Atm inhibitors

Abstract

A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: R 1 and R 2 together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and R N1 is selected from hydrogen, an optionally substituted C 1-7 alkyl group, an optionally substituted C 3-20 heterocyclyl group, an optionally substituted C 5-20 aryl group, an acyl group, an ester group and an amido group, and its use as a pharmaceutical.

1 . A compound of formula III: 
       
         
           
           
               
               
           
         
       
       and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein:
 R 1  and R 2  together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; 
 R C3  is of formula: 
 
       
         
           
           
               
               
           
         
       
       wherein r is 0 or 1, and q can be 1 or 2 when r is 0 and q is 1 when
 r is 1, and 
 wherein R N4  and R N5  are independently selected from hydrogen, optionally substituted C 1-7  alkyl groups, optionally substituted C 3-20  heterocyclyl groups and optionally substituted C 5-20  aryl groups, or together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms. 
 
     
     
         2 . A compound according to  claim 1 , wherein r=0. 
     
     
         3 . A compound according to  claim 1 , wherein R N4  and R N5  are independently selected from hydrogen, optionally substituted C 1-7  alkyl groups, or together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms. 
     
     
         4 . A compound according to  claim 3 , wherein one of R N4  and R N5  is an optionally substituted C 1-7  alkyl group, the other is preferably H, and the optional substituents are selected from hydroxy, amino, cyano, C 3-20  heterocylyl and C 5-20  aryl (more preferably C 5-7  aryl). 
     
     
         5 . A compound according to  claim 1 , wherein one of R N4  and R N5  is of formula IIb: 
       
         
           
           
               
               
           
         
       
       wherein r is from 1 to 3; and
 R N2  and R N3  are independently selected from hydrogen, optionally substituted C 1-7  alkyl groups, optionally substituted C 3-20  heterocyclyl groups and optionally substituted C 5-20  aryl groups, or together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms. 
 
     
     
         6 . A compound according to  claim 5 , wherein R N2  and R N3  are independently selected from hydrogen, optionally substituted C 1-7  alkyl groups or together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms. 
     
     
         7 . A compound according to  claim 1 , wherein R N4  and R N5  together form, along with the nitrogen atom to which they are attached, a ring selected from piperidine, homopiperidine, piperazine, homopiperazine and morpholino. 
     
     
         8 . A compound according to  claim 7 , wherein the ring is piperazine or homopiperazine, and the other nitrogen ring atom is substituted by a group selected from an optionally substituted C 1-7  alkyl group, an optionally substituted C 3-20  heterocyclyl group, an optionally substituted C 5-20  aryl group, an acyl group, an ester group or an amido group. 
     
     
         9 . A compound of formula VI: 
       
         
           
           
               
               
           
         
       
       and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein:
 R 1  and R 2  together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and 
 R C4  is of formula: 
 
       
         
           
           
               
               
           
         
       
       wherein r is 0 or 1, and q can be 1 or 2 when r is 0 and q is 1 when r is 1, and
 wherein R N4  and R N5  are independently selected from hydrogen, optionally substituted C 1-7  alkyl groups, optionally substituted C 3-20  heterocyclyl groups and optionally substituted C 5-20  aryl groups, or together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms. 
 
     
     
         10 . A compound according to  claim 9 , wherein r=0. 
     
     
         11 . A compound according to  claim 9 , wherein R N4  and R N5  are independently selected from hydrogen, optionally substituted C 1-7  alkyl groups, or together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms. 
     
     
         12 . A compound according to  claim 11 , wherein one of R N4  and R N5  is an optionally substituted C 1-7  alkyl group, the other is preferably H and the optional substituents are selected from hydroxy, halo, C 1-7  alkoxy, thiol, C 1-7  thioether, amino, ester, cyano, C 3-20  heterocylyl and C 5-20  aryl. 
     
     
         13 . A compound according to  claim 9 , wherein, one of R N4  and R N5  is of formula IIb: 
       
         
           
           
               
               
           
         
       
       wherein r is from 1 to 3; and
 R N2  and R N3  are independently selected from hydrogen, optionally substituted C 1-7  alkyl groups, optionally substituted C 3-20  heterocyclyl groups and optionally substituted C 5-20  aryl groups, or together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms. 
 
     
     
         14 . A compound according to  claim 13 , wherein R N2  and R N3  are independently selected from hydrogen, optionally substituted C 1-7  alkyl groups or together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms. 
     
     
         15 . A compound according to  claim 14 , wherein R N4  and R N5  together form, along with the nitrogen atom to which they are attached, a ring selected from piperidine, homopiperidine, piperazine, homopiperazine and morpholino. 
     
     
         16 . A compound according to  claim 15 , wherein the ring is piperazine or homopiperazine, and the other nitrogen ring atom is substituted by a group selected from an optionally substituted C 1-7  alkyl group, an optionally substituted C 3-20  heterocyclyl group, an optionally substituted C 5-20  aryl group, an acyl group, an ester group and an amido group. 
     
     
         17 . A compound according to  claim 1 , wherein R 1  and R 2  form, along with the nitrogen atom to which they are attached, a ring selected from morpholino and thiomorpholino. 
     
     
         18 . A compound according to  claim 9 , wherein R 1  and R 2  form, along with the nitrogen atom to which they are attached, a ring selected from morpholino and thiomorpholino.