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 he
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.
대표청구항▼
1. A compound of structural Formula (I): or salts thereof, wherein:R1 is hydrogen, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, halo, haloalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalk
1. A compound of structural Formula (I): or salts 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;j and k are independently 0, 1 or 2;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 is hydrogen;R7 is alkyl or substituted alkyl comprising at least one fluorine atom;X is NR8—;Z is —CH2— or —NR9—;a is 0;R8 is hydrogen;R9, 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; andR101 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. 2. The compound of claim 1 of structural formula (XIII): wherein R7 is R10 is substituted alkyl comprising at least one fluorine atom;Y is —S(O)kR117—OR12 or —NR13R14;k is 0, 1 or 2;b is 1, 2, 3 or 4R11 is alkyl, substituted alkyl, acyl, substituted acyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, halo, haloalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; andR12-R14 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. 3. The compound of claim 2, wherein: R1 is hydrogen, alkyl, substituted alkyl, heteroalkyl or substituted heteroalkyl;R2 is alkyl, substituted alkyl, acyl, halo, —OR111, —C(O)NR114R115 or —CO2R118;n is 0 or 1;R3 is hydrogen, alkyl, substituted alkyl, heteroalkyl or substituted heteroalkyl;R4 and R5 are independently hydrogen, alkyl, substituted alkyl, —OR120 or together with the atoms to which they are attached form a double bond;b is 1 or 2;Y is —OR12 or —NR13R14; andR9, R12-R14, R102-R104 and R111-R123 are independently hydrogen, alkyl, substituted alkyl, arylalkyl or substituted arylalkyl. 4. The compound of claim 2, wherein: R1 is hydrogen, alkyl, substituted alkyl, heteroalkyl or substituted heteroalkyl;R2 is alkyl, substituted alkyl, acyl, halo, —OR111, —C(O)NR114R115 or —CO2R118;n is 0 or 1;R3 is hydrogen, alkyl, substituted alkyl, heteroalkyl or substituted heteroalkyl;R4 and R5 are independently hydrogen, alkyl, substituted alkyl, —OR120 or together with the atoms to which they are attached form a double bond;b is 1 or 2;Y is —OR12 or —NR13R14; andR9, R12-R14, R102-R104 and R111-R123 are independently hydrogen, alkyl or arylalkyl. 5. The compound of claim 2 wherein: R1 is hydrogen, halo, alkyl or substituted alkyl;R3 is alkyl; andY is —OR12. 6. The compound of claim 1 of structural Formula (VIII): wherein:R1 is alkyl or halo;R3 is hydrogen, alkyl;R4 and R5 are independently hydrogen, halo, —OR120, —OC(O)NR121R122, —OC(O)R123 or together with the atoms to which they are attached form a double bond;R120 is hydrogen, methyl or alkyl;R121 and R122 are independently hydrogen or alkyl; andR123 is alkyl. 7. A composition comprising the compound of claim 1 and a vehicle. 8. The compound of claim 1, wherein R1 is (C1-C4) alkyl or (C1-C4) substituted alkyl. 9. The compound of claim 1, wherein R1 is cyclopropyl, substituted cyclopropyl cyclobutyl or substituted cyclobutyl. 10. The compound of claim 1 having the structure: 11. The compound of claim 1 having the structure: 12. The compound of claim 1 having the structure: 13. The compound of claim 1 having the structure: 14. The compound of claim 1 having the structure: 15. The compound of claim 1 having the structure: 16. The compound of claim 1 having the structure: 17. The compound of claim 1 having the structure: 18. The compound of claim 1 having the structure: 19. The compound of claim 1 having the structure: 20. The compound of claim 1 having the structure: 21. The compound of claim 1 having the structure: 22. The compound of claim 1 having the structure: 23. The compound of claim 1 having the structure: 24. The compound of claim 1 having the structure: 25. The compound of claim 1 having the structure: 26. The compound of claim 1 having the structure: 27. A compound having the structure: 28. A compound selected from the following: 29. A compound of structural formula (VIII): or salts thereof, wherein:R1 C3-C6 cycloalkyl or substituted C3-C6 cycloalkyl;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 is hydrogen;R7 is alkyl or substituted alkyl;R8 is hydrogen; andR120-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. 30. The compound of claim 29, wherein the C3-C6 cycloalkyl is selected from cyclopropyl, cyclobutyl, or cyclopentyl. 31. The compound of claim 30, wherein the C3-C6 cycloalkyl is cyclopropyl. 32. The compound of claim 29 having the structure: 33. The compound of claim 29 having the structure: 34. The compound of claim 29 having the structure:
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