Cancer treatment

Abstract

This invention is a method of treating cancer, including carcinomas and sarcomas through the administration of a pharmaceutical composition containing an aldehyde 5-oxo-1,2,4-triazine hydrazide derivative. The aldehyde 5-oxo-1,2,4-triazine hydrazide derivative is selected from the group consisting of those with the formula: wherein R and R 1 are independently selected from the group consisting of hydrogen, or alkyl wherein the alkyl group has up to 7 carbon atoms and wherein R 3 is selected from the group consisting of alkyl having 1 to 7 carbon atoms, cycloalkyl having up to 7 carbon atoms, and substituted alkyl having up to 12 carbons wherein the alkyl group is substituted with one more halogen, hydroxy, amino, sulfhydryl or alkoxy having up to 10 carbon atoms, or wherein X is independently selected from hydrogen, alkyl of less than 7 carbons, halogen, amino, hydroxy and sulfhydryl and n is 4 or less, pharmaceutical salt, prodrug, metabolites and mixtures thereof. Pharmaceutical compositions comprising these compounds and their use in various treatment methods are claimed. The compounds can be used in conjunction with other chemotherapeutic agents and potentiators. The corresponding hydrazine of the formula: wherein R and R 1 are independently selected from the group consisting of hydrogen, or alkyl wherein the alkyl group has up to 7 carbon atoms also have anticancer activity.

What is claimed is:  
     
         1 . A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a composition comprising an aldehyde 5-oxo-1,2,4-triazine hydrazide compound selected from the group consisting of those with the formula:  
       
         
           
           
               
               
           
         
       
       wherein R and R 1  are independently selected from the group consisting of hydrogen, or alkyl wherein the alkyl group has up to 7 carbon atoms and wherein R 3  is selected from the group consisting of alkyl having 1 to 7 carbon atoms, cycloalkyl having up to 7 carbon atoms, and substituted alkyl having up to 12 carbons wherein the alkyl group is substituted with one more  
       halogen, hydroxy, amino, sulfhydryl or alkoxy having up to 10 carbon atoms , or  
       
         
           
           
               
               
           
         
       
       wherein X is independently selected from hydrogen, alkyl of less than 7 carbons, halogen, amino, hydroxy and sulfhydryl and n is 4 or less, pharmaceutical salt, prodrug, metabolites and mixtures thereof.  
     
     
         2 . A method according to  claim 1  wherein said cancer is prostate cancer.  
     
     
         3 . A method according to  claim 1  wherein said cancer is breast cancer.  
     
     
         4 . A method according to  claim 1  wherein said cancer is leukemia.  
     
     
         5 . A method according to  claim 1  wherein said cancer is pancreatic cancer.  
     
     
         6 . A method according to  claim 1  wherein said cancer is lung cancer.  
     
     
         7 . A method according to  claim 1  wherein said cancer is colon cancer.  
     
     
         8 . A method according to  claim 1  wherein said cancer is a sarcoma.  
     
     
         9 . A method according to  claim 1  wherein said cancer is a lymphoma.  
     
     
         10 . A method according to  claim 1  wherein said aldehyde 5-oxo-1,2,4-triazine hydrazide compound is benzaldehyde, 2-hydroxy-, (4-hydro-5-oxo-1,2,4-triazin-3-yl)hydrazide or benzaldehyde, 2-hydroxy-, (4-hydro-5-oxo-6-methyl-1,2,4-triazin-3-yl)hydrazide, pharmaceutical salts and prodrug, metabolites thereof.  
     
     
         11 . A method according to  claim 1  wherein wherein R and R 1  are independently selected from the group consisting of hydrogen, or alkyl wherein the alkyl group has up to 4 carbon atoms and wherein R 3  is  
       
         
           
           
               
               
           
         
       
       wherein X is independently selected from hydrogen, alkyl of less than 7 carbons, halogen, amino, hydroxy and sulfhydryl and n is 4 or less.  
     
     
         12 . A pharmaceutical composition comprising a therapeutically effective amount of a composition comprising an aldehyde 5-oxo-1,2,4-triazine hydrazide compound selected from the group consisting of those with the formula:  
       
         
           
           
               
               
           
         
       
       wherein R and R 1  are independently selected from the group consisting of hydrogen, or alkyl wherein the alkyl group has up to 7 carbon atoms and wherein R 3  is selected from the group consisting of alkyl having 1 to 7 carbon atoms, cycloalkyl having up to 7 carbon atoms, and substituted alkyl having up to 12 carbons wherein the alkyl group is substituted with one more halogen, hydroxy, amino, sulfhydryl or alkoxy having up to 10 carbon atoms, or  
       
         
           
           
               
               
           
         
       
       wherein X is independently selected from hydrogen, alkyl of less than 7 carbons, halogen, amino, hydroxy and sulfhydryl and n is 4 or less, pharmaceutical salt, prodrug, metabolites and mixtures thereof.  
     
     
         13 . A pharmaceutical composition of  claim 12  further comprising a pharmaceutical carrier.  
     
     
         14 . A pharmaceutical composition according to  claim 12  wherein R 3  is  
       
         
           
           
               
               
           
         
       
       wherein X is independently selected from hydrogen, alkyl of less than 7 carbons, halogen, amino, hydroxy and sulfhydryl and n is 4 or less.  
     
     
         15 . A liposome composition comprising an aldehyde 5-oxo-1,2,4-triazine hydrazide compound selected from the group consisting of those with the formula:  
       
         
           
           
               
               
           
         
       
       wherein R and R 1  are independently selected from the group consisting of hydrogen, or alkyl wherein the alkyl group has up to 7 carbon atoms and X is independently selected from hydrogen, alkyl of less than 7 carbons, halogen, amino, hydroxy and sulfhydryl and n is 4 or less, pharmaceutical salt, prodrug, metabolites and mixtures thereof.  
     
     
         16 . A liposome composition according to  claim 15  selected from the group of consisting of unilamallar vesicle and multilamallar vesicles.  
     
     
         17 . A liposome composition according to  claim 16  formed from phospholipids cholesterol, stearylamine or phosphatidyl choline.  
     
     
         18 . The pharmaceutical composition of  claim 12  wherein the aldehyde 5-oxo-1,2,4-triazine hydrazide is a hydrochloride salt of benzaldehyde, 2-hydroxy-, (4-hydro-5-oxo-1,2,4-triazin-3-yl)hydrazide or benzaldehyde, 2-hydroxy-, (4-hydro-5-oxo-6-methyl-1,2,4-triazin-3-yl)hydrazide.  
     
     
         19 . A pharmaceutical composition comprising a therapeutically effective amount of a composition comprising an 5-oxo-1,2,4-triazine hydrazine compound selected from the group consisting of those with the formula:  
       
         
           
           
               
               
           
         
       
       wherein R and R 1  are independently selected from the group consisting of hydrogen, or alkyl wherein the alkyl group has up to 7 carbon atoms, pharmaceutical salt, prodrug, metabolites and mixtures thereof.  
     
     
         20 . A pharmaceutical composition of  claim 19  further comprising a pharmaceutical carrier.