyosarcoma, rhabdomyocarcinoma, renal cell tumor (Wilm's tumor), head and neck cancer, leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, lipoma, lipoblastoma, hibernation tumor, liposarcoma, leiomyoma, leiomyosarcoma, neurofibroma, and malignant Schwannoma, but is not limited thereto, and may include all forms of carcinoma, melanoma, blastoma, sarcoma, lymphoma, and leukemia.

[0554] In one example, the cancer may be accompanied by abnormal HPK1 and / or abnormal regulation of HPK1, or it may be a cancer unrelated to HPK1 (i.e., a cancer that developed for reasons unrelated to abnormal HPK1 and / or abnormal regulation of HPK1).

[0555] The above abnormal HPK1 refers to an abnormality in the expression and / or function of HPK1, for example, it may refer to the overexpression and / or overactivation of HPK1. The above abnormal regulation of HPK1 refers to an abnormality in other factors or signaling pathways that directly or indirectly regulate the expression or function of HPK1, and may be included without limitation as long as it results in the overexpression or overactivation of HPK1.

[0556] The above-mentioned effects of preventing, improving, and / or treating cancer include the effect of eliminating (killing) cancer cells, the effect of inhibiting the occurrence and / or growth of cancer cells, the effect of inhibiting the exacerbation of cancer due to migration, invasion, metastasis, etc., and the effect of inhibiting tumor growth.

[0557]

[0558] Meanwhile, the compound of Formula I or II of the present invention can achieve a more potent anticancer effect through combination with anticancer immunotherapy.

[0559] Accordingly, the compound of Formula I or II of the present invention, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt may be used in combination with anticancer immunotherapy. Here, the term "combination use" means that it is used in combination with anticancer immunotherapy to ultimately prevent, improve, and / or treat cancer.

[0560] The aforementioned anticancer immunotherapy is a treatment method that activates the patient's immune system to attack tumors, and immune checkpoint inhibitors can be cited as a representative example.

[0561] Accordingly, the present invention provides a composition for the combined administration of an immune checkpoint inhibitor comprising a compound of Formula I or II, etc. In one example, the compound of Formula I or II, etc. may be included as an active ingredient in the composition. In one example, the composition may be a pharmaceutical composition. In one example, the composition may be used for the prevention, improvement, and / or treatment of cancer.

[0562] Another example of the present invention relates to a method for the prevention, improvement, and / or treatment of cancer, comprising the step of administering a compound of Formula I or II, etc., to a subject requiring prevention, improvement, and / or treatment of cancer. In one example, the method may further include the step of administering an immune checkpoint inhibitor to the subject. Here, the step of administering the compound of Formula I or II, etc., and the step of administering the immune checkpoint inhibitor may be performed sequentially, simultaneously, or separately, regardless of the order. Here, the compound of Formula I or II, etc., and the immune checkpoint inhibitor may be formulated into a single preparation and administered, or they may be formulated separately and then administered simultaneously, at different times, or sequentially, but are not limited thereto. Here, in the case of sequential administration, the order of administration is not limited, and the administration regimen may be appropriately adjusted according to the patient's condition, etc. In one example, the method may further include the step of identifying a subject requiring prevention, improvement, and / or treatment of cancer prior to the administration step.

[0563] In addition, the present invention provides a composition for the prevention, improvement, or treatment of cancer, comprising (a) a compound of Formula I or II, etc.; and (b) an immune checkpoint inhibitor. Herein, the composition may be a composition for co-administration. Herein, the composition may be a pharmaceutical composition. In one example, (a) a compound of Formula I or II, etc.; and (b) an immune checkpoint inhibitor may each be included as an active ingredient in the composition.

[0564] In one example, the above (a) compound of Formula I or II, etc.; and (b) immune checkpoint inhibitor may be formulated for concomitant administration. In one example, the above (a) compound of Formula I or II, etc.; and (b) immune checkpoint inhibitor may be formulated as a single preparation or as separate preparations; and if as separate preparations, each preparation may be used separately, either mixed or unmixed. If the above (a) compound of Formula I or II, etc.; and (b) immune checkpoint inhibitor are formulated separately, the two preparations may be administered sequentially regardless of the order, simultaneously, or separately. Here, in the case of sequential administration, the order of administration is not limited, and the administration regimen may be appropriately adjusted according to the patient's condition, etc.

[0565] Another example of the present invention relates to a method for the prevention, improvement, and / or treatment of cancer, comprising the step of (a) a compound of Formula I or II, etc.; and (b) co-administering an immune checkpoint inhibitor to a subject requiring prevention, improvement, and / or treatment of cancer. Herein, the method may further include the step of identifying a subject requiring prevention, improvement, and / or treatment of cancer prior to the administration step.

[0566] In one example, the administration steps of (a) the compound of Formula I or II, etc.; and (b) the immune checkpoint inhibitor, etc. may be performed sequentially regardless of the order, simultaneously, or separately. Additionally, (a) the compound of Formula I or II, etc.; and (b) the immune checkpoint inhibitor may be formulated into a single agent and administered, or they may be formulated separately and then administered simultaneously, at different times, or sequentially, but are not limited thereto. Here, in the case of sequential administration, the order of administration is not limited, and the administration regimen may be appropriately adjusted according to the patient's condition, etc.

[0567] Another example of the present invention relates to the use of a compound of Formula I or II, etc., for the preparation of a combination formulation of an immune checkpoint inhibitor. In one example, the combination formulation may be formulated separately from the immune checkpoint inhibitor, or may be formulated as a single formulation with the immune checkpoint inhibitor. When formulated separately, the combination formulation containing the compound of Formula I or II, etc., and the immune checkpoint inhibitor may be administered sequentially regardless of the order, simultaneously, or separately. In the case of sequential administration, the order of administration is not limited, and the administration regimen may be appropriately adjusted according to the patient's condition, etc.

[0568] Another example of the present invention relates to the use of compounds of Formula I or II, etc., for the manufacture of a drug for cancer treatment. Herein, the drug may further include an immune checkpoint inhibitor. In one example, the compound of Formula I or II, etc.; and the immune checkpoint inhibitor may be formulated into a single agent and included in the drug, or they may be formulated separately. In the case of separate formulations, each agent may be mixed and included in the drug, or they may be included separately without mixing. In the case of separate formulations, the two agents may be administered sequentially regardless of the order, simultaneously, or separately. Herein, in the case of sequential administration, the order of administration is not limited, and the administration regimen may be appropriately adjusted according to the patient's condition, etc.

[0569] Another example of the present invention may be to provide a combination kit of immune checkpoint inhibitors comprising a compound of Formula I or II, etc.

[0570] The above immune checkpoint inhibitor (ICI) refers to a drug capable of enhancing an anti-tumor immune response by inhibiting an immune checkpoint capable of blocking the activation of immune cells. In one example, the immune checkpoint may be selected from CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, TIM-3, Galectin-9, CEACAM-1, BTLA, TIGIT, VISTA, 2B4, GARP, and PD1H, but is not limited thereto.

[0571] The above immune checkpoint inhibitor may include, without limitation, any that can reduce the level and / or activity of immune checkpoints or interfere with the function of immune checkpoints. For example, the above immune checkpoint inhibitor includes an antagonist that targets immune checkpoints.

[0572] The above immune checkpoint inhibitors are included without limitation as long as they are capable of targeting and inhibiting immune checkpoints, but in one example, the above immune checkpoint inhibitors may target one or more selected from the group consisting of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, TIM-3, Galectin-9, CEACAM-1, BTLA, TIGIT, VISTA, 2B4, GARP, and PD1H. In one example, the above immune checkpoint inhibitors may be one or more antagonists selected from the group consisting of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, TIM-3, Galectin-9, CEACAM-1, BTLA, TIGIT, VISTA, 2B4, GARP, and PD1H.

[0573] In one example, the immune checkpoint inhibitor is a miRNA, siRNA, dsRNA, shRNA, antisense oligonucleotide, CRISPR / Cas, and combinations thereof that bind complementarily to or recognize a sequence encoding CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, TIM-3, Galectin-9, CEACAM-1, BTLA, TIGIT, VISTA, 2B4, GARP, or PD1H; and may be one or more selected from the group consisting of one or more antibodies that bind complementarily to one or more selected from the group consisting of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, TIM-3, Galectin-9, CEACAM-1, BTLA, TIGIT, VISTA, 2B4, GARP, and PD1H, or active fragments thereof (e.g., Fab, F(ab'), F(ab')2, and Fv, etc.), aptamers, peptides, peptide mimics, compounds, and combinations thereof.

[0574] In one example, the immune checkpoint inhibitor may be selected from the group consisting of pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab, avelumab, tislellizumab, ipilimumab, tremelimumab, dostarlimab, retipanlimab, camrelizumab, syntilimab, envapolimab, relatlimab, and sasanimab, but is not limited thereto.

[0575] In addition, the compound according to the present invention may be used in combination with an immune activator. Therefore, the description regarding the immune checkpoint inhibitor applies equally to the immune activator.

[0576] The above immune activator refers to a substance that increases antigen-specific or non-specific immune responses by directly or indirectly enhancing the activation signal of immune cells.

[0577] Accordingly, the above-mentioned immunoactivator may include, without limitation, any agent capable of enhancing an immune response, but in one example, the above-mentioned immunoactivator comprises one or more agents selected from the group consisting of CD28, 4-1BB (CD137), ICOS, OX40, GITR, CD27, and CD40; and

[0578] It may be one or more selected from the group consisting of one or more receptor agonists selected from the group consisting of B7-1, B7-2, 4-1BBL, ICOS-L, OX40L, GITRL, and CD70.

[0579] Meanwhile, the compound of Formula I or II of the present invention can be used to inhibit hematopoietic progenitor kinase 1 (HPK1).

[0580] Accordingly, the present invention may provide a composition for inhibiting hematopoietic progenitor kinase 1 (HPK1), comprising a compound of Formula I or II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or a pharmaceutically acceptable salt. In one example, the compound of Formula I or II, etc., may be included as an active ingredient in the composition. In one example, the composition may be a pharmaceutical composition.

[0581] Another example of the present invention relates to a method for inhibiting HPK1, comprising the step of administering a compound of Formula I or II, etc., to a subject requiring inhibition of HPK1. Herein, the method may further comprise the step of identifying a subject requiring inhibition of HPK1 prior to the administration step. Herein, the compound of Formula I or II, etc., may be administered in a pharmaceutically effective amount.

[0582] Another example of the present invention relates to the use of compounds of formula I or II, etc., for inhibiting HPK1.

[0583] Another example of the present invention relates to the use of compounds of formula I or II, etc., for the manufacture of HPK1 inhibitors.

[0584] Another example of the present invention relates to a kit for inhibiting HPK1, comprising a compound of formula I or II, etc.

[0585] The inhibition of HPK1 described above may include a decrease in HPK1 activity, a decrease in HPK1 normal function, a decrease in signal transduction by HPK1, and a decrease in interactions between HPK1 and other proteins.

[0586] In one example, the HPK1 inhibitor refers to a substance having HPK1 inhibitory efficacy, wherein HPK1 inhibition has the meaning described above. Here, the HPK1 inhibitor can exert preventive, corrective, and / or therapeutic effects on HPK1-related diseases or disorders through HPK1 inhibition.

[0587] In one example, a subject administered with a compound of Formula I or II, etc., or a composition containing the same, may have lower HPK1 activity and / or function compared to a control group. Here, the control group may be the HPK1 activity and / or function of other cancer patients or the compound of Formula I or II, etc., or the HPK1 activity and / or function of the subject prior to administration of the composition, but is not limited thereto.

[0588] In one example, the compound of Formula I or II, etc.; or a composition containing the same may inhibit HPK1 but not inhibit GLK (Germinal Center Kinase-Like Kinase). That is, the compound of Formula I or II, etc.; or a composition containing the same may have no inhibitory ability against GLK, or may have a lower specificity (or inhibitory ability) against GLK compared to the specificity (or inhibitory ability) against HPK1.

[0589] The above-mentioned GLK (Germinal Center Kinase-Like Kinase) belongs to the Ste20 family of kinases, just like HPK1; however, unlike HPK1, it is known to induce T cell proliferation and cytokine secretion by activating the MAPK (Mitogen-Activated Protein Kinase) signaling pathway involved in T cell activation. GLK is a known protein, and its function and sequence information are publicly available; for example, specific information can be retrieved from the database Uniprot (Reference No.: F5H5A3).

[0590] In one example, the compound of Formula I or II, etc.; or a composition containing the same may have an inhibitory ability on phosphorylated SLP-76 (pSLP-76). The phosphorylated SLP-76 may be SPL-76 with a phosphorylated serine residue. Inhibition of the phosphorylated SLP-76 may include a decrease in the activity of pSLP-76, a decrease in the normal function of pSLP-76, a decrease in signal transduction by pSLP-76, a decrease in the interaction between pSLP-76 and other proteins, and the induction of degradation of pSLP-76. In one example, the SPL-76 with a phosphorylated serine residue may be SPL-76 with a phosphorylated serine residue at position 376.

[0591] The above SLP-76 is an adapter protein of the TCR signaling pathway, and the activity of the TCR signal varies depending on the phosphorylation site of SLP-76. When the tyrosine residues of SLP-76 (e.g., tyrosine residues 113, 128, and / or 145) are phosphorylated (activating phosphorylation), downstream signaling proteins of the TCR signaling pathway gather to amplify the activation of T cells, but when the serine residues of SLP-76 (e.g., serine residue 376) are phosphorylated (inhibitory phosphorylation), the activity and tyrosine phosphorylation of SLP-76 are inhibited, and ubiquitination and proteasome degradation of SLP-76 are induced, thereby blocking the TCR signal. SLP-76 is a known protein, and its function and sequence information are known, and specific information can be found in the database GenBank, for example (Reference number: AAC50135.1).

[0592] In one example, the compound of Formula I or II, etc.; or a composition containing the same may induce inhibitory phosphorylation of SLP-76. In one example, the compound of Formula I or II, etc.; or a composition containing the same may induce phosphorylation of a serine residue of SLP-76.

[0593]

[0594] Meanwhile, the compound of Formula I or II of the present invention can activate the immune system or immune function by inhibiting HPK1, etc. Therefore, the compound of Formula I or II can be used for immune enhancement purposes.

[0595] Accordingly, the present invention may provide an immunostimulating composition comprising a compound of Formula I or II, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt. In one example, the compound of Formula I or II, etc., may be included as an active ingredient in the composition. In one example, the composition may be a pharmaceutical composition or a food composition.

[0596] Another example of the present invention relates to a method for enhancing immunity (e.g., a method for inducing an increase in immunity or improving immunity, etc.), comprising the step of administering a compound of Formula I or II, etc., to a subject requiring immune enhancement. Herein, the method may further include the step of identifying a subject requiring immune enhancement prior to the step of administration. Herein, the compound of Formula I or II, etc., may be administered in a pharmaceutically effective amount.

[0597] Another example of the present invention relates to the use of compounds of Formula I or II, etc., for immune enhancement.

[0598] Another example of the present invention relates to the use of compounds of Formula I or II, etc., for the manufacture of immunoadjuvants.

[0599] Another example of the present invention relates to an immune-enhancing kit comprising a compound of formula I or II, etc.

[0600] The above "immunostimulation (or immune enhancement)" may mean inducing an initial immune response to an antigen or increasing an existing immune response, and may be interchangeable with terms such as immune stimulation, immune enhancement, and immune activation. In one example, immune enhancement may mean one or more selected from the group consisting of, but not limited to, the enhancement (activation) and / or proliferation of immune cells (effector T cells, e.g., cytotoxic T cells; CD3+ T cells, CD4+ T cells, CD8+ T cells, NK cells, dendritic cells, etc.), inhibition and / or depletion of regulatory T cells (Treg), and increased production and / or secretion of immune proteins (e.g., cytokines, etc.).

[0601] In one example, a subject administered with a compound of Formula I or II, etc.; or a composition containing the same may have higher immune cell activity and / or levels of activated immune cells compared to a control group.

[0602] The compound of Formula I or II provided in this specification; or the subject of administration of a pharmaceutical composition containing the same may be any animal or cell, for example, an animal selected from mammals including humans, primates such as monkeys, rats, mice, etc., or cells, tissues, body fluids (e.g., serum) derived from (isolated from) said animal, or a culture thereof, for example, a human or cells, tissues, body fluids (e.g., serum) isolated from a human.

[0603] In one example, the pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier, a diluent, and / or an excipient in addition to a compound of Formula I or II, etc. The pharmaceutically acceptable carrier, diluent, and / or excipient may be any of those generally used in the formulation of the compound of Formula I or II, etc. For example, pharmaceutically acceptable carriers include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0604] In this specification, the term “carrier” means a compound that facilitates the addition of a compound into a cell or tissue, and the term “pharmaceutically acceptable” means a composition that is physiologically acceptable and, when administered to a human, does not typically cause allergic reactions such as gastrointestinal disturbances or dizziness, or similar reactions.

[0605] A pharmaceutical composition according to one example of the present invention may further include one or more selected from the group consisting of lubricants, humectants, sweeteners, flavor enhancers, emulsifiers, suspending agents, preservatives, etc.

