POLYMORPHS OF (S)-3-AMINOMETHYL-7-(3-HYDROXY-PROPOXY)-3H-BENZO[C][1,2]OXABOROL-1-OL

• US 20110152217A1
• Filed: 12/17/2009
• Published: 06/23/2011
• Est. Priority Date: 12/17/2008
• Status: Active Grant

• Current Assignee: GlaxoSmithKline LLC (GlaxoSmithKline PLC), Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: GlaxoSmithKline LLC (GlaxoSmithKline PLC), Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: Chen, Pingyun, Norton, Beth A., Wheeler, Conrad, Todd, Dan
• Granted Patent: US 8,461,364 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

This invention provides, among other things, polymorphs of the hydrochloride salt of (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol.

Claims

1. A crystalline polymorph characterized by having essentially any of the °

2θ

values listed in Table 1±

0.2°

2θ

;

2. The crystalline polymorph of claim 1, comprising any 4 peaks, ±

0.2°

2θ

, as depicted in Table 1.

3. The crystalline polymorph of claim 1, comprising any 7 peaks, ±

0.2°

2θ

, as depicted in Table 1.

4. The crystalline polymorph of claim 1, comprising any 10 peaks, ±

0.2°

2θ

, as depicted in Table 1.

5. The crystalline polymorph of claim 1, comprising all peaks, ±

0.2°

2θ

, as depicted in Table 1.

6. The crystalline polymorph of claim 1, wherein said polymorph is a polymorph of a hydrochloride salt of (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol.

10. A pharmaceutical composition comprising:

a) the crystalline polymorph of claim 1; and

b) at least one excipient or carrier.

11. A method for treating a disease in an animal suffering from the disease, comprising:

administering to the animal a therapeutically effective amount of the crystalline polymorph of claim 1,

wherein said disease is associated with a bacteria.

12. The method of claim 10, wherein the bacteria is a Gram negative bacteria.

13. The method of claim 10, wherein the bacteria is selected from the group consisting of Neisseria species, Escherichia species, Shigella species, Salmonella species, Yersinia species, Klebsiella species, Proteus species, Enterobacter species, Serratia species, Vibrio species, Campylobacter species, Helicobacter species, Pseudomonas species, Bacteroides species, Haemophilus species, Bordetella species, Legionella species, Francisella species, Brucella species, Pasteurella species, Gardnerella species, Spirochetes species, Chlamydia species and Rickettsiae species.

14. The method of claim 10, wherein the disease is selected from the group consisting of meningitis, gonorrhea, otitis, otitis extema, folliculitis, diarrhea, urinary tract infections, sepsis, HAP, bacteremia, endocarditis, gastroenteritis, Typhoid fever, supsis, endocarditis, sinusitis, bubonic plague, enteric fever, hospital-acquired infection, skin and skin-structure infection, pneumonia, cholera, chronic gastritis, osteomylitis, burn-wound infections, corneal infections, periodontal disease, aspriation pneumonia, piglottitis, septic arthritis, chancroid, vaginitis, whooping cough, pontiac fever, tularemia, brucellosis, syphilis, Lyme disease, chlamydia, Rocky Mountain spotted fever, typhus, tracheobronchitis, walking pneumonia, urethritis, pyelonenephritis, intra-abdominal infection, febrile neutropenia, pelvic infection, bacteraemia, and septicaemia.

15. The method of claim 10, wherein the disease is pneumonia.

7. A crystalline polymorph of a hydrochloride salt of (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol having, upon X-ray crystallographic analysis, crystal parameters of substantially the following values:

Crystallographic system;

orthorhombic

Space group;

P2₁2₁2₁

Crystal dimensions;

a=9.1045(2) Å

, b=10.3107(2) Å

, c=14.5988(3) Å

α

=90.00°

, β

=90.00°

, γ

=90.00°

Volume 1370.44(5) A³

Z, calculated density 4, 1.326 g cm<sup>−

3</sup>.

8. A crystalline polymorph of a hydrochloride salt of (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol, characterized by having a

upon Raman spectroscopic analysis, any of the peaks having substantially the wavenumbers (cm⁻

1) selected from the group consisting of 3076.4, 3054.6, 2987.4, 2975.5, 2954.2, 2928.0, 2909.8, 2896.0, 1578.6, 1298.2, 1291.6, 1263.0, 1226.8, 1068.9, and 694.9, ±

50 wave numbers.

9. The crystalline polymorph of claim 8, having a multiplet of peaks between about 2800 and about 3200 cm⁻

1, ±

50 wavenumbers, and another multiplet of peaks between about 1600 and about 600 cm<sup>−

1</sup>, ±

50 wavenumbers, and an essential absence of peaks between about 1800 and about 2200 cm<sup>−

1</sup>, ±

50 wavenumbers.

16. Crystalline (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol.HCl, form HCl4.

20. A method of preparing the crystalline polymorph of claim 16.

17. Crystalline (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol.HCl, form HCl3.

18. Crystalline (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol.HCl, form HCl2.

19. Crystalline (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol.HCl, form HCl1.