Substituted aminoquinoxalines as tyrosine threonine kinase inhibitors

摘要

The present invention relates to substituted aminoquinoxaline compounds of general formula (I) in which (II), R2, R3, R4, R6, R7, n and m are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.;

主权项

1. A compound of general formula (I):in which: represents a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocyclic ring, optionally further containing 1 heteroatom-containing group selected from O and NR1 in which R1 represents hydrogen, or a group selected from: C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, hydroxyl-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6—, aryloxy-C1-C6-alkyl-, C2-C10-alkenyl-, C2-C10-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C1-C6-alkylene-aryl, a 4- or 5-(1,3-benzodioxolinyl)- group, —C1-C6-alkylene-heteroaryl, C1-C6-alkylene-aryl-, C1-C6-alkylene-heteroaryl-, —C1-C6-alkylene-C3-C10-cycloalkyl, —C1-C6-alkylene-(3- to 10-membered heterocycloalkyl), —C(═O)R8, —C(═O)O—C1-C6-alkyl, —C(═O)O—C3-C10-cycloalkyl, —C(═O)NR9R10, —S(═O)R8, —S(═O)2R8, —S(═O)2NR9R10; wherein said group is optionally substituted one or more times, identically or differently, with a substituent selected from: halo-, hydroxyl-, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C10-alkenyl-, C2-C10-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, C1-C6-alkylene-aryl-, C1-C6-alkylene-heteroaryl-, —C1-C6-alkylene-C3-C10-cycloalkyl, —C1-C6-alkylene-(3- to 10-membered heterocycloalkyl), —OR8, —C(═O)H, —C(═O)R8—, C(═O)OH, —C(═O)O—C1-C6-alkyl, —C(═O)O—C3-C10-cycloalkyl, —OC(═O)—C1-C6-alkyl, —OC(═O)—C3-C10-cycloalkyl, —N(H)C(═O)R8, —N(C1-C6-alkyl)C(═O)R8, —N(H)S(═O)2R8, —N(C1-C6-alkyl)S(═O)2R8, —C(═O)NR9R10, —OC(═O)NR9R10, —N(H)C(═O)OR8, —N(C1-C6-alkyl)C(═O)OR8, —N(H)C(═O)NR9R10, —N(C1-C6-alkyl)C(═O)NR9R10, —SR8, —S(═O)R8, —S(═O)2R8, —S(═O)2NR9R10, —NR9R10; R1 and R7 can form together a 5-7 membered ring which is optionally substituted with ═O; R2, R3, R4, R6, represent hydrogen; R5, R7 represent, independently from each other, a substituent selected from hydrogen, halo-, hydroxyl-, cyano-, nitro-, or a substituent group selected from: C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C10-alkenyl-, C2-C10-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C1-C6-alkylene-aryl, C1-C6-alkylene-aryl-, C1-C6-alkylene-heteroaryl-, —C1-C6-alkylene-C3-C10-cycloalkyl, —C1-C6-alkylene-(3- to 10-membered heterocycloalkyl), —OR8, —C(═O)H, —C(═O)R8, —C(═O)OH, —C(═O)O—C1-C6-alkyl, —C(═O)O—C3-C10-cycloalkyl, —OC(═O)—C1-C6-alkyl, —OC(═O)—C3-C10-cycloalkyl, —N(H)C(═O)R8, —N(C1-C6-alkyl)C(═O)R8, —N(H)S(═O)2R8, —N(C1-C6-alkyl)S(═O)2R8, —C(═O)NR9R10, —OC(═O)NR9R10, —N(H)C(═O)OR8, —N(C1-C6-alkyl)C(═O)OR8, —N(H)C(═O)NR9R10, —N(C1-C6-alkyl)C(═O)NR9R10, —SR8, —S(═O)R8, —S(═O)2R8, —S(═O)2NR9R10, —NR9R10; wherein, when m or n represent, independently from each other, an integer of 2, or 3, then said substituent or substituent group is, independently from each other, identical or different; wherein said substituent group is optionally