KR101721357B1 - A composition comprising moracin M derivatives for preventing and treating respiratory inflammatory diseases - Google Patents

Abstract

Provided is a pharmaceutical composition for preventing and treating respiratory inflammatory diseases, wherein the pharmaceutical composition comprises a moracin M derivative represented by formula 1 or a pharmaceutically allowable salt of the moracin M derivative as an active ingredient. In formula 1, R^1, R^2, and R^3 are any one selected from the group consisting of H, formyl, acetyl, propanoyl, isopropanoyl, butanoyl, pivaloyl, dimethylcarbamoyl, diethylcarbamoyl, dipropylcarbamoyl, dibutylcarbamoyl methylcarbamoyl, and ethylcarbamoyl groups, and R^1, R^2, and R^3 are not simultaneously H.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for preventing and treating respiratory inflammatory diseases,

The present invention relates to a composition for the prevention and treatment of respiratory inflammatory diseases, which comprises a morazin M derivative as an active ingredient. More particularly, the present invention relates to a composition for prevention and treatment of respiratory inflammatory diseases, which is superior to a strong steroid anti- The present invention relates to a composition for prevention and treatment of respiratory inflammatory diseases, which comprises, as an active ingredient, a morazin M derivative which can be safely used as a therapeutic agent for respiratory inflammatory diseases while having activity.

Our body's respiratory system is one of the institutes that are constantly defending against physicochemical stimuli. Most of the stimulants are caught in the nose and can not enter the respiratory system when the stimulant is introduced into the respiratory system. However, It is sent up or out by the movement of fine cilia on the wall. These respiratory illnesses cause inflammation in the respiratory tract and cause fatal consequences for infants and the elderly.

To solve this problem, the present inventor discloses a pharmaceutical composition for the prevention and treatment of respiratory inflammatory diseases based on Moracin M compound in patent document 10-2015--0090529.

 However, morazin M has a problem in bioavailability as an oral administration agent and thus does not exhibit a strong inhibitory effect in actual administration. Therefore, when oral administration of MORICIN M, a new technique is needed to maximize the prevention and therapeutic effect of respiratory inflammatory diseases.

Accordingly, a problem to be solved by the present invention is to provide a pharmaceutical composition for the prevention and treatment of respiratory inflammatory disease having excellent activity even when administered orally.

In order to solve the above problems, the present invention provides a pharmaceutical composition for preventing and treating respiratory inflammatory diseases, which comprises, as an active ingredient, a morazin M derivative represented by the following formula 1 or a pharmaceutically acceptable salt of the morazin M derivative to provide.

[Formula 1]

(And wherein R ^1, R ^2, R ³ is H, formyl, acetyl, propanoyl, isopropanoyl, butanoyl, pivaloyl, dimethylcarbamoyl, diethylcarbamoyl, dipropylcarbamoyl, any one selected from the group consisting of a dibutylcarbamoyl methylcarbamoyl and ethylcarbamoyl, R ^1, R ² And R < ³ > are not simultaneously H)

In one embodiment of the present invention, the morasin M derivative is any one of the compounds represented by the following formula (2).

In one embodiment of the present invention, the morasin M derivative is any one of the compounds represented by the following formula (3).

[Formula 3]

The present invention provides a pharmaceutical composition for the prevention and treatment of respiratory inflammatory disease, wherein the composition for the prevention and treatment of respiratory inflammatory disease is an anti-inflammatory and an immunomodulator.

The present invention also provides a pharmaceutical composition for the prevention and treatment of respiratory inflammatory disease, characterized in that the pharmaceutical composition for the prevention and treatment of respiratory inflammatory disease is a therapeutic agent for respiratory inflammatory disease, wherein the respiratory inflammatory disease is selected from the group consisting of cold, influenza, Chronic bronchitis, pneumonia, emphysema, pulmonary fibrosis disease and chronic obstructive pulmonary disease (COPD).

The present invention provides a derivative having a novel structure for solving the problem of oral administration of morazine M. As a result, it has excellent activity as a preventive and therapeutic agent for respiratory inflammatory diseases, and can be safely used as a therapeutic agent for respiratory inflammatory diseases safely, having superior activity than a strong steroid anti-inflammatory agent.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a diagram illustrating morasin M and its derivatives according to an embodiment of the present invention. FIG.

