Malate salts, and polymorphs of (3S,5S)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid

Abstract

The present invention is directed to malate salts of (3S,5S)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid, and its polymorphs. The present invention is also directed to pharmaceutical compositions comprising the described salts and polymorphs.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a representative X-ray Diffraction Pattern for D,L-malate hemi-hydrate polymorph salt of Compound I.

FIG. 2 shows a representative X-ray Diffraction Pattern for D-malate hydrate polymorph salt of Compound I.

FIG. 3 shows a representative X-ray Diffraction Pattern for L-malate hydrate polymorph salt of Compound I.

FIG. 4 shows a representative solid-state ¹³C NMR spectrum for D,L-malate hemi-hydrate polymorph salt of Compound I.

FIG. 5 shows a representative solid-state ¹³C NMR spectrum for D-malate hydrate polymorph salt of Compound I.

FIG. 6 shows a representative solid-state ¹³C NMR spectrum for L-malate hydrate polymorph salt of Compound I.

FIG. 7 shows a representative solid-state ¹³C NMR spectrum for D-malate anhydrate polymorph salt of Compound I.

FIG. 8 shows a representative solid-state ¹³C NMR spectrum for L-malate anhydrate polymorph salt of Compound I.

FIG. 9 shows a representative infrared spectrum for D,L-malate hemi-hydrate polymorph salt of Compound I.

FIG. 10 shows a representative infrared spectrum for D-malate hydrate polymorph salt of Compound I.

FIG. 11 shows a representative infrared spectrum for L-malate hydrate polymorph salt of Compound I.

FIG. 12 shows a representative infrared spectrum for D-malate anhydrate polymorph salt of Compound I.

FIG. 13 shows a representative infrared spectrum for L-malate anhydrate polymorph salt of Compound I.

Claims

1. A malate salt of (3S,5S)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid.

2. A polymorphic malate salt of (3S,5S)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid, wherein there is between about 0% and about 5% water by weight present.

3. A compound according to claim 2, wherein there is between about 1% and about 5% water by weight present.

4. A compound according to claim 2, wherein there is between about 0% and about 2% water by weight present.

5. A compound according to claim 3, having an X-ray diffraction pattern characterized substantially in accordance with the pattern of FIG. 1.

6. A compound according to claim 3, having an X-ray diffraction pattern characterized substantially in accordance with the pattern of FIG. 2.

7. A compound according to claim 3, having an X-ray diffraction pattern characterized substantially in accordance with the pattern of FIG. 3.

8. A compound according to claim 3, having a solid-state 13C NMR spectrum characterized substantially in accordance with the pattern of FIG. 4.

9. A compound according to claim 3, having a solid-state 13C NMR spectrum characterized substantially in accordance with the pattern of FIG. 5.

10. A compound according to claim 3, having a solid-state 13C NMR spectrum characterized substantially in accordance with the pattern of FIG. 6.

11. A compound according to claim 4, having a solid-state 13C NMR spectrum characterized substantially in accordance with the pattern of FIG. 7.

12. A compound according to claim 4, having a solid-state 13C NMR spectrum characterized substantially in accordance with the pattern of FIG. 8.

13. A compound according to claim 3, having an infrared spectrum pattern characterized substantially in accordance with the pattern of FIG. 9.

14. A compound according to claim 3, having an infrared spectrum pattern characterized substantially in accordance with the pattern of FIG. 10.

15. A compound according to claim 3, having an infrared spectrum pattern characterized substantially in accordance with the pattern of FIG. 11.

16. A compound according to claim 4, having an infrared spectrum pattern characterized substantially in accordance with the pattern of FIG. 12.

17. A compound according to claim 4, having an infrared spectrum pattern characterized substantially in accordance with the pattern of FIG. 13.

18. A compound according to claim 3, having characteristic X-ray diffraction peaks at about 10.7, about 11.98 and about 12.5 degrees 2 theta.

19. A compound according to claim 3, having characteristic X-ray diffraction peaks at about 9.3, about 12.1 and about 22.6 degrees 2 theta.

20. A compound according to claim 3, having characteristic X-ray diffraction peaks at about 9.5, about 11.7 and about 12.3 degrees 2 theta.

21. A polymorphic salt according to claim 2, selected from the group consisting of D,L-malate hemi-hydrate, D-malate hydrate, L-malate Hydrate, D-malate anhydrate and L-malate anhydrate.

22. A D,L-malate hemi-hydrate polymorphic salt of (3S,5S)-7-[3-amino-5-methyl-piperidinyl]-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid.

23. A pharmaceutical composition comprising: (a) a safe and effective amount of a compound according to claim 1; and(b) a pharmaceutically acceptable carrier.

24. A pharmaceutical composition comprising: (a) a safe and effective amount of a compound according to claim 2; and(b) a pharmaceutically acceptable carrier.

25. A pharmaceutical composition comprising: (a) a safe and effective amount of a compound according to claim 22; and(b) a pharmaceutically acceptable carrier.

26. A method of treating or preventing an infectious disorder in a human or other animal in need of such treatment, comprising: (a) identifying a human or other animal in need of treating or preventing an infectious disorder; and(b) administering to the human or other animal a safe and effective amount of a compound according to claim 1.