COMPOSITION FOR TREATING OR PREVENTING INFLAMMATORY BOWEL DISEASE

Abstract

The present invention relates to a compound or a salt thereof which can be usefully used for the treatment, improvement, or prevention of inflammatory bowel disease. In addition, it relates to a pharmaceutical composition for treating or preventing inflammatory bowel disease comprising the compound or a pharmaceutically acceptable salt thereof. In addition, it relates to a food composition for improving or preventing inflammatory bowel disease comprising the compound or a sitologically acceptable salt thereof.

Claims

1. A compound represented by Formula 1 or a pharmaceutically or sitologically acceptable salt thereof: ##STR00023## wherein, R.sub.1 is H, OH or halogen; and X is one to five substituent group independently selected from H, OH, alkoxy and halogen, provided that the compound is not broussochalcone A.

2. The compound or pharmaceutically or sitologically acceptable salt thereof according to claim 1, wherein X are two substituent groups.

3. The compound or pharmaceutically or sitologically acceptable salt thereof according to claim 1, wherein the compound is selected from the group consisting of: ##STR00024## ##STR00025##

4. A pharmaceutical composition for treating or preventing an inflammatory bowel disease, comprising the compound or pharmaceutically acceptable salt thereof according claim 1.

5. The pharmaceutical composition according to claim 4, wherein the inflammatory bowel disease is selected from ulcerative colitis and Crohn's disease.

6. A food composition for improving or preventing an inflammatory bowel disease, comprising the compound or sitologically acceptable salt thereof according claim 1.

7. The food composition according to claim 6, wherein the inflammatory bowel disease is selected from ulcerative colitis and Crohn's disease.

8. A method for treating or preventing an inflammatory bowel disease, comprising administering the compound or pharmaceutically acceptable salt thereof according claim 1 to a subject in need thereof.

Description

BRIEF DESCRIPTION OF FIGURES

[0058] The Figures attached to this specification show the average value of the data repeated three times.

[0059] FIGS. 1a to 1c are graphs showing changes in the mRNA expression level of the inflammatory cytokine TNFα increased by LPS stimulation in RAW 264.7 macrophages.

[0060] FIGS. 2a and 2b are graphs representing the mRNA expression level of the inflammatory cytokine COX2 increased by LPS stimulation in RAW 264.7 macrophages.

[0061] FIGS. 3a and 3b are graphs representing the mRNA expression level of the inflammatory cytokine iNOS increased by LPS stimulation in RAW 264.7 macrophages.

[0062] FIG. 4 is a graph representing the mRNA expression level of the inflammatory cytokine IL-1α increased by LPS stimulation in RAW 264.7 macrophages.

[0063] FIG. 5 is a graph representing the mRNA expression level of the inflammatory cytokine IL-1β increased by LPS stimulation in RAW 264.7 macrophages.

[0064] FIG. 6 is a graph representing the mRNA expression level of the inflammatory cytokine MCP1 increased by LPS stimulation in RAW 264.7 macrophages.

[0065] FIGS. 7a and 7b are graphs showing changes in NO concentration (μM) increased by LPS stimulation in RAW 264.7 macrophages.

EXAMPLES

[0066] Hereinafter, the present invention will be described in more detail by examples. However, the examples are provided for easier understanding of the present invention, and the contents of the present invention are not limited by the following examples. In addition, those skilled in the art will be able to make various changes and modifications to the present invention within a range that does not impair the spirit of the present invention. Terms not specifically defined herein should be understood to have meanings commonly used in the technical field to which the present invention belongs.

[0067] In the following, examples of preparation of compounds of Formula 1 according to the present invention are described together with specific preparation steps and representative examples corresponding thereto. Compounds having different substituents were prepared through similar steps, but not all examples are described here. Referring to the following representative examples, those skilled in the art will be able to easily prepare compounds of Formula 1 having different substituents.

