METHODS OF TREATING ALZHEIMER'S DISEASE, HUNTINGTON'S DISEASE, AUTISM, OR OTHER DISORDERS

1 . A method for treating autism in a patient in need thereof, comprising administering to said patient:

a pharmaceutically effective amount of GLYX-13:

 or pharmaceutically acceptable salt thereof,

or

a pharmaceutically effective amount of a compound represented by Formula I:

and pharmaceutically acceptable salts, stereoisomers, and N-oxides thereof; wherein T is, independently for each occurrence, CR 4 R 4 ′, and n is 0, 1, 2 or 3;

A is optionally present and is selected from phenyl or pyridine, wherein A is optionally substituted by one or more substituents selected from R a ;

R 1 is selected from the group consisting of H, hydroxyl, —S(O) 2 —C 1-4 alkyl; —SO 2 , C 1-4 alkyl, C 2 -C 4 alkenyl, phenyl, R 7 , and

 wherein C 1-4 alkyl, C 2-4 alkenyl, or phenyl is optionally substituted by one or more substituents selected from R a ;

X is CH or N;

R 3 and R 3 ′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C 1-4 alkyl, amido, amine, and C 2-4 alkenyl, wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 4 and R 4 ′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C 1-4 alkyl, amido, amine, C 1-4 alkoxy or C 2-4 alkenyl, wherein C 1-4 alkyl, C 2-4 alkenyl, C 1-4 alkoxy, and phenyl are optionally substituted by one or more substituents selected from R a ;

R 2 is selected from the group consisting of H, R 7 , —S(O) 2 , S(O) 2 —C 1 -C 4 alkyl, C 1-4 alkyl, hydroxyl, and phenyl wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 5 and R 5 ′ are each independently selected from group consisting of H, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl, cyano, amino, phenyl, and hydroxyl, wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 7 is selected from group consisting of —C(O)—R 9 , —C(O)—O—R 9 , and —C(O)—NR d —R 9 ;

R 9 is selected from the group consisting of H, C 1-4 alkyl, phenyl, or heterocyclic, wherein C 1-4 alkyl, phenyl and heterocyclic is optionally substituted by 1, 2 or 3 substituents selected from R b ;

R 8 is selected from group consisting of H, —C(O)— C 1-4 alkyl and C(O)—O— C 1-4 alkyl, wherein C 1-4 alkyl is optionally substituted by 1, 2 or 3 substituents selected from R a ;

R a is selected, independently for each occurrence, from carboxy, hydroxyl, halogen, amino, phenyl, C 1-4 alkyl, and C 1-4 alkoxy;

R b is selected, independently for each occurrence, from the group consisting of carboxy, hydroxyl, halogen, amino, phenyl, C 1-4 alkyl, C 1-4 alkoxy, and —NH—R c ;

R c is selected, independently for each occurrence from the group consisting of: —C(O)—O—C 1-4 alkyl; and —C(O)—C 1-4 alkyl; and

R d is selected, independently for each occurrence, H and C 1-4 alkyl;

and pharmaceutically acceptable salts, N-oxides or stereoisomers thereof.

2 . The method of claim 1 , wherein about 1 day after administration, the patient has substantial improvement in one or more autism symptoms.

3 . The method of claim 1 , wherein about 8 days after administration the patient has substantial improvement in one or more autism symptoms

4 . A method of treating a condition selected from the group consisting of epilepsy, AIDS dementia, multiple system atrophy, progressive supra-nuclear palsy, Friedrich's ataxia, Down's syndrome, fragile X syndrome, tuberous sclerosis, olivio-ponto-cerebellar atrophy, cerebral palsy, drug-induced optic neuritis, peripheral neuropathy, myelopathy, ischemic retinopathy, diabetic retinopathy, glaucoma, cardiac arrest, behavior disorders, and impulse control disorders, in a patient in need thereof, comprising administering to said patient:

a pharmaceutically effective amount of GLYX-13:

 or pharmaceutically acceptable salt thereof,

or

a pharmaceutically effective amount of a compound represented by Formula I:

wherein

T is, independently for each occurrence, CR 4 R 4 ′, and n is 0, 1, 2 or 3;

A is optionally present and is selected from phenyl or pyridine, wherein A is optionally substituted by one or more substituents selected from R a ;

R 1 is selected from the group consisting of H, hydroxyl, —S(O) 2 —C 1-4 alkyl; —SO 2 , C 1-4 alkyl, C 2 -C 4 alkenyl, phenyl, R 7 , and

 wherein C 1-4 alkyl, C 2-4 alkenyl, or phenyl is optionally substituted by one or more substituents selected from R a ;