[0606] In one example, the compound of Formula I or II, etc., and / or the pharmaceutical composition may be administered to a subject orally or parenterally.

[0607] More specifically, the compound of Formula I or II, etc., and / or the pharmaceutical composition may be administered by a route selected from the group consisting of oral administration, topical administration, subcutaneous administration, intradermal administration, intraperitoneal administration, intravenous administration, intramuscular administration, spinal administration, sublingual administration, buccal administration, rectal administration, vaginal administration, intracerebral administration, ocular administration, ear administration, nasal administration (e.g., inhalation, spray, etc.), transdermal administration, and endodermal administration.

[0608] In one example, the compound of Formula I or II, etc., and / or the pharmaceutical composition may be administered to a subject in a pharmaceutically effective amount. In this specification, the term "pharmaceutical effective amount" may mean an amount of active ingredient that can exert a pharmaceutically meaningful effect on the prevention, improvement, and / or treatment of a target disease (e.g., cancer). The appropriate dosage of the pharmaceutical composition represented by the amount of the compound of Formula I or II, etc., may be prescribed differently depending on various factors such as age, body weight, gender, pathological condition, diet, excretion rate and / or patient response sensitivity, type of formulation, time of administration, route of administration, and mode of administration. For example, the daily dosage of the compound of Formula I or II, etc., is preferably 1 mg / kg to 1000 mg / kg and may be administered once or several times a day as needed. In one example, the pharmaceutically effective amount of the compound of formula I or II, etc., or the suitable dosage of the pharmaceutical composition may be about 0.001 to about 1000 mg (amount of the compound of formula I or II, etc.) / kg (body weight) per day for an adult, about 0.01 to about 100 mg / kg, or about 0.1 to about 50 mg / kg.

[0609] In one example, the pharmaceutical composition of the present invention may be administered once a day or divided into several doses. The composition may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. Taking all of the above factors into consideration, it may be administered in an amount that obtains maximum effect with a minimum amount without side effects.

[0610] In one example, the pharmaceutical composition of the present invention may be formulated into a unit or multiple formulations by a method that can be easily performed by a person skilled in the art together with a pharmaceutically acceptable carrier and / or excipient. The formulation may be an oil- or aqueous medium, a suspension, an emulsion, an extract, and may be formulated and used in the form of external preparations such as powders, granules, sustained-release granules, enteric granules, liquids, eye drops, oxylic agents, emulsions, suspensions, ethanol tablets, troches, fragrances, limonene adrenergic agents, tablets, sustained-release tablets, enteric tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, irrigation solutions, warning agents, lotions, pastes, sprays, inhalants, patches, sterile injectable solutions, or aerosols; and the above external preparations may be creams, gels, patches, sprays, ointments, warning agents, lotions, liniments, pastes, or It may have formulations such as cataplasms.

[0611] In one example, when formulating the pharmaceutical composition of the present invention, it is prepared using a diluent or excipient such as a commonly used filler, extender, binder, wetting agent, disintegrant, or surfactant. In addition, the formulation may further include a dispersant or a stabilizer.

[0612] Solid dosage forms for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid dosage forms are prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc., with one or more compounds. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid dosage forms for oral administration include suspensions, liquids, emulsions, and syrups; in addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as humectants, sweeteners, flavorings, and preservatives, may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, and emulsions. As non-aqueous solvents and suspension solvents, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used.

[0613] In one example, the pharmaceutical composition of the present invention may be prepared in a unit dose form or contained in a multi-dose container by formulation using a pharmaceutically acceptable carrier according to a method that can be clearly carried out by a person skilled in the art to which the invention pertains.

[0614] In the present invention, “prevention” refers to any act of suppressing or delaying the onset of a target disease, “treatment” refers to any act of improving or beneficially altering the target disease and associated metabolic abnormality symptoms through the administration of a pharmaceutical composition according to the present invention, and “improvement” refers to any act of reducing parameters related to the target disease, such as the severity of symptoms, through the administration of a composition according to the present invention.

[0615] The composition of the present invention may be provided in the form of a food composition.

[0616] That is, the present invention may provide a food containing a compound of Formula I or II, etc. For example, the present invention may provide a food for the prevention or improvement of cancer; a food for inhibiting HPK1; or a food for immune enhancement, etc., containing a compound of Formula I or II, etc. In one example, the food may be a health functional food.

[0617] In one example, the food composition or food may be intended to be used in combination with an immune checkpoint inhibitor.

[0618] When the compounds of Formula I or II of the present invention are used as food additives, they may be added as they are, used together with other foods or food ingredients, or used appropriately according to conventional methods. The amount of the active ingredient can be appropriately determined according to the purpose of use (prevention, health, or therapeutic treatment). Generally, when manufacturing food or beverages, the compounds of Formula I or II of the present invention may be added in an amount of 15% by weight or less, or 10% by weight or less, relative to the raw materials. However, in the case of long-term consumption for the purpose of health and hygiene or health control, the above amount may be less than the above range, and since there are no issues regarding safety, the active ingredient may be used in an amount greater than the above range.

[0619] There are no specific restrictions on the types of the above-mentioned foods. Examples of foods to which the above-mentioned substance may be added include meat, sausage, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and include all health functional foods in the conventional sense.

[0620] In addition to the above, the composition of the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. Furthermore, the composition of the present invention may contain fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not critical, it is generally selected in the range of 0.01 to 0.20 parts by weight per 100 parts by weight of the composition of the present invention.

[0621] The above-mentioned health functional food is the same term as food for special health use (FosHU), and refers to a food with high medical or health effects that is processed to efficiently exhibit bio-regulatory functions in addition to nutritional supply. The above-mentioned food can be manufactured in various forms such as tablets, capsules, powders, granules, liquids, and pills to obtain the desired effect.

[0622] In addition to compounds of Formula I or II of the present invention and / or compositions containing the same, the kit of the present invention may further include other components, compositions, solutions, devices, etc. that are typically required for the preservation, efficacy, stability, and utilization (administration, etc.) of the said components.

[0623] In one example, the kit may further include an immune checkpoint inhibitor.

[0624] The compound according to the present invention and the pharmaceutically acceptable salt thereof can be usefully used for the prevention or treatment of diseases mediated by abnormal HPK1 regulation.

[0625] Hereinafter, preferred manufacturing examples and embodiments are presented to aid in understanding the present invention. However, the following embodiments are provided merely to facilitate a better understanding of the present invention, and the scope of the present invention is not limited by these embodiments.

[0626] Various synthesis methods for starting materials for synthesizing the compounds of the present invention are known, and if the starting materials are commercially available, they may be purchased from suppliers. Reagent suppliers include companies such as Sigma-Aldrich, TCI, Wako, Kanto, Fluorchem, Acros, Alfa, Fluka, and Dae-Jung, but are not limited thereto. Furthermore, unless otherwise specified, all commercially available materials were used without additional purification.

[0627] First, the compounds used in the synthesis of the following examples were prepared as described in the following preparation examples. The following preparation examples can be prepared using the general formulas described below, and, as a representative example, general formulas 1 and 2 corresponding to the preparation process of the compound in Example 1 are shown below.

[0628] This is an example of a compound represented by Chemical Formula 1 of Reaction Scheme 1, and can be appropriately modified to correspond to the structure of the example to be prepared.

[0629] General formula 1:

[0630]

[0631] Scheme 1. Reagents and Conditions: (a) Paraformaldehyde, sodium methoxide, methanol, sodium borohydride, 25–60 °C, 6 h; (b) Triethyl orthoformate, 140 °C, 12 h; (c) Bis(pinacollato)diborone, Pd(dppf)Cl2, potassium acetate, dimethylformamide, 100 °C, 16 h;

[0632]

[0633] [Preparation Example 1]

[0634] 5-Bromo-N3 -methylpyridine-3,4-diamine

[0635]

[0636] NaOMe (460 g, 2.55 mol, purity 30.0%) was added dropwise under N2 at 0 °C to a solution of 5-bromopyridine-3,4-diamine (160 g, 851 mmol) and paraformaldehyde (28.1 g, 936 mmol) dissolved in methanol (3000 mL), and the mixture was stirred at 25 °C for 4 hours. Sodium borohydride (32.2 g, 851 mmol) was added to the reaction mixture at 0 °C, and the mixture was stirred at 20 °C for 1 hour, then heated to 60 °C and stirred for 1 hour. The reaction mixture was stopped by treating it with 1.2 M hydrochloric acid (1000 mL) at 10 °C, and the solvent was removed by concentrating the reaction mixture under reduced pressure. The residue was diluted with a saturated aqueous solution of potassium carbonate (1000 mL) and extracted with ethyl acetate (800 mL × 3). The combined organic layer was washed with brine (500 mL), dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. This crude product was solidified using ethyl acetate / petroleum ether (1:1, 1500 mL). The mixture was filtered and dried under reduced pressure to obtain 5-bromo-N 3 -Methylpyridine-3,4-diamine (150 g, 742 mmol, 87.0%) was obtained as a yellow solid. 1 H NMR (400 MHz, MeOD-d4) δ 7.78 (s, 1H), 7.49 (s, 1H), 2.85 (s, 3H).

[0637]

[0638] [Preparation Example 2]

[0639] 7-Bromo-3-methyl-3H-imidazo[4,5-c]pyridine

[0640]

[0641] 5-Bromo-N 3methylpyridine-3,4-diamine (140 g, 693 mmol) was added to triethyl orthoformate (3000 mL), and the mixture was stirred at 140 °C for 12 hours. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (SiO2, petroleum ether / ethyl acetate and ethanol mixture = 10 / 1–1 / 1). Subsequently, it was solidified at 25 °C using petroleum ether / ethyl acetate (3 / 1, 500 mL). The mixture was filtered and dried to obtain 7-bromo-3-methyl-3H-imidazo[4,5-c]pyridine (120 g, 566 mmol, 82.0%) as a yellow solid. LCMS (M+H) + : 212.0

[0642]

[0643] [Preparation Example 3]

[0644] 3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-imidazo[4,5-c]pyridine

[0645]

[0646] Pd(dppf)Cl2 (24.2 g, 33.0 mmol) and potassium acetate (139 g, 1.41 mol) were added to a solution of 7-bromo-3-methyl-3H-imidazo[4,5-c]pyridine (100 g, 472 mmol) and bis(pinacolato)diborone (240 g, 943 mmol) dissolved in dimethylformamide (1000 mL) at 25 °C under N2, and the mixture was stirred at 100 °C for 16 hours. The reaction mixture was purified by column chromatography (SiO2, dichloromethane / methanol = 10 / 1~1 / 1) and concentrated to obtain the residue. This crude product was dissolved in dichloromethane (1000 mL), and the black solution was added dropwise to petroleum ether / ethyl acetate (5 L, 2 / 1) to separate a large amount of precipitate. After stirring at 25 °C for 10 minutes, the suspension was filtered. The filter cake was dried under reduced pressure, added to ethyl acetate (10 L) and stirred for 24 hours, then filtered, and the filtrate was concentrated under reduced pressure. It was dissolved again in dichloromethane (500 mL) and added to petroleum ether (5 L) to separate a large amount of precipitate. The suspension was filtered, and the filter cake was dried under reduced pressure to obtain 3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-imidazo[4,5-c]pyridine (41.2 g, 159 mmol, 33.0%) as a brown solid. 1 H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.56 (s, 1H), 8.38 (s, 1H), 3.94 (s, 3H), 1.33 (s, 12H).

[0647]

[0648] General formula 2:

[0649]

[0650] Scheme 1. Reagents and Conditions: (a) di-tert-butyl dicarbonate, 4-dimethylaminopyridine, acetonitrile, 60 °C, 0.5 h; (b) cyclopropylboronic acid, Pd(dppf)Cl2, cesium carbonate, 1,4-dioxane, 100 °C, 2 h; (c) trifluoroacetic acid, dichloromethane, 25 °C, 2 h; (d) N-bromosuccinimide, acetonitrile, 25 °C, 1 h; (e) 3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-imidazo[4,5-c]pyridine, Pd(PPh3)2Cl2, cesium carbonate, 1,4-dioxane, 100 ℃, 3 h;

[0651]

[0652] [Preparation Example 4]

[0653] Methyl 3-[bis[(1,1-dimethylethoxy)carbonyl]amino]-5-bromo-2-pyridinecarboxylate

[0654]

[0655] 4-dimethylaminopyridine (66 g, 541 mmol) was added to a solution of methyl 3-amino-5-bromopicolinate (50 g, 216.4 mmol) dissolved in acetonitrile (500 mL), followed by the addition of di-tert-butyl dicarbonate (117.94 g, 541 mmol). The resulting mixture was stirred at 60 °C for 1 hour. Subsequently, 4-dimethylaminopyridine (13.2 g, 108.2 mmol) and di-tert-butyl dicarbonate (23.59 g, 108.2 mmol) were added at room temperature. The reaction mixture was stirred at 60 °C for 0.5 hours. The mixture was extracted with ethyl acetate (1 L) and distilled water (100 mL). The aqueous layer was extracted again with ethyl acetate (200 mL × 2). The organic layer was washed with brine (100 mL), dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (10-20% ethyl acetate / petroleum ether) to obtain methyl 3-[bis[(1,1-dimethylethoxy)carbonyl]amino]-5-bromo-2-pyridinecarboxylate (86.3 g, 200 mmol, 92%), a white solid. LCMS (M+H) + : 431, 433.

[0656]

[0657] [Preparation Example 5]

[0658] Methyl 3-[bis[(1,1-dimethylethoxy)carbonyl]amino]-5-cyclopropyl-2-pyridinecarboxylate

[0659]

[0660] A mixture of methyl 3-[bis[(1,1-dimethylethoxy)carbonyl]amino]-5-bromo-2-pyridinecarboxylate (60 g, 139.1 mmol), cyclopropylboronic acid (35.85 g, 417.4 mmol), Pd(dppf)Cl2 (13.22 g, 18.1 mmol), cesium carbonate (63.46 g, 194.8 mmol), and 1,4-dioxane (1 L) was vacuumed and refilled with nitrogen three times. The resulting mixture was stirred at 100 °C under N2 for 2.5 hours. The mixture was filtered and washed with dichloromethane (400 mL). The filtrate was concentrated. The residue was purified by column chromatography (petroleum ether / ethyl acetate / dichloromethane = 6 / 1 / 1–4 / 1 / 1) to obtain the brown solid methyl methyl 3-[bis[(1,1-dimethylethoxy)carbonyl]amino]-5-cyclopropyl-2-pyridinecarboxylate (52.3 g, 133 mmol, 96%). LCMS (M+H) + : 393.

[0661]

[0662] [Preparation Example 6]

[0663] Methyl 3-amino-5-cyclopropylpicolinate

[0664]

[0665] Trifluoroacetic acid (250 mL) was added at 0 °C to a solution of 3-[bis[(1,1-dimethylethoxy)carbonyl]amino]-5-cyclopropyl-2-pyridinecarboxylate (52.3 g, 133.27 mmol) dissolved in dichloromethane (500 mL). The resulting mixture was stirred at room temperature for 2 hours. The mixture was concentrated, the residue was diluted with dichloromethane (600 mL), and neutralized to pH = 7 with an aqueous sodium bicarbonate solution. The aqueous solution was extracted with dichloromethane (200 mL × 2). The combined organic layer was washed with brine (80 mL), dried with anhydrous sodium sulfate, filtered, and concentrated to obtain methyl 3-amino-5-cyclopropylpicolinate (28 g, 146 mmol, >99%) as a brown solid. The product was used directly in the next step without further purification. LCMS (M+H) + : 193. 1 H NMR (400 MHz, DMSO-d6) δ 7.68 (d, J = 2.4 Hz, 1H), 6.78 (d, J = 2.4 Hz, 1H), 6.56 (brs, 2H), 3.77 (s, 3H), 1.92-1.84 (m, 1H), 1.05-1.00 (m, 2H), 0.74-0.69 (m, 2H).

[0666]

[0667] [Preparation Example 7]

[0668] Methyl 3-amino-6-bromo-5-cyclopropylpicolinate

[0669]

[0670] N-bromosuccinimide (25.93 g, 145.67 mmol) was added to a solution of methyl 3-amino-5-cyclopropylpicolinate (28 g, 145.67 mmol) dissolved in acetonitrile (500 mL) at 0 °C. The resulting mixture was stirred at room temperature for 1 hour. The mixture was extracted with ethyl acetate (500 mL) and distilled water (100 mL). The aqueous solution was extracted once more with ethyl acetate (200 mL × 2). The combined organic layer was washed with sodium thiosulfate (aqueous 50 mL) and brine (50 mL), dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash (Biotage) column chromatography (0-30% ethyl acetate / petroleum ether) to obtain methyl 3-amino-6-bromo-5-cyclopropylpicolinate (27.2 g, 100 mmol, 69%) as a yellow solid. LCMS (M+H) + : 271, 273. 1 H NMR (400 MHz, DMSO-d6) δ 6.85 (s, 1H), 6.70 (brs, 2H), 3.79 (s, 3H), 2.03-1.94 (m, 1H), 1.10-1.03 (m, 2H), 0.69-0.63 (m, 2H).

