Method and composition for rejuvinating cells, tissues organs, hair and nails

Abstract

In one embodiment, the present invention relates to compounds and compositions including pharmaceutical compositions containing the compounds and associated methods that uncouple sugar-mediated coupling of proteins, lipids, nucleic acids, and other biomaterials, and any combination thereof. In another embodiment, the compositions and associated methods have utility in vivo to reduce the deleterious effects of sugar-mediated coupling processes in an organism, when the organism is exposed to the compound or composition internally, by ingestion, transdermal application, or other means. In yet another embodiment, the compositions and associated methods are useful for the ex-vivo treatment of organs, cells and tissues and external treatment of hair, nails and skin to rejuvenate them by changing deformability and increase the tissue diffusion coefficient. In a further embodiment, the present invention relates to novel compounds and pharmaceutical compositions.

1 . A compound of formula  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is hydrogen, or —C(═O)—R 6  wherein R 6  is selected from the group consisting of C 1 -C 18  alkyl, C 1 -C 18  alkoxy, phenyl, halosubstituted phenyl, C 1 -C 18  alkoxysubstituted phenyl and naphthyl;  
 R 2  is hydrogen, phenyl or a C 1-5  alkyl group;  
 R 3  and R 4  and independently selected from the group consisting of hydrogen, C 1 -C 18  alkyl or hydroxyalky, or phenyl, or R 2  and R 3  together are a bridge of 3-6 methylene units, or R 3  and R 4  together with their ring atoms may be an aromatic ring system of 6-10 carbons, optionally substituted with one or more halo, lower alkyl, lower alkoxy, or amino groups;  
 R 5  is hydrogen, phenyl or C 1 -C 5  alkyl group and;  
 X −  is a pharmaceutically acceptable anion such as halide.  
 
   
   
       2 . A compound of the formula:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  and R 4  are independently selected from hydrogen, phenyl or C 1 -C 5  alkyl;  
 R 2  and R 3  are independently selected from the group consisting of hydrogen, C 1 -C 18  alkyl or hydroxyalky, or phenyl, or R 2  and R 3  together are a bridge of 3-6 methylene units, or R 2  and R 3  together with their ring atoms may be an aromatic ring system of 6-10 carbons, optionally substituted with one or more halo, lower alkyl, lower alkoxy, or amino groups; and  
 X −  is a pharmaceutically acceptable anion such as halide.  
 
   
   
       3 . A compound of the formula:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  and R 4  are independently selected from hydrogen, phenyl or C 1 -C 5  alkyl;  
 R 2  and R 3  are independently selected from the group consisting of hydrogen, C 1 -C 18  alkyl or hydroxyalky, or phenyl, or R 2  and R 3  together are a bridge of 3-6 methylene units, or R 2  and R 3  together with their ring atoms may be an aromatic ring system of 6-10 carbons, optionally substituted with one or more halo, lower alkyl, lower alkoxy, or amino groups;  
 R 5  is phenyl, halosubstituted phenyl, C 1 -C 18  alkoxysubstituted phenyl, or C 5-7  aromatic or unsaturated or saturated heterocyclic ring having one to three heteroatoms selected from the group consisting of N, O and S; and  
 X −  is a pharmaceutically acceptable anion such as halide.  
 
   
   
       4 . A compound of the formula:  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is hydrogen, or —C(═O)—R 6  wherein R 6  is selected from the group consisting of C 1 -C 18  alkyl, C 1 -C 18  alkoxy, phenyl, halosubstituted phenyl, C 1 -C 18  alkoxysubstituted phenyl and naphthyl;  
 R 2  is hydrogen, phenyl or a C 1-5  alkyl group;  
 R 3  and R 4  and independently selected from the group consisting of hydrogen, C 1 -C 18  alkyl or hydroxyalky, or phenyl, or R 2  and R 3  together are a bridge of 3-6 methylene units, or R 3  and R 4  together with their ring atoms may be an aromatic ring system of 6-10 carbons, optionally substituted with one or more halo, lower alkyl, lower alkoxy, or amino groups; and  
 X −  is mesitylene-2-sulfonate or other pharmaceutically acceptable anion.  
 
   
   
       5 . A compound of a formula  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is selected from hydoxy, C 1 -C 18  alkoxy, amino optionally substituted with 1-2 independent C 1 -C 18  alkyl groups, phenyl, halosubstituted phenyl, C 1 -C 18  alkoxysubstituted phenyl, or a heterocyclic group defined as a 5 to 10 membered aromatic or unsaturated or saturated heterocyclic system of 1-2 rings having one or more heteroatoms selected from the group consisting of N, O, or S;  
 A is selected from hydroxy, C1-C18 alkoxy, amino optionally substituted with 1-2 independent C 1 -C 18  alkyl groups, phenyl, halosubstituted phenyl, C 1 -C 18  alkoxysubstituted phenyl, a heterocyclyl group as defined for R 1  above with the proviso that the ring through which A is attached contains at least one heteroatom, or a group —C(═O)Z wherein is hydroxy, or Z is C 1 -C 18  alkoxy, or Z is amino optionally substituted with 1-2 independent C 1 -C 18  alkyl groups, or Z is heterocyclyl as defined for R 1  above;  
 R 2  and R 3  are independently selected from hydrogen, amino, or C1-C18 alkyl groups, or, if attached to adjacent ring positions, R 2  andR 3  taken together may form a carbocyclic or heterocyclic ring; and  
 X −  is halide, preferably chloride or bromide, or other pharmaceutically acceptable anion; and at least one of R1 or A or Z is a heterocyclyl group as defined for the respective groups above.  
 
   
   
       6 . A compound of formula  
     
       
         
         
             
             
         
       
     
     wherein 
 A is hydrogen, cyano, or a C 6 -C 10  aryl group, said aryl groups optionally substituted by one or more lower alkyl, lower alkoxy, or halo groups;  
 Z is Ch or N;  
 R 1  is hydroxy, C 1 -C 18  alkoxy, amino optionally substituted with 1-2 independent C 1 -C 18  alkyl groups, phenyl, halosubstituted phenyl, C 1 -C 18  alkoxysubstituted phenyl, naphthyl, or a 4 to 10 membered aromatic heterocyclic or unsaturated heterocyclic or saturated heterocyclic ring system of 1 to 2 rings having one to three heteroatoms selected from the group consisting of N, O, and S;  
 R 2  and R 3  are independently selected from hydrogen, amino, or C 1 -C 18  alkyl groups, or R 2  and R 3  taken together may form a carbocyclic or heterocyclic ring, and  
 X— is halide, preferably chloride or bromide, or other pharmaceutically acceptable anion;  
 and if A is hydrogen, then R 1  is selected from phenyl, halosubstituted phenyl, C 1 -C 18  alkoxysubstituted phenyl, or a 4 to 10 memebered aromatic heterocyclic or unsaturated hetrocyclic or staturated heterocyclic ring system of 1 to 2 rings having one to three heteroatoms selected from the group consisting of N, O, and S.