KR20140130084A - Azaindole derivatives, Trk inhibitoring composition and pharmaceutical compositions for prevention and treatment of diseases linked to Trk comprising the same - Google Patents

Abstract

The present invention relates to azaindole derivatives represented by chemical formula 1, a tropomyosin-related kinase (Trk) inhibiting composition comprising the same, and a pharmaceutical composition for preventing and treating diseases associated with Trk. The azaindole derivative and a pharmaceutically acceptable salt thereof, according to the present invention, are Trk inhibitors which can be used as anti-cancer agents or pain relief agents for treating Trk associated diseases, particularly, cancer or pain disorder.

Description

Azaindole derivatives, a Trk inhibitor composition containing the same, and a pharmaceutical composition for preventing and treating Trk-related diseases,

The present invention relates to a pharmaceutical composition for use in the prophylaxis and treatment of an azaindole derivative, a tropomyosin-related kinase (hereinafter abbreviated as " Trk ") inhibitor composition and a disease associated with Trk .

Receptor tyrosine kinase (RTK) is a receptor that penetrates the cell membrane and phosphorylates tyrosine residues that are specific for various protein substrates. Trk (Tropomysin-related kinase) is also involved in RTKs and acts as a receptor for neurotrophins and plays an important role in the development and maintenance of the central nervous system and peripheral nervous system. There are three subtypes of Trk, TrkA, TrkB and TrkC, each of which is also known as NTRK1, NTRK2, and NTRK3.

Trk is activated by binding of neurotrophin, an extracellular growth factor, to the domain, thereby inducing autophosphorylation in the various tyrosine sites of Trk inside the cell membrane. Subsequent activation of the signal transduction pathway by this mechanism influences neuron growth and survival.

In addition, there is experimental evidence that Trk is associated with malignant transformation, chemotaxis, metastasis, and survival signaling in human cancer.

For example, malignant prostatic epithelial cells secrete a variety of neurotrophins for one Trk, and neurotrophin-Trk interactions through parenchymal and autocrine actions in pancreatic cancer, The effect was reported. TrkB is also reported to be overexpressed in metastatic pancreatic cancer cells, and structurally activated TrkA fusion proteins have been reported in papillary thyroid cancer and colorectal cancer. In addition, studies have shown that breast cancer, acute myelogenous leukemia, neuroblastoma, and lung cancer are associated with Trk.

Since Trk is a receptor associated with the nervous system, it is also considered as an important mediator of pain. In particular, the deficiency of TrkA has been shown to provide sufficient protection against painful stimuli in patients of various ethnicities. Similarly, the efficacy of low molecular weight TrkA inhibitors in the treatment of pain has been demonstrated through animal models. Therefore, Trk has been proven as a new target for the development of clinical treatments for cancer and pain.

As a result, numerous efforts have been made to develop a competitive inhibitor of Trk ATP, which can be developed as a new anticancer drug and pain relieving agent. In addition, 4-aminopyrazolepyrimidine, indenopyrrolocarbazole, isothiazololeoxyindole, Indole and 2-aminothiazole group were discovered as Trk inhibitors.

In addition, numerous Trk inhibitors have been reported and many compounds have entered clinical trials, but no FDA-approved substances are present, and few substances selectively inhibit Trk. This means that the drug is more likely to cause side effects. Therefore, the development of selective inhibitors for Trk is desired.

On the other hand, an azindole derivative which is a compound of the present invention to be described later has not hitherto been known, and further, its usefulness as an anticancer agent having Trk inhibitory action of this derivative has not been known.

Accordingly, an object to be solved by the present invention is to provide an azindole derivative compound or a pharmaceutically acceptable salt thereof which acts as a Trk inhibitor and is applicable to various anti-cancer drugs or pain relief preparations.

In addition, a problem to be solved by the present invention is to provide a pharmaceutical composition for preventing or treating Trk-related diseases and a Trk inhibitor pharmaceutical composition containing an azaindole derivative compound as an active ingredient together with a pharmaceutically acceptable carrier or diluent.

In order to solve the above problems,

There is provided an azindole derivative represented by the following formula 1 or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

In the above formula (1)

Each of R ₁ and R ₂ is independently selected from a substituted or unsubstituted aryl group having 5 to 8 carbon atoms and a substituted or unsubstituted heteroaryl group having 5 to 13 carbon atoms.

According to one embodiment of the present invention, in the above R ₁ , the substituents of the substituted aryl group and the substituted heteroaryl group are each independently an alkyl group having 1 to 6 carbon atoms, a substituted or unsubstituted alkoxy group having 1 to 6 carbon atoms An amine group and a cyano group, and the substituent of the substituted alkoxy group may be an alkyl group having 1 to 6 carbon atoms.

According to another embodiment of the present invention, in the R ₂ , the substituent of the substituted aryl group or the substituted heteroaryl group may be a substituted or unsubstituted arylsulfonamide group, a morpholinosulfonyl group, a dimethylaminosulfonyl group, An alkyl group having 1 to 3 carbon atoms, an amine group, a cyano group, a substituted or unsubstituted alkoxy group having 1 to 6 carbon atoms, a halogen group, an amide group and an acetylamide group, The substituent of the arylsulfonamide group is halogen or an alkyl group having 1 to 6 carbon atoms, and the substituent of the substituted alkoxy group may be substituted with an alkyl group having 1 to 6 carbon atoms. Wherein the substituted alkyl group may be either a dimethylamine group or a morpholine group. The amido group includes both the case where the carbon side is bonded to the aryl group in the amide group and the case where the nitrogen side is bonded to the aryl group.

According to another embodiment of the present invention, R < ₁ > may be any one selected from the group represented by the following structural formula (1).

[Structural formula 1]

According to another embodiment of the present invention, R < ₂ > may be any one selected from the group represented by the following structural formula (2).

[Structural formula 2]

According to another embodiment of the present invention, the pharmaceutically acceptable salts include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, formic acid, acetic acid, trifluoroacetic acid, , At least one member selected from the group consisting of oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, ethanesulfonic acid, aspartic acid and glutamic acid.

In order to solve the above problems,

There is provided a pharmaceutical composition for Trk inhibition containing an azaindole derivative compound according to the above formula (1) as an active ingredient together with a pharmaceutically acceptable carrier or diluent.

In addition, the pharmaceutical composition of the present invention can be used in combination with a pharmaceutically acceptable carrier or diluent for a proliferative disease, a painful disease, an immunological disease, a cardiovascular disease, a neurological disease, an inflammatory disease, an endocrine disorder A pharmaceutical composition for treating a disease or a virus infectious disease.

According to one embodiment of the present invention, the proliferative disease is cancer, and the cancer is leukemia, brain tumor, renal cancer, gastric cancer, skin cancer, bladder cancer, breast cancer, uterine cancer, lung cancer, colon cancer, prostate cancer, ovarian cancer, liver cancer, Cancer, peritoneal cancer, peritoneal metastatic cancer, and pancreatic cancer.

According to another embodiment of the present invention, the pain disorder comprises acute or chronic pain and neuropathic pain, wherein the acute or chronic pain is pain associated with cancer, surgery, arthritis, trauma, musculoskeletal injury or intestinal disease , Wherein said neuropathic pain is any one selected from postherpetic neuralgia, diabetic neuropathy, drug-induced neuropathy, HIV-mediated neuropathy, reflex sympathetic dystrophy, fibromyalgia, facial pain and seizure neuropathy have.

According to another embodiment of the present invention, the immunological disease may be any one selected from the group consisting of rheumatoid arthritis, autoimmune malignant anemia, and type I diabetes.

According to another embodiment of the present invention, the cardiovascular disease may be any one selected from the group consisting of myocardial infarction, hypertension, and angina.

According to another embodiment of the present invention, the neurological disease may be neurogenic gastritis or irritable bowel syndrome.

According to another embodiment of the present invention, the inflammatory disease may be degenerative arthritis or sinusitis.

According to another embodiment of the present invention, the endocrine disorder may be diabetes.

According to another embodiment of the present invention, the viral infection disease may be any one selected from the group consisting of AIDS, avian influenza and swine flu.

In the definition of substituents and terms of the azaindole derivative compound of the formula (1) according to the present invention,

The term " alkoxy ", unless otherwise defined, refers to an alkyloxy having 1 to 6 carbon atoms, preferably an alkoxy group having preferably 1 to 3 carbon atoms.

The term " alkyl " means an aliphatic hydrocarbon radical. Alkyl may be a "saturated alkyl" that does not include an alkenyl or alkynyl moiety, or an "unsaturated alkyl" that includes at least one alkenyl or alkynyl moiety. &Quot; Alkenyl " means a group containing at least one carbon-carbon double bond, and 'alkynyl " means a group including at least one carbon-carbon triple bond. Alkyl, when used alone or in combination with alkoxy, may be branched or straight chain, respectively.

The alkyl group may be lower alkyl having 1 to 6 carbon atoms, and is preferably an alkyl group having 1 to 3 carbon atoms unless otherwise defined.

Typical alkyl groups include but are not limited to methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, hexyl, ethenyl, propenyl, butenyl and the like. For example, C ₁ -C ₄ -alkyl has from 1 to 4 carbon atoms in the alkyl chain and is selected from the group consisting of methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and t- Group.

The term " aryl " includes at least one ring having a covalent pi electron system and includes, for example, a monocyclic or fused ring polycyclic (i.e., rings that divide adjacent pairs of carbon atoms) groups . That is, in the present specification, aryl may include phenyl, naphthyl, etc., and a biaryl, unless otherwise defined.

The term " heteroaryl ", unless otherwise defined, includes heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O and S, preferably heteroaryl containing one or more N atoms. Examples of monocyclic heteroaryl include thiazole, oxazole, thiophene, furan, pyrrole, imidazole, isoxazole, isothiazole, pyrazole, triazole, triazine, thiadiazole, tetrazole, oxadiazole Sol, pyridine, pyridazine, pyrimidine, pyrazine, and similar groups. Examples of bicyclic heteroaryls include indole, indoline, benzothiophene, benzofuran, benzimidazole, benzoxazole, benzisoxazole, benzthiazole, benzthiadiazole, benztriazole, quinoline, isoquinoline, purine , Furopyridine, and similar groups.

Specific examples of the term "halogen group" include fluorine (F), chlorine (Cl), bromine (Br) and the like, preferably fluorine (F) and chlorine (Cl).

The term " cyano group ", which can be represented by -CN, has a triple bond at an atomic group where one atom of carbon and nitrogen is bonded, and another atom or group is bonded to a carbon atom to form a hydrogen atom, have.

The term " sulfonyl " refers to an SO ₂ -R group where R can be hydrogen, aryl, heteroaryl, alkyl, alkylamino, heteroarylamino, morpholino, An alkylsulfonylamino group, a heteroarylsulfonamino group, and the like.

Specific examples of the morpholino group include a morpholino group, a 2-methylmorpholino group, a 3-methylmorpholino group, a 4-methylmorpholino group, a 2-ethylmorpholino group, -Butylmorpholino group, 2,4-dimethylmorpholino group, 2,6-dimethylmorpholino group and 4-phenylmorpholino group, and similar groups, but are not limited thereto.

The term " treatment " refers to stopping or delaying the progress of a disease when used in an object having an onset symptom.

The 'pharmaceutical composition' may include, if necessary, a pharmaceutically acceptable carrier, diluent, excipient, or a combination thereof together with the compound of the present invention.

The term "carrier" refers to a substance that facilitates the addition of a compound into a cell or tissue.

The term 'diluent' is defined as a substance that not only stabilizes the biologically active form of the compound of interest but also dilutes in water to dissolve the compound.

The term " pharmaceutically acceptable " means a property that does not impair the biological activity and physical properties of the compound.

Other terms and abbreviations used herein can be interpreted as commonly understood by a person skilled in the art to which the present invention belongs, unless otherwise defined.

The azaindole derivative compounds and pharmaceutically acceptable salts thereof according to the present invention are inhibitors against Trk and can be used as anticancer agents or pain relieving agents capable of treating diseases associated with Trk, particularly cancer or painful diseases.

Hereinafter, the present invention will be described in more detail.

Trk is a neurotrophin-activated receptor tyrosine kinase, which acts as a mediator of pain due to the growth and maintenance of the central nervous system and peripheral nervous system. In addition, Trk induces chemotaxis, metastasis metastasis, malignant transformation, and survival signaling. Specifically, neurotrophin, a ligand of Trk, is hypersecreted or Trk is overexpressed or activated in breast cancer, acute myelogenous leukemia, neuroblastoma, prostate cancer, pancreatic cancer, papillary thyroid cancer, colorectal cancer, lung cancer and the like. Thus, Trk has been demonstrated as a target for the development of clinical treatments for cancer and pain, and it is necessary to develop selective inhibitors of Trk.

Accordingly, the present invention provides an azaindole derivative compound represented by the following formula (1), or a pharmaceutically acceptable salt thereof, which can act as an effective drug for Trk kinase associated with painful diseases and cancer diseases.

[Chemical Formula 1]

In the above formula (1)

Each of R ₁ and R ₂ is independently selected from a substituted or unsubstituted aryl group having 5 to 8 carbon atoms and a substituted or unsubstituted heteroaryl group having 5 to 13 carbon atoms.

The scope of the present invention is not limited thereto, but the formula 1 may be specifically selected from the group consisting of the following formulas (2) to (37).

[Chemical Formula 2] < EMI ID =

[Chemical Formula 4]

[Chemical Formula 6] < EMI ID =

[Chemical Formula 8]

[Chemical Formula 10]

*

[Chemical Formula 12]

[Chemical Formula 14]

[Chemical Formula 16]

[Chemical Formula 18]

[Chemical Formula 20]

[Chemical Formula 22]

[Chemical Formula 24]

[Chemical Formula 26]

[Chemical Formula 28]

[Chemical Formula 30]

[Chemical Formula 32]

[Chemical Formula 35]

[Chemical Formula 36]

The azaindole compound represented by the above formula (1) according to the present invention or a pharmaceutically acceptable salt thereof may be an inhibitor which inhibits one or more of TrkA and TrkB, and in particular, Trk kinase inhibitory activity is excellent.

In order to confirm competitive inhibition of ATP of Trk kinases of an azaindole compound represented by the above formula (1) or a pharmaceutically acceptable salt thereof according to the present invention in combination with 1 μM ATP, The compounds according to the present invention were cultured together to determine IC ₅₀ , which is the enzyme activity of the substance, which is more effective as the concentration of the substance administered at 50% inhibition of enzyme activity is smaller. This will be described later.

The pharmaceutically acceptable salts in the present invention include salts with inorganic acids such as sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid and the like, which are non-toxic acid addition salts containing pharmacologically acceptable anions, And organic acids such as formic acid, citric acid, acetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, lactic acid, malonic acid, malic acid, salicylic acid, succinic acid, oxalic acid, propionic acid, And acid addition salts formed with sulfonic acids and the like, such as p-toluenesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid and the like, and may be represented by the formula (1) The azelaindole compounds may include the acid addition salts described above and the salts of sodium, calcium and ammonium.

In addition, it is also possible to use a pharmaceutically acceptable base addition salt such as an alkali metal or alkaline earth metal salt formed by lithium, sodium, potassium, calcium, magnesium or the like, an amino acid salt of lysine, arginine, guanidine or the like and dicyclohexylamine , Organic salts such as N-methyl-D-glucamine, tris (hydroxymethyl) methylamine, diethanolamine, choline, triethylamine and the like.

The azaindole compound of the formula (1) according to the present invention can be converted into a salt thereof by a conventional method. The preparation of the salt is easily carried out by a person skilled in the art based on the structure of the formula (1) .

Unless otherwise stated, the azaindole compounds of formula (I) include pharmaceutically acceptable salts thereof, all of which should be construed as being included within the scope of the present invention. For convenience of explanation, they are simply represented by the compound of formula (1) in the present specification.

The azaindole derivative compound according to the present invention can be used as an inhibitor of Trk, particularly as a TrkA isotype inhibitor, and therefore can be used for proliferative diseases, Cardiovascular diseases, neurological diseases, inflammatory diseases, endocrine diseases and viral infectious diseases.

Specifically, the proliferative disease is cancer, and the cancer is leukemia, brain tumor, renal cancer, gastric cancer, skin cancer, bladder cancer, breast cancer, uterine cancer, lung cancer, colon cancer, prostate cancer, ovarian cancer, liver cancer, colon cancer, peritoneal cancer, Cancer, and pancreatic cancer, wherein the painful condition includes acute or chronic pain and neuropathic pain, wherein the acute or chronic pain is pain associated with cancer, surgery, arthritis, trauma, musculoskeletal injury or visceral disease, The pathological pain may be postherpetic neuralgia, diabetic neuropathy, drug-induced neuropathy, HIV-mediated neuropathy, reflex sympathetic neurotrophic factor, fibromyalgia, facial pain and seizure neuropathy, and the immune disease is rheumatoid arthritis , Autoimmune malignant anemia, type I diabetes, and the cardiovascular disease may be myocardial infarction, hypertension and angina, and the neurological disease may be neurogenic gastritis, hypersensitivity Chapter syndrome may be, the inflammatory disease may be arthritis, sinusitis, endocrine disorders can be diabetes, and viral infections can be Aids, avian flu, swine flu.

Hereinafter, a method for preparing an azaindole derivative according to the present invention will be described in order to understand the present invention.

First, azaindole (starting material) is prepared by introducing iodine through N-iodosuccinimide at the C3 position using commercially available 5-bromo-7-azaindole, Lt; / RTI > group.

From the azaindole [starting material], the R1 aryl group is introduced through the Suzuki coupling with palladium as a catalyst at the position C3. Subsequently, the benzenesulfonyl group is removed to obtain an azindole [intermediate 1]. When an aniline derivative substituted at the C5 position is to be coupled, [intermediate 2] is obtained through a boronation reaction of C5 bromine in particular. The substituted aniline derivative is synthesized in the form of a substituted aniline bromide capable of Suzuki coupling according to [Reaction Formula I] and [Reaction Scheme II] shown below.

[Reaction Scheme I]

[Starting material] [Intermediate 1] [Formula 1]

[Reaction Scheme II]

[Starting material] [Intermediate 2] [Formula 1]

Since through the [intermediate] or Suzuki coupling (Suzuki Coupling) to the palladium in the C5 position as the catalyst using the [Intermediate 2; R ₂ An aryl group is introduced to prepare an azaindole derivative compound represented by the formula (1) according to the present invention.

Specifically, the synthesis of the C3-position derivative can be carried out by using a coupling reaction of Suzuki type using various arylboronic acids, a palladium catalyst (II) and a potassium carbonate base, and reacting 1,4-dioxane and water (ratio 3: 1) in a solvent, and heated to 80 ℃ and stirred R ₁ in the C3 position Aryl or heteroaryl group.

[Intermediate 1] or [Intermediate 2] is then obtained along the path A and B in order to introduce R ₂ at the C 5 position. Specifically, the synthesis of [intermediate 1] via route A can be obtained by adding an aqueous 4 N potassium hydroxide solution to the azaindole starting material after the introduction of R1, and heating the mixture at 80 ° C for 30 minutes to remove the benzene sulfonyl group. [Synthesis of intermediate 2] via route B can be carried out by using miyauraboronation reaction using bispinacolatodiborone, palladium catalyst, and potassium acetate base after introducing R1 into the starting material, and reacting 1,4- The mixture is heated to 100 ° C with stirring and stirred to replace the boron ester at the C5 site.

In the reaction for introducing R ₂ at the C 5 position, a Suzuki coupling reaction using a palladium catalyst (II) or potassium carbonate base together with [Intermediate 1], arylboron ester or intermediate 2, aryl bromide, 4-dioxane and water (ratio 3: 1) as a solvent were heated to 100 ° C and stirred to obtain R ₂ Aryl or heteroaryl group.

Each of R ₁ and R ₂ is independently selected from a substituted or unsubstituted aryl group having 5 to 8 carbon atoms and a substituted or unsubstituted heteroaryl group having 5 to 13 carbon atoms.

However, those of ordinary skill in the art will recognize that compounds of formula (I) can be prepared by various methods based on the structure of formula (I), all of which are within the scope of the present invention Should be interpreted to include.

That is, it is understood that the compounds of formula (1) can be prepared by any combination of the synthesis methods described in the present specification or disclosed in the prior art, and it is understood that it belongs to the scope of the present invention, The present invention is not limited to the embodiments described below and the following embodiments.

The present invention provides a pharmaceutical composition for inhibiting Trk containing the azaindole derivative compound of the above formula (1) as an active ingredient together with a pharmaceutically acceptable carrier or diluent, and further comprising a pharmaceutically acceptable carrier or diluent together with an active ingredient There is provided a pharmaceutical composition for the treatment of a proliferative disease, a painful disease, an immunological disease, a cardiovascular disease, a neurological disease, an inflammatory disease, an endocrine disease or a viral infectious disease containing the azaindole derivative compound of the above formula 1.

According to one embodiment of the present invention, a salt dissolved in a buffer solution is used as a diluent, and a buffer solution that is usually used may be phosphate buffer saline that mimics the salt form of a human solution. Since buffer salts can control the pH of the solution at low concentrations, the buffer diluent does not alter the biological activity of the compound.

The compounds of the present invention may be formulated for use as pharmaceutical or veterinary compositions also containing a pharmaceutically or veterinarily acceptable carrier or diluent. The composition according to the present invention can be generally prepared according to a conventional method, and can be administered in a pharmaceutically or veterinarily appropriate form.

According to one embodiment of the present invention, it may be administered orally, such as in the form of tablets, capsules, sugar-coated tablets, film-coated tablets, liquid solutions or suspensions, or may be administered orally or intravenously May be administered parenterally.

The dosage can be determined according to various factors including the patient's age, body weight and condition and administration route. The daily dose can vary within wide limits and can be tailored to individual requirements in each individual case. However, in general, when administering the present compound alone to an adult, the dose of administration adopted per route of administration is 0.0001 to 50 mg / kg body weight, for example in the range of 0.001 to 10 mg / kg body weight, for example, 0.01 to 1 mg / kg You can lose weight.

Such dosage can be provided, for example, 1 to 5 times per day. For intravenous injection, the appropriate daily dose is 0.0001 to 1 mg / kg body weight, preferably 0.0001 to 0.1 mg / kg body weight. The daily dose may be administered as a single dose or according to a divided dose schedule.

Hereinafter, the present invention will be described in detail with reference to preferred embodiments and effects of Trk inhibitory activity. It will be apparent to those skilled in the art, however, that these examples are provided to further illustrate the present invention, and the scope of the present invention is not limited thereto.

<Production Example>

The azaindole derivative compounds represented by formula (1) according to the present invention were prepared by a general preparation procedure according to the following Reaction Scheme I and Reaction Scheme II.

[Reaction Scheme I]

[Starting material] [Intermediate 1] [Formula 1]

[Reaction Scheme II]

[Starting material] [Intermediate 2] [Formula 1]

Preparation of 5-bromo-3-iodo-1- (phenylsulfonyl) -lH-pyrrolo [2,3-b] pyridine

Acetone was added to 5-bromo azine (5-bromo-lH-pyrrolo [2,3-b] pyridine) (1 eq.) And N-iodosuccinimide (1.2 eq.). The mixture was reacted under nitrogen at room temperature for 2 hours. After completion of the reaction, the mixture was filtered under a cold acetone. To the obtained material, benzene sulfonyl chloride (2.2 equivalents), tetra-n-butylammonium hydrogen sulfate (0.25 equivalents), 50% sodium hydroxide and dichloromethane (DCM) were added and reacted at room temperature for 9 hours to protect the azaindole. After completion of the reaction, dichloromethane was added to dilute the mixture, and saturated sodium chloride solution was added thereto, followed by extraction with dichloromethane and water. Water was removed from the extracted solution with magnesium sulfate, and the solvent was blown off under low pressure. Cold methanol was added to the obtained material, and the mixture was reacted at 0 ° C for 1 hour and then filtered under a cold methanol to obtain a compound represented by the above [starting material].