Hereinafter, embodiments and examples of the present invention will be described in detail with reference to the accompanying drawings, which will be readily apparent to those skilled in the art to which the present invention pertains.

It should be understood, however, that the present invention may be embodied in many different forms and is not limited to the embodiments and examples described herein. In order to clearly illustrate the present invention, parts not related to the description are omitted, and similar parts are denoted by like reference characters throughout the specification.

Throughout this specification, when an element is referred to as "including " an element, it is understood that the element may include other elements as well, without departing from the other elements unless specifically stated otherwise.

The terms "about "," substantially ", etc. used to the extent that they are used throughout the specification are intended to be taken to mean the approximation of the manufacturing and material tolerances inherent in the stated sense, Accurate or absolute numbers are used to help prevent unauthorized exploitation by unauthorized intruders of the referenced disclosure. The word " step (or step) "or" step "used to the extent that it is used throughout the specification does not mean" step for.

Throughout this specification, the term "combination thereof" included in the expression of the machine form means one or more combinations or combinations selected from the group consisting of the constituents described in the expression of the machine form, And the like.

The present invention provides a morphine M derivative represented by the following formula (1) to solve the above-mentioned problem of morasin M.

(And wherein R ^1, R ^2, R ³ is H, formyl, acetyl, propanoyl, isopropanoyl, butanoyl, pivaloyl, dimethylcarbamoyl, diethylcarbamoyl, dipropylcarbamoyl, any one selected from the group consisting of a dibutylcarbamoyl methylcarbamoyl and ethylcarbamoyl, R ^1, R ² And R < ³ > are not simultaneously H)

1 is a view showing morasin M and its derivatives according to an embodiment of the present invention. However, the scope of the present invention is not limited to the derivatives shown in Fig.

1, a novel derivative was synthesized on the basis of morasin M shown in FIG. 1, and its pharmacological activity was examined. As a result, it was found that a cold, an influenza, acute, chronic bronchitis, pneumonia, emphysema, (COPD), and it shows a strong activity as an oral administration agent by solving the problem of oral administration of morasin M, in particular, as a prophylactic and therapeutic agent for respiratory inflammatory diseases such as pulmonary fibrosis disease and chronic obstructive pulmonary disease Respectively. That is, KW-001 to 008 corresponding to derivatives of morasin M have higher activity than morasin M through the following experimental examples, and each synthesis example will be described below.

Synthesis Example 1

Morazin M and intermediate synthesis

The following Reaction Scheme 1 is a reaction formula explaining the morasin M and intermediate synthesis method in the experimental example according to the present invention.

[Reaction Scheme 1]

Synthesis Example 2

Synthesis of morazine M derivatives KW-001, KW-002 and KW-006

Scheme 2 is a reaction formula for describing the synthesis method of morasin M derivatives KW-001, KW-002 and KW-006 according to an embodiment of the present invention.

[Reaction Scheme 2]

Synthesis Example 3

Synthesis of morazine M derivative KW-003

The following Reaction Scheme 3 is a reaction formula explaining the synthesis method of the morasin M derivative KW-003 according to one embodiment of the present invention.

[Reaction Scheme 3]

Synthesis Example 4

Synthesis of morazine M derivatives KW-004 and 005

Scheme 4 is a reaction formula describing a method for synthesizing morazin M derivative KW-004 and 005 according to an embodiment of the present invention.

[Reaction Scheme 4]

Synthesis Example 5

Synthesis of morazine M derivative KW-007

The following Reaction Scheme 5 is a reaction formula explaining the method of synthesizing the morasin M derivative KW-007 according to an embodiment of the present invention.

[Reaction Scheme 5]

Synthesis Example 6

Synthesis of morazine M derivative KW-008

The following Reaction Scheme 6 is a reaction formula explaining the synthesis method of the morazin M derivative KW-008 according to one embodiment of the present invention.

[Reaction Scheme 6]

A specific synthesis method of the intermediates shown in Reaction Schemes 1 to 6 is as follows.

2- (3,5-bis (benzyloxy) phenyl) benzofuran-6-yl acetate (3).

