Antiproliferative compounds and methods of use thereof

Abstract

Compounds of formula I for treating, preventing or managing cancer are disclosed. Also disclosed are methods of treating, preventing or managing cancer, such as leukemia, comprising administering the compounds. In certain embodiments, the method of treatment comprise administering a compound provided herein in combination with a second agent. Pharmaceutical compositions and single unit dosage forms comprising the compounds are also disclosed.

1 - 24 . (canceled) 
     
     
         25 . Compound N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoro-2-(p-tolyl)acetamide or a stereoisomer or mixture of stereoisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof. 
     
     
         26 . A pharmaceutical composition comprising the compound of claim  1  and a pharmaceutically acceptable excipient. 
     
     
         27 . A method of treating leukemia in a mammal comprising administering to the mammal a therapeutically effective amount of the compound of  claim 25 . 
     
     
         28 . The method of  claim 27 , wherein the leukemia is chronic lymphocytic leukemia, chronic myelocytic leukemia, acute lymphoblastic leukemia or acute myeloid leukemia. 
     
     
         29 . The method of  claim 28 , wherein the leukemia is an acute myeloid leukemia. 
     
     
         30 . The method of  claim 27 , wherein the leukemia is relapsed, refractory or resistant to conventional therapy. 
     
     
         31 . The method of  claim 27 , further comprising administering a therapeutically effective amount of another second active agent or a support care therapy. 
     
     
         32 . The method of  claim 31 , wherein the other second active agent is a therapeutic antibody that specifically binds to a cancer antigen, hematopoietic growth factor, cytokine, anti-cancer agent, antibiotic, cox-2 inhibitor, immunomodulatory agent, immunosuppressive agent, corticosteroid or a pharmacologically active mutant or derivative thereof.