KR20210105102A - Pharmaceutical Composition for preventing or treating asthma or bronchitis - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of asthma or bronchitis, wherein the pharmaceutical composition according to the present invention significantly reduces the number of inflammatory cells and inflammatory cytokines in alveolar lavage fluid in a mouse model of asthma, and significantly alleviates side effects of lymphopenia, so that it is expected to be widely used as an agent for alleviating, preventing, or treating asthma or bronchitis without side effects.

Description

The pharmaceutical composition for preventing or treating asthma or bronchitis {Pharmaceutical Composition for preventing or treating asthma or bronchitis}

The present invention relates to a pharmaceutical composition for preventing or treating asthma or bronchitis.

Bronchitis is a disease in which the bronchial mucosa is damaged by stimuli such as viruses, bacteria, smoking, air pollution, and dust, and a large amount of inflammation and mucus is generated, causing symptoms such as sputum and cough.

Asthma is a chronic inflammatory disease of the airways or lungs caused by a complex immune response. Extensive stenosis of the airway is caused by various stimuli, which causes clinical symptoms such as wheezing, shortness of breath, and cough, which can be improved spontaneously or by treatment. Most asthma is an allergic disease common in modern society. In addition to chronic airway inflammation, allergen-specific immunoglobulin (Immunoglobulin E, IgE) antibodies are formed, or airway obstruction due to excessive secretion of airway mucus and airway hypersensitivity appears.

Asthma can be divided into allergic asthma and non-allergic asthma according to the cause. In the case of allergic asthma, symptoms appear when exposed to a causative antigen. Skin tests or bronchial provocation tests for the causative antigen show a positive result, and the onset age is usually young. House dust and mites are the most common causative antigens, while pollen, animal epithelium, mold, etc. act as causative antigens. In the case of non-allergic asthma, upper respiratory tract infection, exercise, emotional instability, and changes in cold climate and humidity cause or worsen asthma, which is commonly seen in adult asthma. Others include drug-induced asthma, exercise-induced asthma, and occupational asthma.

Various asthma treatments have been used so far, but a significant number of treatments require caution when using them due to many side effects. Currently, inhaled corticosteroids are the most used treatment and show excellent effects, but when used for a long period of time, they are known to cause adrenal suppression, decreased bone density, growth disorders, and complications of the eyes and skin in proportion to the dose and time of use. . In addition, if asthma is not controlled during the growth period, growth of the whole body as well as the lungs may be inhibited, so maintaining normal lung function through steady treatment is essential for growth. However, as it has been found that it is most important to use safe drugs for continuous treatment and to manage airway inflammation well, it is necessary to carefully consider the side effects as well as the asthma alleviation effect when selecting a treatment.

Accordingly, the present inventors completed the present invention by confirming that the compound according to the present invention has a preventive or therapeutic effect on asthma or bronchitis while making intensive efforts to develop a therapeutic agent for the respiratory-related disease.

Republic of Korea Patent Publication No. 10-2013-0079281

Accordingly, the present inventors confirmed that the compound of Formula 2 included in the compound of Formula 1 exhibits a significant therapeutic effect on an asthma animal model, and completed the present invention.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating asthma or bronchitis, comprising the compound represented by Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a food composition for preventing or improving asthma or bronchitis, comprising the compound represented by Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating asthma or bronchitis, comprising a compound represented by the following formula (1), an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient to provide.

In addition, the present invention provides a food composition for preventing or ameliorating asthma or bronchitis, comprising as an active ingredient a compound represented by the following formula (1), an optical isomer thereof, or a pharmaceutically acceptable salt thereof:

[Formula 1]

이고;In Formula 1, R ₁ is hydrogen or

ego;

R ₂ is hydrogen, unsubstituted or substituted C _1-5 linear or branched alkylcarbonyl, wherein the substituted alkylcarbonyl is selected from the group consisting of hydroxy, halogen, cyano, nitro and amino. one or more substituents selected are substituted;

A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;

B is C _1-11 linear or branched alkylene;

C is a single bond or C _6-10 arylene;

D is -H, or C _1-15 straight or branched chain alkyl; and

X is a single bond, C _1-5 alkylene, C _2-5 alkenylene or C _2-5 alkynylene.

이고;In one embodiment of the present invention, R ₁ is hydrogen or

ego;

R ₂ is hydrogen, C _1-3 linear or branched alkylcarbonyl,

A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;

B is C _1-9 straight-chain or branched alkylene;

C is a single bond or C _6-10 arylene;

D is -H or C _3-12 straight or branched chain alkyl; and

X may be a single bond, C _1-3 alkylene, C _2-3 alkenylene, or C _2-3 alkynylene, but is not limited thereto.

이고;In another embodiment of the present invention, R ₁ is hydrogen or

ego;

R ₂ is hydrogen or acetyl,

A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;

B is C _2-8 alkylene;

C is a single bond or phenylene;

D is -H, or C _6-10 straight or branched chain alkyl; and

X may be a single bond, -CH ₂ CH ₂ -, -CH=CH-, or -C≡C-, but is not limited thereto.

In another embodiment of the present invention, the compound represented by Formula 1 may be one or more selected from the following compound group, but is not limited thereto:

(1) 2-amino-2-(2-(3-decylisooxazol-5-yl)ethyl)propane-1,3-diol;

(2) 2-amino-2-(2-(1-decyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;

(3) 2-amino-2-((3-octylisooxazol-5-yl)ethynyl)propane-1,3-diol;

(4) 2-amino-2-(2-(3-octylisooxazol-5-yl)ethyl)propane-1,3-diol;

(5) 2-amino-2-(hydroxymethyl)-4-(3-octylisooxazol-5-yl)butyl dihydrogen phosphate;

(6) 2-amino-2-((3-decylisooxazol-5yl)ethynyl)propane-1,3-diol;

(7) 2-amino-4-(3-decylisooxazol-5-yl)-2-(hydroxymethyl)butyl dihydrogen phosphate;

(8) 2-amino-2-(2-(3-(4-hexylphenethyl)isoxazol-5-yl)ethyl)propane-1,3-diol;

