Antiproliferative compounds and methods of use thereof
Provided herein is 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof, and methods for treating, preventing or managing multiple myeloma using such compounds. Also provided are pharmaceutical compositions comprising the compounds, and methods of use of the compositions.
1. A compound, wherein the compound is Compound 1of formula
or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
2. A compound, wherein the compound is Compound 2 of formula
or a tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound is Compound 1 of formula
4. The compound of claim 1 , wherein the compound is an enantiomer of Compound 1.
5. The compound of claim 1 , wherein the compound is a mixture of enantiomers of Compound 1.
6. The compound of claim 1 , wherein the compound is a pharmaceutically acceptable salt of Compound 1.
7. The compound of claim 2 , wherein the compound is Compound 2 of formula
8. The compound of claim 2 , wherein the compound is a pharmaceutically acceptable salt of Compound 2.
9. A pharmaceutical composition, comprising the compound of claim 1 .
10. A pharmaceutical composition, comprising the compound of claim 2 .
11. A method of treating multiple myeloma comprising administering a therapeutically effective amount of the compound of claim 1 to a patient in need thereof.
12. The method of claim 11 , wherein the multiple myeloma is relapsed, refractory or resistant.
13. The method of claim 12 , wherein the multiple myeloma is refractory or resistant to lenalidomide.
14. The method of claim 12 , wherein the multiple myeloma is refractory or resistant to pomalidomide.
15. The method of claim 11 , wherein the multiple myeloma is newly diagnosed multiple myeloma.
16. The method of claim 11 , additionally comprising administering a second active agent.
17. The method of claim 16 , wherein the second active agent is dexamethasone.
18. The method of claim 16 , wherein the second active agent is bortezomib.
19. A method of treating multiple myeloma comprising administering a therapeutically effective amount of the compound of claim 2 to a patient in need thereof.
20. The method of claim 19 , wherein the multiple myeloma is relapsed, refractory or resistant.
21. The method of claim 20 , wherein the multiple myeloma is refractory or resistant to lenalidomide.
22. The method of claim 20 , wherein the multiple myeloma is refractory or resistant to pomalidomide.
23. The method of claim 19 , wherein the multiple myeloma is newly diagnosed multiple myeloma.
24. The method of claim 19 , additionally comprising administering a second active agent.
25. The method of claim 24 , wherein the second active agent is dexamethasone.
26. The method of claim 24 , wherein the second active agent is bortezomib.