Novel Cabergoline Derivatives

Abstract

Provided herein are novel cabergoline analogs and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HT 2B receptor and 5-HT 2C receptors the using the compounds and compositions disclosed herein.

What is claimed is: 
     
         1 . A method of treating and/or preventing central nervous system disorders in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein R 1  is hydrogen, (C 1 -C 4 ) alkyl or (C 1 -C 4 ) alkyl substituted with one or more fluorine atoms, R 5  is hydrogen or (C 1 -C 3 ) alkyl, and R 11  is (C 1 -C 3 ) alkyl substituted with one or more fluorine atoms. 
     
     
         2 . The method of  claim 1 , wherein R 1  is hydrogen, —CH 3  or —CF 3 , R 5  is hydrogen, methyl or allyl, and R 11  is —CF 3 . 
     
     
         3 . The method of  claim 1 , wherein R 1  is —CH 3  or —CF 3 , R 5  is methyl or allyl, and R 11  is —CF 3 . 
     
     
         4 . The method of  claim 1 , wherein R 1  is —CH 3  or —CF 3 , R 5  is methyl or allyl, and R 11  is —CF 3 . 
     
     
         5 . A method of treating and/or preventing migraine in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein R 1  is hydrogen, (C 1 -C 4 ) alkyl or (C 1 -C 4 ) alkyl substituted with one or more fluorine atoms, R 5  is hydrogen or (C 1 -C 3 ) alkyl, and R 11  is (C 1 -C 3 ) alkyl substituted with one or more fluorine atoms. 
     
     
         6 . The method of  claim 5 , wherein R 1  is hydrogen, —CH 3  or —CF 3 , R 5  is hydrogen, methyl or allyl, and R 11  is —CF 3 . 
     
     
         7 . The method of  claim 5 , wherein R 1  is —CH 3  or —CF 3 , R 5  is methyl or allyl, and R 11  is —CF 3 . 
     
     
         8 . The method of  claim 5 , wherein R 1  is —CH 3  or —CF 3 , R 5  is methyl or allyl, and R 11  is —CF 3 . 
     
     
         9 . A method of treating and/or preventing Parkinson's disease in a subject comprising administering to the subject in need thereof a therapeutically effective amount of the compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein R 1  is hydrogen, (C 1 -C 4 ) alkyl or (C 1 -C 4 ) alkyl substituted with one or more fluorine atoms, R 5  is hydrogen or (C 1 -C 3 ) alkyl, and R 11  is (C 1 -C 3 ) alkyl substituted with one or more fluorine atoms. 
     
     
         10 . The method of  claim 9 , wherein R 1  is hydrogen, —CH 3  or —CF 3 , R 5  is hydrogen, methyl or allyl, and R 11  is —CF 3 . 
     
     
         11 . The method of  claim 9 , wherein R 1  is —CH 3  or —CF 3 , R 5  is methyl or allyl, and R 11  is —CF 3 . 
     
     
         12 . The method of  claim 9 , wherein R 1  is —CH 3  or —CF 3 , R 5  is methyl or allyl, and R 11  is —CF 3 .