X is CH or N;

R 3 and R 3 ′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C 1-4 alkyl, amido, amine, and C 2-4 alkenyl, wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 4 and R 4 ′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C 1-4 alkyl, amido, amine, C 1-4 alkoxy and C 2-4 alkenyl, wherein C 1-4 alkyl, C 2-4 alkenyl, C 1-4 alkoxy, and phenyl are optionally substituted by one or more substituents selected from R a ;

R 2 is selected from the group consisting of H, R 7 , —S(O) 2 , S(O) 2 —C 1 -C 4 alkyl, C 1-4 alkyl, hydroxyl, and phenyl wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 5 and R 5 ′ are each independently selected from group consisting of H, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl, cyano, amino, phenyl, and hydroxyl, wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 7 is selected from group consisting of —C(O)—R 9 , —C(O)—O—R 9 , and —C(O)—NR d —R 9 ,

R 9 is selected from the group consisting of H, C 1-4 alkyl, phenyl, and heterocyclic, wherein C 1-4 alkyl, phenyl or heterocyclic is optionally substituted by 1, 2 or 3 substituents selected from R b

R 8 is selected from group consisting of H, —C(O)— C 1-4 alkyl and C(O)—O— C 1-4 alkyl, wherein C 1-4 alkyl is optionally substituted by 1, 2 or 3 substituents selected from R a ;

R a is selected, independently for each occurrence, from carboxy, hydroxyl, halogen, amino, phenyl, C 1-4 alkyl, and C 1-4 alkoxy;

R b is selected, independently for each occurrence, from the group consisting of carboxy, hydroxyl, halogen, amino, phenyl, C 1-4 alkyl, C 1-4 alkoxy, and —NH—R c ;

R c is selected, independently for each occurrence from the group consisting of: —C(O)—O—C 1-4 alkyl; and —C(O)—C 1-4 alkyl; and

R d is selected, independently for each occurrence, H and C 1-4 alkyl;

and pharmaceutically acceptable salts, N-oxides or stereoisomers thereof.

5 . The method of claim 4 , wherein the condition is fragile X syndrome.

6 . The method of claim 1 , wherein the compound is administered intravenously, intraperitoneally, intranasally, orally, intramuscularly, or subcutaneously.

7 . The method of claim 1 , wherein the method comprises administering a single-dose of said compound.

8 . A method of modulating an autism target gene expression in a cell comprising contacting a call with an effective amount of the compound:

or pharmaceutically acceptable salts thereof.

9 . The method of claim 8 , wherein the autism target is selected from ABAT, APOE, CHRNA4, GABRA5, GFAP, GRIN2A, PDYN, an d PENK.

10 . A method of modulating synaptic plasticity in a patient suffering from a synaptic plasticity related disorder, comprising administering to the patient an effective amount of the compound:

or pharmaceutically acceptable salts thereof.

11 . The method of claim 1 , wherein the patient is a pediatric patient.

12 . A method of treating attention deficit disorder, ADHD, schizophrenia, anxiety, amelioration of opiate, nicotine and/or ethanol addiction, traumatic brain injury, spinal cord injury, post-traumatic stress syndrome and/or Huntington's chorea, in a patient in need thereof, comprising administering to the patient:

a pharmaceutically effective amount of GLYX-13:

 or pharmaceutically acceptable salt thereof,

or

a pharmaceutically effective amount of a compound represented by Formula I:

and pharmaceutically acceptable salts, stereoisomers, and N-oxides thereof; wherein T is, independently for each occurrence, CR 4 R 4 ′, and n is 0, 1, 2 or 3;

A is optionally present and is selected from phenyl or pyridine, wherein A is optionally substituted by one or more substituents selected from R a ;

R 1 is selected from the group consisting of H, hydroxyl, —S(O) 2 —C 1-4 alkyl; —SO 2 , C 1-4 alkyl, C 2 -C 4 alkenyl, phenyl, R 7 , and

 wherein C 1-4 alkyl, C 2-4 alkenyl, or phenyl is optionally substituted by one or more substituents selected from R a ;

X is CH or N;

R 3 and R 3 ′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C 1-4 alkyl, amido, amine, and C 2-4 alkenyl, wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 4 and R 4 ′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C 1-4 alkyl, amido, amine, C 1-4 alkoxy and C 2-4 alkenyl, wherein C 1-4 alkyl, C 2-4 alkenyl, C 1-4 alkoxy, and phenyl are optionally substituted by one or more substituents selected from R a ;