Preparation Example 1

[0068] A compound in which the substituent R.sub.1 is OH in Formula 1 was prepared according to the following steps.

##STR00003##

[0069] In order to introduce a prenyl group at position 3 of the starting material acetophenone, an alkylation reaction and a rearrangement reaction were performed. After that, when the reaction was performed using a strong base such as KOH or NaOH, the yield was low and it was difficult to separate and purify it if the material comprises a specific hydroxyl group. In order to solve this problem, the inventors protected the —OH group using DHP (dihydropyran) and proceeded with the condensation reaction of acetophenone and various benzaldehydes, and then deprotected the THP group under weakly acidic conditions to obtain the desired final product.

[0070] Chemical structures and .sup.1H NMR, .sup.13C NMR, LRMS, HRMS, and m.p values of Compounds A1 to A6 prepared in Preparation Example 1 are shown below, respectively.

##STR00004##

[0071] .sup.1H NMR (400 MHz, acetone) δ 13.53 (1H, s), 8.68 (2H, brs), 7.96 (1H, s), 7.77 (1H, d, J=15.2 Hz), 7.68 (1H, d, J=7.2 Hz), 7.68 (1H, d, J=2.0 Hz), 7.21 (1H, dd, J=8.0, 2.0 Hz), 6.92 (1H, d, J=8.4 Hz), 6.41 (1H, s), 5.38-5.33 (1H, m), 3.32 (2H, d, J=7.2 Hz), 1.74 (6H, d, J=8.0 Hz); .sup.13C NMR (100 MHz, acetone) δ 192.7, 165.8, 163.4, 149.1, 146.3, 145.2, 132.2, 128.3, 123.9, 123.4, 121.3, 118.5, 116.4, 115.8, 114.3, 103.4, 28.8, 25.9, 17.9; LRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.5 [M+H].sup.+: 341.13, found: 341.10; HRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.5 [M+H].sup.+: 341.1311, found: 341.1395; m.p=192.6° C.

##STR00005##

[0072] .sup.1H NMR (400 MHz, acetone) δ 13.50 (1H, s), 9.44 (1H, brs), 8.96 (1H, brs), 7.96 (1H, s), 7.83 (1H, d, J=17.2 Hz), 7.76 (1H, s), 7.71 (2H, d, J=8.4 Hz), 6.95 (2H, d, J=11.6 Hz), 6.41 (1H, s), 5.38-5.33 (1H, m), 3.32 (2H, d, J=6.8 Hz), 1.74 (6H, d, J=8.4 Hz); .sup.13C NMR (100 MHz, acetone) δ 192.7, 165.9, 160.9, 144.8, 132.3, 132.2, 131.6, 127.6, 123.9, 121.3, 118.5, 118.4, 116.7, 114.3, 103.4, 28.8, 25.8, 17.9; LRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.4 [M+H].sup.+: 325.13, found: 325.10; HRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.4 [M+H].sup.+: 325.1362, found: 325.1443; m.p=170.6° C.

##STR00006##

[0073] .sup.1H NMR (400 MHz, acetone) δ 13.35 (1H, s), 9.55 (1H, brs), 8.59 (1H, brs), 7.99 (1H, s), 7.86 (1H, d, J=15.6 Hz), 7.79 (1H, d, J=15.6 Hz), 7.33-7.25 (3H, m), 6.99-6.94 (1H, m), 6.43 (1H, s), 5.38-5.33 (1H, m), 3.32 (2H, d, J=6.8 Hz), 1.74 (6H, d, J=8.0 Hz); .sup.13C NMR (100 MHz, acetone) δ 192.6, 165.9, 158.7, 144.6, 137.3, 132.4, 130.8, 123.8, 121.7, 121.5, 121.0, 118.5, 115.9, 114.2, 103.4, 28.7, 25.8, 17.9; LRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.4 [M+H].sup.+: 325.13, found: 325.10; HRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.4 [M+H].sup.+: 325.1362, found: 325.1447; m.p=196.2° C.