2,4-diacetoxybenzyl) triphenylphosphonium bromide (15.0 g, 29.6 mmol), prepared in the manner reported by J. Chem. Soc. Perkin Trans. 1, 3453, 1998, in dichloromethane (CH ₂ Cl ₂ , 296 mL) , Dicyclohexylcarbodiimide (6.7 g, 32.6 mmol) and 4-dimethylaminopyridine (361 mg, 2.96 mmol) were successively added thereto at room temperature, and the mixture was stirred at room temperature overnight. The reaction mixture was completely concentrated and dried, then 1,4-dioxane (148 mL) and triethylamine (20.6 mL) were added. The reaction mixture was refluxed overnight. The reaction mixture was cooled at room temperature and filtered using filter paper. The filtrate was concentrated and purified by silica gel column chromatography (25% EtOAc / hexanes). The resulting solid was suspended in an appropriate amount of hot ether, cooled, and then filtered to give pure target compound (8.5 g, 62%) as a white solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.53 (d, J = 8.4 Hz, 1H), 7.48-7.28 (m, 11H), 7.10 (d, J = 2.5 Hz, 2H), 6.99-6.96 (m, 2H), 6.63 (t, J = 2.2 Hz, 1H), 5.11 (s, 4H), 2.34 (s, 3H).

2- (3,5-bis (benzyloxy) phenyl) benzofuran-6-ol (4).

6-yl acetate (4.0 g, 8.61 mmol) was dissolved in EtOH / H ₂ O (5/1, 43 mL) and KOH (966 mg, 17.2 mmol) . The reaction mixture was refluxed for 1 hour and then cooled. The reaction mixture was diluted with water, and then the ethanol was distilled off under reduced pressure. The reaction mixture was adjusted to pH ~ 3 by adding an appropriate amount of aqueous HCl solution (1 M). The resulting precipitate was filtered and dried, dissolved in an appropriate amount of hot EtOH, and recrystallized to obtain pure target compound (3.8 g, 98%) as a white solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.48-7.31 (m, 11H), 7.08 (d, J = 2.3 Hz, 2H), 7.00 (d, J = 2.1 Hz, 1H), 6.90 (d, J = 0.7 Hz, 1 H), 6.77 (dd, J = 8.4, 2.2 Hz, 1H), 6.60 (t, J = 2.2 Hz, 1H), 5.11 (s, 4H).

5- (6-hydroxybenzofuran-2-yl) benzene-1,3-diol (Moracin M)

Dissolve 2- (3,5-bis (benzyloxy) phenyl) benzofuran-6-ol (3.55 g, 8.40 mmol) in EtOH / EtOAc (5/1, 120 mL) and add 5% Pd / C gave. The reaction mixture was stirred at room temperature under a hydrogen atmosphere for 48 hours. The reaction mixture was filtered through a pad of celite, and the filtrate was concentrated under reduced pressure. The concentrate was purified by column chromatography (50% EtOAc / hexanes) to give the pure objective compound Moracin M (1.83 g, 90%) as a white solid.

^{1 H NMR (300 MHz, DMSO-} d 3) δ 9.43 (br s, 3H), 7.38 (d, 8.4 Hz, 1H), 7.07 (d, J = 0.6 Hz, 1H), 6.92 (d, J = 1.7 Hz, 1H), 6.73 (dd , J = 8.4, 2.1 Hz, 1H), 6.68 (d, J = 2.1 Hz, 2H), 6.21 (t, J = 2.2 Hz, 1H).

2- (3,5-dihydroxyphenyl) benzofuran-6-yl acetate (KW-001).

Suspension was made by dispersing 2- (3,5-bis (benzyloxy) phenyl) benzofuran-6-yl acetate (520 mg, 1.1 mmol) in THF (20 mL) and 5% Pd / C gave. Then, the mixture was stirred under a hydrogen atmosphere at room temperature for 40 hours using a hydrogen balloon. The reaction mixture was filtered through a pad of Celite and washed with an appropriate amount of methanol. The filtrate was collected and concentrated under reduced pressure to obtain the target compound KW-001 (308 mg, 96%) as a white solid.

^{1 H NMR (300 MHz, CD} 3 OD) δ 7.55 (d, J = 8.4 Hz, 1H), 7.30 (s, 1H), 7.04 (s, 1H), 7.006.94 (m, 1H), 6.82 (d J = 2.2 Hz, 2H), 6.30 (t, J = 2.1 Hz, 1H), 2.30 (s, 3H).

