KR102651320B1 - Novel heteroaryl substituted derivative, and pharmaceutical composition for the prevention or treatment of neurodegenerative disease, cancer, and inflammatory disease comprising thereof - Google Patents

Abstract

The present invention relates to novel heteroaryl-substituted derivatives and compositions containing the same for the prevention or treatment of neurodegenerative diseases, cancer, and inflammatory diseases. The heteroaryl-substituted derivatives according to the present invention have excellent LRRK2 inhibitory activity and blood brain activity. It efficiently passes through the barrier (BBB) and can be usefully used as a pharmaceutical composition for preventing or treating neurodegenerative diseases, cancer, and inflammatory diseases.

Description

Novel heteroaryl substituted derivative, and pharmaceutical composition for the prevention or treatment of neurodegenerative disease, cancer, and inflammatory disease comprising the same }

It relates to novel heteroaryl-substituted derivatives and compositions containing the same for preventing or treating neurodegenerative diseases, cancer, and inflammatory diseases.

Neurodegenerative disease is a brain disease that occurs with age and is known to occur due to the accumulation of environmental and genetic factors.

It refers to a disease that causes various symptoms as degenerative changes occur due to gradual and steady death of nerve cells in the central nervous system, and is characterized by loss of nerve structure and function, including cell damage and memory impairment. Representative examples include Parkinson's disease, Alzheimer's disease, Huntington's disease, Pick's disease, amyotrophic lateral sclerosis, prion disease, and motor neuropathy. Examples include motor neuron disease, spinocerebellar ataxia, spinal muscular atrophy, Creutzfeldt-Jakob disease, and alcohol related dementia.

Parkinson's disease, along with Alzheimer's disease, is one of the representative neurodegenerative diseases. It is caused by a lack of the neurotransmitter dopamine due to the loss of dopaminergic neurons in the substantia nigra of the brainstem. As a result, protein aggregates called Lewy bodies are formed within nerve cells, causing motor function abnormalities such as stooped posture, tremors, stiffness, and instability, as well as mental symptoms such as depression, anxiety, and sleep disorders.

Although the exact cause of Parkinson's disease is not known, it is believed to be caused by a combination of factors such as environmental factors, genetic factors, aging, mitochondrial dysfunction, and abnormalities in the processing of unnecessary proteins. Most Parkinson's diseases occur sporadically, but 5-10% are known to be genetic diseases caused by gene mutations. The causative genes include parkin, PINK1, DJ-1, and α-synuclein. ), LRRK2 (leucine-rich repeat kinase 2), etc. are known.

Among these, the G2019S mutation of the LRRK2 gene appears most frequently as a dominant genotype. LRRK2 is a protein belonging to the leucin-rich repeat kinase family and consists of a sequence of 2527 amino acids with high similarity between species. , It has both GTPase and serine-threonine kinase activities in one protein. LRRK2 has been reported to be highly expressed in dopaminergic neurons present in the cerebral cortex, substantia nigra, striatum, hippocampus, and cerebellum of the brain, which are related to the pathogenesis of Parkinson's disease. Increased activity of LRRK2 has been shown to affect the onset and progression of Parkinson's disease. It is known. It has been confirmed that when normal LRRK2 is overexpressed in neurons, it induces apoptosis, and in LRRK2 hyperactive mutant animals, dopaminergic neuron death, Lewy bodies, and movement disorders similar to Parkinson's disease symptoms have been reported. In the case of LRRK2 knock-out animals, neurite outgrowth and inhibition of age-dependent α-synuclein increase, which is closely related to Parkinson's disease, were observed in the brain, and the possibility of treating Parkinson's disease by inhibiting LRRK2 has been confirmed in animal models. . In addition, LRRK2 is known to be involved in the transfer of mild cognitive impairment related to Alzheimer's disease, so compounds and compositions effective in regulating LRRK2 activity can provide therapeutic effects for neurodegenerative diseases. Therefore, selective inhibition of LRRK2 activity may be a beneficial target for the development of new drugs for disease treatment.

In addition to the above neurodegenerative diseases, anticancer activity through LRRK2 inhibition is being studied in various cancer types as a mechanism to inhibit proliferation and promote death of cancer cells. In particular, LRRK2 has been reported to be overexpressed in kidney, thyroid, and liver cancer tissues, and it is known that overactivation of LRRK2 due to LRRK2 mutation (particularly G2019S type) increases the risk of breast cancer. In addition, research results have reported that patients with overexpressed LRRK2 in the tissues of domestic brain cancer patients have a significantly shorter survival time. In this regard, Voronoi recently received approval to enter phase 1 clinical trials for its LRRK2 inhibitor as a treatment for brain cancer. Therefore, selective inhibition of LRRK2 activity can be a target for the development of a wide range of new drugs, not only for the treatment of neurodegenerative diseases but also for anti-cancer treatment. The LRRK2 expression profile was confirmed to be useful for studying colitis function in experimental models such as dextran sulfate sodium (DSS)-induced colitis, in which innate immune cells play an important role in the pathogenesis of the disease. This revealed that compared to LRRK2 wild-type mice, LRRK2-deficient mice were more susceptible to DSS-induced colitis due to rapid weight loss, worsening clinical symptoms, and more severe colonic abnormalities. The LRRK2 inflammatory signaling pathway is believed to be related to the MAPK pathway, and it has recently been demonstrated that LRRK2 kinase activity plays an important role in inflammation and toxicity through activation of the sub-pathway of MAPK signaling in both macrophages and microglia. (Kim, J. et al. (2019) LRRK2 kinase plays a critical role in manganese-induced inflammation and apoptosis in microglia. PLoS One 14) LRRK2 activity as a factor influencing chronic inflammatory changes, especially for Crohn's disease and ulcerative colitis. Alternatively, changes in expression levels may increase intestinal inflammation, which suggests that regulating LRRK2 activity will play a very important role as a treatment for inflammatory diseases in the future.

Meanwhile, as a prior art document related to a composition for preventing or treating neurodegenerative diseases containing a heteroaryl-substituted derivative as an active ingredient, Korean Patent No. 10-1566091 discloses a pyrazole aminopyrimidine derivative as an LRRK2 regulator; Korean Patent No. 10-2025451 discloses a 2-(phenyl or pyrid-3-yl) aminopyrimidine derivative as a regulator of the kinase LRRK2 for the treatment of Parkinson's disease, and Korean Patent No. 10-1208198, LRRK2 A pharmaceutical composition for the treatment or prevention of Parkinson's disease containing a compound with phosphorylation enzyme inhibitory activity as an active ingredient is disclosed, and Korean Patent Publication No. 10-2019-0018676 discloses piri as an LRRK2 inhibitor for use in the treatment of neurodegenerative disorders. Midin-2-ylamino-1H-pyrazole has been disclosed. However, there are no previous reports mentioning heteroaryl-substituted derivatives such as Formula 1 of the present invention and their LRRK2 inhibitory activity and the possibility of treating neurodegenerative diseases therefrom. Accordingly, in the process of studying LRRK2 derivatives, the present inventors confirmed that heteroaryl-substituted derivatives such as Formula 1 of the present invention have excellent LRRK2 inhibitory activity and efficiently pass through the blood brain barrier (BBB), thereby demonstrating the present invention. Completed.

One object of the present invention is to provide novel heteroaryl-substituted derivatives.

Another object of the present invention is to provide a method for producing novel heteroaryl-substituted derivatives.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating neurodegenerative diseases, cancer, or inflammatory diseases, containing a novel heteroaryl-substituted derivative as an active ingredient.

Another object of the present invention is to provide a health functional food for preventing or improving neurodegenerative diseases, cancer, or inflammatory diseases containing a novel heteroaryl-substituted derivative as an active ingredient.

In order to achieve the above purpose,

Provided is a compound represented by the following formula (1), a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.

[Formula 1]

Y is hydrogen, halogen, or unsubstituted or halogen-substituted C ₁ -C ₆ alkyl;

Z is hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted benzyl, substituted or unsubstituted C ₃ -C ₁₂ cycloalkyl, substituted or unsubstituted C ₃ -C ₁₂ heterocycloalkyl, is substituted with one or more substituents selected from the group consisting of substituted or unsubstituted C ₄ -C ₁₂ aryl, or substituted or unsubstituted C ₄ -C ₁₂ heteroaryl;

The substituted alkyl, benzyl, C ₃ -C ₁₂ cycloalkyl, C ₄ -C ₁₂ aryl, C ₄ -C ₁₂ heteroaryl are halogen, hydroxy, cyano, amino, amide, nitro, C ₁ -C ₆ alkyl. , C ₁ -C ₆ alkoxy, C ₃ -C ₁₂ heterocycloalkyl, C ₄ -C ₁₂ aryl-C ₁ -C ₆ alkoxy, or -C(=O)O-alkyl(C ₁ -C ₆ ). is substituted with one or more substituents selected from the group;

X is unsubstituted or substituted phenyl or heteroaryl of 5-6 atoms,

The substituted phenyl or heteroaryl of 5-6 atoms is,

Unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or halogen-substituted C ₁ -C ₆ alkoxy, unsubstituted or substituted C ₃ -C ₆ cyclo Alkyloxy, halogen, unsubstituted or substituted heteroaryl of 5-6 atoms, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B and -(CH ₂ )p- is substituted with one or more substituents of CONAB,

p is an integer from 0 to 5,

A is hydrogen or C ₁ -C ₆ alkyl,

B is unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO- B, or -(CH ₂ )p-CONAB is C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,

or,

A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3-7 atoms,

Here, the substituted C ₁ -C ₆ alkyl, substituted C ₃ -C ₆ cycloalkyl, substituted 5-6 atom heteroaryl and substituted 3-7 atom heterocycloalkyl are independently C ₁ -C ₆ Alkyl, C ₁ -C ₆ alkoxy, cyano, amino unsubstituted or substituted with C ₁ -C ₆ alkyl, unsubstituted heteroaryl of 5-6 atoms, or 3 unsubstituted or substituted with C ₁ -C ₆ alkyl -Substituted with 7-atom heterocycloalkyl.

In addition, the present invention, as shown in Scheme 1 below,

Provided is a method for producing a compound represented by Formula 1 of claim 1, comprising the step of preparing a compound represented by Formula 1 by reacting a compound represented by Formula 2 with a compound represented by Formula 3:

[Scheme 1]

In Scheme 1, W is halogen,

X, Y, and Z are as defined in Formula 1 above.

According to another aspect of the present invention, prevention of neurodegenerative diseases, cancer or inflammatory diseases containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. Alternatively, a pharmaceutical composition for treatment is provided.

According to another aspect of the present invention, a treatment for neurodegenerative diseases, cancer, or inflammatory diseases containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. Health functional foods for prevention or improvement are provided.

According to another aspect of the present invention, administering to a subject in need a pharmaceutical composition containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. Provides a method for preventing or treating neurodegenerative diseases, cancer, or inflammatory diseases, including.

According to another aspect of the present invention, a compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable compound thereof is used in the prevention or treatment of neurodegenerative diseases, cancer, or inflammatory diseases. Provided is the use of a pharmaceutical composition containing a salt.

The novel heteroaryl-substituted derivative according to the present invention has excellent LRRK2 inhibitory activity and efficiently passes the blood brain barrier (BBB), making it useful as a pharmaceutical composition for the prevention or treatment of neurodegenerative diseases, cancer, or inflammatory diseases. Available.

Hereinafter, the present invention will be described in detail.

One aspect of the present invention provides a compound represented by the following formula (1), a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.

[Formula 1]

Y is hydrogen, halogen, or unsubstituted or halogen-substituted C ₁ -C ₆ alkyl;

Z is hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted benzyl, substituted or unsubstituted C ₃ -C ₁₂ cycloalkyl, substituted or unsubstituted C ₃ -C ₁₂ heterocycloalkyl, is substituted with one or more substituents selected from the group consisting of substituted or unsubstituted C ₄ -C ₁₂ aryl, or substituted or unsubstituted C ₄ -C ₁₂ heteroaryl;

The substituted alkyl, benzyl, C ₃ -C ₁₂ cycloalkyl, C ₄ -C ₁₂ aryl, C ₄ -C ₁₂ heteroaryl are halogen, hydroxy, cyano, amino, amide, nitro, C ₁ -C ₆ alkyl. , C ₁ -C ₆ alkoxy, C ₃ -C ₁₂ heterocycloalkyl, C ₄ -C ₁₂ aryl-C ₁ -C ₆ alkoxy, or -C(=O)O-alkyl(C ₁ -C ₆ ). is substituted with one or more substituents selected from the group;

X is unsubstituted or substituted phenyl or heteroaryl of 5-6 atoms,

The substituted phenyl or heteroaryl of 5-6 atoms is,

Unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or halogen-substituted C ₁ -C ₆ alkoxy, unsubstituted or substituted C ₃ -C ₆ cyclo Alkyloxy, halogen, unsubstituted or substituted heteroaryl of 5-6 atoms, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B and -(CH ₂ )p- is substituted with one or more substituents of CONAB,

p is an integer from 0 to 5,

A is hydrogen or C ₁ -C ₆ alkyl,

B is unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO- B, or -(CH ₂ )p-CONAB is C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,

or,

A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3-7 atoms,

Here, the substituted C ₁ -C ₆ alkyl, substituted C ₃ -C ₆ cycloalkyl, substituted 5-6 atom heteroaryl and substituted 3-7 atom heterocycloalkyl are independently C ₁ -C ₆ Alkyl, C ₁ -C ₆ alkoxy, cyano, amino unsubstituted or substituted with C ₁ -C ₆ alkyl, unsubstituted heteroaryl of 5-6 atoms, or 3 unsubstituted or substituted with C ₁ -C ₆ alkyl -Substituted with 7-atom heterocycloalkyl.

In another embodiment of the present invention,

The X above is ego,

Ar is phenyl or heteroaryl of 5-6 atoms;

R ^1a and R ^1b are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or halogen-substituted C ₁ -C ₆ alkoxy, unsubstituted or substituted C ₃ -C ₆ cycle. alkyl oxy, unsubstituted or substituted 3-7 membered heterocycloalkyl, or unsubstituted or substituted C ₃ -C ₆ cycloalkyl;

R ² is unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted heteroaryl of 5-6 atoms, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO -B, or -(CH ₂ )p-CONAB,

p is an integer from 0 to 5,

A is hydrogen or C ₁ -C ₆ alkyl,

B is unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, or -(CH2)p-CO- B and -(CH ₂ )p-CONAB are C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,

or,

A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3 to 7 atoms;

Here, the substituted C ₁ -C ₆ alkyl, substituted C ₃ -C ₆ cycloalkyl, substituted 5-6 atom heteroaryl and substituted 3-7 atom heterocycloalkyl are independently C ₁ -C ₆ Alkyl, C ₁ -C ₆ alkoxy, cyano, amino unsubstituted or substituted with C ₁ -C ₆ alkyl, unsubstituted heteroaryl of 5-6 atoms, or 3 unsubstituted or substituted with C ₁ -C ₆ alkyl -Substituted with 7-atom heterocycloalkyl.

Additionally, in another embodiment of the present invention,

Y is halogen or C ₁ -C ₆ alkyl substituted with halogen;

X is , , , , or ego;

R ^1a , R ^1b , R ³ , R ⁴ , R ⁵ , and R ⁶ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or halogen-substituted C ₁ -C ₆ alkoxy , unsubstituted or substituted C ₃ -C ₆ cycloalkyl oxy, unsubstituted or substituted 3-7 membered heterocycloalkyl, or unsubstituted or substituted C ₃ -C ₆ cycloalkyl;

R ² is unsubstituted or substituted heteroaryl of 5-6 atoms, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B, or -(CH ₂ )p-CONAB ego,

p is an integer from 0 to 5,

A is hydrogen or C ₁ -C ₆ alkyl,

B is unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, or -(CH2)p-CO- B and -(CH ₂ )p-CONAB are C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,

or,

A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3 to 7 atoms;

Here, the substituted C ₁ -C ₆ alkyl, substituted C ₃ -C ₆ cycloalkyl, substituted 5-6 atom heteroaryl and substituted 3-7 atom heterocycloalkyl are independently C ₁ -C ₆ Alkyl, C ₁ -C ₆ alkoxy, cyano, amino unsubstituted or substituted with C ₁ -C ₆ alkyl, unsubstituted heteroaryl of 5-6 atoms, or 3 unsubstituted or substituted with C ₁ -C ₆ alkyl -Substituted with 7-atom heterocycloalkyl.

Additionally, in another embodiment of the present invention,

Y is halogen or C ₁ -C ₆ alkyl substituted with halogen;

Z is hydrogen or C ₁ -C ₆ alkyl;

X is , , , , or ego,

R ^1a and R ^1b are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₅ alkyl, unsubstituted or halogen-substituted C ₁ -C ₅ alkoxy, unsubstituted or substituted C ₃ -C ₆ cycle. alkyloxy, unsubstituted or substituted C ₃ -C ₆ cycloalkyl,

R ² is unsubstituted or substituted heteroaryl of 5-6 atoms, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B, or -(CH ₂ )p-CONAB ego,

Here, p is an integer from 0 to 4,

A is hydrogen or C ₁ -C ₅ alkyl,

B is unsubstituted or substituted C ₁ -C ₅ alkyl, unsubstituted or substituted C ₃ -C ₅ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-6 atoms, or -(CH2)p-CO- B and -(CH ₂ )p-CONAB are C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,

or,

A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3-6 atoms,

R ³ is unsubstituted or substituted C ₁ -C ₅ alkyl, or unsubstituted or substituted heterocycloalkyl of 3-7 atoms,

R ⁴ , R ⁵ , and R ⁶ are each independently hydrogen or unsubstituted or substituted C ₁ -C ₅ alkyl,

Here, the substituted C ₁ -C ₅ alkyl, substituted C ₃ -C ₆ cycloalkyl, substituted 5-6 atom heteroaryl, and substituted 3-7 atom heterocycloalkyl are each independently C ₁ -C ₅ alkyl, C ₁ -C ₅ alkoxy, cyano, amino substituted with C ₁ -C ₆ alkyl, unsubstituted heteroaryl of 5-6 atoms, or 3-7 unsubstituted or substituted with C ₁ -C ₆ alkyl The atom is substituted with heterocycloalkyl.