<General Manufacturing Procedure 1>

Palladium (II) (0.2 equiv.) Was added to the round bottom flask, and the mixture was stirred at room temperature for 1 hour, The mixture was heated under nitrogen at 80 占 폚 for 3 hours in a solution of 4: 1 dioxane and water in a ratio of 3: 1 to effect a Suzuki reaction. The solvent was removed under reduced pressure, extracted with dichloromethane and water, dried over magnesium sulfate and filtered. The solvent was removed from the obtained solution under reduced pressure to obtain an azide substance into which R1 was introduced through column chromatography.

<General Production Procedure 2> Preparation of [Intermediate 1]

Without further purification in <General Preparation Procedure 1>, a further 4 N aqueous potassium hydroxide solution was added and heated at the same temperature for 30 minutes to remove the benzene sulfonyl group. After completion of the reaction, the reaction mixture was neutralized with a 10% aqueous solution of hydrogen chloride at 0 ° C, and the solvent was removed. The reaction mixture was extracted with dichloromethane and water, dried over magnesium sulfate and filtered. The solvent was removed from the obtained solution under reduced pressure, and [intermediate 1] was obtained through column chromatography.

<General Production Procedure 3> Preparation of [Intermediate 2]

(1 equivalent), bispinacolatodiborone (1.2 equivalents), potassium acetate (3 equivalents), and bis (diphenylphosphine) ferrocene-palladium (II) (0.05 equivalents) -Dioxane solvent under nitrogen at &lt; RTI ID = 0.0 &gt; 100 C &lt; / RTI &gt; for 12 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the reaction mixture was extracted with dichloromethane and water to give [Intermediate 2] which was not completely purified.

<General Production Procedure 4> Preparation of [Formula 1]

Palladium (II) (0.2 eq.) Was added to a round-bottomed flask, followed by addition of 1, 2, 3, 4, The mixture was heated at 100 &lt; 0 &gt; C for 5 hours under a 3: 1 solution of 4-dioxane and water. After completion of the reaction, the mixture was dissolved in dichloromethane and methanol, and then filtered under silica and celite. Then, a substance represented by the formula (1) was obtained by column chromatography.

<General Production Procedure 5> Preparation of [Formula 1]

Palladium (II) (0.2 eq.) Were added to a round-bottomed flask, followed by addition of a solution of the intermediate [2] (1.2 eq), aryl bromide (1 eq), potassium carbonate (3 eq.) And bis (diphenylphosphine) The mixture was heated at 100 &lt; 0 &gt; C for 5 hours in a solution of 3: 1 dioxane and water. After completion of the reaction, an aqueous 4 N potassium hydroxide solution was further added, and the mixture was heated at the same temperature for 30 minutes to remove the benzenesulfonyl group. After completion of the reaction, the reaction mixture was neutralized with a 10% aqueous hydrogen chloride solution at 0 ° C, and the solvent was removed. The residue was filtered with silica and celite in dichloromethane and methanol. Then, a substance represented by the formula (1) was obtained by column chromatography.

EXAMPLES Synthesis of an azaindole derivative represented by the formula (1)

Example 1 5-Bromo-1- (phenylsulfonyl) -3- (pyridin-4-yl) -lH- pyrrolo [2,3- b] pyridine

[Reaction Scheme 1]

Pyrrolo [2,3-b] pyridine (1.5 g, 3.24 mmol), 4-pyridineboronic acid Acid (398 mg, 3.24 mmol), and the reaction was carried out according to the above <General Production Scheme 1>. Thereafter, column chromatography using ethyl acetate and hexane gave 5-bromo-1- (phenylsulfonyl) -3- (pyridin-4-yl) -lH- pyrrolo [2,3- b] . (0.98 g, 73%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 7.62-7.67 (m, 2H), 7.73-7.78 (m, 1H), 7.85-7.87 (m, 2H), 8.15-8.18 (m, 2H), 8.56 (d, J = 2.1Hz, 1 H), 8.62-8.65 (m, 3H), 8.67 (d, J = 2.2 Hz, 1H).

Example 2: Synthesis of 5-bromo-3- (pyridin-4-yl) -lH-pyrrolo [2,3- b] pyridine

[Reaction Scheme 2]

The reaction was carried out according to the above <General Production Scheme 2> by adding 4 N aqueous potassium hydroxide solution according to [Reaction Scheme 2] without purification in Example 1 above. Thereafter, column chromatography using dichloromethane and methanol gave 5-bromo-3- (pyridin-4-yl) -lH-pyrrolo [2,3-b] pyridine. (242 mg, 73%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 12.69 (s, 1H), 7.97 (d, J = 5.9 Hz, 2H) 8.41 (d, J = 2.2 Hz, 1H), 8.47 (d, J = 3.0 1H), 8.60 (d, J = 6.0 Hz, 2H), 8.70 (d, J = 2.1 Hz, 1H), 12.69 (s, 1H).

Example 3 Synthesis of 1- (phenylsulfonyl) -3- (pyridin-4-yl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane- ) -LH-pyrrolo [2,3-b] pyridine

[Reaction Scheme 3]

Pyrrole [2,3-b] pyridine (1.0 g, 0.25 mmol), which is an aryl bromide, was added to a solution of 5-bromo-1- (phenylsulfonyl) -3- , 2.41 mmol) was subjected to the reaction according to <General Production Procedure 3> above. Then, after dissolving in dichloromethane, ethyl acetate and hexane were filtered with silica-celite in a solvent to obtain (phenylsulfonyl) -3- (pyridin-4-yl) -5- (4,4,5,5-tetra Methyl-1,3,2-dioxaborane-2-yl) - lH-pyrrolo [2,3-b] pyridine. (590 mg, 53%).

Example 4 Synthesis of an azaindole derivative compound represented by Formula 8

[Reaction Scheme 4]

[Chemical Formula 8]

Aniline boronic acid (69.5 mg, 0.41 mmol) was added to 5-bromo-3- (pyridin-4-yl) -lH- pyrrolo [2,3- b] pyridine Mg, 0.45 mmol) was added thereto, and the reaction was carried out according to the above <General Production Scheme 4>. After completion of the reaction, column chromatography was conducted to obtain 3- (3- (pyridin-4-yl) -1 H-pyrrolo [2,3-b] pyridin-5-yl) aniline represented by Formula 8. (28 mg, 24%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.18 (s, 2H), 6.59 (d, J = 8.2 Hz, 1H), 6.90 (d, J = 7.7 Hz, 1H), 6.93 (s, 1H) , 7.14 (t, J = 7.7 Hz, 1H), 7.81 (d, J = 6.0 Hz, 2H), 8.25 (s, 1H), 8.45 (d, J = 1.8 Hz, 1H), 8.50 (d, J = 1.7 Hz, 1H), 8.56 (d, J = 5.9 Hz, 2H), 12.28 (s, 1H).

Example 5 Synthesis of an azaindole derivative compound represented by Formula 12

[Reaction Scheme 5]

[Chemical Formula 12]

(1) N- (3-bromophenyl) acetamide

3-Bromoaniline (500 mg, 2.90 mmol), potassium carbonate (602 mg, 4.36 mmol) and acetyl chloride (0.25 mL, 3.45 mmol) were reacted to obtain N- (3-bromophenyl) acetamide.

^{1 H NMR (300 MHz, CDCl} 3) δ 2.16 (s, 3H), 7.13-7.15 (m, 2H), 7.38 (d, J = 7.7 Hz, 1H), 7.73 (s, 1H).

(2) The azindole derivative compound represented by the formula (12)

(4, 5-dihydroxyphenyl) -3- (pyridin-4-yl) -5- (4-methoxyphenyl) Pyrrolor2,3-blpyridine (60 mg, 0.130 mmol) was added to a solution of The reaction was carried out according to Procedure 5 &gt;. After completion of the reaction, the residue was purified by column chromatography using dichloromethane and methanol to obtain N- (3- (3- (pyridin-4-yl) -1H-pyrrolo [2,3- b] pyridine- Yl) phenyl) acetamide. (1.1 mg, 9%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.07 (s, 3H), 7.38-7.50 (m, 2H), 7.66 (d, J = 7.5 Hz, 1H), 7.82 (d, J = 5.7 Hz, 2H), 7.88 (s, 1H), 8.27 (d, 1H), 8.51-8.57 (m, 4H), 10.06 (s, 1H), 12.33 (s, 1H).

Example 6 Synthesis of an azaindole derivative compound represented by formula (13)

[Reaction Scheme 6]

[Chemical Formula 13]

(1) Synthesis of tert-butyl 3-bromophenylcarbamate

3-Bromoaniline (616 mg, 3.58 mmol) was dissolved in dichloromethane (5 ml), and di-tert-butyl dicarbonate (781 g, 3.58 mmol) was added and the mixture was stirred at room temperature for 18 hours. Water was added at 0 ° C and extracted three times with dichloromethane. Water was removed from the organic layer with anhydrous magnesium sulfate, and the solvent was blown off to obtain tert-butyl 3-bromophenylcarbamate.

¹ H NMR (300 MHz, CDCl ₃ - d ₁ )? 1.49 (s, 9H), 6.44 (s, 1H), 7.06-7.20 (m, 3H), 7.65

(2) 3-Bromo-N-methylaniline

Tert-butyl 3-bromophenylcarbamate (974 mg, 3.58 mmol) and NaH 60% (215 mg, 5.37 mmol) were dissolved in anhydrous DMF (3 ml) and stirred for 10 minutes. Iodomethane (0.45 mL, 7.16 mmol) was slowly added. After stirring at room temperature for 20 hours, 4N aqueous sodium hydroxide solution (5 ml) was added and stirred for 30 minutes. Extracted three times with ethyl acetate, and water was removed with anhydrous sodium carbonate. After the solvent was blown off, dichloromethane (3 ml) and TFA (3 ml) were added, and the mixture was stirred at room temperature for 12 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to neutralize and extracted three times with dichloromethane. After removing water with anhydrous magnesium sulfate, 3-bromo-N-methylaniline was obtained through column chromatography (EA: HX = 1:10) using ethyl acetate and hexane (200 mg, 30%

(3) The azindole derivative compound represented by the formula (13)

(Phenylsulfonyl) -3- (pyridin-4-yl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2 (25 mg, 0.134 mmol) and 3-bromo-N-methylaniline (60 mg, 0.130 mmol) Lt; / RTI &gt; After completion of the reaction, N-methyl-3- (3- (pyridin-4-yl) -1H-pyrrolo [2,3-d] pyrimidin- 2,3-b] pyridin-5-yl) aniline. (2.6 mg, 7%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.75 (d, J = 5.0 Hz, 3H), 5.75-5.72 (m, 1H), 6.57 (d, J = 7.8 Hz, 1H), 6.86 (s, 1H), 6.92 (d, J = 7.7 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 7.81 (d, J = 6.0, 2H), 8.24 (s, 1H), 8.47 (d, J = 1.9 Hz, 1H), 8.53 (d, J = 1.8 Hz, 1H), 8.56 (d, J = 6.0 Hz, 2H), 12.27 (s, 1H).

Example 7 Synthesis of an azaindole derivative compound represented by Formula 16

[Reaction Scheme 7]

[Chemical Formula 16]

(1) 2-Amino-5-bromopyridine-3-sulfonyl chloride

2-Amino-5-bromopyridine (5 g, 28.9 mmol) was dissolved in chlorosulfonic acid at 0 占 폚 and reacted at 130 占 폚 for 4 hours. The reaction solution was slowly poured into ice water, extracted with dichloromethane and water, dried over magnesium sulfate and filtered to give 2-amino-5-bromopyridine-3-sulfonyl chloride as yellow. (1.41 g, 18%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 5.96 (s, 2H), 8.14 (d, J = 2.4 Hz, 1H), 8.38 (d, J = 2.3 Hz, 1H).

