Imidazopyridazines as Akt kinase inhibitors

摘要

The present invention relates to a method for the treatment of a cancer that is sensitive to Pi3K/Akt pathway inhibition by administering a therapeutically effective amount of a compound of formula (I);

主权项

1. A method for the treatment of a cancer that is responsive to inhibition of an AKT kinase in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) in which R1 is hydrogen, hydroxy, NR5R6, halogen, cyano, CO(NR8R9), C(O)OR8, C(O)(1-6C-alkyl), NHC(O)(1-6C-alkyl), NHS(O)2R11, NHC(O)NHR11, —S(O)n-1-6C-alkyl, —S(O)2NR5R6 or a group selected from 1-6C-alkyl, 1-6C-alkoxy, 3-7C-cycloalkyl, aryl, heteroaryl, -(1-6C-alkyl)-aryl, -(1-6C-alkyl)-heteroaryl, —O-(3-7C-cycloalkyl), —O-aryl, —O-(3-7C-heterocyclyl), —O-heteroaryl, —O-(1-6C-alkyl)-heteroaryl, —O-(1-6C-alkyl)-(3-7C-heterocyclyl), —O-(1-6C-alkyl)-aryl, 2-6C-alkenyl, 2-6C-alkynyl,
wherein said group being optionally substituted, one or more times, identically or differently, with a substituent selected from:hydroxy, halogen, 1-6C-alkyl, 1-4C-haloalkyl, 1-6C-alkoxy, —NR8R9, cyano, —C(O)NR8R9, —C(O)OR10, —NHC(O)R11, —NHC(O)NHR11, —NHS(O)2R11, 3-7-cycloalkyl, 3-7C-heterocyclyl, aryl, R2 is hydrogen, hydroxy, NR5R6, halogen, cyano, CO(NR8R9), C(O)OR8, C(O)(1-6C-alkyl), NHC(O)(1-6C-alkyl), NHS(O)2R11, NHC(O)NHR11, —S(O)n-1-6C-alkyl, —S(O)2NR5R6 or a group selected from 1-6C-alkyl, 1-6C-alkoxy, 3-7C-cycloalkyl, aryl, heteroaryl, -(1-6C-alkyl)-aryl, -(1-6C-alkyl)-heteroaryl, —O-(3-7C-cycloalkyl), —O-aryl, —O-(3-7C-heterocyclyl), —O-heteroaryl, —O-(1-6C-alkyl)-heteroaryl, —O-(1-6C-alkyl)-(3-7C-heterocyclyl), —O-(1-6C-alkyl)-aryl, 2-6C-alkenyl, 2-6C-alkynyl,
wherein said group being optionally substituted, one or more times, identically or differently, with a substituent selected from:hydroxy, halogen, 1-6C-alkyl, 1-4C-haloalkyl, 1-6C-alkoxy, —NR8R9, cyano, —C(O)NR8R9, —C(O)OR10, —NHC(O)R11, —NHC(O)NHR11, —NHS(O)2R11, 3-7C-heterocyclyl, aryl, R3 is hydrogen, hydroxy, NR5R6, halogen, cyano, CO(NR8R9), C(O)OR8, C(O)(1-6C-alkyl), NHS(O)2R11, NHC(O)NHR11, —S(O)n-1-6C-alkyl, —S(O)2NR5R6 or a group selected from 1-6C-alkyl, 1-6C-alkoxy 3-7C-cycloalkyl, aryl, heteroaryl, -(1-6C-alkyl)-aryl, -(1-6C-alkyl)-heteroaryl, —O-(3-7C-cycloalkyl), —O-aryl, —O-(3-7C-heterocyclyl), —O-heteroaryl, —O-(1-6C-alkyl)-heteroaryl, —O-(1-6C-alkyl)-(3-7C-heterocyclyl), —O-(1-6C-alkyl)-aryl, NHC(O)(1-6C-alkyl), 2-6C-alkenyl, 2-6C-alkynyl,
wherein said group being optionally substituted, one or more times, identically or differently, with a substituent selected from:hydroxy, halogen, 1-6C-alkyl, 1-4C-haloalkyl, 1-6C-alkoxy, —NR8R9, cyano, —C(O)NR8R9, —C(O)OR10, —NHC(O)R11, —NHC(O)NHR11, —NHS(O)2R11, 3-7C-heterocyclyl, aryl, R4 is phenyl which is optionally substituted one, two or three times, identically or differently, with a halogen atom; R5 is hydrogen, 1-6C-alkyl, R6 is hydrogen, 1-6C-alkyl, R8 is hydrogen, 1-6C-alkyl which optionally is substituted with hydroxy, R9 is hydrogen, 1-6C-alkyl, R10 is hydrogen, 1-6C-alkyl, R11 is hydrogen, 1-6C-alkyl, X, Y is CH2; n is 0, 1, 2; or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer.