Phosphonocephem compound

• US 6,906,055 B2
• Filed: 08/10/2001
• Issued: 06/14/2005
• Est. Priority Date: 08/10/2000
• Status: Expired due to Term

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Ishikawa, Tomoyasu, Iizawa, Yuji, Hashiguchi, Shohei
• Primary Examiner(s): Berch, Mark L.
• Application Number:
  US10/343,285
• Publication Number:
  US 20040023943A1
• Time in Patent Office: 1,404 Days
• Field of Search: 544/225, 514/203
• US Class Current: 514/203
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07F 9/65613 containing the ring system (X = CH2, O, S, NH) optionally with an additional double bond and/or substituents, e.g. cephalosporins and analogs

Abstract

A cephem compound (particularly its crystal) represented by the formula [I], wherein X is CH₃COOH, CH₃CH₂COOH or CH₃CN, and n is 0 to 5, is useful as an antibacterial agent (particularly anti-MRSA agent) and shows superior quality such as high solid stability, possible long-term stable preservation and the like.

Claims

1. A compound of the formula:

wherein X is CH₃COOH or CH₃CH₂COOH, and n is 0 to 5.

2. The compound of claim 1, which is in the form of a crystal.

3. The compound of claim 1, wherein n is 1.

4. The compound of claim 1, wherein X is CH₃COOH.

5. The compound of claim 4, having peaks near diffraction angles of 16.32, 19.06, 19.90, 20.98 and 23.24°

in powder X-ray diffraction (CuKα

).

6. The compound of claim 4, having peaks near diffration angles of 11.82, 17.16, 17.80, 19.32, 20.00, 21.20, 21.78, 22.94, 24.10 and 27.02°

in powder X-ray diffraction (CuKα

).

7. The compound of claim 1, wherein X is CH₃CH₂COOH.

8. The compound of claim 7, having peaks near diffraction angles of 16.30, 18.84, 19.70, 21.80 and 23.18°

in powder X-ray diffraction (CuKα

).

9. A pharmaceutical composition, comprising the compound of claim 1 and a pharmaceutically acceptable carrier, diluent or exipient.

16. The compound of claim 2, wherein X is CH₃COOH.

17. The compound of claim 2, wherein X is CH₃CH₂COOH.

18. A pharmaceutical composition, comprising the compound of claim 2 and a pharmaceutically acceptable carrier, diluent or excipient.

10. A production method of a crystal of a compound represented by the formula:

wherein X is CH₃COOH or CH₃CH₂COOH, and n is 0 to 5, which comprises mixing [i] a compound represented by the formula;

[ii] CH₃COOH or CH₃CH₂COOH and [iii] water, dissolving them and allowing crystallization to take place.

11. The production method of claim 10, wherein the proportion (volume ratio) to be used of CH₃COOH or CH₃CH₂COOH:

water is 1;

0.1-10.

12. A crystal obtained by mixing [i] a compound represented by the formula:

[iii] CH₃COOH or CH₃CH₂COOH and [iii] water, dissolving them and allowing crystallization to take place.

13. A disodium salt of a compound represented by the formula:

14. The disodium salt of claim 13, which is in the form of a crystal.

15. The disodium salt of claim 13, having peaks near diffraction angles of 17.02, 18.94, 22.86, 23.36 and 26.48°

in powder X-ray diffraction (CuKα

).

19. The disodium salt of claim 14, having peaks near diffraction angles of 17.02, 18.94, 22.86, 23.36 and 26.48°

in powder X-ray diffraction (CuKα

).

20. A method for making a crystal of a compound of formula (I):

wherein X is CH₃COOH or CH₃CH₂COOH, and n is 0 to 5, comprising crystallizing a compound of formula (Ia);

from CH₃COOH or CH₃CH₂COOH and water.

21. A crystal obtained by crystallizing a compound of formula (Ia):

from CH₃COOH or CH₃CH₂COOH and water.