Compositions comprising zopiclone derivatives and methods of making and using the same
The invention is directed to racemic and stereomerically pure compounds of Formula 3: and to pharmaceutical compositions comprising them, methods of their use, and methods of their preparation.
1. An enantiomerically pure compound of Formula 3:
or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof, wherein: X is O or NR 3 ; R 1 and R 1′ are both H or when taken together are ═O; R 2 and R 2′ are both H or when taken together are ═O; and R 3 is H, alkyl, aryl, arylalkyl or —COR 4 , wherein R 4 is H, amine, alkyl, alkoxy, aryl, aryloxy, arylalkyl, or O-arylalkyl; provided that when X is NR 3 and R 1 , R 1′ , R 2 , and R 2′ are all H, then R 3 is not H or methyl.
2. The compound of claim 1 wherein X is NR 3 and R 1 and R 1′ are both H.
3. The compound of claim 2 wherein R 2 and R 2′ are taken together to be ═O.
4. The compound of claim 1 wherein X is NR 3 and R 1 and R 1′ are taken together to be =O and R 2 and R 2′ are taken together to be ═O.
5. The compound of claim 1 wherein X is NR 3 and R 1 , R 1′ , R 2 , and R 2′ are all H and R 3 is —COR 4 , wherein R 4 is H, alkyl, NH 2 , or alkoxyalkyl.
6. The compound of claim 5 wherein R 4 is H, CH 3 , NH 2 or —OCH 2 CH 3 .
7. The compound of claim 1 , wherein X is O and R 1 , R 1′ , R 2 and R 2′ are all H.
8. A compound selected from the following:
or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.
9. A pharmaceutical composition comprising a compound of Formula 3:
or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof, wherein: X is O or NR 3 ; R 1 and R 1′ are both H or when taken together are ═O; R 2 and R 2′ are both H or when taken together are ═O; and R 3 is H, alkyl, aryl, arylalkyl or —COR 4 , wherein R 4 is H, amine, alkyl, alkoxy, aryl, aryloxy, arylalkyl, or O-arylalkyl; provided that when X is NR 3 and R 1 , R 1′ , R 2 , and R 2′ are all H, then R 3 is not H or methyl; and a pharmaceutically acceptable excipient.
10. The pharmaceutical composition of claim 9 wherein X is NR 3 and R 1 and R 1′ are both H.
11. The pharmaceutical composition of claim 10 wherein R 2 and R 2′ are taken together to be ═O.
12. The pharmaceutical composition of claim 9 wherein X is NR 3 and R 1 and R 1′ are taken together to be ═O and R 2 and R 2′ are taken together to be ═O.
13. The pharmaceutical composition of claim 9 wherein X is NR 3 and R 1 , R 1′ , R 2 , and R 2′ are all H and R 3 is —COR 4 , wherein R 4 is H, alkyl, NH 2 or alkoxyalkyl.
14. The pharmaceutical composition of claim 13 wherein R 4 is H, CH 3 , NH 2 or —OCH 2 CH 3 .
15. The pharmaceutical composition of claim 9 wherein X is O and R 1 , R 1′ , R 2 and R 2′ are all H.
16. The pharmaceutical composition of claim 9 wherein the compound of Formula 3 is stereomerically pure.