Novel anticonvulsant derivative salts

• US 20030069190A1
• Filed: 07/03/2002
• Published: 04/10/2003
• Est. Priority Date: 07/09/2001
• Status: Active Grant

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Inventors: Abdel-Magid, Ahmed, Maryanoff, Cynthia
• Granted Patent: US 7,098,188 B2
• Time in Patent Office: Days
• US Class Current: 514/23
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: C07H 11/00 Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof halo-sugars C07H5/02; thio-, seleno-, or telluro-sugars C07H5/08

Abstract

The invention relates to novel pharmaceutically acceptable salts of anticonvulsant derivatives, processes for preparation of and pharmaceutical compositions containing said salts, useful in the treatment of epilepsy.

Claims

1. A salt of a compound of formula (I)

2. A salt as in claim 1, wherein the compound of formula (I) is topiramate.

3. A salt as in claim 1, wherein an alkali metal or magnesium cation displaces one hydrogen atom of the sulfamate.

4. A salt as in claim 1, wherein the salt of the compound of formula (I) is a sodium salt of topiramate.

5. A salt as in claim 4, of the formula (II)

6. A salt as in claim 5, characterized essentially by the following X-ray diffraction pattern:

7. A salt as in claim 5, characterized essentially by the following X-ray diffraction pattern:

8. A salt as in claim 5, characterized essentially by the following X-ray diffraction pattern:

9. A salt as in claim 5, characterized essentially by the following X-ray diffraction pattern:

10. A salt as in claim 1, wherein the salt of the compound of formula (I) is a potassium salt of topiramate.

11. A salt as in claim 10, of the formula (III)

12. A salt as in claim 11, characterized essentially by the following X-ray diffraction pattern:

13. A salt as in claim 11, characterized essentially by the following X-ray diffraction pattern:

14. A salt as in claim 11, characterized essentially by the following X-ray diffraction pattern:

15. A salt as in claim 11, characterized essentially by the following X-ray diffraction pattern:

16. A salt as in claim 1, wherein the salt of the compound of formula (I) is a lithium salt of topiramate.

17. A salt as in claim 16, of the formula (IV)

18. A salt as in claim 1, wherein the salt of the compound of formula (I) is a magnesium salt of topiramate.

19. A salt as in claim 18, of the formula (V)

20. A pharmaceutical composition comprising a salt of claim 1 and a pharmaceutically acceptable carrier.

21. A pharmaceutical composition prepared by combining a salt of claim 1 and a pharmaceutically acceptable carrier.

22. A process for making a pharmaceutical composition comprising combining a salt of claim 1 with a pharmaceutically acceptable carrier.

23. A process for preparing an alkali metal salt of a compound of formula (I) comprising

reacting a compound of formula (I)

with an alkali metal hydride under anhydrous condition, an alkali metal hydroxide, an alkali metal lower alkoxide or an alkali metal amide under anhydrous conditions, in an organic solvent;

and precipitating the product.

24. A process as in claim 23, wherein the alkali metal hydride is sodium hydride, the alkali metal hydroxide is sodium hydroxide, the alkali metal lower alkoxide is sodium lower alkoxide or the alkali metal amide is sodium amide.

25. A process as in claim 23, wherein the alkali metal hydride is potassium hydride, the alkali metal hydroxide is potassium hydroxide, the alkali metal lower alkoxide is potassium lower alkoxide or the alkali metal amide is potassium amide.

28. A process as in claim 23, wherein the compound of formula (I) is a topiramate.

29. A process as in claim 24, wherein the compound of formula (I) is topiramate.

30. A process as in claim 25, wherein the compound of formula (I) is topiramate.

26. A process for preparing a lithium salt of a compound of formula (I) comprising

reacting a compound of formula (I)

with lithium hydride under anhydrous conditions, lithium hydroxide, lithium lower alkoxide, alkyl lithium under anhydrous conditions or lithium amide under anhydrous conditions, in an organic solvent;

and precipitating the product.

31. A process as in claim 26, wherein the compound of formula (I) is topiramate.

27. A process for preparing a magnesium salt of a compound of formula (I) comprising

reacting a compound of formula (I)

with a magnesium lower alkoxide, under anhydrous conditions, in an organic solvent;

and precipitating the product.

32. A process as in claim 27, wherein the compound of formula (I) is topiramate.