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Novel compound having immune disease treatment effect and use thereof

Inactive Publication Date: 2017-04-27
THE CATHOLIC UNIV OF KOREA IND ACADEMIC COOPERATION FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention introduces a new molecule that can effectively prevent and treat immune diseases. This new compound has the ability to inhibit the production of inflammatory cytokines, increase the activity of regulatory T cells, inhibit the production of auto-antibodies, and inhibit the differentiation of osteoclasts. Due to these effects, this new molecule can be used to treat a wide range of immune diseases caused by abnormal regulation of various immune responses.

Problems solved by technology

Accordingly, while the host is not controlled due to the lack of the inflammatory response, the host is damaged (that is, inflected), and therefore, due to the chronic inflammation, partially, some of the aforementioned mediators are excessively generated and the mediated inflammatory diseases are caused.
However, such a pharmacological therapy acts on a variety of targets to entirely decrease the immune function.
If not, in the case of using the pharmacological therapy for a long time, a variety of cytotoxic actions become the problem to suppress the immune system by a non-specific manner and thus the patients may be exposed to the risk of infections and cancer.
Calcineurin and glucocorticoid have another problem due to their nephrotoxicity and diabetes induced characteristics, and thus in the case of some of the clinical symptoms (e.g., renal insufficiency, diabetes, etc.), the use thereof is restricted.

Method used

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  • Novel compound having immune disease treatment effect and use thereof
  • Novel compound having immune disease treatment effect and use thereof
  • Novel compound having immune disease treatment effect and use thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Synthesis of Novel Compound having Effect of Treating Immune Diseases according to the Present Invention

[0166]The novel compounds represented by chemical formulas in the following Table 1 were prepared by a method of the following reaction formula. In detail, first, in a sealed reactor, an aniline compound of 1.0 mmol was dissolved in an acetonitrile solvent and then added with 1.0 mmol dicyandiamide and 1.0 mmol concentrated sulfuric acid, sealed, and stirred for 1 hr at 175° C. Thereafter, the solution was cooled at room temperature to produce a white solid and washed by hexane and isopropyl alcohol after the solvent was removed to synthesize the following compounds having a white solid form.

[0167]In processes for synthesizing a total of 24 compounds, other compounds except for an aniline compound were synthesized under the same condition, and a kind of aniline used for the synthesis of each compound and chemical names and structural formulas of the synthesized compounds are as di...

experimental example 1

Analysis Result of Cytotoxicity of Novel Compounds according to the Present Invention

[0189]In order to verify whether the novel compounds synthesized in Example 1 have the cytotoxicity, a cell survival rate was verified through the MTT assay by targeting cells in each test group disclosed in Table 3 above. That is, the cells of each test group were divided according to the number of 2×105 cells per well and treated with the novel synthesized compounds of the present invention for each concentration, and the cell survival rate was analyzed.

[0190]As a result, in SD-281, SD-282, SD-283, and SD-284 compounds, it can be seen that when compared with a control group or a metformin-treated group, the cytotoxicity was not observed according to treatment for each cell concentration and the compounds had no cytotoxicity according to normal cells and disease-group cells.

experimental example 2

[0191]Result of Effect on Autoantibody Production and Immune Response Regulation of Novel Compounds according to the Present Invention

[0192]In order to examine an effect on an immune response by producing auto-antibodies of the novel compounds synthesized in Example 1, the blood was obtained from each mouse group through orbital bleeding from mice in the four groups described above and the serum was isolated from the blood, and the amount of IgG, IgG1, and IgG2a was measured.

[0193]As a result, in the compounds of the present invention, it was shown that the amount of immunoglobulin (total IgG, IgG1, and IgG2) which was in the auto-antibody production state under the disease condition was reduced for each processing concentration of the compound, and it can be seen that in compounds disclosed in the following Table 4, an immunoregulatory function of inhibiting excessive immune response was excellent.

TABLE 4Total IgGIgG1IgG2ABCABCABCControl1183.2141.5311.4286422.3103.2109.6151.9groupS...

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Abstract

The present invention relates to a novel compound capable of effectively preventing and treating immune diseases and a use thereof. The novel compound of the present invention has effects of inhibiting the production of inflammatory cytokines, increasing the activity of regulatory T cells having immunoregulatory functions, inhibiting the production of auto-antibodies to regulate excessive immune responses, and inhibiting the differentiation of osteoclasts, and thus can be used for treating immune diseases, such as autoimmune disease, inflammatory disease, and transplant rejection diseases, which are caused by abnormal regulation of various kinds of immune response

Description

TECHNICAL FIELD[0001]The present invention relates to a novel compound capable of effectively preventing and treating immune diseases and a use thereof.BACKGROUND ART[0002]An immune disease is a disease mean diseases in which components cause, mediate, or contribute the pathological conditions of the mammals, and particularly, inflammatory disorder is one of the most important health problems around the world. Inflammation is a generally localized protective response of body tissues to the host intrusion by external substances or harmful stimuli. The cause of inflammation may be a state associated with infectious causes such as bacteria, viruses, and parasites; physical causes such as burns or radiation; chemicals such as toxins, drugs, or industrial agents; it may be a condition associated with the immune responses such as allergy and autoimmune responses, or oxidative stress.[0003]The inflammation is characterized by pain, a red phenomenon, swelling, heat, and an eventual function...

Claims

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Application Information

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IPC IPC(8): C07C279/18
CPCC07C279/18C07C279/26A61P1/04A61P1/16A61P11/06A61P13/12A61P15/00A61P17/00A61P17/06A61P17/14A61P19/02A61P21/00A61P21/04A61P25/00A61P27/16A61P29/00A61P37/00A61P37/02A61P37/06A61P5/14A61P7/00A61P7/06A61P9/00A61P3/10
Inventor CHO, MI-LASHIN, DONG-YUNPARK, SUNG-HWANYANG, CHUL-WOOCHOI, JONG-YOUNGPARK, MIN-JUNGSON, HYE-JINLEE, SUNG-HEELEE, SEON-YEONGKIM, EUN-KYUNGKIM, JAE-KYUNGLEE, SEUNG-HUNPARK, SEONG-HYEOK
Owner THE CATHOLIC UNIV OF KOREA IND ACADEMIC COOPERATION FOUND