Boron-containing small molecules

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

wherein R 5 is H or halogen,

one of R a2 , R a3 , R a5 and R a6 is —NHC(O)OR 30 or alkyl substituted with —C(O)OR 30 or alkyl substituted with —S(O) 2 R 30 or alkyl substituted with halogen or alkyl substituted with hydroxy or alkyl substituted with cyano or alkyl substituted with —NHC(O)OR 30 or alkyl substituted with unsubstituted oxazolyl or alkyl substituted with alkyl substituted oxazolyl or alkyl substituted with unsubstituted oxadiazolyl or alkyl substituted with alkyl substituted oxadiazolyl or alkyl substituted with —C(O)NHR 35 , wherein R 30 is unsubstituted alkyl and R 35 is unsubstituted alkyl or unsubstituted cycloalkyl,

and the remaining members of R a2 , R a3 , R a5 and R a6 are H, R 10 and R 11 are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

wherein each hydrogen in said compound, or a salt thereof, is independently H or D.

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

wherein R 5 is or halogen,

R a2 is —NHC(O)OR 30 or alkyl substituted with —C(O)OR 30 or alkyl substituted with —S(O) 2 R 30 or alkyl substituted with halogen or alkyl substituted with hydroxy or alkyl substituted with cyano or alkyl substituted with —NHC(O)OR 30 or alkyl substituted with unsubstituted oxazolyl or alkyl substituted with alkyl substituted oxazolyl or alkyl substituted with unsubstituted oxadiazolyl or alkyl substituted with alkyl substituted oxadiazolyl or alkyl substituted with —C(O)NHR 35 ,

wherein R 30 is unsubstituted alkyl and R 35 is unsubstituted alkyl or unsubstituted cycloalkyl,

R 10 and R 11 are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl

wherein each hydrogen in said R a2 or said R 5 is independently H or D.

3. The compound of claim 1 , wherein R 5 is H.

4. The compound of claim 1 , wherein R 5 is F.

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

6. The compound of claim 5 , wherein R a2 is CH 2 NHC(O)OR 30 or CH 2 C(O)OR 30 or CH 2 S(O) 2 R 30 or CH 2 CN or CH 2 C(O)NHR 35 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 R 30 is unsubstituted alkyl and R 35 is unsubstituted alkyl or unsubstituted cycloalkyl.

7. The compound of claim 6 , wherein each hydrogen in said R 30 or said R 35 is independently H or D.

8. The compound of claim 6 , wherein R a2 is CH 2 NHC(O)OR 30 or CH 2 C(O)OR 30 or CH 2 S(O) 2 R 30 , and R 30 is CH 3 or CH 2 CH 3 or CH 2 CH 2 CH 3 or CH(CH 3 ) 2 or CH 2 CH 2 CH 2 CH 3 or C(CH 3 ) 3 or C(CH 3 )(CH 2 CH 3 )

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

9. The compound of claim 6 , wherein R a2 is CH 2 NHC(O)OR 30 or CH 2 C(O)OR 30 or CH 2 S(O) 2 R 30 , and R 30 is CH 3 or CD 2 H or CDH 2 or CH 2 CH 3 or CH 2 CD 3 or CH 2 CD 2 H or CH 2 CDH 2 or CH 2 CH 2 CH 3 or CH 2 CH 2 CD 3 or CH 2 CH 2 CD 2 H or CH 2 CH 2 CDH 2 or CH(CH 3 ) 2 or CH(CD 3 ) 2 or CH(CD 3 )(CH 3 ) or CH 2 CH 2 CH 2 CH 3 or CH 2 CH 2 CH 2 CD 3 or CH 2 CH 2 CH 2 CD 2 H or CH 2 CH 2 CH 2 CDH 2 or C(CH 3 ) 3 or C(CD 3 ) 3 or C(CD 3 )(CH 3 ) 2 or C(CD 3 ) 2 (CH 3 ) or CH(CH 3 )(CH 2 CH 3 ) or CH(CD 3 )(CH 2 CH 3 ) or CH(CH 3 )(CH 2 CD 3 ) or CH(CD 3 )(CH 2 CD 3 ).