(9) 2-amino-2-((3-dodecylisooxazol-5-yl)ethynyl)propane-1,3-diol;

(10) 2-amino-2-(2-(3-dodecylisooxazol-5-yl)ethyl)propane-1,3-diol;

(11) 2-amino-4-(3-dodecylisoxazol-5-yl)-2-(hydroxymethyl)butyl dihydrogen phosphate;

(12) 2-amino-2-(2-(1-octyl-1H-1,2,3-triazol-4-yl)ethynyl)propane-1,3-diol;

(13) 2-amino-2-(2-(1-octyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;

(14) 2-amino-2-((1-decyl-1H-1,2,3-triazol-4-yl)ethynyl)propane-1,3-diol;

(15) 2-amino-2-(2-(1-(4-hexylphenethyl)-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;

(16) 2-amino-2-(1-butyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol;

(17) 2-amino-2-(3-dodecylisooxazol-5-yl)propane-1,3-diol;

(18) (E)-2-amino-2-(2-(3-decylisooxazol-5-yl)vinyl)propane-1,3-diol;

(19) (E)-2-amino-2-(1-butyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol;

(20) 2-amino-2-(2-(3-(8-phenyloctyl)-isooxazol-5-yl)ethyl)propane-1,3-diol;

(21) 2-amino-2-(2-(1-(8-phenyloctyl)-1H-1,2,3-triazolbutyl-4-yl)propane-1,3-diol;

(22) N-(2-(1-dodecyl-1H-1,2,3-triazol-4-yl)-1,3-dihydrooxypropan-2-yl)acetamide;

(23) N-(2-(3-dodecylisoxazol-5-yl)-1,3-dihydrooxypropan-2-yl)acetamide;

(24) N-(4-(1-decyl-1H-1,2,3-triazol-4-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide;

(25) N-(4-(3-decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide; and

(26) N-(4-(1-(4-hexylphenethyl)-1H-1,2,3-triazol-4-yl)-1-hydroxy-2-(hydroxymethyl)butane-2 -il) acetamide.

In another embodiment of the present invention, the compound represented by Formula 1 may be a compound represented by Formula 2 below, but is not limited thereto.

[Formula 2]

In another embodiment of the present invention, the bronchitis is selected from the group consisting of acute bronchitis, chronic bronchitis, allergic bronchitis, infectious bronchitis, traumatic bronchitis, catarrhal bronchitis, suppurative bronchitis, obstructive bronchitis, ulcerative bronchitis and infiltrative bronchitis. It may be one or more, but is not limited thereto.

In another embodiment of the present invention, the asthma may be one or more selected from the group consisting of bronchial asthma, atopic asthma, non-topic asthma, exercise-induced asthma, aspirin asthma, psychogenic asthma, and alveolar asthma, but is limited thereto. it's not going to be

In another embodiment of the present invention, the compound represented by Formula 1 may reduce the number of inflammatory cells in the bronchi or lung, but is not limited thereto.

In another embodiment of the present invention, the compound represented by Formula 1 may improve lymphopenia, but is not limited thereto.

In addition, the present invention provides a method for treating asthma or bronchitis comprising administering to an individual a composition comprising a compound represented by the following formula (1), an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a use for preventing or treating asthma or bronchitis of a composition comprising a compound represented by the following formula (1), an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides the use of the compound represented by the following formula (1) for producing a medicament used for asthma or bronchitis.

The composition comprising the compound of Formula 1 according to the present invention as an active ingredient significantly reduced the number of inflammatory cells and inflammatory cytokines in the alveolar lavage fluid in the asthma mouse model, and significantly improved the side effects of lymphopenia. Asthma without side effects Or it is expected to be widely used as an improvement, prevention, or therapeutic agent for bronchitis.

1 is an eosinophilic asthma mouse model induced with OVA / Alum, and mice using a feed containing the compound of Formula 2 and a general diet (control) to analyze the preventive efficacy of the compound of Formula 2 (compound 2) The breeding protocol is shown.
2 is a histopathological examination result for a mouse model of asthma, A is the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) (macrophages, Macro; lymphocytes, Lymph; neutrophils, Neutro; eosinophils, Eosino), B is IL-4 level in BALF, C indicates the infiltration of inflammatory cells through lung histologic examination.
3 shows a nasal administration protocol of the compound of Formula 2, which was carried out to induce an eosinophilic asthma mouse model with OVA/Alum, and to analyze the anti-inflammatory therapeutic efficacy of the compound of Formula 2 (compound 2).
Figure 4 shows the results of nasal administration, A is the number of inflammatory cells in BALF (macrophages, Macro; lymphocytes, Lymph; neutrophils, Neutro; eosinophils, Eosino), B is the IL-4 and IL-17 levels in BALF. will be.
5 shows a single or three nasal administration protocol for inducing a mouse model of eosinophilic asthma with OVA/Alum and analyzing the anti-inflammatory therapeutic efficacy according to the number of administrations of the compound of Formula 2 (compound 2).
Figure 6 shows the results according to the number of administration, A is the number of inflammatory cells in BALF (macrophages, Macro; lymphocytes, Lymph; neutrophils, Neutro; eosinophils, Eosino), B is the IL-4 level in BALF, C is the lung IL-4, IL-17, IFN-γ levels in cells and lymphocytes are shown.
7 is an eosinophilic asthma mouse model induced by OVA / Alum, and the compound of Formula 2 and FTY720 (S1PR inhibitor), dexamethasone to verify the efficacy and side effects of the compound of Formula 2 (compound 2) and existing therapeutic agents This is a protocol to check whether lymphopenia, known as a major side effect of S1PR agonists, occurs after each nasal administration.
8 is a result showing the number of pulmonary inflammatory cells and lymphocytes according to the administration (5 mpk, 1 mpk) of the compound of Formula 2 (S, compound 2), FTY720 (F), and dexamethasone (D).

