Pyrrolopyrimidine and purine derivatives

Abstract

The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, T, V, W, X, Y, Z, ring A, R 1 , R 2 , R 3 , R 4 , R 5 , R 5a , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 and m are defined herein. There novel pyrrolopyrimidine and purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

What is claimed is: 
     
         1 . A compound of formula (II): 
       
         
           
           
               
               
           
         
       
       wherein
 X is N or CR 7 ; 
 Y is absent, O, S or NR 8 ; 
 Q and V are each independently C or N, provided that at least one of Q and V is N, and further provided that when Q is N, at least one of R 1  and R 2  is absent; 
 R 1  and R 4  are each independently absent, hydrogen, cyano, difluoromethyl, trifluoromethyl, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, —N(R 9 )(R 10 ), C 3 -C 5  cycloalkyl, or 4-6 membered heterocycloalkyl, wherein the C 1 -C 6  alkyl may be optionally substituted by halogen, hydroxy, C 1 -C 6  alkoxy, or N(R 11 )(R 12 ); 
 R 2  and R 3  are each independently absent, hydrogen, C 1 -C 6  alkyl, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, C 3 -C 7  cycloalkyl or 3-7 membered heterocycloalkyl, wherein the C 1 -C 6  alkyl and C 1 -C 6  alkoxy in R 2  and R 3  are each independently optionally substituted by one or more R 13  groups, and further wherein the C 3 -C 7  cycloalkyl and the 3-7 membered heterocycloalkyl in R 2  and R 3  are each independently optionally substituted by one or more R 14  groups; or 
 R 1  and R 2  or R 2  and R 3  may combine to form a C 5 -C 7  cycloalkyl ring or a 5-7 membered heterocycloalkyl ring, wherein the C 5 -C 7  cycloalkyl ring and the 5-7 membered heterocycloalkyl ring are each independently optionally substituted by one or more R 13  groups; 
 ring A is absent, C 3 -C 10  cycloalkyl, 3-10 membered heterocycloalkyl, C 5 -C 10  aryl or 5-12 membered heteroaryl; 
 R 5  and R 5a  are each independently absent, halogen, cyano, hydroxy, difluoromethyl, trifluoromethyl, C 1 -C 3  alkyl, C 1 -C 3  alkoxy, C 3 -C 5  cycloalkyl or C 3 -C 5  heteroaryl, wherein the C 1 -C 3  alkyl is optionally substituted by hydroxy, difluoromethyl, trifluoromethyl, C 1 -C 3  alkoxy or C 3 -C 5  cycloalkyl; 
 R 6  is 
 
       
         
           
           
               
               
           
         
         Z is absent when the attachment point of R 6  on ring A is a nitrogen atom, and Z is —NR 17 — when ring A is absent or when the attachment point of R 6  on ring A is a carbon atom; 
         R 7  is hydrogen, halogen, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or 4-6 membered heteroaryl, wherein the C 1 -C 6  alkyl may be optionally substituted by hydroxy or C 1 -C 3  alkoxy, and further wherein the 4-6 membered heteroaryl may be optionally substituted by C 1 -C 3  alkyl; 
         R 8  is hydrogen or C 1 -C 3  alkyl; 
         R 9  and R 10  are each independently hydrogen or C 1 -C 6  alkyl; or R 9  and R 10  together with the nitrogen to which they are attached, may combine to form a 4-7 membered ring, when R 9  and R 10  are each C 1 -C 3  alkyl, wherein the 4-7 membered ring is optionally substituted by one or more R 14  groups; 
         R 11  and R 12  are each independently hydrogen or C 1 -C 3  alkyl; 
         each R 13  is independently halogen, cyano, hydroxy, C 1 -C 6  alkoxy, —N(R 9 )(R 10 ), —CON(R 9 )(R 10 ), 3-7 membered heterocycloalkyl, wherein the 3-7 membered heterocycloalkyl in R 13  is optionally substituted by one or more R 14  groups; 
         each R 14  is independently halogen, C 1 -C 3  alkyl, hydroxy, C 1 -C 6  alkoxy, —NH 2 , —NHCH 3 , or N(CH 3 ) 2 ; 
         R 15  and R 16  are each independently hydrogen or C 1 -C 6  alkyl, wherein the C 1 -C 6  alkyl of one of R 15  and R 16  is optionally substituted by —N(R 9 )(R 10 ); 
         R 17  is hydrogen or C 1 -C 3  alkyl; and 
         m is 0, 1 or 2, provided that when ring A is absent, m is 2; or 
         a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound or salt of  claim 1 , wherein X is CR 7 . 
     
     
         3 . The compound or salt of  claim 1 , wherein Y is O. 
     
     
         4 . The compound or salt of  claim 1 , wherein Y is NR 8 . 
     
     
         5 . The compound or salt of  claim 2 , wherein R 7  is hydrogen, halogen, cyano or 4-6 membered heteroaryl. 
     
     
         6 . The compound or salt of  claim 2 , wherein R 7  is hydrogen. 
     
     
         7 . The compound or salt of  claim 5 , wherein the halogen is fluorine. 
     
     
         8 . The compound or salt of  claim 5 , wherein the halogen is chlorine. 
     
     
         9 . The compound or salt of  claim 2 , wherein R 7  is cyano 
     
     
         10 . The compound or salt of  claim 2 , wherein R 7  is 4-6 membered heteroaryl optionally substituted by C 1 -C 3  alkyl. 
     
     
         11 . The compound or salt of  claim 1 , wherein m is 0. 
     
     
         12 . The compound or salt of  claim 1 , wherein m is 1. 
     
     
         13 . The compound or salt of  claim 1 , wherein Q and V are N. 
     
     
         14 . The compound or salt of  claim 1 , wherein V is N. 
     
     
         15 . The compound or salt of  claim 1 , having formula (IIa): 
       
         
           
           
               
               
           
         
       
       wherein
 G is CH or N; and 
 p is 1 or 2. 
 
     
     
         16 . The compound or salt of  claim 15 , wherein G is CH. 
     
     
         17 . The compound or salt of  claim 15 , wherein G is N. 
     
     
         18 . The compound or salt of  claim 15 , wherein p is 1. 
     
     
         19 . The compound or salt of  claim 15 , wherein p is 2. 
     
     
         20 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.