BORON CONTAINING SMALL MOLECULES

• US 20110124597A1
• Filed: 08/31/2010
• Published: 05/26/2011
• Est. Priority Date: 09/25/2009
• Status: Abandoned Application

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: PLATTNER, Jacob, DING, Charles, ZHANG, Yong-Kang, ZHANG, Yanchen, HERNANDEZ, Vincent S., ALLEY, Michael Richard Kevin
• Application Number:
  US12/873,036
• Publication Number:
  US 20110124597A1
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

This invention provides, among other things, novel compounds useful for treating bacterial infections, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent.

Claims

1. A compound having a structure which is:

2. The compound of claim 1, wherein A comprises a moiety which is a quinolone or an oxazolidinone.

3. The compound of claim 2, wherein A comprises an oxazolidinone, and the oxazolidinone is selected from the group consisting of linezolid, torezolid, posizolid, ranbezolid, radezolid and eperezolid.

4. The compound of claim 1, wherein said compound has a structure which is:

5. The compound of claim 4, wherein said compound has a structure which is:

6. The compound of claim 2, wherein A is a quinolone, and the quinolone is fluoroquinolone or non-fluoroquinolone.

7. The compound of claim 2, wherein A is a quinolone, which is selected from the group consisting of nalidixic acid, oxolinic acid, piromidic acid, pipemidic acid, cinoxacin and flumequine.

8. The compound of claim 2, wherein A is a quinolone, which is selected from the group consisting of ciprofloxacin, enoxacin, fleroxacin, lomefloxacin, nadifloxacin, norfloxacin, ofloxacin, pefloxacin and rufloxacin.

9. The compound of claim 2, wherein A is a quinolone, which is selected from the group consisting of balofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, pazufloxacin, sparfloxacin, temafloxacin and tosufloxacin.

10. The compound of claim 2, wherein A is a quinolone, which is selected from the group consisting of clinafloxacin, besifloxacin, gemifloxacin, sitafloxacin, alatrofloxacin, trovafloxacin and prulifloxacin.

11. The compound of claim 2, wherein A is a quinolone, which is garenoxacin or delafloxacin.

12. The compound of claim 2, wherein A is a quinolone, which is selected from the group consisting of danofloxacin, difloxacin, enrofloxacin, ibafloxacin, marbofloxacin, rosoxacin, orbifloxacin and sarafloxacin.

13. The compound of claim 1, wherein said compound has a structure which is selected from the group consisting of:

14. The compound of claim 1, wherein R³ is selected from the group consisting of H, —

CH₂NH₂ and —

CH₂NO₂.

15. The compound of claim 14, wherein R³ is —

CH₂NH₂.

16. The compound of claim 1, having a structure which is selected from the group consisting of:

17. The compound of claim 1, having a structure which is

18. The compound of claim 17, with the proviso that when R³ is not H, C* is a stereocenter which has a configuration which is (S).

19. A composition comprising:

a) a first stereoisomer of the compound of claim 17;

b) at least one additional stereoisomer of the first stereoisomer;

wherein the first stereoisomer is present in an enantiomeric excess of at least 80% relative to said at least one additional stereoisomer.

20. The composition of claim 19, wherein said enantiomeric excess is at least 92%.

21. The composition of claim 19, wherein the C* stereocenter of the first stereoisomer is in a (S) configuration.

22. The composition of claim 19, wherein R³ is —

CH₂NH₂.

23. A composition comprising the compound of claim 17, wherein R³ is not H and the C* stereocenter is in a (S) configuration, and said composition is substantially free of a compound wherein the C* stereocenter is in a (R) configuration.

24. A composition comprising the compound of claim 17, wherein the composition is substantially free of the enantiomer of the compound.

25. A combination comprising the compound of claim 1, or a pharmaceutically acceptable salt thereof, together with at least one other therapeutically active agent.

26. A pharmaceutical formulation comprising:

a) the compound of claim 1, or a pharmaceutically acceptable salt thereof; and

b) a pharmaceutically acceptable excipient.

27. The pharmaceutical formulation of claim 26 wherein the pharmaceutical formulation is a unit dosage form.

28. A method of inhibiting an enzyme, comprising:

contacting the enzyme with the compound of claim 1, thereby inhibiting the enzyme.

29. The method of claim 28, wherein the enzyme is a t-RNA synthetase which comprises an editing domain.

30. The method of claim 28, wherein the enzyme is a leucyl t-RNA synthetase.

31. A method of killing and/or preventing the growth of a microorganism, comprising:

contacting the microorganism with an effective amount of the compound of claim 1, thereby killing and/or preventing the growth of the microorganism.

32. The method of claim 31, wherein the microorganism is a bacterium.

33. A method of treating and/or preventing a disease in an animal, comprising:

administering to the animal a therapeutically effective amount of the compound of claim 1, or a pharmaceutically-acceptable salt thereof, thereby treating and/or preventing the disease.

34. The method of claim 33, wherein the disease is caused by, or is mediated by, or involves a bacteria.

35. The method of claim 33, wherein the disease is caused by, or is mediated by, or involves a drug resistant bacterium.

36. The method of claim 33, wherein the disease is pneumonia.

37. The method of claim 33, wherein the animal is a human.

38. The compound of claim 1, wherein the salt is a pharmaceutically acceptable salt.