Substituted Porphyrins

Abstract

The present invention relates, in general, to a method of modulating physiological and pathological processes and, in particular, to a method of modulating cellular levels of oxidants and thereby processes in which such oxidants are a participant. The invention also relates to compounds and compositions suitable for use in such methods.

1 . A compound of formula  
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, 
 wherein 
 each R is, independently, a C 1 -C 8  alkyl group, and  
 each P is, independently, an electron withdrawing group or hydrogen,  
 
 wherein when each R is methyl and each P is hydrogen, said compound is completed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.  
 
     
     
         2 . The compound according to  claim 1  where each R is independently a C 1 -C 4  alkyl group.  
     
     
         3 . The compound according to  claim 2  wherein each R is, independently, a methyl, ethyl or isopropyl group.  
     
     
         4 . The compound according to  claim 3  wherein each R is, independently, a methyl or an ethyl group.  
     
     
         5 . The compound according to  claim 1  wherein each P is, independently, hydrogen or an electron withdrawing group selected from the group consisting of —NO 2 , a halogen, a nitrile, a vinyl group and a formyl group.  
     
     
         6 . The compound according to  claim 1  wherein at least one P is a halogen.  
     
     
         7 . The compound according to  claim 1  wherein one or two P's are formyl groups and the remaining P's are hydrogen.  
     
     
         8 . The compound according to  claim 1  wherein one P is a formyl group and the remaining P's are hydrogen.  
     
     
         9 . The compound according to  claim 1  wherein one or two P's are —NO 2  and the remaining P's are hydrogen.  
     
     
         10 . The compound according to  claim 1  wherein said compound is completed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.  
     
     
         11 . The compound according to  claim 10  wherein said compound is completed with manganese.  
     
     
         12 . The compound according to  claim 1  wherein each R is a methyl or ethyl group, each P is a hydrogen, and said compound is completed with manganese.  
     
     
         13 . The compound according to  claim 1  wherein each R is a methyl or ethyl group, at least one 2 is Br and the remaining P's are hydrogen and said compound is complexed with manganese.  
     
     
         14 . The compound according to  claim 1  wherein said compound is a mixture of atrocoisomers αααα, αααβ, ααββ and αβαβ.  
     
     
         15 . The compound according to  claim 1  wherein said compound is a mixture of αααβ and αααα atropoisomers.  
     
     
         16 . A method of protecting cells from oxidant-induced toxicity comprising contacting said cells with a protective amount of a compound of formula  
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, 
 wherein 
 each R is, independently, a C 1 -C 8  alkyl group, and  
 each P is, independently, an electron withdrawing group or hydrogen.  
 
 
     
     
         17 . The method according to  claim 16  wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.  
     
     
         18 . The method according to  claim 16  wherein said cells are mammalian cells.  
     
     
         19 . A method of treating a pathological condition of a patient resulting from oxidant-induced toxicity comprising administering to said patient an effective amount of a compound of formula  
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, 
 wherein 
 each R is, independently, a C 1 -C 8  alkyl group, and  
 each P is, independently, an electron withdrawing group or hydrogen.  
 
 
     
     
         20 . The method according to  claim 19  wherein said compound is completed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.  
     
     
         21 . A method of treating a pathological condition of a patient resulting from degradation of NO. or a biologically active form thereof, comprising administering to said patient an effective amount of a compound of formula  
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, 
 wherein 
 each R is, independently, a C 1 -C 8  alkyl group, and  
 each P is, independently, an electron withdrawing group or hydrogen.  
 
 
     
     
         22 . The method according to  claim 21  wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.  
     
     
         23 . A method of treating a patient for inflammatory lung disease comprising administering to said patient an effective amount of a compound of formula  
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof, 
 wherein 
 each R is, independently, a C 1 -C 8  alkyl group, and  
 each P is, independently, an electron withdrawing group or hydrogen.  
 
 
     
     
         24 . The method according to  claim 23  wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.  
     
     
         25 . The method according to  claim 24  wherein said metal is manganese.  
     
     
         26 . The method according to  claim 23  wherein said inflammatory lung disease is a hyper-reactive airway disease.  
     
     
         27 . The method according to  claim 23  wherein said inflammatory lung disease is asthma.