Thalidomide analogs
Thalidomide analogs that modulate tumor necrosis factor alpha (TNF-α) activity and angiogenesis are disclosed. In particularly disclosed embodiments, the thalidomide analogs are isosteric sulfur-containing analogs. Also disclosed are methods of treating a subject with the analogs.
1. A compound, the compound having the formula:
wherein Y is oxygen; X is oxygen or sulfur; each of R 2 -R 5 are independently hydrogen, and R 1 is
wherein W and Z are each independently oxygen or sulfur; R 20 is hydrogen; and R 15 -R 19 are each independently hydrogen; and further wherein at least two of X, W and Z are sulfur; or
a stereoisomer or pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the compound is 2,3-dihydro-3-thioxo-2-(2-oxo-6-thioxo-3-piperidinyl)-1H-isoindol-1-one or 2,3-Dihydro-3-thioxo-2-(2,6-dithioxo-3-piperidinyl)-1H-isoindol-1-one.
3. The compound of claim 1 , wherein X, W and Z are each S.
4. The compound of claim 1 , wherein X is S.
5. The compound of claim 1 , wherein the compound has the structure:
6. A pharmaceutical composition comprising at least one compound according to claim 1 , and a pharmaceutically acceptable carrier.
7. The composition of claim 6 , wherein the compound has the formula:
wherein X is sulfur or oxygen; or a stereoisomer or pharmaceutically acceptable salt thereof.
8. The compound of claim 1 , wherein W and Z are each S, and X is O.
9. A pharmaceutical composition comprising a compound according to claim 5 , and a pharmaceutically acceptable carrier.
10. The compound of claim 1 , wherein X and Z are each S, and W is O.
11. A pharmaceutical composition comprising a compound according to claim 10 , and a pharmaceutically acceptable carrier.