[0671]

[0672] [Preparation Example 8]

[0673] Methyl 3-amino-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0674]

[0675] A mixture of methyl 3-amino-6-bromo-5-cyclopropylpicolinate (2.0 g, 7.38 mmol), 3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-imidazo[4,5-c]pyridine (2.23 g, 8.85 mmol), cesium carbonate (3.12 g, 9.59 mmol), Pd(dppf)Cl2 (1.08 g, 1.48 mmol), dioxane (60 mL), and distilled water (6 mL) was vacuumed and refilled with nitrogen three times. The resulting mixture was stirred for 3 hours under N2 while maintaining a temperature of 100 °C. The mixture was filtered and washed with dichloromethane. The filtrate was extracted with dichloromethane and distilled water, and the organic layer was concentrated. The residue was purified by flash (Biotage) column chromatography (0-8% methanol / dichloromethane) to obtain methyl 3-amino-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (1.90 g, 5.88 mmol, 80%) as a brown solid. LCMS (M+H) + : 324. 1 H NMR (400 MHz, DMSO-d6) δ 8.97-9.05 (m, 1H), 8.35-8.39 (m, 1H), 8.27 (s, 1H), 6.86 (s, 1H), 6.65 (s, 2H), 5.76 (s, 1H), 3.99 (s, 3H), 3.76 (s, 3H), 1.65-1.75 (m, 1H), 0.65-0.76 (m, 2H), 0.48-0.64 (m, 2H).

[0676]

[0677] [Preparation Example 9]

[0678] methyl 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0679]

[0680] A mixture of methyl 3-amino-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (80 mg, 0.25 mmol), 4-bromo-1-(cyclopropylmethyl)-1H-pyrazole (75 mg, 0.37 mmol), tBubrettphos-Pd-G3 (42 mg, 0.05 mmol), cesium carbonate (121 mg, 0.37 mmol), and 1,4-dioxane (6 mL) was vacuumed and refilled with nitrogen three times. The resulting mixture was stirred under nitrogen at 100 °C for 20 hours. After concentrating the mixture, the residue was purified by flash (Biotage) column chromatography (0-10% methanol / dichloromethane) to obtain methyl 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (30 mg, 0.068 mmol, 27%) as a yellow solid. LCMS (M+H) + : 444.

[0681]

[0682] [Preparation Example 10]

[0683] 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 1]

[0684]

[0685] Methyl 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (30 mg, 0.068 mmol) and 7 M methanolic ammonia (6 mL) were added to a sealed tube. The reaction mixture was stirred at 100 °C for 8 hours. The progress was monitored using LCMS. After concentrating the mixture, the residue was purified for 10 minutes using prep-HPLC (Boston pHlex ODS, 21.2 × 250 mm, 10 μm, 25-55% acetonitrile / distilled water (10 mM NH4HCO3)) to obtain 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 1] (10.3 mg, 0.024 mmol, 36%) as a bright yellow solid. LCMS (M+H) + : 429.0. 1 H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.92 (s, 1H), 7.88 (d, J = 2.8 Hz, 1H), 7.56 (d, J = 3.2 Hz, 1H), 7.50 (s, 1H), 6.87 (s, 1H), 3.99-3.95 (m, 5H), 1.89-1.80 (m, 1H), 1.30-1.19 (m, 1H), 0.70-0.62 (m, 2H), 0.57-0.52 (m, 2H), 0.51~0.47(m, 2H), 0.41~0.36(m, 2H).

[0686]

[0687] [Example 2]

[0688] 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0689]

[0690] 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 2] was prepared by a method similar to that of [Example 1] (9.2 mg, 0.022 mmol, 38%). LCMS (M+H) + : 417.0. 1 H NMR (400 MHz, CDCl3) δ 9.54 (s, 1H), 8.90 (s, 1H), 8.62 (s, 1H), 7.99 (s, 1H), 7.94 (s, 1H), 7.49 (s, 1H), 7.40 (s, 1H), 6.92 (s, 1H), 5.30 (s, 1H), 4.53-4.47 (m, 1H), 4.01 (s, 3H), 1.94-1.87 (m, 1H), 1.54 (dd,J= 6.6, 2.6 Hz, 6H), 0.74-0.70 (m, 2H), 0.54 (d,J= 4.6 Hz, 2H).

[0691]

[0692] [Example 3]

[0693] 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide.

[0694]

[0695] Step 1] Preparation of 3-Bromo-1-cyclopropyl-5-methyl-1H-pyrazole

[0696]

[0697] A mixture of 3-bromo-5-methyl-1H-pyrazole (600 mg, 3.73 mmol), cyclopropylboronic acid (640 mg, 7.45 mmol), copper II acetate (745 mg, 3.73 mmol), 2,2'-bipyridine (583 mg, 3.73 mmol), sodium bicarbonate (626 mg, 7.45 mmol), and 1,2-dichloroethane (30 mL) was vacuumed and refilled with oxygen three times. The resulting mixture was stirred under O2 at 70 °C for 12 hours. The mixture was filtered and washed with dichloromethane (100 mL). The organic layer was washed with distilled water (20 mL) and brine (20 mL), dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash (Biotage) column chromatography (0-10% ethyl acetate / petroleum ether) to obtain 3-bromo-1-cyclopropyl-5-methyl-1H-pyrazole (430 mg, 2.13 mmol, 57%), a colorless oil. LCMS (M+H) + : 201.

[0698] Step 2] Preparation of methyl 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0699]

[0700] Nitrogen was bubbled into a mixture of methyl 3-amino-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (60 mg, 0.19 mmol), 3-bromo-1-cyclopropyl-5-methyl-1H-pyrazole (93 mg, 0.46 mmol), t-Bubrettphos-Pd-G3 (32 mg, 0.037 mmol), cesium carbonate (91 mg, 0.28 mmol), and dioxane (1.5 mL). The resulting mixture was stirred in a microwave reactor at 105 °C for 2.5 hours. The mixture was concentrated. The residue was purified by flash (Biotage) column chromatography (0-13% methanol / dichloromethane) to obtain methyl 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (77 mg, 0.17 mmol, 93%) as a yellow solid. LCMS (M+H) + : 444.

[0701] Step 3] Preparation of 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide

[0702]

[0703] Methyl 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (77 mg, 0.17 mmol) and 7 M methanolic ammonia (8 mL) were added to a sealed tube. The resulting reaction mixture was stirred at 100 °C for 6 hours. The progress was monitored using LCMS. The mixture was concentrated. The residue was purified for 10 minutes using prep-HPLC (Boston pHlex ODS, 21.2 × 250 mm, 10 μm, 30–60% acetonitrile / distilled water (10 mM NH4HCO3)) to obtain 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide (36.3 mg, 0.09 mmol, 49%) as a yellow solid. LCMS (M+H) + : 429.1. 1 H NMR (500 MHz, DMSO-d6) δ 10.82 (s, 1H), 9.01 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.23 ​​(s, 1H), 7.95 (d, J = 3.0 Hz, 1H), 7.63 (d, J = 2.5 Hz, 1H), 3.98 (s, 3H), 3.51-3.46 (m, 1H), 2.32 (s, 3H), 1.90-1.84 (m, 1H), 1.08-1.05 (m, 2H), 1.01-0.96 (m, 2H), 0.82-0.77 (m, 2H), 0.65-0.61(m, 2H).

[0704]

[0705] [Example 4]

[0706] 5-cyclopropyl-3-((1-ethyl-1H-1,2,4-triazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0707]

[0708] 5-cyclopropyl-3-((1-ethyl-1H-1,2,4-triazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 4] was prepared by a method similar to that of [Example 1] (9.7 mg, 0.024 mmol, 36%). LCMS (M+H) + : 404.0 1 H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.03 (s, 1H), 8.49 (s, 1H), 8.47 (s, 1H), 8.41 (s, 1H), 8.38 (s, 1H), 8.06 (d, J = 2.8 Hz, 1H), 7.78 (d, J = 2.8 Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 3.99 (s, 3H), 1.95-1.87 (m, 1H), 1.43 (d, J = 7.2 Hz, 3H), 0.83-0.78 (m, 2H), 0.67-0.62 (m, 2H).

[0709]

[0710] [Example 5]

[0711] 5-cyclopropyl-3-((3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0712]

[0713] 5-cyclopropyl-3-((3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 5] was prepared by a method similar to that of [Example 1] (23.7 mg, 0.050 mmol, 61%). LCMS (M+H) + : 471.1. 1H NMR (500 MHz, DMSO-d6) δ 11.12 (s, 1H), 9.02 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.37 (s, 1H), 8.01 (d, J = 3.0 Hz, 1H), 7.68 (d, J = 3.0 Hz, 1H), 7.60 (s, 1H), 5.00 (q, J = 9.0 Hz, 2H), 3.99 (s, 3H), 2.01 (s, 3H), 1.89-1.83 (m, 1H), 0.80-0.75 (m, 2H), 0.64-0.60 (m, 2H).

[0714]

[0715] [Example 6]

[0716] 5-cyclopropyl-3-((1-(1-hydroxy-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0717]

[0718] Step 1] Preparation of methyl 2-(4-bromo-1H-pyrazole-1-yl)-2-methylpropanoate

[0719]

[0720] Cesium carbonate (19.95 g, 61.2 mmol) was added to a solution of 4-bromo-1H-pyrazole (3 g, 20.4 mmol) dissolved in dimethylformamide (60 mL), and then methyl 2-bromo-2-methylpropanoate (4.43 g, 24.5 mmol) was added at 0 °C. The resulting mixture was stirred at 80 °C for 2 hours. After extracting the mixture with distilled water and ethyl acetate, the organic layer was washed with brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash (Biotage) column chromatography (0-20% ethyl acetate / petroleum ether) to obtain methyl 2-(4-bromo-1H-pyrazole-1-yl)-2-methylpropanoate (4.36 g, 17.6 mmol, 86%), a white solid. LCMS (M+H) + : 247, 249.

[0721] Step 2] Preparation of 2-(4-bromo-1H-pyrazole-1-yl)-2-methylpropan-1-ol

[0722]

[0723] Sodium borohydride (646 mg, 17 mmol) was added at 0 °C to a solution of methyl 2-(4-bromo-1H-pyrazole-1-yl)-2-methylpropanoate (2.1 g, 8.5 mmol) dissolved in methanol (50 mL). The resulting mixture was stirred at 50 °C for 3 hours. The mixture was extracted with an aqueous sodium bicarbonate solution and dichloromethane. The organic layer was washed with brine, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 2-(4-bromo-1H-pyrazole-1-yl)-2-methylpropan-1-ol (1.74 g, 7.9 mmol, 94%) as a yellow solid. LCMS (M+H) + : 219.

[0724] Step 3] Preparation of 2-(4-bromo-1H-pyrazol-1-yl)-2-methylpropyl tert-butyl carbonate

[0725]

[0726] Triethylamine (0.27 mL, 1.92 mmol) was added to a mixture of 2-(4-bromo-1H-pyrazole-1-yl)-2-methylpropan-1-ol (210 mg, 0.96 mmol) and 4-dimethylaminopyridine (58 mg, 0.48 mmol) in dichloromethane (5 mL), and then di-tert-butyl dicarbonate (251 mg, 1.15 mmol) was added at 0 °C. The reaction mixture was stirred at room temperature for 16 hours and then concentrated. The residue was purified by flash (Biotage) column chromatography (0-8% ethyl acetate / petroleum ether) to obtain 2-(4-bromo-1H-pyrazole-1-yl)-2-methylpropyl tert-butyl carbonate (220 mg, 0.69 mmol, 72%) as a white solid. LCMS (M+H) + : 319.

[0727] Step 4] Preparation of methyl 3-((1-(1-((tert-butoxycarbonyl)oxy)-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0728]

[0729] Nitrogen was bubbled into a mixture of methyl 3-amino-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (90 mg, 0.28 mmol), 2-(4-bromo-1H-pyrazol-1-yl)-2-methylpropyl tert-butyl carbonate (178 mg, 0.56 mmol), tBubrettphos-Pd-G3 (48 mg, 0.056 mmol), cesium carbonate (136 mg, 0.42 mmol), and 1,4-dioxane (2.5 mL). The resulting mixture was stirred in a microwave reactor at 100 °C for 2 hours. After the reaction was complete, the mixture was concentrated, and the residue was purified by flash (Biotage) column chromatography (0-8% methanol / dichloromethane) to obtain methyl 3-((1-(1-((tert-butoxycarbonyl)oxy)-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (100 mg, 0.18 mmol, 64%) as a yellow solid. LCMS (M+H) + : 562.

[0730] Step 5] Preparation of 5-cyclopropyl-3-((1-(1-hydroxy-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide

[0731]

[0732] Methyl 3-((1-(1-((tert-butoxycarbonyl)oxy)-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (100 mg, 0.18 mmol) and 7 M methanolic ammonia (15 mL) were added to a sealed tube. The reaction mixture was stirred at 100 °C for 7 hours, and after the reaction was finished, the mixture was concentrated. The residue was purified for 10 minutes using prep-HPLC (Boston pHlex ODS, 21.2 × 250 mm, 10 μm, 25-55% acetonitrile / distilled water (10 mM NH4HCO3)) to obtain 5-cyclopropyl-3-((1-(1-hydroxy-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide (17.5 mg, 0.04 mmol, 22%) as a white solid. LCMS (M+H) + : 447.3. 1 H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.91 (s, 1H), 7.87 (d, J = 3.2 Hz, 1H), 7.54 (d, J = 3.2 Hz, 1H), 7.52 (s, 1H), 6.89 (s, 1H), 4.98 (t, J = 5.6 Hz, 1H), 3.98 (s, 3H), 3.58 (d, J = 5.6 Hz, 2H), 1.88-1.80 (m, 1H), 1.48 (s, 6H), 0.68~0.63(m, 2H), 0.51~0.47(m, 2H).

[0733]

[0734] [Example 7]

[0735] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)picolinamide

[0736]

[0737] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)picolinamide [Example 7] was prepared by a method similar to that of [Example 1] (20.8 mg, 0.045 mmol, 43%). LCMS (M+H) + : 457.1. 1 H NMR (500 MHz, DMSO-d6) δ 11.04 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.40 (s, 1H), 8.26 (s, 1H), 8.00 (d, J = 2.5 Hz, 1H), 7.80 (d, J = 2.5 Hz, 1H), 7.70 (d, J = 3.0 Hz, 1H), 6.14 (d, J = 2.5 Hz, 1H), 5.06 (q, J = 9.0 Hz, 2H), 3.99 (s, 3H), 1.90-1.84 (m, 1H), 0.80-0.75 (m, 2H), 0.65-0.61 (m, 2H).

[0738]

[0739] [Example 8]

[0740] 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0741]

[0742] 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 8] was prepared by a method similar to that of [Example 1] (16.7 mg, 0.04 mmol, 58%). LCMS (M+H) + : 417.3. 1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.92 (s, 1H), 7.88 (d, J = 2.8 Hz, 1H), 7.56 (d, J = 3.2 Hz, 1H), 7.50 (s, 1H), 6.87 (s, 1H), 3.99-3.95 (m, 5H), 1.89-1.80 (m, 1H), 1.30-1.19 (m, 1H), 0.70-0.62 (m, 2H), 0.57-0.52 (m, 2H), 0.51-0.47 (m, 2H), 0.41-0.36 (m, 2H).

[0743]

[0744] [Example 9]

[0745] 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0746] Step 1] Preparation of methyl 3-bromo-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0747]

[0748] To a solution of methyl 3-amino-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (500 mg, 1.55 mmol) dissolved in acetonitrile (40 mL), tert-butyl nitrite (239 mg, 2.32 mmol) was added, followed by the addition of cupric bromide (345 mg, 1.55 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 16 hours. Afterward, the mixture was filtered and the filtrate was concentrated. The residue was extracted with dichloromethane (150 mL) and distilled water (30 mL), and the organic layer was concentrated. The residue was purified by flash (Biotage) column chromatography (0-6% methanol / dichloromethane) to obtain methyl 3-bromo-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (150 mg, 0.39 mmol, 25%) as a bright yellow solid. LCMS (M+H) + : 387.1, 389.1.

[0749] Step 2] Preparation of methyl 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0750]

[0751] Nitrogen was bubbled into a mixture of methyl 3-bromo-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (50 mg, 0.13 mmol), 4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-amine (46 mg, 0.26 mmol), XantPhos (30 mg, 0.05 mmol), Pd2(dba)3 (24 mg, 0.026 mmol), cesium carbonate (84 mg, 0.26 mmol), and toluene (2 mL). The reaction mixture was stirred in a microwave reactor at 100 °C for 2 hours and then concentrated. The residue was purified by flash (Biotage) column chromatography (0-13% methanol / dichloromethane) to obtain methyl 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (42 mg, 0.09 mmol, 67%) as a yellow solid. LCMS (M+H) + : 486.

