Substituted-imidazopyridazines

Patent metadata

Field	Value
Publication number	US-2016287589-A1
Application number	US-201414769091-A
Country	US
Kind code	A1
Filing date	Feb 18, 2014
Priority date	Feb 20, 2013
Publication date	Oct 6, 2016
Grant date	—

Abstract

The present invention relates to amido-substituted imidazopyridazine compounds of general formula (I): (Ia) (Ib) (Ic) (Id) in which A, Y, R1, R2, R3, R4 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.

First claim

1 . A compound of general formula (I):

selected from:

in which:

in formulae (Ia) and (Ib) represents a:

in formulae (Ic) and (Id) represents a:

wherein * indicates the point of attachment of said group with the rest of the molecule; and

in formulae (Ia) and (Id) represents a:

or a

wherein * indicates the point of attachment of said groups to R1;
R1 in formula (Ia) represents a substituent selected from:
a linear C 1 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl-, or a C 3 -C 6 -cycloalkyl 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-, 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)NH 2 , —C(═O)N(H)R′, —C(═O)N(R′)R″, C(═O)OH, —C(═O)OR′, —NHR′, —N(R′)R″, —N(H)C(═O)R′, —N(R′)C(═O)R′, —N(H)S(═O)R′, —N(R1S(═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;

R1 in formulae (Ib) and (Ic) represents a substituent selected from:
a linear C 1 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl- or a C 3 -C 10 -cycloalkyl 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-, 4- to 10-membered heterocycloalkyl- optionally substituted one or more times, independently from each other, with an R5 substituent; -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)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)OR′, —N(R′)C(═O)OR′, —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″, —S(═O)(═NR′)R″, —S(═O)(═N(CN))R″ group;

or a 4- to 10-membered heterocycloalkyl group optionally substituted one or more times, independently from each other with an R5 substituent;

and
R1 in formula (Id) represents a substituent selected from:
a linear C 1 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl-, or a C 3 -C 6 -cycloalkyl 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-, 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)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;

R2 in formulae (Ia), (Ib), (Ic) and (Id) represents a hydrogen atom;
R3 in formulae (Ia) and (Id) 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 3 -C 6 -cycloalkyl-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;

and
R3 in formulae (Ib) and (Ic) represents a substituent selected from:
a N(R6)R7 group, or a 4- to 10-membered nitrogen atom containing heterocycloalkyl group which is optionally substituted one or more times, independently from each other with an R5 substituent, said heterocycloalkyl group being attached to the rest of the molecule via a nitrogen ring atom of the heterocycloalkyl group;

R4 in formulae (Ia) and (Id) 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- 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)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;

and
R4 in formulae (Ib) and (Ic) represents a substituent selected from:
a hydrogen atom, a halogen atom, a —CN, C 1 -C 6 -alkyl-, C 1 -C 6 -haloalkyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-group;

R5 in formulae (Ia) and (Id) represents a substituent selected from:
a 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-, C 3 -C 10 -cycloalkyl-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, aryl-C 1 -C 6 -alkyl-, C 1 -C 6 -hydroxyalkyl, 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;

or
together with a carbon atom of R1, represents a 4-, 5-, 6- or 7-membered cyclic amide group, which is optionally substituted with a substituent selected from:
a halogen ato

Assignees

• Bayer Pharma AG

Inventors

• Fis Knut
• Puehler Florian
• Zorn Ludwig
• Schulze Volker
• Sülzle Detlev
• Lienau Philip
• Wengner Antje Margret
• Petersen Kirstin
• Bömer Ulf

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

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

• A61P35/02

  specific for leukemia · CPC title