Patent RU-2315043-C2 (RU)
IPC: A61K31/506
Filed: 2003-06-27
Granted: 2008-01-20
Abstract: FIELD: organic chemistry, medicine, oncology, pharmacy, biochemistry. 
     SUBSTANCE: invention relates to amide derivative represented by the following formula [1]:  
     
       
         
               
               
               
               
             
                 
                   
                 
                   
                   
                   
               
                   
                   
                   
               
                   
                   
                   
               
           
              
              
              
             
          
         
       
     
      in any of the following cases (A) or (B), or its salt. In the case (A) R 1  represents 5-7-membered saturated cyclic group comprising 1-2 nitrogen atoms as atom forming cycle (saturated cyclic amino-group can be substituted with 1-3 similar or different substitutes chosen from group consisting of (C 1 -C 10 )-alkyl, (C 1 -C 10 )-alkoxycarbonyl), mono-(C 1 -C 10 )-alkylamino- or di-(C 1 -C 10 )-alkylamino-group; R 2  represents (C 1 -C 10 )-alkyl, halogen atom, halogen-(C 1 -C 10 )-alkyl, (C 1 -C 10 )-alkoxy-group, (C 1 -C 10 )-alkoxycarbonyl, nitro-group, mono-(C 1 -C 10 )-alkylcarbamoyl, di-(C 1 -C 10 )-alkylcarbamoyl or cyano-group; R 3  represents hydrogen atom, halogen atom or (C 1 -C 10 )-alkoxy-group; Het1 represents any of the following formulae: [2]  , [3]  , [4]  , [5]  , [6]  , [7]   and [8]  ; Het2 represents pyridyl, pyrimidinyl, pyrazinyl or 1,2-dihydropyridazinyl (wherein Het2 can be substituted with 1-3 similar or different substitutes chosen from halogen atom) but except for compound wherein R 1  means (i) pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl and each of them can be substituted with 1-3 similar or different substitutes chosen from group consisting of alkyl, alkoxycarbonyl, halogen atom, halogenalkyl, hydroxyalkyl, amino-, monoalkylamino-, dialkylamino-group, carbamoyl, monoalkylcarbamoyl and dialkylcarbamoyl; (ii) monoalkylamino-group, or (iii) dialkylamino-group; Het1 means group of the formula [6], and Het2 means pyrazinyl or pyridyl and each of them can mean a substituted alkyl. In case the (B) R 1  represents 4-methylpiperazin-1-yl, 1-pyrrolidinyl, piperidino-group, 4-ethylpiperazin-1-yl, 4-n-propylpiperazin-1-yl, cis-3,5-dimethylpiperazin-1-yl, morpholino-, dimethylamino- or diethylamino-group; R 2  represents methyl, halogen atom, trifluoromethyl, methoxy-group, methoxycarbonyl, nitro-group, dimethylcarbamoyl or cyano-group; R 3  represents hydrogen atom, bromine atom or methoxy-group; Het1 represents compound of the formula [6]; Het2 represents 3-pyridyl. Invention relates to a pharmaceutical composition possessing inhibitory activity with respect to BCR-ABL tyrosine kinase comprising amide derivative of the formula (I) or its salt as active component and a pharmaceutically acceptable nontoxic and inert carrier. Also, invention relates to BCR-ABL tyrosine kinase inhibitor, therapeutic agents comprising amide derivative of the formula (I) or its salt and, optionally, a pharmaceutically acceptable nontoxic and inert carrier used in treatment of chronic myelogenous leukemia, acute lymphoblast cell leukemia, acute myelogenous leukemia. Invention provides and proposes amide derivative inhibiting activity of BCR-ABL tyrosine kinase. 
     EFFECT: valuable medicinal properties of compounds and pharmaceutical composition. 
     8 cl, 2 tbl, 83 ex