Additionally, in another embodiment of the present invention,

Y is halogen or C ₁ -C ₆ alkyl substituted with halogen;

Z is hydrogen or C ₁ -C ₄ alkyl;

X is , , , , or ego,

R ^1a and R ^1b are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₄ alkyl, unsubstituted or halogen-substituted C ₁ -C ₄ alkoxy, unsubstituted or substituted C ₃ -C ₅ cycle. alkyloxy, unsubstituted or substituted C ₃ -C ₅ cycloalkyl,

R ² is unsubstituted or substituted heteroaryl of 5-6 atoms, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B, or -(CH ₂ )p-CONAB ego,

Here, p is an integer from 0 to 3,

A is hydrogen or C ₁ -C ₃ alkyl,

B is unsubstituted or substituted C ₁ -C ₄ alkyl, unsubstituted or substituted C ₃ -C ₅ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, or -(CH2)p-CO- B and -(CH ₂ )p-CONAB are C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,

or,

A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3-7 atoms,

R ³ is unsubstituted or substituted C ₁ -C ₄ alkyl, or unsubstituted or substituted heterocycloalkyl of 3-7 atoms,

R ⁴ , R ⁵ , and R ⁶ are each independently hydrogen or unsubstituted or substituted C ₁ -C ₄ alkyl,

Here, the substituted C ₁ -C ₄ alkyl, substituted C ₃ -C ₅ cycloalkyl, substituted 5-6 atom heteroaryl, and substituted 3-7 atom heterocycloalkyl are each independently C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, cyano, amino substituted with C ₁ -C ₆ alkyl, unsubstituted heteroaryl of 5-6 atoms, or 3-7 unsubstituted or substituted with C ₁ -C ₆ alkyl The atom is substituted with heterocycloalkyl.

Examples of the compound represented by Formula 1 according to the present invention include the following compounds:

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Example 1 );

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4- 1) Benzamide (Example 2);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-(dimethylamino)piperidine -1-yl)methanone (Example 3);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-(1-methylpiperidin-4- 1) Benzamide (Example 4);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluorophenyl)(4-(dimethylamino)piperidine -1-yl)methanone (Example 5);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(1-methylpiperidin-4-yl )Benzamide (Example 6);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-(dimethylamino)piperidine-1 -1) Methanone (Example 7);

(3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(dimethylamino)piperidine- 1-day)methanone (Example 8);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(oxetane-3- 1) Benzamide (Example 9);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-(1-methylpiperidin-4- 1) Benzamide (Example 10);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 11);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-(oxetan-3-yl)benzamide (Example 12);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(oxetane-3- 1) Benzamide (Example 13);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxyphenyl)(morpholino)methanone (Example 14);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-(oxetan-3-yl)benz Amide (Example 15);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-(oxetan-3-yl)benz Amide (Example 16);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-methyl-N-(1-methylp peridin-4-yl)benzamide (Example 17);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxyphenyl)(pyrrolidin-1-yl)methane On (Example 18);

(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-((tetrahydrofuran- 2-yl)methyl)benzamide (Example 19);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-(oxetan-3-yl)benzamide (Example 20);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-methyl-N-( oxetan-3-yl)benzamide (Example 21);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(morpholino) Methanone (Example 22);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-methyl-N-( 1-methylpiperidin-4-yl)benzamide (Example 23);

3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)benzamide ( Example 24);

3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl )Benzamide (Example 25);

2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl )Benzamide (Example 26);

2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidine -4-yl)benzamide (Example 27);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(pyrrolidin-1-yl)methanone ( Example 28);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxyphenyl)(morpholino)methanone (practice Example 29);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-(oxetan-3-yl)benzamide (Example 30);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 31);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluorophenyl)(4-(4-methylpiperazine- 1-yl)piperidin-1-yl)methanone (Example 32);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-methyl-N-(oxetane-3- 1) Benzamide (Example 33);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluorophenyl)(4-(4-methylpiperazine- 1-yl)piperidin-1-yl)methanone (Example 34);

2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(1-methylpiperidin-4-yl )Benzamide (Example 35);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 36);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-(oxetan-3-yl)benzamide (Example 37);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-methyl-N-(oxetane-3- 1) Benzamide (Example 38);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-((tetrahydrofuran- 2-yl)methyl)benzamide (Example 39);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)-3-(2,2 ,2-trifluoroethoxy)benzamide (Example 40);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,2-dimethyl-N-(oxetan-3-yl)benz Amide (Example 41);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,3-dimethyl-N-(1-methylpiperidin-4 -1)benzamide (Example 42);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methylphenyl)(pyrrolidin-1-yl)methanone ( Example 43);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methylphenyl)(4-(dimethylamino)piperidine-1 -1) Methanone (Example 44);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-(1-methylpiperidin-4-yl)benzamide (Example 45);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-((tetrahydrofuran-2-yl)methyl)benzamide (Example 46);

(2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(4-methylpiperazine-1 -yl)piperidin-1-yl)methanone (Example 47);

3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(furan-2-ylmethyl)benzamide ( Example 48);

2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-methyl-N-(ox cetan-3-yl)benzamide (Example 49);

(2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxyphenyl)(morpholino)methane On (Example 50);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl)-3- (2,2,2-trifluoroethoxy)benzamide (Example 51);

3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)benzamide ( Example 52);

3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(furan-2-ylmethyl)-N- methylbenzamide (Example 53);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropylphenyl)(morpholino)methanone (Example 54);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-(oxetan-3-yl)benzamide (Example 55);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-methyl-N-(oxetane-3- 1) Benzamide (Example 56);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(oxetan-3-yl)benzamide ( Example 57);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,3-dimethyl-N-(oxetan-3-yl)benz Amide (Example 58);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 59);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide (Example 60);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,2,5-trimethyl-N-(oxetan-3-yl )Benzamide (Example 61);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(pyrrolidin-1-yl) Methanone (Example 62);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-(dimethylamino)piperi din-1-yl)methanone (Example 63);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-(1-methylpiperidin-4- 1) Benzamide (Example 64);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidin-4-yl )-3-(2,2,2-trifluoroethoxy)benzamide (Example 65);

2-Chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-methyl-N-(1 -methylpiperidin-4-yl)benzamide (Example 66);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethyl-N-(oxetan-3-yl)benz Amide (Example 67);

(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(tetra hydrofuran-3-yl)benzamide (Example 68);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-(oxetane-3 -1)benzamide (Example 69);

2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-(oxetane-3- 1) Benzamide (Example 70);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methyl-N-(oxetan-3-yl)benzamide ( Example 71);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-((1r,3r)-3-meth Toxycyclobutyl)benzamide (Example 72);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(2-methoxy-2-methylpropyl )Benzamide (Example 73);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(1-methoxy-2-methylpropane -2-yl)benzamide (Example 74);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(3-morpholinoazetidine-1 -1) Methanone (Example 75);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 76);

3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidine -4-yl)benzamide (Example 77);

3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(tetrahydro-2H-pyran -4-yl)benzamide (Example 78);

(3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(3-morpholinoazetidine-1- 1) Methanone (Example 79);

(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-( tetrahydrofuran-3-yl)benzamide (Example 80);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-((1r,3r )-3-methoxycyclobutyl)benzamide (Example 81);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-(1-methoxy -2-methylpropan-2-yl)benzamide (Example 82);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(4-morpholy nopiperidin-1-yl)methanone (Example 83);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxyphenyl)(morpholino)methanone (practice Example 84);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-(oxetan-3-yl)benz Amide (Example 85);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-methyl-N-(oxetane-3 -1)benzamide (Example 86);

4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-(1-methylpiperidin-4 -1)benzamide (Example 87);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxyphenyl)(4-(dimethylamino)piperi din-1-yl)methanone (Example 88);

(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(tetrahydrofuran-3 -1)benzamide (Example 89);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-(dimethylamino)piperidine -1-yl)methanone (Example 90);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxyphenyl)(4-(dimethylamino)piperi din-1-yl)methanone (Example 91);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1 -1) Methanone (Example 92);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-(pyrrolidin-1-yl) piperidin-1-yl)methanone (Example 93);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-morpholinopiperidin-1-yl ) Methanone (Example 94);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(3-morpholinoazetidin-1-yl ) Methanone (Example 95);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2,2-trifluoroethoxy)phenyl )(4-(dimethylamino)piperidin-1-yl)methanone (Example 96);

(2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(dimethylamino)piperidine- 1-yl)methanone (Example 97);

2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-N-(oxetane-3 -1)acetamide (Example 98);

2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-1-morpholinoethane- 1-one (Example 99);

2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-N-(1-methylp peridin-4-yl)acetamide (Example 100);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-(pyrrolidin-1 -yl)piperidin-1-yl)methanone (Example 101);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-morpholinopiperidine- 1-day)methanone (Example 102);

(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(3-morpholinoazetidine- 1-yl)methanone (Example 103);

3-methoxy-N-methyl-4-((4-(1-methyl-1H-pyrrol-3-yl)-5-(trifluoromethyl)pyrididin-2-yl)amino)-N-( oxetan-3-yl)benzamide (Example 104);

2-chloro-5-methoxy-N-methyl-4-((4-(1-methyl-1H-pyrrol-3-yl)-5-(trifluoromethyl)pyrididin-2-yl)amino) -N-(oxetan-3-yl)benzamide (Example 105);

(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(tetrahydrofuran-3- 1) Benzamide (Example 106);

(4-((5-chloro-4-(1-isopropyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (practice Example 107);

(R)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(tetrahydrofuran-3 -1)benzamide (Example 108);

5-chloro-N-(2-methoxy-4-morpholinophenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine (Example 109);

5-chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyrididine- 2-amine (Example 110);

5-chloro-N-(4-(2,4-dimethyloxazol-5-yl)-2-methoxyphenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2- Amines (Example 111);

5-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylisoindolin-1-one (Example 112);

5-chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(6-morpholinopyridin-3-yl)pyrididin-2-amine (Example 113);

2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methyl-1H-pyrazol-1-yl)- 2-methylpropanenitrile (Example 114);

6-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3,4-dihydronaphthalen-1(2H)-one (Example 115);

5-chloro-N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine (Example 116);

N-(5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)-5-methylthiazol-2-amine (Example 117)

5-chloro-N-(2-fluoro-4-morpholinophenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine (Example 118);

5-Chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(4-morpholino-2-(trifluoromethyl)phenyl)pyrididin-2-amine (Example 119) .

The compound represented by Formula 1 of the present invention can be used in the form of a pharmaceutically acceptable salt, and an acid addition salt formed by a pharmaceutically acceptable free acid is useful as the salt. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc., aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. Non-toxic organic acids such as dioate, aromatic acids, aliphatic and aromatic sulfonic acids, 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. get it from These pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and nitrate. Odide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, sube. Latex, sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, Includes glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate, etc.

The acid addition salt according to the present invention can be prepared by conventional methods, for example, the precipitate produced by dissolving the derivative of Formula 1 in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc. and adding an organic acid or inorganic acid. It can be prepared by filtering and drying, or by distilling the solvent and excess acid under reduced pressure, drying it, and crystallizing it in an organic solvent.

Additionally, a pharmaceutically acceptable metal salt can be prepared using a base. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically appropriate to prepare sodium, potassium, or calcium salts as metal salts. Additionally, the corresponding salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable negative salt (e.g., silver nitrate).

Furthermore, the present invention includes not only the compound represented by Formula 1 and its pharmaceutically acceptable salts, but also solvates, stereoisomers, hydrates, etc. that can be prepared therefrom.

The term "alkyl" refers to a straight or branched chain fully saturated hydrocarbon group, examples of alkyl include methyl (Me), ethyl (Et), propyl (e.g. n-propyl and isopropyl groups, butyl (e.g. n -Butyl, isobutyl, s-butyl, t-butyl), pentyl (eg, n-pentyl, isopentyl (Isopentyl group), neopentyl group), etc.

The term “cycloalkyl” refers to a saturated hydrocarbon group with a ring-shaped single bond. For example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[3.1.1]heptyl, spiro[4.5]decyl, spiro[5.5]undecyl, adamantyl, etc. You can.

The terms “halo” and “halogen” are used in their conventional sense to refer to a fluoro (F), chloro (Cl), bromo (Br) or iodo (I) substituent.

The term “haloalkyl” includes alkyl substituted with one or more halogens, either monosubstituted (eg -CH2F) or multiply substituted (eg -CF3).

The term “alkoxy” refers to an oxygen group to which a single bond of straight or branched saturated hydrocarbon is bonded. Examples include methoxy, ethoxy, propoxy, n-butoxy, tert-butoxy, and 1-methylpropoxy.

The term “heterocycloalkyl” refers to a ring-shaped, single-bonded saturated hydrocarbon group containing one or more heteroatoms such as N, O, or S, and depending on the number and type of heteroatoms contained in the ring and the number of carbon atoms, Nyl, pyrrolidinyl, piperidinyl, oxopiperidinyl, morpholinyl, piperazinyl, oxopiperazinyl, morpholinyl, thiomorpholinyl, azepanyl, diazepanyl, oxazepanil, tiazepa These include nil, dioxothiazepanyl, azocanyl, tetrahydrofuranyl, tetrahydropyranyl, oxazolidinyl, dioxanyl, dioxolanyl, etc.

The term “heteroaryl” refers to an aromatic ring compound containing one or more heteroatoms such as N, O, or S, and depending on the number and type of heteroatoms contained in the ring and the number of carbon atoms, it may be pyridyl, pyrrolyl, or pyrrolyl. Dinyl, pyridinyl, furanyl, quinolidinyl, indolyl, pyrimidinyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, pyranyl, thiophenyl, thiazolyl, dibenzothiophenyl, Dibenzofuranyl, dibenzoselenophen, thiophene, benzofuran, benzothiophenyl, benzoselenophenyl, carbazolyl, indolocarbazolyl, pyridyl indolyl, pyrrolodipyridinyl, pyrazolyl, imyzolyl Dazolyl, triazolyl, oxazinyl, thiazolyl, oxadiazolyl, oxatriazolyl, dioxazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrazinyl, triazinyl, oxazinyl, oxathiazinyl, oxazolyl diazinyl, indoleyl, benzimidazolyl, indazolyl, indoxazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, cynolinyl, quinazolinyl, quinoxalinyl, Naphthyridinyl, phthalazinyl, pteridinyl, xanthenyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, benzofuropyridinyl, furodipyridinyl, benzothienopyridinyl, thienodiyl. These include pyridinyl, benzoselenophenopyridinyl, and selenophenodipyridinyl.

The term “hydrate” refers to a compound of the present invention containing a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces. or its salt. The hydrate of the compound represented by Formula 1 of the present invention may contain a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces. The hydrate may contain more than 1 equivalent of water, preferably 1 to 5 equivalents of water. Such hydrates can be prepared by crystallizing the compound represented by Formula 1 of the present invention, its stereoisomer, its solvate, its hydrate, or its pharmaceutically acceptable salt from water or a water-containing solvent.

The term “solvate” refers to a compound of the invention or a salt thereof containing a stoichiometric or non-stoichiometric amount of solvent bound by non-covalent intermolecular forces. Preferred solvents therefor are solvents that are volatile, non-toxic, and/or suitable for administration to humans.

The term “isomer” refers to a compound of the present invention or a salt thereof that has the same chemical or molecular formula but is structurally or sterically different. These isomers include structural isomers, including tautomers, and stereoisomers. Stereoisomers include enatiomers and diastereomers that appear by having one or more asymmetric carbon centers, and geometric isomers. (trans, cis) are all included. All these isomers and mixtures thereof are also included within the scope of the present invention.

In the present invention, “substituted with one or more substituents” means substituted with 1 to 3 substituents among the listed substituents.

Additionally, the compound, its stereoisomer, its solvate, its hydrate, or its pharmaceutically acceptable salt can inhibit LRRK2.

Another aspect of the present invention is the prevention of neurodegenerative diseases, cancer, or inflammatory diseases containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. Alternatively, a pharmaceutical composition for treatment is provided.

The pharmaceutical composition may further include a pharmaceutically acceptable carrier in addition to the active ingredient.

The neurodegenerative disease refers to a disease that causes various symptoms as degenerative changes occur due to gradual and steady death of neurons in the central nervous system, and includes Parkinson's disease, Alzheimer's disease, and Huntington's disease. disease, Pick's disease, amyotrophic lateral sclerosis, Prion disease, Motor neuron disease, Spinocerebellar ataxia, Spinal muscular atrophy It may be selected from the group consisting of muscular atrophy, Creutzfeldt-Jakob disease, and alcohol related dementia, but is not particularly limited thereto.

In addition, the above cancers include kidney cancer, thyroid cancer, breast cancer, liver cancer, brain cancer, lung cancer, ovarian cancer, colon cancer, melanoma, stomach cancer, gastrointestinal cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, skin or eye melanoma, uterine cancer, rectal cancer, It may be selected from the group consisting of colon cancer, esophageal cancer, laryngeal cancer, small intestine cancer, sarcoma of soft tissue, urethral cancer, penile cancer, prostate cancer, and multiple myeloma, and preferably consists of kidney cancer, thyroid cancer, breast cancer, liver cancer, and brain cancer. It may be selected from the group, but is not particularly limited thereto.

In addition, the inflammatory diseases include inflammatory bowel disease, ulcerative colitis, inflammatory skin disease, pancreatitis, allergic rhinitis, allergic conjunctivitis, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, ankylosing spondylitis, enteropathy spondylitis, and juvenile spondylitis. Ankylosing spondylitis, infectious arthritis, polyarteritis nodosa, hypersensitivity vasculitis, arthrocellular arteritis, bursitis, tenosynovitis, epicondylitis, neonatal multisystem inflammatory disease, contact dermatitis, keratitis, conjunctivitis, retinitis, retinal vasculitis, uveitis , blepharitis, allergic conjunctivitis, polymyositis, autoimmune encephalomyelitis, polyarteritis nodosa, and fibromyalgia syndrome, but is not particularly limited thereto.

The compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be administered in various oral and parenteral dosage forms during clinical administration. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain one or more compounds and at least one excipient, such as starch, calcium carbonate, sucrose, or lactose ( It is prepared by mixing lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. there is. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, and emulsions. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable esters such as ethyl oleate.

A pharmaceutical composition containing the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient can be administered parenterally, and parenteral administration can be done by subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. It depends on how you do it.

At this time, in order to formulate a formulation for parenteral administration, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is mixed with water along with a stabilizer or buffer to prepare a solution or suspension, which is administered in ampoule or vial unit dosage form. It can be manufactured with The composition may be sterilized and/or contain auxiliaries such as preservatives, stabilizers, wetting agents or emulsification accelerators, salts and/or buffers for adjusting osmotic pressure, and other therapeutically useful substances, and may be mixed, granulated, etc. using conventional methods. It can be formulated according to the coating or coating method.

Dosage forms for oral administration include, for example, tablets, pills, hard/soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, troches, etc. These dosage forms contain a diluent (e.g. lactose) in addition to the active ingredient. , dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine), lubricants (e.g. silica, talc, stearic acid and its magnesium or calcium salts and/or polyethylene glycol). The tablets may contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases, boron agents such as starch, agar, alginic acid or its sodium salt, etc. The releasing or boiling mixture may contain absorbents, colorants, flavoring agents, and sweeteners.

