GluN2C/D subunit selective antagonists of the N-methyl-D-aspartate receptor

1. A compound of Formula (I) or a salt thereof,

wherein R 1 and R 5 , in each occurrence, are individually and independently a halogen;

wherein R 7 , in each occurrence, is individually and independently a C1 to C3 alkyl, alkoxy, halogen or trifluoroalkyl;

wherein R 2 , R 3 , R 2′ and R 3′ are individually and independently H or a halogen;

wherein R 4 is an amino, hydroxyl or C1 to C3 alkoxy;

wherein R 6 and R 6′ are individually and independently S, O or absent;

wherein R 6 is absent, the carbon connected to R 6 is —CH 2 —;

wherein Ring B is a 5 or 6 membered aryl or heteroaryl;

wherein Ring A is thiophene or furan;

wherein Ring C is a monocyclic or bicyclic aryl or heteroaryl ring;

wherein the dashed bond represented by is a single bond or a double bond;

wherein when the dashed bond represented by is a double bond, R 3 and R 3′ are absent;

wherein, for Ring A and Ring B, n, in each occurrence, is individually and dependently 1, 2 or 3;

wherein, for Ring C, n is 0, 1, 2 or 3; and

wherein R 2 , R 3 , R 2′ , R 3′ , R 4 , and R 7 are, individually and independently, optionally substituted with R 10 , which is a halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

2. The compound of claim 1 , wherein R 4 is NH 2 , OH, OMe or OEt.

3. The compound of claim 1 , wherein R 6′ is a S or O when Ring C is a bicyclic aryl or heteroaryl ring or is absent when Ring C is a monocyclic aryl or heteroaryl ring.

4. The compound of claim 1 , wherein R 1 and R 5 , in each occurrence, are individually and independently chloro or fluoro.

5. The compound of claim 1 , wherein each of R 2 and R 3 is a fluoro when each of R 2′ and R 3′ is H or wherein each of R 2 and R 3 is a H when each of R 2′ and R 3′ is fluoro.

6. The compound of claim 1 , wherein Ring B is a phenyl, pyridine, pyrazine or thiophene and Ring C is a phenyl or a quinolinone or quinolinethione ring system.

7. The compound of claim 1 , wherein Ring B, when considered together with its R 1 substitutent(s), is:

8. The compound of claim 1 , which is a compound of Formula (IC) or (ID), or a salt thereof:

wherein R 1 , R 2 , R 3 , R 2′ , R 3′ , R 4 , R 5 , R 6 , R 6′ , R 7 , and n are as defined in claim 1 ;

wherein Y, in each occurrence, is independently N or CH; and

wherein Z is S or O.

9. The compound of claim 1 , which is:

or a salt thereof.

10. A method of treating a neurological disorder in a subject in need thereof, the method comprising administering an effective amount of the compound of claim 1 to the subject.

11. The method of claim 10 , wherein the treating of the neurological disorder comprises providing neuroprotection, preventing neurodegeneration, treating neuropathic pain or treating schizophrenia, psychoses or depression.

12. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient, wherein the pharmaceutical composition is in the form of tablets, capsules, pills, gels, granules, aerosols, aqueous buffers, nanoparticle formulations, emulsions or liposomes.

13. The pharmaceutical composition of claim 12 , further comprising one or more further active agents.

14. The method of claim 10 , wherein the compound is administered in combination with one or more further active agents.

15. The compound of claim 1 , wherein Ring C is a monocyclic aryl or heteroaryl ring.

16. The compound of claim 1 , wherein R 6′ is O.

17. The compound of claim 1 , wherein the dashed bond represented by is a single bond.

18. The compound of claim 7 , wherein Ring A, when considered together with its R 5 substitutent(s), is

19. The compound of claim 18 , wherein the compound has the following structure of a salt thereof:

20. The composition comprising a compound of claim 1 , wherein the compound is a purified S enantiomer of Formula (I) as shown below:

or a salt thereof.