Amino-substituted imidazopyridazines

Patent metadata

Field	Value
Publication number	US-9499547-B2
Application number	US-201214342977-A
Country	US
Kind code	B2
Filing date	Sep 5, 2012
Priority date	Sep 6, 2011
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

The present invention relates to amino-substituted imidazopyridazine compounds of general formula (I): in which A, R1, R3 and n 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.

First claim

The invention claimed is:

1. A compound of general formula (I):

in which:
R1 represents a linear C 2 -C 6 -alkyl-, a linear C 1 -C 6 -alkyl-O -linear C 1 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl-, a C 3 -C 6 -cycloalkyl, a linear C 1 -C 6 -alkyl-C 3 -C 6 -cycloalkyl-or a C 3 -C 6 -cycloalkyl-linear C 1 -C 6 -alkyl-group which is optionally substituted, one or more times, independently from each other, with a substituent selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, Ci-C 6 -haloalkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 10 -cycloalkyl- which is optionally connected as spiro, a 3- to 10-membered heterocycloalkyl which is optionally connected as spiro, aryl-, aryl which is optionally substituted one or more times independently from each other with R, heteroaryl-, heteroaryl- which is optionally substituted one or more times independently from each other with R, —C(═O)NH 2 , —C(═O)N(H)R′,—C(═O)N(R′)R″,—C(═O)OH, —C(═O)OR′,—NH 2 , —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) 2 R′, —N(R′)S(═O) 2 R′, —N═S(═O)(R′)R″, —OH, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy-, —OC(═O)R′, —OC(═O)NH 2 , —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C 1 -C 6 -alkyl-S-, —S(═O)R′, —S(═O) 2 R′, —S(═O) 2 NH 2 , —S(═O) 2 NHR′, —S(═O) 2 N(R′)R″ group;

 represents a:

 group;
wherein * indicates the point of attachment of said group with the rest of the molecule; and
R3 represents a substituent selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, —C(═O)R′, —C(═O)NH 2 , —C(═O)N(H)R′,—C(═O)N(R′)R″, —NH 2 , —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)C(═O)NH 2 , —N(H)C(═O)NHR′, —N(H)C(═O)N(R′)R″, —N(R′)C(═O)NH 2 , —N(R′)C(═O)NHR′, —N(R′)C(═O)N(R′)R″, —N(H)C(═O)OR′, —N(R′)C(═O)OR′, —NO 2 , —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O) 2 R′, —N(R′)S(═O) 2 R′, —N═S(═O)(R′)R″, —OH, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy-, —OC(═O)R′, —SH, C 1 -C 6 -alkyl-S—, —S(═O)R′, —S(═O) 2 R′, —S(═O) 2 NH 2 , —S(═O) 2 NHR′, —S(═O) 2 N(R′)R″, —S(═O)(═NR′)R″ group;
R represents a substituent selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C(═O)R′, —C(═O)NH 2 , —C(═O)N(H)R′,—C(═O)N(R′)R″, —C(═O)OR′, —NH 2 , —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)C(═O)NH 2 , —N(H)C(═O)NHR′, —N(H)C(═O)N(R′)R″, —N(R′)C(═O)NH 2 , —N(R′)C(═O)NHR′, —N(R′)C(═O)N(R′)R″, —N(H)C(═O)OR′, —N(R′)C(═O)OR′, —NO 2 , —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O) 2 R′, —N(R′)S(═O) 2 R′, —N═S(═O)(R′)R″, —OH, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy-, —OC(═O)R′, —OC(═O)NH 2 , —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C 1 -C 6 -alkyl-S—, —S(═O)R′, —S(═O) 2 R′, —S(═O) 2 NH 2 , —S(═O) 2 NHR′, —S(═O) 2 N(R′)R″, —S(═O)(═NR′)R″ group;
R′ and R″ represent, independently from each other, a substituent selected from:
C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-;
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.

