SUBSTITUTED BENZIMIDAZOLES

摘要

The present invention relates to substituted benzimidazole compounds of general formula (I) in which R3, R5 and A are as defined in the claims, to methods of 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: A represents wherein * indicates the point of attachment of said groups with the rest of the molecule; Z represents a —C(═O)N(H)R1 or —C(═S)N(H)R1 group; R1 represents a hydrogen atom or a C1-C6-alkyl- or C3-C6-cycloalkyl-group;
wherein said C1-C6-alkyl- or C3-C6-cycloalkyl-group is optionally substituted, identically or differently, with 1, 2, 3 or 4 groups selected from: halogen, —OH, —CN, C1-C6-alkyl-, C1-C6-alkoxy-; R2 represents a hydrogen atom or a C1-C6-alkyl- or C3-C6-cycloalkyl-group;
wherein said C1-C6-alkyl- or C3-C6-cycloalkyl-group is optionally substituted, identically or differently, with 1, 2, 3 or 4 groups selected from: halogen, OH, —CN, C1-C6-alkyl-, C1-C6-alkoxy-; R3 represents a hydrogen atom or a halogen atom or a —CN, C1-C6-alkyl-, —(CH2)m—C2-C6-alkenyl, —(CH2)m—C4-C8-cycloalkenyl, —(CH2)m—C2-C6-alkynyl, —(CH2)m—C3-C6-cycloalkyl, —(CH2)m-(3- to 7-membered heterocycloalkyl), —(CH2)m-(4- to 8-membered heterocycloalkenyl), aryl-C1-C6-alkyl-, heteroaryl-C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C2-C6-alkenyl-, C4-C8-cycloalkenyl-, C2-C6-alkynyl-, aryl-, —C1-C6-alkyl-aryl, —C1-C6-alkyl-heteroaryl, heteroaryl-, C1-C6-alkyl-X—, —X—(CH2)m—C2-C6-alkenyl, —X—(CH2)m—C4-C8-cycloalkenyl, —X—(CH2)m—C2-C6-alkynyl, —X—(CH2)m—C3-C6-cycloalkyl, —X—(CH2)m-(3- to 7-membered heterocycloalkyl), —X—(CH2)m-(4- to 8-membered heterocycloalkenyl), aryl-X—, heteroaryl-X—, —C(═O)R6, —C(═O)N(H)R6a, —C(═O)N(R6a)R6b, —C(═O)O—R6, —N(R6a)R6b, —NO2, —N(H)C(═O)R6, —OR6, SR6, —S(═O)R6, —S(═O)2R6, —S(═O)(═NR6a)R6b, —S(═O)2N(R6b)R6c, —S—(CH2)n—N(R6a)R6b, or —S—(CH2)n-(3- to 7-membered heterocycloalkyl) group;
saidC1-C6-alkyl-, —(CH2)m—C2-C6-alkenyl, —(CH2)m—C2-C6-alkynyl, —(CH2)m—C3-C6-cycloalkyl, aryl-C1-C6-alkyl-, heteroaryl-C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C2-C6-alkenyl-, C4-C8-cycloalkenyl-, C2-C6-alkynyl-, aryl-, C1-C6-alkyl-X—, —X—(CH2)m—C2-C6-alkenyl, —X—(CH2)m—C4-C8-cycloalkenyl, —X—(CH2)m—C2-C6-alkynyl, —X—(CH2)m—C3-C6-cycloalkyl, —X—(CH2)m-(3- to 7-membered heterocycloalkyl), —X—(CH2)m-(4- to 8-membered heterocycloalkenyl), aryl-X—, heteroaryl-X—, —C1-C6-alkyl-aryl, —C1-C6-alkyl-heteroaryl or heteroaryl-group being optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R7 groups; R4a, R4b, R4c,
represent, independently from each other, a hydrogen or halogen atom, or a —CN, C1-C6-alkyl-, C1-C6-alkoxy-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, NC—C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-group; R5 represents a hydrogen atom or a C1-C6-alkyl-, —(CH2)n—C2-C6-alkenyl, —(CH2)n—C2-C6-alkynyl, —(CH2)m—C3-C6-cycloalkyl, —(CH2)m-(3- to 7-membered heterocycloalkyl), aryl-C1-C6-alkyl-, heteroaryl-C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, —C1-C6-alkyl-CN, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C4-C8-cycloalkenyl-, aryl- or heteroaryl-group;
