Novel use of porphyrin derivatives

Abstract

The present invention is related to novel use of photopyrin compounds useful as an anticancer agent by way of reproducing singlet state oxygen radical and the inventive compounds showed potent inhibition effect on colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer. Accordingly, the porphyrin compound of the present invention can be useful in treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in human or mammal.

1 . A method of treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in a mammal said method comprises administering a therapeutically effective amount of porphyrin derivatives represented by the following formula (I), and the pharmaceutically acceptable salts thereof:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1 , R 2  is independently a straight or branched lower alkyl or alkoxy group having 1 to 6 carbon atoms, a polyethyleneglycol group or a sulfonyl group;  
 R 3  is a hydrogen atom, an alkoxy group having 1 to 6 carbon atoms or a polyethyleneglycol group;  
 R 4  is a hydrogen atom, a hydroxyl group or an alkoxy group having 1 to 6 carbon atom,  
 A is linked directly or bridged with oxygen atom, which can be chelating with transition metal ion comprising Ni metal ion.  
 
   
   
       2 . The method of  claim 1 , said porphyrin derivative represented by the formula (I), comprise the compounds wherein R 1 , R 2  is selected from the group consisting of an ethyl group, a propyl group, an ethyleneglycol group, diethyleneglycol group, triethyleneglycol group, tetraethyleneglycol group, hexaethyleneglycol group, heptaethyleneglycol group or a methoxyethyleneglycol group; R 3  is selected from the group consisting of a hydrogen atom, an ethyl group, a propyl group, a methoxy, an ethoxy group, an ethyleneglycol group, triethyleneglycol group, hexaethylene group; R 4  is a hydrogen atom, a hydroxyl group or an methoxy group; and A is linked directly providing that R 1  and R 2  is the same group and R 2  is different from R 1  or R 3 .  
   
   
       3 . A method of treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in a mammal said method comprises administering a therapeutically effective amount of porphyrin derivatives represented by the following formula (II), and the pharmaceutically acceptable salts thereof:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1 , R 2  is independently a straight or branched lower alkyl or alkoxy group having 1 to 6 carbon atoms, a polyethyleneglycol group or a sulfonyl group, which can be chelating with transition metal ion comprising Ni metal ion.  
 wherein X is oxygen atom; A is —CH 2 —; R 1  is hydrogen atom or aminoethyl group; R 2  is an hydrogen or halogen atom or an alkyl group having 1 to 6 carbon atoms.  
 
   
   
       4 . A method of treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in a mammal said method comprises administering a therapeutically effective amount of porphyrin derivatives represented by the following general formula (III), and the pharmaceutically acceptable salts thereof:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is a polyethyleneglycol group;  
 R 4  is a hydrogen atom or a hydroxyl group.  
 
   
   
       5 . A method of treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in a mammal said method comprises administering a therapeutically effective amount of porphyrin derivatives represented by the following general formula (IV), and the pharmaceutically acceptable salts thereof:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 2  is a bromopropyl group, or a polyethyleneglycol group;  
 R 4  is a hydrogen atom or a hydroxyl group.  
 
   
   
       6 . A method of treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in a mammal said method comprises administering a therapeutically effective amount of porphyrin derivatives represented by the following general formula (V), the pharmaceutically acceptable salts thereof:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is a methyl, ethyl group, or an ethyleneglycol group.  
 
   
   
       7 . A method of treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in a mammal said method comprises administering a therapeutically effective amount of porphyrin derivatives represented by the following general formula (VI), the pharmaceutically acceptable salts thereof:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1 , R 2  is independently a polyethyleneglycol group.  
 
   
   
       8 . A method of treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in a mammal said method comprises administering a therapeutically effective amount of porphyrin derivatives represented by the following general formula (VII), the pharmaceutically acceptable salts thereof:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is a polyethyleneglycol group.  
 
   
   
       9 . The method of  claim 1 , said porphyrin derivative represented by the formula (VII), comprise the compounds wherein X is oxygen atom; A is —NHCH 2 —; R 1  is hydrogen atom or aminoethyl group; R 2  is an hydrogen or halogen atom or an alkyl group having 1 to 6 carbon atoms.  
   
   
       10 . The method of  claim 1 , said porphyrin derivative represented by the formula (I) comprise the compound which is one selected from the group consisting of 
 N-[4-(3,4-dimethylphenyl)-2-(pivaloyloxymethyl)butyl]-N-[4-hydroxy-3-methoxybenzyl]thiourea,    N-[4-t-bytulphenyl-2-(pivaloyloxymethyl)butyl]-N-[4-hydroxy-3-methoxybenzyl]thiourea,    N-[4-(3,4-dimethylphenyl)-2-(pivaloyloxymethyl)butyl]-N-[4-hydroxy-3-methoxybenzyl]urea,    N--[4-t-dimethylphenyl-2-(pivaloyloxymethyl)butyl]-N-[4-hydroxy-3-methoxybenzyl]urea,    N-[4-(3,4-dimentylphenyl-2-(pivaloyloxymethyl)butyl)-2-[4-hydroxy-3-methoxyphenyl]acetamide,    N-[4-(4-t-butylphenyl)-2-(pivaloyloxymethyl)butyl]-2-[4-hydroxy-3-methoxyphenyl]acetamide,    N-[4-(3,4-dimethylphenyl)-2-(pivaloyloxymethyl)butyl]-2-[4-(2-aminoethoxy)-3-methoxyphenyl]acetamide,    N-[4-(4-t-butylphenyl)-2-(pivaloyloxymethyl)butyl]-2-[4-(2-aminethoxy)-3-methoxyphenyl]acetamide.    
   
   
       11 . A use of porphyrin compound selected from the group consisting of compounds of formula (I) to (VII) as set forth in claims  1  and  3  to  8  or pharmaceutical acceptable salts thereof as an anticancer agent to treat or prevent colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer.  
   
   
       12 . A use of porpyrin compound (I) to (VII) as set forth in  claim 1  and  3  to  8  for the manufacture of medicament employed for treating or preventing colon cancer, cervical cancer, gastric cancer, cystic cancer or lung cancer in human or mammal.