Novel methysergide derivatives

Abstract

Provided herein are novel methysergide derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders or symptoms thereof, such as, migraine and Parkinson's disease using the compounds and compositions disclosed herein. In still other embodiments, provided herein, such as, for example, are methods for antagonizing the 5-HT 2B receptor without agonizing the 5-HT 2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein such as, for example, are methods of agonizing the 5-HT 1A receptor using the compounds and compositions disclosed herein.

What is claimed is: 
     
         1 . A compound of Formula (I) or (II): 
       
         
           
           
               
               
           
         
         or salts, polymorphs, hydrates or solvates thereof, wherein: 
         R 1  is hydrogen; 
         R 2  is (C 1 -C 4 ) alkyl, substituted (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkyl substituted with one or more fluorine atoms, (C 1 -C 4 ) acyl, substituted (C 1 -C 4 ) acyl, —OH, (C 1 -C 4 ) heteroalkyl or substituted (C 1 -C 4 ) heteroalkyl; 
         R 3  is alkyl, substituted alkyl, acyl, substituted acyl, halo, heteroalkyl, substituted heteroalkyl, —NO 2 , —N 3 , —OH, —S(O) k R 100 , —OR 101 , —NR 102 R 103 , —CONR 104 R 105 , —CO 2 R 106  or —O 2 CR 107 ; 
         R 4  is hydrogen, (C 1 -C 3 ) alkyl, (C 1 -C 3 ) substituted alkyl or (C 1 -C 3 ) alkyl substituted with one or more fluorine atoms; 
         R 5  is hydrogen, (C 1 -C 4 ) alkyl, substituted (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkyl substituted with one or more fluorine atoms, (C 1 -C 4 ) heteroalkyl or substituted (C 1 -C 4 ) heteroalkyl; 
         R 6  is (C 1 -C 4 ) alkyl, substituted (C 1 -C 4 ) alkyl, (C 1 -C 3 ) alkyl substituted with one or more fluorine atoms, (C 1 -C 4 ) heteroalkyl or substituted (C 1 -C 4 ) heteroalkyl; 
         n is 0, 1, 2 or 3; 
         o is 0, 1, 2, 3 or 4; 
         k is 0, 1 or 2; and 
         R 100 -R 107  are independently hydrogen, alkyl, substituted alkyl, acyl, substituted acyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl. 
       
     
     
         2 . The compound of  claim 1 , having the structure of Formula (III) or Formula (IV) 
       
         
           
           
               
               
           
         
       
     
     
         3 . A composition comprising the compound of  claim 1  and a vehicle. 
     
     
         4 . The compound of  claim 2 , wherein R 2  is a (C 1 -C 4 ) alkyl substituted with one or more fluorine atoms. 
     
     
         5 . The compound of  claim 2 , wherein R 4  is a (C 1 -C 4 ) alkyl. 
     
     
         6 . The compound of  claim 4 , wherein R 4  is a (C 1 -C 4 ) alkyl. 
     
     
         7 . A composition comprising the compound of  claim 6  and a vehicle. 
     
     
         8 . The composition of  claim 7 , wherein the composition is formulated as an oral dosage form. 
     
     
         9 . The composition of  claim 8 , wherein the oral dosage form is in the form of a tablet, pill, capsule or troche.