6,6-BICYCLIC RING SUBSTITUTED HETEROBICYCLIC PROTEINKINASE INHIBITORS Russian patent published in 2010 - IPC C07D471/04 A61K31/4375 A61K31/4985 A61P35/00 

FIELD: medicine.

SUBSTANCE: invention concerns compounds of general formula I or to their pharmaceutically acceptable salts, where X₁ - CH; X₂ - N or CH; Q¹ represents ,

where X₁₁ - CH or C-halogen; X₁₂ - CH, C-halogen or C-CF₃; X₁₃ - CH; X₁₄ - C-E¹¹, and E¹¹ represents C_0-10alkyl or C_0-10alkoxy; X₁₅ - CH or N; X₁₆ - N or N⁺ -0; G¹ - phenyl or 5-6-members unsaturated ring containing one heteroatom N or S; R¹ - C_0-10alkyl, cycloC_3-10alkyl or piperidinyl, any of which is optionally substituted with 1-2 independent substitutes G¹¹, or R¹ represents phenyl; G¹¹ is chosen from: OR²¹ where R²¹ represents C_0-10alkyl; -oxo; -cycloC_3-8alkyl; -C_0-10alkyl optionally substituted with group N(C_0-10alkyl)(C_0-10alkyl) wherein C_0-10alkyl is optionally substituted with group N(C_0-10alkyl)C(O)C_0-10alkyl; group OR²²²¹, where R²²²¹ - C_0-10alkyl; group N(C_0-10alkyl)C(O)C_0-10alkyl; group N(C_0-10alkyl)SO₂(C_0-10alkyl); group -N(C_0-10alkyl)C(O)N(C_0-10alkyl)(C_0-10alkyl); group -N(C_0-10alkyl)C(=O)R³³³¹, where R³³³¹ - C_1-10alkoxy C_1-10alkyl or tetrahydrofuranyl; -N(R²¹)R³¹ where R²¹ and R³¹ independently represent C_0-10alkyl optionally substituted with thiophenyl, morphlinyl, furanyl; cycloC_3-8alkyl; C_1-10alkoxyC_1-10alkyl; tetrahydropyranyl; piperidylC_0-10alkyl; or piperidyl optionally substituted with C_0-10alkyl; or R²¹ and R³¹ optionally taken together with nitrogen atom whereto attached, form 3-10-members saturated ring optionally substituted with one or more independent substitutes G¹¹¹¹, and optionally including one or more heteroatoms different from nitrogen whereto R²¹ and R³¹ are attached; where G¹¹¹¹ - C_0-10alkyl optionally substituted with group OR⁷⁷ where R⁷⁷ - C_0-10alkyl, or G¹¹¹¹ represents C_1-10alkoxyC_1-10alkyl, pirimidinyl, pyrazinyl, imidazolylmethyl; C(O)N(R²¹)R³¹ where R²¹ and R³¹ independently represent C_0-10alkyl; -C(O)O(C_0-10alkyl); -C(O) C_0-10alkyl optionally substituted with N(C_0-10alkyl)(C_0-10alkyl) or halogen; -heterocyclylC_0-10alkyl where heterocyclyl represents 4-6-members saturated ring containing 1 or 2 heteroatoms, independently chosen from N, O or S optionally substituted with a substitute chosen from: 1) OR²²²¹, where R²²²¹ - pyrimidinyl or C_0-10lkyl; 2) C(O)OR²²²¹, where R²²²¹ - C_0-10alkyl or phenyl-C_0-10alkyl; 3) C(O)C_0-10alkyl optionally substituted with N(C_0-10alkyl)(C_0-10alkyl) or C_1-10alkoxy C_1-10alkyl; 4) C(O)N(C_0-10alkyl)(C_0-10alkyl); 5) S(O)₂C_0-10alkyl; 6) SO₂N(C_0-10alkyl)(C_0-10alkyl); 7) -NR²²²¹R³³³¹, where R²²²¹ and R³³³¹ taken together with nitrogen atom whereto attached, form pyrrolidinyl; or G¹¹ represents C, which taken together with carbon whereto attached, forms C=C double bond substituted with R⁵ and G¹¹¹ where R⁵ and G¹¹¹ are hydrogens. The invention also specifically concerns cys-3-[8-amino-1-(2-phenylquinoline-7-yl)-imidazo[1,5-α]pyrazine-3-yl]-1-methl-cyclobutanole or its pharmaceutically acceptable salt. The specified compounds and their pharmaceutically acceptable salts are applicable in treatment of conditions mediated by activity IGF-1R proteinkinase, particularly angiogenesis, vascular permeability, immune response, cell apoptosis, tumour growth or inflammation. The invention also concerns a pharmaceutical composition.

EFFECT: improved efficiency of the composition and method of treatment.

14 cl, 3 tbl, 171 ex