The present invention provides a pharmaceutical composition for preventing or treating asthma or bronchitis, comprising a compound represented by Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

이고;(In Formula 1, R ₁ is hydrogen or

ego;

R ₂ is hydrogen, unsubstituted or substituted C _1-5 linear or branched alkylcarbonyl, wherein the substituted alkylcarbonyl is selected from the group consisting of hydroxy, halogen, cyano, nitro and amino. one or more substituents selected are substituted;

A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;

B is C _1-11 linear or branched alkylene;

C is a single bond or C _6-10 arylene;

D is -H, or C _1-15 straight or branched chain alkyl; and

X is a single bond, C _1-5 alkylene, C _2-5 alkenylene or C _2-5 alkynylene.)

이고;In addition, in Formula 1, R ₁ is hydrogen or

ego;

R ₂ is hydrogen, C _1-3 linear or branched alkylcarbonyl,

A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;

B is C _1-9 straight-chain or branched alkylene;

C is a single bond or C _6-10 arylene;

D is -H or C _3-12 straight or branched chain alkyl; and

X may be a single bond, C _1-3 alkylene, C _2-3 alkenylene or C _2-3 alkynylene.

이고;In addition, in Formula 1, R ₁ is hydrogen or

ego;

R ₂ is hydrogen or acetyl,

A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;

B is C _2-8 alkylene;

C is a single bond or phenylene;

D is -H, or C _6-10 straight or branched chain alkyl; and

X may be a single bond, -CH ₂ CH ₂ -, -CH=CH- or -C≡C-.

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

(1) 2-amino-2-(2-(3-decylisooxazol-5-yl)ethyl)propane-1,3-diol;

(2) 2-amino-2-(2-(1-decyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;

(3) 2-amino-2-((3-octylisooxazol-5-yl)ethynyl)propane-1,3-diol;

(4) 2-amino-2-(2-(3-octylisooxazol-5-yl)ethyl)propane-1,3-diol;

(5) 2-amino-2-(hydroxymethyl)-4-(3-octylisooxazol-5-yl)butyl dihydrogen phosphate;

(6) 2-amino-2-((3-decylisooxazol-5yl)ethynyl)propane-1,3-diol;

(7) 2-amino-4-(3-decylisooxazol-5-yl)-2-(hydroxymethyl)butyl dihydrogen phosphate;

(8) 2-amino-2-(2-(3-(4-hexylphenethyl)isoxazol-5-yl)ethyl)propane-1,3-diol;

(9) 2-amino-2-((3-dodecylisooxazol-5-yl)ethynyl)propane-1,3-diol;

(10) 2-amino-2-(2-(3-dodecylisooxazol-5-yl)ethyl)propane-1,3-diol;

(11) 2-amino-4-(3-dodecylisoxazol-5-yl)-2-(hydroxymethyl)butyl dihydrogen phosphate;

(12) 2-amino-2-(2-(1-octyl-1H-1,2,3-triazol-4-yl)ethynyl)propane-1,3-diol;

(13) 2-amino-2-(2-(1-octyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;

(14) 2-amino-2-((1-decyl-1H-1,2,3-triazol-4-yl)ethynyl)propane-1,3-diol;

(15) 2-amino-2-(2-(1-(4-hexylphenethyl)-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;

(16) 2-amino-2-(1-butyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol;

(17) 2-amino-2-(3-dodecylisooxazol-5-yl)propane-1,3-diol;

(18) (E)-2-amino-2-(2-(3-decylisooxazol-5-yl)vinyl)propane-1,3-diol;

(19) (E)-2-amino-2-(1-butyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol;

(20) 2-amino-2-(2-(3-(8-phenyloctyl)-isooxazol-5-yl)ethyl)propane-1,3-diol;

(21) 2-amino-2-(2-(1-(8-phenyloctyl)-1H-1,2,3-triazolbutyl-4-yl)propane-1,3-diol;

(22) N-(2-(1-dodecyl-1H-1,2,3-triazol-4-yl)-1,3-dihydrooxypropan-2-yl)acetamide;

(23) N-(2-(3-dodecylisoxazol-5-yl)-1,3-dihydrooxypropan-2-yl)acetamide;

(24) N-(4-(1-decyl-1H-1,2,3-triazol-4-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide;

(25) N-(4-(3-decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide; and

(26) N-(4-(1-(4-hexylphenethyl)-1H-1,2,3-triazol-4-yl)-1-hydroxy-2-(hydroxymethyl)butane-2 -il) acetamide.

The chemical structures of (1) to (26) are shown in Table 1 below.

No. chemical structure No. chemical structure (One)

(14)

(2)

(15)

(3)

(16)

(4)

(17)

(5)

(18)

(6)

(19)

(7)

(20)

(8)

(21)

(9)

(22)

(10)

(23)

(11)

(24)

(12)

(25)

(13)

(26)

In addition, examples of the compound represented by Formula 1 according to the present invention include 2-amino-2-(2-(1-decyl-1H-1,2,3-triazole-) which is a compound represented by Formula 2 below. 4-yl)ethyl)propane-1,3-diol.

[Formula 2]

The compound represented by Formula 1 according to the present invention may be purchased commercially or may be prepared by a known method. In the present specification, the compound represented by Formula 1 refers to a compound represented by Formula 1 and a racemate thereof. , enantiomers, isomers, hydrates, and solvates are used in the meaning of all.

As used herein, the term “asthma” refers to a condition in which the bronchi in the lungs are very sensitive, sometimes narrowing the bronchi, causing shortness of breath and a croaking sound, and a disease showing severe coughing, allergic inflammatory reaction of the bronchial tubes. It is an allergic disease caused by The typical symptoms of asthma are shortness of breath, cough, wheezing (wheezing, rough breathing), etc. A symptom reliever (bronchodilator) that relieves narrowed bronchi in a short time, or a disease control agent that prevents asthma attacks by suppressing allergic inflammation of the bronchi ( Anti-inflammatory drugs and leukotriene modulators) are used as representative therapeutic agents. In the present invention, the asthma may be bronchial asthma, atopic asthma, non-topic asthma, exercise-induced asthma, aspirin asthma, psychogenic asthma, or alveolar asthma, but is not limited thereto.

As used herein, the term “bronchitis” includes acute bronchitis, chronic bronchitis, allergic bronchitis, infectious bronchitis, traumatic bronchitis, catarrhal bronchitis, suppurative bronchitis, obstructive bronchitis, ulcerative bronchitis and infiltrative bronchitis, but is limited thereto. no.

In one embodiment of the present invention, as a result of feeding the asthma mouse model a feed containing the compound of Formula 2, the number of inflammatory cells and the inflammatory cytokine IL-4 in the alveolar lavage fluid were significantly reduced as compared to the general feed intake control group, As a result of the lung histopathology, it was confirmed that the infiltration of inflammatory cells was significantly reduced (see Example 1 and FIG. 2).

In another embodiment of the present invention, as a result of nasal administration of the compound of Formula 2 to an asthma mouse model, the number of inflammatory cells in the alveolar lavage fluid was significantly reduced compared to the non-administration group, and the inflammatory cytokines IL-4 and IL-17 were significantly It was confirmed that the decrease (see Example 2 and Figure 4).

In another embodiment of the present invention, as a result of nasal administration of the compound of Formula 2 once or three times to a mouse model of asthma, the number of inflammatory cells in the alveolar lavage fluid was significantly reduced, and the number of inflammatory cells in the lung cells was significantly reduced according to the number of administrations. It was confirmed that the cytokines IL-4, IL-17 and IFN-γ were significantly reduced (see Example 3 and Figure 6).

In another embodiment of the present invention, as a result of administering the compound of Formula 2, FTY720, and dexamethasone to a mouse model of asthma, respectively, it was confirmed that the compound of Formula 2 can be safely used without side effects because there is no lymphopenia (Example) 4 and 8).

The present invention may also include a pharmaceutically acceptable salt of the compound represented by Formula 1 as an active ingredient. As used herein, the term "pharmaceutically acceptable salt" includes salts derived from pharmaceutically acceptable inorganic acids, organic acids, or bases.

Examples of suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid , benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, hydrobromic acid, hydroiodic acid, nitrous acid, benzoic acid, citric acid, lactic acid, and the like. Acid addition salts can be prepared by conventional methods, for example, by dissolving a compound in an aqueous solution of an excess of acid, and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. It can also be prepared by heating an equimolar amount of the compound and an acid or alcohol in water and then evaporating the mixture to dryness, or by suction filtration of the precipitated salt.

Salts derived from suitable bases may include, but are not limited to, alkali metals such as sodium and potassium, alkaline earth metals such as magnesium, and ammonium. The alkali metal or alkaline earth metal salt can be obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. In this case, it is pharmaceutically suitable to prepare a sodium, potassium or calcium salt as the metal salt, and the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

The content of the compound in the composition of the present invention can be appropriately adjusted according to the symptoms of the disease, the degree of progression of the symptoms, the condition of the patient, etc., for example, 0.0001 to 99.9% by weight, 0.001 to 80% by weight or 0.01 based on the total weight of the composition. to 50% by weight, but is not limited thereto. The content ratio is a value based on the dry amount from which the solvent is removed.

The pharmaceutical composition according to the present invention may further include suitable carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions. The excipient may be, for example, at least one selected from the group consisting of a diluent, a binder, a disintegrant, a lubricant, an adsorbent, a humectant, a film-coating material, and a controlled-release additive.

The pharmaceutical composition according to the present invention can be prepared according to a conventional method according to a conventional method, such as powders, granules, sustained-release granules, enteric granules, liquids, eye drops, elsilic, emulsions, suspensions, alcohols, troches, fragrances, and limonaade. , tablets, sustained release tablets, enteric tablets, sublingual tablets, hard capsules, soft capsules, sustained release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, perfusates, Warnings, lotions, pastas, sprays, inhalants, patches, sterile injection solutions, or external preparations such as aerosols can be formulated and used, and the external preparations are, for example, creams, gels, patches, sprays, ointments, etc. , a warning agent, a lotion, a liniment agent, a pasta agent, or a cataplasma agent.

Carriers, excipients and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

In the case of formulation, it is prepared using diluents or excipients, such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Corn starch, potato starch, wheat starch, lactose, sucrose, glucose, fructose, di-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, phosphoric acid as additives for tablets, powders, granules, capsules, pills, and troches according to the present invention Calcium monohydrogen, calcium sulfate, sodium chloride, sodium hydrogen carbonate, purified lanolin, microcrystalline cellulose, dextrin, sodium alginate, methyl cellulose, sodium carboxymethyl cellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropyl methyl excipients such as cellulose, 1928, 2208, 2906, 2910, propylene glycol, casein, calcium lactate, and primogel; Gelatin, gum arabic, ethanol, agar powder, cellulose acetate phthalate, carboxymethylcellulose, calcium carboxymethylcellulose, glucose, purified water, sodium caseinate, glycerin, stearic acid, sodium carboxymethylcellulose, sodium methylcellulose, methylcellulose, microcrystalline cellulose, dextrin , hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, purified shellac, starch powder, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, etc. Hydroxypropyl methylcellulose, corn starch, agar powder, methylcellulose, bentonite, hydroxypropyl starch, sodium carboxymethylcellulose, sodium alginate, calcium carboxymethylcellulose, calcium citrate, sodium lauryl sulfate, silicic anhydride, 1-hydroxy Propylcellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde treated casein and gelatin, alginic acid, amylose, guar gum, sodium bicarbonate, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, disintegrants such as amylopectin, pectin, sodium polyphosphate, ethyl cellulose, sucrose, magnesium aluminum silicate, di-sorbitol solution, light anhydrous silicic acid; Calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopodite, kaolin, petrolatum, sodium stearate, cacao butter, sodium salicylate, magnesium salicylate, polyethylene glycol 4000, polyethylene glycol 6000, liquid paraffin, hydrogenated soybean oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, macrogol, synthetic aluminum silicate, silicic anhydride, higher fatty acids, higher alcohols, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, starch, A lubricant such as sodium chloride, sodium acetate, sodium oleate, dl-leucine, light silicic anhydride; may be used.

