KINASE INHIBITORS, PRODRUG FORMS THEREOF AND USE THEREOF IN THERAPY Russian patent published in 2015 - IPC C07D471/04 A61K31/519 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to pyrido[3,4-d]pyrimidine compounds of formula (III), having Pan-erbB kinase inhibiting properties. In the compound of formula

,

where X is a halide, (1) R₁ is H, and (a) R₂ is (3-chlorobenzyl)oxy- and R₃ is chloro; (b) R₂ and R₃, together with the carbon atom with which they are bonded, form 1-(3-fluorobenzyl)-1H-pyrazole; (c) R₂ is 2-pyridinylmethoxy and R₃ is chloro; (d) R₂ and R₃ are both chloro; (e) R₂ is chloro and R₃ is bromo; (f) R₂ and R₃ are both bromo; (g) R₂ is fluoro and R₃ is ethynyl; (h) R₂ is chloro and R₃ is ethynyl; (i) R₂ is bromo and R₃ is ethynyl; (j) except in cases when R₂ is in position 3 coupled with R₃ in position 4, R₂ is bromo and R₃ is fluoro; (k) R₂ is 2-pyridinylmethoxy and R₃ is fluoro; or (1) R₂ is 2-pyridinylmethoxy and R₃ is bromo; or (2) at least one of R₁, R₂ and R₃ is selected from benzyloxy, 3-chlorobenzyloxy and 2-pyridinylmethoxy, and when at least one of R₁, R₂ and R₃ is not benzyloxy, 3-chlorobenzyloxy or 2-pyridinylmethoxy, each of the rest is independently selected from H, halogen and C₂-C₄alkynyl, under the condition that when one of R₁, R₂ and R₃ is benzyloxy 2-pyridinylmethoxy, the other two of R₁, R₂ and R₃ may not be H; or (3) two of R₁, R₂ and R₃, together with carbon atoms with which they are bonded, form 1-(3-fluorobenzyl)-1H-pyrazole, and the rest is selected from H, halogen and C₂-C₄alkynyl; R₄ is selected from H, methyl, ethyl, trifluoromethyl, -CN, -CONH₂ and propyn-1-yl, and R₅ is C₁-C₆alkyl.

EFFECT: compounds can be used in treating cancer, which is mediated by the activity of said kinase.

12 cl, 16 dwg, 6 tbl