Another aspect of the present invention is the prevention of neurodegenerative diseases, cancer, or inflammatory diseases containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. Or provide health functional foods for improvement.

The compound represented by Formula 1 according to the present invention exhibits excellent LRRK2 inhibitory ability, and is manufactured as a pharmaceutical composition as a health functional food composition for preventing or improving neurodegenerative diseases, cancer, or inflammatory diseases, or as a food, beverage, etc. It can be added to health functional supplements.

The compound represented by Formula 1 according to the present invention can be added as is to food or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention or improvement). In general, the amount of the above compound in health food can be 0.1 to 90 parts by weight of the total weight of the food. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

Another aspect of the present invention is to provide a pharmaceutical composition or health functional food containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient to a subject in need thereof. Provided is a method for preventing or treating neurodegenerative diseases, cancer, or inflammatory diseases, including the step of administering.

Another aspect of the present invention is the use of the compound represented by Formula 1, its stereoisomer, its solvate, its hydrate, or its pharmaceutically acceptable salt in the prevention or treatment of neurodegenerative diseases, cancer, or inflammatory diseases. Provides a purpose.

The compound represented by Formula 1 of the present invention, its stereoisomer, its solvate, its hydrate, or its pharmaceutically acceptable salt or pharmaceutical composition is administered in a “pharmaceutically effective amount.” In the present invention, the term “pharmaceutically effective amount” means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment or improvement, and the effective dose level is determined by the type and severity of the individual, age, It can be determined based on factors including gender, drug activity, sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field. For example, effective amounts of 0.001 mg/kg to 1000 mg/kg, 0.01 mg/kg to 100 mg/kg or 0.1 to 20 mg/kg or 0.1 to 500 mg/kg are included. The amount of the pharmaceutical composition of the present invention can be selected and implemented by a person skilled in the art within an appropriate range.

The compound represented by Formula 1 of the present invention can be prepared by the following manufacturing method.

[Scheme 1]

In Scheme 1, W is halogen,

X, Y, and Z are as defined in Formula 1 above.

The coupling reaction of Scheme 1 may proceed by a substitution reaction and may proceed in the presence of a transition metal catalyst. Additionally, the process may be carried out in the presence of a base, and an organic solvent may be used as the solvent.

As a catalyst, Pd(PPh ₃ ) ₄ may be used, and the organic solvent may include 1,4-dioxane, tetrahydrofuran, DMF, DMSO, chloroform, etc.

Bases include organic or inorganic bases. Organic bases may include primary, secondary, and tertiary amines, and inorganic bases may include carbonates and hydroxides of alkali metals or alkaline earth metals.

Additionally, some embodiments of the present invention can be prepared by Scheme 2 below.

[Scheme 2]

In Scheme 2, Ar, R ^1a , R ^1b , Y, Z, p, A and B are as defined in Formula 1 above.

Reaction Scheme 2 is an amidation reaction that can be performed in an organic solvent under the conditions of addition of a catalyst or an acid activator.

The catalyst may be an acid catalyst and includes an inorganic or organic acid.

The acid activator may be a carbodiimide such as EDCl, HOBt, or an acylating agent.

If necessary, a tertiary amine such as DIPEA may be further included as a base.

Additionally, in Scheme 2, the carboxylic acid derivative can be prepared according to Scheme 3 below.

[Scheme 3]

In Scheme 3, W is halogen,

Ar, R ^1a , R ^1b , Y, Z, and p are as defined in Formula 1 above.

Reaction Scheme 3 consists of the following steps.

Step 1 is a combination reaction of pyrrole derivatives and proceeds as a substitution reaction in an organic solvent in the presence of a catalyst and a base.

Regarding organic solvents, catalysts, and bases, the matters mentioned in Scheme 1 can be applied as is.

Step 2 is a substitution reaction with an amine derivative, and the reaction conditions of step 1 can be applied as is.

As a catalyst, one or more types selected from XantPhos and Pd(OAc) ₂ may be used.

Step 3 is a hydrolysis reaction of an ester bond, which can be performed under an acid or base catalyst. The base mentioned in Scheme 1 can be applied as is, and the acid can be an inorganic or organic acid. Inorganic acids include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, etc. When a base is used as a catalyst, workup can be performed under acid conditions to obtain the target product in acid form.

Hereinafter, the present invention will be described in detail through preparation examples and examples.

However, the following preparation examples and examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following preparation examples and examples.

<Preparation Example 1> Preparation of methyl 4-amino-3-ethoxybenzoate

According to the above reaction formula, methyl 4-amino-3-hydroxybenzoate (1.5 g, 8.97 mmol) was dissolved in 100 ml RBF with DMF, and then K ₂ CO ₃ (1.865 g, 13.5 mmol) and iodoethane (1.469 g) , 9.42 mmol) was added at room temperature. The mixture was stirred at room temperature for 10 minutes and then heated at 50°C for 16 hours. After completion of the reaction, the mixture was concentrated under reduced pressure and extracted several times with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, concentrated under reduced pressure, and purified through column chromatography to obtain the target compound (white solid, 1.6 g, 91%).

<Preparation Example 2> Preparation of methyl 4-amino-3-(2,2,2-trifluoroethoxy)benzoate

According to the above reaction formula, methyl 4-amino-3-hydroxybenzoate (1 g, 5.98 mmol) was completely dissolved in 100 ml RBF with DMF, and then K2CO3 (1.239 g, 8.97 mmol) and 2,2,2-trifluoride. Roethyl trifluoromethanesulfonate (1.666 g, 7.18 mmol) was added at room temperature. The mixture was stirred at room temperature for 10 minutes and then heated at 50°C for 16 hours. After completion of the reaction, the mixture was concentrated under reduced pressure and extracted several times with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, concentrated under reduced pressure, and purified through column chromatography to obtain the target compound (white solid, 462 mg, 31%).

<Preparation Example 3> Preparation of methyl 4-amino-3-cyclopropylbenzoate

According to the above reaction formula, methyl 4-amino-3-bromobenzoate (1 g, 4.07 mmol) was completely dissolved in 1,4-dioxane in 100 ml RBF, and then cyclopropylbroic acid (457 mg, 5.33 mmol) , Pd(dppf)Cl ₂ ·CH ₂ Cl ₂ (334 mg, 0.41 mmol), and K ₃ PO ₄ (3.046 g, 14.4 mmol) were added at room temperature. The mixture was stirred at room temperature for 10 minutes and then heated at 100°C for 3 hours. After completion of the reaction, the mixture was filtered under reduced pressure with celite bad and extracted several times with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, concentrated under reduced pressure, and purified through column chromatography to obtain the target compound (white solid, 555 mg, 66%).

<Preparation Example 4> Preparation of 4-amino-3-cyclopropoxybenzoate

The compound of Preparation Example 4 was prepared according to the above reaction scheme.

Step 1) According to the above reaction formula, methyl 3-fluoro-4-nitrobenzoate (2 g, 10.1 mmol) was completely dissolved in 100 ml RBF with DMF, and then Cs ₂ CO ₃ (4.913 g. 15.1 mmol) and cyclopropanol. (759 mg, 13.1 mmol) was added at room temperature. The mixture was stirred at room temperature for 5 minutes and then heated at 80°C for 16 hours. After completion of the reaction, it was concentrated under reduced pressure and purified through column chromatography to obtain methyl 3-cyclopropoxy-4-nitrobenzoate (light yellow solid, 1.295 g, 53%).

Step 2) Methyl 3-cyclopropoxy-4-nitrobenzoate (1.259 g, 5.31 mmol) was completely dissolved in 100 ml RBF with methanol, then Zn (519 mg. 7.95 mmol), HCO ₂ HN ₄ (534 mg, 8.48 mmol) mmol) was added at room temperature. The mixture was stirred at room temperature for 10 minutes and then heated at 80°C for 16 hours. After completion of the reaction, the mixture was filtered under reduced pressure with a celite bad, concentrated under reduced pressure, and purified through column chromatography to obtain the target compound (yellow solid, 900 mg, 82%).

<Preparation Example 5> Preparation of methyl 4-amino-3-(2,2-difluoroethoxy)benzoate

According to the above reaction formula, methyl 4-amino-3-hydroxybenzoate (500 mg, 2.99 mmol) was completely dissolved in 100 ml RBF with DMF, then K ₂ CO ₃ (619 mg, 4.48 mmol), 1,1-di Fluoro-2-iodoethane (631 mg. 3.28 mmol) was added at room temperature. The mixture was stirred at 80° C. for 16 hours. After completion of the reaction, extraction was performed several times with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, concentrated under reduced pressure, and purified through column chromatography to obtain the target compound (yellow solid, 452 mg, 67%).

<Example 1> (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino) Preparation of Methanone

The compound of Example 1 was prepared according to the above reaction scheme.

Step 1) Preparation of 2,5-dichloro-4-(1-methyl-1H-pyrrol-3-yl)pyrimidine

2,4,5-Trichloropyrimidine (11.5 g, 62.98 mmol) was dissolved in 200 mL of 1,4-dioxane, then 1-methyl-3-(4,4,5,5-tetramethyl-1) ,3,2-dioxaborolan-2-yl)-1H-pyrrole (15 g, 72.4 mmol), Pd(PPh3)4 (946 mg, 0.81 mmol), 2M Na ₂ CO ₃ solution (50 mL) Add and stir at 105°C for 6 hours. The organic layer extracted by adding ethyl acetate, saturated NaCl aqueous solution, and water is dried, filtered, and concentrated using MgSO ₄ . The obtained crude product was separated by column chromatography to obtain 13.55 g (94% yield) of the target compound as a yellow solid.

Step 2) Preparation of methyl 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrimidin-2-yl)amino)-3-methoxybenzoate

Methyl 4-amino-3-methoxybenzoate (716 mg, 3.95 mmol) was dissolved in 20 mL of 1,4-dioxane, then 2,5-dichloro-4-(1-methyl-1H-pyrrole-3- 1) Add _{pyrimidine (} 992 mg _, 4.35 mmol), Stir for a while. The reaction mixture is filtered under reduced pressure on a Celite pad, and the filtrate is extracted with ethyl acetate, saturated NaCl aqueous solution, and water. The extracted organic layer is dried, filtered, and concentrated using MgSO ₄ . The obtained crude product was separated by column chromatography to obtain 1146 mg (77.8% yield) of the target compound as a yellow solid.

Step 3) Preparation of 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrimidin-2-yl)amino)-3-methoxybenzoic acid

Methyl 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrimidin-2-yl)amino)-3-methoxybenzoate (1140 mg, 3.05 mmol) was dissolved in 15 mL of THF. , potassium hydroxide (514 mg, 9.17 mmol) dissolved in 5 mL of MeOH and then dissolved in 5 mL of H2O was added and stirred at 75°C for 4 hours. The reaction mixture is concentrated under reduced pressure and extracted by adding ethyl acetate and water. A 1N HCl solution was added to pH 2 to the extracted aqueous solution layer, and the resulting solid was filtered under reduced pressure. 736 mg (67.2% yield) of the target compound was obtained as a white solid, and the obtained solid was used in the next reaction without further purification.

Step 4) (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone manufacture of

Methyl 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrimidin-2-yl)amino)-3-methoxybenzoate (350 mg, 0.97 mmol) was dissolved in 10 mL of THF. After dissolving in , morpholine (169 mg, 1.95 mmol), EDCI-HCl (372 mg, 1.95 mmol), HOBt (65 mg, 0.48 mmol), and DIPEA (188 mg, 1.46 mmol) were added and incubated at room temperature for 12 hours. Stir. The organic layer extracted by adding ethyl acetate, saturated NaCl aqueous solution, and water is dried using MgSO4, filtered, and concentrated. The obtained crude product was separated by column chromatography to obtain 402 mg (94.1% yield) of the target compound as a white solid.

Examples 1 to 108 were prepared using the reaction prepared in Example 1, and the names and NMR spectrum data of the prepared compounds are summarized in Table 1 below, and the structures of the compounds are summarized in Table 2.