2- (3,5-bis ((dimethylcarbamoyl) oxy) phenyl) benzofuran-6-yl acetate (KW-002).

To the anhydrous carbon dichloride (10 mL) was added 2- (3,5-dihydroxyphenyl) benzofuran-6-yl acetate (KW- 0.85 g, 3.42 mmol) and DMAP (41.8 mg, 0.10 equiv) and pyridine (10 mL). The ice-cooled reaction mixture was slowly added with dimethylcarbamoyl chloride (1.57 mL, 17.1 mmol) while stirring. The reaction mixture was stirred at room temperature for 24 hours and then concentrated under reduced pressure. Water (20 mL) was added to the reaction concentrate and extracted with dichloromethane (3 mL 20 mL). The combined extracts were washed with 1 N HCl (30 mL) and an appropriate amount of saturated brine, dried over anhydrous MgSO _4, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (4% MeOH / CH ₂ Cl ₂ ) to obtain the target compound KW-002 (1.3 g, 88%) as a white solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.53 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 2.1 Hz, 2H), 7.26 (s, 1H), 6.98 (ddd, J = 5.8, 3.0, 1.4 Hz, 3H), 3.11 (s, 6H), 3.03 (s, 6H), 2.34 (s, 3H).

5- (6-acetoxybenzofuran-2-yl) -1,3-phenylene diacetate (KW-003).

To a solution of 5- (6-hydroxybenzofuran-2-yl) benzene-1,3-diol (Moracin M, 50 mg, 0.21 mmol), DMAP (2.5 mg, 0.10 eq) and pyridine (166 μL , 10 eq). Acetic anhydride (78 μL, 0.83 mmol) was slowly added to the ice-cooled reaction mixture. The reaction mixture was stirred overnight at room temperature and then diluted with dichloromethane (20 mL). The reaction mixture was washed with an appropriate amount of water, 1 N HCl (10 mL) and an appropriate amount of saturated brine. The oil layer was dried over anhydrous MgSO ₄ and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (10% EtOAc / hexanes) to obtain the desired compound KW-003 (60 mg, 78%) as a solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.54 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 1.9 Hz, 2H), 7.27 (s, 1H), 7.036.96 (m, 2H) , 6.92 (s, 1H), 2.33 (d, J = 3.2 Hz, 10H).

2- (3,5-bis (benzyloxy) phenyl) benzofuran-6-yl dimethylcarbamate (5).

Was dissolved in anhydrous acetonitrile (100 mL) 2- (3,5- bis (benzyloxy) phenyl) benzofuran-6-ol (compound 4) (550 mg, 1.3 mmol) in dimethylcarbamoyl chloride (175 mg, 1.6 mmol ) and K ₂ CO ₃ (8.35 g, 60.5 mmol) was added thereto. The reaction mixture was stirred overnight and then concentrated under reduced pressure. Water (25 mL) was added and extracted with dichloromethane (3 ㅧ 25 mL). The combined oil layers were dried over anhydrous MgSO ₄ and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (40% EtOAc / hexanes) to obtain the desired compound (500 mg, 78%) as a white solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.50 (d, J = 8.4 Hz, 1H), 7.487.30 (m, 11H), 7.10 (d, J = 2.3 Hz, 2H), 7.00 (dd, J = 8.4, 2.1 Hz, 1H), 6.95 (d, J = 0.9 Hz, 1H), 6.62 (t, J = 2.2 Hz, 1H), 5.11 (s, 4H), 3.14 (s, 3H), 3.04 (s, 3H).

2- (3,5-dihydroxyphenyl) benzofuran-6-yl dimethylcarbamate (KW-004).

2- (3,5-bis (benzyloxy) phenyl) benzofuran-6-yl dimethylcarbamate (450 mg, 0.91 mmol) was dissolved in THF (15 mL), and 5% Pd / C (50 mg) was added thereto. Then, the mixture was stirred under a hydrogen atmosphere at room temperature for 40 hours using a hydrogen balloon. The reaction mixture was filtered through a pad of celite, washed with an appropriate amount of methanol, and the filtrate was collected and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (60% EtOAc / hexanes) to obtain the target compound KW-004 (215 mg, 85%) as a white solid.

