PYRROLOTRIAZINE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH ANGIOGENESIS Russian patent published in 2010 - IPC C07D487/04 A61K31/53 A61K31/5377 A61K31/496 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to pyrrolotriazines of formula (I) , where R¹ is selected from a group which includes phenyl, naphthyl, benzyl and heteroaryl, which denotes a mono- or bicyclic radical containing 5-10 ring atoms and up to 2 heteroatoms selected from a group consisting of nitrogen, oxygen and sulphur, at least one ring of which is aromatic, where, if necessary, phenyl and heteroaryl may be substituted with 0, 1 or 2 substitutes independently selected from a group consisting of -(C₁-C₄)alkyl, where -(C₁-C₄)alkyl can be substituted with 0, 1, 2 or 3 halogens, 0 or 1 pyrrolidine, -(C₁-C₃)alkoxy group, where, if necessary, the (C₁-C₃)alkoxy group may be substituted with a (C1-C3)alkylamino group, halogen, trifluoromethyl, trifluoromethoxy group, phenyl, if necessary substituted with 1 or 2 halogens, - , where X denotes O, nitro group, - (C₁-C₃)alkylthio group, trifluoromethylthio group, - (C₁-C₃)alkylcarbonyl, - (C₁-C₆)alkoxycarbonyl, and a phenoxy group, and where the benzyl can be substituted with 0, 1, 2 or 3 groups selected from a group which includes halogen; R² is selected from a group consisting of hydrogen, halogen; R³ is selected from a group consisting of carboxyl, - (C₁-C₆)alkylcarbonyl, - (C₃-C₆)cycloalkylcarbonyl, - (C₁-C₆)alkoxycarbonyl, if necessary substituted with 0, 1, 2 or 3 groups selected from a group which includes amino group and (C₁-C₆)alkoxycarbonyl; aminocarbonyl, -(C₁-C₆)alkylaminocarbonyl, where (C₁-C₆)alkylaminocarbonyl which, if necessary, can be substituted with 0, 1, 2 or 3 substitutes independently selected from a group consisting of (C₃-C₆)cycloalkyl, halogen, amino group, (C₁-C₆)alkylamino group, hydroxy group, (C₁-C₆)alkoxy group, (C₁-C₆))alkoxycarbonyl, (C₁-C₆)alkylthio group, (C₁-C₆)alkoxycarbonylamino group,and where, if necessary, (C₁-C₆)alkylaminocarbonyl may be substituted with 0 or 1 heterocyclyl, which denotes a monocyclic, non-aromatic radical containing 5-8 ring atoms and up to 2 heteroatoms selected from nitrogen and oxygen, where, if necessary, the hetecyclyl may be substituted with 0 or 1 (C₁-C₆)alkyl, heterocyclylcarbonyl, if necessary substituted with 0 or 1 (C₁-C₆)alkylamino group, cycloalkyl or (C₁-C₆)alkyl,where, if necessary, (C₁-C₆)alkyl may be substituted with 0 or 1 (C₁-C₆)alkylamino group, and where heterocyclyl denotes a monocyclic, non-aromatic radical containing 5-8 ring atoms and up to 2 heteroatoms selected from nitrogen and oxygen, -(C₁-C₆)alkyl if necessary substituted with 0, 1 or 2 substitutes independently selected from a group consisting of a) hydroxyl, b) (C₁-C₆)alkylamino group, where (C₁-C₆)alkylamino group may be substituted with 0, 1 or 3 substitutes independently selected from a group consisting of halogen, alkylamino group, methoxy group, methylthio group and methylsulphonyl, c) phenylamino group, where the phenylamino group may be substituted with 0, 1 or 2 substitutes independently selected from a group consisting of (C₁-C₆)alkoxy group and trifluoromethyl, d) heterocyclyl, where heterocyclyl denotes a monocyclic, non-aromatic radical containing 5-8 ring atoms and up to 2 heteroatoms selected from nitrogen and oxygen, and where the heterocyclyl may be substituted with 0 or 1 (C₁-C₆)alkyl, where (C₁-C₆)alkyl may be substituted with 0 or 1 methoxy groups or pyridyls, e) imidazolyl, f) pyridylamino group, g) (C₁-C₃)alkoxy group, if necessary substituted with fluorine or piperidine,where, if necessary, the piperidine may be substituted with 0 or 1 (C₁-C₆)alkyl, h) (C₁-C₃)alkoxy(C₂-C₃)alkoxy group, and i) (C₁-C₆)alkoxycarbonyl, j) (C₃-C₆)cycloalkyl, k) cyano group, - (C₃-C₆)cycloalkylaminocarbonyl, cyano group, heteroaryl, where heteroaryl denotes a monocyclic radical containing 5-6 ring atoms and up to 3 heteroatoms selected from a group consisting of nitrogen and oxygen, the ring of which is aromatic, where the heteroaryl may be substituted with 0, 1 or 2 groups independently selected from a group consisting of q) (C₁-C₆)alkyl, where the (C₁-C₆)alkyl may be substituted with 0 or 1 morpholine or 0 or 1 hydroxy group, r) (C₁-C₆)alkoxycarbonyl, thiophene carbonyl, and R4 is selected from a group consisting of hydrogen; to a pharmaceutically acceptable salt thereof. The invention also pertains to methods of obtaining said compounds.

EFFECT: obtaining novel compounds which can be used in medicine for preventing or treating hyper-proliferative disorders and diseases associated with angiogenesis.

5 cl, 313 ex