IP Library › Granted Patent US 12,384,765
Granted Patent B2
US 12,384,765 · App. 17/606,319 · Granted Aug 12, 2025

Catecholamine prodrugs for use in the treatment of Parkinson's Disease

Inventors: Morten Jørgensen (Valby, DK); Martin Juhl (Valby, DK); Klaus Gjervig Jensen (Valby, DK); Lisbet Kværnø (Valby, DK)
Assignee: H. Lundbeck A/S
C07D405/12
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Quick Facts
Patent No.
US 12,384,765
App. No.
17/606,319
Granted
Aug 12, 2025
Kind
B2
Abstract

The present invention provides compounds of formula (Id) that are prodrugs of catecholamine for use in treatment of neurodegenerative diseases and disorders. The present invention also provides pharmaceutical compositions comprising compounds of the invention and methods of treating neurodegenerative or neuropsychiatric diseases and disorders using the compounds of the invention, in particular Parkinson's disease.

Claims (166)

1. A compound according to formula (Id)

wherein

a) R1 is selected from the group consisting of H, C 1 -C 6 alkyl, methyl substituted with C 3 -C 6 cycloalkyl, benzyl and —C(O)C 1 -C 6 alkyl, and R2 is selected from the group consisting of the substituents (i) and (ii) below; or

b) R1 is selected from the group consisting of the substituents (i) and (ii) below and R2 is selected from the group consisting of H, C 1 -C 6 alkyl, methyl substituted with C 3 -C 6 cycloalkyl, benzyl and —C(O)C 1 -C 6 alkyl; or

c) R1 and R2 are independently selected from the group consisting of substituent (i) and substituent (ii) below; or

d) R1 and R2 are both substituent (i) below; or

e) R1 and R2 are both substituent (ii) below;

wherein * indicates the attachment point; and

wherein the carbon atom at the attachment point on substituent (i) is in the S-configuration; and

wherein R3 is selected from the group consisting of H, C 1 -C 6 alkyl and benzyl; and

wherein R4 is selected from the group consisting of H, —C(O)C 1 -C 6 alkyl and —C(O)phenyl;

or a pharmaceutically acceptable salt thereof;

with the proviso that when both of R3 and R4 in substituent (i) are H, then R1 and R2 cannot both be substituent (i);

and with the proviso that when one of R1 and R2 is substituent (i) wherein both of R3 and R4 in substituent are H, then the other of R1 and R2 cannot be H.

2. A compound according to formula (Id)

wherein

a) R1 is selected from the group consisting of H, C 1 -C 6 alkyl, methyl substituted with C 3 -C 6 cycloalkyl, benzyl and —C(O)C 1 -C 6 alkyl, and R2 is selected from the group consisting of the substituents (i) and (ii) below; or

b) R1 is selected from the group consisting of the substituents (i) and (ii) below and R2 is selected from the group consisting of H, C 1 -C 6 alkyl, methyl substituted with C 3 -C 6 cycloalkyl, benzyl and —C(O)C 1 -C 6 alkyl; or

c) R1 and R2 are independently selected from the group consisting of substituent (i) and substituent (ii) below; or

d) R1 and R2 are both substituent (i) below; or

e) R1 and R2 are both substituent (ii) below;

wherein * indicates the attachment point; and

wherein the carbon atom at the attachment point on substituent (i) is in the S-configuration; and

wherein R3 is selected from the group consisting of H, C 1 -C 6 alkyl and benzyl; and

wherein R4 is selected from the group consisting of H, —C(O)C 1 -C 6 alkyl and —C(O)phenyl;

or a pharmaceutically acceptable salt thereof;

with the proviso that when both of R3 and R4 in substituent (i) are H, then R1 and R2 cannot both be substituent (i);

with the proviso that when one of R1 and R2 is substituent (i) wherein both of R3 and R4 in substituent are H, then the other of R1 and R2 cannot be H;

and with the proviso that the compound of formula (Id) is not one of the following compounds (2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate,

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-6-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-7-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate, and

methyl (2S,3S,4S,5R,6S)-6-[[(4aR,10aR)-1-propyl-6-[(2S,3R,4S,5S,6S)-3,4,5-triacetoxy-6-methoxycarbonyl-tetrahydropyran-2-yl]oxy-3,4,4a,5,10,10a-hexahydro-2H-benzo[g]quinolin-7-yl]oxy]-3,4,5-triacetoxy-tetrahydropyran-2-carboxylate.

3. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein

R1 is H and R2 is substituent (i); or

R1 is substituent (i) and R2 is H; or

R1 and R2 are both represented by substituent (i); and

wherein R3 is selected from the group consisting of H, C 1 -C 6 alkyl and benzyl; and

wherein R4 is selected from the group consisting of H, —C(O)C 1 -C 6 alkyl and —C(O)phenyl;

with the proviso that R3 and R4 are not both H.

4. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein

R1 is H and R2 is substituent (ii); or

R1 is substituent (ii) and R2 is H; or

R1 and R2 are both represented by substituent (ii); and

wherein R3 is selected from the group consisting of H, C 1 -C 6 alkyl and benzyl; and

wherein R4 is selected from the group consisting of H, —C(O)C 1 -C 6 alkyl and —C(O)phenyl.

5. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R1 is selected from the group consisting of H, C 1 -C 4 alkyl, methyl substituted with C 3 -C 6 cycloalkyl, benzyl and —C(O)C 1 -C 4 alkyl.

6. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R1 is selected from the group consisting of H, C 1 -C 3 alkyl, and benzyl.

7. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R2 is selected from the group consisting of H, C 1 -C 4 alkyl, methyl substituted with C 3 -C 6 cycloalkyl, benzyl and —C(O)C 1 -C 4 alkyl.

8. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R2 is selected from the group consisting of H, C 1 -C 3 alkyl, and benzyl.

9. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R3 is selected from the group consisting of H, C 1 -C 4 alkyl, and benzyl.

10. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R4 is selected from the group consisting of H, —C(O)C 1 -C 4 alkyl and —C(O)phenyl.

11. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R4 is selected from the group consisting of H and —C(O)C 1 -C 4 alkyl.

12. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R1 and R2 are both represented by substituent (i) or R1 and R2 are both represented by substituent (ii).

13. The compound according to claim 1 , wherein the compound is selected from the group consisting of:

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2R,3R,4S)-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl) oxy)-6-(methoxycarbonyl)-3,4-dihydro-2H-pyran-3,4-diyl diacetate;

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-((benzyloxy)carbonyl)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-((benzyloxy)carbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-3,4,5-triacetoxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2R,3R,4S)-3,4-dihydroxy-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4-dihydro-2H-pyran-6-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl) tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-2-(ethoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

ethyl (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-(ethoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3S,4S,5R,6S)-2-((benzyloxy) carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-3,4,5-triacetoxy-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-2-((benzyloxy) carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3S,4S,5R,6S)-2-((methoxy) carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-((ethoxy) carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl) tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate); and

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-7-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

or a pharmaceutically acceptable salt of any of these compounds.

14. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R2 is represented by substituent (i).

15. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R2 is represented by substituent (ii).

16. The compound of claim 2 with the formula below

or a pharmaceutically acceptable salt thereof.

17. The compound of claim 2 with the formula below

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 2 with the formula below

or a pharmaceutically acceptable salt thereof.

19. The compound of claim 2 with the formula below

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 2 with the formula below

or a pharmaceutically acceptable salt thereof.

21. The compound of claim 2 with the formula below

or a pharmaceutically acceptable salt thereof.

22. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 1 , and one or more pharmaceutically acceptable carriers or diluents.

23. The pharmaceutical composition according to claim 22 , wherein the compound or pharmaceutically acceptable salt thereof is selected from the group consisting of:

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl) tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2R,3R,4S)-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl) oxy)-6-(methoxycarbonyl)-3,4-dihydro-2H-pyran-3,4-diyl diacetate;

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-((benzyloxy)carbonyl)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl) oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-((benzyloxy)carbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-3,4,5-triacetoxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2R,3R,4S)-3,4-dihydroxy-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4-dihydro-2H-pyran-6-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-2-(ethoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

ethyl (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl) tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-(ethoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3S,4S,5R,6S)-2-((benzyloxy) carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl) oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-3,4,5-triacetoxy-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-2-((benzyloxy)carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3S,4S,5R,6S)-2-((methoxy) carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-((ethoxy)carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate); and

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-7-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

and pharmaceutically acceptable salts of any of these compounds.

24. A pharmaceutical composition comprising a compound selected from the group consisting of

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate,

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-6-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-7-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate, and

methyl (2S,3S,4S,5R,6S)-6-[[(4aR,10aR)-1-propyl-6-[(2S,3R,4S,5S,6S)-3,4,5-triacetoxy-6-methoxycarbonyl-tetrahydropyran-2-yl] oxy-3,4,4a,5,10,10a-hexahydro-2H-benzo[g]quinolin-7-yl] oxy]-3,4,5-triacetoxy-tetrahydropyran-2-carboxylate,

or pharmaceutically acceptable salt thereof;

and one or more pharmaceutically acceptable excipients.

25. A method for the treatment of a neurodegenerative disease or disorder selected from the group consisting of Parkinson's Disease, Huntington's disease, Restless leg syndrome and Alzheimer's disease; or a neuropsychiatric disease or disorder selected from the group consisting of schizophrenia, attention deficit hyperactivity disorder and drug addiction; which method comprises the administration of a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 , or which method comprises the administration of a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of:

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl) oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate,

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-6-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-7-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate, and

methyl (2S,3S,4S,5R,6S)-6-[[(4aR,10aR)-1-propyl-6-[(2S,3R,4S,5S,6S)-3,4,5-triacetoxy-6-methoxycarbonyl-tetrahydropyran-2-yl]oxy-3,4,4a,5,10,10a-hexahydro-2H-benzo[g]quinolin-7-yl]oxy]-3,4,5-triacetoxy-tetrahydropyran-2-carboxylate;

to a patient in need thereof.

26. A method for the treatment of a neurodegenerative disease or disorder selected from the group consisting of Parkinson's Disease, Huntington's disease, Restless leg syndrome and Alzheimer's disease; or a neuropsychiatric disease or disorder selected from the group consisting of schizophrenia, attention deficit hyperactivity disorder and drug addiction; which method comprises the administration of a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 , to a patient in need thereof.

27. The method of claim 26 , wherein the compound or pharmaceutically acceptable salt thereof is selected from the group consisting of:

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2R,3R,4S)-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)-3,4-dihydro-2H-pyran-3,4-diyl diacetate;

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-((benzyloxy)carbonyl)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-((benzyloxy)carbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-3,4,5-triacetoxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2R,3R,4S)-3,4-dihydroxy-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4-dihydro-2H-pyran-6-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-2-(ethoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

ethyl (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl) tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-(ethoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris (2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3S,4S,5R,6S)-2-((benzyloxy)carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-3,4,5-triacetoxy-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(ethoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

(2S,3S,4S,5R,6S)-2-((benzyloxy)carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3S,4S,5R,6S)-2-((methoxy)carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-((ethoxy)carbonyl)-6-(((4aR,10aR)-7-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy) tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-3,4,5-tris(pivaloyloxy)tetrahydro-2H-pyran-2-carboxylic acid;

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate);

(2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate); and

(2S,3R,4S,5S,6S)-2-(((4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-7-yl) oxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate;

and pharmaceutically acceptable salts of any of these compounds.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2022
From: JUHL, MARTIN; JENSEN, KLAUS GJERVIG; JØRGENSEN, MORTEN; KVÆRNØ, LISBET
To: H. LUNDBECK A/S
Reel/Frame 059860/0929 →
Priority Claims (1)
DK PA201900608 · May 21, 2019 · national
Continuity (1)
Related Publication 20220213071A1 · Jul 7, 2022
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