2. The compound according to claim 1 , wherein:
R1 represents a linear C 2 -C 6 -alkyl-, a linear C 1 -C 6 -alkyl-O-linear C 1 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl-, a C 3 -C 6 -cycloalkyl, a linear C 1 -C 6 -alkyl-C 3 -C 6 -cycloalkyl- or a C 3 -C 6 -cycloalkyl-linear C 1 -C 6 -alkyl- group which is optionally substituted, one or more times, independently from each other, with a substituent selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 10 -cycloalkyl- which is optionally connected as spiro, a 3- to 10-membered heterocycloalkyl which is optionally connected as spiro, aryl-, aryl which is optionally substituted one or more times independently from each other with R, heteroaryl-, heteroaryl- which is optionally substituted one or more times independently from each other with R, —C(═O)NH 2 , —C(═O)N(H)R′,—C(═O)N(R′)R″, —C(═O)OH, —C(═O)OR′, —NH 2 , —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) 2 R′, —N(R′)S(═O) 2 R′, —N═S(═O)(R′)R″, —OH, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy-, —OC(═O)R′, —OC(═O)NH 2 , —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C 1 -C 6 -alkyl-S—, —S(═O)R′, —S(═O) 2 R′, —S(═O) 2 NH 2 , —S(═O) 2 NHR′, —S(═O) 2 N(R′)R″ group;

 represents a:

 group;
wherein * indicates the point of attachment of said group with the rest of the molecule; and
R3 represents a substituent selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, —OH, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy- group;
R represents a substituent selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C(═O)R′, —C(═O)NH 2 , —C(═O)N(H)R′,—C(═O)N(R′)R″, —C(═O)OR′, —NH 2 , —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)C(═O)NH 2 , —N(H)C(═O)NHR′, —N(H)C(═O)N(R′)R″, —N(R′)C(═O)NH 2 , —N(R′)C(═O)NHR′, —N(R′)C(═O)N(R′)R″, —N(H)C(═O)OR′, —N(R′)C(═O)OR′, —NO 2 , —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O) 2 R′, —N(R′)S(═O) 2 R′, —N═S(═O)(R′)R″, —OH, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy-, —OC(═O)R′, —OC(═O)NH 2 , —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C 1 -C 6 -alkyl-S—, —S(═O)R′, —S(═O) 2 R′, —S(═O) 2 NH 2 , —S(═O) 2 NHR′, —S(═O) 2 N(R′)R″, —S(═O)(═NR′)R″ group;
R′ and R″ represent, independently from each other, a substituent selected from:
C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-;
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.

3. The compound according to claim 1 , wherein:
R1 represents a linear C 2 -C 5 -alkyl-, a linear C 1 -C 5 -alkyl-O-linear C 1 -C 5 -alkyl-, a branched C 3 -C 5 -alkyl-, a C 4 -C 6 -cycloalkyl, a linear C 1 -C 6 -alkyl-C 4 -C 6 -cycloalkyl- or a C 4 -C 6 -cycloalkyl-linear C 1 -C 6 -alkyl- group which is optionally substituted, one or more times, independently from each other, with a substituent selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 10 -cycloalkyl- which is optionally connected as spiro, a 3- to 10-membered heterocycloalkyl which is optionally connected as spiro, aryl-, aryl which is optionally substituted one or more times independently from each other with R, heteroaryl-, heteroaryl- which is optionally substituted one or more times independently from each other with R, —C(═O)NH 2 , —C(═O)N(H)R′, —C(═O)N(R′)R″, —C(═O)OH, —C(═O)OR′, —NH 2 , —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) 2 R′, —N(R′)S(═O) 2 R′, —N═S(═O)(R′)R″, —OH, C 1 -C 6 -alkoxy-, C 1 -C 6 -haloalkoxy-, —OC(═O)R′, —OC(═O)NH 2 , —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C 1 -C 6 -alkyl-S—, —S(═O)R′, —S(═O) 2 R′, —S(═O) 2 NH 2 , —S(═O) 2 NHR′, —S(═O) 2 N(R′)R″ group;

 represents a:

Assignees

• Eis Knut
• Puehler Florian
• Zorn Ludwig
• Scholz Arne
• Lienau Philip
• Gnoth Mark Jean
• Bömer Ulf
• Günther Judith
• Hitchcock Marion
• Bayer Ip Gmbh

Inventors

• Eis Knut
• Puehler Florian
• Zorn Ludwig
• Scholz Arne
• Lienau Philip
• Gnoth Mark Jean
• Bömer Ulf
• Günther Judith
• Hitchcock Marion

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title