NOVEL COMPOUNDS FOR THE TREATMENT OF CANCER

摘要

The present invention relates to novel compounds showing an inhibitory effect on Mps-1 kinase, 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 formula (I): in which: A is selected from: wherein * represents the point of attachment to the nitrogen atom and ** represents the point of attachment to the R1 group; R1 represents a phenyl-group
which is substituted, one or more times, identically or differently, with a substituent selected from:—OH, —N(H)C(═O)R6, —N(R7)C(═O)R6, —N(H)C(═O)NR6R7, —N(R7)C(═O)NR6R7, —NH2, —NR6R7, —C(═O)N(H)R6, and —C(═O)NR6R7;andwhich is optionally substituted, one or more times, identically or differently, with a C1-C6-alkyl-group; R2 represents a hydrogen atom or a group selected from phenyl-, and pyridyl-;
said group being substituted, one or more times, identically or differently, with a substituent selected from:halo-, hydroxy-, 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-,R9—, R9—(C1-C6-alkyl)-, R9—(CH2)n(CHOH)(CH2)m—, R9—(C1-C6-alkoxy)-, R9—(CH2)n(CHOH)(CH2)p—O—, R9—(C1-C6-alkoxy-C1-C6-alkyl)-, R9—(C1-C6-alkoxy-C1-C6-alkyl)-O—, —O—(CH2)n—C(═O)NR9R7, R9—O—, —C(═O)R9, —C(═O)O—R9, —OC(═O)—R9, —N(H)C(═O)R9, —N(R7)C(═O)R9, —N(H)C(═O)NR9R7, —N(R7)C(═O)NR9R7, —NR9R7, —C(═O)N(H)R9, —C(═O)NR9R7, R9—S—, R9—S(═O)—, R9—, —S(═O)2—, —N(H)S(═O)R9, —N(R7)S(═O)R9, —S(═O)N(H)R9, —S(═O)NR9R7, —N(H)S(═O)2R9, —N(R7)S(═O)2R9, —S(═O)2N(H)R9, —S(═O)2NR9R7, —S(═O)(═NR9)R7, —S(═O)(═NR7)R9 and —N═S(═O)(R9)R7; or R2 represents a group selected from: wherein * indicates the point of attachment of said group with the rest of the molecule; B represents a 4- to 6-membered heterocyclic ring; which is optionally substituted, one or more times, identically or differently, with halo-, —CN, —OH, 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-, R8—(C1-C6-alkoxy)-, R8—O—, —NR8R7, R8—S—, R8—S(═O)—, R8—S(═O)2—, or (C3-C6-cycloalkyl)-(CH2)n—O—; C represents a 4- to 6-membered heterocyclic ring; which is optionally substituted, one or more times, identically or differently, with halo-, —CN, —OH, 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-, R8—(C1-C6-alkoxy)-, R8—O—, —NR8R7, R8—S—, R8—S(═O)—, R8—S(═O)2—, or (C3-C6-cycloalkyl)-(CH2)n—O—; each R5a independently represents a group selected from:halo-, 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-, R8—(C1-C6-alkoxy)-, R8—O—, —NR8R7, R8—S—, R8—S(═O)—, R8—S(═O)2—, and (C3-C6-cycloalkyl)-(CH2)n—O—; R6 represents a group selected from:
C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —(CH2)q—(C3-C6-cycloalkyl), —(CH2)q-heteroaryl, —(CH2)q-(3- to 10-membered heterocycloalkyl), and —(CH2)q-aryl;said group being optionally substituted, one or more times, identically or differently, with a substituent selected from:halo-, hydroxy-, 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-, R8—(C1-C6-alkyl)-, R8—(CH2)n(CHOH)(CH2)m—, R8—(C1-C6-alkoxy)-, R8—(CH2)n(CHOH)(CH2)p—O—, R8—(C1-C6-alkoxy-C1-C6-alkyl)-, R8—(C1-C6-alkoxy-C1-C6-alkyl)-O—, aryl-, R8—O—, —C(═O)R8, —C(═O)O—R8, —OC(═O)—R8, —N(H)C(═O)R8, —N(R7)C(═O)R8, —N(H)C(═O)NR8R7, —N(R7)C(═O)NR8R7, —NR8R7, —C(═O)N(H)R8, —C(═O)NR8R7, R8—S—, R8—S(═O)—, R8 —S(═O)2—, —N(H)S(═O)R8, —N(R7)S(═O)R8, —S(═O)N(H)R8, —S(═O)NR8R7, —N(H)S(═O)2R8, —N(R7)S(═O)2R8, —S(═O)2N(H)R8, —S(═O)2NR8R7, —S(═O)(═NR8)R7, —S(═O)(═NR7)R8, and —N═S(═O)(R8)R7; R7 represents a hydrogen atom, a C1-C6-alkyl-, or C3-C6-cycloalkyl-group; or R6 and R7,
together with the nitrogen atom to which they are attached, represent a 3- to 10-membered heterocycloalkyl-group; R8 represents a hydrogen atom, a C1-C6-alkyl- or C3-C6-cycloalkyl-group; R9 represents a C1-C6-alkyl- or C3-C6-cycloalkyl-group; or R9 and R7,
together with the nitrogen atom to which they are attached, represent a 3- to 10-membered heterocycloalkyl-group, which is optionally substituted with halogen; n, m, and p
represent, independently from each other, an integer of 0, 1, 2, 3, 4, or 5; q represents an integer of 0, 1, 2 or 3; and t represents an integer of 0, 1 or 2; or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.