(2) 2-Amino-5-bromo-N, N-dimethylpyridine-3-sulfonamide

(1.41 g, 5.19 mmol) was dissolved in 1.4-dioxane, and dimethylammonium chloride (508 mg, 6.23 mmol) and pyridine (0.5 ml, 6.23 mmol) were added at 0 ° C. mmol) were added. The reaction mixture was reacted at room temperature for 2 hours, and the reaction temperature was raised to 60 占 폚 for 7 hours. This was extracted with dichloromethane and water, and the residue was extracted with magnesium sulfate anhydrate and filtered. The solvent was removed from the organic layer under reduced pressure, and the residue was purified by silica gel column chromatography using methanol and dichloromethane to obtain 2-amino-5-bromo-N, N-dimethylpyridine-3-sulfonamide. (1.06 g, 73%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.71 (s, 6H), 6.87 (s, 2H), 7.86 (d, J = 2.5 Hz, 1H), 8.32 (d, J = 2.5 Hz, 1H) .

(3) Synthesis of 2-amino-N, N-dimethyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaboran-2- yl) pyridine-

2-Amino-5-bromo-N, N-dimethylpyridine-3-sulfonamide (1.0 g, 3.57 mmol) of the above Reaction Scheme 7 was subjected to the reaction according to the above <General Production Scheme 3>. This was dissolved in dichloromethane and methanol and then filtered through silica and celite to obtain 2-amino-N, N-dimethyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane -2-yl) pyridine-3-sulfonamide was obtained and used in the next reaction. (1.3 g)

¹ H NMR (300 MHz, CDCl ₃ - d ₁ )? 1.30 (s, 12H), 5.98 (s, 2H), 8.19 (s, 1H), 8.54 (s,

(4) The azindole derivative compound represented by the formula (16)

2-amino-N, N-dimethyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl) pyridine-3-sulfone Pyridine (100 mg, 0.365 mmol) was added to a solution of the above compound (143 mg, 0.438 mmol) and 5-bromo-3- (pyridin- 4 &gt;. After completion of the reaction, the residue was subjected to column chromatography using dichloromethane and methanol to obtain 2-amino-N, N-dimethyl-5- (3- (pyridin- , 3-b] pyridin-5-yl) pyridine-3-sulfonamide. (35 mg, 24%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.75 (s, 6H), 6.79 (s, 2H), 7.83-7.85 (m, 2H), 8.06 (d, J = 2.3 Hz, 1H), 8.24 ( s, 1 H), 8.52-8.55 (m, 4H), 8.70 (d, J = 2.4 Hz, 1H), 12.30 (s, 1H).

Example 8 Azaindole derivative compound represented by the formula (19)

[Reaction Scheme 8]

[Chemical Formula 19]

(1) 4-Bromo-2-nitrobenzoic acid

Water (50 ml) was added to 4-bromo-1-methyl-2-nitrobenzene (1 g, 4.63 mmol) and potassium permanganate (2.2 g, 13.9 mmol) and the mixture was stirred at 110 ° C for 6 hours. It was cooled to room temperature and filtered under celite. Washed several times with 4 N sodium hydroxide solution, and the pH was adjusted to 1 by adding 13 N aqueous hydrogen chloride solution to the collected solution. Extracted three times with ethyl acetate, and water was removed with anhydrous sodium sulfate to obtain 4-bromo-2-nitrobenzoic acid. (410 mg, 40%).

¹ H NMR (300 MHz, CDCl ₃ - d ₁ )? 8.10 (d, J = 2.13 Hz, 1H), 7.80-7.74 (m, 2H).

(2) 4-Bromo-1-chloro-2-nitrobenzene

(150 mg, 1.12 mmol), potassium carbonate (15.5 mg, 0.056 mmol) and potassium hydroxide (63 mg, 1.13 mmol) were added to a solution of 4-bromo-2-nitrobenzoic acid (125 mg, 0.560 mmol) DMF (3 ml) and DMSO (1.8 ml) were added, and the mixture was stirred at 140 ° C for 20 hours under oxygen conditions. After completion of the reaction, all of the reaction solvent was removed, and 4-bromo-1-chloro-2-nitrobenzene was obtained through column chromatography (EA: HX = 1:10) using ethyl acetate and hexane. (30 mg, 23%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 7.41 (d, J = 8.6 Hz, 1H), 7.63 (dd, J = 8.6, 2.3 Hz, 1H), 8.00 (d, J = 2.3 Hz, 1H ).

(3) 5-Bromo-2-chloroaniline

Nitrobenzene (30 mg, 0.217 mmol) was dissolved in ethyl acetate: dichloromethane = 3: 1 (1 ml), and tin chloride dehydroate (143 mg, 0.634 mmol) And the reduction reaction was carried out. After completion of the reaction, saturated sodium hydrogencarbonate solution was added to neutralize. Filtered under celite to remove the resulting substitution, extracted three times with dichloromethane, and then water was removed with anhydrous magnesium sulfate. The desired 5-bromo-2-chloroaniline was obtained (22 mg, 84%) by column chromatography (EA: HX = 1: 10) using ethyl acetate and hexane.

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 4.01 (s, 2H), 6.76 (dd, J = 8.4, 2.2 Hz, 1H), 6.88 (d, J = 2.2 Hz, 1H), 7.06 (d , &Lt; / RTI &gt; J = 8.5 Hz, 1H).

(6) An azindole derivative represented by the formula (19)

(Phenylsulfonyl) -3- (pyridin-4-yl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2 (22 mg, 0.106 mmol) and 5-bromo-2-chloroaniline (130 mg, 0.282 mmol) Lt; / RTI &gt; After completion of the reaction, 2-chloro-5- (3- (pyridin-4-yl) -1H-pyrrolo [2,3-d] pyrimidin- 2,3-b] pyridin-5-yl) aniline. (6.0 mg, 18%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.24 (s, 2H), 6.96 (dd, J = 8.1, 1.5 Hz, 1H), 7.17 (d, J = 1.7 Hz, 1H), 7.29 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 5.6 Hz, 2H), 8.24 (s, 1H), 8.48 (d, J = 9.5 Hz, 2H), 8.55 (d, J = 5.6 Hz, 2H) , 12.30 (s, 1 H).

Example 9 Synthesis of an azaindole derivative compound represented by the general formula [21]

[Reaction Scheme 9]

[Chemical Formula 21]

(1) 4-Bromo-1-methoxy-2-nitrobenzene

DMF was added to the starting material (500 mg, 2.29 mmol) of the above scheme and NaH (66 mg, 2.75 mmol) at 0 ° C and stirred at room temperature under nitrogen for 30 minutes. Iodomethane (488 mg, 3.44 mmol) dissolved in DMF was added thereto, and the mixture was stirred at room temperature overnight. Then, the mixture was extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous solution of sodium chloride, and the remaining water was removed with magnesium sulfate. The solvent was removed from the organic layer under reduced pressure, and 4-bromo-1-methoxy-2-nitrobenzene was obtained by silica gel column chromatography. (454 mg, 85%).

^{1 H NMR (300 MHz, CDCl} 3 - d) δ 3.93 (s, 3H), 6.97 (d, J = 8.9 Hz, 1H), 7.62 (dd, J = 2.5, 8.9 Hz, 1H), 7.96 (d, J = 2.5 Hz, 1H).

(2) 5-Bromo-2-methoxyaniline

4-Bromo-1-methoxy-2-nitrobenzene (106.2 mg, 0.457 mmol) was dissolved in ethyl acetate, and tin chloride dehydroate (413 mg, 1.83 mmol) Respectively. After the reaction, the reaction mixture was neutralized by adding 4 N aqueous sodium hydroxide solution at 0 ° C. The resulting solid was filtered off under celite, extracted three times with ethyl acetate, and then water was removed with anhydrous sodium sulfate. Column chromatography (EA: HX = 1: 10) using ethyl acetate and hexane gave 5-bromo-2-methoxyaniline. (46 mg, 49%).

¹ H NMR (300 MHz, CDCl ₃ - d ₁ )? 3.80 (s, 5H), 6.62 (d, 1H), 6.77-6.80 (m, 2H).

(3) Azaindole derivative represented by the formula (21)

(35 mg, 0.173 mmol) and 1- (phenylsulfonyl) -3- (pyridin-4-yl) -5- 2,3,5-tetrahydro-2H-pyrrolo [2,3-b] pyridine (200 mg, 0.433 mmol) &Lt; / RTI > After completion of the reaction, the residue was subjected to column chromatography using dichloromethane and methanol to obtain 2-methoxy-5- (3- (pyridin-4-yl) -1 H- pyrrolo [2,3- b] Pyridin-5-yl) aniline. (5.9 mg, 11%).

_{^{1 H NMR (DMSO- d 6,}} 300 MHz) δ 3.80 (s, 3H), 4.81 (s, 2H), 6.88-6.95 (m, 2H) 7.02 (d, J = 1.7 Hz, 1H), 7.78-7.80 (m, 2H), 8.21 (s, 1H), 8.40 (d, J = 1.9 Hz, 1H), 8.47 (d, J = 1.9 Hz, 1H), 8.54-8.56 1H).

Example 10 Synthesis of an azaindole derivative compound represented by the formula (22)

[Reaction Scheme 10]

[Chemical Formula 22]

(1) Synthesis of tert-butyl 5-bromo-2-hydroxyphenylcarbamate

4-Bromo-2-nitrophenol (500 mg, 2.29 mmol) was dissolved in ethyl acetate, tin chloride decahydrate (2.07 g, 9.17 mmol) was added and the mixture was heated to reflux for reduction. After completion of the reaction, 4 N aqueous sodium hydroxide solution was added at 0 캜 to neutralize the solution. The resulting solid was filtered off under celite, extracted three times with ethyl acetate, and then water was removed with anhydrous sodium sulfate. The desired 4-bromo-2-aminophenol was obtained (264 mg, 61%) by column chromatography (MeOH: MC = 1: 30) using methanol and dichloromethane.

4-Bromo-2-aminophenol (100 mg, 0.531 mmol) was dissolved in dichloromethane, and di-tert-butyl dicarbonate (127 mg, 0.585 mmol) was added and reacted at room temperature for 5 days. A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction solution to terminate the reaction, extracted with dichloromethane, and washed with a saturated aqueous sodium chloride solution. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and evaporated to remove the solvent. The remaining material was purified by silica gel column chromatography to obtain the desired tert-butyl 5-bromo-2-hydroxyphenylcarbamate. (126 mg, 82%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 1.50 (s, 9H), 6.77 (s, 1H), 6.65 (s, 1H) 6.78 (d, J = 8.6 Hz, 1H), 7.08 (dd, J = 2.3, 8.6 Hz, 1H), 7.34 (d, J = 2.3 Hz, 1H), 7.84 (s, 1H).

(2) 5-Bromo-2- (2- (dimethylamino) ethoxy) aniline

Butyl-5-bromo-2-hydroxyphenylcarbamate (126 mg, 0.437 mmol) and 60% sodium hydride (0.437 mmol) were dissolved in DMF under nitrogen atmosphere and stirred at room temperature for 30 minutes. TBAI (32 mg, 0.087 mmol) and 60% sodium hydride (0.481 mmol) were dissolved in DMF, stirred at room temperature for 30 minutes, Was slowly added to the reaction solution. After stirring overnight at room temperature, the reaction solution was extracted with ethyl acetate, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and filtered. The solvent was removed under reduced pressure, dichloromethane was added, triflouroacetic acid (2 ml) was added, and the mixture was stirred at room temperature for 3 hours to remove the protecting group. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution to terminate the reaction. The reaction mixture was extracted with ethyl acetate, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent of the organic layer was removed under reduced pressure, and the remainder was purified by silica gel column chromatography using methanol and dichloromethane to obtain 5-bromo-2- (2- (dimethylamino) ethoxy) aniline.