Example name NMR assignment One (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.62 (d, J = 8.2 Hz, 1H), 8.31 (s, 1H), 7.82 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.09 - 7.02 (m, 1H), 7.05 (s, 2H), 6.70 (t, J = 2.5 Hz, 1H), 3.95 (s, 3H), 3.76 (s, 3H), 3.71 (s, 8H). 2 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4- 1) Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.65 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.88 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.38 - 7.27 (m, 1H), 7.14 - 7.03 (m, 1H), 6.72 - 6.62 (m, 1H), 5.96 (d, J = 8.0 Hz, 1H), 4.10 (s, 1H), 3.99 (s, 2H), 3.91 (s, 1H), 3.76 (s, 2H), 2.83 (s, 2H), 2.31 (d, J = 4.9 Hz, 3H), 2.18 (t , J = 10.6 Hz, 2H), 2.04 (d, J = 4.2 Hz, 3H), 1.30 - 1.22 (m, 1H). 3 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-(dimethylamino)piperidine -1-day) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.61 (d, J = 8.3 Hz, 1H), 8.30 (s, 1H), 7.82 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.05 (ddd, J = 11.2, 8.1, 1.8 Hz, 3H), 6.69 (t, J = 2.5 Hz, 1H), 3.93 (s, 3H), 3.75 (s, 3H), 2.90 (d, J = 8.2 Hz, 2H), 2.54 - 2.44 (m, 2H), 2.39 (dt, J = 8.1, 3.4 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H), 1.88 (s, 2H), 1.52 - 1.44 (m, 2H). 4 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-(1-methylpiperidin-4- 1) Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.33 (s, 1H), 8.05 (t, J = 8.9 Hz, 1H), 7.96 (dd, J = 15.6, 2.1 Hz, 1H), 7.73 (t, J = 1.9 Hz, 1H), 7.29 (s, 1H), 7.19 (dd, J = 8.6, 2.1 Hz, 1H), 7.03 (dd, J = 2.9, 1.8 Hz, 1H), 6.74 - 6.67 (m, 1H), 6.62 (dd, J = 13.9, 7.7 Hz, 1H), 4.05 (s, 1H), 3.77 (s, 3H), 2.82 (s, 2H), 2.33 (s, 3H), 2.23 (d, J = 11.4 Hz) , 2H), 2.06 (d, J = 10.8 Hz, 2H), 1.65 (t, J = 11.7 Hz, 2H). 5 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluorophenyl)(4-(dimethylamino)piperidine -1-day) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.31 (s, 1H), 7.87 (d, J = 12.3 Hz, 1H), 7.75 - 7.70 (m, 1H), 7.34 (t, J = 8.0 Hz, 1H) , 7.20 (d, J = 9.4 Hz, 2H), 7.03 (dd, J = 2.8, 1.8 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 4.82 (d, J = 13.1 Hz, 1H) , 3.76 (s, 3H), 2.86 - 2.65 (m, 2H), 2.44 (s, 6H), 2.09 - 1.81 (m, 6H). 6 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(1-methylpiperidin-4-yl )Benzamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.29 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.60 - 7.53 (m, 1H), 7.49 (s, 1H), 7.37 (d, J = 8.3 Hz, 1H), 7.08 (s, 1H), 7.03 (dd, J = 2.9, 1.8 Hz, 1H), 6.72 - 6.66 (m, 1H), 5.63 (d, J = 8.1 Hz, 1H), 3.99 (s, 1H), 3.75 (s, 3H), 2.84 (s, 2H), 2.49 (s, 3H), 2.33 (s, 3H), 2.19 (s, 2H), 2.07 (d, J = 12.6 Hz , 2H), 1.61 (s, 2H). 7 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-(dimethylamino)piperidine-1 -1) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.28 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.54 (d, J = 9.8 Hz, 2H), 7.21 (s, 1H), 7.14 (s, 1H), 7.02 (dd, J = 2.9, 1.7 Hz, 1H), 6.68 (t, J = 2.5 Hz, 1H), 4.82 (d, J = 13.4 Hz, 1H), 3.75 (s, 3H) , 3.65 (d, J = 13.4 Hz, 1H), 3.35 - 3.14 (m, 1H), 2.97 (t, J = 12.9 Hz, 1H), 2.79 (s, 2H), 2.50 (d, J = 12.2 Hz, 1H), 2.35 (s, 6H), 2.31 (s, 3H), 2.00 (d, J = 9.7 Hz, 1H), 1.79 (s, 1H). 8 (3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(dimethylamino)piperidine- 1-day) Methanone ^1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 8.6 Hz, 1H), 8.34 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.67 (s, 1H), 7.50 ( d, J = 2.0 Hz, 1H), 7.37 (dd, J = 8.5, 2.0 Hz, 1H), 7.04 (dd, J = 2.9, 1.7 Hz, 1H), 6.75 - 6.62 (m, 1H), 3.76 (s) , 3H), 2.40 (t, J = 11.1 Hz, 1H), 2.31 (s, 6H), 1.88 (s, 2H), 1.48 (s, 2H), 1.24 - 1.10 (m, 1H), 0.87 (d, J = 7.1 Hz, 1H). 9 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(oxetane-3- 1) Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.63 (d, J = 8.5 Hz, 1H), 8.32 (s, 1H), 7.84 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.11 - 6.96 (m, 3H), 6.70 (t, J = 2.5 Hz, 1H), 5.33 - 5.26 (m, 1H), 4.84 (d, J = 6.8 Hz, 4H), 3.94 (s, 3H), 3.76 ( s, 3H), 3.23 (s, 3H). 10 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-(1-methylpiperidin-4- 1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.67 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.88 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.44 ( d, J = 1.9 Hz, 1H), 7.29 (dd, J = 8.5, 1.9 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 5.94 (d, J = 7.9 Hz, 1H), 4.22 (q, J = 7.0 Hz, 2H), 4.05 - 3.92 (m, 1H), 3.76 (s, 3H), 2.89 - 2.78 (m, 2H), 2.32 (s, 3H), 2.23 - 2.12 (m, 2H), 2.10 - 2.04 (m, 2H), 1.72 - 1.55 (m, 2H), 1.51 (t, J = 7.0 Hz, 3H). 11 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.3 Hz, 1H), 8.31 (s, 1H), 7.81 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.05 ( dd, J = 2.9, 1.7 Hz, 1H), 7.03 (d, J = 8.5 Hz, 1H), 6.97 (s, 1H), 6.69 (t, J = 2.5 Hz, 1H), 4.15 (q, J = 7.0 Hz, 2H), 3.76 (s, 3H), 2.94 (s, 3H), 2.27 (s, 3H), 1.91 (s, 2H), 1.71 (s, 1H), 1.62 - 1.59 (m, 6H), 1.50 (t, J = 7.0 Hz, 3H). 12 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-(oxetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 8.5 Hz, 1H), 8.33 (s, 1H), 7.90 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.43 ( d, J = 1.9 Hz, 1H), 7.36 (dd, J = 8.5, 1.9 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 6.59 (d, J = 7.5 Hz, 1H), 5.25 (p, J = 7.0 Hz, 1H), 5.03 (t, J = 7.1 Hz, 2H), 4.63 (t, J = 6.5 Hz, 2H), 4.21 ( q, J = 7.0 Hz, 2H), 1.58 (s, 5H), 1.51 (t, J = 7.0 Hz, 3H). 13 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(oxetane-3- 1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.64 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.84 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.05 ( dd, J = 2.9, 1.7 Hz, 1H), 7.00 (s, 2H), 6.69 (t, J = 2.5 Hz, 1H), 5.29 (p, 1H), 4.83 (d, J = 6.9 Hz, 4H), 4.16 (q, J = 7.0 Hz, 2H), 3.76 (s, 3H), 3.22 (s, 3H), 1.50 (t, J = 7.0 Hz, 3H). 14 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxyphenyl)(morpholino)methanone ^1H NMR (400 MHz, CDCl3) δ 8.64 (d, J = 8.3 Hz, 1H), 8.31 (s, 1H), 7.82 (s, 1H), 7.72 (t, J = 1.9 Hz, 1H), 7.14 - 7.03 (m, 2H), 7.02 (d, J = 1.8 Hz, 1H), 6.69 (dd, J = 2.9, 2.2 Hz, 1H), 4.17 (q, J = 7.0 Hz, 2H), 3.76 (s, 3H) ), 3.74 - 3.58 (m, 9H), 1.62 (s, 1H), 1.50 (t, J = 7.0 Hz, 3H). 15 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-(oxetan-3-yl)benz amides ^1H NMR (400 MHz, CDCl ₃ ) δ 8.65 (d, J = 8.5 Hz, 1H), 8.32 (s, 1H), 7.84 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 7.02 (s, 2H), 6.70 (t, J = 2.5 Hz, 1H), 5.32 - 5.24 (m, 1H), 4.84 (d, J = 6.8 Hz, 4H), 4.67 (p, J = 6.1 Hz, 1H), 3.76 (s, 3H), 3.23 (s, 3H), 1.42 (d, J = 6.1 Hz, 6H). 16 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-(oxetan-3-yl)benz amides ^1H NMR (400 MHz, CDCl ₃ ) δ 8.71 (d, J = 8.4 Hz, 1H), 8.33 (s, 1H), 7.90 (s, 1H), 7.74 (t, J = 1.9 Hz, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.34 (dd, J = 8.5, 2.0 Hz, 1H), 7.07 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H) , 5.33 - 5.20 (m, 1H), 5.04 (t, J = 7.1 Hz, 2H), 4.76 (p, J = 6.1 Hz, 1H), 4.63 (t, J = 6.5 Hz, 2H), 3.77 (s, 3H), 1.42 (d, J = 6.1 Hz, 6H). 17 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-methyl-N-(1-methylp Peridine-4-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.63 (d, J = 8.3 Hz, 1H), 8.31 (s, 1H), 7.81 (s, 1H), 7.72 (t, J = 1.9 Hz, 1H), 7.09 - 6.96 (m, 3H), 6.72 - 6.66 (m, 1H), 4.66 (p, J = 6.1 Hz, 1H), 3.76 (s, 3H), 2.94 (s, 3H), 2.28 (s, 3H), 1.99 - 1.53 (m, 8H), 1.41 (d, J = 6.0 Hz, 6H). 18 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxyphenyl)(pyrrolidin-1-yl)methane on ^1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.4 Hz, 1H), 8.31 (s, 1H), 7.83 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.20 ( dd, J = 8.3, 1.8 Hz, 1H), 7.15 (d, J = 1.8 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 4.17 (q, J = 6.9 Hz, 2H), 3.76 (s, 3H), 3.65 (t, J = 6.9 Hz, 2H), 3.55 (t, J = 6.6 Hz, 2H), 2.00 - 1.81 (m, 4H) ), 1.49 (t, J = 7.0 Hz, 3H). 19 (S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-((tetrahydrofuran- 2-yl)methyl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.66 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.87 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.46 ( d, J = 1.9 Hz, 1H), 7.35 (dd, J = 8.5, 1.9 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.72 - 6.67 (m, 1H), 6.49 (s) , 1H), 4.21 (q, J = 7.0 Hz, 2H), 4.08 (qd, J = 7.1, 3.1 Hz, 1H), 3.91 (dt, J = 8.3, 6.7 Hz, 2H), 3.84 - 3.78 (m, 2H), 3.77 (s, 3H), 3.37 (ddd, J = 13.7, 7.3, 4.9 Hz, 2H), 2.04 (td, J = 12.5, 6.7 Hz, 2H), 1.93 (p, J = 6.8 Hz, 2H) ), 1.69 - 1.60 (m, 1H), 1.50 (t, J = 7.0 Hz, 3H). 20 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-(oxetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.73 (t, J = 8.5 Hz, 1H), 8.34 (s, 1H), 7.73 (t, J = 1.9 Hz, 1H), 7.64 - 7.55 (m, 2H), 7.46 (d, J = 3.9 Hz, 1H), 7.03 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 6.55 (d, J = 7.4 Hz, 1H), 5.25 (h, J = 6.9 Hz, 1H), 5.03 (t, J = 7.1 Hz, 2H), 4.62 (t, J = 6.5 Hz, 2H), 3.77 (s, 3H). 21 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-methyl-N-( Oxetane-3-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.53 (t, J = 12.8 Hz, 1H), 8.34 (s, 1H), 7.88 (s, 1H), 7.74 (t, J = 2.0 Hz, 1H), 7.05 (s, 1H), 6.90 (d, J = 6.0 Hz, 1H), 6.71 (t, J = 2.5 Hz, 1H), 5.04 (s, 1H), 4.98 - 4.77 (m, 4H), 3.92 (s, 3H), 3.77 (s, 3H), 1.25 (s, 3H). 22 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(morpholino) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.53 (d, J = 12.4 Hz, 1H), 8.33 (s, 1H), 7.86 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.05 (dd, J = 2.9, 1.8 Hz, 1H), 6.92 (d, J = 6.0 Hz, 1H), 6.71 (t, J = 2.5 Hz, 1H), 3.93 (s, 3H), 3.80 - 3.66 (br, 6H), 3.77 (s, 3H), 3.46 (s, 2H). 23 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-methyl-N-( 1-methylpiperidin-4-yl)benzamide ^1H NMR (400 MHz, DMSO) δ 8.51 (d, J = 12.6 Hz, 1H), 8.29 (s, 1H), 7.79 (s, 1H), 7.43 (t, J = 2.0 Hz, 1H), 6.96 - 6.92 (br, 2H), 6.76 (s, 1H), 3.93 (s, 3H), 3.80 (d, J = 6.1 Hz, 1H), 3.94 (s, 3H), 3.74 (s, 3H), 3.30 (s) , 3H), 3.22 (m, 1H), 2.34 - 1.91 (br, 4H), 1.37 (m, 7H) 24 3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.80 (d, J = 8.7 Hz, 1H), 8.35 (s, 1H), 7.88 (d, J = 2.1 Hz, 1H), 7.81 - 7.65 (m, 3H) , 7.04 (dd, J = 2.9, 1.7 Hz, 1H), 6.75 - 6.65 (m, 1H), 6.57 (d, J = 7.4 Hz, 1H), 5.31 - 5.19 (m, 1H), 5.04 (t, J) = 7.1 Hz, 2H), 4.62 (dd, J = 7.0, 6.0 Hz, 2H), 3.77 (s, 3H). 25 3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl )Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 8.6 Hz, 1H), 8.35 (s, 1H), 7.82 - 7.65 (m, 2H), 7.03 (dd, J = 2.9, 1.7 Hz, 1H ), 6.70 (t, J = 2.5 Hz, 1H), 5.41 - 5.15 (m, 1H), 4.83 (q, J = 8.2 Hz, 4H), 3.76 (s, 3H), 3.22 (s, 3H). 26 2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl )Benzamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.32 (s, 1H), 8.09 (s, 1H), 7.73 (s, 1H), 7.45 - 7.37 (m, 1H), 7.20 (dd, J = 16.9, 8.6 Hz, 2H), 7.03 (s, 1H), 6.70 (t, J = 2.5 Hz, 1H), 5.61 (d, J = 7.1 Hz, 1H), 4.99 - 4.76 (m, 4H), 4.71 (d, J = 6.5 Hz, 1H), 3.76 (s, 3H), 3.38 (s, 2H), 3.05 (s, 1H). 27 2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidine -4-day)Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.31 (d, J = 5.2 Hz, 1H), 8.14 - 8.03 (m, 1H), 7.73 (d, J = 2.0 Hz, 1H), 7.40 (d, J = 8.7 Hz, 1H), 7.23 - 7.12 (m, 2H), 7.06 - 7.00 (m, 1H), 6.69 (d, J = 2.7 Hz, 1H), 3.76 (d, J = 2.4 Hz, 3H), 3.03 ( s, 2H), 2.77 (s, 2H), 2.33 (s, 3H), 2.25 - 2.13 (m, 4H), 0.88 (t, J = 6.6 Hz, 3H). 28 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(pyrrolidin-1-yl)methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.28 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.55 - 7.48 (m, 2H), 7.19 (d, J = 8.9 Hz, 1H) , 7.09 - 7.00 (m, 2H), 6.68 (t, J = 2.5 Hz, 1H), 3.75 (s, 3H), 3.66 (t, J = 7.0 Hz, 2H), 3.21 (t, J = 6.7 Hz, 2H), 2.35 (s, 3H), 1.98 - 1.93 (m, 2H), 1.89 - 1.84 (m, 2H). 29 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxyphenyl)(morpholino)methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.65 (d, J = 8.2 Hz, 1H), 8.31 (s, 1H), 7.82 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.08 - 7.01 (m, 3H), 6.70 (t, J = 2.5 Hz, 1H), 4.68 (h, J = 6.2 Hz, 1H), 3.76 (s, 3H), 3.70 (s, 8H), 1.42 (d, J = 6.1 Hz, 6H). 30 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-(oxetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.69 (d, J = 8.4 Hz, 1H), 8.33 (s, 1H), 7.76 - 7.68 (m, 2H), 7.04 (dd, J = 2.9, 1.7 Hz, 2H), 6.70 (t, J = 2.5 Hz, 1H), 6.38 - 5.95 (m, 1H), 5.28 (t, J = 7.2 Hz, 1H), 4.83 (q, J = 6.4 Hz, 4H), 4.32 ( td, J = 12.9, 4.0 Hz, 2H), 3.77 (s, 3H), 3.23 (s, 3H). 31 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-methyl-N-(1-methylpiperi din-4-yl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.64 (t, J = 8.3 Hz, 1H), 8.33 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.38 (d, J = 3.7 Hz, 1H), 7.21 (t, J = 10.8 Hz, 2H), 7.03 (dd, J = 2.9, 1.8 Hz, 1H), 6.79 - 6.63 (m, 1H), 3.76 (s, 3H), 2.99 (m, 2H) ), 2.93 (m, 1H), 2.35 (d, J = 14.0 Hz, 3H), 2.31 (m, 3H), 2.03 - 1.89 (m, 4H), 1.72 (s, 2H). 32 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluorophenyl)(4-(4-methylpiperazine- 1-yl) piperidin-1-yl) methanone ^1H NMR (400 MHz, CDCl3) δ 8.63 (t, J = 8.3 Hz, 1H), 8.32 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.36 (d, J = 3.7 Hz, 1H), 7.25 - 7.16 (m, 2H), 7.02 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 3.76 (s, 3H), 3.06 - 2.76 (m , 4H), 2.71 - 2.41 (m, 5H), 2.31 (s, 3H), 1.97 - 1.42 (m, 8H). 33 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-methyl-N-(oxetane-3- 1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.67 (t, J = 8.4 Hz, 1H), 8.34 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.40 (d, J = 3.8 Hz, 1H), 7.22 (d, J = 11.4 Hz, 2H), 7.03 (dd, J = 2.9, 1.8 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 5.26 (s, 1H), 4.83 ( q, J = 7.6 Hz, 4H), 3.76 (s, 3H), 3.22 (s, 3H). 34 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluorophenyl)(4-(4-methylpiperazine- 1-yl) piperidin-1-yl) methanone ^1H NMR (400 MHz, CDCl3) δ 8.31 (s, 1H), 7.92 - 7.81 (m, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.24 (s, 1H), 7.18 (dd, J = 8.4, 2.1 Hz, 1H), 7.02 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 4.77 (d , J = 13.3 Hz, 1H), 3.75 (s, 3H), 3.16 - 2.79 (m, 2H), 2.68 - 2.43 (m, 8H), 2.29 (s, 3H), 1.96 -1.55 (m, 6H). 35 2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(1-methylpiperidin-4-yl )Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.32 (d, J = 3.2 Hz, 1H), 8.08 (d, J = 2.2 Hz, 1H), 7.77 - 7.72 (m, 2H), 7.41 (dd, J = 8.6, 2.2 Hz, 1H), 7.19 (s, 1H), 7.04 (dd, J = 2.9, 1.7 Hz, 1H), 6.71 - 6.69 (m, 1H), 6.32 (d, J = 8.1 Hz, 1H), 4.03 (s, 1H), 3.76 (s, 3H), 2.79 (s, 2H), 2.31 (s, 4H), 2.26 - 2.16 (m, 3H), 2.12 - 2.01 (m, 3H). 36 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-methyl-N-(1-methylpiperi din-4-yl)benzamide ¹ H NMR (400 MHz, CDCl3) δ 8.36 - 8.25 (m, 1H), 7.86 (dd, J = 12.6, 2.4 Hz, 1H), 7.74 - 7.70 (m, 1H), 7.39 - 7.26 (m, 2H) , 7.21 - 7.14 (m, 1H), 7.06 - 7.02 (m, 1H), 6.76 - 6.64 (m, 1H), 4.65 - 4.48 (m, 1H), 3.76 (d, J = 3.4 Hz, 3H), 3.03 - 2.89 (m, 2H), 2.83 (d, J = 1.8 Hz, 3H), 2.31 (d, J = 3.6 Hz, 2H), 2.21 (s, 2H), 2.16 (dd, J = 14.5, 8.7 Hz, 2H), 2.02 - 1.56 (m, 6H). 37 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-(oxetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 8.07 - 7.97 (m, 2H), 7.74 (t, J = 2.0 Hz, 1H), 7.34 (s, 1H), 7.25 - 7.15 (m , 2H), 7.03 (dd, J = 2.9, 1.8 Hz, 1H), 6.71 (t, J = 2.5 Hz, 1H), 5.28 (td, J = 7.5, 5.5 Hz, 1H), 5.02 (t, J = 7.1 Hz, 2H), 4.63 (t, J = 6.5 Hz, 2H), 3.77 (s, 3H). 