Chemical compounds

Abstract

or pharmaceutically-acceptable salts thereof, wherein R1 to R5 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

1 . A pharmaceutical composition comprising a compound and a pharmaceutically-acceptable diluent or carrier, wherein the compound is (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid or a pharmaceutically-acceptable salt thereof. 
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein the compound is (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid. 
     
     
         3 . A pharmaceutical composition according to  claim 1 , wherein the compound is the maleic acid salt of (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid. 
     
     
         4 . A pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition contains less than 5% w/w of (R,E)-3-(3,5-difluoro-4-(2-(2-fluoro-2-methylpropyl)-3-methyl-4,9-dihydro-3H-pyrido[3,4-b]indol-2-ium-1-yl)phenyl)acrylate. 
     
     
         5 . A pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition further comprises an anti-oxidant and optionally further comprises a metal-chelating agent. 
     
     
         6 . A method for making a compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are each independently H or F; 
         R 3  is H or methyl; and 
         either: 
         a) R 4  is H and R 5  is F; or 
         b) R 4  is F and R 5  is H, 
         comprising hydrolysis of a compound of Formula (II): 
       
       
         
           
           
               
               
           
         
         wherein R 6  is (1-6C) alkyl. 
       
     
     
         7 . A method according to  claim 6 , wherein the compound of Formula (I) is (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid. 
     
     
         8 . A method according to  claim 7 , wherein R 6  is methyl. 
     
     
         9 . (E)-methyl 3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate. 
     
     
         10 . A method for making a compound of Formula (II): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are each independently H or F; 
         R 3  is H or methyl; 
         either: 
         a) R 4  is H and R 5  is F; or 
         b) R 4  is F and R 5  is H; 
         R 6  is (1-6C) alkyl, 
         comprising a reaction of a compound of Formula (III): 
       
       
         
           
           
               
               
           
         
         with a compound of Formula (IV): 
       
       
         
           
           
               
               
           
         
       
     
     
         11 . A method according to  claim 10 , wherein the compound of Formula (II) is (E)-methyl 3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate.