Pyrrolopyrimidine compounds and their uses

Abstract

The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases, particularly pyrrolopyrimidine compounds and derivatives are described which inhibit protein kinases. The organic compounds are useful in treating proliferative disease.

1 - 43 . (canceled) 
     
     
         44 . A method for the treatment of cancer comprising administration of an effective amount of a compound according to formula (I) or a pharmaceutically acceptable salt thereof to a subject in need of treatment thereof 
       
         
           
           
               
               
           
         
       
       wherein:
 the dashed line indicates a double bond; 
 A is N; 
 R 2  is hydrogen and R 3  is selected from the group consisting of hydrogen, hydroxyl, C 1 -C 3 -alkyl, C 3 -C 8 -cycloalkyl, heterocyclyl, aryl, heteroaryl, substituted C 1 -C 3 -alkyl, substituted C 3 -C 8 -cycloalkyl, substituted heterocyclyl, substituted aryl and substituted heteroaryl; 
 R 4  is selected from the group consisting of hydrogen, branched C 1 -C 5 -alkyl, branched C 1 -C 5 -alkyl substituted by phenyl and C 3 -C 6 -cycloalkyl; 
 X is CR 11  and Y is CR 12 ; 
 R 11  is hydrogen or C 1 -C 3 -alkyl and 
 R 12  is BC(O)NR 13 R 14 ; wherein B is a bond, C 1 -C 3 -alkyl or branched C 1 -C 3 -alkyl; wherein R 13  and R 14  are each, independently, selected from the group consisting of hydrogen, C 1 -C 3 -alkyl, C 3 -C 8 -cycloalkyl, heterocyclyl, aryl, heteroaryl, substituted alkyl, substituted cycloalkyl, substituted heterocyclyl, substituted aryl, and substituted heteroaryl. 
 
     
     
         45 . The method of  claim 44 , wherein R 4  is C(H)(CH 2 CH 3 ) 2 , C(H)(CH 2 CH 3 )Ph, CH 2 CH 3 , cyclopropyl, cyclopentyl or cyclohexyl. 
     
     
         46 . The method of  claim 44 , wherein R 3  is an aryl group, which is further independently substituted one or more times by halogen, C 1 -C 4 -alkoxy, R 15 -amine, R 15 -heterocycle, or R 15 -heteroaryl, wherein R 15  is a bond, C(O), N(H)C(O), N(H)SO 2 , OC(O) or (CH 2 ) 1-4 , wherein the (CH 2 ) 14  group may be interrupted by O, N(CH 3 ) or N(H). 
     
     
         47 . The method of  claim 46 , wherein the aryl group is phenyl. 
     
     
         48 . The method of  claim 44 , wherein R 3  is phenyl which is further independently substituted one or more times with fluoro, methoxy, diethylamine, R 15 -piperazinyl, R 15 -morpholinyl, R 15 -piperidinyl, R 15 -triazolyl, R 15 -phenyl, R 15 -pyridinyl, R 15 -piperazinyl, R 15 -indazolyl, R 15 -pyrrolidinyl or R 15 -imidazolyl, wherein the piperazinyl, morpholinyl, piperidinyl, triazolyl, phenyl, pyridinyl, piperazinyl, indazolyl, pyrrolidinyl or imidazolyl groups may be further substituted with C 1 -C 4 -alkyl, C(O)C 1 -C 4 -alkyl, S(O) 2 C 1 -C 4 -alkyl, OH, C(O)(CH 2 ) 1-3 CN or N(H)C(O)C 1 -C 4 -alkyl and wherein R 15  is a bond, C(O), N(H)C(O), N(H)SO 2 , OC(O) or (CH 2 ) 14 , wherein the (CH 2 ) 14  group may be interrupted by O, N(CH 3 ) or N(H). 
     
     
         49 . The method of  claim 44 , wherein R 3  is phenyl which is further substituted by N(H)C(O)aryl, C(O)N(H)C 1 -C 4 -alkyl, C(O)N(C 1 -C 4 -alkyl) 2  or C(O)N(H)C 3 -C 6 -cycloalkyl. 
     
     
         50 . The method of  claim 44 , wherein the compound is selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         51 . The method according to  claim 44  wherein the cancer is selected from the group consisting of breast, stomach, ovary, colon, lung, brain, larynx, lymphatic system, genitourinary tract, ovarian, gastric, bone, and pancreatic cancer. 
     
     
         52 . The method according to  claim 44  wherein the cancer is selected from the group consisting of bladder, head and neck, breast, stomach, ovary, colon, lung, brain, larynx, lymphatic system, genitourinary tract, gastrointestinal, ovarian, prostate, gastric, bone, small-cell lung, glioma, colorectal and pancreatic cancer. 
     
     
         53 . The method according to  claim 44  wherein the compound or pharmaceutically acceptable salt thereof is administered simultaneously or sequentially with an anti-inflammatory, antiproliferative, chemotherapeutic, immunosuppressant, anti-cancer, or cytotoxic agent. 
     
     
         54 . The method according to  claim 44  wherein the compound or pharmaceutically acceptable salt thereof is administered simultaneously or sequentially with a PTK inhibitor, cyclosporin A, CTLA4-Ig, an antibody selected from the group consisting of anti-ICAM-3, anti-IL-2 receptor, anti-CD45RB, anti-CD2, anti-CD3, anti-CD4, anti-CD80, anti-CD86, and monoclonal antibody OKT3, an agent blocking the interaction between CD40 and gp39, a fusion protein constructed from CD40 and gp39, an inhibitor of NF-kappa B function, a non-steroidal anti-inflammatory drug, a steroid, a gold compound, an antiproliferative agent, FK506, mycophenolate mofetil, a cytotoxic drug, a TNF-α inhibitor, an anti-TNF antibody, soluble TNF receptor, rapamycin, leflunimide, cyclooxygenase-2 inhibitor, paclitaxel, cisplatin, carboplatin, doxorubicin, caminomycin, daunorubicin, aminopterin, methotrexate, methopterin, mitomycin C, ecteinascidin 743, porfiromycin, 5-fluorouracil, 6-mercaptopurine, gemcitabine, cytosine arabinoside, podophyllotoxin, etoposide, etoposide phosphate, teniposide, melphalan, vinblastine, vincristine, leurosidine, epothilone, vindesine, or leurosine.