[0752] Step 3] Preparation of 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide

[0753]

[0754] Methyl 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (40 mg, 0.082 mmol) and 7 M methanolic ammonia (6 mL) were added to a sealed tube. The resulting reaction mixture was stirred at 100 °C for 6 hours, after which the mixture was concentrated. The residue was purified for 10 minutes using prep-HPLC (Boston pHlex ODS, 21.2 × 250 mm, 10 μm, 25-55% acetonitrile / distilled water (10 mM NH4HCO3)) to obtain 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide (23.7 mg, 0.05 mmol, 61%) as a white solid. LCMS (M+H) + : 471.3. 1 H NMR (500 MHz, DMSO-d6) δ 11.12 (s, 1H), 9.02 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.37 (s, 1H), 8.01 (d, J = 3.0 Hz, 1H), 7.68 (d, J = 3.0 Hz, 1H), 7.60 (s, 1H), 5.00 (q, J = 9.0 Hz, 2H), 3.99 (s, 3H), 2.01 (s, 3H), 1.89-1.83 (m, 1H), 0.80-0.75 (m, 2H), 0.64-0.60 (m, 2H).

[0755]

[0756] [Example 10]

[0757] 5-cyclopropyl-3-((1,5-dimethyl-1H-imidazole-4-yl)amino)-6-(3-methyl-3H-imidazoz[4,5-c]pyridine-7-yl)picolineamide

[0758]

[0759] 5-cyclopropyl-3-((1,5-dimethyl-1H-imidazole-4-yl)amino)-6-(3-methyl-3H-imidazō[4,5-c]pyridine-7-yl)picolinamide [Example 10] was prepared by a method similar to that of [Example 9] (5.2 mg, 0.013 mmol, 13%). LCMS (M+H) + : 403.2. 1 H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 8.99 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.89 (d,J= 2.8 Hz, 1H), 7.54 (d,J= 2.8 Hz, 1H), 7.51 (s, 1H), 7.32 (s, 1H), 3.99 (s, 3H), 3.57 (s, 3H), 2.10 (s, 3H), 1.89-1.81 (m, 1H), 0.69-0.63 (m, 2H), 0.44-0.39 (m, 2H).

[0760]

[0761] [Example 11]

[0762] 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0763] Step 1] Preparation of 1-isopropyl-4-methyl-3-nitro-1H-pyrazole

[0764]

[0765] Cesium carbonate (1.79 g, 5.51 mmol) was added to a solution of 4-methyl-3-nitro-1H-pyrazole (350 mg, 2.75 mmol) dissolved in dimethylformamide (10 mL), followed by the addition of 2-bromopropane (406 mg, 3.3 mmol) at 0 °C. The reaction mixture was stirred at 80 °C for 2 hours. The mixture was filtered and washed with ethyl acetate. The filtrate was partitioned with distilled water and ethyl acetate. The organic layer was washed with brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash (Biotage) column chromatography (0-35% ethyl acetate / petroleum ether) to obtain 1-isopropyl-4-methyl-3-nitro-1H-pyrazole (344 mg, 2.03 mmol, 74%) as a white solid. LCMS (M+H) + : 170.

[0766] Step 2] Preparation of 1-Isopropyl-4-Methyl-1H-Pyrazole-3-Amine

[0767]

[0768] 10% Pd / C (100 mg) was added to a solution of 1-isopropyl-4-methyl-3-nitro-1H-pyrazole (344 mg, 2.03 mmol) dissolved in methanol (30 mL). The reaction mixture was stirred at room temperature under H2 for 3 hours, and after the reaction was complete, the mixture was filtered and washed with methanol. The filtrate was concentrated and dried under high vacuum to obtain 1-isopropyl-4-methyl-1H-pyrazole-3-amine (270 mg, 1.94 mmol, 95%), a colorless oil. LCMS (M+H) + : 140.

[0769] Step 3] Preparation of methyl 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0770]

[0771] Nitrogen was bubbled into a mixture of methyl 3-bromo-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (50 mg, 0.13 mmol), 1-isopropyl-4-methyl-1H-pyrazole-3-amine (36 mg, 0.26 mmol), XantPhos (30 mg, 0.05 mmol), Pd2(dba)3 (24 mg, 0.026 mmol), cesium carbonate (84 mg, 0.26 mmol), and toluene (2 mL). The resulting mixture was stirred in a microwave reactor at 100 °C for 2 hours. The mixture was concentrated. The residue was purified by flash (Biotage) column chromatography (0-13% methanol / dichloromethane) to obtain methyl 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (40 mg, 0.09 mmol, 70%) as a yellow solid. LCMS (M+H) + : 446.

[0772] Step 4] Preparation of 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide

[0773]

[0774] Methyl 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (40 mg, 0.09 mmol) and 7 M methanolic ammonia (6 mL) were added to a sealed tube. The resulting reaction mixture was stirred at 100 °C for 6 hours, and after the reaction was finished, the mixture was concentrated. The residue was purified for 10 minutes using prep-HPLC (Boston pHlex ODS, 21.2 × 250 mm, 10 μm, 35–65% acetonitrile / distilled water (10 mM NH4HCO3)) to obtain 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide (34.7 mg, 0.08 mmol, 66%) as a white solid. LCMS (M+H) + : 431.2. 1 H NMR (500 MHz, DMSO-d6) δ 10.92 (s, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.36 (s, 1H), 7.97 (d, J = 3.0 Hz, 1H), 7.61 (d, J = 3.0 Hz, 1H), 7.50 (s, 1H), 4.37 (sept, J = 6.5 Hz, 1H), 3.99 (s, 3H), 1.97 (s, 3H), 1.89-1.83 (m, 1H), 1.42 (d, J = 6.5 Hz, 6H), 0.82~0.78(m, 2H), 0.64~0.60(m, 2H).

[0775]

[0776] [Example 12]

[0777] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)picolinamide

[0778]

[0779] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)picolinamide [Example 12] was prepared by a method similar to that of [Example 1] (13.9 mg, 0.03 mmol, 29%). LCMS (M+H) + : 457.2. 1 H NMR (500 MHz, DMSO-d6) δ 9.95 (s, 1H), 9.00 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 8.02 (s, 1H), 7.91 (d, J = 2.5 Hz, 1H), 7.68 (s, 1H), 7.60 (d, J = 2.5 Hz, 1H), 6.83 (s, 1H), 5.14 (dd, J = 18.0, 4.5 Hz, 1H), 3.98 (s, 3H), 1.88-1.81 (m, 1H), 0.70-0.66 (m, 2H), 0.52-0.48 (m, 2H).

[0780]

[0781] [Example 13]

[0782] 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0783]

[0784] 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 13] was prepared by a method similar to that of [Example 1] (8.6 mg, 0.02 mmol, 30%). LCMS (M+H) + : 439.2. 1H NMR (500 MHz, DMSO-d6) δ 9.91 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.95 (s, 1H), 7.90 (d,J= 3.5 Hz, 1H), 7.62 (s, 1H), 7.58 (d,J= 3.5 Hz, 1H), 6.85 (s, 1H), 6.39 (tt,J= 55.5, 4.0 Hz, 1H), 4.63 (dt,J= 15.0, 4.0 Hz, 1H), 3.98 (s, 3H), 1.88-1.82 (m, 1H), 0.69-0.65 (m, 2H), 0.52-0.48 (m, 2H).

[0785]

[0786] [Example 14]

[0787] 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0788]

[0789] 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 14] was prepared by a method similar to that of [Example 9] (6.3 mg, 0.02 mmol, 33%). LCMS (M+H) + : 403.3. 1 H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.89 (d, J = 2.8 Hz, 1H), 7.77 (s, 1H), 7.56 (d, J = 3.0 Hz, 1H), 6.59 (s, 1H), 3.98 (s, 3H), 3.79 (s, 3H), 2.03 (s, 3H), 1.88-1.83 (m, 1H), 0.67-0.63 (m, 2H), 0.45-0.43 (m, 2H).

[0790]

[0791] [Example 15]

[0792] 5-cyclopropyl-3-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0793]

[0794] 5-cyclopropyl-3-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 15] was prepared by a method similar to that of [Example 1] (8.0 mg, 0.02 mmol, 41%). LCMS (M+H) + : 421.4. 1 H NMR (500 MHz, DMSO-d6) δ 9.88 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.93 (s, 1H), 7.89 (d, J = 2.5 Hz, 1H), 7.57-7.56 (m, 2H), 6.86 (s, 1H), 4.78 (dt, J = 49.5, 5.0 Hz, 2H), 4.43 (dt, J = 27.0, 5.0 Hz, 2H), 3.98 (s, 3H), 1.88-1.82 (m, 1H), 0.69-0.64 (m, 2H), 0.51-0.47 (m, 2H).

[0795]

[0796] [Example 16]

[0797] 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0798]

[0799] 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 16] was prepared by a method similar to that of [Example 1] (31.5 mg, 0.07 mmol, 81%). LCMS (M+H) + : 433.2. 1 H NMR (500 MHz, DMSO-d6) δ 9.85 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.95 (s, 1H), 7.88 (d, J = 2.5 Hz, 1H), 7.86 (s, 1H), 7.56 (d, J = 3.0 Hz, 1H), 7.51 (s, 1H), 6.85 (s, 1H), 4.26 (t, J = 5.0 Hz, 2H), 3.98 (s, 3H), 3.70 (t, J = 5.0 Hz, 2H), 3.26 (s, 3H), 1.87-1.82 (m, 1H), 0.69-0.65 (m, 2H), 0.51-0.47 (m, 2H).

[0800]

[0801] [Example 17]

[0802] 5-cyclopropyl-3-((3-fluoro-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0803]

[0804] 5-cyclopropyl-3-((3-fluoro-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 17] was prepared by a method similar to that of [Example 9] (18.3 mg, 0.05 mmol, 65%). LCMS (M+H) + : 407.3. 1H NMR (400 MHz, DMSO-d6) δ 9.69 (s, 1H), 9.01 (s, 1H), 8.42 (s, 1H), 8.39 (s, 1H), 7.92 (d, J = 2.8 Hz, 1H), 7.87 (d, J = 2.4 Hz, 1H),7.62 (d, J = 2.8 Hz, 1H), 6.64 (s, 1H), 3.98 (s, 3H), 3.76 (s, 3H), 1.89-1.82 (m, 1H), 0.70-0.64 (m, 2H), 0.49-0.45 (m, 2H).

[0805]

[0806] [Example 18]

[0807] 5-cyclopropyl-3-((3-(difluoromethyl)-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0808]

[0809] 5-cyclopropyl-3-((3-(difluoromethyl)-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 18] was prepared by a method similar to that of [Example 9] (17.7 mg, 0.04 mmol, 61%). LCMS (M+H) + : 439.3. 1 H NMR (400 MHz, DMSO-d6) δ 10.12 (s, 1H), 9.00 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 8.06 (s, 1H), 7.91 (d, J = 2.8 Hz, 1H), 7.58 (d, J = 2.8 Hz, 1H), 6.97 (t, J = 13.6 Hz, 1H), 6.80 (s, 1H), 3.98 (s, 3H), 3.91 (s, 3H), 1.89-1.82 (m, 1H), 0.70-0.64 (m, 2H), 0.56-0.50 (m, 2H).

[0810]

[0811] [Example 19]

[0812] 5-cyclopropyl-3-((1-isopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0813]

[0814] 5-cyclopropyl-3-((1-isopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 19] was prepared by a method similar to that of [Example 9] (22.5 mg, 0.05 mmol, 53%). LCMS (M+H) + : 431.2. 1 H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.38 (s, 1H), 7.87 (d, J = 2.5 Hz, 1H), 7.84 (s, 1H), 7.53 (d, J = 3.0 Hz, 1H), 6.58 (s, 1H), 4.42 (sept, J = 6.5 Hz, 1H), 3.98 (s, 3H), 2.04 (s, 3H), 1.88-1.81 (m, 1H), 1.41 (d, J = 7.0 Hz, 6H), 0.67-0.63 (m, 2H), 0.48-0.39 (m, 2H).

[0815]

[0816] [Example 20]

[0817] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1-methylpiperidine-4-yl)-1H-pyrazole-4-yl)amino)picolinamide

[0818]

[0819] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1-methylpiperidine-4-yl)-1H-pyrazole-4-yl)amino)picolinamide [Example 20] was prepared by a method similar to that of [Example 1] (32.1 mg, 0.07 mmol, 97%). LCMS (M+H) + : 472.4. 1 H NMR (400 MHz, CDCl3) δ 9.55 (s, 1H), 8.89 (s, 1H), 8.61 (s, 1H), 7.99 (s, 1H), 7.95 (d, J = 4.3 Hz, 1H), 7.49 (s, 1H), 7.42 (s, 1H), 6.91 (s, 1H), 5.34 (d, J = 4.3 Hz, 1H), 4.17 - 4.10 (m, 1H), 4.00 (s, 3H), 3.00 (d, J = 12.2 Hz, 2H), 2.35 (s, 3H), 2.22-2.16 (m, 4H), 2.06 (ddd, J = 16.0, 12.0, 3.4 Hz, 2H), 1.93-1.87 (m, 1H), 0.77-0.69 (m, 2H), 0.56-0.49 (m, 2H).

[0820]

[0821] [Example 21]

[0822] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)picolinamide

[0823]

[0824] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)picolinamide [Example 21] was prepared by a method similar to that of [Example 1] (9.5 mg, 0.02 mmol, 49%). LCMS (M+H) + : 459.3. 1H NMR (400 MHz, DMSO-d6) δ 9.89 (s, 1H), 9.01 (d, J = 3.5 Hz, 1H), 8.43 (d, J = 2.1 Hz, 1H), 8.40 (d, J = 3.7 Hz, 1H), 7.98 (s, 1H), 7.89 (s, 1H), 7.58 (s, 1H), 7.54 (s, 1H), 6.86 (s, 1H), 4.40 (tt, J = 10.5, 5.3 Hz, 1H), 3.98 (s, 4H), 3.96 (d, J = 3.3 Hz, 1H), 3.51-3.45 (m, 2H), 2.02-1.95 (m, 4H), 1.89-1.82 (m, 1H), 0.69-0.64 (m, 2H), 0.52-0.48 (m, 2H).

[0825]

[0826] [Example 22]

[0827] 5-cyclopropyl-3-((1-ethyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0828]

[0829] 5-cyclopropyl-3-((1-ethyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 22] was prepared by a method similar to that of [Example 9] (23.5 mg, 0.06 mmol, 57%). LCMS (M+H) + : 417.3. 1H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 9.00 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 7.88 (s, 1H), 7.82 (s, 1H), 7.55 (s, 1H), 6.59 (s, 1H), 4.07 (q, J = 7.2 Hz, 2H), 3.98 (s, 3H), 2.04 (s, 3H), 1.88-1.82 (m, 1H), 1.37 (t, J = 7.2 Hz, 3H), 0.69-0.62 (m, 2H), 0.46-0.40 (m, 2H).

[0830]

[0831] [Example 23]

[0832] 5-cyclopropyl-3-((1-(difluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0833]

[0834] 5-cyclopropyl-3-((1-(difluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 23] was prepared by a method similar to that of [Example 9] (12.2 mg, 0.03 mmol, 50%). LCMS (M+H) + : 425.3. 1 H NMR (500 MHz, DMSO-d6) δ 10.14 (s, 1H), 9.01 (s, 1H), 8.43 (s, 1H), 8.40 (s, 2H), 7.95 (s, 1H), 7.94 (d, J = 2.5 Hz, 1H), 7.79 (t, J = 59.0 Hz, 1H), 7.63 (d, J = 3.5 Hz, 1H), 6.91 (s, 1H), 3.98 (s, 3H), 1.90-1.84 (m, 1H), 0.71-0.66 (m, 2H), 0.59-0.55 (m, 2H).

[0835]

[0836] [Example 24]

[0837] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-4-yl)amino)picolinamide

[0838]

[0839] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-4-yl)amino)picolinamide [Example 24] was prepared by a method similar to that of [Example 9] (10.7 mg, 0.03 mmol, 44%). LCMS (M+H) + : 443.1. 1 H NMR (500 MHz, DMSO-d6) δ 10.22 (s, 1H), 9.02 (s, 1H), 8.64 (s, 1H), 8.43 (s, 1H), 8.40 (s, 1H), 8.16 (s, 1H), 7.96 (d, J = 2.0 Hz, 1H), 7.67 (d, J = 3.0 Hz, 1H),6.94 (s, 1H), 3.98 (s, 3H), 1.90-1.84 (m, 1H), 0.71-0.66 (m, 2H), 0.63-0.59 (m, 2H).

[0840]

[0841] [Example 25]

[0842] 5-cyclopropyl-3-((1-cyclopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0843]

[0844] 5-cyclopropyl-3-((1-cyclopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 25] was prepared by a method similar to that of [Example 9] (15.3 mg, 0.04 mmol, 63%). LCMS (M+H)+ : 429.3. 1 H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.38 (s, 1H), 7.88 (d, J = 3.0 Hz, 1H), 7.85 (s, 1H), 7.54 (d, J = 2.5 Hz, 1H), 6.58 (s, 1H), 3.98 (s, 3H), 3.69-3.64 (m, 1H), 2.02 (s, 3H), 1.89-1.82 (m, 1H), 1.06-1.01 (m, 2H), 0.95-0.91 (m, 2H), 0.68-0.63 (m, 2H), 0.45-0.41 (m, 2H).