_{^{1 HNMR (300 MHz, CD 3}} OD) δ 7.54 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 1.6 Hz, 1H), 7.04 (d, J = 0.7 Hz, 1H), 6.98 (dd J = 8.4, 2.0 Hz, 1H), 6.81 (d, J = 2.2 Hz, 2H), 6.29 (t, J = 2.2 Hz, 1H), 3.14 (s, 3H), 3.00 (s,

5- (6 - ((dimethylcarbamoyl) oxy) benzofuran-2-yl) -1,3-phenylene diacetate (KW-005).

(KW-004, 100 mg, 0.32 mmol), DMAP (4.0 mg, 0.10 equiv) and pyridine (130 μL) were added to anhydrous dichloromethane (3 mL) And melted. After cooling the reaction mixture with ice water, acetic anhydride (75 μL, 0.80 mmol) was slowly added. The reaction mixture was stirred overnight at room temperature and then diluted with dichloromethane (20 mL). The reaction mixture was washed with an appropriate amount of water, 1N HCl (10 mL) and an appropriate amount of saturated brine (10 mL), dried over anhydrous MgSO _4, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (1% MeOH / CH ₂ Cl ₂ ) to obtain the target compound KW-005 (104 mg, 80%) as a white solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.52 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 2.1 Hz, 2H), 7.29 (d, J = 1.8 Hz, 1H), 7.02 (dd , J = 8.2, 1.5 Hz, 2H), 6.91 (t, J = 2.1 Hz, 1H), 3.14 (s, 3H), 3.04 (s, 3H), 2.33 (s, 6H).

5- (6-hydroxybenzofuran-2-yl) -1,3-phenylene bis (dimethylcarbamate)  ( KW-006 ).

6-yl acetate ( KW-002, 0.90 g, 2.1 mmol) and Amberlyst-15 (450 mg) were added to methanol (20 mL) Lt; / RTI > The reaction mixture was filtered through Celite, washed with methanol (3 x 10 mL), and the filtrate was concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (1% MeOH / CH ₂ Cl ₂ ) to obtain the desired compound KW-006 (650 mg, 80%) as a white solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.29 (d, J = 2.0 Hz, 2H), 7.16 (d, J = 8.4 Hz, 1H), 6.90 (s, 1H), 6.67 (d, J = 19.4 Hz , 3H), 6.59 (dd, J = 8.4, 1.9 Hz, 1H), 3.14 (s, 6H), 3.07 (s, 6H).

2- (3,5-bis (benzyloxy) phenyl) benzofuran-6-yl pivalate (6).

To anhydrous dichloromethane (20 mL) was added 2- (3,5-bis (benzyloxy) phenyl) benzofuran-6-ol (compound 4, 265 mg, 0.63 mmol), DMAP (7.6 mg, 0.06 mmol, 0.10 equiv), and triethylamine (95 mg, 0.94 mmol). After cooling the reaction mixture with ice water, pivaloyl chloride (93.0 μL, 0.75 mmol, 1.2 equiv) was slowly added. The reaction mixture was stirred at room temperature for 2 hours, and then water (5 mL) was added thereto, followed by stirring for 30 minutes. After separating the oil layer and water layer, the oil layer was washed with an appropriate amount of saturated brine, dried over anhydrous MgSO _4, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (10% EtOAc / hexanes) to obtain the desired compound (265 mg, 83%) as a white solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.52 (d, J = 8.4 Hz, 1H), 7.507.30 (m, 11H), 7.10 (d, J = 2.3 Hz, 2H), 6.986.91 (m, 2H), 6.63 (t, J = 2.2 Hz, 1H), 5.11 (s, 4H), 1.39 (s, 9H).

2- (3,5-dihydroxyphenyl) benzofuran-6-yl pivalate (KW-007).

The compound 6, 220 mg, 0.43 mmol) was dissolved in THF (15 mL), and 5% Pd / C (50 mg) was added thereto. . Then, the mixture was stirred under a hydrogen atmosphere at room temperature for 40 hours using a hydrogen balloon. The reaction mixture was filtered through a pad of celite, washed with an appropriate amount of methanol, and the filtrate was collected and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (50% EtOAc / hexanes) to obtain the target compound KW-007 (120 mg, 84%) as a white solid.