^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.21 (s, 6H), 2.61 (t, J = 5.7 Hz, 2H), 3.97 (t, J = 5.8 Hz, 2H), 5.00 (s, 2H) , 6.58 (dd, J = 2.5, 8.4Hz, 1H), 6.71-6.76 (m, 2H).

(3) Azaindole derivative represented by the formula (22)

2- (2-dimethylamino) ethoxy) aniline (20.4 mg, 0.0787 mmol) and 1- (phenylsulfonyl) -3- (pyridin- LH-pyrrolo [2,3-b] pyridine (108.9 mg, 0.236 mmol) was reacted with 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- , And the reaction was carried out according to the above <General Production Scheme 5>. After completion of the reaction, the title compound was obtained as a colorless powder by HPLC from 2- (2- (dimethylamino) ethoxy) -5- (3- (pyridin- Pyridin-5-yl) aniline. (2.4 mg, 8%).

^{_{1 H NMR (CDCl 3 - d}} 1, 300 MHz) δ 2.35 (s, 6H), 2.77 (t, J = 6.0 Hz, 2H), 4.07 (s, 2H), 4.15 (t, J = 6.0 Hz, 2H ), 6.91-6.96 (m, 2H), 6.96 (s, IH), 7.56 (d, J = 5.0 Hz, 2H) , 8.62 (d, J = 5.1 Hz, 2H), 10.73 (s, 1H).

Example 11 Synthesis of an azaindole derivative compound represented by the formula (23)

[Reaction Scheme 11]

(23)

(1) (4-Bromo-4-nitrophenyl) (morpholino) methanone

Bromo-2-nitrobenzoic acid (134 mg, 0.596 mmol) was added with cyionyl chloride (3 ml), and the mixture was stirred at 80 ° C for 3 hours. All the cyionyl chloride was blown off and dissolved in dichloromethane (3 mL). Under nitrogen conditions, morpholine (0.21 mL, 2.39 mmol) was slowly added. After stirring at room temperature for 20 hours, dichloromethane (20 mL) was added and the organic layer was washed once with saturated sodium chloride solution. Water was removed with anhydrous sodium sulfate and (4-bromo-4-nitrophenyl) (morpholino) methanone was obtained through column chromatography (EA: HX = 1: 5) using ethyl acetate and hexane. (111 mg, 59%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 3.20 (t, J = 4.9, 2H), 3.61 (s, 2H), 3.80 (s, 4H), 7.26 (d, J = 8.0 Hz, 1H), 7.83 (dd, J = 8.1, 1.8 Hz, 1 s), 3.82 (d, J = 1.9 Hz, 1 H).

(2) (2-Amino-4-bromophenyl) (morpholino) methanone

(110 mg, 0.349 mmol) was dissolved in ethyl acetate: dichloromethane = 3: 1 (3.5 mL), and tin chloride dehydrate (394 mg, 1.75 mmol) was added to perform the reduction reaction. After completion of the reaction, saturated sodium hydrogencarbonate solution was added to neutralize. Filtered under celite to remove the resulting substitution, extracted three times with dichloromethane, and water was removed with anhydrous magnesium sulfate. (85 mg, 85%) was obtained through column chromatography (EA: HX = 1: 1) using ethyl acetate and hexane.

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.67-3.59 (m, 8H), 4.42 (s, 2H), 6.81 (dd, J = 8.1, 1.8 Hz, 1H), 6.86 (d, J = 1.7 Hz, 1 H), 6.90 (d, J = 13.8 Hz, 1 s).

(3) An azindole derivative represented by the formula (23)

(Phenylsulfonyl) -3- (pyridin-4-yl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2 (2-amino-4-bromophenyl) (morpholino) methanone (34 mg, 0.1192 mmol) was added to a solution of The reaction was carried out according to the general preparation procedure 5 above. After completion of the reaction, N- (3-amino-5- (3- (pyridin-4-yl) - Pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzenesulfonamide. (6.1 mg, 13%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.72-3.70 (m, 8H), 4.53 (s, 2H), 6.99-6.97 (m, 2H), 7.20 (d, J = 8.3 Hz, 1H) , 7.58 (d, J = 5.5 Hz, 2H), 7.72 (s, 1H), 8.38 (s, 1H), 8.59 (s, 1H), 8.65 (d, J = 5.6 Hz, 2H), 9.55 (s, 1H).

Example 12 Synthesis of an azaindole derivative compound represented by Formula 24

[Reaction Scheme 12]

&Lt; EMI ID =

(1) 1-Bromo-3,5-dinitrobenzene

1,3-Dinitrobenzene (1.0 g, 5.94 mmol) was dissolved in concentrated sulfuric acid and N-bromosuccinimide (1.48 g, 8.33 mmol) was added portionwise at 80 ° C for 3 hours. Thereafter, the mixture was stirred at the same temperature for 3 hours, cooled to room temperature, and carefully added to the ice water. The reaction solution was filtered, and the remaining solid was washed with water, which was recrystallized from cold methanol to obtain yellowish white solid 1-bromo-3,5-dinitrobenzene. (1.07 g, 72%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 8.69 (d, J = 2.0 Hz, 2H), 8.99 (t, J = 2.0 Hz, 1H).

(2) Bromo-3-methoxy-5-nitrobenzene

(968 mg, 3.92 mmol) was dissolved in methanol, sodium methoxide (254 mg, 4.70 mmol) was added, and the mixture was refluxed for 10 hours and boiled. The starting material disappeared and the reaction was quenched with 1 N aqueous hydrogen chloride solution and extracted with dichloromethane. The dichloromethane layer was dried with magnesium sulfate, filtered, and then the solvent was removed under reduced pressure. The remaining material was purified through a silica gel column (EA: Hex = 1: 10) to obtain bromo-3-methoxy-5-nitrobenzene. (711 mg, 78%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.87 (s, 3H), 7.35 (m, 1H), 7.66 (m, 1H), 7.95 (m, 1H).

(3) 3-Bromo-5-methoxyaniline

Bromo-3-methoxy-5-nitrobenzene (554 mg, 2.39 mmol) and ethynyl chloride dihydrochloride (2.69 g, 11.9 mmol) dissolved in ethanol were slowly added and refluxed for 2 hours and 30 minutes. The reaction solution was cooled to room temperature, placed in ice water, and adjusted to a pH of 12 or higher by using an aqueous solution of sodium hydroxide. The mixture was extracted with ethyl acetate and washed with a saturated aqueous sodium chloride solution. The combined organic layers were washed with sodium sulfate, filtered, and the solvent was blown off under reduced pressure. The remaining reaction solution was purified through a silica gel column (EA: Hex = 1: 5) to obtain a yellow liquid 3-bromo-5-methoxyaniline (182 mg, 37%

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.68 (s, 2H), 3.71 (s, 3H), 6.11 (t, J = 2.1 Hz, 1H), 6.41-6.45 (m, 2H).

(4) Azaindole derivative represented by the formula (24)

3- (pyridin-4-yl) -5- (4, 4-trifluoromethylpyridin-2-ylamino) Pyrrolo [2,3-b] pyridine (74.8 mg, 0.181 mmol) was added to the above-prepared < 5 >. After completion of the reaction, the residue was subjected to column chromatography using dichloromethane and methanol to obtain 3-methoxy-5- (3- (pyridin-4-yl) -lH- pyrrolo [2,3- b] pyridin- &Lt; / RTI &gt; (5 mg, 26%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.84 (m, 5H), 6.28 (t, J = 2.0 Hz, 1H), 6.56 (dd, J = 1.8 Hz, 8.0, 2H), 7.56-7.58 (m, 2H), 7.72 ( d, J = 1.7 Hz, 1H), 8.39 (d, J = 1.9 Hz, 1H), 8.59 (d, J = 2.0 Hz, 1H), 8.63-6.65 (m, 2H) , 10.02 (s, 1 H).

Example 13 Synthesis of an azaindole derivative compound represented by Formula 26

[Reaction Scheme 13]

(26)

(1) 3-Bromo-4-nitroaniline

A solution of sodium hydrosulfide (50.9 mmol) (3 ml of water, 40 ml of methanol 40 ml) and toluene (100 ml) was added to a solution of 1-bromo-3,5-dinitrobenzene (4.02 g, 16.3 mmol) ML) was slowly added over 30 min. The reaction mixture was stirred at 80 &lt; 0 &gt; C for 10 hours and cooled to room temperature. The resulting solid was filtered off and the remainder was collected and all the solvent was removed, followed by 3-bromo-4-nitroaniline via column chromatography (EA: HX = 1: 5) using ethyl acetate and hexane. (2.47 g, 70%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 4.05 (s, 2H), 7.06 (t, J = 1.9 Hz, 1H), 7.39 (t, J = 2.1 Hz, 1H), 7.68 (t, J = 1.8 Hz, 1H).

(2) N- (3-Bromo-4-nitrophenyl) -N- (phenylsulfonyl) benzenesulfonamide

3-Bromo-4-nitroaniline (2.47 g, 11.5 mmol) was dissolved in DCM (20 mL). Triethylamine (5.0 ml, 35.8 mmol) and benzenesulfonyl chloride (7.4 ml, 58.0 mmol) were added at room temperature, followed by stirring for 12 hours. After completion of the reaction, all of the solvent was blown off, and methanol was added thereto to filter off the insoluble solid to obtain N- (3-bromo-4-nitrophenyl) -N- (phenylsulfonyl) benzenesulfonamide. (4.79 g, 84%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 7.47 (t, J = 1.8 Hz, 1H), 7.62-7.57 (m, 4H), 7.73-7.71 (m, 2H), 7.77 (t, J = 1.9 Hz, 1H), 7.93-7.78 (m, 4H), 8.44 (t, J = 1.9 Hz, 1H).

(3) N- (3-Amino-5-bromophenyl) -N- (phenylsulfonyl) benzenesulfonamide

(4.79 g, 9.63 mmol) was dissolved in ethylacetate: dichloromethane = 3: 1 (120 ml), and a solution of tin chloride The reduction reaction was performed by the addition of die hardate (11 g, 48.8 mmol). After completion of the reaction, saturated sodium hydrogencarbonate solution was added to neutralize. The resulting solid was filtered off under celite, extracted three times with dichloromethane, and water was removed with anhydrous magnesium sulfate. After all the solution was blown, 20 ml of acetonitrile was added and the insoluble solid was filtered to obtain the desired N- (3-amino-5-bromophenyl) -N- (phenylsulfonyl) benzenesulfonamide. (3.4 g, 76%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.79 (s, 2H), 6.27 (t, J = 2.1 Hz, 1H), 6.50 (t, J = 1.8 Hz, 1H), 6.90 (t, J = 1.9 Hz, 1H), 7.62-7.57 (m, 4H), 7.74-7.69 (m, 2H), 8.00-7.97 (m, 4H).

(4) The azindole derivative compound represented by the formula (26)

(Phenylsulfonyl) -3- (pyridin-4-yl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2 (62 mg, 0.1344 mmol) and N- (3-amino-5-bromophenyl) -N- (phenylsulfonyl) benzenesulfonamide (44 mg, Mg, 0.088 mmol), and the reaction was carried out according to the above-mentioned <General Production Scheme 5>. After completion of the reaction, N- (3-amino-5- (3- (pyridin-4-yl) - Pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzenesulfonamide. (4.3 mg, 11%).

^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.26 (s, 2H), 6.43 (s, 1H), 6.52 (s, 1H), 6.56 (s, 1H), 7.60-7.53 (m, 3H), 7.74 (d, J = 5.9 Hz , 2H), 7.82 (d, J = 7.0, 2H), 8.23 (s, 1H), 8.26 (s, 1H), 8.30 (s, 1H), 8.56 (d, J = 5.7 Hz, 2H), 10.13 (s, 1H), 12.25 (s, 1H).

Example 14 Synthesis of azaindole derivative compound represented by formula (31)

[Reaction Scheme 14]

(31)

(1) N- (3-Bromo-5-nitrophenyl) acetamide

1-Bromo-3,5-dinitrobenzene (101.5 mg, 0.467 mmol) was dissolved in pyridine (1 ml) and acetic anhydride (0.1 ml, 1.12 mmol) was added. After reacting at room temperature for 12 hours, water (6.5 ml) was added and stirred for 15 minutes. The resulting solid was filtered, washed with water and dried in vacuo to give N- (3-bromo-5-nitrophenyl) acetamide. (105 mg, 87%).

(2) N- (3-Amino-5-bromophenyl) acetamide

(105 mg, 0.386 mmol) was dissolved in ethyl acetate: dichloromethane = 3: 1 (120 mL) and tin chloride dihydrate (435 mg, 1.93 mmol) ) Was added to perform a reduction reaction. After completion of the reaction, saturated sodium hydrogencarbonate solution was added to neutralize. Filtered under celite to remove the resulting substitution, extracted three times with dichloromethane, and water was removed with anhydrous magnesium sulfate. After the solution was completely blown, it was purified by silica gel column chromatography to obtain the desired N- (3-amino-5-bromophenyl) acetamide. (23.5 mg, 26%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 2.13 (s, 3H), 3.74 (s, 2H), 6.55 (s, 1H), 6.80 (s, 1H), 6.06 (m, 2H).

(3) An azindole derivative represented by the formula (31)

(3-amino-5-bromophenyl) acetamide (23.5 mg, 0.102 mmol) and 1- (phenylsulfonyl) -3- (pyridin- Pyrrolo [2,3-b] pyridine (56 mg, 0.123 mmol) was added to a tetrahydrofuran solution The reaction was carried out according to the above <General Production Scheme 5>. After completion of the reaction, the residue was subjected to column chromatography using dichloromethane and methanol to obtain N- (3-amino-5- (3- (pyridin-4-yl) b] pyridin-5-yl) phenyl) acetamide. (2.3 mg, 6.5%).

_{^{1 H NMR (DMSO- d 6,}} 300 MHz) δ 2.02 (s, 3H), 5.22 (s, 2H), 6.60 (s, 1H), 6.96 (s, 1H), 7.03 (s, 1H), 7.77 ( d, J = 6.1 Hz, 2H ), 8.24 (d, J = 2.6 Hz, 1H), 8.39 (s, 1H), 8.44 (d, J = 1.8 Hz, 1H), 8.56 (d, J = 6.1 Hz, 2H), 9.74 (s, 1 H), 12.28 (s, 1 H).

Example 15 Azaindole derivative compound represented by formula (32)

[Reaction Scheme 15]

(32)

(1) 2-Bromo-5-nitrophenol

3-methoxyphenol (791 mg, 3.41 mmol) was dissolved in anhydrous dichloromethane (7 mL), and tribromoboron (1 M in DCM, 13.7 mL, 13.7 mmol) was slowly added at -20 ° C . The temperature was gradually raised to room temperature and stirred for 25 hours. Methanol was added to terminate the reaction. After the solvent was completely blown off, the desired 2-bromo-5-nitrophenol was obtained through column chromatography (EA: HX = 1: 10) using ethyl acetate and hexane. (429 mg, 58%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 5.58 (s, 1H), 7.33 (t, J = 1.8 Hz, 1H), 7.62 (t, J = 2.1 Hz, 1H), 7.94 (t, J = 1.7 Hz, 1H).

(2) 2- (3-Bromo-5-nitrophenoxy) -N, N-dimethylethanamine

To a solution of 2-bromo-5-nitrophenol (200 mg, 0.917 mmol), potassium carbonate (625 mg, 4.59 mmol) and 2-iodo-N, N-dimethylethanamine (365 mg, 1.83 mmol) 2 ml) was added, and the mixture was allowed to react in a microwave at 140 占 폚 for 30 minutes. Ethyl acetate was added in an excess amount and washed several times with water and then subjected to column chromatography (DCM: MeOH = 10: 1) using dichloromethane and methanol to obtain 2- (3-bromo-5-nitrophenoxy) Dimethylethanamine (75 mg, 28%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 2.33 (s, 6H), 2.74 (t, J = 5.5 Hz, 2H), 4.10 (t, J = 5.5 Hz, 2H), 7.38 (t, J = 2.2 Hz, 1H), 7.68 (t, J = 2.2 Hz, 1H), 7.94 (t, J = 1.8 Hz, 1H).

(3) 2-Bromo-5- (2-dimethylamino) ethoxy) aniline

N, N-Dimethylethanamine (75 mg, 0.259 mmol) was dissolved in ethyl acetate: dichloromethane = 3: 1 (3 mL), and a solution of 2- (293 mg, 1.29 mmol) was added to conduct the reduction reaction. After completion of the reaction, saturated sodium hydrogencarbonate solution was added to neutralize. Filtered under celite to remove the resulting substitution, extracted three times with dichloromethane, and water was removed with anhydrous magnesium sulfate. (54 mg, 80%) of 2-bromo-5- (2-dimethylamino) ethoxy) aniline was obtained by column chromatography using dichloromethane and methanol (DCM: MeOH = 5:

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 2.30 (s, 6H), 2.67 (t, J = 5.7 Hz, 2H), 3.97 (t, J = 5.7 Hz, 2H), 6.14 (t, J = 2.1 Hz, 1H), 6.41 (t, J = 1.9 Hz, 1H), 6.45 (t, J = 1.7 Hz, 1H).

(4) Azaindole derivative represented by the formula (32)

(Phenylsulfonyl) -3- (pyridin-4-yl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2 (56 mg, 0.121 mmol) and N- (4-amino-2-bromophenyl) benzenesulfonamide (26 mg, 0.100 mmol) were added to a solution of The reaction was carried out according to <General Production Procedure 5>. After completion of the reaction, 3- (2- (dimethylamino) ethoxy-5- (3- (((methylamino) Pyridin-4-yl) -lH- pyrrolo [2,3-b] pyridin-5-yl) aniline (12 mg, 25%

^{1 H NMR (300 MHz, MeOD-} d 4) δ 3.01 (s, 6H), 3.64 (t, J = 5.0 Hz, 2H), 4.46 (t, J = 4.9 Hz, 2H), 6.76 (t, J = 1.9 Hz, 1H), 7.09 ( s, 2H), 8.42 (d, J = 7.0 Hz, 2H), 8.57 (s, 1H), 8.67-8.65 (m, 3H), 8.71 (d, J = 1.9 Hz, 1H).

&Lt; Example 16: Synthesis of an azaindole derivative compound represented by the general formula [36]

[Reaction Scheme 16]

(36)

(1) 2-Bromo-4-nitroaniline

N-Bromosuccinimide (1.35 g, 7.60 mmol) was added to a solution of 4-nitroaniline (1 g, 7.24 mmol) in anhydrous DMF (2 mL) at room temperature. The reaction mixture was stirred for 40 minutes and then ice water (5-10 mL) was added. The resulting solid was filtered and then subjected to column chromatography (EA: HX = 1: 5) using ethyl acetate and hexane to obtain 2-bromo-4-nitroaniline. (1.20 g, 76%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 4.81 (s, 2H), 6.72 (d, J = 8.9 Hz, 1H), 8.00 (dd, J = 8.9, 2.5 Hz, 1H), 8.35 (d , &Lt; / RTI &gt; J = 2.4 Hz, 1H).

(2) N- (2-Bromo-4-nitrophenyl) -N- (phenylsulfonyl) benzenesulfonamide

2-Bromo-4-nitroaniline (183 mg, 0.843 mmol) was dissolved in dichloromethane (4 mL). After adding triethylamine (1.10 mL, 4.22 mmol) and 4-dimethylaminopyridine (10 mg, 0.082 mmol) and benzenesulfonyl chloride (0.55 mL, 4.22 mmol) at room temperature in this order, the mixture was stirred for 12 hours . After completion of the reaction, water (4 ml) was added, extracted three times with dichloromethane, and then water was removed with anhydrous magnesium sulfate. All dichloromethane was blown off and methanol was added to filter the insoluble solids to give N- (2-bromo-4-nitrophenyl) -N- (phenylsulfonyl) benzenesulfonamide. (328 mg, 78%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 7.28 (d, J = 8.7 Hz, 1H), 7.69-7.55 (m, 4H), 7.74-7.71 (m, 2H), 7.98-7.95 (m, 4H), 8.15 (dd, J = 8.8,2.6 Hz, 1H), 8.47 (d, J = 2.6 Hz, 1H).

(3) Synthesis of N- (4-amino-2-bromophenyl) -N- (phenylsulfonyl) benzenesulfonamide

(328 mg, 0.660 mmol) was dissolved in ethyl acetate: dichloromethane = 3: 1 (5 ml), and a solution of tin chloride Dihydrate (744 mg, 3.30 mmol) was added to effect the reduction reaction. After completion of the reaction, saturated sodium hydrogencarbonate solution was added to neutralize. Filtered under celite to remove the resulting substitution, extracted three times with dichloromethane, and water was removed with anhydrous magnesium sulfate. N- (4-amino-2-bromophenyl) -N- (phenylsulfonyl) benzenesulfonamide was obtained by column chromatography (EA: HX = 1: 2) using ethyl acetate and hexane. (200 mg, 76%).

After dissolving N- (4-amino-2-bromophenyl) -N- (phenylsulfonyl) benzenesulfonamide (130 mg, 0.278 mmol) in methanol (2 ml) and 50% aqueous potassium hydroxide (2 ml) , And the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the reaction mixture was neutralized with 13 N HCl, extracted three times with dichloromethane, and the organic solvent was collected. After removing water with anhydrous magnesium sulfate, N- (4-amino-2-bromophenyl) benzenesulfonamide was obtained through column chromatography (EA: HX = 1: 2) using ethyl acetate and hexane. (58 mg, 64%).

^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.67 (s, 2H), 6.50 (s, 1H), 6.59 (dd, J = 8.6, 2.6 Hz, 1H), 6.67 (d, J = 2.6 Hz 1H), 7.54-7.36 (m, 4H), 7.63 (d, J = 1.4 Hz, 1H), 7.66 (s, 1H).

(4) The azindole derivative compound represented by the formula (36)

(Phenylsulfonyl) -3- (pyridin-4-yl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2 (45 mg, 0.098 mmol) and N- (4-amino-2-bromophenyl) benzenesulfonamide (27 mg, 0.083 mmol) The reaction was carried out according to <General Production Procedure 5>. After completion of the reaction, N- (4-amino-2- (3- (pyridin-4-yl) - Pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzenesulfonamide. (8 mg, 22%).

^{1 H NMR (300 MHz, MeOD-} d 4) δ 6.75-6.61 (m, 2H), 6.96 (d, J = 8.5 Hz, 1H), 7.12 (t, J = 7.5 Hz, 2H), 7.27-7.21 ( 1H), 7.42-7.30 (m, 2H), 7.84-7.75 (m, 2H), 8.05 (s, 1H), 8.11 (s, 2H), 8.54 (d, J = 5.5 Hz, 2H).

Although there are differences in the structure and physical properties of the substituents depending on the kind of the substituent, the reaction principle and conditions of the above-mentioned examples according to the present invention are nonetheless applicable to the compounds containing substituents not described in the above- It will be apparent to those skilled in the art that the compounds containing these substituents can be easily carried out based on the disclosure of the examples and common sense in the art.

The synthesis of the specific azaindole derivative compound according to the present invention will now be described in detail with reference to each of the final compounds or their intermediates according to the above examples. As a result, it will be apparent to those skilled in the art that all of the specific azaindole compounds It will be obvious that the present invention can be easily carried out.

The azaindole derivative compounds specifically represented by the formulas (2) to (37) in the present invention are shown in Table 1 below.

The rescue name NMR; MS 2

Pyrrolo [2,3-b] pyridin-5-yl) benzonitrile &lt; ^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.09 (s, 2H), 6.49 (dd, J = 7.9 Hz, 1.3, 1H), 6.92 (d, J = 7.7 Hz, 1H), 7.02 (d, J = 1.8 Hz, 1H), 7.09 (t, J = 7.7Hz, 1H), 7.70 (t, J = 7.8Hz, 1H), 7.78 (s, 1H), 7.83 (d, J = 7.8Hz, 1H) , 8.14 (d, J = 8.0Hz , 1H), 8.28 (s, 1H), 8.48 (d, J = 2.2Hz, 1H), 8.61 (d, J = 2.1Hz, 1H), 11.97 (s, 1H) . HRMS (EI +) m / z Calcdfor C ₂₀ H ₁₄ N ₄ [M + Na] ⁺ , 333.1116; found, 333.1098. 3

LH-pyrrolo [2,3-b] pyridin-5-yl) benzonitrile ^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.95 (d, J = 3.2Hz, 6H), 7.00 (d, J = 8.3Hz, 1H), 7.11 (d, J = 1.9Hz, 1H), 7.22 (dd, J = 8.2, 2.0Hz, 1H), 7.54 (d, J = 2.4Hz, 1H), 7.59 (d, J = 7.7Hz, 1H), 7.64-7.63 (m, 1H), 7.91-7.85 (m, 2H), 8.32 (d, J = 2.0 Hz, 1H), 8.57 (d, J = 2.0 Hz, 1H), 10.12 (s, 1H). HRMS (EI +) m / z calcdfor C 22 H 17 N 3 O 2 [M + Na] +, 378.1218; found, 378.1217. 4

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, MeOD-} d 4) δ 3.87 (s, 3H), 3.90 (s, 3H), 6.75-6.68 (m, 1H), 7.06-6.93 (m, 3H), 7.26-7.20 (m , 3H), 7.59 (s, 1H), 8.26 (d, J = 2.0 Hz, 1H), 8.43 (d, J = 2.0 Hz, 1H). HRMS (EI +) m / z Calcdfor C ₂₁ H ₁₉ N ₃ O ₂ [M + H] ⁺ , 346.1556; found, 346.1543. 5

Pyrrolo [2,3-b] pyridin-3-yl) benzonitrile ^{1 H NMR (300 MHz, MeOD-} d 4) δ 6.73 (dd, J = 8.0, 1.3 Hz, 1H), 7.03-6.96 (m, 2H), 7.20 (t, J = 7.8 Hz, 1H), 7.60- 1H), 7.58 (m, 2H), 7.78 (s, 1H), 8.01-7.99 (m, 2H), 8.35 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 1.9 Hz, HRMS (EI +) m / z Calcdfor C ₂₀ H ₁₄ N ₄ [M + Na] ⁺ , 333.1116; found, 333.1101. 6

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, MeOD-} d 4) δ 6.78 (d, J = 1.3 Hz, 1H), 7.03 (d, J = 7.6, 1H), 7.08 (d, J = 1.8 Hz, 1H), 7.25 ( t, J = 7.8 Hz, 1H ), 7.57-7.54 (m, 1H), 7.87 (s, 1H), 8.25-8.22 (m, 1H), 8.54-8.42 (m, 3H), 8.94 (d, J = 1.7 Hz, 1H). HRMS (EI +) m / z calcdfor C 18 H 14 N 4 [M + Na] +, 309.1116; found, 309.1117. 7

3- (3-phenyl-lH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.15 (s, 2H), 6.56 (d, J = 7.9 Hz, 1H), 6.84-6.90 (m, 2H), 7.12 (t, J = 7.7 Hz, J = 7.9 Hz, 2H), 7.75 (d, J = 7.2 Hz, 2H), 7.88 (d, J = 2.5 Hz, 1H), 8.30 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 2.0 Hz, 1H), 11.95 (s, 1H). HRMS (EI +) m / z calcd for C 19 H 15 N 3 [M + H] +, 286.1344; found, 286.1346. 8

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.18 (s, 2H), 6.59 (d, J = 8.2 Hz, 1H), 6.90 (d, J = 7.7 Hz, 1H), 6.93 (s, 1H) , 7.14 (t, J = 7.7Hz , 1H), 7.81 (d, J = 6.0Hz, 2H), 8.25 (s, 1H), 8.45 (d, J = 1.8Hz, 1H), 8.50 (d, J = 1H), 8.56 (d, J = 5.9 Hz, 2H), 12.28 (s, 1H). HRMS (EI +) m / z calcdfor C 18 H 14 N 4 [M + H] +, 287.1297; found, 287.1289. 9

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.20 (s, 2H), 6.68 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 6.2 Hz, 2H), 8.19 (d, J = 2.8 Hz, 2H), 8.40 ( s, 1H), 8.48 (s, 1H), 8.54 (d, J = 6.0 Hz, 2H), 12.17 (s, 1HHRMS (EI +) m / z calcdfor C 18 H 14 N 4 [M + H] &lt; ⁺ &gt;,287.1297; found, 287.1295. 10

LH-pyrrolo [2,3-b] pyridine hydrochloride ^{1 H NMR (300 MHz, MeOD-} d 4) δ 7.34 (m, 1H), 7.43-7.48 (m, 2H), 7.65-7.68 (m, 2H), 7.77-7.79 (m, 2H), 8.00 (s , &Lt; / RTI &gt; 1H), 8.47-8.52 (m, 4H). HRMS (EI +) m / z calcd for C 18 H 13 N 3 [M + H] +, 272.1188; found, 272.1204. 11

LH-pyrrolo [2,3-b] pyridine prepared in Step 2 of Example 1 was used in place of 5- (3-methoxyphenyl) -3- ^{1 H NMR (300 MHz, MeOD-} d 4) δ 3.89 (s, 3H), 6.96 (dd, J = 7.8, 1.8 Hz, 1H), 7.27-7.22 (m, 2H), 7.41 (t, J = 7.9 Hz, 1H), 7.80 (dd , J = 4.7, 1.5 Hz, 2H), 8.02 (s, 1H), 8.54-8.52 (m, 4H) .HRMS (EI +) m / z calcdfor C 19 H 15 N 3 O [M + Na] &lt; ⁺ &gt;,324.1113; found, 324.1113. 12

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) acetamide ^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.07 (s, 3H), 7.38-7.50 (m, 2H), 7.66 (d, J = 7.5 Hz, 1H), 7.82 (d, J = 5.7 Hz, 2H), 7.88 (s, 1H), 8.27 (d, 1H), 8.51-8.57 (m, 4H), 10.06 (s, 1H), 12.33 (s, 1H). HRMS (EI +) m / z calcd for C 20 H 16 N 4 O [M + H] +, 329.1402; found, 329.1399. 13

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.75 (d, J = 5.0 Hz, 3H), 5.75-5.72 (m, 1H), 6.57 (d, J = 7.8 Hz, 1H), 6.86 (s, 1H), 6.92 (d, J = 7.7 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 7.81 (d, J = 6.0, 2H), 8.24 (s, 1H), 8.47 (d, J = 1.9 Hz, 1H), 8.53 (d, J = 1.8 Hz, 1H), 8.56 (d, J = 6.0 Hz, 2H), 12.27 (s, 1H) .HRMS (EI +) m / z calcdfor C 19 H 16 N ₄ [M + Na] &lt; ⁺ &gt;,323.1273; found, 323.1252. 14

Pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.03 (s, 6H), 6.79 (dd, J = 8.1, 2.1 Hz, 1H), 6.99-6.94 (m, 2H), 7.36 (t, J = 7.7 Hz, 1H), 7.59 (dd, J = 4.6, 1.6 Hz, 2H), 7.78 (s, 1H), 8.44 (d, J = 1.9 Hz, 1H), 8.65-8.63 s, 1H). HRMS (EI +) m / z calcdfor C 20 H 18 N 4 [M + H] &lt; ⁺ &gt;,315.1610; found, 315.1613. 15

Pyrrol o [2,3-b] pyridin-5-yl) pyridin-2-amine ^{1 H NMR (300 MHz, DMSO} -d 6) δ 3.07-3.10 (m, 4H), 3.61-3.64 (m, 4H), 6.81 (s, 2H), 7.83-7.85 (m, 2H), 8.05 (d , J = 2.4 Hz, 1H) , 8.25 (s, 1H), 8.53-8.56 (m, 4H), 8.72 (d, J = 2.4 Hz, 1H), 12.30 (s, 1H). HRMS (EI +) m / z calcd for C 21 H 20 N 6 O 3 S [M + H] +, 437.1396; found 437.1396. 16

LH-pyrrolo [2,3-b] pyridin-5-yl) pyridine-3-sulfonamide ^{1 H NMR (300 MHz, DMSO} -d 6) δ 2.75 (s, 6H), 6.79 (s, 2H), 7.83-7.85 (m, 2H), 8.06 (d, J = 2.3 Hz, 1H), 8.24 ( s, 1 H), 8.52-8.55 (m, 4H), 8.70 (d, J = 2.4 Hz, 1H), 12.30 (s, 1H). HRMS (EI +) m / z calcd for C 19 H 18 N 6 O 2 S [M + H] +, 395.1290; found 395.1290. 17

LH-pyrrolo [2,3-b] pyridin-5-yl) pyridin-3-amine ^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.40 (s, 2H), 7.25 (t, J = 2.3, 1H), 7.83 (dd, J = 4.6, 1.6 Hz, 2H), 7.95 (d, J = 4.3 Hz, 1H), 8.15 (d, J = 2.0 Hz, 1H), 8.26 (s, 1H), 8.52 (s, 2H), 8.55 (dd, J = 4.6, 1.5 Hz, 2H), 12.38 , 1H). HRMS (EI +) m / z calcdfor C 17 H 13 N 5 [M + Na] &lt; ⁺ &gt;,310.1069; found, 310.1065. 18

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, MeOD-} d 4) δ 2.91 (s, 3H), 5.97 (dd, J = 8.6, 2.8 Hz, 1H), 6.06 (d, J = 2.7 Hz, 1H), 6.12 (d, J = 8.6 Hz, 1H), 6.97 (d, J = 4.7, 1.7 Hz, 2H), 7.20 (s, 1H), 7.59 (d, J = 1.9 Hz, 1H), 7.65 (d, J = 2.0 Hz, 1H), 7.70 (dd, J = 4.7, 1.6 Hz, 2H) .HRMS (EI +) m / z calcdfor C 19 H 16 N 4 O [m + H] +, 317.1402; found, 317.1409. 19

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.24 (s, 2H), 6.96 (dd, J = 8.1, 1.5 Hz, 1H), 7.17 (d, J = 1.7 Hz, 1H), 7.29 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 5.6 Hz, 2H), 8.24 (s, 1H), 8.48 (d, J = 9.5 Hz, 2H), 8.55 (d, J = 5.6 Hz, 2H) , 12.30 (s, 1 H). HRMS (EI +) m / z calcdfor C 18 H 13 C l N 4 [M + H] +, 321.0907; Found, 321.0924. 20

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, MeOD-} d 4) δ 2.17 (s, 3H), 6.91 (dd, J = 7.7, 1.8 Hz, 1H), 7.03 (d, J = 1.7 Hz, 1H), 7.07 (d, J = 7.7 Hz, 1H), 7.75 (d, J = 4.8, 1.4 Hz, 2H), 7.96 (s, 1H), 8.48-8.45 (m, 4H) .HRMS (EI +) m / z calcdfor C 19 H 16 N ₄ [M + Na] &lt; ⁺ &gt;,323.1273; found, 323.1267. 21

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, DMSO-} d 6) δ 3.80 (s, 3H), 4.81 (s, 2H), 6.88-6.95 (m, 2H) 7.02 (d, J = 1.7 Hz, 1H), 7.78-7.80 (m, 2H), 8.21 (s, 1H), 8.40 (d, J = 1.9 Hz, 1H), 8.47 (d, J = 1.9 Hz, 1H), 8.54-8.56 1H). HRMS (EI +) m / z calcd for C 19 H 16 N 4 O [M + H] +, 317.1402; found, 317.1384. 22

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 2.35 (s, 6H), 2.77 (t, J = 6.0 Hz, 2H), 4.07 (s, 2H), 4.15 (t, J = 6.0 Hz, 2H ), 6.91-6.96 (m, 2H), 6.96 (s, IH), 7.56 (d, J = 5.0 Hz, 2H) , 8.62 (d, J = 5.1 Hz, 2H), 10.73 (s, 1H). HRMS (EI +) m / z calcd for C 22 H 23 N 5 O [M + H] +, 374.1981; found, 374.1982. 23

2,3-b] pyridin-5-yl) phenyl) (morpholino) methanone ^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.72-3.70 (m, 8H), 4.53 (s, 2H), 6.99-6.97 (m, 2H), 7.20 (d, J = 8.3 Hz, 1H) , 7.58 (d, J = 5.5 Hz, 2H), 7.72 (s, 1H), 8.38 (s, 1H), 8.59 (s, 1H), 8.65 (d, J = 5.6 Hz, 2H), 9.55 (s, 1H). HRMS (EI +) m / z Calcdfor C ₂₃ H ₂₁ N ₅ O ₂ [M + H] ⁺ , 400.1773; found, 400.1808. 24

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, CDCl} 3 - d 1) δ 3.84 (m, 5H), 6.28 (t, J = 2.0 Hz, 1H), 6.56 (dd, J = 1.8 Hz, 8.0, 2H), 7.56-7.58 (m, 2H), 7.72 ( d, J = 1.7 Hz, 1H), 8.39 (d, J = 1.9 Hz, 1H), 8.59 (d, J = 2.0 Hz, 1H), 8.63-6.65 (m, 2H) , 10.02 (s, 1 H). HRMS (EI +) m / z calcd for C 19 H 16 N 4 O [M + H] +, 317.1402; found, 317.1390. 25

(3-amino-5- (3- (pyridin-4-yl) -lH-pyrrolo [2,3- b] pyridin- ^{1 H NMR (400 MHz, CDCl} 3 - d 1, 60 ℃) δ 3.64-3.67 (m, 8H), 3.85 (s, 2H), 6.70 (dd, J = 1.4 Hz, 2.2, 1H), 6.95 (t , J = 1.8 Hz, 1H) , 7.00 (t, J = 1.4 Hz, 1H), 7.54-7.55 (m, 2H), 7.66 (s, 1H), 8.35 (d, J = 2.0 Hz, 1H), 8.56 (d, J = 2.0 Hz, 1H), 8.64-8.66 (m, 2H), 9.03 (s, 1H). HRMS (EI +) m / z calcd for C ₂₃ H ₂₁ N ₅ O ₂ [M + H] ⁺ , 400.1773; found, 400.1752. 26

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzenesulfonamide ^{1 H NMR (300 MHz, DMSO-} d 6) δ 5.26 (s, 2H), 6.43 (s, 1H), 6.52 (s, 1H), 6.56 (s, 1H), 7.60-7.53 (m, 3H), 7.74 (d, J = 5.9 Hz , 2H), 7.82 (d, J = 7.0, 2H), 8.23 (s, 1H), 8.26 (s, 1H), 8.30 (s, 1H), 8.56 (d, J = 5.7 Hz, 2H), 10.13 (s, 1H), 12.25 (s, 1H). HRMS (EI +) m / z calcd for C ₂₄ H ₁₉ N ₅ O ₂ S [M + H] ⁺ , 442.1338; found 442.1349. 27

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) -2,4-difluorobenzenesulfonamide ^{1 H NMR (300 MHz, MeOD-} d 4) δ6.75-6.61 (m, 2H), 6.96 (d, J = 8.5 Hz, 1H), 7.12 (t, J = 7.5 Hz, 2H), 7.27-7.21 (m, 2H), 7.42-7.30 (m, 2H), 7.84-7.75 (m, 2H), 8.05 (s, 1H), 8.11 (s, 2H), 8.54 (d, J = 5.5 Hz, 2H). HRMS (EI +) m / z calcd for C ₂₄ H ₁₇ F ₂ N ₅ O ₂ S [M + H] ⁺ , 478.1149; found, 478.1120. 28

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) -4-methylbenzenesulfonamide ^{1 H NMR (300 MHz, DMSO-} d 6) δ2.31 (s, 3H), 5.26 (s, 2H), 6.42 (s, 1H), 6.54 (d, J = 5.8 Hz, 2H), 7.34 (d , J = 8.2 Hz, 2H) , 7.69 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 6.1 Hz, 2H), 8.23 (s, 1H), 8.28 (d, J = 2.0 Hz, 1H ), 8.31 (d, J = 1.9 Hz, 1H), 8.56 (d, J = 6.0 Hz, 2H), 10.00 (s, 1H), 12.27 (s, 1H). HRMS (EI +) m / z calcd for C 25 H 21 N 5 O 2 S [M + H] +, 456.1494; found, 456.1476. 29

Yl) phenyl) -3- (trifluoromethyl) benzenesulfonamide The title compound, MS: m / e = Amide ^{1 H NMR (300 MHz, DMSO-} d 6) δ 1 H NMR (DMSO-d 6, 300 MHz) δ 5.33 (s, 2H), 6.44 (s, 1H), 6.50 (s, 1H), 6.60 (s , 1H), 7.74 (d, J = 6.1 Hz, 2H), 7.83 (m, 1H), 8.00 (d, J = 7.5 Hz, 1H), 8.07 (s, 2H), 8.24 (d, J = 2.6 Hz , 8.28 (d, J = 3.8 Hz, 2H), 8.55 (d, J = 6.0 Hz, 2H), 10.23 (s, 1H), 12.30 (s, 1H). HRMS (EI +) m / z calcd for C 25 H 18 F 3 N 5 O 2 S [M + H] +, 510.1212; found, 510.1183. 30

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) methanesulfonylamide ^{1 H NMR (300 MHz, DMSO-} d 6) δ2.99 (s, 3H), 5.34 (s, 2H), 6.51 (s, 1H), 6.66 (s, 2H), 7.77 (d, J = 6.1 Hz 2H), 8.24 (s, IH), 8.39 (s, IH), 8.44 (s, IH), 8.55 (d, J = 6.0 Hz, 2H), 12.30 (s, HRMS (EI +) m / z calcd for C 19 H 17 N 5 O 2 S [M + H] +, 380.1181; found, 380.1179. 31

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) acetamide ¹ H NMR (300 MHz, DMSO-d ₆ )? 2.02 (s, 3H), 5.22 (s, 2H), 6.60 (s, (d, J = 6.1 Hz, 2H), 8.24 (d, J = 2.6 Hz, 1H), 8.39 (s, 1H), 8.44 (d, J = 1.8 Hz, 1H), 8.56 (d, J = 6.1 Hz , 2H), 9.74 (s, 1 H), 12.28 (s, 1 H). HRMS (EI +) m / z calcd for C 20 H 17 N 5 O [M + Na] +, 366.1331; found, 344.1328. 32

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, MeOD-} d 4) δ 3.01 (s, 6H), 3.64 (t, J = 5.0 Hz, 2H), 4.46 (t, J = 4.9 Hz, 2H), 6.76 (t, J = 1.9 Hz, 1H), 7.09 ( s, 2H), 8.42 (d, J = 7.0 Hz, 2H), 8.57 (s, 1H), 8.67-8.65 (m, 3H), 8.71 (d, J = 1.9 Hz, 1H) .HRMS (EI +) m / z calcdfor C 22 H 23 N 5 O [M + H] +, 374.1981; found, 374.2013. 33

LH-pyrrolo [2,3-b] pyridin-5-yl) aniline ^{1 H NMR (300 MHz, MeOD-} d 4) δ2.63 (t, J = 4.6 Hz, 4H), 2.83 (t, J = 5.4 Hz, 2H), 3.72 (t, J = 4.7 Hz, 4H), 4.17 (t, J = 5.4 Hz , 2H), 6.35 (s, 1H), 6.58 (s, 1H), 6.65 (s, 1H), 7.79 (d, J = 6.4 Hz, 2H), 8.01 (s, 1H ), 8.52-8.48 (m, 4H). HRMS (EI +) m / z Calcdfor C ₂₄ H ₂₅ N ₅ O ₂ [M + H] ⁺ , 416.2087; found, 416.2086. 34

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzenesulfonamide ^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.52 (s, 3H), 5.27 (s, 2H), 6.42 (s, 1H), 6.55-6.53 (m, 2H), 7.60-7.49 (m, 5H ), 7.82-7.80 (m, 2H) , 8.18 (d, J = 2.4 Hz, 1H), 8.25 (d, J = 1.9 Hz, 1H), 8.29 (d, J = 1.9 Hz, 1H), 8.43 (d , J = 5.2 Hz, 1 H), 10.09 (s, 1 H), 12.23 (s, 1 H). HRMS (EI +) m / z calcdfor C 25 H 21 N 5 O 2 S [M + H] +, 456.1494; found, 456.1473. 35

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzenesulfonamide ^{1 H NMR (300 MHz, DMSO-} d 6) δ 2.35 (s, 3H), 5.22 (s, 2H), 6.39 (s, 1H), 6.46 (s, 1H), 6.50 (s, 1H), 7.43 ( d, J = 5.0 Hz, 1H ), 7.56-7.48 (m, 3H), 7.83-7.77 (m, 4H), 8.32 (d, J = 1.9 Hz, 1H), 8.45 (d, J = 5.0 Hz, 1H ), 8.53 (s, IH), 10.13 (s, IH), 12.18 (s, IH). HRMS (EI +) m / z calcdfor C 25 H 21 N 5 O 2 S [M + H] +, 456.1494; found, 456.1473. 36

LH-pyrrolo [2,3-b] pyridin-5-yl) phenyl) benzenesulfonamide ^{1 H NMR (300 MHz, MeOD-} d 4) δ6.75-6.61 (m, 2H), 6.96 (d, J = 8.5 Hz, 1H), 7.12 (t, J = 7.5 Hz, 2H), 7.27-7.21 (m, 2H), 7.42-7.30 (m, 2H), 7.84-7.75 (m, 2H), 8.05 (s, 1H), 8.11 (s, 2H), 8.54 (d, J = 5.5 Hz, 2H). HRMS (EI +) m / z calcd for C ₂₄ H ₁₉ N ₅ O ₂ S [M + H] ⁺ , 442.1338; found, 442.1320.

Experimental Example 1 Trk inhibitory activity assay.

The activity of the Trk inhibitory activity of the azaindole derivative represented by formula (1) according to the present invention was measured as follows.

In order to measure the biological and biochemical inhibitory effects of Trk inhibitor, TkrA activity was measured by Reaction Biology Corp. (Malvern, PA, USA), and the activity was measured according to the concentration. The measured results are shown in Table 2 below as IC ₅₀ values.

IC ₅₀ is the molar concentration of the compound used when the activity of the enzyme is inhibited to 50%.

The TrkA IC ₅₀ division TrkA IC ₅₀ 7 <1 μM 22 <1 μM 9 <1 μM 23 <1 μM 10 <1 μM 24 <1 μM 11 <1 μM 25 <1 μM 12 <1 μM 26 <1 μM 13 <1 μM 27 <1 μM 14 <1 μM 28 <1 μM 15 <1 μM 29 <1 μM 16 <1 μM 30 <1 μM 17 <1 μM 31 <1 μM 18 <1 μM 32 <1 μM 19 <1 μM 33 <1 μM 20 <1 μM 34 <1 μM 21 <1 μM 35 <1 μM

As shown in <Experimental Example 1> and <Table 2>, the azaindole derivative compound of the present invention represented by the formula (1) according to the present invention exhibited a 50% inhibition of the activity of Trk, It can be confirmed that the effect of Trk inhibition is also small even in a small amount of less than μM.

Claims (1)

An azaindole derivative which is any one selected from the group consisting of the following formulas (1) to (33)