NZ742006B2 - Valbenazine salts and polymorphs thereof - Google Patents
Valbenazine salts and polymorphs thereof Download PDFInfo
- Publication number
- NZ742006B2 NZ742006B2 NZ742006A NZ74200616A NZ742006B2 NZ 742006 B2 NZ742006 B2 NZ 742006B2 NZ 742006 A NZ742006 A NZ 742006A NZ 74200616 A NZ74200616 A NZ 74200616A NZ 742006 B2 NZ742006 B2 NZ 742006B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- crystalline form
- theta
- relative humidity
- increase
- compound
- Prior art date
Links
- GEJDGVNQKABXKG-CFKGEZKQSA-N [(2r,3r,11br)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1h-benzo[a]quinolizin-2-yl] (2s)-2-amino-3-methylbutanoate Chemical class C1CN2C[C@@H](CC(C)C)[C@H](OC(=O)[C@@H](N)C(C)C)C[C@@H]2C2=C1C=C(OC)C(OC)=C2 GEJDGVNQKABXKG-CFKGEZKQSA-N 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 4
- 238000002360 preparation method Methods 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims 8
- 238000000113 differential scanning calorimetry Methods 0.000 claims 6
- 238000000634 powder X-ray diffraction Methods 0.000 claims 6
- 238000002411 thermogravimetry Methods 0.000 claims 6
- 238000001757 thermogravimetry curve Methods 0.000 claims 6
- 238000001816 cooling Methods 0.000 claims 4
- 239000002002 slurry Substances 0.000 claims 4
- 238000010438 heat treatment Methods 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- 239000002552 dosage form Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000012902 Nervous system disease Diseases 0.000 abstract 2
- 208000025966 Neurological disease Diseases 0.000 abstract 2
- 208000000269 Hyperkinesis Diseases 0.000 abstract 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 abstract 1
- 208000016285 Movement disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 208000024891 symptom Diseases 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/32—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/29—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings
- C07C309/30—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings of six-membered aromatic rings substituted by alkyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
- C07D455/06—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine containing benzo [a] quinolizine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
Provided herein are salts of (S)-2-amino-3 -methyl-butyric acid (2R,3R, 1 1bR)-3-isobutyl- 9, 10-dimethoxy-1, 3, 4,6,7,11b-hexahydro-2H-pyrido[2,l-a]isoquinolin-2-yl ester in amorphous and crystalline forms, and processes of preparation, and pharmaceutical compositions thereof. Also provided are methods of their use for treating, preventing, or ameliorating one or more symptoms of neurological disorders and diseases including hyperkinetic movement disorders or diseases.
Claims (30)
1. A crystalline form of a compound of Formula I: which has an X-ray powder diffraction pattern comprising peaks at 6.3, 17.9, and 19.7 degrees two-theta ± 0.2 theta.
2. A crystalline form of claim 1, which has a differential scanning calorimetry thermogram comprising an endothermic event with an onset temperature of 240 °C and a peak at 243 °C.
3. A crystalline form of claim 1 or claim 2, which has a thermal gravimetric analysis plot comprising a mass loss of less than 0.4% when heated from 25 °C to 140 °C.
4. A crystalline form of any one of claims 1 to 3, which is stable upon exposure to 25 °C and 60% relative humidity for 3 months.
5. A crystalline form of any one of claims 1 to 4, which exhibits a mass increase of 1% when subjected to an increase in relative humidity from 0% to 95% relative humidity.
6. A crystalline form of a compound of Formula I: which has an X-ray powder diffraction pattern comprising peaks at 5.7, 15.3, and 22.5 degrees two-theta ± 0.2 theta.
7. A crystalline form of claim 6, which has a differential scanning calorimetry thermogram comprising an endothermic event with an onset temperature of 143 °C and a peak at 155 °C; and another endothermic event with an onset temperature of 232 °C and a peak at 235 °C.
8. A crystalline form of claim 6 or claim 7, which has a thermal gravimetric analysis plot comprising a mass loss of 2.2% when heated from 25 °C to 140 °C.