38 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-methyl-N-(oxetane-3- 1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.89 (d, J = 12.8 Hz, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.35 (t, J = 8.1 Hz, 1H), 7.21 - 7.11 (m, 1H), 7.05 - 6.91 (m, 1H), 6.70 (t, J = 2.5 Hz, 1H), 5.52 (s, 1H), 5.08 - 4.88 (m, 2H), 4.83 (s, 3H), 3.76 (s, 3H), 3.37 (s, 2H), 3.11 (s, 1H). 39 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-((tetrahydrofuran- 2-yl)methyl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 8.3 Hz, 1H), 8.30 (s, 1H), 7.80 (s, 1H), 7.71 (t, J = 1.9 Hz, 1H), 7.08 ( dd, J = 8.3, 1.8 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 7.02 (d, J = 1.8 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 4.21 (s, 1H), 4.15 (q, J = 7.0 Hz, 2H), 4.08 - 3.83 (m, 4H), 3.75 (s, 3H), 3.60 - 3.21 (m, 2H), 3.15 (s, 3H) , 2.00 - 1.75 (m, 2H), 1.49 (t, J = 7.0 Hz, 3H). 40 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)-3-(2,2 ,2-trifluoroethoxy)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 8.5 Hz, 1H), 8.34 (s, 1H), 7.74 (dd, J = 4.0, 2.1 Hz, 2H), 7.48 (d, J = 1.9) Hz, 1H), 7.45 (dd, J = 8.5, 1.9 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 6.63 (d, J = 7.4 Hz, 1H), 5.25 (hept, J = 6.4 Hz, 1H), 5.04 (t, J = 7.1 Hz, 2H), 4.62 (dd, J = 7.0, 6.0 Hz, 2H), 4.52 (q, J = 8.0 Hz, 2H), 3.77 (s, 3H). 41 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,2-dimethyl-N-(oxetan-3-yl)benz amides ^1H NMR (400 MHz, CDCl ₃ ) δ 8.29 (s, 1H), 7.71 (t, J = 1.9 Hz, 1H), 7.53 (t, J = 3.6 Hz, 2H), 7.40 (d, J = 17.9 Hz) , 1H), 7.01 (dd, J = 2.9, 1.7 Hz, 2H), 6.67 (t, J = 2.5 Hz, 1H), 4.94 (s, 2H), 4.81 (t, J = 6.6 Hz, 1H), 4.71 (s, 2H), 3.73 (d, J = 1.5 Hz, 3H), 3.47 - 2.85 (m, 3H), 2.44 - 2.08 (m, 3H). 42 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,3-dimethyl-N-(1-methylpiperidin-4 -1) Benzamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.38 - 8.23 (m, 2H), 7.70 (q, J = 2.7 Hz, 1H), 7.31 - 7.19 (m, 2H), 7.07 - 6.96 (m, 2H), 6.67 (t, J = 2.6 Hz, 1H), 4.66 (s, 1H), 3.74 (s, 3H), 3.30 (s, 2H), 2.95 (s, 3H), 2.66 - 2.49 (m, 2H), 2.35 (s, 3H), 2.32 - 2.13 (m, 2H), 1.84 (s, 2H), 1.47 (d, J = 6.7 Hz, 3H). 43 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methylphenyl)(pyrrolidin-1-yl)methanone ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.33 - 8.25 (m, 2H), 7.68 (t, J = 1.9 Hz, 1H), 7.48 - 7.40 (m, 2H), 7.03 - 6.97 (m, 2H), 6.65 (t, J = 2.5 Hz, 1H), 3.72 (s, 3H), 3.64 (t, J = 6.9 Hz, 2H), 3.52 (t, J = 6.6 Hz, 2H), 2.34 (s, 3H), 1.95 (p, J = 6.7 Hz, 2H), 1.86 (p, J = 6.3 Hz, 2H). 44 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methylphenyl)(4-(dimethylamino)piperidine-1 -1) Methanone ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.33 - 8.26 (m, 2H), 7.69 (t, J = 1.9 Hz, 1H), 7.34 - 7.26 (m, 2H), 7.03 - 6.95 (m, 2H), 6.67 (t, J = 2.5 Hz, 1H), 4.47 - 3.84 (m, 2H), 3.73 (s, 3H), 2.91 (s, 2H), 2.54 (tt, J = 10.9, 3.5 Hz, 1H), 2.37 (s, 6H), 2.35 (s, 3H), 1.93 (s, 2H), 1.52 (s, 2H). 45 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-(1-methylpiperidin-4-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.66 (d, J = 8.4 Hz, 1H), 8.33 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.67 (s, 1H), 7.11 (d, J = 8.3 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 7.00 (s, 1H), 6.69 (t, J = 2.5 Hz, 1H), 6.39 - 5.98 (m, 1H), 4.31 (td, J = 12.9, 4.0 Hz, 2H), 3.76 (s, 3H), 2.94 (s, 4H), 2.29 (s, 2H), 1.94 (s, 2H), 1.72 (s, 2H) ), 1.60 (s, 5H). 46 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-((tetrahydrofuran-2-yl)methyl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.66 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.72 (t, J = 1.9 Hz, 1H), 7.67 (s, 1H), 7.18 (dd, J = 8.3, 1.7 Hz, 1H), 7.07 (s, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.72 - 6.66 (m, 1H), 6.36 - 6.00 (m, 1H) ), 4.31 (td, J = 12.9, 4.1 Hz, 2H), 3.92 (s, 1H), 3.76 (s, 5H), 3.33 (s, 1H), 3.16 (s, 3H), 2.10 - 1.79 (m, 4H). 47 (2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(4-methylpiperazine-1 -1-yl)piperidine-1-yl)methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.31 (s, 1H), 8.12 - 7.99 (m, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.40 (dd, J = 15.7, 8.3 Hz, 1H), 7.25 - 7.10 (m, 2H), 7.03 (t, J = 2.3 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 4.79 (d, J = 13.6 Hz, 1H), 3.76 ( s, 3H), 3.59 (s, 1H), 3.15 - 2.89 (m, 1H), 2.81 (q, J = 13.9 Hz, 1H), 2.63 (s, 2H), 2.49 (s, 2H), 2.31 (s , 3H), 1.98 (d, J = 14.1 Hz, 2H), 1.79 (d, J = 12.9 Hz, 2H). 48 3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(furan-2-ylmethyl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.76 (d, J = 8.7 Hz, 1H), 8.34 (s, 1H), 7.88 (d, J = 2.1 Hz, 1H), 7.79 - 7.65 (m, 3H) , 7.40 (dd, J = 1.9, 0.9 Hz, 1H), 7.03 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 6.42 - 6.22 (m, 3H), 4.65 (d, J = 5.4 Hz, 2H), 3.76 (s, 3H). 49 2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-methyl-N-(ox Cetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.82 (d, J = 6.8 Hz, 1H), 8.33 (d, J = 1.7 Hz, 1H), 7.77 (d, J = 3.6 Hz, 1H), 7.74 (t , J = 2.0 Hz, 1H), 6.78 (d, J = 7.4 Hz, 1H), 6.71 (t, J = 2.5 Hz, 1H), 5.08 - 4.65 (m, 5H), 3.91 (d, J = 3.8 Hz) , 3H), 3.76 (s, 3H), 3.39 (s, 2H), 3.07 (s, 1H). 50 (2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxyphenyl)(morpholino)methane on ^1H NMR (400 MHz, CDCl3) δ 8.81 (s, 1H), 8.32 (s, 1H), 7.75 (d, J = 5.0 Hz, 2H), 7.06 (dd, J = 2.9, 1.8 Hz, 1H), 6.80 (s, 1H), 6.70 (t, J = 2.5 Hz, 1H), 3.92 (s, 4H), 3.83 - 3.76 (m, 4H), 3.76 (s, 3H), 3.60 (ddd, J = 11.2, 6.0, 3.0 Hz, 1H), 3.42 (ddd, J = 13.6, 6.2, 3.1 Hz, 1H), 3.28 (ddd, J = 13.4, 6.9, 3.1 Hz, 1H). 51 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl)-3- (2,2,2-trifluoroethoxy)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 8.4 Hz, 1H), 8.34 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.69 (s, 1H), 7.07 - 7.02 (m, 2H), 6.72 - 6.67 (m, 1H), 5.29 - 5.20 (m, 1H), 4.83 (q, J = 7.0 Hz, 4H), 4.48 (q, J = 8.0 Hz, 2H), 3.76 (s, 3H), 3.22 (s, 3H), 1.58 (s, 3H). 52 3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.80 (d, J = 8.7 Hz, 1H), 8.35 (s, 1H), 7.88 (d, J = 2.1 Hz, 1H), 7.81 - 7.65 (m, 3H) , 7.04 (dd, J = 2.9, 1.7 Hz, 1H), 6.75 - 6.65 (m, 1H), 6.57 (d, J = 7.4 Hz, 1H), 5.31 - 5.19 (m, 1H), 5.04 (t, J) = 7.1 Hz, 2H), 4.62 (dd, J = 7.0, 6.0 Hz, 2H), 3.77 (s, 3H). 53 3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(furan-2-ylmethyl)-N- Methylbenzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.71 (d, J = 8.6 Hz, 1H), 8.33 (s, 1H), 7.75 - 7.66 (m, 2H), 7.42 (t, J = 1.3 Hz, 1H) , 7.03 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 6.37 (dd, J = 3.2, 1.9 Hz, 1H), 6.30 (s, 1H), 3.76 ( s, 3H), 3.04 (s, 3H), 1.30 - 1.22 (m, 2H). 54 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropylphenyl)(morpholino)methanone ^1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.4 Hz, 1H), 8.31 (s, 1H), 7.72 (d, J = 1.8 Hz, 2H), 7.34 (dd, J = 8.4, 2.1 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.04 (dd, J = 2.9, 1.8 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 3.76 (s, 3H), 3.73 - 3.56 (m, 8H), 1.85 (ddd, J = 13.7, 8.3, 5.4 Hz, 1H), 1.11 - 1.04 (m, 2H), 0.76 - 0.69 (m, 2H). 55 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-(oxetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.6 Hz, 1H), 8.33 (s, 1H), 7.82 (s, 1H), 7.73 (t, J = 1.9 Hz, 1H), 7.70 ( dd, J = 8.6, 2.3 Hz, 1H), 7.66 (d, J = 2.2 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 6.54 (d, J = 7.5 Hz, 1H), 5.26 (p, J = 6.8 Hz, 1H), 5.03 (t, J = 7.1 Hz, 2H), 4.62 (t, J = 6.5 Hz, 2H), 3.77 ( s, 3H), 1.91 - 1.81 (m, 1H), 1.14 - 1.07 (m, 2H), 0.79 - 0.72 (m, 2H). 56 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-methyl-N-(oxetane-3- 1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.73 (dd, J = 4.9, 2.9 Hz, 2H), 7.35 - 7.28 (m, 2H) ), 7.04 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 5.26 (s, 1H), 4.83 (d, J = 6.8 Hz, 4H), 3.76 (s , 3H), 3.21 (s, 3H), 1.85 (ddd, J = 13.8, 8.4, 5.3 Hz, 1H), 1.12 - 1.04 (m, 2H), 0.75 - 0.68 (m, 2H). 57 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(oxetan-3-yl)benzamide ¹ H NMR (400 MHz, CD ₃ OD_SPE) δ 8.28 (s, 1H), 7.80 (s, 1H), 7.72 - 7.63 (m, 2H), 7.41 (d, J = 8.4 Hz, 1H), 6.99 (d) , J = 2.0 Hz, 1H), 6.77 (t, J = 2.5 Hz, 1H), 5.48 (s, 1H), 5.11 (t, J = 7.2 Hz, 1H), 4.95 (d, J = 6.7 Hz, 2H) ), 4.68 (t, J = 6.5 Hz, 2H), 4.61 (s, 1H), 3.75 (s, 3H), 2.43 (s, 3H). 58 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,3-dimethyl-N-(oxetan-3-yl)benz amides ¹ H NMR (400 MHz, CH ₂ Cl ₂ ) δ 8.91 - 8.73 (m, 2H), 8.19 (dp, J = 6.5, 1.8 Hz, 1H), 7.78 (d, J = 4.9 Hz, 2H), 7.56 - 7.46 (m, 2H), 7.16 (ddt, J = 6.5, 4.3, 2.6 Hz, 1H), 5.89 - 5.67 (m, 1H), 5.33 (t, J = 5.6 Hz, 4H), 4.26 - 4.18 (m, 3H), 3.72 (s, 3H), 2.85 (dd, J = 7.1, 3.6 Hz, 3H). 59 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.61 (d, J = 8.3 Hz, 1H), 8.31 (s, 1H), 7.81 (s, 1H), 7.72 (t, J = 1.9 Hz, 1H), 7.08 - 7.00 (m, 2H), 6.99 (s, 1H), 6.69 (t, J = 2.5 Hz, 1H), 3.93 (s, 3H), 3.76 (s, 3H), 2.93 (s, 3H), 2.54 ( s, 1H), 2.34 (s, 3H), 2.04 (s, 4H), 1.97 (d, J = 9.8 Hz, 4H), 1.88 - 1.67 (m, 4H). 60 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.69 (d, J = 8.5 Hz, 1H), 8.33 (s, 1H), 7.90 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 7.37 (dd, J = 8.5, 1.9 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H) , 6.60 (d, J = 7.4 Hz, 1H), 5.26 (p, J = 6.8 Hz, 1H), 5.04 (t, J = 7.1 Hz, 2H), 4.63 (t, J = 6.5 Hz, 2H), 3.98 (s, 3H), 3.77 (s, 3H). 61 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,2,5-trimethyl-N-(oxetan-3-yl )Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.27 (s, 1H), 8.14 (s, 1H), 7.69 (t, J = 1.9 Hz, 1H), 7.00 - 6.99 (m, 2H), 6.99 - 6.85 ( m, 1H), 6.65 (t, J = 2.5 Hz, 1H), 4.96 - 4.91 (m, 2H), 4.81 (t, J = 6.6 Hz, 1H), 4.71 (s, 2H), 3.71 (s, 3H) ), 3.42 - 2.86 (m, 3H), 2.34 - 2.16 (m, 6H). 62 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(pyrrolidin-1-yl) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.26 (s, 1H), 8.11 (s, 1H), 7.68 (t, J = 2.0 Hz, 1H), 7.06 - 6.97 (m, 2H), 6.92 (s, 1H), 6.65 (t, J = 2.5 Hz, 1H), 3.71 (s, 3H), 3.65 (t, J = 7.0 Hz, 2H), 3.21 (t, J = 6.7 Hz, 2H), 2.34 (s, 3H), 2.28 (s, 3H), 1.96 (ddd, J = 13.4, 7.3, 5.8 Hz, 2H), 1.90 - 1.79 (m, 2H). 63 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-(dimethylamino)piperi din-1-yl)methanone ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.28 (s, 1H), 8.14 (s, 1H), 7.70 (t, J = 2.0 Hz, 1H), 7.04 - 6.94 (m, 2H), 6.84 (s, 1H), 6.67 (t, J = 2.5 Hz, 1H), 4.84 (d, J = 13.4 Hz, 1H), 3.74 (s, 3H), 3.69 (d, J = 13.9 Hz, 1H), 2.98 (t, J = 12.8 Hz, 1H), 2.80 (t, J = 12.6 Hz, 1H), 2.58 (s, 1H), 2.40 (s, 6H), 2.29 (s, 6H), 2.03 (d, J = 11.9 Hz, 1H), 1.85 (d, J = 12.7 Hz, 1H), 1.54 (s, 1H), 1.39 (d, J = 11.6 Hz, 1H). 64 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-(1-methylpiperidin-4- 1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 9.3 Hz, 1H), 8.32 (s, 1H), 7.78 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.64 ( d, J = 1.9 Hz, 2H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 5.89 (d, J = 8.0 Hz, 1H), 4.05 - 3.91 (m, 1H), 3.76 (s, 3H), 2.83 (d, J = 11.4 Hz, 2H), 2.31 (s, 3H), 2.22 - 2.11 (m, 2H), 2.06 (d, J = 8.8 Hz) , 2H), 1.85 (ddd, J = 13.8, 8.5, 5.4 Hz, 1H), 1.68 - 1.50 (m, 2H), 1.15 - 1.04 (m, 2H), 0.76 (td, J = 5.8, 4.2 Hz, 2H) ). 65 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidin-4-yl )-3-(2,2,2-trifluoroethoxy)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.67 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.65 (s, 1H), 7.13 ( d, J = 8.4 Hz, 1H), 7.04 (dd, J = 2.8, 1.7 Hz, 1H), 7.01 (d, J = 1.7 Hz, 1H), 6.68 (t, J = 2.5 Hz, 1H), 4.47 ( q, J = 8.0 Hz, 2H), 3.75 (s, 3H), 2.93 (s, 3H), 2.90 (s, 2H), 2.27 (s, 3H), 1.91 (s, 3H), 1.71 (s, 3H) ). 66 2-Chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-methyl-N-(1 -methylpiperidin-4-yl)benzamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.87 - 8.77 (m, 1H), 8.33 (d, J = 5.0 Hz, 1H), 7.75 (m, 2H), 7.11 - 7.04 (m, 1H), 6.77 ( s, 1H), 6.75 - 6.67 (m, 1H), 3.91 (s, 3H), 3.77 (s, 3H), 3.03 (s, 1H), 2.79 (s, 1H), 2.38 (m, 2H), 2.23 (s, 1H), 1.99 - 1.66 (m, 5H), 1.33 - 1.22 (m, 3H), 0.92 - 0.81 (m, 2H). 67 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethyl-N-(oxetan-3-yl)benz amides ^1H NMR (400 MHz, CDCl ₃ ) δ 8.27 (s, 1H), 8.20 (s, 1H), 7.70 (t, J = 1.9 Hz, 1H), 7.25 (s, 1H), 7.01 (dd, J = 2.9, 1.7 Hz, 1H), 6.87 (s, 1H), 6.68 (t, J = 2.5 Hz, 1H), 6.38 - 6.33 (m, 1H), 5.23 (q, J = 6.3 Hz, 1H), 5.02 ( t, J = 7.1 Hz, 2H), 4.59 (t, J = 6.5 Hz, 2H), 3.74 (s, 3H), 2.49 (s, 3H), 2.30 (s, 3H). 68 (S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(tetra hydrofuran-3-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.61 (d, J = 8.3 Hz, 1H), 8.31 (s, 1H), 7.81 (s, 1H), 7.72 (t, J = 1.9 Hz, 1H), 7.08 - 6.98 (m, 3H), 6.72 - 6.66 (m, 1H), 4.08 (td, J = 8.7, 4.5 Hz, 1H), 3.94 (s, 3H), 3.89 (dd, J = 9.8, 3.9 Hz, 1H) ), 3.76 (s, 3H), 3.66 (d, J = 8.0 Hz, 1H), 3.02 (s, 3H), 2.25 (s, 1H), 2.04 (q, J = 7.3 Hz, 2H). 69 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-(oxetane-3 -1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 15.4 Hz, 1H), 8.35 (s, 1H), 7.96 (s, 1H), 7.75 (s, 1H), 7.53 (d, J = 7.1 Hz, 1H), 7.35 - 7.27 (m, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.72 (s, 1H), 5.27 (p, J = 6.6 Hz, 1H), 5.02 (s) , 2H), 4.64 (t, J = 6.6 Hz, 2H), 3.96 (s, 3H), 3.78 (s, 3H). 70 2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-(oxetane-3- 1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.34 (s, 1H), 7.84 (s, 1H), 7.76 (t, J = 2.0 Hz, 1H), 7.45 (s, 1H), 7.39 (d, J = 7.3 Hz, 1H), 7.08 (dd, J = 2.9, 1.7 Hz, 1H), 6.72 (m, 1H), 5.28 (dp, J = 13.6, 6.5 Hz, 1H), 5.03 (t , J = 7.1 Hz, 2H), 4.66 (t, J = 6.5 Hz, 2H), 3.96 (s, 3H), 3.77 (s, 3H). 71 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methyl-N-(oxetan-3-yl)benzamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.49 - 8.42 (m, 1H), 8.31 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.69 (d, J = 2.2 Hz, 1H) , 7.67 (s, 1H), 7.02 (dd, J = 2.9, 1.7 Hz, 1H), 7.00 (s, 1H), 6.68 (t, J = 2.5 Hz, 1H), 6.60 (d, J = 7.5 Hz, 1H), 5.34 - 5.20 (m, 1H), 5.03 (t, J = 7.1 Hz, 2H), 4.62 (t, J = 6.5 Hz, 2H), 3.76 (s, 3H), 2.39 (s, 3H). 72 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-((1r,3r)-3-meth Toxycyclobutyl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.65 (d, J = 8.5 Hz, 1H), 8.32 (s, 1H), 7.88 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.47 (d, J = 1.9 Hz, 1H), 7.31 (dd, J = 8.5, 1.9 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H) , 6.26 (d, J = 6.6 Hz, 1H), 4.62 (h, J = 6.1 Hz, 1H), 4.18 - 4.05 (m, 1H), 3.98 (s, 3H), 3.76 (s, 3H), 3.28 ( s, 3H), 2.52 (ddd, J = 12.7, 8.1, 4.1 Hz, 2H), 2.28 (dt, J = 13.0, 6.4 Hz, 2H). 73 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(2-methoxy-2-methylpropyl )Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.66 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.88 (s, 1H), 7.73 (t, J = 1.9 Hz, 1H), 7.49 (d, J = 1.9 Hz, 1H), 7.35 (dd, J = 8.5, 2.0 Hz, 1H), 7.07 (dd, J = 2.8, 1.7 Hz, 1H), 6.73 - 6.67 (m, 1H), 6.45 ( d, J = 6.0 Hz, 1H), 3.99 (s, 3H), 3.77 (s, 3H), 3.50 (d, J = 5.5 Hz, 2H), 3.26 (s, 3H), 1.24 (s, 6H). 74 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(1-methoxy-2-methylpropane -2-day)Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.62 (d, J = 8.4 Hz, 1H), 8.31 (s, 1H), 7.86 (s, 1H), 7.72 (t, J = 1.9 Hz, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.29 (d, J = 1.9 Hz, 1H), 7.06 (dd, J = 2.9, 1.8 Hz, 1H), 6.69 (t, J = 2.6 Hz, 1H), 6.35 (s, 1H), 3.97 (s, 3H), 3.76 (s, 3H), 3.47 (s, 2H), 3.43 (s, 3H), 1.48 (s, 6H). 