The liquid additives according to the present invention include water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, monostearate sucrose, polyoxyethylene sorbitol fatty acid esters (Twinester), polyoxyethylene monoalkyl ethers, lanolin ethers, Lanolin esters, acetic acid, hydrochloric acid, aqueous ammonia, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethyl cellulose, sodium carboxymethyl cellulose, and the like can be used.

In the syrup according to the present invention, a sucrose solution, other sugars or sweeteners may be used, and if necessary, a fragrance, colorant, preservative, stabilizer, suspending agent, emulsifying agent, thickening agent, etc. may be used.

Purified water may be used in the emulsion according to the present invention, and if necessary, an emulsifier, preservative, stabilizer, fragrance, etc. may be used.

Suspending agents such as acacia, tragacantha, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose, 1828, 2906, and 2910 may be used in the suspending agent according to the present invention, If necessary, surfactants, preservatives, stabilizers, colorants, and fragrances may be used.

Injectables according to the present invention include distilled water for injection, 0.9% sodium chloride injection, ring gel injection, dextrose injection, dextrose + sodium chloride injection, PEG (PEG), lactated ring gel injection, ethanol, propylene glycol, non-volatile oil-sesame oil , solvents such as cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristate, and benzene benzoate; Solubilizing aids such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, tweens, nijeongtinamide, hexamine, and dimethylacetamide; Weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, buffers such as albumin, peptone, gum; isotonic agents such as sodium chloride; sodium bisulfite (NaHSO ₃ ) carbon dioxide gas, sodium metabisulfite (Na ₂ S ₂ O ₃ ), sodium sulfite (Na ₂ SO ₃ ), nitrogen gas (N ₂ ), stabilizers such as ethylenediaminetetraacetic acid; sulphating agents such as sodium bisulfide 0.1%, sodium formaldehyde sulfoxylate, thiourea, disodium ethylenediaminetetraacetate, acetone sodium bisulfite; analgesic agents such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; suspending agents such as SiMC sodium, sodium alginate, Tween 80, and aluminum monostearate.

The suppository according to the present invention includes cacao fat, lanolin, Witepsol, polyethylene glycol, glycerogelatin, methyl cellulose, carboxymethyl cellulose, a mixture of stearic acid and oleic acid, Subanal, cottonseed oil, peanut oil, palm oil, cacao butter + Cholesterol, Lecithin, Lanet Wax, Glycerol Monostearate, Tween or Span, Imhausen, Monolene (Propylene Glycol Monostearate), Glycerin, Adeps Solidus, Butyrum Tego -G), Cebes Pharma 16, Hexalide Base 95, Cotomar, Hydroxote SP, S-70-XXA, S-70-XX75 (S-70-XX95), Hydro Hydrokote 25, Hydrokote 711, Idropostal, Massa estrarium, A, AS, B, C, D, E, I, T, Massa-MF, Masupol, Masupol-15, Neosupostal-N, Paramound-B, Suposiro (OSI, OSIX, A, B, C, D, H, L), Suppository IV type (AB, B, A, BC, BBG, E, BGF, C, D, 299), supostal (N, Es), Wecobi (W, R, S, M, Fs), tester triglyceride base (TG-95, MA, 57) and The same mechanism may be used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations include at least one excipient in the extract, for example, starch, calcium carbonate, sucrose ) or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate talc are also used.

Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, drug activity, and type of the patient's disease; Sensitivity to the drug, administration time, administration route and excretion rate, treatment period, factors including concurrent drugs and other factors well known in the medical field may be determined. The dosage of the composition of the present invention is 0.1 mg/kg to 100 mg/kg, 0.1 mg/kg to 50 mg/kg, 0.1 mg/kg to 40 mg/kg, 0.1 mg/kg to 1 day based on the active ingredient. 30 mg/kg, 0.1 mg/kg to 20 mg/kg, 0.1 mg/kg to 10 mg/kg, or 1 mg/kg to 10 mg/kg, but is not limited thereto. Administration may be administered once a day, or may be administered in several divided doses.

The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple. In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by a person skilled in the art to which the present invention pertains.

The pharmaceutical composition of the present invention may be administered to an individual by various routes. All modes of administration can be envisaged, for example, oral administration, subcutaneous injection, intraperitoneal administration, intravenous injection, intramuscular injection, paraspinal (intrathecal) injection, sublingual administration, buccal administration, rectal insertion, vaginal It can be administered according to internal insertion, ocular administration, ear administration, nasal administration, inhalation, spraying through the mouth or nose, skin administration, transdermal administration, and the like.

The pharmaceutical composition of the present invention is determined according to the type of drug as an active ingredient along with several related factors such as the disease to be treated, the route of administration, the patient's age, sex, weight, and the severity of the disease.

In the present invention, "individual" means a subject in need of treatment for a disease, and more specifically, human or non-human primates, mice, rats, dogs, cats, horses, cattle, etc. means the mammals of

In the present invention, "administration" means providing a predetermined composition of the present invention to an individual by any suitable method.

In the present invention, “prevention” means any action that suppresses or delays the onset of a target disease, and “treatment” means that the target disease and metabolic abnormalities are improved or It means all actions that are beneficially changed, and “improvement” means all actions that reduce the parameters related to the desired disease, for example, the degree of symptoms by administration of the composition according to the present invention.

In addition, the present invention provides a food composition comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

As used herein, the term “food pharmaceutically acceptable salt” includes salts derived from pharmaceutically acceptable organic acids, inorganic acids, or bases.

When the compound represented by Formula 1 of the present invention is used as a food additive, the compound may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In general, in the production of food or beverage, the compound of the present invention is added in an amount of 15% by weight or less, or 10% by weight or less based on the raw material. However, in the case of long-term intake for health and hygiene or health control, the amount may be less than 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.

There is no particular limitation on the type of the food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and includes all health functional foods in the ordinary sense.

The health beverage composition according to the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients, like a conventional beverage. The above-mentioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as taumatine and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01-0.20 g, or about 0.04-0.10 g per 100 mL of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, Carbonating agents used in carbonated beverages, etc. may be contained. In addition, the composition of the present invention may contain fruit for the production of natural fruit juice, fruit juice beverage, and vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not critical, but is generally selected in the range of 0.01-0.20 parts by weight per 100 parts by weight of the composition of the present invention.