[0845]

[0846] [Example 26]

[0847] 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0848]

[0849] 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 26] was prepared by a method similar to that of [Example 9] (13.4 mg, 0.03 mmol, 40%). LCMS (M+H) + : 457.1. 1 H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H), 9.01 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 8.19 (s, 1H), 7.95 (s, 1H), 7.63 (s, 1H), 6.82 (s, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 1.89-1.81 (m, 1H), 0.71-0.64 (m, 2H), 0.58-0.53 (m, 2H).

[0850]

[0851] [Example 27]

[0852] 5-cyclopropyl-3-((1-(difluoromethyl)-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0853]

[0854] 5-cyclopropyl-3-((1-(difluoromethyl)-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 27] was prepared by a method similar to that of [Example 9] (17.1 mg, 0.04 mmol, 50%). LCMS (M+H) + : 439.3. 1 H NMR (500 MHz, DMSO-d6) δ 10.11 (s, 1H), 9.01 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 8.34 (s, 1H), 7.95 (d, J = 3.5 Hz, 1H), 7.70 (t, J = 59.0 Hz, 1H), 7.64 (d, J = 2.5 Hz, 1H), 6.70 (s, 1H), 3.98 (s, 3H), 2.16 (s, 3H), 1.90-1.84 (m, 1H), 0.70-0.65 (m, 2H), 0.55-0.50 (m, 2H).

[0855]

[0856] [Example 28]

[0857] 5-cyclopropyl-3-((1-isobutyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0858]

[0859] 5-cyclopropyl-3-((1-isobutyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 28] was prepared by a method similar to that of [Example 11] (13.2 mg, 0.03 mmol, 54%). LCMS (M+H) + : 499.4. 1 H NMR (500 MHz, DMSO-d6) δ 10.14 (s, 1H), 9.01 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 8.25 (s, 1H), 7.94 (d, J = 2.5 Hz, 1H), 7.63 (d, J = 2.5 Hz, 1H), 6.75 (s, 1H), 4.04 (d, J = 7.0 Hz, 2H), 3.98 (s, 3H), 2.17 (sept, J = 7.0 Hz, 1H), 1.86-1.80 (m, 1H), 0.89 (d, J = 7.0 Hz, 6H),0.71-0.66 (m, 2H), 0.52-0.48 (m, 2H).

[0860]

[0861] [Example 29]

[0862] 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0863]

[0864] 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 29] was prepared by a method similar to that of [Example 9] (15.4 mg, 0.03 mmol, 48%). LCMS (M+H) + : 403.4. 1H NMR (400 MHz, DMSO-d6) δ 9.59 (s, 1H), 9.02 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.03 (d, J = 2.0 Hz, 1H), 7.75 (d, J = 2.8 Hz, 1H), 6.88 (s, 1H), 5.99 (s, 1H), 3.98 (s, 3H), 3.62 (s, 3H), 2.16 (s, 3H),1.91-1.83 (m, 1H), 0.72-0.67 (m, 2H), 0.53-0.49 (m, 2H).

[0865]

[0866] [Example 30]

[0867] 5-cyclopropyl-3-((3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0868]

[0869] 5-cyclopropyl-3-((3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 30] was prepared by a method similar to that of [Example 11] (10.2 mg, 0.02 mmol, 39%). LCMS (M+H) + : 473.3. 1H NMR (400 MHz, CDCl3) δ 9.37 (s, 1H), 8.90 (s, 1H), 8.61 (s, 1H), 7.99 (s, 1H), 7.95 (d, J = 4.4 Hz, 1H), 7.37 (s, 1H), 6.60 (s, 1H), 5.31 (d, J = 4.3 Hz, 1H), 4.32-4.26 (m, 1H), 4.13 (dd, J = 11.2, 3.6 Hz, 2H), 4.01 (s, 3H), 3.56 (td, J = 11.6, 2.0 Hz, 2H), 2.16 (s, 3H), 2.13 (d, J = 2.0 Hz, 1H), 2.09-2.00 (m, 2H), 1.92-1.88 (m, 1H), 1.25 (s, 1H), 0.75-0.70 (m, 2H), 0.51-0.47 (m, 2H).

[0870]

[0871] [Example 31]

[0872] 5-cyclopropyl-3-((1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0873]

[0874] 5-cyclopropyl-3-((1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 31] was prepared by a method similar to that of [Example 11] (23.5 mg, 0.05 mmol, 57%). LCMS (M+H) + : 485.3. 1H NMR (400 MHz, CDCl3) δ 9.70 (s, 1H), 8.91 (s, 1H), 8.62 (s, 1H), 8.00 (s, 1H), 7.96 (d, J = 4.0 Hz, 1H), 7.51 (s, 1H), 6.74 (s, 1H), 5.35 (d, J = 4.4 Hz, 1H), 4.56 (dt, J = 13.4, 6.8 Hz, 1H), 4.01 (s, 3H), 1.94-1.90 (m, 1H), 1.56 (d, J = 6.4 Hz, 6H), 0.76-0.71 (m, 2H), 0.53-0.49 (m, 2H).

[0875]

[0876] [Example 32]

[0877] 5-cyclopropyl-3-((3-cyclopropyl-1-methyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0878]

[0879] 5-cyclopropyl-3-((3-cyclopropyl-1-methyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 32] was prepared by a method similar to that of [Example 9] (14.4 mg, 0.03 mmol, 60%). LCMS (M+H) + : 429. 1 H NMR (400 MHz, DMSO-d6) δ 10.53 (s, 1H), 9.02 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.02 (s, 1H), 7.74 (d, J = 2.2 Hz, 1H), 6.86 (s, 1H), 5.93 (s, 1H), 3.99 (s, 3H), 3.60 (s, 3H), 1.87-1.83 (m, 2H), 0.86-0.83 (m, 2H), 0.71-0.65 (m, 4H), 0.51-0.50 (m, 2H).

[0880]

[0881] [Example 33]

[0882] 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0883]

[0884] 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 33] was prepared by a method similar to that of [Example 9] (13.5 mg, 0.03 mmol, 64%). LCMS (M+H) + : 415.3. 1 H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 9.00 (s, 1H), 8.40 (d, J = 11.6 Hz, 2H), 7.93 (s, 1H), 7.89 (d, J = 2.4 Hz, 1H), 7.57 (d, J = 2.8) Hz, 1H), 7.51 (s, 1H), 6.86 (s, 1H), 3.98 (s, 3H), 3.75 (tt, J = 7.4, 3.8 Hz, 1H), 1.88-1.82 (m, 1H), 1.09-1.05 (m, 2H), 0.99-0.94 (m, 2H), 0.69-0.64 (m, 2H), 0.52-0.48 (m, 2H).

[0885]

[0886] [Example 34]

[0887] 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0888] Step 1] 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0889]

[0890] To a reaction mixture in which methyl 3-amino-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (60.0 mg, 0.19 mmol) and 3-bromo-1-(2,2-difluoroethyl)pyrazole (79.9 mg, 0.37 mmol) were dissolved in isopropyl alcohol (2 mL), tBubrettphos-Pd-G3 (31.7 mg, 0.04 mmol) and cesium carbonate (181.4 mg, 0.56 mmol) were added, and the resulting mixture was stirred in a microwave reactor at 110 °C for 3 hours. After concentrating the mixture, it was divided into ethyl acetate and distilled water, and then 2N hydrochloric acid aqueous solution was added dropwise to the aqueous layer until the pH reached 3. The aqueous layer was extracted again with dichloromethane, concentrated under reduced vacuum pressure, and used in the next step without further purification. LCMS (M+H) + : 440.

[0891] Step 2] Preparation of methyl 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate

[0892]

[0893] Unpurified 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinic acid was added to a sealed tube, and methanol (2 mL) was added dropwise. Subsequently, concentrated sulfuric acid (0.1 mL) was added, and the mixture was stirred at 80 °C for 15 hours. After the reaction was complete, the solution was concentrated under reduced pressure and used in the next step without further purification. LCMS (M+H) + : 454.

[0894] Step 3] Preparation of 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinic acid

[0895]

[0896] Methyl 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate and 7 M methanolic ammonia (2 mL) were added to a sealed tube. The reaction mixture was stirred at 100 °C for 15 hours, and after the reaction was finished, the mixture was concentrated. The residue was purified for 10 minutes using prep-HPLC (Boston pHlex ODS, 21.2 × 250 mm, 10 μm, 25-55% acetonitrile / distilled water (10 mM NH4HCO3)) to obtain 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinic acid (18.0 mg, 0.04 mmol, 22%) as a white solid. LCMS (M+H) + : 439.5. 1 H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.18 (s, 1H), 8.01 (br d, J=2.63 Hz, 1H), 7.75 (d, J=2.38 Hz, 1H), 7.70 (br d, J=2.75 Hz, 1H), 6.22-6.55 (m, 1H), 6.11 (d, J=2.50 Hz, 1H), 5.77 (s, 1H), 4.57 (dt, J=3.63, 15.07 Hz, 2H), 3.99 (s, 3H), 1.82-1.92 (m, 1H), 0.73-0.80 (m, 2H), 0.61-0.68 (m, 2H).

[0897]

[0898] [Example 35]

[0899] 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0900]

[0901] 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 35] was prepared by a method similar to that of [Example 34] (6.0 mg, 0.02 mmol, 8%). LCMS (M+H) + : 415.2. 1 H NMR (400 MHz, DMSO-d6) δ 10.90-10.94 (m, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.18 (s, 1H), 7.99 (br d, J=2.63 Hz, 1H), 7.75 (d, J=2.38 Hz, 1H), 7.68 (t, J=2.50 Hz, 1H), 6.01 (d, J=2.38 Hz, 1H), 3.99 (s, 3H), 3.66-3.73 (m, 1H), 1.88 (tt, J=5.25, 8.32 Hz, 1H), 1.03-1.11 (m, 2H), 0.92-1.00 (m, 2H), 0.73-0.83 (m, 2H), 0.59-0.67 (m, 2H).

[0902]

[0903] [Example 36]

[0904] 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0905]

[0906] 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 36] was prepared by a method similar to that of [Example 34] (11.0 mg, 0.03 mmol, 14%). LCMS (M+H) + : 429.2. 1 H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.22 (s, 1H), 7.99 (br d, J=2.63 Hz, 1H), 7.71 (d, J=2.25 Hz, 1H), 7.68 (br d, J=2.88 Hz, 1H), 6.00 (d, J=2.38 Hz, 1H), 3.99 (s, 3H), 3.92 (d, J=7.00 Hz, 2H), 1.84-1.94 (m, 1H), 1.24-1.31 (m, 1H), 0.75-0.82 (m, 2H), 0.61-0.67 (m, 2H), 0.54-0.60 (m, 2H), 0.37-0.46 (m, 2H).

[0907]

[0908] [Example 37]

[0909] 5-cyclopropyl-3-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0910]

[0911] 5-cyclopropyl-3-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 37] was prepared by a method similar to that of [Example 34] (25.0 mg, 0.06 mmol, 31%). LCMS (M+H) + : 431.1. 1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.16 (s, 1H), 8.00 (br d, J=2.75 Hz, 1H), 7.69 (br d, J=2.88 Hz, 1H), 5.86 (s, 1H), 5.77 (s, 1H), 4.78 (s, 2H), 4.03-4.11 (m, 4H), 3.99 (s, 3H), 1.86-1.95 (m, 1H), 0.72-0.81 (m, 2H), 0.57-0.68 (m, 2H).

[0912]

[0913] [Example 38]

[0914] 5-cyclopropyl-3-((1-ethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0915]

[0916] 5-cyclopropyl-3-((1-ethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 38] was prepared by a method similar to that of [Example 34] (20.0 mg, 0.05 mmol, 27%). LCMS (M+H) + : 403.2. 1 H NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.18 (s, 1H), 7.97 (br d, J=2.63 Hz, 1H), 7.67-7.70 (m, 1H), 7.65 (br d, J=2.75 Hz, 1H), 6.00 (d, J=2.38 Hz, 1H), 4.04-4.12 (m, 2H), 3.99 (s, 3H), 1.83-1.95 (m, 1H), 1.42 (t, J=7.25 Hz, 3H), 0.75-0.82 (m, 2H), 0.58-0.66 (m, 2H).

[0917]

[0918] [Example 39]

[0919] 5-cyclopropyl-3-((1-isobutyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0920]

[0921] 5-cyclopropyl-3-((1-isobutyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 39] was prepared by a method similar to that of [Example 34] (25.0 mg, 0.06 mmol, 31%). LCMS (M+H) + : 431.5. 1 H NMR (400 MHz, DMSO-d6) δ 10.86 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.40 (s, 1H), 8.16 (s, 1H), 7.97 (br d, J=2.75 Hz, 1H), 7.61-7.71 (m, 2H), 6.00 (d, J=2.25 Hz, 1H), 3.99 (s, 3H), 3.88 (d, J=7.00 Hz, 2H), 2.16 (td, J=6.75, 13.51 Hz, 1H), 1.79-1.92 (m, 1H), 0.91 (d, J=6.63 Hz, 6H), 0.74-0.82 (m, 2H), 0.56-0.64 (m, 2H).

[0922]

[0923] [Example 40]

[0924] 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0925]

[0926] 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 40] was prepared by a method similar to that of [Example 34] (11.0 mg, 0.03 mmol, 16%). LCMS (M+H) + : 433.5. 1 H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.16 (s, 1H), 7.98 (br d, J=2.50 Hz, 1H), 7.63-7.71 (m, 2H), 6.00 (d, J=2.25 Hz, 1H), 4.21 (t, J=5.25 Hz, 2H), 3.99 (s, 3H), 3.74 (t, J=5.25 Hz, 2H), 3.27 (s, 3H), 1.85-1.93 (m, 1H), 0.74-0.82 (m, 2H), 0.61-0.67 (m, 2H).

[0927]

[0928] [Example 41]

[0929] 5-cyclopropyl-3-((5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide

[0930]

[0931] 5-cyclopropyl-3-((5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 41] was prepared by a method similar to that of [Example 34] (37.0 mg, 0.09 mmol, 48%). LCMS (M+H) + : 415.2. 1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 9.02 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.11 (s, 1H), 7.97 (br d, J=2.75 Hz, 1H), 7.64 (br d, J=2.75 Hz, 1H), 5.76-5.82 (m, 1H), 4.05 (t, J=7.13 Hz, 2H), 3.99 (s, 3H), 2.86 (t, J=7.32 Hz, 2H), 2.45-2.50 (m, 2H), 1.91 (tt, J=5.22, 8.41 Hz, 1H), 0.69-0.81 (m, 2H), 0.54-0.64 (m, 2H).

[0932]

[0933] [Example 42]

[0934] 3-((1-(tert-butyl)-3-methyl-1H-pyrazole-4-yl)amino)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0935]

[0936] 3-((1-(tert-butyl)-3-methyl-1H-pyrazole-4-yl)amino)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 42] was prepared by a method similar to that of [Example 11] (12.5 mg, 0.03 mmol, 56%). LCMS (M+H) + : 445.4. 1H NMR (400 MHz, DMSO-d6) δ 9.64 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.38 (s, 1H), 7.90 (s, 1H), 7.87 (d, J = 2.8 Hz, 1H), 7.53 (d, J = 2.8 Hz, 1H), 6.57 (s, 1H), 3.98 (s, 3H), 2.05 (s, 3H), 1.89-1.81 (m, 1H), 1.52 (s, 9H), 0.68-0.63 (m, 2H), 0.42-0.38 (m, 2H).

[0937]

[0938] [Example 43]

[0939] 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0940]

[0941] 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 43] was prepared by a method similar to that of [Example 9] (6.8 mg, 0.01 mmol, 50%). LCMS (M+H) + : 457.2. 1 H NMR (400 MHz, DMSO-d6) δ 10.81 (s, 1H), 9.03 (s, 1H), 8.45 (s, 1H), 8.41 (s, 1H), 8.08 (s, 1H), 7.81 (s, 1H), 6.91 (s, 1H), 6.75 (s, 1H), 3.99 (s, 3H), 3.80 (s, 3H), 1.91-1.84 (m, 1H), 0.72-0.67 (m, 2H), 0.57- 0.54 (m, 2H).

[0942]

[0943] [Example 44]

[0944] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)picolinamide

[0945]

[0946] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)picolinamide [Example 44] was prepared by a method similar to that of [Example 9] (16.6 mg, 0.036 mmol, 61%). LCMS (M+H) + : 459.1. 1 H NMR (500 MHz, DMSO-d6) δ 10.61 (s, 1H), 9.02 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.05 (d, J = 2.5 Hz, 1H), 7.77 (d, J = 2.5 Hz, 1H), 7.54 (d, J = 2.0 Hz, 1H), 6.82 (s, 1H), 6.23 (d, J = 1.5 Hz, 1H), 4.41-4.36 (m, 1H), 3.98 (s, 3H), 3.96 (d, J = 4.0 Hz, 2H), 3.48-3.43 (m, 2H), 2.11-2.03 (m, 2H), 1.86-1.84 (m, 1H), 1.83-1.79 (m, 2H), 0.71-0.67 (m, 2H), 0.48-0.44 (m, 2H).

