Substituted aminoimidazopyridazines

Patent metadata

Field	Value
Publication number	US-9730929-B2
Application number	US-201214123511-A
Country	US
Kind code	B2
Filing date	May 30, 2012
Priority date	Jun 1, 2011
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

The present invention relates to substituted aminoimidazopyridazine compounds of general formula (I): in which A, R1, R2, R3 and R4 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:
A represents a group selected from:

wherein one or more R3 substituents, independent from each other, is (are) present in any position of the A group; and
wherein * indicates the point of attachment of said groups with the rest of the molecule R1 represents a C 1 -C 6 -alkyl-group,
said group being substituted with one or more —OH groups and optionally substituted with one or more substituents independently selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, aryl-substituted with one or more R substituents, 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)H, —N(H)C(═O)R′, —N(R′)C(═O)H, —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′, —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O)NH 2 , —N(H)S(═O)NHR′, —N(H)S(═O)N(R′)R″, —N(R′)S(═O)NH 2 , —N(R′)S(═O)NHR′, —N(R′)S(═O)N(R′)R″,
—N(H)S(═O) 2 R′, —N(R′)S(═O) 2 R′, —N═S(═O)(R′)R″, —OH, C 1 -C 6 -alkoxy-, —OC(═O)R′, —OC(═O)NH 2 , —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C 1 -C 6 -alkyl-S—, —S(═O) 2 NH 2 , —S(═O) 2 NHR′, —S(═O) 2 N(R′)R″, —S(═O)(═NR′)R″, —S(═O)R′, —S(═O) 2 R′ group;
R2 represents a C 1 -C 6 -alkyl-group or a C 3 -C 10 -cycloalkyl-group, wherein C 1 -C 6 -alkyl-, or C 3 -C 10 -cycloalkyl- is optionally substituted one or more times with a substituent selected from:
-Hal, or an —OH, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-group;
R3 represents a substituent selected from:
a hydrogen atom, 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;
R4 represents a substituent selected from:
a hydrogen atom, 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)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 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)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-;
or a stereoisomer, a tautomer, or a salt thereof, or a mixture of same.

2. The compound according to claim 1 , wherein:
A represents a group selected from:

wherein one or more R3 substituents, independent from each other, is (are) present in any position of the A group; and
wherein * indicates the point of attachment of said groups with the rest of the molecule;
R1 represents a C 1 -C 6 -alkyl-group,
said group being substituted with one or more —OH groups and optionally substituted with one or more substituents independently selected from:
a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, aryl-substituted with one or more R substituents, 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)H, —N(H)C(═O)R′, —N(R′)C(═O)H, —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′, —N(H)S(═O)R′, —N(R′)S(═O)R′, —N(H)S(═O)NH 2 , —N(H)S(═O)NHR′, —N(H)S(═O)N(R′)R″, —N(R′)S(═O)NH 2 , —N(R′)S(═O)NHR′, —N(R′)S(═O)N(R′)R″, —N(H)S(═O) 2 R′, —N(R′)S(═O) 2 R′, —N═S(═O)(R′)R″, —OH, C 1 -C 6 -alkoxy-, —OC(═O)R′,
—OC(═O)NH 2 , —OC(═O)NHR′, —OC(═O)N(R′)R″, —SH, C 1 -C 6 -alkyl-S—, —S(═O) 2 NH 2 , —S(═O) 2 NHR′, —S(═O) 2 N(R′)R″, —S(═O)(═NR′)R″, —S(═O)R′, —S(═O) 2 R′ group;
R2 represents a C 1 -C 6 -alkyl-group or a C 3 -C 10 -cycloalkyl-group, wherein C 1 -C 6 -alkyl-, or C 3 -C 10 -cycloalkyl- is optionally substituted with one or more substituents independently selected from:
-Hal, or an —OH, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-group;
R3 represents a substituent selected from:
a hydrogen atom, 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;
R4 represents a substituent selected from:
a hydrogen atom, 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)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 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)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)

Assignees

• Eis Knut
• Pühler Florian
• Zorn Ludwig
• Scholz Arne
• Lienau Philip
• Gnoth Mark Jean
• Bömer Ulf
• Günther Judith
• Fanghänel Jörg
• Korr Daniel
• Bayer Ip Gmbh

Inventors

• Eis Knut
• Pühler Florian
• Zorn Ludwig
• Scholz Arne
• Lienau Philip
• Gnoth Mark Jean
• Bömer Ulf
• Günther Judith
• Fanghänel Jörg
• Korr Daniel

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title