Beta lactams as modulators of glutamate uptake and methods for use thereof

1. A compound having formula (I):

or hydrates, solvates, pharmaceutically acceptable salts thereof, wherein:

A is selected from the group consisting of

R is selected from the group consisting of hydrogen, C 1-6 linear alkyl, C 1-6 branched alkyl, optionally substituted aryl, C(O)R 2 , C(O)OR 3 , C(O)NR 4a R 4b , SO 2 R 5 , and SO 2 NH 2 ;

R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , R 1g and R 1h are each independently selected from the group consisting of hydrogen, C 1-6 linear alkyl, and C 1-6 branch alkyl;

R 2 is selected from the group consisting of C 1-6 linear alkyl, C 1-6 branched alkyl, and optionally substituted aryl;

R 3 is selected from the group consisting of C 1-6 linear alkyl, C 1-6 branched alkyl, and optionally substituted aryl;

R 4a is selected from the group consisting of C 1-6 linear alkyl, C 1-6 branched alkyl, and optionally substituted aryl;

R 4b is selected from the group consisting of C 1-6 linear alkyl, C 1-6 branched alkyl, and optionally substituted aryl;

R 5 is selected from the group consisting of C 1-6 linear alkyl, C 1-6 branched alkyl, and optionally substituted aryl;

R 6 is selected from the group consisting of hydrogen, C 1-6 linear alkyl, and C(O)R 8 ;

R 7a , R 7b , R 7c , and R 7d are each independently selected from the group consisting of are each independently selected from a group consisting of hydrogen, halogen, OH, C 1-6 linear alkyl, C 1-6 branched alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, cyano, NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , NHC(O)R 8 , C(O)NHR 8 , C(O)N(R 8 ) 2 , SH, SC 1-6 alkyl, SO 2 NH 2 , SO 2 NHR 8 , SO 2 R 8 , and NHSO 2 R 8 ; and

R 8 is independently selected at each occurrence from a group consisting of hydrogen, C 1-6 linear alkyl, C 1-6 branched alkyl, and C 3-7 cycloalkyl.

2. A compound according to claim 1 wherein R 1b and R 1g are joined together with the atoms to which they are bound to form a ring containing 5, 6, or 7 atoms.

3. A compound according to claim 1 wherein R 1b and R 1f are joined together with the atoms to which they are bound to form a ring containing 5, 6, or 7 atoms.

4. A compound according to claim 1 wherein R 1d and R 1f are joined together with the atoms to which they are bound to form a ring containing 5, 6, or 7 atoms.

5. A compound according to claim 1 wherein R 1b and R 1c are joined together with the atoms to which they are bound to form a ring containing 5 or 6 atoms.

6. A compound of the claim 1 that is:

(3S, 4R)-3-((R)-(1-hydroxy-ethyl)-4-((R)-[1-methyl-2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-azetidin-2-one;

tert-butyl 4-((R)-2-((2R,3 S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl) propanoyl)piperazine-1-carboxylate;

(3S, 4R)-3-((R)-(1-Hydroxy-ethyl)-4-((R)-(1-methyl-2-oxo-2-piperazin-1-yl-ethyl)-azetidin-2-one;

(3S, 4R)-4-((R)-(1-(4-acetylpiperazin-1-yl)-1-oxopropan-2-yl)-3-((R) (1-hydroxyethyl)azetidin-2-one;

(3 S,4R)-4-((R)-1-(4-ethylpiperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-1-hydroxyethyl)azetidin-2-one;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-(4-(methyl sulfonyl) piperazin-1-yl)-1-oxopropan-2-yl)azetidin-2-one;

(3 S,4R)-4-((R)-1-(4-cyclohexylpiperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-1-hydroxyethyl)azetidin-2-one;

