Heterocyclyl aminoimidazopyridazines

Patent metadata

Field	Value
Publication number	US-9284319-B2
Application number	US-201214129043-A
Country	US
Kind code	B2
Filing date	Jun 21, 2012
Priority date	Jun 22, 2011
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

The present invention relates to heterocyclyl 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;

represents a group selected from:

said group being substituted with one or more substituents independently selected from an —OH group and a HO—C 1 -C 6 -alkyl-, and
wherein * indicates the point of attachment of said groups with the rest of the molecule;
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 hydrogen atom;
R′ represent a substituent selected from:
C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-;
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:
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;

represents a group selected from:

said group being substituted with one or more substituents selected independently from each other from an —OH group and a HO-C 1 -C 6 -alkyl-; and
wherein * indicates the point of attachment of said groups with the rest of the molecule;
R3 represents a substituent selected from:
a hydrogen atom, a halogen atom, a C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy- group;
R4 represents a hydrogen atom;
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 , which is selected from the group consisting of:
{(2S)-1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-2-yl}methanol;
{(2R)-1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-2-yl}methanol;
1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-ol;
(3R)-1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]piperidin-3-ol;
{(3S)-1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]piperidin-3-yl}methanol;
1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]azetidin-3-ol;
{(3R)-1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-yl}methanol;
(3S)-1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-ol;
(3R)-1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-ol and {(3S)-1-[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]pyrrolidin-3-yl}methanol.

4. A method of preparing a compound of general formula (I) according to claim 1 , said method comprising the step of allowing an intermediate compound of general formula (V):

in which A, R3 and R4 are as defined in claim 1 , and X represents a leaving group, to react with a compound of general formula (III):

in which R1 and R2 are as defined in claim 1 ,
thereby giving a compound of general formula (I):

in which A, R1, R2, R3 and R4 are as defined in claim 1 .

5. A pharmaceutical composition comprising a compound of general formula (I), or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, or a mixture of same, according to claim 1 , and a pharmaceutically acceptable diluent or carrier.

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

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

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