##STR00007##

[0074] .sup.1H NMR (400 MHz, acetone) δ 13.51 (1H, s), 9.49 (1H, brs), 8.25 (1H, brs), 7.93 (1H, s), 7.82 (1H, d, J=15.6 Hz), 7.76 (1H, d, J=15.6 Hz), 7.47 (1H, d, J=2.0 Hz), 7.33 (1H, dd, J=8.4, 2.0 Hz,), 6.93 (1H, d, J=8.0 Hz), 6.42 (1H, s), 5.38-5.33 (1H, m), 3.96 (3H, s), 3.30 (2H, d, J=7.2 Hz), 1.75 (6H, s); .sup.13C NMR (100 MHz, acetone) δ 192.6, 165.9, 148.7, 145.2, 132.5, 132.1, 128.0, 124.5, 123.8, 121.2, 118.6, 116.2, 114.3, 112.1, 103.4, 56.3, 28.6, 25.8, 17.9; LRMS (ESI) calcd. for C.sub.21H.sub.23O.sub.5 [M+H].sup.+: 355.14, found: 355.10; HRMS (ESI) calcd. for C.sub.21H.sub.23O.sub.5 [M+H].sup.+: 355.1467, found: 355.1551; m.p=157.3° C.

##STR00008##

[0075] .sup.1H NMR (400 MHz, acetone) δ 13.49 (1H, s), 9.49 (1H, brs), 8.01 (1H, brs), 7.81-7.72 (2H, m), 7.36 (1H, d, J=2.0 Hz), 7.26 (1H, dd, J=8.4, 2.0 Hz), 7.04 (1H, d, J=8.4 Hz,), 6.42 (s, 1H), 55.38-5.33 (1H, m), 3.93 (3H, s), 3.32 (2H, d, J=7.2 Hz), 1.74 (6H, d, J=8.0 Hz); .sup.13C NMR (100 MHz, acetone) δ 192.6, 165.9, 165.4, 163.5, 150.9, 147.7, 144.9, 132.3, 129.2, 123.9, 123.4, 121.3, 119.3, 114.7, 114.3, 112.2, 103.4, 56.3, 28.8, 25.8, 17.9; LRMS (ESI) calcd. for C.sub.21H.sub.23O.sub.5 [M+H].sup.+: 355.14, found: 355.10; HRMS (ESI) calcd. for C.sub.21H.sub.23O.sub.5 [M+H].sup.+: 355.1467, found: 355.1549; m.p=159.1° C.

##STR00009##

[0076] .sup.1H NMR (400 MHz, acetone) δ 13.42 (1H, s), 9.39 (1H, brs), 8.00 (1H, s), 7.81 (2H, d, J=3.2 Hz), 7.68 (1H, dd, J=12.4, 2.0 Hz,), 7.49 (1H, dd, J=9.2, 2.8 Hz,), 7.09 (1H, t, J=8.8 Hz,), 6.42 (1H, s), 5.38-5.33 (1H, m), 3.31 (2H, d, J=7.2 Hz,), 1.74 (6H, d, J=9.2 Hz); .sup.13C NMR (100 MHz, acetone) δ 192.5, 165.9, 165.5, 163.6, 152.4 (d, J=239.8 Hz), 148.2, 143.6, 132.3, 128.6, 127.4, 123.9, 121.4, 120.2, 118.9, 116.3 (d, J=18.6 Hz), 114.2, 103.4, 28.8, 25.8, 17.9; LRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.4 [M+H].sup.+: 343.12, found: 343.10; HRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.4 [M+H].sup.+: 355.1267, found: 343.1350; m.p=160.8° C.

Preparation Example 2

[0077] A compound in which the substituent R.sub.1 is H or halogen in Formula 1 was prepared according to the following steps.

