Bendamustine derivatives and methods of using same

Abstract

The present invention is directed to bendamustine esters and bendamustine amides and their use for the treatment of cancer.

1 . (canceled) 
     
     
         2 . A method of treating cancer in a patient, the method comprising administering to said patient a pharmaceutical composition, wherein said pharmaceutical composition comprises:
 (a) a compound of formula (II)   
       
         
           
           
               
               
           
         
       
       wherein R 2  is C 1 -C 24 alkylene and R 3  is —COOC 1-3 alkyl; or R 2 -R 3  is C 8 C 24 alkyl, or a pharmaceutically acceptable salt thereof; and
 (b) a means for increasing the circulation time of the compound of formula (II), or a pharmaceutically acceptable salt thereof, in an aqueous environment. 
 
     
     
         3 . The method according to  claim 2 , wherein said cancer is in the form of a solid tumor or a liquid tumor. 
     
     
         4 . The method according to  claim 3 , wherein said cancer is in the form of a solid tumor. 
     
     
         5 . The method according to  claim 4 , wherein said cancer is sarcoma, bladder cancer, cervical cancer, testicular cancer, melanoma, glioblastoma, colon cancer, head and neck cancer, ovarian cancer, prostate cancer, breast cancer, or lung cancer. 
     
     
         6 . The method according to  claim 3 , wherein said cancer is in the form of a liquid tumor. 
     
     
         7 . The method according to  claim 6 , wherein said cancer is lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or acute lymphocytic leukemia. 
     
     
         8 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 10 -C 24  alkyl. 
     
     
         9 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 12 -C 24  alkyl. 
     
     
         10 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 14 -C 24  alkyl. 
     
     
         11 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 16 -C 24  alkyl. 
     
     
         12 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 18 -C 24  alkyl. 
     
     
         13 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 10  alkyl. 
     
     
         14 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 12  alkyl 
     
     
         15 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 14  alkyl. 
     
     
         16 . The method according to  claim 2 , wherein in the compound of formula (II) R 2 -R 3  is C 16  alkyl. 
     
     
         17 . The method according to  claim 8 , wherein said cancer is in the form of a solid tumor or a liquid tumor. 
     
     
         18 . The method according to  claim 17 , wherein said cancer is in the form of a solid tumor. 
     
     
         19 . The method according to  claim 18 , wherein said cancer is sarcoma, bladder cancer, cervical cancer, testicular cancer, melanoma, glioblastoma, colon cancer, head and neck cancer, ovarian cancer, prostate cancer, breast cancer, or lung cancer. 
     
     
         20 . The method according to  claim 17 , wherein said cancer is in the form of a liquid tumor. 
     
     
         21 . The method according to  claim 20 , wherein said cancer is lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or acute lymphocytic leukemia.