[0947]

[0948] [Example 45]

[0949] 5-cyclopropyl-3-((5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0950]

[0951] 5-cyclopropyl-3-((5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 45] was prepared by a method similar to that of [Example 9] (16.9 mg, 0.036 mmol, 58%). LCMS (M+H) + : 473.1. 1 H NMR (400 MHz, DMSO-d6) δ 10.63 (s, 1H), 9.02 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.05 (d, J = 2.4Hz, 1H), 7.76 (d, J = 2.0 Hz, 1H), 6.87 (s, 1H), 6.01 (s, 1H), 4.33-4.25 (m, 1H), 3.99 (s, 3H), 3.97-3.94(m, 2H), 3.46-3.43 (m, 2H), 2.19 (s, 3H), 2.05 (qd, J = 12.5, 4.5 Hz, 2H), 1.90-1.83 (m, 1H), 1.77 (dd, J = 12.5, 2.2 Hz, 2H), 0.72-0.67 (m, 2H), 0.50-0.46 (m, 2H).

[0952]

[0953] [Example 46]

[0954] 5-cyclopropyl-3-((1-(2,2-difluoropropyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0955]

[0956] 5-cyclopropyl-3-((1-(2,2-difluoropropyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 46] was prepared by a method similar to that of [Example 34] (40.0 mg, 0.09 mmol, 48%). LCMS (M+H) + : 453.3. 1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.40 (s, 1H), 8.24 (s, 1H), 8.00 (br d, J=2.75 Hz, 1H), 7.73 (d, J=2.38 Hz, 1H), 7.68 (br d, J=2.50 Hz, 1H), 6.10 (d, J=2.50 Hz, 1H), 4.58 (t, J=12.94 Hz, 2H), 3.99 (s, 3H), 1.87 (tt, J=8.40, 5.17 Hz, 1H), 1.67 (t, J=19.07 Hz, 3H), 0.74 - 0.80 (m, 2H), 0.60 - 0.66 (m, 2H).

[0957]

[0958] [Example 47]

[0959] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-3-yl)amino)picolinamide

[0960]

[0961] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-3-yl)amino)picolinamide [Example 47] was prepared by a method similar to that of [Example 34] (40.0 mg, 0.08 mmol, 55%). LCMS (M+H) + : 473.3. 1H NMR (400 MHz, DMSO-d6) δ 10.87 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.40 (s, 1H), 8.15 (s, 1H), 7.98 (br d, J=2.88 Hz, 1H), 7.67 (d, J=2.25 Hz, 1H), 7.65 (br d, J=2.88 Hz, 1H), 6.00 (d, J=2.25 Hz, 1H), 3.99 (s, 3H), 3.96 (d, J=6.88 Hz, 2H), 3.86 (br dd, J=10.88, 3.25 Hz, 2H), 3.29 (br d, J=1.88 Hz, 2H), 2.07 - 2.14 (m, 1H), 1.88 (tt, J=8.38, 5.19 Hz, 1H), 1.45 - 1.51 (m, 2H), 1.29 (br dd, J=12.88, 4.25 Hz, 2H), 0.77 - 0.82 (m, 2H), 0.59 - 0.64 (m, 2H).

[0962]

[0963] [Example 48]

[0964] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-yl)amino)picolinamide

[0965]

[0966] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-yl)amino)picolinamide [Example 48] was prepared by a method similar to that of [Example 34] (26.0 mg, 0.06 mmol, 33%). LCMS (M+H) + : 429.4. 1H NMR (400 MHz, DMSO-d6) δ 10.87 (s, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.17 (s, 1H), 7.96 (br d, J=2.63 Hz, 1H), 7.63 (br d, J=2.75 Hz, 1H), 5.75-5.78 (m, 1H), 3.96-4.05 (m, 6H), 2.73 (br t, J=6.25 Hz, 2H), 1.95-2.04 (m, 2H), 1.87-1.94 (m, 1H), 1.74-1.84 (m, 2H), 0.73-0.79 (m, 2H), 0.57-0.67 (m, 2H).

[0967]

[0968] [Example 49]

[0969] 5-cyclopropyl-3-((5-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0970]

[0971] 5-cyclopropyl-3-((5-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 49] was prepared by a method similar to that of [Example 1] (10.2 mg, 0.022 mmol, 53%). LCMS (M+H) + : 417.2. 1H NMR (400 MHz, CDCl3) δ 9.54 (s, 1H), 8.90 (s, 1H), 8.62 (s, 1H), 7.99 (s, 1H), 7.94 (s, 1H), 7.49 (s, 1H), 7.40 (s, 1H), 6.92 (s, 1H), 5.30 (s, 1H), 4.53-4.47 (m, 1H), 4.01 (s, 3H), 1.94-1.87 (m, 1H), 1.54 (dd,J= 6.6, 2.6 Hz, 6H), 0.74-0.70 (m, 2H), 0.54 (d,J= 4.6 Hz, 2H).

[0972]

[0973] [Example 50]

[0974] 5-cyclopropyl-3-((1-(cyclopropylmethyl)-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0975]

[0976] 5-cyclopropyl-3-((1-(cyclopropylmethyl)-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 50] was prepared by a method similar to that of [Example 3] (36.3 mg, 0.082 mmol, 49%). LCMS (M+H) + : 443.1. 1 H NMR (500 MHz, DMSO-d6) δ 10.82 (s, 1H), 9.01 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.23 ​​(s, 1H), 7.95 (d, J = 3.0 Hz, 1H), 7.63 (d, J = 2.5 Hz, 1H), 3.98 (s, 3H), 3.51-3.46 (m, 1H), 2.32 (s, 3H), 1.90-1.84 (m, 1H), 1.08-1.05 (m, 2H), 1.01-0.96 (m, 2H), 0.82-0.77 (m, 2H), 0.65-0.61 (m, 2H).

[0977]

[0978] [Example 51]

[0979] 5-cyclopropyl-3-((1-isopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[0980]

[0981] 5-cyclopropyl-3-((1-isopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 51] was prepared by a method similar to that of [Example 1] (16.5 mg, 0.038 mmol, 43%). LCMS (M+H) + : 431.4. 1 H NMR (400 MHz, DMSO-d6) δ 10.81 (s, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.32 (s, 1H), 7.95 (d, J = 2.8 Hz, 1H), 7.62 (d, J = 2.8 Hz, 1H), 5.75 (s, 1H), 4.45 (sept, J = 6.4 Hz, 1H), 3.98 (s, 3H), 2.25 (s, 3H), 1.89-1.81 (m, 1H), 1.39 (d, J = 6.8 Hz, 6H), 0.84-0.78 (m, 2H), 0.67-0.62 (m, 2H).

[0982]

[0983] [Example 52]

[0984] (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolineamide

[0985] Step 1] Preparation of (S)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate

[0986]

[0987] 4-toluenesulfonyl chloride (2.6 g, 13.6 mmol) was added to a solution of (S)-tetrahydrofuran-3-ol (1.0 g, 11.3 mmol) dissolved in dichloromethane (10 mL), and then triethylamine (2.3 g, 22.7 mmol) was added at 0 °C. The resulting mixture was stirred overnight at room temperature. The mixture was divided into dichloromethane (20 mL) and distilled water (10 mL). The aqueous layer was extracted with dichloromethane (10 mL × 2). The combined organic layer was washed with brine (20 mL), dried with anhydrous sodium sulfate, and concentrated after filtration. The residue was purified by flash (Biotage) column chromatography (0-15% ethyl acetate / petroleum ether) to obtain (S)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (624 mg, 2.58 mmol, 23%) as a colorless oil. LCMS (M+NH4) + : 260.1. 1 H NMR (500 MHz, CDCl3) δ 7.80 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 5.13-5.10 (m, 1H), 3.91-3.79 (m, 4H), 2.46 (s, 3H), 2.11-2.05(m, 2H).

[0988] Step 2] Preparation of (R)-3-bromo-1-(tetrahydrofuran-3-yl)-1H-pyrazole

[0989]

[0990] (S)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (593 mg, 2.45 mmol) was added to a solution of 3-bromo-1H-pyrazole (300 mg, 2.04 mmol) dissolved in dimethylformamide (10 mL), and then cesium carbonate (1326 mg, 4.08 mmol) was added at 0 °C. The resulting mixture was stirred at 70 °C for 4 hours. The mixture was divided into ethyl acetate (100 mL) and distilled water (100 mL). The organic layer was washed with brine (30 mL × 3), dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash (Biotage) column chromatography (0-15% ethyl acetate / petroleum ether) to obtain the yellow oil (R)-3-bromo-1-(tetrahydrofuran-3-yl)-1H-pyrazole (129 mg, 0.59 mmol, 29%). LCMS (M+H) + : 217, 219.

[0991] Step 3] Preparation of methyl(R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinate

[0992]

[0993] A mixture of methyl 3-amino-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinate (60 mg, 0.186 mmol), (R)-3-bromo-1-(tetrahydrofuran-3-yl)-1H-pyrazole (79.9 mg, 0.372 mmol), tBubrettphos-Pd-G3 (31.7 mg, 0.037 mmol), cesium carbonate (121 mg, 0.371 mmol), and dioxane (1.5 mL) was vacuumed and refilled with nitrogen three times. The resulting mixture was stirred in a microwave reactor at 100 °C for 3 hours. After concentrating the mixture, the residue was purified by flash (Biotage) column chromatography (0-15% methanol / dichloromethane) to obtain the yellow solid methyl(R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinate (59 mg, 0.129 mmol, 69%). LCMS (M+H) + : 460.

[0994]

[0995] Methyl (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinate (59 mg, 0.129 mmol) and 7 M methanolic ammonia (8 mL) were added to a sealed tube. The resulting reaction mixture was stirred at 100 °C for 6 hours. After the reaction was complete, the mixture was concentrated. The residue was purified for 10 minutes using prep-HPLC (Boston pHlex ODS, 21.2 × 250 mm, 10 μm, 15-45% acetonitrile / distilled water (10 mM NH4HCO3)) to obtain (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide (35.2 mg, 0.079 mmol, 62%) as a white solid. LCMS (M+H) + : 445.4. 1 H NMR (500 MHz, DMSO-d6) δ 10.97 (s, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.26 (s, 1H), 7.98 (d, J = 2.0 Hz, 1H), 7.74 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 2.5 Hz, 1H), 6.01 (d, J = 2.0 Hz, 1H), 5.00-4.96 (m, 1H), 4.05-4.00 (m, 2H), 3.99 (s, 3H), 3.93-3.86 (m, 2H), 2.38-2.30(m, 2H), 1.88-1.85(m, 1H), 0.81-0.77(m, 2H), 0.67-0.64(m, 2H).

[0996]

[0997] [Example 53]

[0998] (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolineamide

[0999]

[1000] (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide [Example 53] was prepared by a method similar to that of [Example 52] (29.7 mg, 0.069 mmol, 51%). LCMS (M+H) + : 445.4. 1 H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.26 (s, 1H), 7.98 (d, J = 2.8 Hz, 1H), 7.74 (d, J = 3.2 Hz, 1H), 7.66 (d, J = 3.2 Hz, 1H), 6.01 (d, J = 2.4 Hz, 1H), 5.00-4.94 (m, 1H), 4.00-3.99 (m, 2H), 3.98 (s, 3H), 3.94-3.85 (m, 2H), 2.42-2.26 (m, 2H), 1.90-1.82 (m, 1H), 0.82-0.76 (m, 2H), 0.67-0.63 (m, 2H).

[1001]

[1002] [Example 54]

[1003] 5-cyclopropyl-3-((3-fluoro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[1004]

[1005] 5-cyclopropyl-3-((3-fluoro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 54] was prepared by a method similar to that of [Example 9] (5.7 mg, 0.012 mmol, 33%). LCMS (M+H) + : 475.1. 1 H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.01 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 8.07 (d, J = 2.4 Hz, 1H), 7.94 (d, J = 2.8 Hz, 1H), 7.65 (d, J = 2.4 Hz, 1H), 6.65 (s, 1H), 5.07 (q, J = 8.9 Hz, 2H), 3.98 (s, 3H), 1.88-1.83 (m, 1H), 0.72-0.67 (m, 2H), 0.49-0.45 (m, 2H).

[1006]

[1007] [Example 55]

[1008] 5-cyclopropyl-3-((3-fluoro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide

[1009]

[1010] 5-cyclopropyl-3-((3-fluoro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 55] was prepared by a method similar to that of [Example 9] (23.5 mg, 0.049 mmol, 56%). LCMS (M+H) + : 477.1. 1H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 1H), 9.01 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 8.01 (d, J = 1.5 Hz, 1H), 7.91 (d, J = 2.5 Hz, 1H), 7.60 (d, J = 2.5 Hz, 1H), 6.65 (s, 1H), 4.32-4.26 (m, 1H), 3.98 (s, 3H), 3.98-3.95 (m, 2H), 3.46 (td, J = 11.6, 2.0 Hz, 2H), 2.01-1.98 (m, 2H), 1.95-1.89 (m, 2H), 1.87-1.83 (m, 1H), 0.70-0.65 (m, 2H), 0.48-0.45 (m, 2H).

[1011]

[1012] [Example 56]

[1013] 5-cyclopropyl-3-((1-cyclopropyl-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[1014]

[1015] 5-cyclopropyl-3-((1-cyclopropyl-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 56] was prepared by a method similar to that of [Example 9] (12.5 mg, 0.029 mmol, 43%). LCMS (M+H) + : 433.2. 1H NMR (500 MHz, DMSO-d6) δ 9.69 (s, 1H), 9.00 (s, 1H), 8.42 (s, 1H), 8.38 (s, 1H), 7.97 (d, J = 2.0 Hz, 1H), 7.90 (d, J = 2.5 Hz, 1H), 7.59 (d, J = 3.0 Hz, 1H), 6.64 (s, 1H), 3.98 (s, 3H), 3.69-3.64 (m, 1H), 1.89-1.82 (m, 1H), 1.06-1.02 (m, 2H), 0.97-0.92 (m, 2H), 0.69-0.64 (m, 2H), 0.49-0.46 (m, 2H).

[1016]

[1017] [Example 57]

[1018] 5-cyclopropyl-3-((1-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[1019]

[1020] 5-cyclopropyl-3-((1-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 57] was prepared by a method similar to that of [Example 34] (23.0 mg, 0.059 mmol, 43%). LCMS (M+H) + : 389.2. 1 H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.40 (s, 1H), 8.11 (s, 1H), 7.97 (br d, J=2.75 Hz, 1H), 7.64 (d, J=2.25 Hz, 2H), 6.01 (d, J=2.38 Hz, 1H), 3.99 (s, 3H), 3.81 (s, 3H), 1.90 (tt, J=8.40, 5.24 Hz, 1H), 0.79 - 0.74 (m, 2H), 0.65 - 0.59 (m, 2H).

[1021]

[1022] [Example 58]

[1023] 5-cyclopropyl-3-((1,5-dimethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[1024]

[1025] 5-cyclopropyl-3-((1,5-dimethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 58] was prepared by a method similar to that of [Example 34] (16.0 mg, 0.040 mmol, 28%). LCMS (M+H) + : 403.5. 1 H NMR (400 MHz, DMSO-d6) δ 10.80 (s, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.11 (s, 1H), 7.96 (br d, J=2.88 Hz, 1H), 7.62 (br d, J=2.75 Hz, 1H), 5.82(d, J=0.63 Hz, 1H), 3.99 (s, 3H), 3.68 (s, 3H), 2.25 (s, 3H), 1.90 (tt, J=8.43, 5.27 Hz, 1H), 0.79 - 0.73 (m, 2H), 0.63 - 0.59 (m, 2H).

[1026]

[1027] [Example 59]

[1028] (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolineamide

[1029]

[1030] (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolinamide [Example 59] was prepared by a method similar to that of [Example 9] (23.0 mg, 0.049 mmol, 26%). LCMS (M+H) + : 471.2. 1 H NMR (400 MHz, DMSO-d6) δ 11.05 (s, 1H), 9.02 (s, 1H), 8.50 - 8.44 (m, 1H), 8.41 (s, 1H), 8.33 (s, 1H), 8.01 (br d, J=2.75 Hz, 1H), 7.85 (d, J=2.50 Hz, 1H), 7.69 (br d, J=2.75 Hz, 1H), 6.13 (d, J=2.38 Hz, 1H), 5.33 (dt, J=14.38, 7.19 Hz, 1H), 4.00 (s, 3H), 1.90 - 1.81 (m, 1H), 1.71 (d, J=7.00

[1031] Hz, 3H), 0.84 - 0.76 (m, 2H), 0.69 - 0.61 (m, 2H).

[1032]

[1033] [Example 60]

[1034] (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolineamide

[1035] (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolinamide [Example 60], prepared by a method similar to [Example 9] (12.0 mg, 0.026 mmol, 14%). LCMS (M+H) + : 471.4. 1H NMR (400 MHz, DMSO-d6) δ 11.05 (s, 1H), 9.02 (s, 1H), 8.47 (s, 1H), 8.41 (s, 1H), 8.33 (s, 1H), 8.01 (br d, J=2.75 Hz, 1H), 7.85 (d, J=2.50 Hz, 1H), 7.69 (br d, J=3.00 Hz, 1H), 6.13 (d, J=2.50 Hz, 1H), 5.33 (dt, J=14.38, 7.19 Hz, 1H), 4.00 (s, 3H), 1.91 - 1.80 (m, 1H), 1.71 (d, J=7.00 Hz, 3H), 0.83 - 0.78 (m, 2H), 0.65 (dt, J=4.60, 2.52 Hz, 2H).

