Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis
Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.
1. A compound of Formula I-R or Formula I-S or a mixture thereof in any ratio:
or pharmaceutically acceptable salt thereof,
wherein
X is —NH 2 , —NHC(═O)CH 3 or —NHCH 2 COOH, and
Y is —CN.
2. The compound of claim 1 wherein X is —NH 2 .
3. The compound of claim 1 wherein X is —NHC(═O)CH 3 .
4. The compound of claim 1 wherein X is —NHCH 2 COOH.
5. The compound of claim 1 wherein the compound is a racemic mixture of Formula I-R and Formula I-S.
6. The compound of claim 1 wherein the compound is enriched in Formula I-R compared to Formula I-S.
7. The compound of claim 6 wherein the compound is a substantially enantiomerically pure form of Formula I-R.
8. The compound of claim 7 wherein the level of enrichment of Formula I-R with respect to Formula I-S is at least 95%.
9. The compound of claim 7 wherein the level of enrichment of Formula I-R with respect to Formula I-S is at least 99%.
10. The compound of claim 1 wherein the compound is enriched in Formula I-S compared to Formula I-R.
11. The compound of claim 10 wherein the compound is a substantially enantiomerically pure form of Formula I-S.
12. The compound of claim 11 wherein the level of enrichment of Formula I-S with respect to Formula I-R is at least 95%.
13. The compound of claim 11 wherein the level of enrichment of Formula I-S with respect to Formula I-R is at least 99%.
14. A composition comprising a compound of any one of claims 1 - 13 in combination with a pharmaceutically acceptable carrier or diluent.
15. An isolated optical isomer of Formula I-R:
or pharmaceutically acceptable salt thereof,
wherein
X is —NH 2 , —NHC(═O)CH 3 or —NHCH 2 COOH, and
Y is —CN.
16. The isomer of claim 15 wherein X is —NH 2 .
17. The isomer of claim 15 wherein X is —NHC(═O)CH 3 .
18. The isomer of claim 15 wherein X is —NHCH 2 COOH.
19. A composition comprising an isomer of any one of claims 15 - 18 in combination with a pharmaceutically acceptable carrier or diluent.
20. An isolated optical isomer of Formula I-S:
or pharmaceutically acceptable salt thereof,
wherein
X is —NH 2 , —NHC(═O)CH 3 or —NHCH 2 COOH, and
Y is —CN.
21. The isomer of claim 20 wherein X is —NH 2 .
22. The isomer of claim 20 wherein X is —NHC(═O)CH 3 .
23. The isomer of claim 20 wherein X is —NHCH 2 COOH.
24. A composition comprising an isomer of any one of claims 20 - 23 in combination with a pharmaceutically acceptable carrier or diluent.