9. A crystalline form of any one of claims 6 to 8, which exhibits a mass increase of 0.5% when subjected to an increase in relative humidity from 0% to 95% relative humidity.
10. A crystalline form of a compound of Formula I: which has an X-ray powder diffraction pattern comprising peaks at 6.3, 18.3, 18.9, 19.8, and 20.4 degrees two-theta ± 0.2 theta.
11. A crystalline form of claim 10, which has a differential scanning calorimetry thermogram comprising endothermic events with temperatures of 93 °C, 158 °C, and 230 °C.
12. A crystalline form of claim 10 or claim 11, which has a thermal gravimetric analysis plot comprising two mass losses of 2.7% and 8.86% when heated from 25 °C to 140 °C.
13. A crystalline form of a compound of Formula I: which has an X-ray powder diffraction pattern comprising peaks at 6.2, 10.4, 17.9, 19.2, 19.9, and 20.2 degrees two-theta ± 0.2 theta.
14. A crystalline form of claim 13, which has a differential scanning calorimetry thermogram comprising endothermic events with temperatures of 128 °C, 159 °C, and 237
15. A crystalline form of claim 13 or claim 14, which has a thermal gravimetric analysis plot comprising a mass loss of 3.3% when heated from 25 °C to 140 °C.
16. A crystalline form of any one of claims 13 to 15, which exhibits a mass increase of 3.4% when subjected to an increase in relative humidity from 0% to 95% relative humidity.
17. A crystalline form of a compound of Formula I: which has an X-ray powder diffraction pattern comprising peaks at 6.7, 7.9, 10.7, 12.8, 17.1, and 23.7 degrees two-theta ± 0.2 theta.
18. A crystalline form of claim 17, which has a differential scanning calorimetry thermogram comprising endothermic events with temperatures of 113 °C and 181 °C.
19. A crystalline form of claim 17 or claim 18, which has a thermal gravimetric analysis plot comprising a mass loss of 4.1% when heated from 25 °C to 140 °C.
20. A crystalline form of any one of claims 17 to 19, which exhibits a mass increase of 1% when subjected to an increase in relative humidity from 0% to 95% relative humidity.
21. A crystalline form of a compound of Formula I: which has an X-ray powder diffraction pattern comprising peaks at 6.8, 8.0, 16.3, and 17.5 degrees two-theta ± 0.2 theta.
22. A crystalline form of claim 21, which has a differential scanning calorimetry thermogram comprising endothermic events with temperatures of 175 °C and 238 °C.
23. A crystalline form of claim 21 or claim 22, which has a thermal gravimetric analysis plot comprising a mass loss of 1% when heated from 25 °C to 140 °C.
24. A crystalline form of any one of claims 21 to 23, which exhibits a mass increase of 0.5% when subjected to an increase in relative humidity from 40% to 80% relative humidity.
25. A pharmaceutical composition comprising a crystalline form of any one of claims 1 to 24 and a pharmaceutically acceptable carrier.
26. A pharmaceutical composition of claim 25, wherein the composition is formulated for oral administration.
27. A pharmaceutical composition of claim 25 or 26, wherein the composition is formulated as a single dosage form.
28. A process for the preparation of a crystalline form of any one of claims 1 to 24, comprising the steps of: (a) preparing a slurry of a compound of Formula I in a solvent at a first temperature; (b) generating the crystalline form by cooling the slurry to a second temperature.
29. A process for the preparation of a crystalline form of any one of claims 1 to 24, comprising the steps of: (a) preparing a solution of a compound of Formula I in a solvent at a first temperature; (b) forming a slurry by cooling the solution to a second temperature; and (c) generating the crystalline form by treating the slurry with one or more heating and cooling cycles.
30. A process of claim 29, wherein the heating and cooling cycle is performed in a temperature range from -50 °C to
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562249074P | 2015-10-30 | 2015-10-30 | |
| PCT/US2016/059306 WO2017075340A1 (en) | 2015-10-30 | 2016-10-28 | Valbenazine salts and polymorphs thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ742006A NZ742006A (en) | 2024-10-25 |
| NZ742006B2 true NZ742006B2 (en) | 2025-01-28 |
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