[1036]

[1037] [Example 61]

[1038] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-3-yl)amino)picolinamide

[1039]

[1040] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-3-yl)amino)picolinamide [Example 61] was prepared by a method similar to that of [Example 34] (22.0 mg, 0.050 mmol, 52%). LCMS (M+H) + : 443.0. 1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 9.04 (s, 1H), 8.48 (s, 1H), 8.42 (s, 1H), 8.40 - 8.37 (m, 2H), 8.10 (br d, J=2.25 Hz, 1H), 7.82 (br d, J=2.25 Hz, 1H), 6.56 (d, J=2.88 Hz, 1H), 4.00 (s, 3H), 1.96 - 1.88 (m, 1H), 0.86 - 0.78 (m, 2H), 0.68 - 0.61 (m, 2H).

[1041]

[1042] [Example 62]

[1043] 5-cyclopropyl-3-((3-fluoro-1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[1044]

[1045] 5-cyclopropyl-3-((3-fluoro-1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 62] was prepared by a method similar to that of [Example 9] (23.6 mg, 0.046 mmol, 54%). LCMS (M+H) + : 435.1. 1 H NMR (400 MHz, DMSO-d6) δ 9.68 (s, 1H), 9.01 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 7.97 (d, J = 2.0 Hz, 1H), 7.91 (d, J = 2.4Hz, 1H), 7.61 (d, J = 2.8 Hz, 1H), 6.64 (s, 1H), 4.41-4.34 (m, 1H), 3.98 (s, 3H), 1.89-1.82 (m, 1H), 1.41 (d, J = 6.4 Hz, 6H), 0.70-0.65 (m, 2H), 0.47-0.43 (m, 2H).

[1046]

[1047] [Example 63]

[1048] 5-cyclopropyl-3-((1-(cyclopropylmethyl)-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[1049]

[1050] 5-cyclopropyl-3-((1-(cyclopropylmethyl)-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 63] was prepared by a method similar to that of [Example 9] (20.7 mg, 0.046 mmol, 52%). LCMS (M+H) + : 435.1. 1 H NMR (400 MHz, DMSO-d6) δ 9.69 (s, 1H), 9.01 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 7.96 (d, J = 2.0 Hz, 1H), 7.92 (d, J = 2.4 Hz, 1H), 7.61 (d, J = 2.8 Hz, 1H), 6.66 (s, 1H), 3.98 (s, 3H), 3.87 (d, J = 7.2 Hz, 2H), 1.88-1.83 (m, 1H), 1.27-1.23 (m, 1H), 0.71-0.66 (m, 2H), 0.58-0.53 (m, 2H), 0.49-0.45 (m, 2H), 0.40-0.36 (m, 2H).

[1051]

[1052] [Example 64]

[1053] (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolineamide

[1054]

[1055] (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide [Example 64] was prepared by a method similar to that of [Example 9] (27.3 mg, 0.059 mmol, 59%). LCMS (M+H) + : 459.2. 1 H NMR (500 MHz, DMSO-d6) δ 10.92 (s, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 8.40 (s, 1H), 8.22 (s, 1H), 7.97 (d, J = 2.5 Hz, 1H), 7.75 (d, J = 2.0 Hz, 1H), 7.65 (d, J = 3.5 Hz, 1H), 6.01 (d, J = 2.5 Hz, 1H), 4.26-4.19 (m, 1H), 4.03 (dd, J = 10.5, 4.0 Hz, 1H), 3.99 (s, 3H), 3.83 (dt, J = 10.5, 3.5 Hz, 1H), 3.63 (dd, J = 11.0, 9.0 Hz, 1H), 3.40 (td, J = 10.5, 2.5 Hz, 1H), 2.20-2.15 (m, 1H), 2.14-2.06 (m, 1H), 1.90-1.84 (m, 1H), 1.80-1.73 (m, 1H), 1.72-1.64 (m, 1H), 0.83-0.78 (m, 2H), 0.67-0.63 (m, 2H).

[1056]

[1057] [Example 65]

[1058] (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolineamide

[1059]

[1060] (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide [Example 65] was prepared by a method similar to that of [Example 9] (25.0 mg, 0.054 mmol, 41%). LCMS (M+H) + : 459.1. 1 H NMR (500 MHz, DMSO-d6) δ 10.92 (s, 1H), 9.01 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.22 (s, 1H), 7.97 (d, J = 2.5 Hz, 1H), 7.76 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 3.5 Hz, 1H), 6.02 (d, J = 3.0 Hz, 1H), 4.25-4.20 (m, 1H), 4.03 (dd, J = 14.0, 4.0 Hz, 1H), 3.99 (s, 3H), 3.83 (dt, J = 10.5, 3.5 Hz, 1H), 3.63 (dd, J = 12.0, 14.0 Hz, 1H), 3.40 (td, J = 14.0, 3.5 Hz, 1H), 2.20-2.08 (m, 2H), 1.89-1.85 (m, 1H), 1.79-1.65 (m, 1H), 0.83-0.78 (m, 2H), 0.67-0.63 (m, 2H).

[1061]

[1062] [Example 66]

[1063] 5-cyclopropyl-3-((1-((1s,3s)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[1064]

[1065] 5-cyclopropyl-3-((1-((1s,3s)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 66] was prepared by a method similar to that of [Example 9] (23.3 mg, 0.051 mmol, 60%). LCMS (M+H) + : 459.2. 1 H NMR (500 MHz, DMSO-d6) δ 10.97 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.40 (s, 1H), 8.37 (s, 1H), 7.98 (d, J = 2.5 Hz, 1H), 7.71 (d, J = 2.5 Hz, 1H), 7.66 (d, J = 3.0 Hz, 1H), 5.98 (d, J = 2.5 Hz, 1H), 4.47 - 4.40 (m, 1H), 3.99 (s, 3H), 3.78 - 3.73 (m, 1H), 3.20 (s, 3H), 2.78 - 2.72 (m, 2H), 2.47 - 2.41 (m, 2H), 1.89 - 1.84 (m, 1H), 0.82 - 0.78 (m, 2H), 0.72 - 0.69 (m, 2H).

[1066]

[1067] [Example 67]

[1068] 5-cyclopropyl-3-((1-((1r,3r)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide

[1069]

[1070] 5-cyclopropyl-3-((1-((1r,3r)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide [Example 67] was prepared by a method similar to that of [Example 9] (16.9 mg, 0.037 mmol, 47%). LCMS (M+H) + : 459.2.1 H NMR (400 MHz, DMSO-d6) δ 11.00 (s, 1H), 9.02 (s, 1H), 8.47 (s, 1H), 8.41 (s, 1H), 8.35 (s, 1H), 7.99 (d, J = 2.8 Hz, 1H), 7.72 (d, J = 2.4 Hz, 1H), 7.68 (d, J = 2.4 Hz, 1H), 5.99 (d, J = 2.0 Hz, 1H), 4.91 - 4.84 (m, 1H), 4.30 - 4.24 (m, 1H), 3.99 (s, 3H), 3.22 (s, 3H), 2.69 - 2.63 (m, 2H), 2.50 - 2.44 (m, 2H), 1.91 - 1.84 (m, 1H), 0.85 - 0.80 (m, 2H), 0.70 - 0.66 (m, 2H).

[1071]

[1072] [Example 68]

[1073] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((1s,3s)-3-(trifluoromethyl)cyclobutyl)-1H-pyrazole-3-yl)amino)picolinamide

[1074]

[1075] 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((1s,3s)-3-(trifluoromethyl)cyclobutyl)-1H-pyrazole-3-yl)amino)picolinamide [Example 68] was prepared by a method similar to that of [Example 9] (10.1 mg, 0.020 mmol, 47%). LCMS (M+H) + : 459.2. 1H NMR (400 MHz, DMSO-d6) δ 11.09 (s, 1H), 9.02 (s, 1H), 8.46 (s, 1H), 8.40 (s, 1H), 8.38 (s, 1H), 7.99 (d, J = 2.5 Hz, 1H), 7.73 (d, J = 2.0 Hz, 1H), 7.67 (d, J = 2.5 Hz, 1H), 5.98 (d, J = 2.5 Hz, 1H), 4.84-4.78 (m, 1H), 3.99 (s, 3H), 3.11-3.06 (m, 1H), 2.72-2.66 (m, 2H), 2.64-2.59 (m, 2H), 1.90-1.84 (m, 1H), 0.80-0.76(m, 2H), 0.69-0.66 (m, 2H).

[1076]

[1077] The structures of the example compounds prepared in Examples 1 to 68 above are summarized in the table below.

[1078] Example Structure Example Structure 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68

[1079] [Experimental Example]

[1080] <Experimental Example 1> Analysis of HPK1 and GLK Inhibitory Activity

[1081] 1-1. Analysis of HPK1 Inhibitory Activity

[1082] The inhibitory activity of compounds represented by Chemical Formula I or II of the present invention against hematopoietic progenitor kinase 1 (HPK1) was analyzed. The kinase activity of HPK1 following treatment with compounds according to one example of the present invention was measured using Promega’s ADP-Glo™ kinase assay, and the specific analysis method is as follows:

[1083] A 10 mM DMSO stock of the test compound stored at -70℃ or below was sufficiently thawed, and a total of 6 concentrations were prepared by serially diluting the test compound with DMSO at 0.025 mmol / L in 1 / 5 increments in a 96-well plate. Subsequently, all compounds were diluted in 1 / 10 increments using 1X kinase buffer (40 mM Tris, 7.5; 20 mM MgCl2; 0.1 mg / ml BSA; 50 μM DTT).

[1084] ATP, substrate, and enzyme (HPK1) were each prepared by diluting them in the aforementioned 1X kinase buffer of the same composition. 5 μL of the prepared ATP (50 μM) was added to 5 μL of substrate (0.25 mg / ml MBP) and 5 μL of the diluted compound, followed by the addition of 10 μL of the diluted enzyme, and the reaction was carried out at 30°C for 40 minutes. Additionally, a blank well without the enzyme and a positive control well without the compound were prepared and reacted at 30°C for 40 minutes.

[1085] Subsequently, 25 μL of ADP-Glo ​​was added to each well and incubated at 30°C for 40 minutes to stop the reaction and degrade residual ATP. Next, 50 μL of kinase detection reagent was added to each well and incubated at room temperature for 40 minutes to convert the ADP product into ATP. 90 μL of the reaction mixture was transferred to a 96-well white plate, and luminescence was measured using a plate reader. Finally, the IC50 of the treated compounds for HPK1 was analyzed using the GraphPad Prism (Graphpad, ver. 8.4.3, USA) analysis program. 50 Calculated.

[1086]

[1087] 1-2. Analysis of GLK Inhibitory Activity

[1088] GLK (Germinal Center Kinase-Like Kinase) is a protein kinase also known as MAP4K3 (Mitogen-activated protein kinase kinase 3). Like HPK1, it belongs to the Ste20 family of kinases, but unlike HPK1, it is known to induce T cell proliferation and cytokine secretion by activating the MAPK (Mitogen-Activated Protein Kinase) signaling pathway involved in T cell activation. Therefore, unlike the inhibition of HPK1, inhibition of GLK can actually suppress anti-cancer immunity.

[1089] Accordingly, to verify the selectivity of the compound according to the present invention toward HPK1, the inhibitory activity of the compound toward GLK (Germinal Center Kinase-Like Kinase) was analyzed. Similar to Experimental Example 1-1, GLK kinase activity following treatment with the compound according to one example of the present invention was measured using Promega’s ADP-Glo™ kinase assay, and the specific analysis method is as follows:

[1090] A 10 mM DMSO stock of the test compound stored at -70℃ or below was sufficiently thawed, and a total of 6 concentrations were prepared by serially diluting the test compound with DMSO at 0.5 mmol / L in 1 / 5 increments in a 96-well plate. Subsequently, all compounds were diluted in 1 / 10 increments using 1X kinase buffer (40 mM Tris, 7.5; 20 mM MgCl2; 0.1 mg / ml BSA; 50 μM DTT).

[1091] ATP, substrate, and enzyme (GLK) were each prepared by diluting them in the aforementioned 1X kinase buffer of the same composition. 5 μL of the prepared ATP (500 μM) was added to 5 μL of substrate (1 mg / mL PKA) and 5 μL of the diluted compound, followed by the addition of 10 μL of the diluted enzyme, and the reaction was carried out at 30°C for 40 minutes. Additionally, a blank well without the enzyme and a positive control well without the compound were prepared and reacted at 30°C for 40 minutes.

[1092] Subsequently, 25 μL of ADP-Glo ​​was added to each well and incubated at 30°C for 40 minutes to stop the reaction and degrade residual ATP. Next, 50 μL of kinase detection reagent was added to each well and incubated at room temperature for 40 minutes to convert the ADP product into ATP. 90 μL of the reaction mixture was transferred to a 96-well white plate, and luminescence was measured using a plate reader. Finally, the IC50 for GLK of the treated compounds was analyzed using the GraphPad Prism (Graphpad, ver. 8.4.3, USA) analysis program. 50 Calculated.

[1093]

[1094] The results of the analysis of the inhibitory activity of a compound represented by Formula I or II on HPK1 or GLK, according to an example of the present invention, are shown in Table 2 below. The inhibitory activity was expressed according to the following criteria.

[1095] a) HPK1 inhibitory activity:

[1096] +++: IC 50 < 10 nM,

[1097] ++: 10 nM ≤ IC 50 <100 nM,

[1098] +: IC 50 ≥ 100 nM

[1099] b) GLK inhibitory activity:

[1100] +++: IC 50 < 10 nM,

[1101] ++: 10 nM ≤ IC 50 < 100 nM,

[1102] +: IC 50 ≥ 100 nM

[1103] c) GLK / HPK1 비:

[1104] +++: (GLK IC 50 / HPK1 IC 50 ) > 100 fold,

[1105] ++: 10 fold ≤ (GLK IC 50 / HPK1 IC 50 ) < 100 fold,

[1106] +: (GLK IC 50 / HPK1 IC 50 ) < 10 fold

[1107] 실시예HPK1 IC 50 a) GLK IC 50 b) GLK / HPK1 비 c)1+++++++2+++++++3+++++++4++--5+++++++6+++++++7+++++++8+++++++9++--10++--11++--12+++++++13+++++++14++++++15+++++++16+++++++17++++++18++--19+++++++20+++++++21+++++++22++--23+++++++24++--25++--26+--27++--28++--29++--30+++++++31++--32++--33+++--34+++++++35+++++++36+++++++37+++ ++++38+++++++39++++++40++++++41+++++++42++++++43++++++44+++++45++++46+++++++47+++++++48+++++++49+++++++50+++++++51+++++++52+++++++53+++++++54+++++++55+++++++56+++++++57+++++++58+++++++59+++++++60+++++++61+++++++62+++++++63+++++++64+++++++65+++++++66+++++++67+++++++68+++++++

[1108] <Experimental Example 2> Analysis of pSLP-76 Inhibitory Activity in Human T Lymphocytes

[1109] SLP-76 is an adapter protein of the TCR signaling pathway. When the TCR recognizes an antigen, SLP-76 binds to various signaling proteins to form a signaling complex, and the intensity of the T cell response and the activation time are regulated according to the composition of this complex. Here, the activity of the TCR signal varies depending on the phosphorylation site of SLP-76. When tyrosine residues of SLP-76 (e.g., Y113, Y128, and / or Y145) are phosphorylated (activating phosphorylation), downstream signaling proteins of the TCR signaling pathway gather to amplify T cell activation. However, when serine residues of SLP-76 (especially serine residue 376) are phosphorylated (inhibitory phosphorylation), the activity and tyrosine phosphorylation of SLP-76 are inhibited, and ubiquitination and proteasome degradation of SLP-76 are induced, thereby blocking the TCR signal. Accordingly, in this embodiment, it was confirmed whether the compound according to the present invention inhibits SLP-76 (pSLP-76) in which the serine residue at position 376 is phosphorylated.

[1110] Specifically, Jurkat cells, which are human leukemia T lymphocytes and a representative model characterizing T cell receptor signaling pathway 1, were maintained in RPMI1640 medium supplemented with 10% FBS and 100 U / mL penicillin / streptomycin, and then cultured in a CO2 incubator at 37°C. The cells were 6×10 5 Up to 8×10 5 When the cell / mL level was 1:4, the cells were suspended in fresh medium. Appropriate aliquots of the cell suspension were added to new culture vessels (T25 = 5 mL; T75 = 15 mL; T175 = maximum volume 30 mL).

[1111] 4×10 cells in a 96-well plate 5 Cells were seeded at a density of 90 μL / well and stabilized in a CO2 incubator at 37°C for 2 hours.

[1112] A 10 mM DMSO stock of a test compound according to an example of the present invention, which had been stored at -70℃ or below, was sufficiently thawed, and the test compound was prepared at a total of five concentrations by serially diluting it in 1 / 5 increments from 1 μmol / L in complete medium in a 96-well plate. 10 μL of the diluted compound was added to a 96-well plate seeded with cells and reacted in a 37℃ CO2 incubator for 1 hour.

