ISOERGOLINE COMPOUNDS AND USES THEREOF

摘要

Provided herein are isoergoline compounds and pharmaceutical compositions thereof. In other 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.

主权项

1. A compound of structural Formula (I): or polymorphs, salts, hydrates or solvates thereof, wherein: R1 is hydrogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, halo, haloalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —S(O)jR101, —C(O)NR102R103 or —CO2R104; R2 is alkyl, substituted alkyl, acyl, substituted acyl, halo, haloalkyl, heteroalkyl, substituted heteroalkyl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —NO2, —N3, —S(O)kR110, —OR111, —NR112R113, —C(O)NR114R115, —OC(O)NR116R117, —CO2R118 or —OC(O)R119; n is 0, 1, 2 or 3; R3 is hydrogen, alkyl, substituted alkyl, haloalkyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; R4 and R5 are independently hydrogen, alkyl, substituted alkyl, halo, haloalkyl, —OR120, —OC(O)NR121R122, —OC(O)R123 or together with the atoms to which they are attached form a double bond; R6 and R7 are independently hydrogen, acyl, subsisted acyl, alkyl, substituted alkyl, haloalkyl, heteroalkyl or substituted heteroalkyl, provided that both R6 and R7 are not both hydrogen or alkyl or combinations thereof; X is —S—, —SO2— or —NR8—; a is 0 or 1; R8, R102-R104 and R111-R123 are independently hydrogen, alkyl, substituted alkyl, acyl, substituted acyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, haloalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; R101 and R110 are independently alkyl, substituted alkyl, acyl, substituted acyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, halo, haloalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; and optionally, R1 and R8 along with the atoms to which they are attached form a 5, 6 or 7 membered ring; provided that R1 and R8 are not both hydrogen; provided that R1 and R8 are not both alkyl; provided that R1 and R8 are not both substituted alkyl; provided that R1 is not hydrogen when R8 is alkyl or substituted alkyl; and provided that R8 is not hydrogen when R1 is alkyl or substituted alkyl.