US 2015/0087631 A1 · AMINO-SUBSTITUTED IMIDAZOPYRIDAZINES

Abstract

The present invention relates to amino-substituted imidazopyridazine compounds of general formula (I), in which A, R1, R2, R3, R4, R5 and n are as defined in the claims, 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.

A compound of general formula (I):

in which:
represents a:
wherein * indicates the point of attachment of said group with the rest of the molecule;
and
R1 represents a linear C1-C6-alkyl-, a branched C3-C6-alkyl-, or a C3-C6-cycloalkyl group which is optionally substituted, one or more times, independently from each other, with a substituent selected from:
a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, aryl-, —C(═O)NH2, —C(═O)N(H)R′, —C(═O)N(R′)R″, —C(═O)OH, —C(═O)OR′, —NH2, —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O)2R′, —N(R′)S(═O)2R′, —N═S(═O)(R′)R″, —OH, C1-C6-alkoxy-, C1-C6-haloalkoxy-, —OC(═O)R′, —OC(═O)NH2, —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C1-C6-alkyl-S—, —S(═O)R′, —S(═O)2R′, —S(═O)2NH2, —S(═O)2NHR′, —S(═O)2N(R′)R″ group;
R2 represents a hydrogen atom;
R3 represents a substituent selected from:
a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, —C(═O)R′, —C(═O)NH2, —C(═O)N(H)R′, —C(═O)N(R′)R″, —NH2, —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)C(═O)NH2, —N(H)C(═O)NHR′, —N(H)C(═O)N(R′)R″, —N(R′)C(═O)NH2, —N(R′)C(═O)NHR′, —N(R′)C(═O)N(R′)R″, —N(H)C(═O)OR′, —N(R′)C(═O)OR′, —NO2, —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O)2R′, —N(R′)S(═O)2R′, —N═S(═O)(R′)R″, —OH, C1-C6-haloalkoxy-, —OC(═O)R′, —SH, C1-C6-alkyl-S—, —S(═O)R′, —S(═O)2R′, —S(═O)2NH2, —S(═O)2NHR′, —S(═O)2N(R′)R″, —S(═O)(═NR′)R″ group;
R4 represents a substituent selected from:
a hydrogen atom, a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-optionally substituted one or more times, independently from each other, with an R substituent;
heteroaryl- optionally substituted one or more times, independently from each other, with an R substituent;
—C(═O)NH2, —C(═O)N(H)R′, —C(═O)N(R′)R″, —C(═O)OR′, —NH2, —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)C(═O)NH2, —N(H)C(═O)NHR′, —N(H)C(═O)N(R′)R″, —N(R′)C(═O)NH2, —N(R′)C(═O)NHR′, —N(R′)C(═O)N(R′)R″, —N(H)C(═O)OR′, —N(R′)C(═O)OR′, —NO2, —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O)2R′, —N(R′)S(═O)2R′, —N═S(═O)(R′)R″, —OH, C1-C6-alkoxy-, C1-C6-haloalkoxy-, —OC(═O)R′, —OC(═O)NH2, —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C1-C6-alkyl-S—, —S(═O)R′, —S(═O)2R′, —S(═O)2NH2, —S(═O)2NHR′, —S(═O)2N(R′)R″, —S(═O)(═NR′)R″ group;
R represents a substituent selected from:
a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C(═O)R′, —C(═O)NH2, —C(═O)N(H)R′, —C(═O)N(R′)R″, —C(═O)OR′, —NH2, —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)C(═O)NH2, —N(H)C(═O)NHR′, —N(H)C(═O)N(R′)R″, —N(R′)C(═O)NH2, —N(R′)C(═O)NHR′, —N(R′)C(═O)N(R′)R″, —N(H)C(═O)OR′, —N(R′)C(═O)OR′, —NO2, —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O)2R′, —N(R′)S(═O)2R′, —N═S(═O)(R′)R″, —OH, C1-C6-haloalkoxy-, —OC(═O)R′, —OC(═O)NH2, —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C1-C6-alkyl-S—, —S(═O)R′, —S(═O)2R′, —S(═O)2NH2, —S(═O)2NHR′, —S(═O)2N(R′)R″, —S(═O)(═NR′)R″group;
R′ and R″ represent, independently from each other, a substituent selected from:
a C1-C6-alkyl-, C3-C10-cycloalkyl-, C1-C6-haloalkyl group;
R5 represents:
either:
a substituent selected from a C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, C3-C10-cycloalkyl-C1-C6-alkyl-, aryl-, —C(═O)NH2, —C(═O)N(H)R′, —C(═O)N(R′)R″, —S(═O)R′, —S(═O)2R′ group;
or:
together, with the nitrogen atom to which it is bound, and with a carbon atom of R1, form a 3- to 7-membered cyclic secondary amine group, which is optionally substituted with a substituent selected from:
a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, aryl-, —C(═O)NH2, —C(═O)N(H)R′, —C(═O)N(R′)R″, —C(═O)OH, —C(═O)OR′, —NH2, —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O)2R′, —N(R′)S(═O)2R′, —N═S(═O)(R′)R″, —OH, C1-C6-haloalkoxy-, —OC(═O)R′, —OC(═O)NH2, —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C1-C6 alkyl-S—, —S(═O)R′, —S(═O)2R′, —S(═O)2NH2, —S(═O)2NHR′, —S(═O)2N(R′)R″ group;
n represents an integer of 0, 1, 2, 3, 4 or 5;
or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

22 more elements

Amino-substituted imidazopyridazines

Life of this patent

Amino-substituted imidazopyridazines

Life of this patent

Abstract

Claims18