Histone Deacetylase (hdac) Inhibitors For The Treatment Of Cancer

Abstract

The present invention relates generally to methods for treating cancer. In one respect, the present invention relates to a method of treating a hematological cancer (e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof a therapeutically affective amount of a histone deacetylase inhibitor, for example, a histone deacetylase (HDAC) inhibitor as described herein, for example, PXD-101. In another respect, the present invention relates to a method of treating cancer (e.g., solid tumour cancer, e.g., rectal cancer, colon cancer, ovarian cancer, hematological cancer, e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof, a first amount of a histone deacetylase (HDAC) inhibitor, for example, a histone deacetylase inhibitor as described herein, for example, PXD-101, and a second amount of another chemotherapeutic agent, for example, another chemotherapeutic agent selected from: an antibody against VEGF, AVASTIN® (bevacizumab), an antibody against CD20, rituximab, bortezomib, thalidomide, dexamethasone, vincristine, doxorubicin, and melphalan, wherein the first and second amounts together comprise a therapeutically effective amount.

1 . A method of treating cancer comprising administering to a patient in need thereof, a first amount of a histone deacetylase inhibitor, and a second amount of another chemotherapeutic agent, wherein the first and second amounts together comprise a therapeutically effective amount; wherein the histone deacetylase inhibitor is selected from compounds of the following formula and pharmaceutically acceptable salts and solvates thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 A is an unsubstituted phenyl group; 
 Q 1  is a covalent bond, a C 1-7  alkylene group, or a C 2-7  alkenylene group; 
 J is: 
 
       
         
           
           
               
               
           
         
         R 1  is hydrogen, C 1-7  alkyl, C 3-20  heterocyclyl, C 5-20  aryl, or C 5-20  aryl-C 1-7  alkyl; and, 
         Q 2  is: 
       
       
         
           
           
               
               
           
         
       
       and
 wherein the other chemotherapeutic agent is melphalan. 
 
     
     
         2 . The method of  claim 1 , wherein the histone deacetylase inhibitor is selected from the following compound and pharmaceutically acceptable salts and solvates thereof: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , wherein the histone deacetylase inhibitor is the following compound: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method of  claim 1 , wherein the cancer is at least one cancer selected from a group consisting of a solid tumour cancer and hematological cancer. 
     
     
         5 . The method of  claim 4 , wherein the hematological cancer is multiple myeloma, lymphoma, or leukaemia. 
     
     
         6 . The method of  claim 5 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         7 . The method of  claim 5 , wherein the leukemia is lymphocytic leukemia or myelogenous leukaemia. 
     
     
         8 . The method of  claim 7 , wherein the myelogenous leukaemia is selected from the group consisting of acute myelogenous leukaemia and chronic myelogenous leukaemia. 
     
     
         9 . The method of  claim 7 , wherein the lymphocytic leukaemia is selected from the group consisting of acute lymphocytic leukaemia and chronic lymphocytic leukaemia. 
     
     
         10 . The method of  claim 4 , wherein the solid tumour cancer is at least one cancer selected from the group consisting of rectal cancer, colon cancer, and ovarian cancer. 
     
     
         11 . A kit or kit-of-parts comprising:
 (a) a histone deacetylase inhibitor as a component of a pharmaceutically acceptable formulation, and provided in a suitable container and/or with suitable packaging; and   (b) another chemotherapeutic agent a component of a pharmaceutically acceptable formulation, and provided in a suitable container and/or with suitable packaging;   wherein the kit or kit-of-parts is suitable for use in a method of treating cancer;   wherein the histone deacetylase inhibitor is selected from compounds of the following formula and pharmaceutically acceptable salts and solvates thereof:   
       
         
           
           
               
               
           
         
       
       wherein:
 A is an unsubstituted phenyl group; 
 Q 1  is a covalent bond, a C 1-7  alkylene group, or a C 2-7  alkenylene group; 
 J is: 
 
       
         
           
           
               
               
           
         
         R 1  is hydrogen, C 1-7  alkyl, C 3-20  heterocyclyl, C 5-20  aryl, or C 5-20  aryl-C 1-7  alkyl; and, 
         Q 2  is: 
       
       
         
           
           
               
               
           
         
       
       and
 wherein the other chemotherapeutic agent is melphalan. 
 
     
     
         12 . The method of  claim 11 , wherein the histone deacetylase inhibitor is selected from the following compound and pharmaceutically acceptable salts and solvates thereof: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 11 , wherein the histone deacetylase inhibitor is the following compound: