Method for the treatment of fatty liver disease

Abstract

The invention provides a method of treating, inhibiting and/or preventing fatty liver disease in a patient in need thereof, comprising administering an effective amount of a cyclohexenone compound of the following formula (I) to said patient,

1 . A method of treating, inhibiting and/or preventing fatty liver disease in a patient in need thereof, comprising administering an effective amount of a cyclohexenone compound of the following formula (I) to said patient, 
       
         
           
           
               
               
           
         
         wherein each of X and Y independently is oxygen, NR 5  or sulfur; 
         R is a hydrogen or C(═O)C 1 -C 8 alkyl; 
         each of R 1 , R 2  and R 3  independently is a hydrogen, methyl or (CH 2 ) m —CH 3 ; 
         R 4  is NR 5 R 6 , OR 5 , OC(═O)R 7 , C(═O)OR 5 , C(═O)R 5 , C(═O)NR 5 R 6 , halogen, 5 or 6-membered lactone, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, glucosyl, wherein the 5 or 6-membered lactone, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, and glucosyl are optionally substituted with one or more substituents selected from NR 5 R 6 , OR 5 , OC(═O)R 7 , C(═O)OR 5 , C(═O)R 5 , C(═O)NR 5 R 6 , C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, and C 1 -C 8  haloalkyl; 
         each of R 5  and R 6  is independently a hydrogen or C 1 -C 8 alkyl; 
         R 7  is a C 1 -C 8 alkyl, OR 5  or NR 5 R 6 ; 
         m=1-12; and 
         n=1-12; or a pharmaceutically acceptable salt, metabolite, solvate or prodrug thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the cyclohexenone compound is isolated from the organic solvent extracts of  Antrodia camphorate.    
     
     
         3 . The method of  claim 1 , wherein R is a hydrogen, C(═O)C 3 H 8 , C(═O)C 2 H 5 , or C(═O)CH 3 . 
     
     
         4 . The method of  claim 1 , wherein R 1  is a hydrogen or methyl. 
     
     
         5 . The method of  claim 1 , wherein R 2  is a hydrogen, methyl, ethyl, propyl, butyl, pentyl or hexyl. 
     
     
         6 . The method of  claim 1 , wherein R 4  is halogen, NH 2 , NHCH 3 , N(CH 3 ) 2 , OCH 3 , OC 2 H 5 , C(═O)CH 3 , C(═O)C 2 H 5 , C(═O)OCH 3 , C(═O)OC 2 H 5 , C(═O)NHCH 3 , C(═O)NHC 2 H 5 , C(═O)NH 2 , OC(═O)CH 3 , OC(═O)C 2 H 5 , OC(═O)OCH 3 , OC(═O)OC 2 H 5 , OC(═O)NHCH 3 , OC(═O)NHC 2 H 5 , or OC(═O)NH 2 . 
     
     
         7 . The method of  claim 1 , wherein R 4  is C 2 H 5 C(CH 3 ) 2 OH, C 2 H 5 C(CH 3 ) 2 OCH 3 , CH 2 COOH, C 2 H 5 COOH, CH 2 OH, C 2 H 5 OH, CH 2 Ph, C 2 H 5 Ph, CH 2 CH═C(CH 3 )(CHO), CH 2 CH═C(CH 3 )(C(═O)CH 3 ), 5 or 6-membered lactone, C 1 -C 8  alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, and glucosyl, wherein 5 or 6-membered lactone, C 1 -C 8  alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, and glucosyl are optionally substituted with one or more substituents selected from NR 5 R 6 , OR 5 , OC(═O)R 7 , C(═O)OR 5 , C(═O)R 5 , C(═O)NR 5 R 6 , C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 3 -C 8  cycloalkyl, and C 1 -C 8  haloalkyl. 
     
     
         8 . The method of  claim 1 , wherein R 4  is CH 2 CH═C(CH 3 ) 2 . 
     
     
         9 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 1 , wherein the cyclohexenone compound is administered with a second ingredient. 
     
     
         11 . The method of  claim 10 , wherein the second ingredient is ergosterol. 
     
     
         12 . The method of  claim 11 , wherein the amounts of the cyclohexenone compound in combination with ergosterol range from 50% (w/w) to 90% (w/w) and 50% (w/w) to 10% (w/w), respectively. 
     
     
         13 . The method of  claim 1 , wherein the fatty liver disease is the primary fatty liver disease or the secondary fatty liver disease. 
     
     
         14 . The method of  claim 13 , wherein the primary fatty liver disease is NAFLD or NASH. 
     
     
         15 . The method of  claim 13 , wherein the secondary fatty liver disease is alcohol liver disease, fatty liver associated with chronic hepatitis infection, total parental nutrition (TPN), Reye's Syndrome, gastrointestinal disorders, or gastroparesis and irritable bowel (IBS) disorders. 
     
     
         16 . The method of  claim 1 , wherein the fatty liver disease is cirrhosis or fibrosis. 
     
     
         17 . The method of  claim 1 , wherein the cyclohexenone compound, or a pharmaceutically acceptable salt, metabolite, solvate or prodrug thereof, is administered orally, parenterally or intravenously. 
     
     
         18 . The method of  claim 17 , wherein the cyclohexenone compound, or a pharmaceutically acceptable salt, metabolite, solvate or prodrug thereof, is administered orally.