Organoarsenic compounds and methods for the treatment of cancer

Abstract

A method for treating a lymphoma selected from non-Hodgkin's and Hodgkin's lymphoma comprising administering an organoarsenic compound having a structure of the formula (I) wherein X is S or Se and R 1 and R 2 are independently C 1-30 alkyl(R 3 , R 3′ , R 4 , R 5 , W and “n” are as defined in claim 1 ) in particular where the compound is S-dimethylarsinoglutathione, N-(2-S-dimethylarsinothiopropionyl)glycine, 2-amino-3-(dimethylarsino)thio-3-methylbutanoic acid, S-dimethylarsino-thiosuccinic acid or S-dipropylarsino- 1 -thioglycerol.

1 . A method for treating a lymphoma selected from non-Hodgkin's and Hodgkin's lymphoma, comprising administering a compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
         wherein 
         X is S or Se; 
         W is O, S, or (R)(R), where each occurrence of R is independently H or a C 1-2 alkyl; 
         n is and integer from 0 to 20; 
         R 1  and R 2  are independently C 1-30 alkyl; 
         R 3  is —H, C 1-10 alkyl, or C 0-6 alkyl-COOR 6 ; 
         R 3′  is H, amino, cyano, halogen, aryl, aralkyl, heteroaryl, heteroaralkyl, carboxyl, C 1-10 alkyl, C 1-10 alkenyl, or C 1-10 alkynyl; 
         R 4  is —OH, —H, —CH 3 , amino, —OC(O)C 1-10 aralkyl, —OC(O)C 1-10 alkyl, —OC(O)aryl, or a glutamine substituent; 
         R 5  is —OH, cyano, C 1-10 alkoxy, amino, O-aralkyl, —OC(O)C 1-10 aralkyl, —OC(O)C 1-10 alkyl, —OC(O)aryl, or a glycine substituent; and 
         R 6  is H or C 1-10 alkyl. 
       
     
     
         2 . A method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         3 . A method of  claim 1  or  2 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         4 . A method of  claim 1  or  2 , wherein the lymphoma is Hodgkin's lymphoma. 
     
     
         5 . A method of  claim 1  or  2 , wherein the lymphoma is selected from peripheral T-cell lymphoma (PTCL), diffuse large B-cell, marginal zone lymphoma, and Hodgkin's nodular sclerosis. 
     
     
         6 . A method of any one of  claims 1  to  5 , wherein the compound is administered intravenously. 
     
     
         7 . A method of any one of  claims 1  to  6 , wherein a dose of the compound is 200-420 mg/m 2 . 
     
     
         8 . A method of  claim 7 , wherein a dose of the compound is 300 mg/m 2 . 
     
     
         9 . A method of any one of  claims 1  to  8 , wherein the compound is administered daily for five days every four weeks. 
     
     
         10 . A method of  claim 9 , wherein the compound is administered daily for five consecutive days every four weeks. 
     
     
         11 . Use of a compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a lymphoma selected from non-Hodgkin's and Hodgkin's lymphoma 
       
         
           
           
               
               
           
         
         wherein 
         X is S or Se; 
         W is O, S, or (R)(R), where each occurrence of R is independently H or a C 1-2 alkyl; 
         n is and integer from 0 to 20; 
         R 1  and R 2  are independently C 1-30 alkyl; 
         R 3  is —H, C 1-10 alkyl, or C 0-6 alkyl-COOR 6 ; 
         R 3′  is H, amino, cyano, halogen, aryl, aralkyl, heteroaryl, heteroaralkyl, carboxyl, C 1-10 alkyl, C 1-10 alkenyl, or C 1-10 alkynyl; 
         R 4  is —OH, —H, —CH 3 , amino, —OC(O)C 1-10 aralkyl, —OC(O)C 1-10 alkyl, —OC(O)aryl, or a glutamine substituent; 
         R 5  is —OH, cyano, C 1-10 alkoxy, amino, O-aralkyl, —OC(O)C 1-10 aralkyl, —OC(O)C 1-10 alkyl, —OC(O)aryl, or a glycine substituent; and 
         R 6  is H or C 1-10 alkyl. 
       
     
     
         12 . Use of  claim 11 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
         13 . Use of  claim 11  or  12 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         14 . Use of  claim 11  or  12 , wherein the lymphoma is Hodgkin's lymphoma. 
     
     
         15 . Use of  claim 11  or  12 , wherein the lymphoma is selected from peripheral T-cell lymphoma (PTCL), diffuse large B-cell, marginal zone lymphoma, and Hodgkin's nodular sclerosis. 
     
     
         16 . Use of any one of  claims 11  to  15 , wherein the compound is administered intravenously. 
     
     
         17 . Use of any one of  claims 11  to  16 , wherein a dose of the compound is 200-420 mg/m 2 . 
     
     
         18 . Use of  claim 17 , wherein a dose of the compound is 300 mg/m 2 . 
     
     
         19 . Use of any one of  claims 11  to  18 , wherein the compound is administered daily for five days every four weeks. 
     
     
         20 . Use of  claim 19 , wherein the compound is administered daily for five consecutive days every four weeks.