In addition, the present invention provides a veterinary composition comprising the compound as an active ingredient.

The veterinary composition of the present invention may further include appropriate excipients and diluents according to conventional methods. The excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, Polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearyl alcohol, liquid paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben and mineral oil, but are not limited thereto. In addition, the veterinary composition according to the present invention may further include a filler, an anti-agglomeration agent, a lubricant, a wetting agent, a spice, an emulsifier, a preservative, and the like.

The veterinary composition according to the present invention may be formulated using methods well known in the art to provide rapid, sustained or delayed release of an active ingredient after administration to an animal, and the formulation may be a powder, granule, tablet, It may be in the form of capsules, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, suppositories, sterile injection solutions, sterile external preparations, and the like, but is not limited thereto.

The dosage of the veterinary composition according to the present invention may vary depending on the age, sex, and weight of the animal, but an amount of 0.0001 to 100 mg/kg may be administered once to several times a day, and the route of administration, the degree of disease , may be increased or decreased according to gender, weight, age, etc. Accordingly, the above dosage does not limit the scope of the present invention in any way.

Hereinafter, preferred examples are presented to help the understanding of the present invention. However, the following examples are only provided for easier understanding of the present invention, and the contents of the present invention are not limited by the following examples.

Example 1. Confirmation of the effect of the feed containing the compound of Formula 2 on the asthma mouse animal model

A mouse model of eosinophilic asthma was induced with egg white albumin/aluminum (OVA/Alum), and in order to analyze the preventive efficacy of the compound of Formula 2, a feed containing 10 mg/kg of the compound of Formula 2 and a general diet (control) were used. were reared for 4 weeks.

Specifically, according to the experimental protocol shown in FIG. 1, 20 μg of ovalbumin and 2 mg of Alum were mixed with PBS on days 0 and 14 to make 200 μL, and then administered intraperitoneally to induce systemic sensitization to ovalbumin. At 21-23 days, an animal model of asthma was induced by nasal sensitization with 50 μg of egg white albumin. After one day, mice were dissected and the number of inflammatory cells (macrophages, lymphocytes, neutrophils, eosinophils) in bronchoalveolar lavage fluid (BALF) was analyzed, respectively. After perfusion of the lung tissue with physiological saline, the left lung was fixed in 10% formalin for histopathological examination, and the rest was separated for protein and RNA extraction and stored at -80°C. The fixed lung tissue was fixed for one day and then embedded using paraffin melted at a temperature of less than 61 ° C. The reaction was confirmed.

Inflammatory cell counting was performed as follows. The total number of cells introduced into the bronchi and alveoli was counted using a hemocytometer and trypan blue reagent, and then, 100,000 cells were plated on a slide. After staining the smeared cells using Diff-quick reagent, 300-400 cells were sampled and counted through a microscope according to the characteristics of each cell. Through this, the fraction of each cell was derived, and the number of inflammatory cells was calculated by multiplying the total number of cells.

As a result, as shown in A of FIG. 2, eosinophils in BALF were significantly reduced in the group fed the feed containing the compound of Formula 2 compared to the control group.

In addition, as shown in FIG. 2B , when the amount of inflammatory cytokines in BALF was measured, it was confirmed that IL-4 related to the Th2 inflammatory response was significantly reduced by the compound of Formula 2 .

In addition, as shown in FIG. 2C , it was confirmed that the inflammatory cell infiltration was significantly reduced by the compound of Formula 2 in the lung pathologic examination.

That is, when the OVA (ovalbumin)/Alum-induced asthma mouse model was ingested in advance with a feed containing the compound of Formula 2 before asthma induction, compared to the control group fed with the general feed, the alveolar lavage fluid (BALF) The number of inflammatory cells and IL-4, an inflammatory cytokine, were significantly reduced, and it was confirmed that the inflammatory cell infiltration was significantly reduced in the lung histopathology examination.

Example 2. Confirmation of the effect of nasal administration of the compound of Formula 2 on the asthma mouse animal model

A mouse model of eosinophilic asthma was induced with egg white albumin/aluminum (OVA/Alum), and the compound of Formula 2 was intranasally administered (1 mg/kg, 5 mg/kg, 10 mg/kg) to analyze the therapeutic efficacy of the compound of Formula 2. .

Specifically, according to the experimental protocol shown in FIG. 3, mice were dissected one day after the final nasal administration of OVA, and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) was analyzed in the same manner as in Example 1.

As a result, as shown in A of FIG. 4 , it was confirmed that the number of inflammatory cells was significantly reduced depending on the dose of the compound of Formula 2 administered.

In addition, as shown in FIG. 4B , it was confirmed that IL-4 and IL-17, which are inflammatory cytokines in BALF, were decreased by the compound of Formula 2 .

Example 3. Confirmation of the effect of nasal administration of the compound of Formula 2 according to the number of administration

A mouse model of eosinophilic asthma was induced with egg white albumin/aluminum (OVA/Alum), and in order to confirm the effect according to the number of administrations of the compound of Formula 2, single (1mg/Kg, day 21) or three times (1mg/Kg) Nasal administration was performed.

Specifically, according to the experimental protocol shown in FIG. 5, mice were dissected one day after the final nasal administration of OVA and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) was analyzed in the same manner as in Example 1.

As a result, as shown in A of FIG. 6 , it was confirmed that the number of inflammatory cells in the BALF was further decreased as the number of administration of the compound of Formula 2 increased.

In addition, as shown in FIG. 6B , when the amount of cytokines in BALF was measured, it was confirmed that IL-4 decreased regardless of the number of administrations of the compound of Formula 2 .

In addition, as shown in FIG. 6C , as a result of measuring the amount of cytokines generated after separation and stimulation of total lung cells and lymph node cells, inflammatory cytokines according to the number of administration of the compound of Formula 2 It was confirmed that the kinases IL-4, IL-17, and IFN-γ were decreased.