75 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(3-morpholinoazetidine-1 -1) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.62 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.88 (s, 1H), 7.72 (t, J = 1.9 Hz, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 8.4, 1.8 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.73 - 6.65 (m, 1H), 4.39 - 4.04 (m, 4H), 3.99 (s, 1H), 3.96 (s, 3H), 3.79 - 3.72 (m, 7H), 2.41 (s, 4H). 76 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.3 Hz, 1H), 8.31 (s, 1H), 7.81 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.05 ( dd, J = 2.9, 1.7 Hz, 1H), 7.03 (d, J = 8.5 Hz, 1H), 6.97 (s, 1H), 6.69 (t, J = 2.5 Hz, 1H), 4.15 (q, J = 7.0 Hz, 2H), 3.76 (s, 3H), 2.94 (s, 3H), 2.27 (s, 3H), 1.91 (s, 2H), 1.71 (s, 1H), 1.62 - 1.59 (m, 6H), 1.50 (t, J = 7.0 Hz, 3H). 77 3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidine -4-day)Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.70 (d, J = 8.6 Hz, 1H), 8.34 (s, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.67 (s, 1H), 7.47 (s, 1H), 7.04 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 3.76 (s, 3H), 2.93 (s, 6H), 2.29 (s, 4H), 1.28 (dd, J = 14.9, 7.7 Hz, 4H). 78 3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(tetrahydro-2H-pyran -4-day)Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.71 (d, J = 8.5 Hz, 1H), 8.34 (d, J = 2.6 Hz, 1H), 7.76 - 7.66 (m, 3H), 7.49 (s, 1H) , 7.04 (d, J = 2.7 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 3.77 (d, J = 2.8 Hz, 3H), 2.94 (s, 3H), 1.90 (s, 2H) , 1.69 (s, 2H), 0.87 (d, J = 7.0 Hz, 1H). 79 (3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(3-morpholinoazetidine-1- 1) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.74 (d, J = 8.7 Hz, 1H), 8.34 (s, 1H), 7.73 (d, J = 1.9 Hz, 3H), 7.64 - 7.57 (m, 1H) , 7.04 (t, J = 2.3 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 3.76 (d, J = 6.0 Hz, 8H), 2.40 (s, 5H), 1.30 (s, 4H) . 80 (S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-( tetrahydrofuran-3-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.56 (d, J = 15.3 Hz, 1H), 8.34 (s, 1H), 7.94 (s, 1H), 7.74 (t, J = 2.0 Hz, 1H), 7.56 (d, J = 7.1 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.97 (dd, J = 15.2, 7.0 Hz, 1H), 6.71 (t, J = 2.5 Hz, 1H) , 4.75 (s, 1H), 4.06 - 3.70 (m, 4H), 3.97 (s, 3H), 3.77 (s, 3H), 2.37 (dq, J = 13.7, 7.5 Hz, 1H), 2.07 - 1.88 (m , 1H). 81 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-((1r,3r )-3-methoxycyclobutyl)benzamide ^1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 15.2 Hz, 1H), 8.34 (s, 1H), 7.93 (s, 1H), 7.74 (t, J = 1.9 Hz, 1H), 7.55 ( d, J = 7.1 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.92 (dd, J = 15.2, 7.4 Hz, 1H), 6.71 (t, J = 2.5 Hz, 1H), 4.26 (dt, J = 9.3, 7.1 Hz, 1H), 3.96 (s, 3H), 3.77 (s, 3H), 3.71 (ddd, J = 13.9, 7.5, 6.5 Hz, 1H), 3.28 (s, 3H) , 2.91 - 2.80 (m, 2H), 1.90 (tdd, J = 9.1, 7.4, 2.8 Hz, 2H). 82 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-(1-methoxy -2-methylpropan-2-yl)benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.58 (s, 1H), 8.34 (s, 1H), 7.93 (d, J = 1.7 Hz, 1H), 7.74 (t, J = 1.9 Hz, 1H), 7.58 (d, J = 6.9 Hz, 1H), 7.13 (dt, J = 14.3, 5.3 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 3.97 (s, 3H), 3.77 (s, 3H), 3.53 (dd, J = 5.4, 1.5 Hz, 2H), 3.26 (s, 3H), 1.24 (s, 6H). 83 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(4-morpholy nopiperidin-1-yl)methanone ^1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 12.2 Hz, 1H), 8.33 (s, 1H), 7.85 (s, 1H), 7.73 (t, J = 1.9 Hz, 1H), 7.05 ( dd, J = 2.9, 1.7 Hz, 1H), 6.88 (d, J = 5.9 Hz, 1H), 6.71 (dd, J = 2.9, 2.2 Hz, 1H), 4.76 (d, J = 13.4 Hz, 1H), 3.92 (s, 3H), 3.81 (s, 1H), 3.76 (s, 3H), 3.73 (t, J = 4.6 Hz, 4H), 3.08 (s, 1H), 2.83 (t, J = 12.6 Hz, 1H) ), 2.57 (d, J = 5.5 Hz, 4H), 2.50 - 2.36 (m, 1H), 1.98 (d, J = 12.9 Hz, 1H), 1.83 (d, J = 12.7 Hz, 1H), 1.54 (d , J = 13.5 Hz, 2H). 84 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxyphenyl)(morpholino)methanone ^1H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 8.3 Hz, 1H), 8.30 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.66 (s, 1H), 7.38 ( d, J = 1.8 Hz, 1H), 7.08 (dd, J = 8.3, 1.8 Hz, 1H), 7.05 (s, 1H), 6.69 (dd, J = 2.9, 2.1 Hz, 1H), 3.84 (tt, J = 6.0, 3.6 Hz, 1H), 3.76 (s, 3H), 3.74 - 3.59 (m, 8H), 0.95 - 0.83 (m, 4H). 85 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-(oxetan-3-yl)benz amides ^1H NMR (400 MHz, CDCl3) δ 8.68 (d, J = 8.5 Hz, 1H), 8.32 (s, 1H), 7.78 (d, J = 2.0 Hz, 1H), 7.75 (s, 1H), 7.73 ( t, J = 2.0 Hz, 1H), 7.39 (dd, J = 8.5, 2.0 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (dd, J = 2.9, 2.2 Hz, 1H) ), 6.59 (d, J = 7.4 Hz, 1H), 5.35 - 5.19 (m, 1H), 5.04 (t, J = 7.1 Hz, 2H), 4.64 (dd, J = 7.0, 6.1 Hz, 2H), 3.89 (tt, J = 6.0, 3.4 Hz, 1H), 3.77 (s, 3H), 0.94 - 0.81 (m, 4H). 86 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-methyl-N-(oxetane-3 -1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.4 Hz, 1H), 8.31 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.68 (s, 1H), 7.36 ( s, 1H), 7.04 (dd, J = 2.9, 1.7 Hz, 2H), 6.72 - 6.65 (m, 1H), 5.34 - 5.23 (m, 1H), 4.85 (d, J = 6.9 Hz, 4H), 3.88 - 3.78 (m, 1H), 3.76 (s, 3H), 3.24 (s, 3H), 0.89 - 0.81 (m, 4H). 87 4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-(1-methylpiperidin-4 -1) Benzamide ^1H NMR (400 MHz, CDCl3) δ 8.65 (d, J = 8.5 Hz, 1H), 8.31 (s, 1H), 7.79 (d, J = 1.9 Hz, 1H), 7.72 (d, J = 1.8 Hz, 2H), 7.32 (dd, J = 8.5, 2.0 Hz, 1H), 7.05 (dd, J = 2.9, 1.8 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 5.96 (d, J = 8.0 Hz, 1H), 4.08 - 3.95 (m, 1H), 3.90 (tt, J = 6.1, 3.5 Hz, 1H), 3.76 (s, 3H), 2.85 (d, J = 11.5 Hz, 2H), 2.32 (s) , 3H), 2.26 - 2.14 (m, 2H), 2.07 (d, J = 12.7 Hz, 2H), 1.60 (d, J = 13.0 Hz, 2H), 0.88 (dq, J = 5.8, 2.6 Hz, 4H) . 88 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxyphenyl)(4-(dimethylamino)piperi din-1-yl)methanone ^1H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 8.3 Hz, 1H), 8.30 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.65 (s, 1H), 7.36 ( d, J = 1.8 Hz, 1H), 7.09 (dd, J = 8.3, 1.8 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.69 (dd, J = 2.9, 2.2 Hz, 1H) ), 3.83 (tt, J = 6.2, 2.8 Hz, 1H), 3.76 (s, 3H), 2.92 (s, 4H), 2.39 (d, J = 11.1 Hz, 1H), 2.32 (s, 6H), 1.90 (s, 2H), 1.50 (s, 2H), 0.90 - 0.80 (m, 4H). 89 (S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(tetrahydrofuran-3 -1) Benzamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.66 (d, J = 8.5 Hz, 1H), 8.32 (s, 1H), 7.88 (s, 1H), 7.73 (t, J = 1.9 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 7.31 (dd, J = 8.5, 1.9 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H) , 6.27 (d, J = 7.4 Hz, 1H), 4.80 - 4.71 (m, 1H), 4.02 (q, J = 7.8 Hz, 1H), 3.98 (s, 3H), 3.93 (dd, J = 9.5, 5.3 Hz, 1H), 3.90 - 3.72 (m, 2H), 3.77 (s, 3H), 2.45 - 2.31 (m, 1H), 2.07 - 1.89 (m, 1H). 90 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-(dimethylamino)piperidine -1-day) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.61 (d, J = 8.3 Hz, 1H), 8.31 (s, 1H), 7.81 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.09 - 7.00 (m, 3H), 6.69 (t, J = 2.5 Hz, 1H), 3.94 (s, 3H), 3.76 (s, 3H), 2.92 (s, 2H), 2.56 - 2.45 (m, 2H), 2.36 (s, 6H), 2.17 (s, 1H), 1.92 (s, 2H), 1.51 (s, 2H). 91 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxyphenyl)(4-(dimethylamino)piperi din-1-yl)methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 4.67 (p, J = 6.0 Hz, 1H), 3.76 (s, 3H), 2.92 (s, 2H), 2.50 (s, 2H), 2.35 (s, 6H) , 2.18 (s, 1H), 1.91 (s, 2H), 1.59 - 1.43 (m, 2H), 1.41 (d, J = 6.1 Hz, 6H). 92 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1 -1) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.60 (d, J = 8.3 Hz, 1H), 8.32 (d, J = 9.4 Hz, 1H), 7.81 (s, 1H), 7.72 (t, J = 2.0 Hz) , 1H), 7.03 (dd, J = 10.8, 1.8 Hz, 2H), 6.69 (t, J = 2.5 Hz, 1H), 3.94 (s, 3H), 3.75 (d, J = 6.7 Hz, 7H), 2.59 (d, J = 4.8 Hz, 4H), 2.44 (d, J = 11.2 Hz, 1H), 1.99 - 1.44 (m, 8H). 93 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-(pyrrolidin-1-yl) piperidin-1-yl)methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.29 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.55 (s, 1H), 7.49 (s, 1H), 7.12 (s, 1H) , 7.07 (s, 1H), 7.02 (dd, J = 2.9, 1.8 Hz, 1H), 6.68 (t, J = 2.5 Hz, 1H), 4.72 (d, J = 13.4 Hz, 1H), 3.75 (s, 3H), 3.60 (d, J = 13.2 Hz, 1H), 2.99 (t, J = 12.5 Hz, 1H), 2.95 - 2.84 (m, 1H), 2.60 (s, 4H), 2.33 (s, 4H), 2.04 (s, 1H), 1.81 (s, 6H), 1.60 (s, 1H). 94 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-morpholinopiperidin-1-yl ) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.29 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.52 (s, 2H), 7.24 (s, 1H), 7.11 (d, J = 17.5 Hz, 1H), 7.02 (dd, J = 2.9, 1.7 Hz, 1H), 6.68 (t, J = 2.5 Hz, 1H), 4.80 (d, J = 13.3 Hz, 1H), 3.74 (s, 3H) , 3.73 (t, J = 4.6 Hz, 4H), 3.47 (s, 5H), 2.97 (t, J = 12.7 Hz, 1H), 2.81 (t, J = 12.8 Hz, 1H), 2.55 (q, J = 3.6 Hz, 4H), 2.33 (d, J = 15.9 Hz, 4H). 95 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(3-morpholinoazetidin-1-yl ) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.29 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.54 (d, J = 2.2 Hz, 1H), 7.52 (d, J = 2.1 Hz) , 1H), 7.33 (s, 1H), 7.28 - 7.21 (m, 1H), 7.02 (dd, J = 2.9, 1.7 Hz, 1H), 6.68 (t, J = 2.5 Hz, 1H), 4.20 (dd, J = 10.1, 7.3 Hz, 1H), 4.03 (dd, J = 10.2, 5.4 Hz, 1H), 3.96 (t, J = 8.1 Hz, 1H), 3.86 (dd, J = 9.2, 5.3 Hz, 1H), 3.74 (s, 3H), 3.73 (d, J = 4.4 Hz, 4H), 3.17 (tt, J = 7.3, 5.4 Hz, 1H), 2.44 (s, 3H), 2.40 - 2.29 (m, 4H). 96 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2,2-trifluoroethoxy)phenyl )(4-(dimethylamino)piperidin-1-yl)methanone ^1H NMR (400 MHz, CDCl3) δ 8.68 (d, J = 8.4 Hz, 1H), 8.33 (s, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.66 (s, 1H), 7.16 ( dd, J = 8.4, 1.8 Hz, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 2H), 6.77 - 6.63 (m, 1H), 4.48 (q, J = 8.0 Hz, 2H), 3.76 (s) , 3H), 2.94 (s, 2H), 2.48 - 2.36 (m, 1H), 2.32 (s, 6H), 1.93 - 1.67 (m, 6H), 1.48 (s, 2H). 97 (2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(dimethylamino)piperidine- 1-day) Methanone 1H NMR (500 MHz, DMSO) δ 10.29 (s, 1H), 10.01 (s, 1H), 8.48 (d, J = 1.0 Hz, 1H), 8.19 (d, J = 8.1 Hz, 1H), 7.87 (d) , J = 2.5 Hz, 1H), 7.73 (d, J = 10.0 Hz, 1H), 7.44 - 7.20 (m, 1H), 6.99 - 6.83 (m, 2H), 4.65 (d, J = 13.2 Hz, 1H) , 3.75 (s, 3H), 3.46 (d, J = 13.9 Hz, 2H), 3.17 - 2.99 (m, 1H), 2.78 (t, J = 12.7 Hz, 2H), 2.71 (s, 6H), 2.00 ( d, J = 9.4 Hz, 2H), 1.68 - 1.42 (m, 3H). 98 2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-N-(oxetane-3 -1) Acetamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.59 (d, J = 8.2 Hz, 1H), 8.30 (s, 1H), 7.72 (t, J = 1.9 Hz, 2H), 7.05 (dd, J = 2.8, 1.7 Hz, 1H), 6.91 (dd, J = 8.2, 1.9 Hz, 1H), 6.77 (d, J = 1.9 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H), 5.94 (d, J = 7.4 Hz, 1H), 5.02 (h, J = 6.8 Hz, 1H), 4.87 (t, J = 7.1 Hz, 2H), 4.39 (dd, J = 7.0, 6.1 Hz, 2H), 3.92 (s, 3H) , 3.76 (s, 3H), 3.57 (s, 2H). 99 2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-1-morpholinoethane- 1-on ^1H NMR (400 MHz, CDCl ₃ ) δ 8.51 (d, J = 8.2 Hz, 1H), 8.28 (s, 1H), 7.70 (t, J = 2.0 Hz, 1H), 7.68 (s, 1H), 7.04 (dd, J = 2.8, 1.7 Hz, 1H), 6.85 (dd, J = 8.3, 1.9 Hz, 1H), 6.81 (d, J = 1.9 Hz, 1H), 6.68 (t, J = 2.5 Hz, 1H) , 3.90 (s, 3H), 3.75 (s, 3H), 3.72 (s, 2H), 3.65 (s, 4H), 3.48 (d, J = 6.3 Hz, 4H). 100 2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-N-(1-methylp Peridin-4-yl)acetamide ^1H NMR (400 MHz, CDCl ₃ ) δ 8.54 (d, J = 8.2 Hz, 1H), 8.29 (s, 1H), 7.71 (t, J = 2.0 Hz, 1H), 7.69 (s, 1H), 7.05 (dd, J = 2.9, 1.7 Hz, 1H), 6.88 (dd, J = 8.2, 1.9 Hz, 1H), 6.78 (d, J = 1.9 Hz, 1H), 6.69 (t, J = 2.5 Hz, 1H) , 5.33 (d, J = 8.1 Hz, 1H), 3.90 (s, 3H), 3.76 (s, 3H), 3.53 (s, 2H), 2.67 (s, 2H), 2.23 (s, 3H), 2.11 - 2.01 (m, 2H), 1.90 - 1.82 (m, 2H), 1.48 - 1.30 (m, 2H). 101 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-(pyrrolidin-1 -1)piperidine-1-yl)methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.27 (s, 1H), 8.13 (d, J = 4.7 Hz, 1H), 7.70 (t, J = 2.0 Hz, 1H), 7.05 - 6.97 (m, 2H) , 6.88 (s, 1H), 6.67 (t, J = 2.5 Hz, 1H), 4.78 (d, J = 13.4 Hz, 1H), 3.74 (s, 3H), 3.71 - 3.60 (m, 1H), 2.99 ( t, J = 12.7 Hz, 1H), 2.84 (s, 5H), 2.58 (s, 1H), 2.35 (d, J = 5.1 Hz, 3H), 2.28 (s, 3H), 2.07 (s, 1H), 1.91 (s, 6H), 1.73 (s, 1H), 1.60 (s, 1H). 102 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-morpholinopiperidine- 1-day) Methanone ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.27 (s, 1H), 8.13 (s, 1H), 7.70 (t, J = 1.9 Hz, 1H), 7.03 - 6.93 (m, 2H), 6.86 (s, 1H), 6.67 (t, J = 2.5 Hz, 1H), 4.80 (d, J = 13.4 Hz, 1H), 3.74 (s, 3H), 3.73 - 3.64 (m, 6H), 2.97 (t, J = 12.8 Hz, 1H), 2.86 - 2.75 (m, 1H), 2.59 - 2.50 (m, 4H), 2.35 (s, 2H), 2.29 (d, J = 4.5 Hz, 6H), 1.97 (d, J = 13.2 Hz) , 2H). 103 (4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(3-morpholinoazetidine- 1-day) Methanone ^1H NMR (400 MHz, CDCl ₃ ) δ 8.28 (s, 1H), 8.19 (s, 1H), 7.70 (t, J = 2.0 Hz, 1H), 7.10 (s, 1H), 7.01 (dd, J = 2.9, 1.7 Hz, 1H), 6.88 (s, 1H), 6.67 (t, J = 2.5 Hz, 1H), 4.20 (dd, J = 10.1, 7.3 Hz, 1H), 4.03 (dd, J = 10.2, 5.4 Hz, 1H), 3.95 (t, J = 8.1 Hz, 1H), 3.86 (dd, J = 9.1, 5.3 Hz, 1H), 3.74 (s, 3H), 3.74 (d, J = 9.1 Hz, 4H), 3.17 (tt, J = 7.1, 5.3 Hz, 1H), 2.44 (s, 3H), 2.35 (td, J = 14.2, 8.2 Hz, 4H), 2.29 (s, 3H). 104 3-methoxy-N-methyl-4-((4-(1-methyl-1H-pyrrol-3-yl)-5-(trifluoromethyl)pyrididin-2-yl)amino)-N-( Oxetane-3-yl)benzamide ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.67 - 8.61 (m, 2H), 8.02 (s, 1H), 7.42 (s, 1H), 7.04 (s, 1H), 6.86 (s, 1H), 6.67 ( t, J = 2.5 Hz, 1H), 5.28 (s, 1H), 4.84 (d, J = 6.8 Hz, 4H), 3.95 (s, 3H), 3.75 (s, 3H), 3.23 (s, 3H). 105 2-chloro-5-methoxy-N-methyl-4-((4-(1-methyl-1H-pyrrol-3-yl)-5-(trifluoromethyl)pyrididin-2-yl)amino) -N-(oxetan-3-yl)benzamide ^1H NMR (500 MHz, CDCl3) δ 8.83 (d, J = 9.0 Hz, 1H), 8.64 (d, J = 2.2 Hz, 1H), 7.94 (s, 1H), 7.47 (s, 1H), 6.88 - 6.85 (m, 1H), 6.82 - 6.77 (m, 1H), 6.69 (q, J = 2.2 Hz, 1H), 4.98 - 4.81 (m, 4H), 4.73 (d, J = 6.7 Hz, 0H), 3.92 (s, 3H), 3.75 (s, 3H), 3.39 (s, 1H). 106 (S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(tetrahydrofuran-3- 1) Benzamide ^1H NMR (500 MHz, CDCl ₃ ) δ 8.28 (d, J = 2.3 Hz, 1H), 7.71 (s, 1H), 7.58 (t, J = 9.4 Hz, 1H), 7.49 (s, 1H), 7.37 (d, J = 8.3 Hz, 1H), 7.12 (s, 1H), 7.02 (s, 1H), 6.68 (d, J = 2.9 Hz, 1H), 5.97 (d, J = 7.4 Hz, 1H), 3.98 (q, J = 7.9 Hz, 1H), 3.92 (t, J = 7.3 Hz, 1H), 3.85 (q, J = 7.9 Hz, 2H), 3.79 (d, J = 9.5 Hz, 1H), 3.75 (d , J = 2.2 Hz, 3H), 2.50 (s, 3H), 2.36 (dq, J = 14.8, 7.3 Hz, 2H). 107 (4-((5-chloro-4-(1-isopropyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone ^1H NMR (500 MHz, CDCl3) δ 8.50 (d, J = 8.3 Hz, 1H), 8.43 (s, 1H), 7.82 (s, 1H), 7.08 (s, 1H), 7.05 (s, 1H), 6.98 (d, J = 8.2 Hz, 1H), 6.91 (d, J = 2.8 Hz, 1H), 6.31 (t, J = 3.3 Hz, 1H), 5.18 (p, J = 6.7 Hz, 1H), 3.95 ( s, 3H), 3.70 (s, 8H), 1.54 (s, 3H), 1.43 (d, J = 6.6 Hz, 3H). 108 (R)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(tetrahydrofuran-3 -1) Benzamide ^1H NMR (500 MHz, CDCl3) δ 8.66 (d, J = 8.4 Hz, 1H), 8.32 (s, 1H), 7.88 (s, 1H), 7.73 (t, J = 1.9 Hz, 1H), 7.45 ( d, J = 2.0 Hz, 1H), 7.31 (dd, J = 8.4, 2.0 Hz, 1H), 7.06 (dd, J = 2.9, 1.7 Hz, 1H), 6.70 (t, J = 2.5 Hz, 1H), 6.26 (d, J = 7.5 Hz, 1H), 4.75 (dt, J = 8.1, 2.4 Hz, 1H), 4.06 - 3.97 (m, 1H), 3.98 (s, 3H), 3.93 (dd, J = 9.5, 5.3 Hz, 1H), 3.89 - 3.79 (m, 2H), 3.77 (s, 3H), 2.43 - 2.32 (m, 1H), 2.00 - 1.90 (m, 1H).

