THERAPEUTIC USES OF PHARMACEUTICAL COMPOSITIONS COMPRISING CYCLIC BORONIC ACID ESTER DERIVATIVES

• US 20190076449A1
• Filed: 11/13/2018
• Published: 03/14/2019
• Est. Priority Date: 08/10/2010
• Status: Active Grant

• Current Assignee: Melinta Therapeutics, Inc.
• Original Assignee: Rempex Pharmaceuticals, Inc (Melinta Therapeutics, Inc.)
• Inventors: Hirst, Gavin, Reddy, Raja, Hecker, Scott, Totrov, Maxim, Griffith, David C., Rodny, Olga, Dudley, Michael N., Boyer, Serge
• Granted Patent: US 10,639,318 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/546 containing further heterocyclic rings, e.g. cephalothin
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to cyclic boronic acid ester derivatives and their use as therapeutic agents.

Claims

1. A sterile container comprising:

an antibacterial agent in solid form; and

a compound of Formula (I) in dolid form having the structure;

2. The sterile container of claim 1, wherein the compound has the structure of formula II:

3. The sterile container of claim 2, wherein n is 1.

4. The sterile container of claim 2, wherein R², R³, R⁴, and R⁵ are hydrogen.

5. The sterile container of claim 1, wherein the compound has the structure of formula IIIa, IIIb, IVa, IVb, or IVc:

6. The sterile container of claim 1, wherein R¹ is —

NHC(═

O)C_1-9alkylR¹¹.

7. The sterile container of claim 6, wherein R¹¹ is optionally substituted aryl or optionally substituted heteroaryl.

8. The sterile container of claim 7, wherein R¹¹ is thien-2-yl.

9. The sterile container of claim 1, wherein m is 1.

10. The sterile container of claim 1, wherein R⁶ and each R⁷ and R⁸ is hydrogen.

11. The sterile container of claim 1, wherein X is —

CO₂H.

12. The sterile container of claim 1, wherein the compounds has the structure selected from the group consisting of:

13. The sterile container of claim 1, wherein the compound is:

14. The sterile container of claim 1, wherein the antibacterial agent is a β

-lactam antibacterial agent.

15. The sterile container of claim 14, wherein the β

-lactam antibacterial agent is a carbapenem selected from the group consisting of simipenem, biapenem, doripenem, meropenem, and ertapenem.

16. The sterile container of claim 15, wherein the carbapenem is meropenem.

17. The sterile container of claim 14, wherein the β

-lactam antibacterial agent is selected from the group consisting of Amoxicillin, Ampicillin, Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin, Epicillin, Carbenicillin, Carindacillin, Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam, Pivmecillinam, Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Oxacillin, Meticillin, Nafcillin, Faropenem, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Panipenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefminox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftazidime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefmenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Cefatiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA-101, RWJ-54428, RWJ-333441, ME1036, BAL30072, BAL19764, Ceftiofur, Cefquinome, Cefovecin, Aztreonam, Tigemonam, Carumonam, RWJ-442831, RWJ-333441, and RWJ-333442.

18. The sterile container of claim 1, wherein the compound and the antibacterial agent are blended.

19. The sterile container of claim 1, wherein the compound and the antibacterial agent are not blended.

20. The sterile container of claim 1, wherein the compound is in crystalline form.

21. The sterile container of claim 1, wherein the antibacterial agent is in crystalline form.

22. The sterile container of claim 1, wherein the compound and the antimicrobial agent are lyophiles.

23. The sterile container of claim 1, wherein the molar ratio of compound to antibacterial agent is from 1:

8 to 8;

1.

24. The sterile container of claim 1, wherein the molar ratio of compound to antibacterial agent is from 1:

2 to 2;

1.

25. The sterile container of claim 1, wherein the molar ratio of compound to antibacterial agent is 1:

1.

26. The sterile container of claim 1, further comprising a pH adjuster.

27. The sterile container of claim 26, wherein the pH adjuster is selected from the group consisting of NaOH, citric acid, and sodium carbonate.

28. The sterile container of claim 1, wherein the antibacterial agent comprises meropenem, and the compound is:

31. A method of preparing a pharmaceutical composition for administration, comprising reconstituting the contents of the sterile container of claim 1 using a pharmaceutically acceptable diluent.

32. The method of claim 31, wherein the diluent is selected from the group consisting of a saline solution, a dextrose solution, and a sodium carbonate solution.

33. The method of claim 31, wherein the antibacterial agent comprises meropenem, and the compound is:

34. A method of administration comprising administering the reconstituted solution of claim 31 intravenously to a patient.

35. The method of claim 34, wherein the antibacterial agent comprises meropenem, and the compound is:

29. A sterile container comprising:

meropenem and a compound having a structure of;

30. The sterile container of claim 29, further comprising saline and sodium carbonate.