Novel compound having immune disease treatment effect and use thereof

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

1 . A compound represented by the following Chemical Formula or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         In Chemical Formula, X is at least one of F, Cl, Br, or H; and R is hydrogen or alkyl. 
       
     
     
         2 . The compound of  claim 1 , wherein the compound is any one selected from compounds 1 to 24 disclosed in the following Table. 
       
         
           
                 
                 
                 
                 
               
                     
                 
                     
                   Compound 
                     
                     
                 
                   No. 
                   Code 
                   Compound Name 
                   Compound Structure 
                 
                     
                 
                    1 
                   8D-281 
                   N-(3,4-Difluorophenyl)-N- ethylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    2 
                   8D-282 
                   N-Ethyl-N-(4-fluorophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    3 
                   8D-283 
                   N-(2,4-Difluorophenyl)-N- ethylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    4 
                   8D-284 
                   N-(2,4-Difluorophenyl)-N- methylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    5 
                   8D-562 
                   N-(4-Chlorophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    6 
                   8D-563 
                   N-(4-Bromophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    7 
                   8D-564 
                   N-(3-Chlorophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    8 
                   8D-565 
                   N-(3-Bromophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    9 
                   8D-566 
                   N-(4-Chlorophenyl)-N- ethylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   10 
                   8D-567 
                   N-(4-Bromophenyl)-N- ethylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   11 
                   8D-568 
                   N-(3-Chlorophenyl)-N- ethylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   12 
                   8D-569 
                   N-(3-Bromophenyl)-N- ethylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   13 
                   8D-570 
                   N-Phenylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   14 
                   8D-571 
                   N-(3,5-Difluorophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   15 
                   8D-572 
                   N-(3,4-Difluorophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   16 
                   8D-573 
                   N-Ethyl-N-phenyl biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   17 
                   8D-574 
                   N-Ethyl-N-(2-fluorophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   18 
                   8D-575 
                   N-Ethyl-N-(3-fluorophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   19 
                   8D-576 
                   N-(3,5-Difluorophenyl)-N- ethylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   20 
                   8D-577 
                   N-(2,5-Difluorophenyl)- N-ethylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   21 
                   8D-578 
                   N-Ethyl-N-(2,3,4-trifluorophenyl) biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   22 
                   8D-579 
                   N-Phenyl-N-isopropyl- biguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   23 
                   8D-580 
                   N-(2,4-Difluorophenyl)-N- propylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   24 
                   8D-581 
                   N-(4-Difluorophenyl)-N- propylbiguanide 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         3 . A pharmaceutical composition for preventing or treating immune diseases, the pharmaceutical composition comprising the compound of  claim 1  as an active ingredient. 
     
     
         4 . The pharmaceutical composition for preventing or treating immune diseases of  claim 1 , wherein the compound decreases or inhibits the production of inflammatory cytokines, inhibits the production of auto-antibodies, and inhibits the differentiation of osteoclasts. 
     
     
         5 . The pharmaceutical composition for preventing or treating immune diseases of  claim 4 , wherein the inflammatory cytokine is IL-17, IL-6, TNF-α, IFN-γ, MMP-9, or STAT-3. 
     
     
         6 . The pharmaceutical composition for preventing or treating immune diseases of  claim 4 , wherein the antibody is IgG, IgG1, or IgG2a. 
     
     
         7 . The pharmaceutical composition for preventing or treating immune diseases of  claim 1 , wherein the compound promotes or increases the activity of regulatory T cells and decreases or inhibits the activity of Th17 cells as pathological cells. 
     
     
         8 . The pharmaceutical composition for preventing or treating immune diseases of  claim 1 , wherein the compound is included in the concentration of 0.1 mM to 10 mM in the composition. 
     
     
         9 . The pharmaceutical composition for preventing or treating immune diseases of  claim 1 , wherein the immune disease is selected from the group consisting of autoimmune diseases; inflammatory diseases; and transplantation rejection diseases of cells, tissues or organs. 
     
     
         10 . The pharmaceutical composition for preventing or treating immune diseases of  claim 9 , wherein the immune disease is selected from rheumatoid arthritis, Behcet's disease, multiple myositis or skin myositis, autoimmune hematocytopenia, autoimmune myocarditis, atopic dermatitis, asthma, primary cirrhosis, dermatomyositis, Goodpasture syndrome, autoimmune meningitis, sjogren's syndrome, lupus, Addison's disease, alopecia areata, ankylosing myelitis, autoimmune hepatitis, autoimmune mumps, Crohn's disease, insulin-dependent diabetes, dystrophic epidermolysis bullosa, epididymitis, glomerulonephritis, Graves' disease, Guillain-Barre syndrome, Hashimoto's disease, hemolytic anemia, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, psoriasis, rheumatic fever, sarcoidosis, scleroderma, spinal arthrosis, thyroiditis, vasculitis, vitiligo, myxedema, pernicious anemia, mitochondrial-related syndromes, and ulcerative colitis. 
     
     
         11 . The pharmaceutical composition for preventing or treating immune diseases of  claim 9 , wherein the transplantation rejection disease is a graft versus host disease. 
     
     
         12 . An immunoregulatory agent comprising the compound of  claim 1  as an active ingredient. 
     
     
         13 . A method of decreasing differentiation of undifferentiated T cells into Th17 cells and activity of the Th17 cells, the method comprising treating the compound of  claim 1  to the undifferentiated T cells in vitro. 
     
     
         14 . A method of increasing differentiation of undifferentiated T cells into Treg cells and activity of the Treg cells, the method comprising treating the compound of  claim 1  to the undifferentiated T cells in vitro.