substituted one or more times, identically or differently, with a substituent selected from: halo-, hydroxyl-, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C10-alkenyl-, C2-C10-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, a 4- or 5-(1,3-benzodioxolinyl)- group, C1-C6-alkylene-aryl-, C1-C6-alkylene-heteroaryl-, —C1-C6-alkylene-C3-C10-cycloalkyl, —C1-C6-alkylene-(3- to 10-membered heterocycloalkyl), —C(═O)H, —C(═O)—C1-C6-alkyl, C(═O)OH, —C(═O)O—C1-C6-alkyl, —C(═O)O—C3-C10-cycloalkyl, —OC(═O)—C1-C6-alkyl, —OC(═O)—C3-C10-cycloalkyl, —N(H)C(═O)—C1-C6-alkyl, —N(C1-C6-alkyl)C(═O)—C1-C6-alkyl, —N(H)S(═O)2—C1-C6-alkyl, —N(C1-C6-alkyl)S(═O)2—C1-C6-alkyl, —C(═O)NH2, —C(═O)N(H)C1-C6-alkyl, —C(═O)N(C1-C6-alkyl)2, —OC(═O)N(H)C1-C6-alkyl, —OC(═O)N(C1-C6-alkyl)2, —N(H)C(═O)O—C1-C6-alkyl, —N(C1-C6-alkyl)C(═O)O—C1-C6-alkyl, —N(H)C(═O)NH2, —N(H)C(═O)N(H)C1-C6-alkyl, —N(H)C(═O)N(C1-C6-alkyl)2, —N(C1-C6-alkyl)C(═O)NH2, —N(C1-C6-alkyl)C(═O)N(H)C1-C6-alkyl, —N(C1-C6-alkyl)C(═O)N(C1-C6-alkyl)2, —S—C1-C6-alkyl, —S(═O) —C1-C6-alkyl, —S(═O)2—C1-C6-alkyl, —S(═O)2NH2, —S(═O)2N(H)C1-C6-alkyl, —S(═O)2N(C1-C6-alkyl)2, —NH2, —N(H)C1-C6-alkyl, —N(C1-C6-alkyl)2; R8 represents a group selected from: C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, hydroxy-C1-C6-alkyl, C2-C10-alkenyl-, C2-C10-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, C1-C6-alkylene-aryl-, C1-C6-alkylene-heteroaryl-, —C1-C6-alkylene-C3-C10-cycloalkyl, —C1-C6-alkylene-aryl, —C1-C6-alkylene-heteroaryl, —C1-C6-alkylene-(3- to 10-membered heterocycloalkyl), —NR9R10; wherein said group is optionally substituted one or more times, identically or differently, with a substituent selected from: halo-, hydroxyl-, cyano-, nitro-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C10-alkenyl-, C2-C10-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, C1-C6-alkylene-aryl-, C1-C6-alkylene-heteroaryl-, —C1-C6-alkylene-C3-C10-cycloalkyl, —C1-C6-alkylene-(3- to 10-membered heterocycloalkyl), —C(═O)H, —C(═O)R11—, C(═O)OH, —C(═O)O—C1-C6-alkyl, —C(═O)O—C3-C10-cycloalkyl, —OC(═O)—C1-C6-alkyl, —OC(═O)—C3-C10-cycloalkyl, —N(H)C(═O)R11, —N(C1-C6-alkyl)C(═O)R11, —N(H)S(═O)2R11, —N(C1-C6-alkyl)S(═O)2R11, —C(═O)NR9R10, —OC(═O)NR9R10, —N(H)C(═O)OR11, —N(C1-C6-alkyl)C(═O)OR11, —N(H)C(═O)NR9R10, —N(C1-C6-alkyl)C(═O)NR9R10, —SR11, —S(═O)R11, —S(═O)2R11, —S(═O)2NR9R10, —NR9R10; R9, R10 represent independently from each other hydrogen, or a group selected from: C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C10-alkenyl-, C2-C10-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C1-C6-alkylene-aryl, C1-C6-alkylene-aryl-, C1-C6-alkylene-heteroaryl-, —C1-C6-alkylene-C3-C10-cycloalkyl, —C1-C6-alkylene-(3- to 10-membered heterocycloalkyl), R9 and R10 can form together a 5-7 saturated or partially unsaturated heterocyclic ring, which optionally further contains 1 heteroatom-containing group selected from O; R11 represents C1-C6-alkyl-; n, m represent, independently from each other, an integer of 0, 1, 2, or 3; or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.