##STR00010##

[0078] The triple bond of the intermediate was reduced to a double bond using a Lindlar catalyst, and a desired acetophenone was produced through a rearrangement reaction. Thereafter, a condensation reaction between acetophenone and various benzaldehydes was performed, and then the THP group was deprotected under weakly acidic conditions to obtain the desired final product.

[0079] Chemical structures and .sup.1H NMR, .sup.13C NMR, LRMS, HRMS, and m.p values of Compounds B1 to B6 and C1 to C6 prepared in Preparation Example 2 are shown below, respectively.

##STR00011##

[0080] .sup.1H NMR (400 MHz, acetone) δ 7.69-7.60 (4H, m), 7.34 (1H, dd, J=15.6, 3.2 Hz,), 6.93 (2H, d, J=8.8 Hz,), 6.70 (1H, d, J=12.4 Hz,), 5.37-5.33 (1H, m), 3.35 (2H, d, J=7.2 Hz,), 1.74 (6H, s); .sup.13C NMR (100 MHz, acetone) δ 186.9, 161.8 (d, J=248.6 Hz), 160.8, 160.7, 143.9, 133.2, 132.6, 131.2, 127.6, 125.8, 123.7, 122.9, 119.5 (d, J=12.6 Hz), 116.7, 103.2 (d, J=26.3 Hz), 28.2, 25.8, 17.8; LRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.3 [M+H].sup.+: 327.13, found: 327.10; HRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.3 [M+H].sup.+: 327.1318, found: 327.1402; m.p=145.3° C.

##STR00012##

[0081] .sup.1H NMR (400 MHz, acetone) δ 9.57 (1H, brs), 8.56 (1H, brs), 7.66-7.62 (2H, m), 7.45 (1H, dd, J=15.6, 3.2 Hz), 7.29 (1H, t, J=7.6 Hz), 7.22-7.18 (2H, m), 6.94 (1H, ddd, J=8.0, 2.8, 1.2 Hz,), 6.72 (1H, d, J=12.4 Hz), 5.38-5.33 (1H, m), 3.35 (2H, d, J=8.0 Hz), 1.75 (6H, s); .sup.13C NMR (100 MHz, acetone) δ 186.9, 162.1 (d, J=249.0 Hz), 161.1, 158.7, 143.6, 137.4, 133.3, 132.6, 130.9, 126.6, 122.8, 120.8, 119.2 (d, J=12.4 Hz), 118.4, 115.3, 103.3 (d, J=26.3 Hz), 28.2, 25.8, 17.8; LRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.3 [M+H].sup.+: 327.13, found: 327.10; HRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.3 [M+H].sup.+: 327.1318, found: 327.1402; m.p=161.8° C.

##STR00013##

[0082] .sup.1H NMR (400 MHz, acetone) δ 8.43 (1H, brs), 7.65 (1H, d, J=8.4 Hz), 7.60 (1H, dd, J=15.6, 2.0 Hz), 7.29 (1H, dd, J=15.6, 3.2 Hz), 7.24 (1H, d, J=2.4 Hz), 7.12 (1H, dd, J=8.4, 2.4 Hz), 6.90 (1H, d, J=8.0 Hz), 6.70 (1H, d, J=12.4 Hz), 5.37-5.32 (1H, m), 3.34 (2H, d, J=7.2 Hz), 1.75 (6H, s); .sup.13C NMR (100 MHz, acetone) δ 186.9, 161.9 (d, J=248.4 Hz), 161.1, 160.8, 148.9, 145.3 (d, J=198.2 Hz), 133.2, 132.6, 128.2, 125.9, 123.7, 122.9, 120.8, 119.5 (d, J=12.7 Hz), 116.4, 115.3, 103.2 (d, J=26.5 Hz), 28.2, 25.8, 17.8; LRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.4 [M+H].sup.+: 343.12, found: 343.10; HRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.4 [M+H].sup.+: 343.1267, found: 343.1350; m.p=174.1° C.

