Ep4 receptor antagonists

Abstract

A compound of formula (I): or a salt, solvate and chemically protected form thereof, wherein one of R 2 and R 5 is: (i) H or an optionally substituted C 1-4 alkyl group; or (ii) an optionally substituted C 5-7 aryl; and the other of R 2 and R 5 is the other group; m and n can be 0 or 1, and m+n=1 or 2 R N is H or optionally substituted C 1-4 alkyl R 3 is either: (i) carboxy; (ii) a group of formula (II): (iii) a group of formula (III): wherein R is optionally substituted C 1-7 alkyl, C 5-20 aryl, or NR N3 R N4 , where R N3 and R N4 are independently selected from optionally substituted C 1-4 alkyl; or (iv) tetrazol-5-yl.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         or a salt, solvate and chemically protected form thereof, wherein: 
         either R 2  is H or an optionally substituted C 1-4  alkyl group and R 5  is an optionally substituted C 5-7  aryl; or 
         R 5  is H or an optionally substituted C 1-4  alkyl group and R 2  is an optionally substituted C 5-7  aryl; 
         m and n can be 0 or 1, and m+n=1 or 2 
         R N  is H or optionally substituted C 1-4  alkyl 
         R 3  is either carboxy or tetrazol-5-yl. 
       
     
     
         2 . A compound according to  claim 1 , wherein R 5  is the optionally substituted C 5-7  aryl group and R 2  is H or the optionally substituted C 1-4  alkyl group. 
     
     
         3 . A compound according to  claim 2 , wherein R 2  is selected from H or an optionally substituted C 1-3  alkyl group. 
     
     
         4 . A compound according to  claim 3 , wherein R 2  is a methyl group. 
     
     
         5 . A compound according to  claim 2 , wherein R 5  is a C 6  aryl group. 
     
     
         6 . A compound according to  claim 5 , wherein R 5  is phenyl. 
     
     
         7 . A compound according to  claim 1  wherein the C 5-7  aryl group is substituted by substituents selected from C 1-7  alkoxy groups. 
     
     
         8 . A compound according to  claim 1 , wherein n+m=1. 
     
     
         9 . A compound according to  claim 8 , wherein n is 0 and m is 1. 
     
     
         10 . A compound according to  claim 1 , wherein R N  is H or methyl. 
     
     
         11 . A pharmaceutical composition comprising a compound according to  claim 1  or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent. 
     
     
         12 . A method of treating a condition which can be alleviated by antagonism of an EP 4  receptor, which method comprises administering to a patient in need of treatment an effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         13 . A method according to  claim 12 , wherein the condition which can be alleviated by antagonism of an EP 4  receptor is a primary headache disorder. 
     
     
         14 . A method according to  claim 13 , wherein the primary headache disorder is a migraine. 
     
     
         15 . A method of treating a condition which can be alleviated by antagonism of an EP 4  receptor, which method comprises administering to a patient in need of treatment an effective amount of a compound of claim formula (I), 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         either R 2  is H or an optionally substituted C 1-4  alkyl group and R 5  is an optionally substituted C 5-7  aryl; or 
         R 5  is H or an optionally substituted C 1-4  alkyl group and R 2  is an optionally substituted C 5-7  aryl; 
         m and n can be 0 or 1, and m+n=1 or 2 
         R N  is H or optionally substituted C 1-4  alkyl 
         R 3  is either: 
         (i) carboxy; 
         (ii) a group of formula (II): 
       
       
         
           
           
               
               
           
         
         (iii) a group of formula (III): 
       
       
         
           
           
               
               
           
         
         wherein R is optionally substituted C 1-7  alkyl, C 5-20  aryl, or NR N3 R N4 , where R N3  and R N4  are independently selected from optionally substituted C 1-4  alkyl; or 
         (iv) tetrazol-5-yl. 
       
     
     
         16 . A method of  claim 15 , wherein R 5  is the optionally substituted C 5-7  aryl group and R 2  is H or the optionally substituted C 1-4  alkyl group. 
     
     
         17 . A method according to  claim 16 , wherein R 2  is selected from H or an optionally substituted C 1-3  alkyl group. 
     
     
         18 . A method according to  claim 17 , wherein R 2  is a methyl group. 
     
     
         19 . A method according to  claim 16 , wherein R 5  is a C 6  aryl group. 
     
     
         20 . A method according to  claim 19 , wherein R 5  is phenyl. 
     
     
         21 . A method according to  claim 15  wherein the C 5-7  aryl group is substituted by substituents selected from C 1-7  alkoxy groups. 
     
     
         22 . A method according to  claim 15  wherein R 3  is either:
 (i) a group of formula (II):   
       
         
           
           
               
               
           
         
         (ii) a group of formula (III): 
       
       
         
           
           
               
               
           
         
       
     
     
         23 . A method according to  claim 22 , wherein R is selected from an optionally substituted C 5-20  aryl group, and an optionally substituted C 5-20  aryl-C 1-7  alkyl group. 
     
     
         24 . A method according to  claim 22 , wherein R is a C 1-7  alkyl group. 
     
     
         25 . A method according to  claim 15 , wherein n+m=1. 
     
     
         26 . A method according to  claim 25 , wherein n is 0 and m is 1. 
     
     
         27 . A method according to  claim 15 , wherein R N  is H or methyl.