Substituted porphyrins

Abstract

Substituted metalloporphyrin compounds are described, along with pharmaceutical compositions containing the same, and methods of use thereof in protecting cells from oxidant-induced toxicity and pathological conditions such as inflammatory lung disease, neurodegenerative conditions, radiation injury, cancer, diabetes, cardiac conditions and sickle cell disease. Mn(III) porphyrins bearing oxygen atoms within side chains are particularly described.

What is claimed is: 
     
         1 . A compound of formula 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         when the compound is of Formula I-VI, each R is, independently, —(CH 2 ) m CH 2 OX or —(CH 2 CH 2 O) n X, 
         wherein
 m is 1-6, 
 n is 3-50, 
 X is C 1-12 alkyl (straight chain or branched), 
 
         when the compound is of Formula VII or VIII, at least one R on each imadazole ring is, independently, —(CH 2 ) m CH 2 OX or (CH 2 CH 2 O) n X, the other R being, independently, a C 1 -C 12 alkyl, (straight chain or branched), 
         wherein
 m is 1-6, 
 n is 3-50, 
 X is C 1-12 alkyl (straight chain or branched), 
 
         when the compound is any of Formulas I-VIII, each A is, independently, hydrogen or an electron withdrawing group, 
         M is metal selected from the group consisting of manganese, iron, copper, cobalt, nickel and zinc, and 
         Z −  is a counterion. 
       
     
     
         2 . The compound according to  claim 1  wherein at least one A is halogen, NO 2  or CHO. 
     
     
         3 . The compound according to  claim 1  wherein said compound is of Formula I, III, V or VII and M is manganese 
     
     
         4 . The compound according to  claim 1  where said compound is of Formula V, VI, VII or VIII. 
     
     
         5 . A method of protecting cells from oxidant-induced toxicity comprising treating said cells with a protective amount of the compound of  claim 1  under conditions such that the protection is effected. 
     
     
         6 . The method according to  claim 5  wherein said cells are mammalian cells. 
     
     
         7 . A method of treating a pathological condition of a patient resulting from oxidant-induced toxicity comprising administering to said patient an effective amount of the compound of  claim 1  under conditions such that the treatment is effected. 
     
     
         8 . A method of treating a pathological condition of a patient resulting from degradation of NO. comprising administering to said patient an effective amount of the compound of  claim 1  under conditions such that the treatment is effected. 
     
     
         9 . A method of treating a patient for inflammatory lung disease comprising administering to said patient an effective amount of the compound of  claim 1  under conditions such that the treatment is effected. 
     
     
         10 . A method of treating a neurodegenerative condition of a patient comprising administering to the patient an effective amount of the compound of  claim 1 . 
     
     
         11 . A method of treating radiation injury and cancer of a patient comprising administering to the patient an effective amount of the compound of  claim 1 . 
     
     
         12 . A method of treating a diabetic condition of a patient comprising administering to the patient an effective amount of the compound of  claim 1 . 
     
     
         13 . A method of treating a cardiac condition of a patient comprising administering to the patient an effective amount of the compound of  claim 1 . 
     
     
         14 . A method of treating sickle cell disease in a patient comprising administering to the patient an effective amount of the compound of  claim 1 .