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 or inhibiting collagen deposition in a fatty liver condition of a patient, comprising administering an effective amount of a cyclohexenone compound of the following formula (I) to said patient in need thereof, 
       
         
           
           
               
               
           
         
         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 said compound decreases blood glucose and/or triglyceride level. 
     
     
         3 . The method of  claim 1 , wherein said compound decreases fibrosis of steatohepatitis liver cells. 
     
     
         4 . The method of  claim 1 , wherein said fatty liver condition is caused by non-chemical injury. 
     
     
         5 . The method of  claim 3 , wherein said fatty liver condition is a nonalcoholic fatty liver disease. 
     
     
         6 . The method of  claim 1 , wherein the cyclohexenone compound is isolated from the organic solvent extracts of  Antrodia camphorata , or prepared synthetically or semi-synthetically. 
     
     
         7 . 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 . 
     
     
         8 . The method of  claim 1 , wherein R 1  is a hydrogen or methyl. 
     
     
         9 . The method of  claim 1 , wherein R 2  is a hydrogen, methyl, ethyl, propyl, butyl, pentyl or hexyl. 
     
     
         10 . 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 . 
     
     
         11 . 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. 
     
     
         12 . The method of  claim 1 , wherein R 4  is CH 2 CH═C(CH 3 ) 2 . 
     
     
         13 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 1 , wherein the fatty liver condition is a primary fatty liver disease or a secondary fatty liver disease. 
     
     
         15 . The method of  claim 14 , wherein the primary fatty liver disease is NASH. 
     
     
         16 . The method of  claim 1 , wherein the fatty liver condition 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 1 , wherein the cyclohexenone compound, or a pharmaceutically acceptable salt, metabolite, solvate or prodrug thereof, is administered orally.