PYRIMIDINE-UREA DERIVATIVES AS KINASE INHIBITORS Russian patent published in 2011 - IPC C07D239/48 C07D403/12 C07D401/12 C07D405/12 C07D409/12 A61K31/506 A61K31/5377 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I), which have protein kinase inhibiting properties and can be used in treating diseases which are dependent on any one or more protein kinases from FGFR1, FGFR2, FRF3 and/or FGFR4, KDR, HER1, HER2, Bcr-Abl, Tie2 and/or Ret Such diseases can be proliferative diseases, for example bladder cancer, breast cancer and multiple myeloma. In formula

the left-side ring , right-side ring , there are the following fragments, denoted "left-side ring" and "right-side ring", respectively: where X denotes C-R⁵, and Y and Z both denote N. The left-side ring corresponds to fragment (A):

n equals 0, 1, 2, 3, 4 or 5, X¹ denotes hydrogen, where R¹ denotes a group of formula R^z-NR^a-, where R^a denotes hydrogen and R^z is selected from (1) a straight or branched C₁-C₄alkyl or (2) a group of formula , where ring A denotes phenyl, cyclohexenyl, cyclohexyl or pyridyl, m equals 0, 1 or 2, one or each of R^b is independently selected from a group -L²-NR^cR^d; -L²-RING, where RING denotes a 5- or 6-member saturated heterocyclic ring containing 1 or 2 heteroatoms selected from nitrogen and oxygen, optionally substituted, as indicated below, halogen; hydroxy; amino; cyano, and a straight or branched C₁-C₄alkyl optionally substituted with one or more halogens and/or one or two hydroxy groups, wherein the hydroxy and amino groups are in turn optionally substituted on at least one heteroatom with one or, if necessary, more C₁-C₇aliphatic groups, where L² denotes a direct bond, a link selected from a group comprising -O-, -S-, -C(O)-, -OC(O)-, -NR^aC(O)-, -C(O)-NR^a -OC(O)-NR^a, -NR^a-; or denotes a straight C₁-C₄alkyl which is optionally interrupted and/or ends in one terminal fragment or in two terminal fragments with the said link, and where R^c and R^d are each independently selected from a group comprising hydrogen and straight or branched C₁-C₄alkyl, or R^c and R^d together with a neighbouring nitrogen atom form a 5- or 6-member heterocyclic ring which optionally contains an additional heteroatom selected from nitrogen and oxygen, and optionally substituted as indicated below, said optionally substituted rings are independently substituted with 0, 1, 2, 3, 4 or 5 C₁-C₇aliphatic substitutes which are optionally substituted with one or more halogen atoms; R² denotes hydrogen or C₁-C₄alkyl; R³ denotes hydrogen or straight or branched C₁-C₄alkyl or straight C₁-C₄alkyl substituted with a 5- or 6-member saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatoms in the ring, selected from nitrogen, oxygen and sulphur; R⁴ is selected from hydroxy, protected hydroxy group, alkoxy, alkyl, trifluoromethyl and halogen, where the alkyl or alkyl part of the alkoxy is straight or branched and contains 1, 2, 3 or 4 carbon atoms; or R⁵ denotes hydrogen or C₁-C₄alkyl; or pharmaceutically acceptable salts, hydrates, solvates, ethers, N-oxides thereof, optionally in form of trans-isomers thereof.

EFFECT: improved properties of the compound.

38 cl, 1 tbl, 231 ex