Phenazopyridine Compounds

Abstract

The present invention is directed to substituted phenazopyridines represented by Formula I. The present invention also relates to the discovery that compounds of Formula I have increased bioavailability as compared to unconjugated phenazopyridine.

1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  and R 2  are independently
 (a) hydrogen; 
 (b) the residue of an amino acid or peptide; 
 
       
       
         
           
           
               
               
           
         
         
           wherein R 3  is an optionally substituted alkyl or arylalkyl; or 
           (d) the residue of an amino acid wherein the amine of the amino acid is protected with a t-butylcarbonyl; 
         
         wherein at least one of R 1  and R 2  is other than hydrogen. 
       
     
     
         2 . The compound of  claim 1 , wherein R 1  is an amino acid residue and R 2  is hydrogen. 
     
     
         3 . The compound of  claim 1 , wherein R 1  is an (L—) amino acid residue and R 2  is hydrogen. 
     
     
         4 . The compound of  claim 2 , wherein the amino acid residue is selected from the group consisting of the residues of alanine, arginine, asparagine, aspartic acid, cysteine, glycine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, and valine. 
     
     
         5 . The compound of  claim 3 , wherein the (L-) amino acid residue is selected from the group consisting of the residues of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, and valine. 
     
     
         6 . The compound of  claim 1 , wherein R 1  is the amino acid residue of glycine and R 2  is hydrogen. 
     
     
         7 . The compound of  claim 1 , wherein R 1  is the amino acid residue of lysine and R 2  is hydrogen. 
     
     
         8 . The compound of  claim 1 , wherein R 1  is the amino acid residue of alanine and R 2  is hydrogen. 
     
     
         9 . The compound of  claim 1 , wherein R 1  is (c), R 3  is selected from the group consisting of ethyl, benzyl, isobutyl, dodecyl, ethylhexyl, trichloroethyl, and n-butyl, and R 2  is hydrogen. 
     
     
         10 . The compound of  claim 1 , wherein R 2  is an amino acid residue and R 1  is hydrogen. 
     
     
         11 . The compound of  claim 1 , wherein R 2  is an (L-) amino acid residue and R 1  is hydrogen. 
     
     
         12 . The compound of  claim 10 , wherein the amino acid residue is selected from the group consisting of the residues of alanine, arginine, asparagine, aspartic acid, cysteine, glycine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, and valine. 
     
     
         13 . The compound of  claim 11 , wherein the (L-) amino acid residue is selected from the group consisting of the residues of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, tryptophan, threonine, tyrosine, and valine. 
     
     
         14 . The compound of  claim 1 , wherein R 2  is the amino acid residue of glycine and R 1  is hydrogen. 
     
     
         15 . The compound of  claim 1 , wherein R 2  is the amino acid residue of lysine and R 1  is hydrogen. 
     
     
         16 . The compound of  claim 1 , wherein R 2  is the amino acid residue of alanine and R 1  is hydrogen. 
     
     
         17 . The compound of  claim 1 , wherein R 2  is (c), R 3  is selected from the group consisting of ethyl, benzyl isobutyl, dodecyl, ethylhexyl, trichloroethyl, and n-butyl, and R 2  is hydrogen. 
     
     
         18 . A pharmaceutical composition, comprising a therapeutically effective amount of the compound of  claim 1 . 
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the therapeutically effective amount of the compound is less than 50% of the therapeutically effective amount of an unconjugated phenazopyridine. 
     
     
         20 . A method of treating an individual comprising administering a therapeutically effective amount of the compound of  claim 1 . 
     
     
         21 . The method of  claim 20 , wherein the therapeutically effective amount of the compound is less than 50% of the therapeutically effective amount of an unconjugated phenazopyridine. 
     
     
         22 . The method of  claim 20  for the treatment of urinary tract pain, burning, irritation, discomfort, or urgent or frequent urination caused by urinary tract infections, surgery, injury, or examination procedures. 
     
     
         23 . The method of  claim 20 , wherein the side effects of the administration of the compound are less severe than the side effects of the administration of unconjugated phenazopyridine.