Example 4. Confirmation of the effect of reducing side effects according to the administration of the compound of Formula 2

In order to compare the efficacy and side effects of the compound of Formula 2 and existing therapeutic agents in a mouse model of eosinophilic asthma induced by OVA/Alum, the compound of Formula 2, FTY720 (S1PR inhibitor), and dexamethasone After nasal administration at 5 mpk and 1 mpk (mg/kg/day), respectively, blood was obtained. Through the obtained blood, it was confirmed whether a side effect, lymphopenia, occurred (see FIG. 7 ). The number of inflammatory cells was analyzed in the same manner as in Example 1.

As a result, as shown in FIG. 8 , the lymphocyte count in the asthma model was improved through administration of the compound of Formula 2, FTY720, and dexamethasone, whereas lymphopenia was observed in FTY720 in the normal model, whereas the compound of Formula 2 did not have lymphopenia. It was confirmed that it can be used safely without side effects.

The description of the present invention described above is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive.

Claims (16)

A pharmaceutical composition for preventing or treating asthma or bronchitis, comprising a compound represented by the following formula (1), an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

(In Formula 1, R ₁ is hydrogen or

ego;
R ₂ is hydrogen, unsubstituted or substituted C _1-5 linear or branched alkylcarbonyl, wherein the substituted alkylcarbonyl is selected from the group consisting of hydroxy, halogen, cyano, nitro and amino. one or more substituents selected are substituted;
A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;
B is C _1-11 linear or branched alkylene;
C is a single bond or C _6-10 arylene;
D is -H, or C _1-15 straight or branched chain alkyl; and
X is a single bond, C _1-5 alkylene, C _2-5 alkenylene or C _2-5 alkynylene.)
According to claim 1,
R ₁ is hydrogen or

ego;
R ₂ is hydrogen, C _1-3 linear or branched alkylcarbonyl,
A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;
B is C _1-9 straight-chain or branched alkylene;
C is a single bond or C _6-10 arylene;
D is -H or C _3-12 straight or branched chain alkyl; and
X is a single bond, C _1-3 alkylene, C _2-3 alkenylene or C _2-3 alkynylene, the pharmaceutical composition.
According to claim 1,
R ₁ is hydrogen or

ego;
R ₂ is hydrogen or acetyl,
A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;
B is C _2-8 alkylene;
C is a single bond or phenylene;
D is -H, or C _6-10 straight or branched chain alkyl; and
X is a single bond, -CH ₂ CH ₂ -, -CH=CH- or -C≡C-, characterized in that the pharmaceutical composition.
According to claim 1,
The compound represented by Formula 1 is a pharmaceutical composition, characterized in that at least one selected from the following compound group:
(1) 2-amino-2-(2-(3-decylisooxazol-5-yl)ethyl)propane-1,3-diol;
(2) 2-amino-2-(2-(1-decyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;
(3) 2-amino-2-((3-octylisooxazol-5-yl)ethynyl)propane-1,3-diol;
(4) 2-amino-2-(2-(3-octylisooxazol-5-yl)ethyl)propane-1,3-diol;
(5) 2-amino-2-(hydroxymethyl)-4-(3-octylisooxazol-5-yl)butyl dihydrogen phosphate;
(6) 2-amino-2-((3-decylisooxazol-5yl)ethynyl)propane-1,3-diol;
(7) 2-amino-4-(3-decylisooxazol-5-yl)-2-(hydroxymethyl)butyl dihydrogen phosphate;
(8) 2-amino-2-(2-(3-(4-hexylphenethyl)isoxazol-5-yl)ethyl)propane-1,3-diol;
(9) 2-amino-2-((3-dodecylisooxazol-5-yl)ethynyl)propane-1,3-diol;
(10) 2-amino-2-(2-(3-dodecylisooxazol-5-yl)ethyl)propane-1,3-diol;
(11) 2-amino-4-(3-dodecylisoxazol-5-yl)-2-(hydroxymethyl)butyl dihydrogen phosphate;
(12) 2-amino-2-(2-(1-octyl-1H-1,2,3-triazol-4-yl)ethynyl)propane-1,3-diol;
(13) 2-amino-2-(2-(1-octyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;
(14) 2-amino-2-((1-decyl-1H-1,2,3-triazol-4-yl)ethynyl)propane-1,3-diol;
(15) 2-amino-2-(2-(1-(4-hexylphenethyl)-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;
(16) 2-amino-2-(1-butyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol;
(17) 2-amino-2-(3-dodecylisooxazol-5-yl)propane-1,3-diol;
(18) (E)-2-amino-2-(2-(3-decylisooxazol-5-yl)vinyl)propane-1,3-diol;
(19) (E)-2-amino-2-(1-butyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol;
(20) 2-amino-2-(2-(3-(8-phenyloctyl)-isooxazol-5-yl)ethyl)propane-1,3-diol;
(21) 2-amino-2-(2-(1-(8-phenyloctyl)-1H-1,2,3-triazolbutyl-4-yl)propane-1,3-diol;
(22) N-(2-(1-dodecyl-1H-1,2,3-triazol-4-yl)-1,3-dihydrooxypropan-2-yl)acetamide;
(23) N-(2-(3-dodecylisoxazol-5-yl)-1,3-dihydrooxypropan-2-yl)acetamide;
(24) N-(4-(1-decyl-1H-1,2,3-triazol-4-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide;
(25) N-(4-(3-decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide; and
(26) N-(4-(1-(4-hexylphenethyl)-1H-1,2,3-triazol-4-yl)-1-hydroxy-2-(hydroxymethyl)butane-2 -il) acetamide.
According to claim 1,
The compound represented by Formula 1 is a pharmaceutical composition, characterized in that it is a compound represented by Formula 2 below.
[Formula 2]

