Styryl sulfone anticancer agents

Abstract

Styryl sulfone compounds of the invention selectively inhibit proliferation of tumor cells, and induce apoptosis of tumor cells, while sparing normal cells. The compounds, which are useful in the treatment of cancer and other proliferative disorders, have (a) the formula II: wherein n is zero or one; R 1 is selected from the group consisting of hydrogen, chlorine, fluorine and bromine; R 2 is selected from the group consisting of hydrogen, chlorine, fluorine, bromine, methyl and methoxy; and R 3 is selected from the group consisting of hydrogen, chlorine and fluorine; provided, R 2 may not be methyl or methoxy when R 1 and R 3 are both hydrogen and n is zero or one; and R 1 , R 2 and R 3 may not all be hydrogen when n is one; (b) the formula III: wherein R 1 is selected from the group consisting of hydrogen, chlorine, fluorine and bromine; or (c) or the formula IV: wherein R 1 is selected from the group consisting of fluorine and bromine, and R 2 is selected from the group consisting of 2-chlorophenyl, 4-chlorophenyl, 4-fluorophenyl and 2-nitrophenyl.

1 . A method of treating an individual for a proliferative disease other than cancer comprising administering to said individual an effective amount of a compound of formula II  
       
         
           
           
               
               
           
         
       
       wherein 
 n is zero or one;  
 R 1  is selected from the group consisting of hydrogen, chlorine, fluorine and bromine;  
 R 2  is selected from the group consisting of hydrogen, chlorine, fluorine, bromine, methyl and methoxy; and  
 R 3  is selected from the group consisting of hydrogen, chlorine and fluorine;  
 provided,  
 R 2  may not be methyl or methoxy when R 1  and R 3  are both hydrogen and n is zero or one; and  
 R 1 , r 2  and r 3  may not all be hydrogen when n is one.  
 
     
     
         2 . The method according to  claim 1  wherein the compound is E-4-bromostyryl phenyl sulfone.  
     
     
         3 . The method according to  claim 1  wherein the compound is E-2,4-difluorostyryl 4-fluorobenzyl sulfone.  
     
     
         4 . The method according to  claim 1  wherein the compound is E-2-chloro-4-fluorostyryl 4-chlorobenzyl sulfone.  
     
     
         5 . The method according to  claim 1 , wherein R 3  is hydrogen, and R 1  and R 2  are independently selected from the group consisting of chlorine, fluorine and bromine.  
     
     
         6 . The method according to  claim 5  wherein the compound is E-4-chlorostyryl 4-chlorophenyl sulfone.  
     
     
         7 . The method according to  claim 5  wherein the compound is E-4-bromostyryl 4-chlorophenyl sulfone.  
     
     
         8 . The method according to  claim 5  wherein the compound is E-4-fluorostyryl 4-chlorobenzyl sulfone.  
     
     
         9 . The method according to  claim 5  wherein the compound is E-4-chlorostyryl 4-chlorobenzyl sulfone.  
     
     
         10 . The method according to  claim 5  wherein the compound is E-4-fluorostyryl 4-fluorobenzyl sulfone.  
     
     
         11 . The method according to  claim 5  wherein the compound is E-4-fluorostyryl 4-bromobenzyl sulfone.  
     
     
         12 . The method according to  claim 5  wherein the compound is E-4-bromostyryl 4-bromobenzyl sulfone.  
     
     
         13 . The method according to  claim 5  wherein the compound is E-4-bromostyryl 4-fluorobenzyl sulfone.  
     
     
         14 . The method according to  claim 5  wherein the compound is E-4-chlorostyryl 4-bromobenzyl sulfone.  
     
     
         15 . The method according to  claim 5  wherein the compound is E-4-bromostyryl 4-chlorobenzyl sulfone.  
     
     
         16 . The method according to  claim 1  wherein the proliferative disorder treated is selected from the group consisting of hemangiomatosis in new born, secondary progressive multiple sclerosis, chronic progressive myelodegenerative disease, neurofibromatosis, ganglioneuromatosis, keloid formation, Pagets Disease of the bone, fibrocystic disease of the breast, Peronies and Duputren's fibrosis, restenosis and cirrhosis.  
     
     
         17 . A method of treating an individual for a proliferative disease other than cancer comprising administering to said individual an effective amount of a compound of formula III  
       
         
           
           
               
               
           
         
         wherein R 1  is selected from the group consisting of hydrogen, chlorine, fluorine and bromine.  
       
     
     
         18 . The method according to  claim 17  wherein the proliferative disorder treated is selected from the group consisting of hemangiomatosis in new born, secondary progressive multiple sclerosis, chronic progressive myelodegenerative disease, neurofibromatosis, ganglioneuromatosis, keloid formation, Pagets Disease of the bone, fibrocystic disease of the breast, Peronies and Duputren's fibrosis, restenosis and cirrhosis.  
     
     
         19 . A method of treating an individual for a proliferative disease other than cancer comprising administering to said individual an effective amount of a compound of formula IV  
       
         
           
           
               
               
           
         
         wherein R 1  is selected from the group consisting of fluorine and bromine, and R 2  is selected from the group consisting of 2-chlorophenyl, 4-chlorophenyl, 4-fluorophenyl and 2-nitrophenyl.  
       
     
     
         20 . The method according to  claim 19  wherein the proliferative disorder treated is selected from the group consisting of hemangiomatosis in new born, secondary progressive multiple sclerosis, chronic progressive myelodegenerative disease, neurofibromatosis, ganglioneuromatosis, keloid formation, Pagets Disease of the bone, fibrocystic disease of the breast, Peronies and Duputren's fibrosis, restenosis and cirrhosis.