R 2 is selected from the group consisting of H, R 7 , —S(O) 2 , S(O) 2 —C 1 -C 4 alkyl, C 1-4 alkyl, hydroxyl, and phenyl wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 5 and R 5 ′ are each independently selected from group consisting of H, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl, cyano, amino, phenyl, and hydroxyl, wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 7 is selected from group consisting of —C(O)—R 9 , —C(O)—O—R 9 , and —C(O)—NR d —R 9 ,

R 9 is selected from the group consisting of H, C 1-4 alkyl, phenyl, and heterocyclic, wherein C 1-4 alkyl, phenyl or heterocyclic is optionally substituted by 1, 2 or 3 substituents selected from R b

R 8 is selected from group consisting of H, —C(O)— C 1-4 alkyl and C(O)—O— C 1-4 alkyl, wherein C 1-4 alkyl is optionally substituted by 1, 2 or 3 substituents selected from R a ;

R a is selected, independently for each occurrence, from carboxy, hydroxyl, halogen, amino, phenyl, C 1-4 alkyl, and C 1-4 alkoxy;

R b is selected, independently for each occurrence, from the group consisting of carboxy, hydroxyl, halogen, amino, phenyl, C 1-4 alkyl, C 1-4 alkoxy, and —NH—R c ;

R c is selected, independently for each occurrence from the group consisting of: —C(O)—O—C 1-4 alkyl; and —C(O)—C 1-4 alkyl; and

R d is selected, independently for each occurrence, H and C 1-4 alkyl;

and pharmaceutically acceptable salts, N-oxides or stereoisomers thereof.

13 . A method of treating Alzheimer's disease, or memory loss that accompanies early stage Alzheimer's disease in a patient in need thereof, comprising administering to the patient:

a pharmaceutically effective amount of GLYX-13:

 or pharmaceutically acceptable salt thereof,

or

a pharmaceutically effective amount of a compound represented by Formula I:

and pharmaceutically acceptable salts, stereoisomers, and N-oxides thereof; wherein T is, independently for each occurrence, CR 4 R 4 ′, and n is 0, 1, 2 or 3;

A is optionally present and is selected from phenyl or pyridine, wherein A is optionally substituted by one or more substituents selected from R a ;

R 1 is selected from the group consisting of H, hydroxyl, —S(O) 2 —C 1-4 alkyl; —SO 2 , C 1-4 alkyl, C 2 -C 4 alkenyl, phenyl, R 7 , and

 wherein C 1-4 alkyl, C 2-4 alkenyl, or phenyl is optionally substituted by one or more substituents selected from R a ;

X is CH or N;

R 3 and R 3 ′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C 1-4 alkyl, amido, amine, and C 2-4 alkenyl, wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 4 and R 4 ′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C 1-4 alkyl, amido, amine, C 1-4 alkoxy and C 2-4 alkenyl, wherein C 1-4 alkyl, C 2-4 alkenyl, C 1-4 alkoxy, and phenyl are optionally substituted by one or more substituents selected from R a ;

R 2 is selected from the group consisting of H, R 7 , —S(O) 2 , S(O) 2 —C 1 -C 4 alkyl, C 1-4 alkyl, hydroxyl, and phenyl wherein C 1-4 alkyl, C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 5 and R 5 ′ are each independently selected from group consisting of H, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl, cyano, amino, phenyl, and hydroxyl, wherein C 1-4 alkyl,

C 2-4 alkenyl and phenyl are optionally substituted by one or more substituents selected from R a ;

R 7 is selected from group consisting of —C(O)—R 9 , —C(O)—O—R 9 , and —C(O)—NR d —R 9 ,

R 9 is selected from the group consisting of H, C 1-4 alkyl, phenyl, and heterocyclic, wherein C 1-4 alkyl, phenyl or heterocyclic is optionally substituted by 1, 2 or 3 substituents selected from R b

R 8 is selected from group consisting of H, —C(O)— C 1-4 alkyl or C(O)—O— C 1-4 alkyl, wherein C 1-4 alkyl is optionally substituted by 1, 2 or 3 substituents selected from R a ;

R a is selected, independently for each occurrence, from carboxy, hydroxyl, halogen, amino, phenyl, C 1-4 alkyl, and C 1-4 alkoxy;

R b is selected, independently for each occurrence, from the group consisting of carboxy, hydroxyl, halogen, amino, phenyl, C 1-4 alkyl, C 1-4 alkoxy, and —NH—R c ;

R c is selected, independently for each occurrence from the group consisting of: —C(O)—O—C 1-4 alkyl; and —C(O)—C 1-4 alkyl; and

R d is selected, independently for each occurrence, H and C 1-4 alkyl;

and pharmaceutically acceptable salts, N-oxides or stereoisomers thereof.