IP Library Granted Patent US 9,320,737
Granted Patent B2
US 9,320,737 · App. 14/346,859 · Granted Apr 26, 2016

Substituted imidazopyridazines

Inventors: Knut Eis (Berlin, DE); Florian Puehler (Cambridge, MA); Ludwig Zorn (Berlin, DE); Arne Scholz (Berlin, DE); Philip Lienau (Berlin, DE); Mark Jean Gnoth (Mettmann, DE); Ulf Bömer (Glienicke, DE); Judith Günther (Berlin, DE)
Assignee: BAYER INTELLECTUAL PROPERTY GMBH
A61K31/5025A61K45/06C07D487/04C07D491/048
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Quick Facts
Patent No.
US 9,320,737
App. No.
14/346,859
Granted
Apr 26, 2016
Kind
B2
Abstract

The present invention relates to substituted imidazopyridazine compounds of general formula (I): in which A, Q, R1, 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.

Claims (130)

1. A compound of formula (I):

in which:

Q represents a group selected from:

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

represents a group selected from:

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

R1 represents a linear C 2 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl-, or a C 3 -C 6 -cycloalkyl group which is optionally substituted with one or more substituents selected, independently from each other, 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′, —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— group;

R2 represents a C 1 -C 6 -alkyl-; halo-C 1 -C 6 -alkyl-; phenyl-optionally substituted one or more times, independently from each other, with an R substituent; 5- or 6-membered heteroaryl-optionally substituted one or more times, independently from each other, with an R substituent;

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;

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-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;

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 or 3;

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:

Q represents a group selected from:

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

represents a group selected from:

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

R1 represents a linear C 2 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl-, or a C 3 -C 6 -cycloalkyl group which is optionally substituted with one or more substituents selected, independently from each other, 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′, —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— group;

R2 represents a C 1 -C 6 -alkyl-; halo-C 1 -C 6 -alkyl-; phenyl-optionally substituted one or more times, independently from each other, with an R substituent; 5- or 6-membered heteroaryl-optionally substituted one or more times, independently from each other, with an R substituent;

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;

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 3 -C 10 -cycloalkyl-, aryl-, heteroaryl-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 or 3;

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:

Q represents a group selected from:

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

represents a group selected from:

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

R1 represents a linear C 2 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl-, or a C 3 -C 6 -cycloalkyl group which is optionally substituted with one or more substituents selected, independently from each other, 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′, —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— group;

R2 represents a C 1 -C 6 -alkyl-; halo-C 1 -C 6 -alkyl-; phenyl-optionally substituted one or more times, independently from each other, with an R substituent; 5- or 6-membered heteroaryl-optionally substituted one or more times, independently from each other, with an R substituent;

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;

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 3 -C 10 -cycloalkyl-, aryl-, heteroaryl-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 or 1;

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

4. The compound according to claim 1 , wherein:

Q represents a group selected from:

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

represents a group selected from:

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

R1 represents a linear C 2 -C 6 -alkyl-, a branched C 3 -C 6 -alkyl-, or a C 3 -C 6 -cycloalkyl group which is optionally substituted with one or more substituents selected, independently from each other, from:

a halogen atom, a —CN, C 1 -C 3 -alkyl-, C 1 -C 3 -haloalkyl-, C 3 -C 6 -cycloalkyl-; aryl-optionally substituted one or two times, independently from each other, with an R substituent; heteroaryl-optionally substituted one or two times, independently from each other, with an R substituent; —C(═O)NH 2 , —NH 2 , —NHR′, —N(R′)R″, —OH, C 1 -C 3 -alkoxy-, C 1 -C 3 -haloalkoxy-;

R2 represents a C 1 -C 6 -alkyl-; halo-C 1 -C 6 -alkyl-; phenyl-optionally substituted one or more times, independently from each other, with an R substituent; 5- or 6-membered heteroaryl-optionally substituted one or more times, independently from each other, with an R substituent;

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;

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 3 -C 10 -cycloalkyl-, aryl-, heteroaryl-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 or 1;

