Treatment of Diabetes and Related Pathologies

Abstract

Methods for treating diabetes mellitus and related conditions and symptoms are described. The methods are directed to administering a therapeutically effective amount of a compound. Compounds suitable for the invention include pyridoxal-5′-phosphate, pyridoxal, pyridoxamine, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, or a mixture thereof. Also disclosed are methods directed to concurrently administering a therapeutically effective amount of a compound with other compounds known in the treatment of diabetes mellitus. In one embodiment, a therapeutically effective amount of a compound is administered concurrently with a therapeutically effective amount of insulin. In another embodiment, a therapeutically effective amount of a compound is administered concurrently with a therapeutically effective amount of a hypoglycemic compound.

1 - 27 . (canceled) 
   
   
       28 . A method of treating insulin resistance in a mammal comprising: administering to the mammal a therapeutically effective amount of a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof. 
   
   
       29 . A method according to  claim 28 , wherein the 3-acylated pyridoxal analogue is a compound of the formula 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group. 
 
   
   
       30 . A method according to  claim 28 , wherein the 3-acylated pyridoxal analogue is a compound of the formula 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; and 
 R 2  is of the formula 
 
     
       
         
         
             
             
         
       
     
     wherein R 3  and R 4  are each independently alkyl, alkenyl, cycloalkyl, aryl, or, when R 3  and R 4  are taken together to form a ring with the nitrogen atom, which may optionally be interrupted by a heteroatom; or 
     a pharmaceutically acceptable acid addition salt thereof. 
   
   
       31 . The method of  claim 28  comprising: concurrently administering insulin with the compound. 
   
   
       32 . A method according to  claim 31 , wherein the 3-acylated pyridoxal analogue is a compound of the formula 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group. 
 
   
   
       33 . A method according to  claim 31 , wherein the 3-acylated pyridoxal analogue is a compound of the formula 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; and 
 R 2  is of the formula 
 
     
       
         
         
             
             
         
       
     
     wherein R 3  and R 4  are each independently alkyl, alkenyl, cycloalkyl, aryl, or, when R 3  and R 4  are taken together to form a ring with the nitrogen atom, which may optionally be interrupted by a heteroatom; or 
     a pharmaceutically acceptable acid addition salt thereof. 
   
   
       34 . The method of  claim 28  comprising: concurrently administering a hypoglycemic compound with the compound selected. 
   
   
       35 . A method according to  claim 34 , wherein the 3-acylated pyridoxal analogue is a compound of the formula 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group. 
 
   
   
       36 . A method according to  claim 34 , wherein the 3-acylated pyridoxal analogue is a compound of the formula 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; and 
 R 2  is of the formula 
 
     
       
         
         
             
             
         
       
     
     wherein R 3  and R 4  are each independently alkyl, alkenyl, cycloalkyl, aryl, or, when R 3  and R 4  are taken together to form a ring with the nitrogen atom, which may optionally be interrupted by a heteroatom; or 
     a pharmaceutically acceptable acid addition salt thereof. 
   
   
       37 . A method according to  claim 34 , wherein the hypoglycemic compound is acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, tolazamide, tolbutamide, or a mixture thereof. 
   
   
       38 . A method according to  claim 34 , wherein the hypoglycemic compound is tolbutamide. 
   
   
       39 . A method according to  claim 34  further comprising:
 concurrently administering to the mammal the compound and the hypoglycemic compound in combination with a therapeutically effective amount of insulin.   
   
   
       40 . A method of treating hyperinsulinemia in a mammal comprising: administering to the mammal a therapeutically effective amount of a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof, 
     wherein the 3-acylated pyridoxal analogue is a compound of the formula 
     
       
         
         
             
             
         
       
     
     wherein R 1  is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; and 
     wherein the 3-acylated pyridoxal analogue is a compound of the formula 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; and 
 R 2  is of the formula 
 
     
       
         
         
             
             
         
       
     
     wherein R 3  and R 4  are each independently alkyl, alkenyl, cycloalkyl, aryl, or, when R 3 , and R 4  are taken together to form a ring with the nitrogen atom, which may optionally be interrupted by a heteroatom; or 
     a pharmaceutically acceptable acid addition salt thereof. 
   
   
       41 - 42 . (canceled) 
   
   
       43 . The method of  claim 40  comprising: concurrently administering insulin with the compound. 
   
   
       44 - 45 . (canceled) 
   
   
       46 . The method of  claim 43  comprising: concurrently administering hypoglycemic compound with the compound. 
   
   
       47 - 48 . (canceled) 
   
   
       49 . A method according to  claim 46 , wherein the hypoglycemic compound is acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, tolazamide, tolbutamide, or a mixture thereof. 
   
   
       50 . A method according to  claim 46 , wherein the hypoglycemic compound is tolbutamide. 
   
   
       51 . A method according to  claim 46  further comprising:
 concurrently administering to the mammal the compound and the hypoglycemic compound in combination with a therapeutically effective amount of insulin.   
   
   
       52 - 75 . (canceled)