saidC1-C6-alkyl-, —(CH2)n—C2-C6-alkenyl, —(CH2)n—C2-C6-alkynyl, —(CH2)m—C3-C6-cycloalkyl, —(CH2)m-(3- to 7-membered heterocycloalkyl), aryl-C1-C6-alkyl-, heteroaryl-C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, —C1-C6-alkyl-CN, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C3-C6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C4-C8-cycloalkenyl-, aryl- or heteroaryl-group being optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R8 groups; R6, R6a, R6b, R6c represent, independently from each other, a hydrogen atom or a C1-C6-alkyl-, HO—C1-C6-alkyl-, C3-C6-cycloalkyl-, C2-C6-alkenyl-, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, aryl-C1-C6-alkyl- or heteroaryl-C1-C6-alkyl-group; R7 represents a hydrogen or halogen atom or a HO—, —CN, C1-C6-alkoxy-, halo-C1-C6-alkoxy-, C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-, HO—C1-C6-alkyl-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, —C(═O)R6, —C(═O)N(H)R6a, —C(═O)N(R6a)R6b, —C(═O)O—R6, —N(R6a)R6b, —NO2, —N(H)C(═O)R6, —N(R6c)C(═O)R6, —N(H)C(═O)N(R6a)R6b, —N(R6c)C(═O)N(R6a)R6b, —N(H)C(═O)OR6, —N(R6c)C(═O)OR6, —N(H)S(═O)R6, —N(R6c)S(═O)R6, —N(H)S(═O)2R6, —N(R6c)S(═O)2R6, —N═S(═O)(R6a)R6b, —OR6, —O(C═O)R6, —O(C═O)N(R6a)R6b, —O(C═O)OR6, —SR6 SF5, —S(═O)R6, —S(═O)N(H)R6, —S(═O)N(R6a)R6b, —S(═O)2R6, —S(═O)2N(H)R6, —S(═O)2N(R6a)R6b or —S(═O)(═NR6c)R6 group;wherein said aryl- or heteroaryl-group is optionally substituted, identically or differently, with 1, 2 or 3 C1-C6-alkyl-groups;orwhen 2 R7 groups are present ortho- to each other on an aryl ring, said 2 R7 groups together form a bridge:*O(CH2)2O*, *O(CH2)O*, *NH(C(═O))NH*, wherein * represent the point of attachment to said aryl ring; R8 represents a hydrogen or halogen atom or a —CN, C1-C6-alkoxy-, C1-C6-alkyl-, halo-C1-C6-alkyl-, R6a(R6b)N—C1-C6-alkyl-HO—C1-C6-alkyl-C1-C6-alkoxy-C1-C6-alkyl-halo-C1-C6-alkoxy-C1-C6-alkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, 3- to 7-membered heterocycloalkyl-, aryl-,
heteroaryl-, —C(═O)R6, —C(═O)N(H)R6a, —C(═O)N(R6a)R6b, —C(═O)O—R6, —N(R6a)R6b, —NO2, —N(H)C(═O)R6, —N(R6c)C(═O)R6, —N(H)C(═O)N(R6a)R6b, —N(R6c)C(═O)N(R6a)R6b, —N(H)C(═O)OR6, —N(R6c)C(═O)OR6, —N(H)S(═O)R6, —N(R6c)S(═O)R6, —N(H)S(═O)2R6, —N(R6c)S(═O)2R6, —N═S(═O)(R6a)R6b, —OR6, —O(C═O)R6, —O(C═O)N(R6a)R6b, —O(C═O)OR6, —SR6, —S(═O)R6, —S(═O)N(H)R6, —S(═O)N(R6a)R6b, —S(═O)2R6, —S(═O)2N(H)R6, —S(═O)2N(R6a)R6b, —S(═O)(═NR6c)R6 or —S(═O)2-(3- to 7-membered heterocycloalkyl) group;wherein said 3- to 7-membered heterocycloalkyl- or heteroaryl-group, is optionally substituted, identically or differently, with 1, 2, 3 or 4 C1-C6-alkyl-groups; m is an integer of 0, 1, 2, 3, 4, 5, or 6; n is an integer of 0, 1, 2, 3, 4, or 5; and X is S, S(═O), S(═O)2, O, NR6, CR6aR6b, C(═CR6aR6b), C(═O) or C(OH)(R6a); or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.