Substituted pyrrolopyrimidinylamino-benzothiazolones as MKNK kinase inhibitors

摘要

The present invention relates to substituted pyrrolopyrimidinylamino-benzothiazolone compounds of general formula I as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

主权项

1. A compound of general formula I:in which:
R1a represents a hydrogen atom or a halogen atom or a hydroxy-, cyano-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, C3-C6-cycloalkyloxy-, (3- to 10-membered heterocycloalkyl)-O—, —NR5aR5b, —SCF3 or —SF5 group; R1b represents a hydrogen atom or a halogen atom or a hydroxy-, cyano-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, C3-C6-cycloalkyloxy-, (3- to 10-membered heterocycloalkyl)-O—, —NR5aR5b, —SCF3 or —SF5 group; R1c represents a hydrogen atom or a halogen atom or a hydroxy-, cyano-, C1-C6-alkyl-, halo-C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, C3-C6-cycloalkyloxy-, (3- to 10-membered heterocycloalkyl)-O—, —NR5aR5b, —SCF3 or —SF5 group; Y represents N or CR2a; Z represents N or CR2b; with the proviso that not more than one of Y and Z represents N; R2a represents a hydrogen atom or a halogen atom or a group selected from:
C1-C6-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl-, heteroaryl-, halo-C1-C3-alkyl-, cyano-, —(CH2)q—X—(CH2)p-R3;wherein said C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl- or heteroaryl-group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R4 groups; R2b represents a hydrogen atom or a halogen atom or a group selected from:
C1-C6-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl,heteroaryl-, halo-C 1-C3-alkyl-, cyano-, —(CH2)q—X—(CH2)p—R3;wherein said C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, 4- to 10-membered heterocycloalkenyl-, aryl- or heteroaryl-group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R4 groups; X represents a bond or a bivalent group selected from: —O—, —S—, —S(═O)—, —S(═O)2—, —S(═O)—(NR3a)—, —(NR3a)—S(═O)—, —C(═O)—, —(NR3a)—, —C(═O)—O—, —O—C(═O)—, —C(═S)—O—, —O—C(═S)—, —C(═O)—(NR3a)—, —(NR3a)—C(═O)—, —(NR3a)—C(═O)—(NR3b)—, —O—C(═O)—(NR3a)—, —(NR3a)—C(═O)—O—; R3 represents a hydrogen atom or a group selected from C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, halo-C1-C3-alkyl-;
wherein said C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R4 groups; R3a represents a hydrogen atom or a group selected from C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, halo-C1-C3-alkyl-;
wherein said C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R4 groups; R3b represents a hydrogen atom or a group selected from C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, halo-C1-C3-alkyl-;
wherein said C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R4 groups; or R3 together with R3a or R3b represent a 3- to 10-memberered heterocycloalkyl- or a 4- to 10-membered heterocycloalkenyl- group, which is optionally substituted, one or more times, identically or differently, with halo-, hydroxyl-, cyano-; R4 represents halo-, hydroxy-, oxo- (O═), cyano-, nitro-, C1-C6-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, 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-, R5—O—, —C(═O)—R5, —C(═O)—O—R5, —O—C(═O)—R5, —N(R5a)—C(═O)—R5b, —N(R5a)—C(═O)—NR5bR5c, —NR5aR5b, —C(═O)—NR5aR5b, R5—S—, R5—S(═O)—, R5—S(═O)2—, —N(R5a)—S(═O)—R5b, —S(═O)—NR5aR5b, —N(R5a)—S(═O)2—R5b, —S(═O)2—NR5aR5b, —S(═O)(═NR5a)R5b, —S(═O)(═NR5a)R5b or —N═S(═O)(R5a)R5b; R5 represents a hydrogen atom, a C1-C6-alkyl- or C3-C6-cycloalkyl- group; R5a represents a hydrogen atom, a C1-C6-alkyl- or C3-C6-cycloalkyl- group; R5b represents a hydrogen atom, a C1-C6-alkyl- or C3-C6-cycloalkyl- group; R5c represents a hydrogen atom, a C1-C6-alkyl- or C3-C6-cycloalkyl- group; or R5a and R5b together may form a C2-C6-alkylene group, in which optionally one methylene can be replaced by —O—, —C(═O)—, —NH—, or —N(C1-C4-alkyl)-; or R5a and R5ctogether may form a C2-C6-alkylene group, in which optionally one methylene can be replaced by —O—, —C(═O)—, —NH—, or —N(C1-C4-alkyl)-; or R5b and R5c together may form a C2-C6-alkylene group, in which optionally one methylene can be replaced by —O—, —C(═O)—, —NH—, or —N(C1-C4-alkyl)-; p represents an integer of 0, 1, 2 or 3; q represents an integer of 0, 1, 2 or 3; or a tautomer, a hydrate, a solvate, or a salt thereof, or a mixture of same.