Novel chain-breaking antioxidants

Abstract

Compounds, preferably 5-pyrimidinol and 3-pyridinol derivatives, that act as effective chain breaking antioxidants of both the lipid and water-soluble variety (analogous to the natural Vitamins E and C), many of which are more reactive toward peroxyl radicals than the most potent form of Vitamin E. These compounds may exhibit many chemopreventive effects associated with conditions in which free radical-mediated cellular damage or disruption is implicated and Vitamins E and C are shown to have protective effects. Additionally, these compounds should be excellent oxidation inhibitors as additives to fuels, lubricants, rubber, polymers, chemicals, solvents and foodstuffs.

1 . A compound of the following formula, and acid or base addition salts thereof: 
     
       
         
         
             
             
         
       
     
     wherein,
 R 1  is selected from the group consisting of hydrogen, alkyl, amino, alkylamino, and N,N-dialkylamino; 
 R 2  is selected from the group consisting of hydrogen and alkyl; and 
 R 3  is an electron-donating substituent. 
 
   
   
       2 . A method of inducing antioxidant activity in warm-blooded animals comprising administering to warm-blooded animals an antioxidatingly effective amount of a composition comprising the formula of  claim 1 . 
   
   
       3 . A method of treating free radical-mediated cellular damage in warm-blooded animals, comprising administering to warm-blooded animals an antioxidatively effective amount of a composition comprising the formula of  claim 1 . 
   
   
       4 . A method of inducing antioxidant activity in warm-blooded animals comprising administering to warm-blooded animals an antioxidatingly effective amount of a biologically active composition, the biologically active composition comprising a compound of the following formula, or an acid or base addition salt thereof: 
     
       
         
         
             
             
         
       
       wherein, 
       X is N—R 5  or O; 
       R 1  is selected from the group consisting of hydrogen, and, alkyl; 
       R 2  is selected from the group consisting of hydrogen, alkyl; 
       R 3  is selected from the group consisting of hydrogen, alkyl; 
       R 4  is selected from the group consisting of hydrogen, alkyl; 
       R 5  is selected from the group consisting of hydrogen, alkyl; and 
       n is 1 or 2. 
     
   
   
       5 . The method of  claim 4 , wherein the compound is selected from the following formula: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  is selected from the group consisting of hydrogen and methyl; 
 R 2  is selected from the group consisting of hydrogen, methyl, ethyl, t-butyl, pentyl, octyl, phytyl; 
 R 3  is selected from the group consisting of hydrogen, methyl and t-butyl; and 
 R 4  is selected from the group consisting of hydrogen, methyl, ethyl, t-butyl, pentyl, octyl, phytyl. 
 
   
   
       6 . The method of  claim 4 , wherein the compound is of the following formula or an acid or base addition salt thereof: 
   
   
       7 . A method of treating free radical-mediated cellular damage in warm-blooded animals, comprising administering to warm-blooded animals an antioxidatively effective amount of a compound of the following formula, or an acid or base addition salt thereof: 
     
       
         
         
             
             
         
       
       wherein, 
       X is N—R 5  or O; 
       R 1  is selected from the group consisting of hydrogen, and, alkyl; 
       R 2  is selected from the group consisting of hydrogen, alkyl; 
       R 3  is selected from the group consisting of hydrogen, alkyl; 
       R 4  is selected from the group consisting of hydrogen, alkyl; 
       R 5  is selected from the group consisting of hydrogen, alkyl; and 
       n is 1 or 2. 
     
   
   
       8 . The method of  claim 7 , wherein the compound is selected from the following formula: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  is selected from the group consisting of hydrogen and methyl; 
 R 2  is selected from the group consisting of hydrogen, methyl, ethyl, t-butyl, pentyl, octyl, phytyl; 
 R 3  is selected from the group consisting of hydrogen, methyl and t-butyl; and 
 R 4  is selected from the group consisting of hydrogen, methyl, ethyl, t-butyl, pentyl, octyl, phytyl. 
 