[1113] Next, 0.5 μg / 1 μL of anti-CD3 was added to achieve a final concentration of 4 μg / mL per well, and the samples were incubated in a 37°C CO2 incubator for 15 minutes. The anti-CD3 is intended for T cell stimulation and induces inhibitory phosphorylation of SLP-76.

[1114] Subsequently, the cells were centrifuged at 500×g for 10 minutes at 4°C, and the supernatant was aspirated. The cells collected in the tube were washed once with PBS and centrifuged again at 500×g for 10 minutes at 4°C. After aspirating the supernatant, 50 μL of lysis buffer (1X) was immediately added, and the cells were incubated at room temperature with shaking for at least 30 minutes. The cells were centrifuged at 3000 rpm for 5 minutes at 4°C. After homogenization by pipetting up and down, 16 μL of cell lysate was transferred from the 96-well plate to the HTRF 96-well detection plate. 4 μL of antibody solution, pre-mixed with detection buffer, was added. The plate was covered with a plate sealer and incubated overnight at room temperature. The microplate reader was set to Eu 3+ The system was configured for Cryptate, and fluorescence emission was read at two different wavelengths (665 nm and 620 nm) using a compatible HTRF reader. Subsequently, the % inhibition rate was calculated as (ratio of each well-negative control) / (positive control - negative control) × 100, and the IC50 of phosphorylated SLP-76 was analyzed using the GraphPad Prism (Graphpad, ver. 8.4.3, USA) analysis program. 50 Calculated.

[1115] The results of the pSLP-76 inhibitory activity of compounds represented by Formula I or II, according to one example of the present invention, are shown in Table 3 below. The inhibitory activity is presented below according to each term.

[1116] pSLP-76 inhibitory activity

[1117] +++: IC 50 < 250 nM,

[1118] ++: 250 nM ≤ IC 50 < 500 nM,

[1119] +: IC 50 ≥ 500 nM

[1120] Example pSLP-76 IC 50 Example pSLP-76 IC 50 1+++35-2-36-3+++37+++4-38+++5+++39++6+++40++7+++41+++8+++42-9-43-10-44-11-45-12+++46++13+++47+14-48+++15-49+++16-50+++17-51++18-52+++19+++53+++20-54+++21+++55+++22-56+++23+++57+++24-58+++25-59+++26-60+++27-61-28-62++29-63+++30+++64-31-65-32-66-33+++67-34+++68-

[1121] <Experimental Example 3> Target Selectivity and Pharmacokinetic Analysis

[1122] In this embodiment, the selectivity and pharmacokinetics exposure of a compound according to one example of the present invention for a target (HPK1 or GLK) were measured.

[1123] Selectivity for HPK1 and GLK was analyzed by measuring the inhibitory activity for HPK1 and GLK, respectively, in the same manner as in Experimental Example 1.

[1124] The degree of PK exposure was measured according to the route of administration. When a compound according to one example of the present invention was orally administered to an ICR mouse model (administered at a dose of 3 mpk each), the maximum blood concentration (Maximum Concentration, C max The concentration at time zero (CO) and the area under the blood concentration-time curve (AUC) were analyzed. When the compounds were intravenously administered to ICR mouse models (at a dose of 1 mpk each), the concentration at time zero (CO) and AUC were measured. Specifically, blood samples were collected six times (at 0.5, 1, 2, 3, 5, and 7 hours after administration) following a single oral administration. Additionally, blood samples were collected five times (at 0.083, 0.25, 0.5, 1, and 5 hours after administration) following a single intravenous administration. Blood drug concentrations in the collected samples were analyzed using LC-MS / MS (Sciex QTrap6500), and pharmacokinetic indicators were analyzed after data processing using the Phoenix program (Build 8.5.2.4, Pharsight Corporation, USA).

[1125] The target selectivity and PK exposure of a compound according to one example of the present invention are shown in Table 4 below.

[1126] Item Example 5 HPK1 IC 50 2.1 nMGLK IC 50 2210 nMGLK / HPK1 ratio1,052 foldMouse PO 3mpkCmax: 2,405ng / mlAUC: 6,775ng.h / mlMouse IV 1mpkC0: 2,697ng / mlAUC: 2,990ng.h / ml

[1127] As can be seen in the table above, the compound according to one example of the present invention exhibited potent inhibitory activity while having significantly higher selectivity for HPK1 compared to GLK. These results demonstrate that the compound of the present invention possesses excellent characteristics in terms of inhibitory power and selectivity for HPK1.

[1128] As a result of pharmacokinetic analysis, when the compound according to one example of the present invention is administered orally, C max As it was found that the C0 and AUC were excellent and high even when administered intravenously, it was confirmed that the compound of the present invention acts rapidly and exhibits sufficient blood exposure to exert an immune-activating effect. The above results demonstrate that the compound of the present invention can exhibit sufficient immune-activating efficacy even in small amounts.

Claims

1. Compounds represented by the following chemical formula I, their enantiomers, diastereomers, tautomers, hydrates, solvates, or pharmaceutically acceptable salts: [Chemical Formula I] In the above chemical formula I, X is C or N and; Y1, Y2, Y3, and Y4 are each independently C, N, O, or S; Z1 is absent, or H or C 1-4 It is alkyl; Z2 and Z3 are each independently absent, or H, deuterium, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, 4-12-membered heterocyclil, hydroxyl, halogen, cyano, CO-H, CO-(C 1-4 Alkyl), CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), CO-N(C 1-4 Alkyl)2, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinyl, oxetanil, SO2-(C 1-4 alkyl), SO2-NH2, SO2-NH(C 1-4 alkyl), or SO2-N(C 1-4 Alkyl)2 and, Here, the above C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-10 Hydroxylalkyl, C 3-12 Cycloalkyl, C 6-12 Aril, 4-12 won Heteroaryl, quaternary-12ary heterocyclils, tetrahydrofuranil, tetrahydropyranil, piperazinyl, piperidinyl, and oxetanil are halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranil, CO-morpholino, CO-tetrahydropyranil, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 Substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2; Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It is a haloalkyl.

2. Compounds represented by the following chemical formula II, their enantiomers, diastereomers, tautomers, hydrates, solvates, or pharmaceutically acceptable salts: [Chemical Formula II] In the above chemical formula II, X is C or N and; Y1, Y2, Y3, and Y4 are each independently C, N, O, or S; Z1 is absent, or H or C 1-4 It is alkyl; Cycle A is C3- 12 Cycloalkyl, C3- 12 Cycloalkenyl, C3- 12 Cycloalkinyl, C 6-12 It is an aryl, a 4-12-membered heterocycloalkyl, a 4-12-membered heterocycloalkenyl, a 4-12-membered cycloalkynyl, or a 4-12-membered heteroaryl, and Here, the above Cycle A is deuterium, halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 Substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2; Z4 is absent, or H, deuterium, halo, C 1-4 Alkyl, deuterium C 1-4 alkyl, or C 1-4 It is a haloalkyl.

3. In Paragraph 2, The above Cycle A is cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptyl, cyclooctyl, azetidinyl, benzimidazolyl, benzofuranil, benzofurazanil, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranil, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazolin, isoxazoline, oxetanil, pyranil, pyrazinyl, Pyrazolyl, pyridazinyl, pyridopyridinyl, pyridyl, pyrimidyl, pyrrolyl, morpholino, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranil, tetrahydrothiopyranil, tetrahydroisoquinolinil, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, 1,4-dioxanyl, hexahydroazefinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholyl, thiomofolinyl, dihydrobenzoimidazolyl, dihydrobenzofuranil, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranil, Compounds, enantiomers, diastereomers, tautomers, hydrates, solvates, or pharmaceutically acceptable salts thereof, which are dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl, or tetrahydrothienyl.

4. In Paragraph 1, X is N and; Y2 and Y3 are each N; Z2 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12 heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinil, or oxetanil, and Here, the above Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

5. In Paragraph 1, X is N and; Y1 and Y2 are each N; Z2 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12 heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinil, or oxetanil, and Here, the above Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

6. In Paragraph 1, X is N and; Y1, Y2, and Y4 are each N; Z2 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, quaternary-12 heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinil, or oxetanil, and Here, the above Z2 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

7. In Paragraph 1, X is N and; Y1 and Y3 are each N; Z3 is absent, or H, C 1-10 Alkyl, C 1-10 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-12 Cycloalkyl, C 1-10 Haloalkyl, C 6-10 Aril, 4-12 won Heteroaryl, 4-12-membered heterocyclil, hydroxyl, halogen, cyano, morpholino, tetrahydrofuranil, tetrahydropyranil, piperazinil, piperidinil, oxetanil, and Here, the above Z3 is halo, hydroxyl, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, hydroxylalkyl, cyano, cycloalkyl, tetrahydropyranyl, CO-morpholino, CO-tetrahydropyranyl, CO-NH2, CO-NH(C 1-4 alkyl), and CO-N(C 1-4 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is substituted or unsubstituted with one or more groups selected from the group consisting of alkyl)2.

8. In Paragraph 2, X is N and; Y1 is N and; Cycle A is C 4-6 It is a cycloalkyl or a quaternary to hexavalent heterocycloalkyl, wherein Cycle A is C 4-6 A compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, wherein Y2 and Y3 are each C when the Cycle A is a cycloalkyl, and Y2 is N and Y3 is C, N, O, or S when the Cycle A is a quaternary to hexavalent heterocycloalkyl.

9. In Paragraph 1, The above chemical formula I is a compound, its enantiomer, diastereomer, tautomer, hydrate, solvate, or pharmaceutically acceptable salt, which is represented by any one of the following structures: [Chemical Formula I-1] [Chemical Formula I-2] [Chemical Formula I-3] [Chemical Formula I-4] [Chemical Formula I-5] 10. In Paragraph 1, The compound represented by the above chemical formula I is selected from the group consisting of the following compounds: a compound, its enantiomer, its diastereomer, its solvate, its tautomer, or its pharmaceutically acceptable salt: 1) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 2) 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 3) 5-cyclopropyl-3-((1-cyclopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide 4) 5-cyclopropyl-3-((1-ethyl-1H-1,2,4-triazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 5) 5-cyclopropyl-3-((3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 6) 5-cyclopropyl-3-((1-(1-hydroxy-2-methylpropane-2-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 7) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)picolinamide, 8) 5-cyclopropyl-3-((1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 9) 5-cyclopropyl-3-((4-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 10) 5-cyclopropyl-3-((1,5-dimethyl-1H-imidazole-4-yl)amino)-6-(3-methyl-3H-imidazoo[4,5-c]pyridine-7-yl)picolinamide, 11) 5-cyclopropyl-3-((1-isopropyl-4-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 12) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)picolinamide, 13) 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 14) 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide, 15) 5-cyclopropyl-3-((1-(2-fluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 16) 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 17) 5-cyclopropyl-3-((3-fluoro-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 18) 5-cyclopropyl-3-((3-(difluoromethyl)-1-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 19) 5-cyclopropyl-3-((1-isopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 20) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1-methylpiperidine-4-yl)-1H-pyrazole-4-yl)amino)picolinamide, 21) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)picolinamide, 22) 5-cyclopropyl-3-((1-ethyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide, 23) 5-cyclopropyl-3-((1-(difluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide, 24) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-4-yl)amino)picolinamide, 25) 5-cyclopropyl-3-((1-cyclopropyl-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 26) 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 27) 5-cyclopropyl-3-((1-(difluoromethyl)-3-methyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 28) 5-cyclopropyl-3-((1-isobutyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 29) 5-cyclopropyl-3-((1,3-dimethyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolineamide, 30) 5-cyclopropyl-3-((3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 31) 5-cyclopropyl-3-((1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 32) 5-cyclopropyl-3-((3-cyclopropyl-1-methyl-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 33) 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 34) 5-cyclopropyl-3-((1-(2,2-difluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 35) 5-cyclopropyl-3-((1-cyclopropyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 36) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 38) 5-cyclopropyl-3-((1-ethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 39) 5-cyclopropyl-3-((1-isobutyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 40) 5-cyclopropyl-3-((1-(2-methoxyethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 42) 3-((1-(tert-butyl)-3-methyl-1H-pyrazole-4-yl)amino)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 43) 5-cyclopropyl-3-((1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 44) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)picolinamide, 45) 5-cyclopropyl-3-((5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 46) 5-cyclopropyl-3-((1-(2,2-difluoropropyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 47) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazole-3-yl)amino)picolinamide, 49) 5-cyclopropyl-3-((5-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 50) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 51) 5-cyclopropyl-3-((1-isopropyl-5-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 52) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide, 53) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide, 54) 5-cyclopropyl-3-((3-fluoro-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 55) 5-cyclopropyl-3-((3-fluoro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 56) 5-cyclopropyl-3-((1-cyclopropyl-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 57) 5-cyclopropyl-3-((1-methyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 58) 5-cyclopropyl-3-((1,5-dimethyl-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 59) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolineamide, 60) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(1,1,1-trifluoropropane-2-yl)-1H-pyrazole-3-yl)amino)picolinamide, 61) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(trifluoromethyl)-1H-pyrazole-3-yl)amino)picolinamide, 62) 5-cyclopropyl-3-((3-fluoro-1-isopropyl-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 63) 5-cyclopropyl-3-((1-(cyclopropylmethyl)-3-fluoro-1H-pyrazole-4-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 64) (R)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide, 65) (S)-5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-(tetrahydro-2H-pyran-3-yl)-1H-pyrazole-3-yl)amino)picolinamide, 66) 5-cyclopropyl-3-((1-((1s,3s)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 67) 5-cyclopropyl-3-((1-((1r,3r)-3-methoxycyclobutyl)-1H-pyrazole-3-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, or 68) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((1-((1s,3s)-3-(trifluoromethyl)cyclobutyl)-1H-pyrazole-3-yl)amino)picolinamide.

11. In Paragraph 2, The compound represented by the above chemical formula II is selected from the group consisting of the following compounds: a compound, its enantiomer, its diastereomer, its solvate, its tautomer, or its pharmaceutically acceptable salt: 37) 5-cyclopropyl-3-((6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, 41) 5-cyclopropyl-3-((5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-yl)amino)-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)picolinamide, and 48) 5-cyclopropyl-6-(3-methyl-3H-imidazo[4,5-c]pyridine-7-yl)-3-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-yl)amino)picolineamide.

12. A pharmaceutical composition for the prevention or treatment of cancer, comprising a compound of any one of claims 1 to 11, a mirror image isomer, a diastereomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof.

13. In Paragraph 12, A pharmaceutical composition comprising, further comprising a pharmaceutically acceptable carrier, diluent, or excipient.

14. In Paragraph 12, The above cancers include blastoma, sarcoma, colorectal cancer, rectal cancer, colon cancer, colorectal cancer, thyroid cancer, oral cancer, pharyngeal cancer, laryngeal cancer, cervical cancer, brain cancer, brain tumor, glioblastoma, medulloblastoma, neuroblastoma, lung cancer, small cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous cell carcinoma, ovarian cancer, bladder cancer, kidney cancer, renal cell carcinoma, clear cell renal cell carcinoma, liver cancer, hepatocellular carcinoma, pancreatic cancer, prostate cancer, skin cancer, tongue cancer, breast cancer, uterine cancer, stomach cancer, bone cancer, lymphoma, blood cancer, peritoneal cancer, skin cancer, melanoma, cutaneous melanoma, ocular melanoma, rectal cancer, prostatic cancer, esophageal cancer, small intestine cancer, osteosarcoma, endocrine gland cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, gastric cancer, glioblastoma, ovarian cancer, endometrial cancer, salivary gland cancer, vulvar cancer, ependymoma. A pharmaceutical composition comprising one or more selected from the group consisting of Ewing's sarcoma, rhabdomyosarcoma, rhabdomyocarcinoma, renal cell tumor (Wilm's tumor), head and neck cancer, leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, lipoma, lipoblastoma, hibernation tumor, liposarcoma, leiomyoma, leiomyosarcoma, neurofibroma, and malignant Schwann tumor.

15. A composition for inhibiting hematopoietic progenitor kinase 1 (HPK1), comprising a compound of any one of claims 1 to 11, a mirror image isomer, a diastereomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition for immunostimulating, comprising a compound of any one of claims 1 to 11, a mirror image isomer, a diastereomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof.

17. A method for preparing a compound represented by the formula I of claim 1, comprising the step of performing a Buchwald-Hartwig coupling of a compound represented by the following formula (i): [Chemical formula (i)] In the above chemical formula (i), X is C or N and; W1 is an amine or a halo; W2 is H, hydroxyl, C 1-4 alkyl, or C 1-4 It is an alkoxy.

18. A method for preparing a compound represented by the formula II of claim 2, comprising the step of performing a Buchwald-Hartwig coupling reaction of a compound represented by the following formula (i): [Chemical formula (i)] In the above chemical formula (i), X is C or N and; W1 is an amine or a halo; W2 is H, hydroxyl, C 1-4 alkyl, or C 1-4 It is an alkoxy.

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