Oxopiperazine derivatives for the treatment of pain and epilepsy

1. A compound of the formula:

or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

X is an optionally substituted alkylene (1-6C), alkenylene (2-6C), alkynylene (2-6C), heteroalkylene (2-6C), heteroalkenylene (2-6C), or heteroalkynylene (2-6C);

n is 1 or 2;

each m is, independently, an integer between 0-5;

each R 1 is methyl; and

each R 2 is, independently, selected from halo, CN, NO 2 , CF 3 , OCF 3 , COOR′, CONR′ 2 , OR′, SR′, SOR′, SO 2 R′, NR′ 2 , NR′(CO)R′, and NR′SO 2 R′, wherein each R′ is independently H or an optionally substituted group selected from alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), heteroalkyl (2-6C) heteroalkenyl (2-6), and heteroalkynyl (2-6C); or each R 2 is an optionally substituted group selected from alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), heteroalkyl (2-6C), heteroalkenyl (2-6C), or heteroalkynyl (2-6C).

2. A compound of the formula:

or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

both R 1a and R 1b are unsubstituted 1C-6C alkyl;

X is CH, CH 2 CH, (CH 2 ) 2-4 CH, CH═C, NHCH, or CH 2 S(═O)CH;

each m is, independently, 0, 1, or 2; and

each R 2 is, independently, optionally substituted 1C-6C alkyl or halogen.

3. The compound of claim 2 , wherein both R 1a and R 1b are methyl.

4. A compound of the formula:

or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

R 1a is H and R 1b is unsubstituted 1C-6C alkyl;

X is CH, CH 2 CH, (CH 2 ) 2-4 CH, CH═C, NHCH, or CH 2 S(═O)CH;

each m is, independently, 0, 1, or 2; and

each R 2 is, independently, optionally substituted 1C-6C alkyl or halogen.

5. The compound of claim 4 , wherein said unsubstituted 1C-6C alkyl is methyl.

6. The compound of claim 4 , wherein the carbon to which R 1a and R 1b are bonded has the R configuration.

7. The compound of claim 4 , wherein the carbon to which R 1a and R 1b are bonded has the S configuration.

8. A compound of the formula:

or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

each R 1a and R 1b is selected, independently, from H or unsubstituted 1C-6C alkyl;

X is CH, CH 2 CH, (CH 2 ) 2-4 CH, CH═C, NHCH, or CH 2 S(═O)CH;

each m is 1; and

each R 2 is, independently, optionally substituted 1C-6C alkyl or halogen, and

wherein both R 2 are ortho to X, or

wherein both R 2 are meta to X.

9. The compound of claim 8 , wherein both R 2 are meta to X.

10. The compound of claim 8 , wherein both R 2 are ortho to X.

11. A compound of the formula, wherein said compound has a structure according to

or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein

each R 1a and R 1b is selected, independently, from H or unsubstituted 1C-6C alkyl;

X is CH, CH 2 CH, (CH 2 ) 2-4 CH, CH═C, NHCH, or CH 2 S(═O)CH;

each m is, independently, 0, 1, or 2; and

each R 2 is selected, independently, from chloro or methyl.

12. A compound selected from the group consisting of:

N-benzhydryl-3-oxopiperazine-1-carboxamide;

4-(2-(benzhydrylsulfinyl)acetyl)piperazin-2-one;

4-(3,3-bis(4-chlorophenyl)propanoyl)piperazin-2-one;

4-(3,3-di-tolylpropanoyl)piperazin-2-one;

4-(6,6-diphenylhexanoyl)piperazin-2-one;

4-(2,2-diphenylacetyl)piperazin-2-one;

4-(3,3-diphenylacryloyl)piperazin-2-one;

4-(3,3-bis(4-fluorophenyl)propanoyl)piperazin-2-one;

4-(3,3-diphenylpropanoyl)-3,3-dimethylpiperazin-2-one;

(R)-4-(3,3-diphenylpropanoyl)-3-methylpiperazin-2-one;

(S)-4-(3,3-diphenylpropanoyl)-3-methylpiperazin-2-one;

4-(2,2-bis(4-chlorophenyl)acetyl)piperazin-2-one;

4-(2-(diphenylamino)acetyl)piperazin-2-one; and

4-(3,3-bis(4-fluorophenyl)propanoyl)-3,3-dimethylpiperazin-2-one;

or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

13. The compound of claim 12 , wherein said compound is:

14. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and

(a) the compound of claim 1 ; or

(b) a compound according to formula (III),

or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a stereoisomer thereof, or a conjugate thereof, wherein

X is an optionally substituted alkylene (1-6C), alkenylene (2-6C), alkynylene (2-6C), heteroalkylene (2-6C), heteroalkenylene (2-6C), or heteroalkynylene (2-6C);

n is an integer between 0-6;

each m is, independently, an integer between 0-5;

each R 1 and R 2 is independently selected from halo, CN, NO 2 , CF 3 , OCF 3 , COOR′, CONR′ 2 , OR′, SR′, SOR′, SO 2 R′, NR′ 2 , NR′(CO)R′, and NR′SO 2 R′, wherein each R′ is independently H or an optionally substituted group selected from alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), heteroalkyl (2-6C) heteroalkenyl (2-6), and heteroalkynyl (2-6C); or the optional substituents may be one or more optionally substituted groups selected from alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), heteroalkyl (2-6C), heteroalkenyl (2-6C), or heteroalkynyl (2-6C); and wherein each R 1 may further be selected from ═O and ═NOR′.

15. The pharmaceutical composition of claim 14 , wherein said pharmaceutical composition is formulated in unit dosage form.

16. The pharmaceutical composition of claim 15 , wherein said unit dosage form is a tablet, caplet, capsule, lozenge, film, strip, gelcap, or syrup.

17. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the compound of claim 12 .

18. The pharmaceutical composition of claim 17 , wherein said pharmaceutical composition is formulated in unit dosage form.

19. The pharmaceutical composition of claim 18 , wherein said unit dosage form is a tablet, caplet, capsule, lozenge, film, strip, gelcap, or syrup.

20. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the compound of claim 13 .

21. The pharmaceutical composition of claim 20 , wherein said pharmaceutical composition is formulated in unit dosage form.

22. The pharmaceutical composition of claim 21 , wherein said unit dosage form is a tablet, caplet, capsule, lozenge, film, strip, gelcap, or syrup.