BORON-CONTAINING SMALL MOLECULES

• US 20110172187A1
• Filed: 11/11/2010
• Published: 07/14/2011
• Est. Priority Date: 11/11/2009
• Status: Active Grant

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: LIU, Yang, Li, Xiangeng, PLATTNER, Jacob J., ZHANG, Suoming, AKAMA, Tsutomu, ZHANG, Yanchen, ZHOU, Yasheen, NIEMAN, James A., HERNANDEZ, Vincent S., ALLEY, Michael Richard Kevin
• Granted Patent: US 8,461,134 B2
• 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 relates to, among other items, 6-substituted benzoxaborole compounds and their use for treating bacterial infections.

Claims

1. A compound, or a salt thereof, having a structure which is

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

3. The compound of claim 1, wherein R⁵ is H.

4. The compound of claim 1, wherein R⁵ is F.

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

6. The compound of claim 5, wherein

R^a2 is CH₂NHC(O)OR³⁰ or CH₂C(O)OR³⁰ or CH₂S(O)₂R³⁰ or CH₂CN or CH₂C(O)NHR³⁵ or methyl substituted with unsubstituted oxazolyl or methyl substituted with alkyl substituted oxazolyl or methyl substituted with unsubstituted oxadiazolyl or methyl substituted with alkyl substituted oxadiazolyl,

wherein R³⁰ is unsubstituted alkyl and R³⁵ is unsubstituted alkyl or unsubstituted cycloalkyl.

7. The compound of claim 6, wherein each hydrogen in said R³⁰ or said R³⁵ is independently H or D.

8. The compound of claim 6, wherein R^a2 is CH₂NHC(O)OR³⁰ or CH₂C(O)OR³⁰ or CH₂S(O)₂R³⁰, and R³⁰ is CH₃ or CH₂CH₃ or CH₂CH₂CH₃ or CH(CH₃)₂ or CH₂CH₂CH₂CH₃ or C(CH₃)₃ or C(CH₃)(CH₂CH₃)

wherein each hydrogen in said R^a2 is independently H or D.

9. The compound of claim 6, wherein R^a2 is CH₂NHC(O)OR³⁰ or CH₂C(O)OR³⁰ or CH₂S(O)₂R³⁰, and R³⁰ is CH₃ or CD₂H or CDH₂ or CH₂CH₃ or CH₂CD₃ or CH₂CD₂H or CH₂CDH₂ or CH₂CH₂CH₃ or CH₂CH₂CD₃ or CH₂CH₂CD₂H or CH₂CH₂CDH₂ or CH(CH₃)₂ or CH(CD₃)₂ or CH(CD₃)(CH₃) or CH₂CH₂CH₂CH₃ or CH₂CH₂CH₂CD₃ or CH₂CH₂CH₂CD₂H or CH₂CH₂CH₂CDH₂ or C(CH₃)₃ or C(CD₃)₃ or C(CD₃)(CH₃)₂ or C(CD₃)₂(CH₃) or CH(CH₃)(CH₂CH₃) or CH(CD₃)(CH₂CH₃) or CH(CH₃)(CH₂CD₃) or CH(CD₃)(CH₂CD₃).

10. The compound of claim 6, wherein

R^a2 is CH₂NHC(O)OCH₃ or CH₂C(O)OCH₃ or CH₂S(O)₂CH₃.

11. The compound of claim 6, wherein R⁵ is H and R^a2 is CH₂C(O)OR³⁰, and R³⁰ is CH₃ or CH₂CH₃ or CH₂CH₂CH₃ or CH(CH₃)₂ or CH₂CH₂CH₂CH₃ or C(CH₃)₃ or CH(CH₃)(CH₂CH₃)

wherein each hydrogen in said R^a2 is independently H or D.

12. The compound of claim 6, wherein R⁵ is H and R^a2 is CH₂C(O)OR³⁰, and R³⁰ is CH₃ or CD₃ or CD₂H or CDH₂ or CH₂CH₃ or CH₂CD₃ or CH₂CD₂H or CH₂CDH₂.

13. The compound of claim 1, wherein R^a2 is CH₂C(O)NHR³⁵, wherein R³⁵ is cyclobutyl or cyclopentyl or cyclohexyl.

14. The compound of claim 1, wherein

R^a2 is F or Cl or Br or CH₂CH₂F or CH₂CH₂OH or —

NHC(O)OR³⁰, wherein R³⁰ is methyl or ethyl or propyl or isopropyl or butyl or t-butyl or isobutyl.

15. The compound of claim 1, wherein

R^a2 is methyl substituted with 4-methyloxazol-2-yl or methyl substituted with 5-methyloxazol-2-yl or methyl substituted with 5-propyl-1,3,4 oxadiazol-2-yl or methyl substituted with 5-methyl-1,2,4 oxadiazol-2-yl.

16. A combination comprising:

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

b) a therapeutically active agent.

17. A pharmaceutical formulation comprising:

a) the compound of claim 1 or the combination of claim 16, or a pharmaceutically acceptable salt thereof; and

b) a pharmaceutically acceptable excipient.

18. A method of killing or inhibiting the growth of a bacteria, said method comprising:

contacting said bacteria with an effective amount of the compound of claim 1 or the combination of claim 16, or a pharmaceutically acceptable salt thereof, thereby killing or inhibiting the growth of the bacteria.

19. A method of treating a bacterial infection comprising:

administering to an animal suffering from said infection an effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, thereby treating the bacterial infection.

20. The use of the compound of claim 1 or the combination of claim 16 or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of bacterial infection.