AMIDE DERIVATIVE, PHARMACEUTICAL COMPOSITION AND THERAPEUTIC AGENTS BASED ON THEREOF Russian patent published in 2008 - IPC C07D301/14 C07D401/04 C07D403/14 C07D407/14 A61K31/506 A61K31/497 A61K31/551 A61P35/02 

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) R¹ 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 (C₁-C₁₀)-alkyl, (C₁-C₁₀)-alkoxycarbonyl), mono-(C₁-C₁₀)-alkylamino- or di-(C₁-C₁₀)-alkylamino-group; R² represents (C₁-C₁₀)-alkyl, halogen atom, halogen-(C₁-C₁₀)-alkyl, (C₁-C₁₀)-alkoxy-group, (C₁-C₁₀)-alkoxycarbonyl, nitro-group, mono-(C₁-C₁₀)-alkylcarbamoyl, di-(C₁-C₁₀)-alkylcarbamoyl or cyano-group; R³ represents hydrogen atom, halogen atom or (C₁-C₁₀)-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 R¹ 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) R¹ 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; R² represents methyl, halogen atom, trifluoromethyl, methoxy-group, methoxycarbonyl, nitro-group, dimethylcarbamoyl or cyano-group; R³ 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