Example structure Example structure One 55 2 56 3 57 4 58 5 59 6 60 7 61 8 62 9 63 10 64 11 65 12 66 13 67 14 68 15 69 16 70 17 71 18 72 19 73 20 74 21 75 22 76 23 77 24 78 25 79 26 80 27 81 28 82 29 83 30 84 31 85 32 86 33 87 34 88 35 89 36 90 37 91 38 92 39 93 40 94 41 95 42 96 43 97 44 98 45 99 46 100 47 101 48 102 49 103 50 104 51 105 52 106 53 107 54 108

<Example 109> Preparation of 5-chloro-N-(2-methoxy-4-morpholinophenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrimidin-2-amine

The compound of Example 109 was prepared according to the above reaction scheme.

2,5-dichloro-4-(1-methyl-1H-pyrrol-3-yl)pyrimidine (100 mg, 0.44 mmol, 1 eq), 2-methoxy-4-morpholinoaniline (100 mg, 0.48 mmol, 1.1 eq), , was completely dissolved in 4-dioxane (5 mL, 0.1M) and stirred at 100°C for 16 hours. After completion of the reaction, the mixture was cooled to room temperature, extracted with EtOAc, and the organic layer was washed with brine. Water in the organic layer was removed using MgSO4, then filtered and concentrated under reduced pressure. The mixture was purified using MPLC (EtOAc:Hex) to obtain 5-chloro-N-(4-(2,4-dimethyloxazol-5-yl)-2-methoxyphenyl)-4-(1-methyl-1H -Pyrrol-3-yl)pyrimidin-2-amine (light yellow solid, 120 mg, 69%) was obtained.

The following compounds were prepared using the reaction prepared in Example 109. The names and NMR spectrum data of the prepared compounds are summarized in Table 3 below, and the structures of the compounds are summarized in Table 4.

Example name NMR assignment 109 5-Chloro-N-(2-methoxy-4-morpholinophenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine ^1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.8 Hz, 1H), 8.25 (d, J = 1.3 Hz, 1H), 7.69 (t, J = 1.9 Hz, 1H), 7.45 (s, 1H), 7.04 (dt, J = 3.1, 1.5 Hz, 1H), 6.67 (t, J = 2.5 Hz, 1H), 6.58 (dd, J = 8.8, 2.6 Hz, 1H), 6.54 (d, J = 2.5) Hz, 1H), 3.89 (s, 3H), 3.89 - 3.87 (m, 4H), 3.74 (d, J = 1.5 Hz, 3H), 3.15 - 3.11 (m, 4H). 110 5-chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyrididine- 2-amine ^1H NMR (400 MHz, CDCl3) δ 8.25 (s, 1H), 7.90 (s, 1H), 7.68 (d, J = 2.2 Hz, 1H), 7.56 (s, 1H), 7.01 - 6.94 (m, 2H) ), 6.67 (d, J = 2.6 Hz, 1H), 4.33 (s, 1H), 4.12 (d, J = 11.2 Hz, 2H), 3.74 (s, 3H), 3.55 (td, J = 11.3, 3.4 Hz) , 2H), 2.12 (q, J = 4.5 Hz, 4H). 111 5-chloro-N-(4-(2,4-dimethyloxazol-5-yl)-2-methoxyphenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2- amine ^1H NMR (500 MHz, CDCl3) δ 8.64 (d, J = 8.5 Hz, 1H), 8.30 (s, 1H), 7.77 (s, 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.22 ( dd, J = 8.4, 1.9 Hz, 1H), 7.12 - 7.04 (m, 2H), 6.69 (t, J = 2.5 Hz, 1H), 3.98 (s, 3H), 3.76 (s, 3H), 2.49 (s) , 3H), 2.39 (s, 3H). 112 5-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylisoindolin-1-one ^1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 8.01 (s, 1H), 7.78 (d, J = 8.3 Hz, 1H), 7.72 (t, J = 2.0 Hz, 1H), 7.51 ( dd, J = 8.5, 1.9 Hz, 1H), 7.25 (s, 1H), 7.01 (dd, J = 2.9, 1.7 Hz, 1H), 6.78 - 6.67 (m, 1H), 4.38 (s, 2H), 3.76 (s, 3H), 3.19 (s, 3H). 113 5-chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(6-morpholinopyridin-3-yl)pyrididin-2-amine ^1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 2.7 Hz, 1H), 8.23 (s, 1H), 7.92 (dd, J = 9.0, 2.7 Hz, 1H), 7.67 (d, J = 2.0) Hz, 1H), 6.98 (dd, J = 3.0, 1.7 Hz, 1H), 6.87 (s, 1H), 6.69 (d, J = 9.0 Hz, 1H), 6.65 (t, J = 2.6 Hz, 1H), 3.87 - 3.82 (m, 4H), 3.73 (s, 3H), 3.50 - 3.43 (m, 4H). 114 2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methyl-1H-pyrazol-1-yl)- 2-Methylpropanenitrile ^1H NMR (500 MHz, CDCl ₃ ) δ 8.31 (s, 1H), 8.26 (s, 1H), 7.70 (d, J = 2.0 Hz, 1H), 7.00 (dd, J = 2.9, 1.6 Hz, 1H) , 6.68 (d, J = 2.6 Hz, 1H), 6.55 (s, 1H), 3.74 (s, 3H), 2.29 (s, 3H), 2.00 (s, 6H). 115 6-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3,4-dihydronaphthalen-1(2H)-one ^1H NMR (400 MHz, CDCl3) δ 8.62 - 8.50 (m, 1H), 8.31 - 8.24 (m, 1H), 7.90 (s, 1H), 7.89 (d, J = 1.8 Hz, 1H), 7.68 (s) , 1H), 7.62 - 7.55 (m, 1H), 7.51 (td, J = 7.8, 2.0 Hz, 2H), 3.01 - 2.86 (m, 2H), 2.30 (s, 3H), 1.99 - 1.89 (m, 2H) ), 1.48 (qd, J = 11.5, 3.9 Hz, 2H). 116 5-chloro-N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine ^1H NMR (500 MHz, CDCl3) δ 8.23 (s, 1H), 7.80 (s, 1H), 7.46 (s, 1H), 6.96 (s, 1H), 6.66 (s, 1H), 3.85 (s, 3H) ), 3.73 (s, 3H), 2.25 (s, 3H). 117 N-(5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)-5-methylthiazol-2-amine ^1H NMR (500 MHz, CDCl3) δ 10.07 (s, 1H), 8.44 (s, 1H), 7.82 (s, 1H), 7.23 (s, 1H), 7.17 (s, 1H), 6.72 (s, 1H) ), 3.78 (s, 3H), 2.44 (s, 3H). 118 5-Chloro-N-(2-fluoro-4-morpholinophenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine ^1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 1.2 Hz, 1H), 8.21 (t, J = 9.1 Hz, 1H), 7.69 (t, J = 1.9 Hz, 1H), 7.00 (dt, J = 2.8, 1.4 Hz, 1H), 6.97 (s, 1H), 6.76 - 6.64 (m, 3H), 3.87 (dd, J = 5.7, 4.0 Hz, 4H), 3.74 (d, J = 1.2 Hz, 3H) ), 3.12 (dd, J = 5.7, 3.9 Hz, 4H). 119 5-chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(4-morpholino-2-(trifluoromethyl)phenyl)pyrididin-2-amine ^1H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H), 8.07 (d, J = 8.7 Hz, 1H), 7.67 (t, J = 1.9 Hz, 1H), 7.12 (d, J = 8.2 Hz, 2H), 7.01 (s, 1H), 6.97 (dd, J = 2.9, 1.7 Hz, 1H), 6.65 (t, J = 2.5 Hz, 1H), 3.90 - 3.86 (m, 4H), 3.73 (s, 3H) ), 3.21 - 3.15 (m, 4H).

Example structure Example structure 109 115 110 116 111 117 112 118 113 119 114

<Experimental Example 1> Confirmation of LRRK2 inhibitory activity

The following experiment was performed to evaluate the LRRK2 kinase inhibitory activity of the compounds of Examples 1 to 119 according to the present invention.

First, recombinant LRRK2 kinase (Signal Chem, Richmond, BC, Canada), 0.2 ug/ul LRRKtide (Signal Chem, Richmond, BC, Canada), and 25 umol/L ATP (Invitrogen, Carlsbad, CA) were added to a 384-well plate. Kinase reaction buffer solution (40 mmol/L TrisHCl, 10 mmol/L MgCl2, and 0.1 ug/uL BSA (bovine serum albumin)) was added and mixed. Next, for each of the compounds of Examples 1 to 119, final concentrations of 50 uM, 5 uM, 500 nM, 50 nM, 5 nM, 500 pM, 50 pM, 5 pM, and 0.5 pM were added, and then The reaction was carried out in a °C incubator for 2 hours. After the reaction was completed, an equal amount of Kinase-Glo (Promega, Madison, WI) solution was added and reacted for 40 minutes, and a detection solution was added and reacted at room temperature for an additional 30 minutes. The amount of luciferase was measured using a microplate ELISA reader (Bio-Tek), and the IC50 value of the kinase was calculated. (The IC50 value of the measured kinase was classified into grade A if it was less than 10nM, grade B if it was 10 to 100nM, and grade C if it was more than 100nM, and is summarized in Table 5 below. In addition, the grade A compound G2019S enzyme activity % value is was obtained, and the experiment was conducted at a concentration of 100nM.)

Example Wild type G2019S
(enzyme activity%) Example Wild type G2019S
(enzyme activity%) Example Wild type G2019S
(enzyme activity%) One B - 46 C - 91 B - 2 A 3.88 47 A 2.85 92 A 2.92 3 A 2.71 48 C - 93 A 0.87 4 B - 49 B - 94 A 2.59 5 B - 50 A 6.09 95 B 3.46 6 A 5.50 51 B - 96 A 2.5 7 A - 52 C - 97 A - 8 B - 53 C - 98 B - 9 B - 54 C - 99 C - 10 B 5.96 55 C - 100 B 6.72 11 B - 56 C - 101 A 3.24 12 B - 57 B - 102 B 5.62 13 B - 58 C - 103 B - 14 B - 59 B - 104 B - 15 B - 60 B - 105 C - 16 B - 61 B - 106 C - 17 B - 62 B - 107 C - 18 B 5.26 63 A 7.62 108 B - 19 B 14.97 64 B - 109 B - 20 C - 65 B - 110 B - 21 B 11 66 B - 111 C - 22 B - 67 B - 112 C - 23 B - 68 B - 113 C - 24 C - 69 B - 114 B - 25 C - 70 B 10.42 115 C - 26 C - 71 B - 116 B - 27 C - 72 B 3.86 117 C - 28 B - 73 B - 118 C - 29 C - 74 B 16.99 119 C - 30 B - 75 B 9.54 31 C - 76 B 10.64 32 B - 77 B - 33 C - 78 C - 34 B 8.09 79 C - 35 B - 80 B - 36 C - 81 B 9.87 37 C - 82 B - 38 C - 83 A 3.21 39 C - 84 B - 40 C - 85 B - 41 B - 86 B - 42 B - 87 B - 43 C - 88 A 2.94 44 B - 89 A 8.83 45 B - 90 A -

Very excellent inhibitory activity can be confirmed against the wild type and G2019S mutant type of the protein. Therefore, the compounds according to the present invention are expected to be effective in preventing or treating related diseases caused by hyperactivation of wild type LRRK2 protein or G2019S mutant LRRK2 protein.

<Experimental Example 2> Evaluation of blood-brain barrier (BBB) permeability

To evaluate the blood-brain barrier permeability, the following experiment was performed.

The test substance was prepared at a dosage of 5 mg/kg, and blood was collected from the heart immediately after sacrificing the animal at 1 and 3 hours after oral administration and centrifuged to prepare plasma samples. To remove blood remaining in the body, the heart was perfused with 20 ml of saline solution containing 10 U/ml heparin, and the brain was removed. PBS buffer 3 times the weight of the brain tissue was added and homogenized. LC-MS/MS (Agilent, Santa Clara, CA, USA) was used for quantitative analysis of the prepared plasma and brain tissue. For separation of substances in LC, a mobile phase consisting of 80% acetonitrile and 20% water with 0.1% formic acid was used. The total run time per substance is 3 minutes and the flow rate is 0.3 ml/min. The results are shown in Table 6 below.