10. The compound of claim 6 , wherein R a2 is CH 2 NHC(O)OCH 3 or CH 2 C(O)OCH 3 or CH 2 S(O) 2 CH 3 .

11. The compound of claim 6 , wherein R 5 is H and R a2 is CH 2 C(O)OR 30 , and R 30 is CH 3 or CH 2 CH 3 or CH 2 CH 2 CH 3 or CH(CH 3 ) 2 or CH 2 CH 2 CH 2 CH 3 or C(CH 3 ) 3 or CH(CH 3 )(CH 2 CH 3 ),

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

12. The compound of claim 6 , wherein R 5 is H and R a2 is CH 2 C(O)OR 30 , and R 30 is CH 3 or CD 3 or CD 2 H or CDH 2 or CH 2 CH 3 or CH 2 CD 3 or CH 2 CD 2 H or CH 2 CDH 2 .

13. The compound of claim 1 , wherein R a2 is CH 2 C(O)NHR 35 , wherein R 35 is cyclobutyl or cyclopentyl or cyclohexyl.

14. The compound of claim 1 , wherein R a2 is CH 2 CH 2 F or CH 2 CH 2 OH or —NHC(O)OR 30 , wherein R 30 is methyl or ethyl or propyl or isopropyl or butyl or t-butyl or isohutyl.

15. The compound of claim 1 , wherein

R 2a 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-1,3,4-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 compound of claim 1 , which is D,D,D-Methyl 2-(5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetate.

21. The compound of claim 1 , which is

4-Amino-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-(propylsulfonylmethyl)benzenesulfonamide;

4-Amino-2-(ethylsulfonylmethyl)-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)benzenesulfonamide; or

4-Amino-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-(methylsulfonylmethyl)benzenesulfonamide.

22. The compound of claim 1 , which is

Methyl 2-(5-amino-2-(N-(5-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetate;

Methyl 2-(5-amino-2-((1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methylsulfonyl)phenyl)acetate;

Isopropyl 2-(5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetate;

Ethyl 2-(5-amino-2-(N-(5-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetate;

Ethyl 2-(5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetate; or

tert-Butyl 2-(5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetate.

23. The compound of claim 1 , which is

Methyl-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenylcarbamate;

Isopropyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenylcarbamate;

Ethyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenylcarbamate;

Isopropyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)benzylcarbamate;

Propyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)benzylcarbamate;

Isopropyl 5-amino-2-(N-(5-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenylcarbamate; or

Ethyl 5-amino-2-(N-(5-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenylcarbamate.

24. The compound of claim 1 , which is

4-Amino-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-((5-methyl-1,2,4-oxadiazol-3-yl)methyl)benzenesulfonamide;

4-Amino-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-(oxazol-2-ylmethyl)benzenesulfonamide;

4-Amino-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-((5-methyloxazol-2-yl)methyl)benzenesulfonamide; or

4-Amino-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-((5-propyl-1,3,4-oxadiazol-2-yl)methyl)benzenesulfonamide.

25. The compound of claim 1 , which is

4-Amino-2-(2-fluoroethyl)-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)benzenesulfonamide;

4-Amino-N-(1 hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-(2-hydroxyethyl)benzenesulfonamide;

4-Amino-N-(5-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-2-(2-hydroxyethyl)benzenesulfonamide;

Isopropyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)benzylcarbamate;

Propyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)benzylcarbamate;

4-Amino-2-(cyanomethyl)-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)benzenesulfonamide;

Isobutyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)benzylcarbamate;

2-(5-Amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)-N-cyclopentylacetamide;

Methyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)benzylcarbamate;

Ethyl 5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)benzylcarbamate;

2-(5-Amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)-N-cyclobutylacetamide; or

2-(5-Amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)-N-cyclohexylacetamide.