Ergoline compounds and uses thereof

Abstract

Provided herein are ergoline compounds and pharmaceutical compositions thereof. In some embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1A, 5-HT1B and 5-HT1D receptors without agonizing the 5-HT2B receptor using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the 5-HT2B adrenergic alpha2A and/or the alpha2B receptors using the compounds and pharmaceutical compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing the D2 and D3 receptor using the compounds and pharmaceutical compositions disclosed herein.

1 . (canceled) 
     
     
         2 . A compound represented by structural Formula (VIII): 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein: 
         R 1  is saturated cycloalkyl; 
         R 3  is hydrogen or alkyl; 
         R 4  and R 5  are independently hydrogen, halo, —OR 120 , —OC(O)NR 121 R 122 , —OC(O)R 123  or together with the atoms to which they are attached form a double bond; 
         R 6  and R 7  are independently hydrogen, alkyl or substituted alkyl; 
         R 8  is alkyl; 
         R 120  is hydrogen or alkyl; 
         R 121 , R 122  are independently hydrogen or alkyl; and 
         R 123  is alkyl. 
       
     
     
         3 . The compound or salt of  claim 2 , wherein R 6  is hydrogen. 
     
     
         4 . The compound or salt of  claim 2 , wherein R 1  is cyclopropyl. 
     
     
         5 . The compound or salt of  claim 2 , wherein R 3  is methyl. 
     
     
         6 . The compound or salt of  claim 2 , wherein R 4  and R 5  are independently hydrogen or halo. 
     
     
         7 . The compound or salt of  claim 6 , wherein R 4  is hydrogen. 
     
     
         8 . The compound or salt of  claim 6 , wherein R 5  is hydrogen. 
     
     
         9 . The compound or salt of  claim 2 , wherein R 7  is a substituted alkyl. 
     
     
         10 . The compound or salt of  claim 9 , wherein R 7  is alkyl substituted by hydroxyl or methoxy. 
     
     
         11 . The compound or salt of  claim 2 , wherein R 8  is methyl. 
     
     
         12 . A pharmaceutical composition comprising a compound or salt of  claim 2  and a pharmaceutically acceptable excipient. 
     
     
         13 . A method of treating migraine, comprising administering to a subject in need thereof the pharmaceutical composition of  claim 12 .