Solid forms of (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-carboxylic acid

Patent metadata

Field	Value
Publication number	US-11130775-B2
Application number	US-202016876908-A
Country	US
Kind code	B2
Filing date	May 18, 2020
Priority date	May 20, 2019
Publication date	Sep 28, 2021
Grant date	Sep 28, 2021

Abstract

The present invention relates to new solid forms of the compound (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-carboxylic acid with the formula (Id) below.The compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease.

First claim

The invention claimed is:

1. A solid form of the compound of formula (Id)

wherein said solid form is selected from:
the group consisting of the dihydrate of the zwitterion of compound (Id), the heptahydrate of the zwitterion of compound (Id) and the potassium salt of the compound (Id).

2. The solid form according to claim 1 , wherein said solid form is the dihydrate of the zwitterion of compound (Id) or the potassium salt of the compound (Id).

3. The solid form according to claim 1 , wherein said solid form is the dihydrate characterized by an x-ray powder diffraction pattern as obtained using CuKα1 radiation (λ=1.5406 Å) comprising one or more XRPD peaks as listed for the dihydrate in Table 2, group (a).

4. The solid form according to claim 1 , wherein said solid form is the dihydrate characterized by an x-ray powder diffraction pattern as obtained using CuKα1 radiation (λ=1.5406 Å) comprising peaks at the following 2θ-angles ±0.2° 2θ:10.4, 11.6, 12.3, 13.1, and 13.6°.

5. The solid form according to claim 4 , wherein said x-ray powder diffraction pattern further comprises one or more peaks selected from the group consisting of peaks at the following 2θ-angles ±0.2° 2θ: 14.3, 15.6, 16.0, 16.8, and 18.5°.

6. The solid form according to claim 1 , wherein said solid form is a crystal form characterized by an x-ray powder diffraction pattern as obtained using CuKα1 radiation (λ=1.5406 Å) essentially as depicted in FIG. 8 a.

7. The solid form according to claim 1 , said solid form exhibiting a weight loss of about 7.6% w/w compared to the initial weight when heated from about 30° C. to about 150° C. (heating rate 10° C./min).

8. The solid form according to claim 1 , wherein said solid form is the potassium salt characterized by an x-ray powder diffraction pattern as obtained using CuKα1 radiation (λ=1.5406 Å) comprising one or more XRPD peaks as listed for the potassium salt in Table 2, group (a).

9. The solid form according to claim 8 , wherein said potassium salt has a crystal form characterized by an XRPD obtained using CuKα1 radiation (λ=1.5406 Å) comprising peaks at the following 2θ-angles ±0.2° 2θ: 3.0, 9.0, 12.6, 13.6, and 15.0°.

10. The solid form according to claim 9 , wherein said x-ray powder diffraction pattern further comprises one or more peaks selected from the group consisting of peaks at the following 2θ-angles ±0.2° 2θ: 17.1, 18.0, 18.4, 18.8 and 19.4°.

11. The solid form according to claim 1 , said form exhibiting a weight loss of less than about 1% w/w compared to the initial weight when heated from about 20° C. to about 150° C. (heating rate 10° C/min).

12. A pharmaceutical composition comprising a therapeutically effective amount of the solid form of the compound of formula (Id) according to claim 1 , and one or more pharmaceutically acceptable excipients.

13. A method for the manufacture of a medicament comprising combining the solid form of the compound of formula (Id) according to claim 1 with one or more pharmaceutically acceptable excipients.

14. The solid form according to claim 1 , wherein said solid form is the dihydrate of the zwitterion of compound (Id).

15. The solid form according to claim 1 , wherein said solid form is the heptahydrate of the zwitterion of compound (Id).

16. The solid form according to claim 1 , wherein said solid form is the potassium salt of the compound (Id).

Assignees

• H Lundbeck As

Inventors

• Jensen Klaus Gjervig
• Kværnø Lisbet
• Jørgensen Morten
• Juhl Martin
• De Diego Heidi Lopez
• Fredholt Karin
• Therkelsen Frans Dennis
• Frihed Tobias Gylling
• Jacobsen Mikkel Fog

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• C07H17/02 Primary

  Heterocyclic radicals containing only nitrogen as ring hetero atoms · CPC title

• A61K31/706

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title

• C07H15/26 Primary

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title