Oxazolidinone compounds and methods of use thereof as antibacterial agents

1. A compound, or a pharmaceutically acceptable salt thereof, of formula IB:

wherein A is

R 8 is halogen or SO 2 CH 3 ;

each occurrence of R 2 is independently selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 3 -C 6 cycloalkyl, wherein said C 1 -C 6 alkyl, said C 2 -C 6 alkenyl, and said C 3 -C 6 cycloalkyl are optionally substituted with up to four substituents, which are independently selected from halogen, —OCH 3 , —OH, —NH 2 , —NHCH 3 , and —N(CH 3 ) 2 ;

R 3 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 6 heterocycloalkyl and C 3 -C 6 cycloalkyl, wherein said C 1 -C 6 alkyl, said C 2 -C 6 alkenyl, said C 3 -C 6 heterocycloalkyl and said C 3 -C 6 cycloalkyl are optionally substituted with up to four substituents, which are independently selected from halogen, methyl, —OCH 3 , —OH, —NH 2 , —NHCH 3 , and —N(CH 3 ) 2 ; and

each occurrence of R 9 is independently selected from H, C 1 -C 6 alkyl, and C 3 -C 6 cycloalkyl

m=is 0, 1, 2, or 3;

R 10 is selected from H, C 1 -C 6 alkyl and C 3 -C 6 cycloalkyl, wherein said C 1 -C 6 alkyl and said C 3 -C 6 cycloalkyl are optionally substituted with from one to four substituents, which are independently selected from F, —OCH 3 , —OH, NH 2 , NHCH 3 , and N(CH 3 ) 2 ;

R 11 is selected from H, C 1 -C 6 alkyl and C 3 -C 6 cycloalkyl, —COR 9 , —COOR 9 , —CON(R 9 ) 2 , and —SO 2 R 9 ;

each occurrence of R 12 is independently selected from H, halogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, benzyl, —OCF 3 , —OCHF 2 , —OR 3 , —CN, —NO 2 , —SR 3 , —SF 5 , —SCF 3 , —SOR 3 , —SO 2 R 3 , —S(═O)(═N)R 2 , —N(R 2 ) 2 , —NR 2 COR 3 , —SO 2 N(R 2 ) 2 , —NR 2 SO 2 R 3 , —COOH, —COR 9 , —COOR 3 , —CON(R 2 ) 2 , and —C(R 9 ) 2 N(R 2 ) 2 , wherein said C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, and benzyl are optionally substituted with up to four substituents independently selected from F, —OCH 3 , —OH, NH 2 , NHCH 3 , and N(CH 3 ) 2 ;

R 13 is selected from H, halogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, benzyl, —OCF 3 , —OCHF 2 , —OR 3 , —CN, —NO 2 , —SR 3 , —SF 5 , —SCF 3 , —SOR 3 , —SO 2 R 3 , —S(═O)(═N)R 2 , —N(R 2 ) 2 , —NR 2 COR 3 , —SO 2 N(R 2 ) 2 , —NR 2 SO 2 R 3 , —COOH, —COR 9 , —COOR 3 , —CON(R 2 ) 2 , and —C(R 9 ) 2 N(R 2 ) 2 , wherein said C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, and benzyl are optionally substituted with up to four substituents independently selected from F, —OCH 3 , —OH, NH 2 , NHCH 3 , and N(CH 3 ) 2 ; and

W is selected from O, S, SO, SO 2 , and S(═O)(═NH), wherein when A is

 then W is selected from S, SO, SO 2 , and S(═O)(═NH); and

wherein --- represents a double or a single bond.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is:

and wherein R 8 is halogen or SO 2 CH 3 .

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is:

and

wherein R 8 is halogen or SO 2 CH 3 .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is:

and

wherein R 8 is halogen or SO 2 CH 3 .

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8 is halogen.

6. A compound, or a pharmaceutically acceptable salt thereof, which is:

7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, which is:

8. A pharmaceutical composition which comprises a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

9. A method for treating a bacterial infection which comprises administering to a subject in need of such treatment a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

10. The method of claim 9 , wherein the bacterial infection is due to Mycobacterium tuberculosis.

11. The method according to claim 10 , further comprising the step of administering a second therapeutic agent for treating Mycobacterium tuberculosis.

12. The method of claim 11 , wherein the second therapeutic agent is selected from the group consisting of: ethambutol, pyrazinamide, isoniazid, levofloxacin, moxifloxacin, gatifloxacin, ofloxacin, kanamycin, amikacin, capreomycin, streptomycin, ethionamide, prothionamide, cycloserine, terididone, para-aminosalicylic acid, clofazimine, clarithromycin, amoxicillin-clavulanate, thiacetazone, meropenem-clavulanate, and thioridazine.

13. A pharmaceutical composition which comprises a therapeutically effective amount of a compound according to claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

14. A method for treating a bacterial infection which comprises administering to a subject in need of such treatment a therapeutically effective amount of a compound according to claim 6 , or a pharmaceutically acceptable salt thereof.

15. The method of claim 14 , wherein the bacterial infection is due to Mycobacterium tuberculosis.

16. The method according to claim 15 , further comprising the step of administering a second therapeutic agent for treating Mycobacterium tuberculosis.

17. The method of claim 16 , wherein the second therapeutic agent is selected from the group consisting of: ethambutol, pyrazinamide, isoniazid, levofloxacin, moxifloxacin, gatifloxacin, ofloxacin, kanamycin, amikacin, capreomycin, streptomycin, ethionamide, prothionamide, cycloserine, terididone, para-aminosalicylic acid, clofazimine, clarithromycin, amoxicillin-clavulanate, thiacetazone, meropenem-clavulanate, and thioridazine.