Novel Compounds

Abstract

A compound for use in the treatment of proliferative disorders, such as cancer, having the following formula: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 are as defined in the specification.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomer, amide, ester, ether, chemically protected form or prodrug thereof, wherein: 
         R 1 , R 2  and R 3  are independently H or lower alkyl; 
         R 4 , R 5 , R 6 , R 7  and R 8  are independently H, halo, lower alkyl or —O-lower alkyl, provided that at least one is —O-lower alkyl; or at least one pair of R 4  to R 8 , the members of which pair are adjacent to one another on the ring, are conjoined to form —O—(CR 14 R 15 ) n —O—, where n is 1 or 2 and R 14  and R 15  are independently H or lower alkyl, and the remainder of R 4  to R 8  are independently H, halo, lower alkyl or —O-lower alkyl; and 
         R 9 , R 10 , R 11 , R 12  and R 13  are independently H, halo, lower alkyl or —O— lower alkyl, provided that at least one is —O-lower alkyl; or at least one pair of R 9  to R 13 , the members of which pair are adjacent to one another on the ring, are conjoined to form —O—(CR 16 R 17 ) m —O—, where m is 1 or 2 and R 16  and R 17  are independently H or lower alkyl, and the remainder of R 9  to R 13  are independently H, halo, lower alkyl or —O-lower alkyl. 
       
     
     
         2 . The compound as claimed in  claim 1 , wherein R 6  and R 11  are not both —OMe. 
     
     
         3 . The compound as claimed in  claim 1 , wherein R 9 , R 12  and R 13  are independently H, halo or lower alkyl, and R 10  and R 11  are conjoined to form —O—C(R 16 R 17 ) m —O—, where m is preferably 1. 
     
     
         4 . The compound as claimed in  claim 1 , wherein one of R 9  to R 13  is —O—R 18 , R 18  is lower alkyl, and the remainder are independently H, halo or lower alkyl. 
     
     
         5 . The compound as claimed in  claim 1 , wherein at least two of R 4 , R 5 , R 6 , R 7  and R 8  are —O-lower alkyl. 
     
     
         6 . The compound as claimed in  claim 1 , wherein R 6  is —O—R 19 , R 19  is lower alkyl. 
     
     
         7 . The compound as claimed in  claim 1 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         8 . A metabolite of a compound as claimed in  claim 1 , wherein said metabolite is the product of said compound as a substrate for the CYP1B1 enzyme. 
     
     
         9 . A cytotoxic compound having a formula (X): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomer, amide, ester, ether, chemically protected form or prodrug thereof, wherein: 
         R 1 -R 3  are independently H or lower alkyl; and 
         R 4 -R 13  are independently H, OH, halo, lower alkyl or —O-lower alkyl, provided that at least one of R 4 -R 13  is OH. 
       
     
     
         10 . The cytotoxic compound as claimed in  claim 9 , wherein when R 6  is Cl then R 12  is not OH or OMe; or when R 5  is OMe then R 12  is not OH, or when R 6  is OH then R 11  is not OMe. 
     
     
         11 . The cytotoxic compound as claimed in  claim 9 , wherein at least two of R 4  to R 13  is OH. 
     
     
         12 . The cytotoxic compound as claimed in  claim 9 , wherein at least two of R 9  to R 13  are OH. 
     
     
         13 . The cytotoxic compound as claimed in  claim 9 , wherein when R 5  is OH or —O— lower alkyl and R 6  is OH or —O-lower alkyl. 
     
     
         14 . The cytotoxic compound as claimed in  claim 9 , wherein two of R 9  to R 13  are OH, with the remainder being H, halo, or lower alkyl. 
     
     
         15 . The cytotoxic compound as claimed in  claim 9 , wherein said compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         16 . A method of treating a proliferative disorder comprising administering to a human or non-human animal, in need thereof, a therapeutically effective amount of a compound of group A or group B, wherein said group A is a compound of formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2  and R 3  are independently H or lower alkyl; 
         R 4 , R 5 , R 6 , R 7  and R 8  are independently H, halo, lower alkyl or —O-lower alkyl, provided that at least one is —O-lower alkyl; or at least one pair of R 4  to R 8 , the members of which pair are adjacent to one another on the ring, are conjoined to form —O—(CR 14 R 15 ) n —O—, where n is 1 or 2 and R 14  and R 15  are independently H or lower alkyl, and the remainder of R 4  to R 8  are independently H, halo, lower alkyl or —O-lower alkyl; and 
         R 9 , R 10 , R 11 , R 12  and R 13  are independently H, halo, lower alkyl or —O— lower alkyl, provided that at least one is —O-lower alkyl; or at least one pair of R 9  to R 13 , the members of which pair are adjacent to one another on the ring, are conjoined to form —O—(CR 16 R 17 ) m —O—, where m is 1 or 2 and R 16  and R 17  are independently H or lower alkyl, and the remainder of R 9  to R 13  are independently H, halo, lower alkyl or —O-lower alkyl; 
       
       and wherein said group B is a cytotoxic compound of formula X: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 -R 3  are independently H or lower alkyl; and 
         R 4 -R 13  are independently H, OH, halo, lower alkyl or —O-lower alkyl, provided that at least one of R 4 -R 13  is OH. 
       
     
     
         17 . The compound as claimed in  claim 16 , wherein said proliferative disorder is a cancer. 
     
     
         18 . The compound as claimed in  claim 17 , wherein said cancer is selected from cancer of the lung, colon, breast, ovarian, prostate, liver, pancreas, brain, bladder, kidney and skin. 
     
     
         19 . The method of  claim 16  comprising administering to a human or non-human animal in need thereof a therapeutically effective amount of a cytotoxic compound of group B, wherein said cytotoxic compound is produced in the body. 
     
     
         20 . A pharmaceutical composition comprising one or more compounds of  claim 1 , together with one or more pharmaceutically acceptable excipients.