Ester pro-drugs of [3-(1-(1h-imidazol-4-yl)ethyl)-2-methylphenyl] methanol for treating skin diseases and conditions

Abstract

The present invention relates to method for treating skin diseases and skin conditions in a subject in need of such treatment, which comprises administering a therapeutically effective amount of a composition comprising ester pro-drugs of [3-(1-(1H-imidazol-4-yl) ethyl)-2-methylphenyl]methanol, or enantiomers thereof, pharmaceutical compositions containing them and their use as pharmaceuticals.

What is claimed is: 
     
         1 . A pharmaceutical composition for treating rosacea, administered to a subject in need of such treatment, comprising a compound having a structure of Formula II 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H or optionally substituted C 1-3  alkyl; 
         R 2  is H or optionally substituted C 1-3  alkyl; 
         R 3  is H, optionally substituted C 1-10  alkyl, optionally substituted heterocycle or optionally substituted aryl; and 
         R is optionally substituted C 1-10  alkyl, optionally substituted heterocycle or optionally substituted aryl; or 
         a pharmaceutically acceptable salt thereof; and 
       
       pharmaceutically acceptable carriers, preservatives, auxiliary agents, stabilizing agents, thickening agents, coloring agents and perfumes. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the compound having a structure of Formula II is selected from:
 iso-Butyric acid 3-[(S)-1-(1H-imidazol-4-yl)-ethyl]-2-methyl-benzyl ester;   2,2-Dimethyl-propionic acid 3-[(S)-1-(1H-imidazol-4-yl)ethyl]-2-methyl-benzyl ester;   Acetic acid 3-[(S)-1-(1H-imidazol-4-yl)ethyl]-2-methyl-benzyl ester;   Benzoic acid 3-[(S)-1-(1H-imidazol-4-yl)-ethyl]-2-methyl-benzyl ester;   3-Methyl-butyric acid 3-[(S)-1-(1H-imidazol-4-yl)ethyl]-2-methyl-benzyl ester;   3-Phenyl-propionic acid 3-[(S)-1-(1H-imidazol-4-yl)ethyl]-2-methyl-benzyl ester;   2-Amino-3-methyl-butyric acid 3-[(S)-1-(1H-imidazol-4-yl)-ethyl]-2-methyl-benzyl ester;   2-(2-Amino-3-methyl-butyrylamino)-3-methyl-butyric acid 3-[(S)-1-(1H-imidazol-4-yl)-ethyl]-2-methyl-benzyl ester;   2-(2-Amino-acetylamino)-3-methyl-butyric acid 3-[(S)-1-(1H-imidazol-4-yl)-ethyl]-2-methyl-benzyl ester; and   2-Amino-3-phenyl-propionic acid 3-[(S)-1-(1H-imidazol-4-yl)-ethyl]-2-methyl-benzyl ester.   
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the pharmaceutically acceptable carriers include: glucose, lactose, gum acacia, gelatin, mannitol, starch paste, magnesium trisilicate, talc, corn starch, keratin, colloidal silica, potato starch, urea, medium chain length triglycerides, dextrans. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , further formulated for topical skin application. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , further formulated to enhance long duration of action. 
     
     
         6 . The pharmaceutical composition according to  claim 5 , further formulated with slow releasing pellets. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , further formulated as suspension, gel, solution, lotion, cream, ointment, foams, emulsions, microemulsions, milks, serums, aerosols, sprays, dispersions, microcapsules, vesicles, microparticles, nanoparticles, wet cloths, soaps, cleansing bars, dry cloths, facial cloths. 
     
     
         8 . The pharmaceutical composition according to  claim 6 , further formulated as suspension, gel, solution, lotion, cream, ointment, foams, emulsions, microemulsions, milks, serums, aerosols, sprays, dispersions, microcapsules, vesicles, microparticles, nanoparticles, wet cloths, soaps, cleansing bars, dry cloths, facial cloths. 
     
     
         9 . The pharmaceutical composition according to  claim 1 , further formulated as a solid, semi-solid or liquid. 
     
     
         10 . The pharmaceutical composition according to  claim 1 , further formulated for oral use, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups or elixirs. 
     
     
         11 . A pharmaceutical composition for treating rosacea for topical dermatological, comprising a compound having a structure of Formula II 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H or optionally substituted C 1-3  alkyl; 
         R 2  is H or optionally substituted C 1-3  alkyl; 
         R 3  is H, optionally substituted C 1-10  alkyl, optionally substituted heterocycle or optionally substituted aryl; and 
         R is optionally substituted C 1-10  alkyl, optionally substituted heterocycle or optionally substituted aryl; or 
         a pharmaceutically acceptable salt thereof; and 
       
       formulated as suspension, gel, solution, lotion, cream, ointment, foams, emulsions, microemulsions, milks, serums, aerosols, sprays, dispersions, microcapsules, vesicles, microparticles, nanoparticles, wet cloths, soaps, cleansing bars, dry cloths, facial cloths.