   
   
       9 . The method of  claim 7 , wherein the compound is of the following formula or an acid or base addition salt thereof: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  is selected from the group consisting of hydrogen and methyl; 
 R 2  is selected from the group consisting of hydrogen, methyl, ethyl, t-butyl, pentyl, octyl, phytyl; 
 R 3  is selected from the group consisting of hydrogen, methyl and t-butyl; and 
 R 4  is selected from the group consisting of hydrogen, methyl, ethyl, t-butyl, pentyl, octyl, phytyl. 
 
   
   
       10 . A compound of the following formula, and acid or base addition salts thereof: 
     
       
         
         
             
             
         
       
       wherein, 
       X is N—R 5  or O (when N is 1); or X is O (when N is 2) 
       R 1  is selected from the group consisting of hydrogen, and, alkyl; 
       R 2  is selected from the group consisting of hydrogen, alkyl; 
       R 3  is selected from the group consisting of hydrogen, alkyl; 
       R 4  is selected from the group consisting of hydrogen, alkyl; 
       R 5  is selected from the group consisting of hydrogen, alkyl. 
     
   
   
       11 . A compound of  claim 10 , of following formula: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  is selected from the group consisting of hydrogen and methyl; 
 R 2  is selected from the group consisting of hydrogen, methyl, ethyl, t-butyl, pentyl, octyl, phytyl; 
 R 3  is selected from the group consisting of hydrogen, methyl and t-butyl; and 
 R 4  is selected from the group consisting of hydrogen, methyl, ethyl, t-butyl, pentyl, octyl, phytyl. 
 
   
   
       12 . A method of inhibiting the oxidation of compounds or mixtures comprising the addition of an effective amount of a compound of  claim 10  to said compound or mixture. 
   
   
       13 . The method of  claim 12 , wherein the compound or mixture may be any base oil or mixture thereof suitable for the intended use of a lubricant. 
   
   
       14 . The method of  claim 13 , wherein the base oil is selected from the group consisting of a conventionally refined mineral oil, an oil derived from coal tar or shale, a vegetable oil, an animal oil, a hydrocracked oil, or a synthetic oil, or any mixture thereof. 
   
   
       15 . A method of reducing the oxidative environment in a petroleum composition selected from the group consisting of lubricating compositions and liquid organic fuels, said method comprising adding to said petroleum composition an effective amount of an antioxidant composition, said antioxidant composition comprising a compound of  claim 10 . 
   
   
       16 . A method of inhibiting the oxidation of compounds or mixtures comprising the addition of an effective amount of a compound of the following formula or an acid or base addition salt thereof to said compound or mixture: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  is selected from the group consisting of hydrogen, and, alkyl; 
 R 2  is selected from the group consisting of hydrogen, and alkyl; 
 R 3  is selected from the group consisting of hydrogen, and alkyl; and 
 R 4  is an electron-donating substituent. 
 
   
   
       17 . The method of  claim 16 , wherein the compound or mixture may be any base oil or mixture thereof suitable for the intended use of a lubricant. 
   
   
       18 . The method of  claim 17 , wherein the base oil is selected from the group consisting of a conventionally refined mineral oil, an oil derived from coal tar or shale, a vegetable oil, an animal oil, a hydrocracked oil, or a synthetic oil, or any mixture thereof. 
   
   
       19 . A method of  claim 10 , wherein the mixture is a petroleum composition selected from the group consisting of lubricating compositions and liquid organic fuels, said method comprising adding to said petroleum composition an effective amount of the compound or a composition comprising the compound. 
   
   
       20 . A method of inducing antioxidant activity in warm-blooded animals comprising administering to warm-blooded animals an antioxidatingly effective amount of a biologically active composition, the biologically active composition comprising a compound of the following formula: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  is selected from the group consisting of hydrogen, and, alkyl; 
 R 2  is selected from the group consisting of hydrogen, and alkyl; 
 R 3  is selected from the group consisting of hydrogen, and alkyl; and 
 R 4  is an electron-donating substituent.