Example Kp value One 1.04 3 0.69 50 1.23 68 0.60 70 2.79 72 1.46 80 2.03 81 0.72 84 0.54 85 0.47 89 0.67

Claims (16)

A compound represented by the following formula (1), a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof:
[Formula 1]

Y is halogen or C ₁ -C ₆ alkyl substituted with halogen;
Z is C ₁ -C ₆ alkyl;
X is substituted phenyl or substituted heteroaryl of 5-6 atoms,
Each of the above substituted phenyl and substituted heteroaryl of 5-6 atoms,
Unsubstituted or substituted with cyano C ₁ -C ₆ alkyl, C ₃ -C ₆ cycloalkyl, unsubstituted or substituted with halogen C ₁ -C ₆ alkoxy, C ₃ -C ₆ cycloalkyl oxy, halogen, unsubstituted or One or more of 5-6 atom heteroaryl substituted with C ₁ -C ₆ alkyl, 3-7 atom heterocycloalkyl, -(CH ₂ )p-CO-B and -(CH ₂ )p-CO-NAB is substituted with a substituent,
p is an integer from 0 to 5,
A is hydrogen or C ₁ -C ₆ alkyl,
B is unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO- B or -(CH ₂ )p-CONAB is C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,
or,
A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3-7 atoms,
Here, the substituted C ₁ -C ₆ alkyl is substituted with C ₁ -C ₆ alkoxy, heteroaryl of 5-6 atoms, or heterocycloalkyl of 3-7 atoms,
The substituted C ₃ -C ₆ cycloalkyl is substituted with C ₁ -C ₆ alkoxy, and
The substituted heterocycloalkyl of 3-7 atoms is independently C ₁ -C ₆ alkyl, amino unsubstituted or substituted with C ₁ -C ₆ alkyl, or 3- unsubstituted or substituted with C ₁ -C ₆ alkyl. It is substituted with a 7-atom heterocycloalkyl,
Alternatively, the compound may be 5-chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(4-morpholino-2-(trifluoromethyl)phenyl)pyrididin-2-amine (Example 119).
According to paragraph 1,
The X above is ego,
Ar is phenyl or heteroaryl of 5-6 atoms;
R ^1a and R ^1b are each independently hydrogen, halogen, unsubstituted or cyano-substituted C ₁ -C ₆ alkyl, unsubstituted or halogen-substituted C ₁ -C ₆ alkoxy, cycloalkyloxy, or C ₃ -C ₆ cycloalkyl;
R ² is unsubstituted or substituted with C ₁ -C ₆ alkyl, heteroaryl of 5-6 atoms, heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B, or -(CH ₂ )p -CONAB,
p is an integer from 0 to 5,
A is hydrogen or C ₁ -C ₆ alkyl,
B is unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, or -(CH2)p-CO- B or -(CH2)p-CONAB is C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,
or,
A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3 to 7 atoms;
Here, the substituted C ₁ -C ₆ alkyl is substituted with C ₁ -C ₆ alkoxy, heteroaryl of 5-6 atoms, or heterocycloalkyl of 3-7 atoms,
The substituted C ₃ -C ₆ cycloalkyl is substituted with C ₁ -C ₆ alkoxy, and
The substituted heterocycloalkyl of 3-7 atoms is C ₁ -C ₆ alkyl, amino unsubstituted or substituted with C ₁ -C ₆ alkyl, or 3-7 atoms unsubstituted or substituted with C ₁ -C ₆ alkyl. Characterized by being substituted with heterocycloalkyl of,
A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
According to paragraph 1,
X is , , , , or ego;
R ^1a , R ^1b , R ³ , R ⁴ , R ⁵ , and R ⁶ are each independently hydrogen, halogen, unsubstituted or cyano-substituted C ₁ -C ₆ alkyl, unsubstituted or halogen-substituted C ₁ -C ₆ alkoxy, C ₃ -C ₆ cycloalkyl oxy, 3-7 membered heterocycloalkyl, or C ₃ -C ₆ cycloalkyl;
R ² is unsubstituted or substituted with C ₁ -C ₆ alkyl, heteroaryl of 5-6 atoms, heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B, or -(CH ₂ )p -CONAB,
p is an integer from 0 to 5,
A is hydrogen or C ₁ -C ₆ alkyl,
B is unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, or -(CH2)p-CO- B or -(CH2)p-CONAB is C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,
or,
A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3 to 7 atoms;
Here, the substituted C ₁ -C ₆ alkyl is substituted with C ₁ -C ₆ alkoxy, heteroaryl of 5-6 atoms, or heterocycloalkyl of 3-7 atoms,
The substituted C ₃ -C ₆ cycloalkyl is substituted with C ₁ -C ₆ alkoxy, and
Substituted heterocycloalkyl of 3-7 atoms is C ₁ -C ₆ alkyl, amino unsubstituted or substituted with C ₁ -C ₆ alkyl, or amino of 3-7 atoms unsubstituted or substituted with C ₁ -C ₆ alkyl. Characterized by being substituted with heterocycloalkyl,
A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
According to paragraph 1,
X is , , , , or ego,
R ^1a and R ^1b are each independently hydrogen, halogen, unsubstituted or cyano-substituted C ₁ -C ₅ alkyl, unsubstituted or halogen-substituted C ₁ -C ₅ alkoxy, C ₃ -C ₆ cycloalkyl oxy, or C ₃ -C ₆ cycloalkyl,
R ² is unsubstituted or substituted with C ₁ -C ₅ alkyl, heteroaryl of 5-6 atoms, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B, or - (CH ₂ )p-CONAB,
Here, p is an integer from 0 to 4,
A is hydrogen or C ₁ -C ₅ alkyl,
B is unsubstituted or substituted C ₁ -C ₅ alkyl, unsubstituted or substituted C ₃ -C ₅ cycloalkyl, heterocycloalkyl of 3-6 atoms, or -(CH2)p-CO-B or -(CH2 )p-CONAB is C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,
or,
A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3-6 atoms,
R ³ is unsubstituted or cyano-substituted C ₁ -C ₅ alkyl, or heterocycloalkyl of 3-7 atoms,
R ⁴ , R ⁵ , and R ⁶ are each independently hydrogen or C ₁ -C ₅ alkyl,
Here, the substituted C ₁ -C ₅ alkyl is substituted with C ₁ -C ₅ alkoxy, 5-6 atom heteroaryl, or 3-7 atom heterocycloalkyl,
The substituted C ₃ -C ₆ cycloalkyl is substituted with C ₁ -C ₅ alkoxy, and
The substituted 3-7-membered heterocycloalkyl is C ₁ -C ₅ alkyl, amino substituted with C ₁ -C ₆ alkyl, or 3-7-membered heterocyclo unsubstituted or substituted with C ₁ -C ₆ alkyl. Characterized by substitution with alkyl,
A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
According to paragraph 1,
Z is C ₁ -C ₄ alkyl;
X is , , , , or ego,
R ^1a and R ^1b are each independently hydrogen, halogen, unsubstituted or cyano-substituted C ₁ -C ₄ alkyl, unsubstituted or halogen-substituted C ₁ -C ₄ alkoxy, C ₃ -C ₅ cycloalkyl oxy, or C ₃ -C ₅ cycloalkyl,
R ² is unsubstituted or substituted with C ₁ -C ₄ alkyl, heteroaryl of 5-6 atoms, heterocycloalkyl of 3-7 atoms, -(CH ₂ )p-CO-B, or -(CH ₂ )p -CONAB,
Here, p is an integer from 0 to 3,
A is hydrogen or C ₁ -C ₃ alkyl,
B is unsubstituted or substituted C ₁ -C ₄ alkyl, unsubstituted or substituted C ₃ -C ₅ cycloalkyl, unsubstituted or substituted heterocycloalkyl of 3-7 atoms, or -(CH2)p-CO- B or -(CH ₂ )p-CONAB is C ₁ -C ₆ alkylene bonded to an atom adjacent to the bonded atom,
or,
A and B together with the nitrogen atom to which each is bonded form an unsubstituted or substituted heterocycloalkyl of 3-7 atoms,
R ³ is unsubstituted or substituted C ₁ -C ₄ alkyl, or heterocycloalkyl of 3-7 atoms,
R ⁴ , R ⁵ , and R ⁶ are each independently hydrogen or C ₁ -C ₄ alkyl,
Here, the substituted C ₁ -C ₄ alkyl is substituted with C ₁ -C ₄ alkoxy, heteroaryl of 5-6 atoms, or heterocycloalkyl of 3-7 atoms,
The substituted C ₃ -C ₅ cycloalkyl is substituted with C ₁ -C ₆ alkoxy, and
The substituted 3-7-membered heterocycloalkyl is C ₁ -C ₄ alkyl, amino substituted with C ₁ -C ₆ alkyl, or 3-7-membered heterocyclo unsubstituted or substituted with C ₁ -C ₆ alkyl. Characterized by substitution with alkyl,
A compound, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
According to paragraph 1,
The compound represented by Formula 1 is characterized in that it is any one compound selected from the group of compounds below,
Compound, stereoisomer thereof, solvate thereof, hydrate thereof or pharmaceutically acceptable salt thereof:
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (Example 1 );
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4- 1) Benzamide (Example 2);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-(dimethylamino)piperidine -1-yl)methanone (Example 3);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-(1-methylpiperidin-4- 1) Benzamide (Example 4);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluorophenyl)(4-(dimethylamino)piperidine -1-yl)methanone (Example 5);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(1-methylpiperidin-4-yl )Benzamide (Example 6);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-(dimethylamino)piperidine-1 -1) Methanone (Example 7);
(3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(dimethylamino)piperidine- 1-day)methanone (Example 8);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(oxetane-3- 1) Benzamide (Example 9);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-(1-methylpiperidin-4- 1) Benzamide (Example 10);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 11);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-(oxetan-3-yl)benzamide (Example 12);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(oxetane-3- 1) Benzamide (Example 13);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxyphenyl)(morpholino)methanone (Example 14);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-(oxetan-3-yl)benz Amide (Example 15);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-(oxetan-3-yl)benz Amide (Example 16);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxy-N-methyl-N-(1-methylp peridin-4-yl)benzamide (Example 17);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxyphenyl)(pyrrolidin-1-yl)methane On (Example 18);
(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-((tetrahydrofuran- 2-yl)methyl)benzamide (Example 19);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-(oxetan-3-yl)benzamide (Example 20);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-methyl-N-( oxetan-3-yl)benzamide (Example 21);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(morpholino) Methanone (Example 22);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-methyl-N-( 1-methylpiperidin-4-yl)benzamide (Example 23);
3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)benzamide ( Example 24);
3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl )Benzamide (Example 25);
2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl )Benzamide (Example 26);
2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidine -4-yl)benzamide (Example 27);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(pyrrolidin-1-yl)methanone ( Example 28);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxyphenyl)(morpholino)methanone (practice Example 29);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-(oxetan-3-yl)benzamide (Example 30);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 31);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluorophenyl)(4-(4-methylpiperazine- 1-yl)piperidin-1-yl)methanone (Example 32);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-fluoro-N-methyl-N-(oxetane-3- 1) Benzamide (Example 33);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluorophenyl)(4-(4-methylpiperazine- 1-yl)piperidin-1-yl)methanone (Example 34);
2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(1-methylpiperidin-4-yl )Benzamide (Example 35);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 36);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-(oxetan-3-yl)benzamide (Example 37);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-N-methyl-N-(oxetane-3- 1) Benzamide (Example 38);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-((tetrahydrofuran- 2-yl)methyl)benzamide (Example 39);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)-3-(2,2 ,2-trifluoroethoxy)benzamide (Example 40);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,2-dimethyl-N-(oxetan-3-yl)benz Amide (Example 41);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,3-dimethyl-N-(1-methylpiperidin-4 -1)benzamide (Example 42);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methylphenyl)(pyrrolidin-1-yl)methanone ( Example 43);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methylphenyl)(4-(dimethylamino)piperidine-1 -1) Methanone (Example 44);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-(1-methylpiperidin-4-yl)benzamide (Example 45);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2-difluoroethoxy)-N-methyl -N-((tetrahydrofuran-2-yl)methyl)benzamide (Example 46);
(2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(4-methylpiperazine-1 -yl)piperidin-1-yl)methanone (Example 47);
3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(furan-2-ylmethyl)benzamide ( Example 48);
2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-methyl-N-(ox cetan-3-yl)benzamide (Example 49);
(2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxyphenyl)(morpholino)methane On (Example 50);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(oxetan-3-yl)-3- (2,2,2-trifluoroethoxy)benzamide (Example 51);
3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(oxetan-3-yl)benzamide ( Example 52);
3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-(furan-2-ylmethyl)-N- methylbenzamide (Example 53);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropylphenyl)(morpholino)methanone (Example 54);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-(oxetan-3-yl)benzamide (Example 55);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-methyl-N-(oxetane-3- 1) Benzamide (Example 56);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(oxetan-3-yl)benzamide ( Example 57);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,3-dimethyl-N-(oxetan-3-yl)benz Amide (Example 58);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 59);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide (Example 60);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N,2,5-trimethyl-N-(oxetan-3-yl )Benzamide (Example 61);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(pyrrolidin-1-yl) Methanone (Example 62);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-(dimethylamino)piperi din-1-yl)methanone (Example 63);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropyl-N-(1-methylpiperidin-4- 1) Benzamide (Example 64);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidin-4-yl )-3-(2,2,2-trifluoroethoxy)benzamide (Example 65);
2-Chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-methyl-N-(1 -methylpiperidin-4-yl)benzamide (Example 66);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethyl-N-(oxetan-3-yl)benz Amide (Example 67);
(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-methyl-N-(tetra hydrofuran-3-yl)benzamide (Example 68);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-(oxetane-3 -1)benzamide (Example 69);
2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-5-methoxy-N-(oxetane-3- 1) Benzamide (Example 70);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methyl-N-(oxetan-3-yl)benzamide ( Example 71);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-((1r,3r)-3-meth Toxycyclobutyl)benzamide (Example 72);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(2-methoxy-2-methylpropyl )Benzamide (Example 73);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(1-methoxy-2-methylpropane -2-yl)benzamide (Example 74);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(3-morpholinoazetidine-1 -1) Methanone (Example 75);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-ethoxy-N-methyl-N-(1-methylpiperi din-4-yl)benzamide (Example 76);
3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(1-methylpiperidine -4-yl)benzamide (Example 77);
3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-N-methyl-N-(tetrahydro-2H-pyran -4-yl)benzamide (Example 78);
(3-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(3-morpholinoazetidine-1- 1) Methanone (Example 79);
(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-( tetrahydrofuran-3-yl)benzamide (Example 80);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-((1r,3r )-3-methoxycyclobutyl)benzamide (Example 81);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxy-N-(1-methoxy -2-methylpropan-2-yl)benzamide (Example 82);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(4-morpholy nopiperidin-1-yl)methanone (Example 83);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxyphenyl)(morpholino)methanone (practice Example 84);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-(oxetan-3-yl)benz Amide (Example 85);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-methyl-N-(oxetane-3 -1)benzamide (Example 86);
4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxy-N-(1-methylpiperidin-4 -1)benzamide (Example 87);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-cyclopropoxyphenyl)(4-(dimethylamino)piperi din-1-yl)methanone (Example 88);
(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(tetrahydrofuran-3 -1)benzamide (Example 89);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-(dimethylamino)piperidine -1-yl)methanone (Example 90);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-isopropoxyphenyl)(4-(dimethylamino)piperi din-1-yl)methanone (Example 91);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1 -1) methanone (Example 92);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-(pyrrolidin-1-yl) piperidin-1-yl)methanone (Example 93);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(4-morpholinopiperidin-1-yl ) Methanone (Example 94);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylphenyl)(3-morpholinoazetidin-1-yl ) Methanone (Example 95);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-(2,2,2-trifluoroethoxy)phenyl )(4-(dimethylamino)piperidin-1-yl)methanone (Example 96);
(2-chloro-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)phenyl)(4-(dimethylamino)piperidine- 1-yl)methanone (Example 97);
2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-N-(oxetane-3 -1)acetamide (Example 98);
2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-1-morpholinoethane- 1-one (Example 99);
2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)-N-(1-methylp peridin-4-yl)acetamide (Example 100);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-(pyrrolidin-1 -yl)piperidin-1-yl)methanone (Example 101);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(4-morpholinopiperidine- 1-day)methanone (Example 102);
(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2,5-dimethylphenyl)(3-morpholinoazetidine- 1-yl)methanone (Example 103);
3-methoxy-N-methyl-4-((4-(1-methyl-1H-pyrrol-3-yl)-5-(trifluoromethyl)pyrididin-2-yl)amino)-N-( oxetan-3-yl)benzamide (Example 104);
2-chloro-5-methoxy-N-methyl-4-((4-(1-methyl-1H-pyrrol-3-yl)-5-(trifluoromethyl)pyrididin-2-yl)amino) -N-(oxetan-3-yl)benzamide (Example 105);
(S)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methyl-N-(tetrahydrofuran-3- 1) Benzamide (Example 106);
(4-((5-chloro-4-(1-isopropyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (practice Example 107);
(R)-4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methoxy-N-(tetrahydrofuran-3 -1)benzamide (Example 108);
5-chloro-N-(2-methoxy-4-morpholinophenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine (Example 109);
5-chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyrididine- 2-amine (Example 110);
5-chloro-N-(4-(2,4-dimethyloxazol-5-yl)-2-methoxyphenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2- Amines (Example 111);
5-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-2-methylisoindolin-1-one (Example 112);
5-chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(6-morpholinopyridin-3-yl)pyrididin-2-amine (Example 113);
2-(4-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3-methyl-1H-pyrazol-1-yl)- 2-methylpropanenitrile (Example 114);
6-((5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)amino)-3,4-dihydronaphthalen-1(2H)-one (Example 115);
5-chloro-N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine (Example 116);
N-(5-chloro-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-yl)-5-methylthiazol-2-amine (Example 117)
5-chloro-N-(2-fluoro-4-morpholinophenyl)-4-(1-methyl-1H-pyrrol-3-yl)pyrididin-2-amine (Example 118);
5-Chloro-4-(1-methyl-1H-pyrrol-3-yl)-N-(4-morpholino-2-(trifluoromethyl)phenyl)pyrididin-2-amine (Example 119) .
According to paragraph 1,
The compound is a compound characterized in that it inhibits LRRK2 (leucine-rich repeat kinase 2) activity, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof.
As shown in Scheme 1 below,
A method for producing a compound represented by Formula 1 of claim 1, comprising the step of reacting a compound represented by Formula 2 with a compound represented by Formula 3 to prepare a compound represented by Formula 1:
[Scheme 1]

In Scheme 1, W is halogen,
X, Y, and Z are as defined in Formula 1 of Clause 1.
A pharmaceutical composition for the prevention or treatment of neurodegenerative diseases containing the compound represented by Formula 1 of claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
According to clause 9,
The neurodegenerative diseases include Parkinson's disease, Alzheimer's disease, Huntington's disease, Pick's disease, amyotrophic lateral sclerosis, prion disease, and exercise. Motor neuron disease, Spinocerebellar ataxia, Spinal muscular atrophy, Creutzfeldt-Jakob disease, and Alcohol related dementia. A pharmaceutical composition for preventing or treating neurodegenerative diseases, characterized in that it contains one or more types.
A health functional food for preventing or improving neurodegenerative diseases containing the compound represented by Formula 1 of claim 1, its stereoisomer, its solvate, its hydrate, or its pharmaceutically acceptable salt as an active ingredient.
A pharmaceutical composition for the prevention or treatment of cancer containing the compound represented by Formula 1 of claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
According to clause 12,
The above cancers include kidney cancer, thyroid cancer, breast cancer, liver cancer, brain cancer, lung cancer, ovarian cancer, colon cancer, melanoma, stomach cancer, gastrointestinal cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, skin or eye melanoma, uterine cancer, rectal cancer, and colon cancer. A pharmaceutical composition for the prevention or treatment of cancer, characterized in that it is selected from the group consisting of esophageal cancer, laryngeal cancer, small intestine cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, and multiple myeloma.
A health functional food for preventing or improving cancer containing the compound represented by Formula 1 of claim 1, its stereoisomer, its solvate, its hydrate, or its pharmaceutically acceptable salt as an active ingredient.
A pharmaceutical composition for the prevention or treatment of inflammatory diseases containing the compound represented by Formula 1 of claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient,
A pharmaceutical composition for preventing or treating inflammatory diseases, wherein the inflammatory disease is inflammatory bowel disease or ulcerative colitis.
A health functional food for preventing or improving inflammatory diseases containing the compound represented by Formula 1 of claim 1, its stereoisomer, its solvate, its hydrate, or its pharmaceutically acceptable salt as an active ingredient,
A health functional food for preventing or improving inflammatory diseases, wherein the inflammatory disease is inflammatory bowel disease or ulcerative colitis.