(3 S,4R)-4-((R)-1-(4-benzoylpiperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-1-hydroxyethyl)azetidin-2-one;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-oxo-1-(4-phenyl piperazin-1-yl)propan-2-yl)azetidin-2-one;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-oxo-1-(4-propyl piperazin-1-yl)propan-2-yl)azetidin-2-one;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-(4-(4-methoxyphenyl) piperazin-1-yl)-1-oxopropan-2-yl)azetidin-2-one;

(3 S,4R)-4-((R)-1-(4-(tert-butyl)piperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-1-hydroxyethyl)azetidin-2-one;

4-((R)-2-((2R,3 S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)propanoyl)piperazine-1-carboxamide;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-(4-methyl-3,4-dihydro quinoxalin-1(2H)-yl)-1-oxopropan-2-yl)azetidin-2-one;

(R)-1-((2R,3 S)-2-((R)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl)-4-oxoazetidin-3-yl)ethyl acetate;

(R)-1-((2R,3 S)-2-((R)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl)-4-oxoazetidin-3-yl)ethyl butyrate;

(R)-1-((2R,3 S)-2-((R)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl)-4-oxoazetidin-3-yl)ethyl isobutyrate;

(R)-1-((2R,3 S)-2-((R)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl)-4-oxoazetidin-3-yl)ethyl pivalate;

or a pharmaceutically acceptable salt form thereof.

7. A composition comprising an effective amount of at least one compound according to claim 1 .

8. A composition according to claim 7 , further comprising at least one excipient.

9. A composition according to claim 8 , wherein the at least one compound is at least one member selected from the group consisting of:

(3S, 4R)-3-((R)-(1-hydroxy-ethyl)-4-((R)-[1-methyl-2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-azetidin-2-one;

tert-butyl 4-((R)-2-((2R,3S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)propanoyl)piperazine-1-carboxylate;

(3S, 4R)-3-((R)-(1-Hydroxy-ethyl)-4-((R)-(1-methyl-2-oxo-2-piperazin-1-yl-ethyl)-azetidin-2-one;

(3S, 4R)-4-((R)-(1-(4-acetylpiperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-(1-hydroxyethyl)azetidin-2-one;

(3 S,4R)-4-((R)-1-(4-ethylpiperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-1-hydroxyethyl)azetidin-2-one;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-(4-(methyl sulfonyl)piperazin-1-yl)-1-oxopropan-2-yl)azetidin-2-one;

(3 S,4R)-4-((R)-1-(4-cyclohexylpiperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-1-hydroxyethyl)azetidin-2-one;

(3 S,4R)-4-((R)-1-(4-benzoylpiperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-1-hydroxyethyl)azetidin-2-one;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl)azetidin-2-one;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-oxo-1-(4-propylpiperazin-1-yl)propan-2-yl)azetidin-2-one;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-(4-(4-methoxyphenyl)piperazin-1-yl)-1-oxopropan-2-yl)azetidin-2-one;

(3 S,4R)-4-((R)-1-(4-(tert-butyl)piperazin-1-yl)-1-oxopropan-2-yl)-3-((R)-1-hydroxyethyl)azetidin-2-one;

4-((R)-2-((2R, 3 S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)propanoyl)piperazine-1-carboxamide;

(3 S,4R)-3-((R)-1-hydroxyethyl)-4-((R)-1-(4-methyl-3,4-dihydroquinoxalin-1 (2H)-yl)-1-oxopropan-2-yl)azetidin-2-one;

(R)-1-((2R, 3 S)-2-((R)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl)-4-oxoazetidin-3-yl)ethyl acetate;

(R)-1-((2R,3 S)-2-((R)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl)-4-oxoazetidin-3-yl)ethyl butyrate;

(R)-1-((2R,3 S)-2-((R)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl)-4-oxoazetidin-3-yl)ethyl isobutyrate;

(R)-1-((2R,3 S)-2-((R)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl)-4-oxoazetidin-3-yl)ethyl pivalate;

and a pharmaceutically acceptable salt form thereof.