Agent for inhibition of cytokine production and agent for inhibition of cell adhesion

Abstract

The present invention provides an agent for inhibiting cytokine production or cell adhesion, comprising at least one compound selected from the group consisting of thiazole derivatives represented by the following general formula: [wherein R 1 is a phenyl group which may have a lower alkoxy group(s) as a substituent(s) on the phenyl ring, and R 2 is a group represented by the following general formula: (wherein R 3 's, which may be the same or different, are each a carboxyl group, a lower alkoxy group or the like) or the like] and salts thereof.

1 . An agent for inhibiting cytokine production, comprising, as the active ingredient, at least one compound selected from the group consisting of thiazole derivatives represented by the following general formula:  
       
         
           
           
               
               
           
         
       
       {wherein R 1  is a phenyl group which may have a lower alkoxy group(s) as a substituent(s) on the phenyl ring; and R 2  is a group represented by the following general formula:  
       
         
           
           
               
               
           
         
       
       [wherein the R 3  groups, which may be the same or different, are each a carboxyl group, a lower alkoxy group, a lower alkyl group, a lower alkenyl group, a group represented by —(A) l —NR 4 R 5  (A is a lower alkylene group; R 4  and R 5 , which may be the same or different, are each a hydrogen atom or a lower alkyl group; and l is 0 or 1), a hydroxyl group-substituted lower alkyl group, a lower alkoxy group-substituted lower alkoxy group, a lower alkoxy group-substituted lower alkoxycarbonyl group or a carboxyl group-substituted lower alkoxy group; and m is an integer of 1-3], or a heterocyclic ring residue having 1-2 hetero atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, which heterocyclic ring residue may have, as a substituent(s) on the heterocyclic ring, 1-3 groups selected from the group consisting of carboxyl group and lower alkoxy group} and salts thereof.  
     
     
         2 . An agent for inhibition of adhesion of neutrophils to vascular endothelial cells, comprising, as the active ingredient, at least one compound selected from the thiazole derivatives and salts thereof set forth in  claim 1 .  
     
     
         3 . An agent for inhibiting TNF-α production, comprising, as the active ingredient, at least one compound selected from the thiazole derivatives and salts thereof set forth in  claim 1 .  
     
     
         4 . The agent for inhibiting cytokine production according to  claim 1 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.  
     
     
         5 . The agent for inhibition of adhesion of neutrophils to vascular endothelial cells according to  claim 2 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.  
     
     
         6 . The agent for inhibiting TNF-α production according to  claim 3 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.  
     
     
         7 . Use of a compound for the production of a medicament for inhibiting cytokine production, which medicament comprises, at least one active ingredient selected from the group consisting of thiazole derivatives represented by the following general formula:  
       
         
           
           
               
               
           
         
       
       {wherein R 1  is a phenyl group which may have a lower alkoxy group(s) as a substituent(s) on the phenyl ring; and R 2  is a group represented by the following general formula:  
       
         
           
           
               
               
           
         
       
       [wherein the R 3  groups, which may be the same or different, are each a carboxyl group, a lower alkoxy group, a lower alkyl group, a lower alkenyl group, a group represented by —(A) l —NR 4 R 5  (A is a lower alkylene group; R 4  and R 5 , which may be the same or different, are each a hydrogen atom or a lower alkyl group; and l is 0 or 1), a hydroxyl group-substituted lower alkyl group, a lower alkoxy group-substituted lower alkoxy group, a lower alkoxy group-substituted lower alkoxycarbonyl group or a carboxyl group-substituted lower alkoxy group; and m is an integer of 1-3], or a heterocyclic ring residue having 1-2 hetero atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, which heterocyclic ring residue may have, as a substituent(s) on the heterocyclic ring, 1-3 groups selected from the group consisting of carboxyl group and lower alkoxy group} and salts thereof.  
     
     
         8 . Use of a compound for the production of a medicament for inhibition of adhesion of neutrophils to vascular endothelial cells, which medicament comprises, at least one active ingredient set forth in  claim 7 .  
     
     
         9 . Use of a compound for the production of a medicament for inhibiting TNF-α production, which medicament comprises, at least one active ingredient set forth in  claim 7 .  
     
     
         10 . The use according to  claim 7 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.  
     
     
         11 . The use according to  claim 8 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.  
     
     
         12 . The use according to  claim 9 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.  
     
     
         13 . A method for inhibiting cytokine production by administering to a patient in need thereof an agent for inhibiting cytokine production comprising, as the active ingredient, at least one compound selected from the group consisting of thiazole derivatives represented by the following general formula:  
       
         
           
           
               
               
           
         
       
       {wherein R 1  is a phenyl group which may have a lower alkoxy group(s) as a substituent(s) on the phenyl ring; and R 2  is a group represented by the following general formula:  
       
         
           
           
               
               
           
         
       
       [wherein the R 3  groups, which may be the same or different, are each a carboxyl group, a lower alkoxy group, a lower alkyl group, a lower alkenyl group, a group represented by —(A) l —NR 4 R 5  (A is a lower alkylene group; R 4  and R 5 , which may be the same or different, are each a hydrogen atom or a lower alkyl group; and l is 0 or 1), a hydroxyl group-substituted lower alkyl group, a lower alkoxy group-substituted lower alkoxy group, a lower alkoxy group-substituted lower alkoxycarbonyl group or a carboxyl group-substituted lower alkoxy group; and m is an integer of 1-3], or a heterocyclic ring residue having 1-2 hetero atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, which heterocyclic ring residue may have, as a substituent(s) on the heterocyclic ring, 1-3 groups selected from the group consisting of carboxyl group and lower alkoxy group} and salts thereof.  
     
     
         14 . A method for inhibition of adhesion of neutrophils to vascular endothelial cells by administering to a patient in need thereof an agent for inhibition of adhesion of neutrophils to vascular endothelial cells comprising, as the active ingredient, at least one compound set forth in  claim 13 .  
     
     
         15 . A method for inhibiting TNF-α production by administering to a patient in need thereof an agent for inhibiting TNF-α production comprising, as the active ingredient, at least one compound set forth in  claim 13 .  
     
     
         16 . The method for inhibiting cytokine production according to  claim 13 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.  
     
     
         17 . The method for inhibition of adhesion of neutrophils to vascular endothelial cells according to  claim 14 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.  
     
     
         18 . The method for inhibiting TNF-α production according to  claim 15 , wherein the active ingredient is 6-[2-(3,4-diethoxyphenyl)thiazole-4-yl]pyridine-2-carboxylic acid.