^{1 H NMR (300 MHz, MeOD} ) δ 7.55 (d, J = 8.4 Hz, 1H), 7.25 (d, J = 1.7 Hz, 1H), 7.04 (d, J = 0.8 Hz, 1H), 6.92 (dd, J = 8.4, 2.0 Hz, 1H), 6.82 (d, J = 2.2 Hz, 2H), 6.30 (t, J = 2.2 Hz, 1H), 1.37 (s, 9H).

2- (3,5-bis ((dimethylcarbamoyl) oxy) phenyl) benzofuran-6-yl dimethylcarbamate

(KW-008).

To a solution of moracin M (50 mg, 0.2 mmol) in anhydrous acetonitrile (2 mL) was added dimethylcarbamoyl chloride (88 mg, 0.8 mmol) and K ₂ CO ₃ (170 mg, 1.2 mmol). The reaction mixture was stirred overnight and then concentrated under reduced pressure. Water (10 mL) was added thereto, followed by extraction with dichloromethane (3 ㅧ 10 mL). The combined oil layers were dried over anhydrous MgSO ₄ and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (20% EtOAc / hexanes) to obtain the desired compound KW-008 (500 mg, 78%) as a white solid.

^{1 H NMR (300 MHz, CDCl} 3) δ 7.50 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 2.1 Hz, 2H), 7.297.27 (m, 1H), 7.036.98 (m, 2H), 6.97 (t, J = 2.1 Hz, 1H), 3.14 (s, 3H), 3.11 (s, 6H), 3.02 (d, J = 6.5 Hz, 9H).

The effect of the derivatives synthesized by the above method was tested by the following method.

Experimental Example 1

In vivo formulation of mouse lipopolysaccharide (LPS) -induced bronchitis model

      In order to induce pulmonary inflammation, 50 μl of 2 mg / ml LPS was administered to ICR mice (Nara Biotech. Male, 20 - 22 g) according to the method of Lim et al. (J. Ethnopharmacol. 149, 169, 2013) After intranasal administration, bronchoalveolar lavage fluid (BALF) was obtained 16 hours later. The total cell number in the BALF was counted and the cell number changes such as neutrophil and macrophage in the BALF were confirmed using FACS.

Experimental Example 2

Measurement of bronchial inhibition of new derivatives

The inhibitory potency was tested using the in vivo model of Experimental Example 1. That is, the derivatives shown in FIG. 1 and prepared according to the above-described method were orally administered at 30 mg / kg and 1 hour later, LPS was administered. The inhibition was measured according to the above method. Appeared together.

[Table 1]

Inhibition of Morazin Derivatives on Pulmonary Inflammation in ALI Rats

In the results of Table 1, it was found that all the morazin M derivatives according to the present invention had an inhibitory effect on inflammation. In particular, the activities of KW002 and KW006 derivatives were significantly stronger than morasin M, which is a basic structure, And dexmethasone, an anti-inflammatory agent.

Figure 2 shows the FACS results for KW002.

Experimental Example 3

Acute toxicity test

KW002 was orally administered to ICR mice (male) at a dose of 500 mg / kg, 1 g / kg and 2 g / kg (n = 5). During one week of observation, no deaths occurred and no abnormal behavior was observed in all the treatment groups. Therefore, a new derivative, KW002, can be safely used as a therapeutic agent for respiratory inflammatory disease at an appropriate dose.

Claims (6)

delete delete A pharmaceutical composition for the prevention and treatment of respiratory inflammatory diseases, which comprises as an active ingredient a morazin M derivative or a pharmaceutically acceptable salt of the morazin M derivative, characterized by being any one of compounds represented by the following formula 3:
[Formula 3]

The method of claim 3,
Wherein the pharmaceutical composition for preventing and treating respiratory inflammatory diseases is an anti-inflammatory and immunomodulatory agent. The method of claim 3,
Wherein the pharmaceutical composition for preventing and treating respiratory inflammatory disease is a therapeutic agent for respiratory inflammatory disease. 6. The method of claim 5,
Wherein the respiratory inflammatory disease is any one or more of cold, pandemic influenza, acute, chronic bronchitis, pneumonia, emphysema, pulmonary fibrosis disease and chronic obstructive pulmonary disease (COPD).

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