According to claim 1,
The bronchitis is acute bronchitis, chronic bronchitis, allergic bronchitis, infectious bronchitis, traumatic bronchitis, catarrhal bronchitis, suppurative bronchitis, obstructive bronchitis, ulcerative bronchitis and infiltrating bronchitis, characterized in that at least one bronchitis selected from the group consisting of, pharmaceutical composition.
According to claim 1,
The asthma is at least one selected from the group consisting of bronchial asthma, atopic asthma, non-topic asthma, exercise-induced asthma, aspirin asthma, psychogenic asthma and alveolar asthma, a pharmaceutical composition.
According to claim 1,
The compound is characterized in that it reduces the number of inflammatory cells in the bronchi or lung, a pharmaceutical composition.
A food composition for preventing or improving asthma or bronchitis, comprising as an active ingredient a compound represented by the following Chemical Formula 1, an optical isomer thereof, or a food pharmaceutically acceptable salt thereof.
[Formula 1]

(In Formula 1, R ₁ is hydrogen or

ego;
R ₂ is hydrogen, unsubstituted or substituted C _1-5 linear or branched alkylcarbonyl, wherein the substituted alkylcarbonyl is selected from the group consisting of hydroxy, halogen, cyano, nitro and amino. one or more substituents selected are substituted;
A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;
B is C _1-11 linear or branched alkylene;
C is a single bond or C _6-10 arylene;
D is -H, or C _1-15 straight or branched chain alkyl; and
X is a single bond, C _1-5 alkylene, C _2-5 alkenylene or C _2-5 alkynylene.)
10. The method of claim 9,
R ₁ is hydrogen or

ego;
R ₂ is hydrogen, C _1-3 linear or branched alkylcarbonyl,
A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;
B is C _1-9 straight-chain or branched alkylene;
C is a single bond or C _6-10 arylene;
D is -H or C _3-12 straight or branched chain alkyl; and
X is a single bond, C _1-3 alkylene, C _2-3 alkenylene or C _2-3 alkynylene, characterized in that the food composition.
10. The method of claim 9,
R ₁ is hydrogen or

ego;
R ₂ is hydrogen or acetyl,
A is a pentacyclic hetero arylene containing one or more heteroatoms selected from the group consisting of N, O and S;
B is C _2-8 alkylene;
C is a single bond or phenylene;
D is -H, or C _6-10 straight or branched chain alkyl; and
X is a single bond, -CH ₂ CH ₂ -, -CH=CH- or -C≡C-, characterized in that the food composition.
10. The method of claim 9,
The compound represented by Formula 1 is characterized in that at least one selected from the following compound group, food composition:
(1) 2-amino-2-(2-(3-decylisooxazol-5-yl)ethyl)propane-1,3-diol;
(2) 2-amino-2-(2-(1-decyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;
(3) 2-amino-2-((3-octylisooxazol-5-yl)ethynyl)propane-1,3-diol;
(4) 2-amino-2-(2-(3-octylisooxazol-5-yl)ethyl)propane-1,3-diol;
(5) 2-amino-2-(hydroxymethyl)-4-(3-octylisooxazol-5-yl)butyl dihydrogen phosphate;
(6) 2-amino-2-((3-decylisooxazol-5yl)ethynyl)propane-1,3-diol;
(7) 2-amino-4-(3-decylisooxazol-5-yl)-2-(hydroxymethyl)butyl dihydrogen phosphate;
(8) 2-amino-2-(2-(3-(4-hexylphenethyl)isoxazol-5-yl)ethyl)propane-1,3-diol;
(9) 2-amino-2-((3-dodecylisooxazol-5-yl)ethynyl)propane-1,3-diol;
(10) 2-amino-2-(2-(3-dodecylisooxazol-5-yl)ethyl)propane-1,3-diol;
(11) 2-amino-4-(3-dodecylisoxazol-5-yl)-2-(hydroxymethyl)butyl dihydrogen phosphate;
(12) 2-amino-2-(2-(1-octyl-1H-1,2,3-triazol-4-yl)ethynyl)propane-1,3-diol;
(13) 2-amino-2-(2-(1-octyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;
(14) 2-amino-2-((1-decyl-1H-1,2,3-triazol-4-yl)ethynyl)propane-1,3-diol;
(15) 2-amino-2-(2-(1-(4-hexylphenethyl)-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol;
(16) 2-amino-2-(1-butyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol;
(17) 2-amino-2-(3-dodecylisooxazol-5-yl)propane-1,3-diol;
(18) (E)-2-amino-2-(2-(3-decylisooxazol-5-yl)vinyl)propane-1,3-diol;
(19) (E)-2-amino-2-(1-butyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol;
(20) 2-amino-2-(2-(3-(8-phenyloctyl)-isooxazol-5-yl)ethyl)propane-1,3-diol;
(21) 2-amino-2-(2-(1-(8-phenyloctyl)-1H-1,2,3-triazolbutyl-4-yl)propane-1,3-diol;
(22) N-(2-(1-dodecyl-1H-1,2,3-triazol-4-yl)-1,3-dihydrooxypropan-2-yl)acetamide;
(23) N-(2-(3-dodecylisoxazol-5-yl)-1,3-dihydrooxypropan-2-yl)acetamide;
(24) N-(4-(1-decyl-1H-1,2,3-triazol-4-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide;
(25) N-(4-(3-decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide; and
(26) N-(4-(1-(4-hexylphenethyl)-1H-1,2,3-triazol-4-yl)-1-hydroxy-2-(hydroxymethyl)butane-2 -il) acetamide.
10. The method of claim 9,
The compound represented by Formula 1 is a food composition, characterized in that it is a compound represented by Formula 2 below.
[Formula 2]

10. The method of claim 9,
The bronchitis is acute bronchitis, chronic bronchitis, allergic bronchitis, infectious bronchitis, traumatic bronchitis, catarrhal bronchitis, suppurative bronchitis, obstructive bronchitis, ulcerative bronchitis and infiltrating bronchitis, characterized in that at least one bronchitis selected from the group consisting of, food composition.
10. The method of claim 9,
The asthma is at least one selected from the group consisting of bronchial asthma, atopic asthma, non-topic asthma, exercise-induced asthma, aspirin asthma, psychogenic asthma and alveolar asthma, a food composition.
10. The method of claim 9,
The compound is characterized in that reducing the number of inflammatory cells in the bronchi or lung, food composition.

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