Use Of 2,5-Dihydroxybenzene Compounds And Derivatives For The Treatment Of Skin Cancer

Abstract

The present invention relates to the use of a 2,5-dihydroxybenzene derivative of formula (I) or a pharmaceutically acceptable salt, solvate, isomer, or prodrug thereof for the treatment and/or prophylaxis of, inter alia, skin cancer.

What is claimed is: 
     
         1 . A method for the treatment or prophylaxis of skin cancer, comprising administering to a subject in need thereof, an effective amount of compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is —(CH 2 ) a Y; 
 Y is —SO 3   − .X + , —SO 3 R 3 , wherein R 9  and R 9 ′ are independently selected from —OH and —OR 2  and at least one of R 9  and R 9 ′ is an alkylcarbonyloxy group or an arylcarbonyloxy group; 
 X +  is an organic cation or an inorganic cation, such that the general charge of the compound is neutral; 
 R 2  is an alkylcarbonyl group, an alkylcarbonyl group or an arylcarbonyl group; 
 R 3  is an alkyl group or an aryl group; 
 a is a number selected from 0 and 1. 
 
       
     
     
         2 . The method of  claim 1 , wherein in R 2 , the alkyl of the alkylcarbonyl group has 1-6 carbon atoms or is C(O)—C(CH 3 ) 2 —O—C 6 H 4 C 
     
     
         3 . The method of  claim 1 , wherein R 3  is selected from methyl, ethyl, isopropyl, or C6H5. 
     
     
         4 . The method of  claim 1 , wherein a is 0, Y is —SO 3 R 3 , R 9 ′ and R 9  are both OCOR 2 , thereby the compound is according to Formula (4): 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 1 , wherein a is 0, Y is —SO 3 R 3 , R 9 ′ is OCOR 2 , and R 9  is OH, thereby the compound is according to Formula (5): 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 1 , wherein a is 0, Y is —SO 3 R 3 , R 9 ′ is OH, and R 9  is OCOR 2 , thereby the compound is according to Formula (6): 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method of  claim 1 , wherein a is 1, Y is —SO 3   − .X + , R 9 ′ is OCOR 2 , and R 9  is OH, thereby the compound is according to Formula (7): 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 1 , wherein a is 1, Y is —SO 3   − .X + , R 9 ′ is OH, and R 9  is OCOR 2 , thereby the compound is according to Formula (8): 
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 1 , wherein a is 1, Y is —SO 3   − .X + , R 9 ′ and R 9  are both OCOR 2 , thereby the compound is according to Formula (9): 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 1 , wherein a is 1, Y is —SO 3 R 3 , R 9 ′ and R 9  are both OCOR 2 , thereby the compound is according to Formula (10): 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 1 , wherein a is 1, Y is —SO 3 R 3 , R 9 ′ is OCOR 2 , and R 9  is OH, thereby the compound is according to Formula (11): 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 1 , wherein a is 1, Y is —SO 3 R 3 , R 9 ′ is OH, and R 9  is OCOR 2 , thereby the compound is according to Formula (12): 
       
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 1 , wherein the skin cancer is selected from the group consisting of: lentigo maligna, melanoma, keratoacanthoma, squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), sarcoma, angiosarcoma, cutaneous lymphoma, sweat gland carcinoma, and sebaceous gland carcinoma. 
     
     
         14 . The method of  claim 1 , wherein the compound is administered topically. 
     
     
         15 . The method of  claim 1 , wherein the compound is administered orally, buccally, transdermally, by inhalation, rectally, intravaginally, intraocularly, or otically. 
     
     
         16 . The method of  claim 1 , further comprising administration of at least one additional therapeutic agent. 
     
     
         17 . The method of  claim 16 , wherein the at least one additional therapeutic agent is selected from the group consisting of: imiquimod, diclofenac, glycidic acid, trichloroacetic acid, colchicine, T4 endonuclease, 5-fluorouracil, isotretinoin, acitretin, cidofoir, 5-aminolevulinic acid, methyl aminolevulinate, hypericin, a chemotherapeutic agent, a corticosteroid, an antibiotic, an analgesic, an immunomodulator, an anti-angiogenic, a leukotriene modifier, an aminosalicylate, an anesthetic, a non-steroidal anti-inflammatory, a modifier of a solubilized interleukin receptor, a cytotoxic agent, an inhibitor of a tyrosine-kinase receptor, a protein kinase C inhibitor, and a combination of two or more thereof. 
     
     
         18 . The method of  claim 1 , further comprising at least one coadjuvant therapy selected from the group consisting of: photodynamic therapy, cryotherapy, curettage and surgery. 
     
     
         19 . The method of  claim 14 , wherein the compound is administered at least once per week. 
     
     
         20 . The method of  claim 19 , wherein the compound is administered at least once per day. 
     
     
         21 . The method of  claim 20 , wherein the compound is administered at least twice per day. 
     
     
         22 . The method of  claim 14 , wherein the compound is present in a pharmaceutical composition in an amount of at least about 1% w/w to about 15% w/w.