FIELD: chemistry.
SUBSTANCE: invention relates to organic chemistry and specifically to an irreversible fibroblast growth factor receptor (FGFR) of general formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof:
where R1 and R2 are each independently selected from a group consisting of hydrogen, halogen and C1-6 alkoxy; R3 and R4 are each independently selected from a group consisting of hydrogen, C1-6 alkyl and (C1-6 alkyl)2-amino-C1-6alkyl; Ar is phenyl; ring A is phenyl; ring B is 3–10 membered saturated or unsaturated heterocyclyl containing at least one heteroatom N, optionally substituted with 1–3 groups R6 and the N atom in the ring is directly linked to the active groups; X is N; R6 is selected from a group consisting of: (i) hydrogen, (ii) hydroxy, amino, carboxy, cyano, a halogen atom, C2-4 alkenylcarbonylamino or =CH2, (iii) C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, (C1-6 alkyl)2-amino, halo C1-6 alkyl, halo C1-6 alkoxy or C1-6 alkylthio, optionally substituted with hydroxy, amino, cyano, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkoxy, C1-6 alkylamino, (C1-6 alkyl)2-amino, C1-6 alkylcarbonylamino, C1-6 alkylsulphonylamino or 3–8-member heterocyclyl containing 1–3 heteroatoms selected from O, S and N, and (iv) aminocarbonyl, C1-6 alkylcarbonyl, C1-6 alkylaminocarbonyl, (C1-6 alkyl)2-aminocarbonyl, C1-6 alkoxycarbonyl, 3–8-member cycloalkylcarbonyl or 3–8-member heterocyclylcarbonyl containing 1–3 heteroatoms selected from O, S and N; m1 and m2 are equal to 1 or 2; active group is selected from a group consisting of
R11, R12 and R13 each independently selected from a group consisting of hydrogen and C1-4 alkyl. Also disclosed is a pharmaceutical composition, use and method of treating the disease.
EFFECT: novel compound of general formula (I) having high efficacy and high selectivity with respect to fibroblast growth factor receptor inhibition and can be used for treating diseases mediated by FGF/FGFR abnormality.
17 cl, 2 tbl, 23 ex
активная группа - active group
и - and
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