US2013324532A1PendingUtilityA1

Fak inhibitors

52
Assignee: HOLMES IAN PETERPriority: Feb 17, 2011Filed: Feb 17, 2012Published: Dec 5, 2013
Est. expiryFeb 17, 2031(~4.6 yrs left)· nominal 20-yr term from priority
C07D 401/12A61P 35/02C07D 403/14A61K 31/506C07D 413/12A61K 39/3955C07D 403/12C07D 401/14C07D 239/42A61P 35/00C07D 403/06A61K 39/395A61P 43/00
52
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Claims

Abstract

A compound of the formula (I): where R 1 or R 2 is a cyclc amine group and R 5 is an aromatic group with a carbonyl containing substituent for use as a FAK inhibitor.

Claims

exact text as granted — not AI-modified
1 . A compound of the formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is selected from: H and 
       
       
         
           
           
               
               
           
         
         wherein:
 R N1  is selected from H, C 1-3  alkyl and C(═O)Me; 
 R N2  is selected from H, C 1-3  alkyl and C(═O)Me; 
 R N3  is selected from H, C 1-3  alkyl and C(═O)Me; 
 R N4  is selected from H and CH 3 ; 
 
         R N7  and R N8  are independently selected from H and CH 3 ; 
         R N9  is selected from H, C 1-3  alkyl and C(═O)Me; 
         R N10  is selected from H, C 1-3  alkyl and C(═O)Me; 
         R N11  is selected from H, C 1-3  alkyl and C(═O)Me; 
         R 2  is selected from H and 
       
       
         
           
           
               
               
           
         
         wherein:
 R N5  is selected from H, C 1-3  alkyl and C(═O)Me; 
 R N6  is selected from H, C 1-3  alkyl and C(═O)Me; 
 
         and wherein only one of R 1  and R 2  is H; 
         or R 1  and R 2  together form the group —CH—N(R N12 )—C 2 H 4 —, where R N12  is selected from H, C 1-3  alkyl and C(═O)Me; 
         R 4  is selected from CF 3 , halo, CF 2 H and CN; and 
         R 5  is selected from groups of the following formulae: 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 6  is selected from H, (CHR C1 ) n1 C(O)N(R N6 )Z 1  and (CH 2 ) 2 C(O)OZ 2 ; wherein:
 n1 is 1; 
 
         R C1  is H or Me;
 R N12  is H or CH 3 ; 
 Z 1  is H, CH 3  or OCH 3 ; 
 n2 is 1; and 
 Z 2  is CH 3 ; 
 
         and where only one of R N12  and Z 1  can be CH 3 , 
         R 7 , if present, is selected from H, and (CH 2 ) m1 C(O)N(R M1 )Y 1 , wherein:
 m1 is 0 or 1; 
 R M1  is H; and 
 Y 1  is H, Me or OCH 3 ; 
 
         and one of R 6  and R 7  is not H; and 
         R 8 , if present, is H or, when R 7  is C(═O)NH 2 , R 8  is selected from H and C 1-2  alkyl. 
       
     
     
         2 . A compound according to  claim 1 , wherein R 2  is H and R 1  is selected from the group consisting of:
 (a),   
       
         
           
           
               
               
           
         
       
       wherein R N1  is C(═O)Me;
 (b) 
 
       
         
           
           
               
               
           
         
       
       wherein R N1  is H, methyl or ethyl:
 (c) 
 
       
         
           
           
               
               
           
         
       
       wherein R N2  is selected from H methyl and ethyl;
 (d) 
 
       
         
           
           
               
               
           
         
       
       wherein R N3  is selected from H and methyl;
 (e) 
 
       
         
           
           
               
               
           
         
       
       wherein R N4  selected from H and methyl;
 (f) 
 
       
         
           
           
               
               
           
         
       
       wherein R N7  and R N8  are both H or both methyl;
 (g) 
 
       
         
           
           
               
               
           
         
       
       wherein R N9  is H;
 (h) 
 
       
         
           
           
               
               
           
         
       
       wherein R N10  is selected from H and methyl; and
 (i) 
 
       
         
           
           
               
               
           
         
       
       wherein R N11  is H. 
     
     
         3 - 10 . (canceled) 
     
     
         11 . A compound according to  claim 1 , wherein R 1  is H and R 2  is selected from the group consisting of:
 (a)   
       
         
           
           
               
               
           
         
       
       where R N5  is selected from H and methyl; and
 (b) 
 
       
         
           
           
               
               
           
         
       
       where R N6  is selected from H and methyl. 
     
     
         12 . (canceled) 
     
     
         13 . A compound according to  claim 1 , wherein R 4  is selected from CF 3 , Cl and CF 2 H. 
     
     
         14 . A compound according to  claim 13 , wherein R 4  is CF 3 . 
     
     
         15 . A compound according to  claim 1 , wherein R 5  is a group of the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         16 . A compound according to  claim 1 , wherein R 5  is a group selected from: 
       
         
           
           
               
               
           
         
       
     
     
         17 . A compound according to  claim 15 , wherein R 7  is H and R 6  is selected from CH 2 C(O)NH 2 , CH 2 C(O)NHCH 3 , CHCH 3 C(O)NH 2  and CHCH 3 C(O)NHCH 3 . 
     
     
         18 . A compound according to  claim 17 , wherein R 7  is H and R 6  is selected from CH 2 C(O)NH 2 , CHCH 3 C(O)NH 2  and CH 2 C(O)NHCH 3 . 
     
     
         19 . A compound according to  claim 18 , wherein R 7  is H and R 6  is selected from CH 2 C(O)NH 2 , and CHCH 3 C(O)NH 2 . 
     
     
         20 . A compound according to  claim 15 , wherein R 6  is H and R 7  is selected from C(O)NH 2 , C(O)NHCH 3 , CH 2 C(O)NH 2  and CH 2 C(O)NHCH 3 . 
     
     
         21 . A compound according to  claim 20 , wherein R 6  is H and R 7  is C(O)NH 2 . 
     
     
         22 . A compound according to  claim 21 , wherein R 8  is methyl. 
     
     
         23 . A compound according to  claim 1 , wherein R 5  is a group of the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         24 . A composition comprising a compound according to  claim 1 , and a pharmaceutically acceptable carrier or diluent. 
     
     
         25 - 28 . (canceled) 
     
     
         29 . A method of inhibiting FAK in vitro or in vivo, comprising contacting a cell with an effective amount of a compound according to  claim 1 . 
     
     
         30 . A method of treating a disease ameliorated by the inhibition of FAK comprising administering a compound according to  claim 1 . 
     
     
         31 . A method of treating a disease ameliorated by the inhibition of FAK comprising administering a composition according to  claim 24 . 
     
     
         32 . A compound according to  claim 16 , wherein R 7  is H and R 6  is selected from CH 2 C(O)NH 2 , CH 2 C(O)NHCH 3 , CHCH 3 C(O)NH 2  and CHCH 3 C(O)NHCH 3 . 
     
     
         33 . A compound according to  claim 16 , wherein R 6  is H and R 7  is selected from C(O)NH 2 , C(O)NHCH 3 , CH 2 C(O)NH 2  and CH 2 C(O)NHCH 3 .

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