##STR00014##

[0083] .sup.1H NMR (400 MHz, acetone) δ 7.67-7.62 (2H, m), 7.37-7.32 (2H, m), 7.24 (1H, dd, J=8.0, 2.0 Hz), 6.91 (1H, d, J=8.0 Hz), 6.70 (1H, d, J=12.8 Hz), 5.37-5.33 (1H, m), 3.94 (3H, s), 3.34 (2H, d, J=7.2 Hz), 1.74 (6H, s); .sup.13C NMR (100 MHz, acetone) δ 187.1, 161.8 (d, J=248.4 Hz), 160.7, 160.6, 150.2, 148.7, 144.4, 133.3, 132.5, 128.0, 125.8, 124.0, 122.8, 119.6 (d, J=12.7 Hz), 116.2, 111.9, 103.2 (d, J=26.2 Hz), 56.3, 28.2, 25.8, 17.8; LRMS (ESI) calcd. for C.sub.21H.sub.22FO.sub.4 [M+H].sup.+: 357.14, found: 357.10; HRMS (ESI) calcd. for C.sub.21H.sub.22FO.sub.4 [M+H].sup.+: 357.1424, found: 343.1510; m.p=172.2° C.

##STR00015##

[0084] .sup.1H NMR (400 MHz, acetone) δ 9.52 (1H, brs), 7.84 (1H, brs), 7.67-7.60 (2H, m), 7.34 (1H, dd, J=15.6, 2.8 Hz), 7.25 (1H, d, J=2.0 Hz), 7.19 (1H, dd, J=8.4, 2.0 Hz), 7.03 (1H, d, J=8.4 Hz), 6.71 (1H, d, J=12.4 Hz), 5.38-5.31 (1H, m), 3.92 (3H, s), 3.35 (2H, d, J=7.6 Hz), 1.74 (6H, s); NMR (100 MHz, acetone) δ 186.9, 161.9 (d, J=248.6 Hz), 150.7, 147.8, 143.9, 133.3, 132.6, 129.2, 125.8, 124.5, 124.4, 122.9, 122.8, 119.5 (d, J=12.6 Hz), 114.5, 112.3, 103.3 (d, J=26.5 Hz), 56.3, 28.2, 25.8, 17.8; LRMS (ESI) calcd. for C.sub.21H.sub.22FO.sub.4 [M+H].sup.+: 357.14, found: 357.10; HRMS (ESI) calcd. for C.sub.21H.sub.22FO.sub.4 [M+H].sup.+: 357.1424, found: 357.1509; m.p=167.0° C.

##STR00016##

[0085] .sup.1H NMR (400 MHz, acetone) δ 9.52 (1H, brs), 9.23 (1H, brs), 7.66-7.60 (2H, m), 7.56 (1H, dd, J=12.0, 2.0 Hz), 7.43 (1H, dd, J=8.4, 2.0 Hz), 7.38 (1H, dd, J=15.6, 2.8 Hz), 7.08 (1H, t, J=8.8 Hz), 6.71 (1H, d, J=12.4 Hz), 5.37-5.32 (1H, m), 3.35 (2H, d, J=7.6 Hz), 1.74 (6H, s); .sup.13C NMR (100 MHz, acetone) δ 186.9, 161.9 (d, J=248.9 Hz), 161.0, 160.9, 152.4 (d, J=239.9 Hz), 148.0, 142.7, 133.3, 132.6, 128.5, 126.8, 125.9, 125.1 (d, J=7.9 Hz), 122.8, 119.4 (d, J=12.7 Hz), 118.9, 116.2 (d, J=18.5 Hz), 103.3 (d, J=26.4 Hz), 28.2, 25.8, 17.8; LRMS (ESI) calcd. for C.sub.20H.sub.19F.sub.2O.sub.3 [M+H].sup.+: 345.12, found: 345.10; HRMS (ESI) calcd. for C.sub.20H.sub.19F.sub.2O.sub.3 [M+H].sup.+: 345.1224, found: 345.1308; m.p=176.1° C.

##STR00017##

[0086] .sup.1H NMR (400 MHz, acetone) δ 9.14 (1H, s), 8.92 (1H, s), 7.96 (1H, d, J=2.4 Hz), 7.92 (1H, dd, J=8.0, 2.0 Hz), 7.69 (4H, quar, J=2.4 Hz), 6.97 (1H, d, J=8.4 Hz), 6.93 (2H, d, J=8.4 Hz), 5.37-5.32 (1H, m), 3.35 (2H, d, J=7.6 Hz), 1.74 (6H, s); .sup.13C NMR (100 MHz, acetone) δ 188.1, 160.5, 160.1, 143.7, 132.9, 131.5, 131.3, 131.2, 129.2, 129.1, 127.9, 123.2, 119.8, 116.7, 115.4, 29.1, 25.9, 17.9; LRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.3 [M+H].sup.+: 309.14, found: 309.10; HRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.3 [M+H].sup.+: 309.1412, found: 309.1497; m.p=75.1° C.

##STR00018##

[0087] .sup.1H NMR (400 MHz, acetone) δ 9.19 (1H, brs), 8.59 (1H, brs), 7.96 (1H, d, J=2.4 Hz), 7.94 (1H, dd, J=8.4, 2.4 Hz), 7.77 (1H, d, J=15.6 Hz), 7.66 (1H, d, J=15.6 Hz), 7.27-7.24 (3H, m), 6.99 (1H, d, J=8.4 Hz), 6.95-6.92 (1H, m), 5.41-5.37 (1H, m), 3.41 (2H, d, J=8.0 Hz), 1.75 (6H, d, J=5.6 Hz); .sup.13C NMR (100 MHz, acetone) δ 188.2, 160.3, 158.6, 143.6, 137.6, 132.9, 131.5, 131.2, 130.8, 129.4, 129.2, 123.2, 122.9, 120.7, 118.1, 115.6, 115.5, 29.1, 25.9, 17.9; LRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.3 [M+H].sup.+: 309.14, found: 309.10; HRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.3 [M+H].sup.+: 309.1412, found: 309.1495; m.p=200.9° C.

##STR00019##

[0088] .sup.1H NMR (400 MHz, acetone) δ 9.12 (1H, brs), 7.95 (1H, d, J=2.4 Hz), 7.91 (1H, dd, J=8.4, 2.4 Hz), 7.62 (2H, d, J=4.0 Hz), 7.30 (1H, d, J=2.4 Hz), 7.17 (1H, dd, J=8.4, 2.4 Hz), 6.97 (1H, d, J=8.4 Hz), 6.90 (1H, d, J=8.0 Hz), 5.41-5.37 (1H, m), 3.41 (2H, d, J=7.6 Hz), 1.75 (6H, d, J=6.4 Hz); .sup.13C NMR (100 MHz, acetone) δ 188.1, 160.1, 148.6, 146.2, 144.1, 132.9, 131.5, 131.3, 129.19, 129.12, 128.5, 123.2, 122.8, 119.9, 116.3, 115.5, 115.4, 29.1, 25.9, 17.9; LRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.4 [M+H].sup.+: 325.13, found: 325.10; HRMS (ESI) calcd. for C.sub.20H.sub.21O.sub.4 [M+H].sup.+: 325.1362, found: 325.1444; m.p=92.1° C.

##STR00020##

[0089] .sup.1H NMR (400 MHz, acetone) δ 9.14 (1H, brs), 8.19 (1H, brs), 7.95 (1H, d, J=2.4 Hz), 7.91 (1H, dd, J=8.4, 2.4 Hz), 7.70 (2H, s), 7.46 (1H, d, J=2.0 Hz), 7.28 (1H, dd, J=8.4, 2.0 Hz), 6.97 (1H, d, J=8.4 Hz), 6.91 (1H, d, J=8.0 Hz), 5.41-5.36 (1H, m), 3.94 (3H, s), 3.40 (2H, d, J=7.2 Hz), 1.75 (6H, d, J=6.5 Hz); .sup.13C NMR (100 MHz, acetone) δ 188.1, 160.1, 150.0, 148.6, 144.2, 132.9, 131.5, 131.3, 129.2, 129.1, 128.3, 124.1, 123.2, 120.0, 116.1, 115.4, 111.7, 56.3, 29.0, 25.9, 17.9; LRMS (ESI) calcd. for C.sub.21H.sub.23O.sub.4 [M+H].sup.+: 339.15, found: 339.20; HRMS (ESI) calcd. for C.sub.21H.sub.23O.sub.4 [M+H].sup.+: 339.1518, found: 339.1601; m.p=64.2° C.

##STR00021##

[0090] .sup.1H NMR (400 MHz, acetone) δ 7.94 (1H, d, J=2.4 Hz), 7.90 (1H, dd, J=8.4, 2.4 Hz), 7.68 (2H, s), 7.46 (1H, d, J=2.0 Hz), 7.28 (1H, dd, J=8.4, 2.0 Hz), 6.96 (1H, d, J=8.4 Hz), 6.91 (1H, d, J=8.0 Hz), 5.41-5.37 (1H, m), 3.95 (3H, s), 3.40 (2H, d, J=7.2 Hz), 1.75 (6H, d, J=4.8 Hz); .sup.13C NMR (100 MHz, acetone) δ 188.1, 160.1, 150.5, 147.7, 143.8, 132.9, 131.5, 131.4, 129.5, 129.2, 129.1, 123.2, 122.9, 120.6, 115.5, 114.5, 112.2, 56.2, 29.1, 25.9, 17.9; LRMS (ESI) calcd. for C.sub.21H.sub.23O.sub.4 [M+H].sup.+: 339.15, found: 339.20; HRMS (ESI) calcd. for C.sub.21H.sub.23O.sub.4 [M+H].sup.+: 339.1518, found: 339.1601; m.p=147.3° C.

##STR00022##

[0091] .sup.1H NMR (400 MHz, acetone) δ 9.34 (2H, brs), 7.97-7.93 (2H, m), 7.76-7.63 (3H, m), 7.46 (1H, dd, J=8.4, 1.6 Hz), 7.07 (1H, t, J=8.4 Hz), 6.98 (1H, d, J=8.4 Hz), 5.41-5.36 (1H, m), 3.40 (2H, d, J=7.2 Hz), 1.74 (6H, d, J=7.2 Hz); .sup.13C NMR (100 MHz, acetone) δ 188.0, 160.3, 152.4 (d, J=239.7 Hz), 147.9, 147.8, 142.6, 132.9, 131.4, 131.2, 128.86, 128.80, 127.0, 123.2, 121.3, 118.8, 116.0 (d, J=18.6 Hz), 115.4, 29.1, 25.9, 17.9; LRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.3 [M+H].sup.+: 327.13, found: 327.10; HRMS (ESI) calcd. for C.sub.20H.sub.20FO.sub.3 [M+H].sup.+: 327.1318, found: 327.1404; m.p=87.6° C.

Experimental Example 1

[0092] It is well known that the expression of inflammatory cytokines increases by LPS stimulation in RAW 264.7 macrophages and that nitric oxide (NO) increases by overexpression of iNOS protein. Excessive secretion of inflammatory cytokines and increase in NO are one of the causes of inflammatory bowel disease, and thus inhibiting or reducing them is used as one of the criteria for evaluating anti-inflammatory efficacy.

[0093] Particularly, as the most important pathological process causing mucosal damage in inflammatory bowel disease, the adhesion of monocytes activated by TNFα to the intestinal mucosa and migration into tissues has been recently reported. When TNFα is treated in colonic epithelial cells such as HT29, the expression of chemokines such as MCP-1 and IL-8 is increased, and the expression of adhesion molecules such as ICAM-1 and VCAM-1 is increased.

[0094] Accordingly, in Experimental Example 1, it was confirmed whether secretion of TNFα as an inflammatory cytokine can be inhibited by the Compound according to the present invention.

[0095] RAW 264.7 macrophages were treated with 0.1 μg/mL of E. coli-derived LPS and 25 μM of Compounds A1 to A6, B1 to B6, or C1 to C6, respectively. Then, the mRNA expression level of the inflammatory cytokine TNFα was observed through RT-PCR. The results are shown in FIGS. 1a to 1c.

[0096] As seen in FIGS. 1a to 1c, it shows that the mRNA expression level of TNFα in the E. coli-derived LPS treatment group was significantly increased compared to that in the NC group (negative control group).

[0097] The A1 treatment group shows that the increase in the mRNA expression level of TNFα induced by LPS stimulation is suppressed by treatment with broussochalcone A, which corresponds to the positive control group.

[0098] Groups treated with the compound according to the present invention show that the increase in the mRNA expression level of TNFα is significantly more suppressed than the A1 treatment group. This means that inflammatory cytokines, which are important factors in the mechanism of action of inflammatory bowel disease, can be significantly inhibited by the compound according to the present invention.

Experimental Example 2

[0099] In Experimental Example 2, the mRNA expression level of inflammatory cytokines other than TNFα was observed in the same manner as in Experimental Example 1.

[0100] FIGS. 2a and 2b show the result of representing the mRNA expression level of COX2. FIGS. 3a and 3b show the result of representing the mRNA expression level of iNOS. FIG. 4 shows the result of representing the mRNA expression level of IL-1α. FIG. 5 shows the result of representing the mRNA expression level of IL-1β. FIG. 6 shows the result of representing the mRNA expression level of MCP1.

[0101] As seen in FIGS. 2 to 6, it shows that compared to the NC group (negative control group), the E. coli-derived LPS treatment group significantly increased the mRNA expression level of all other inflammatory cytokines like TNFα. In addition, it was also observed that the increase in the mRNA expression level of these inflammatory cytokines was suppressed by the treatment with broussochalcone A.

[0102] In the groups treated with the compound according to the present invention, the mRNA expression levels of COX2, iNOS, IL-1α, IL-1β, and MCP1 were significantly more suppressed than the A1 treatment group. This means that inflammatory cytokines, which are important factors in the mechanism of action of inflammatory bowel disease, can be significantly inhibited by the compound according to the present invention. Therefore, the compound according to the present invention is an active ingredient capable of treating, improving, and preventing inflammatory bowel disease which can exhibit more excellent effects than conventional therapeutic agents.

Experimental Example 3

[0103] Nitric oxide (NO), which is increased by LPS stimulation in RAW 264.7 macrophages, is one of the causes of inflammatory bowel disease along with inflammatory cytokines. Therefore, in Experimental Example 3, it was confirmed in the same manner as in Experimental Example 1 whether NO produced by LPS stimulation could be reduced by the compound according to the present invention.

[0104] FIGS. 7a and 7b show the results of observing NO concentration (μM).

[0105] As seen in FIG. 7, compared to the NC group (negative control group), the E. coli-derived LPS treatment group significantly increased the NO level, which was suppressed by treatment with broussochalcone A. Groups treated with the compound according to the present invention significantly more suppressed the NO level than the A1 treatment group.

[0106] This means that nitric oxide, which is an important factor in the mechanism of action of inflammatory bowel disease, can be significantly inhibited by the compound according to the present invention. Therefore, the compound according to the present invention is an active ingredient capable of treating, improving, and preventing inflammatory bowel disease, and can exhibit more excellent effects than conventional therapeutic agents.

[0107] Therefore, the compound according to the present invention or a pharmaceutically or sitologically acceptable salt thereof can be usefully used as an active ingredient of a composition for treating, improving, or preventing inflammatory bowel disease.