Boron-containing small molecules

• US 8,703,742 B2
• Filed: 09/07/2011
• Issued: 04/22/2014
• Est. Priority Date: 09/07/2010
• Status: Active Grant

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: Hernandez, Vincent S., Ding, Charles, Plattner, Jacob J., Alley, Michael Richard Kevin, Rock, Fernando, Zhang, Suoming, Easom, Eric, Li, Xianfeng, Zhou, Ding
• Primary Examiner(s): Carter, Kendra D
• Assistant Examiner(s): Deck, Jason A
• Application Number:
  US13/227,444
• Publication Number:
  US 20120115813A1
• Time in Patent Office: 958 Days
• Field of Search: 514/263.34, 514/64, 556/7, 558/288, 435/184
• US Class Current: 514/64
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/06 for tuberculosis
• 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

Abstract

This invention relates to, among other items, benzoxaborole compounds and their use for treating bacterial infections.

Claims

1. A compound having a structure which is:

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

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

4. The compound of claim 2, wherein the C* stereocenter is in a (S) configuration.

5. The compound of claim 1, wherein R³ is —

CH₂NH₂.

6. The compound of claim 1, wherein R⁴ is selected from the group consisting of fluorine, chlorine, bromine, and iodine.

7. The compound of claim 1, wherein Y is O.

8. The compound of claim 1, wherein R⁵ is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, and sec-butyl.

9. The compound of claim 1, wherein R³ is —

CH₂NH₂; and

R⁴ is halogen.

10. The compound of claim 1, wherein R³ is —

CH₂NH₂;

R⁴ is chlorine;

Y is O; and

R⁵ is substituted or unsubstituted alkyl.

11. A composition comprising:

a) a first stereoisomer of the compound of claim 2;

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.

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

13. A pharmaceutical formulation comprising:

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

b) a pharmaceutically acceptable excipient.

14. The compound of claim 1, wherein R⁴ is chlorine or bromine.

15. The compound of claim 1, wherein R⁴ is chlorine.

16. The compound of claim 1, wherein R⁴ is selected from the group consisting of methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and sec-butoxy.

17. The compound of claim 1, wherein R⁴ is methoxy or ethoxy.

18. The compound of claim 4, wherein Y is O.

19. The compound of claim 1, wherein R⁵ is unsubstituted alkyl.

20. The compound of claim 2, wherein

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is methyl;

or

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl;

or

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is propyl;

or

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is isopropyl;

or

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₄ alkyl;

or

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₅ alkyl;

or

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₆ alkyl.

21. The compound of claim 2, wherein

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is methyl;

or

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl;

or

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is propyl.

22. The compound of claim 2, wherein

R⁴ is halogen, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl.

23. The compound of claim 2, wherein

R⁴ is fluorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is methyl;

or

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is methyl;

or

R⁴ is bromine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is methyl;

or

R⁴ is fluorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl;

or

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl;

or

R⁴ is bromine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl;

or

R⁴ is fluorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is propyl;

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is propyl;

R⁴ is bromine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is propyl;

R⁴ is fluorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is isopropyl;

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is isopropyl;

or

R⁴ is bromine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is isopropyl;

or

R⁴ is fluorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₄ alkyl;

or

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₄ alkyl;

or

R⁴ is bromine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₄ alkyl;

R⁴ is fluorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₅ alkyl;

or

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₅ alkyl;

or

R⁴ is bromine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₅ alkyl;

or

R⁴ is fluorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₆ alkyl;

or

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₆ alkyl;

or

R⁴ is bromine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is unsubstituted C₆ alkyl.

24. The compound of claim 2, wherein

R⁴ is fluorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl;

or

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl;

or

R⁴ is bromine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl.

25. The compound of claim 2, wherein

R⁴ is chlorine, R³ is —

CH₂NH₂;

Y is O; and

R⁵ is ethyl.