6-(2-alkyl-phenyl)-pyrido[2,3-d]pyrimidines useful as protein kinase inhibitors

Abstract

Objects of the present invention are the compounds of formula I their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates, the preparation of the above-mentioned compounds, medicaments containing them and their manufacture, as well as the use of the above-mentioned compounds in the control or prevention of illnesses such as cancer.

1 . A compound of formula I 
     
       
         
         
             
             
         
       
       wherein 
       R 1  is —CH 3 ; 
       R 2  is —C(O)—NH-alkyl or —C(O)—N(alkyl) 2 , all alkyl groups being optionally substituted with
 —OH; —NH(alkyl); —N(alkyl) 2 ; -heterocyclyl; or —NH—S(O) 2 -alkyl; 
 
       R 3  is heterocyclyl; 
       —NH—C(O)-alkyl; or 
       —NH—S(O) 2 -alkyl; and 
       R 4  is hydrogen; or alternatively 
       R 3  and R 4  are adjacent and together with the phenyl ring to which they are attached form a 4,4-Dioxo-3,4-dihydro-2H-4lambda*6*-benzo[1,4]oxathiin-6-yl moiety; 
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       2 . (canceled) 
   
   
       3 . A compound according to  claim 1 , selected from the group consisting of: 
     2-(3-Acetylamino-phenylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (2-methylamino-ethyl)-amide; 
     2-(3-Methanesulfonylamino-phenylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (2-methylamino-ethyl)-amide; 
     2-(4-Morpholin-4-yl-phenylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (2-methylamino-ethyl)-amide; 
     2-(3-Acetylamino-phenylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (pyrrolidin-2-ylmethyl)-amide; 
     2-(3-Methanesulfonylamino-phenylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (pyrrolidin-2-ylmethyl)-amide; 
     2-(4-Morpholin-4-yl-penylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (pyrrolidin-2-ylmethyl)-amide; 
     2-(3-Acetylamino-phenylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (2-methanesulfonylamino-ethyl)-amide; 
     2-(3-Methanesulfonylamino-phenylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (2-methanesulfonylamino-ethyl)-amide; and 
     2-(4-Morpholin-4-yl-phenylamino)-6-o-tolyl-pyrido[2,3-d]pyrimidine-7-carboxylic acid (2-methanesulfonylamino-ethyl)-amide. 
   
   
       4 . (canceled) 
   
   
       5 . (canceled) 
   
   
       6 . A process for the manufacture of a compound according to  claim 1 , wherein
 a) the carboxylate group in a compound of formula (III)   
     
       
         
         
             
             
         
       
     
     wherein R 1  is —CH 3 , is converted into an amide derivative with the resulting compound being a compound of formula (IV) 
     
       
         
         
             
             
         
       
     
     wherein R 1  is —CH 3  and R 2  is —C(O)—NH-alkyl or —C(O)—N(alkyl) 2 , all alkyl groups being optionally substituted with —OH, —NH(alkyl), —N(alkyl) 2 , -heterocyclyl, or —NH—S(O) 2 -alkyl;
 b) the sulfanyl group in the compound of formula (IV) is converted to the corresponding sulfoxide group, which sulfoxide group is 
 c) substituted by the respective anilines of formula (VI) 
 
     
       
         
         
             
             
         
       
       wherein R 3  is heterocyclyl, —NH—C(O)-alkyl, or —NH—S(O) 2 -alkyl, and R 4  is hydrogen, or, alternatively, R 3  and R 4  are adjacent and together with the phenyl ring to which they are attached form a 4,4-Dioxo-3,4-dihydro-2H-4lambda*6*-benzo[1,4]oxathiin-6-yl moiety. 
     
   
   
       7 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable adjuvant. 
   
   
       8 . A pharmaceutical composition according to  claim 7  for the treatment of cancer. 
   
   
       9 - 10 . (canceled)