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

5. The compound according to claim 1 , wherein:

Q represents a group selected from:

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

represents a group selected from:

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

R1 represents a linear C 2 -C 6 -alkyl-group;

R2 represents a C 1 -C 6 -alkyl-;

R3 represents a substituent selected from:

a halogen atom, C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-group;

R4 represents a:

a hydrogen atom, a C 1 -C 6 -alkyl-, or aryl group;

n represents an integer of 0 or 1;

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

6. The compound according to claim 1 , which is selected from the group consisting of:

3-(4-Methoxy-1-benzofuran-2-yl)-6-[3-(methylsulfanyl)propoxy]imidazo[1,2-b]-pyridazine;

3-(1-Benzofuran-2-yl)-6-[3-(methylsulfanyl)propoxy]imidazo[1,2-b]pyridazine;

3-(1-Benzofuran-2-yl)-6-[4-(methylsulfanyl)butoxy]imidazo[1,2-b]pyridazine;

3-(1-Benzofuran-2-yl)-6-[2-(methylsulfanyl)ethoxy]imidazo[1,2-b]pyridazine;

3-(4-Methoxy-1-benzofuran-2-yl)-6-[3-(methylsulfinyl)propoxy]imidazo[1,2-b]-pyridazine;

3-(1-Benzofuran-2-yl)-6-[3-(methylsulfinyl)propoxy]imidazo[1,2-b]pyridazine;

3-(1-Benzofuran-2-yl)-6-[4-(methylsulfinyl)butoxy]imidazo[1,2-b]pyridazine;

3-(1-Benzofuran-2-yl)-6-[2-(methylsulfinyl)ethoxy]imidazo[1,2-b]pyridazine

3-(1-Benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]pyridazine;

3-(5-Methoxy-1-benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]-pyridazine;

3-(4-Methoxy-1-benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]-pyridazine;

3-(5-Fluoro-1-benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]pyridazine;

3-(5-Chloro-1-benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]pyridazine;

3-(7-Fluoro-1-benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]pyridazine;

3-(3-Methyl-1-benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]pyridazine;

3-(7-Methyl-1-benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]pyridazine; and

3-(4-Fluoro-1-benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]-pyridazine;

3-(1-Benzofuran-2-yl)-7-methyl-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]-pyridazine;

3-(1-Benzofuran-2-yl)-6-[3-(methylsulfonyl)propoxy]-7-phenylimidazo[1,2-b]-pyridazine;

3-(4-Methoxyfuro[3,2-c]pyridin-2-yl)-6-[3-(methylsulfonyl)propoxy]-imidazo-[1,2-b]-pyridazine;

3-(Furo[3,2-c]pyridin-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]-pyridazine;

3-(Furo[3,2-b]pyridin-2-yl)-6-[3-(methylsulfonyl)propoxy]imidazo[1,2-b]-pyridazine

2,2,2-Trifluoro-N-[(3-{[3-(4-methoxy-1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]oxy}propyl)(methyl)oxido-lambda 6 -sulfanylidene]acetamide;

3-(4-Methoxy-1-benzofuran-2-yl)-6-[3-(S-methylsulfonimidoyl)-propoxy]imidazo-[1,2-b]pyridazine;

N-[(3-{[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]oxy}propyl)(methyl)oxido-lambda 6 -sulfanylidene]-2,2,2-trifluoroacetamide;

3-(1-Benzofuran-2-yl)-6-[3-(S-methylsulfonimidoyl)propoxy]imidazo[1,2-b]pyridazine;

N-[(4-{[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]oxy}butyl)(methyl)oxido-lambda 6 -sulfanylidene]-2,2,2-trifluoroacetamide;

3-(1-Benzofuran-2-yl)-6-[4-(S-methylsulfonimidoyl)butoxy]imidazo[1,2-b]pyridazine;

N-[(2-{[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]oxy}ethyl)(methyl)oxido-lambda 6 -sulfanylidene]-2,2,2-trifluoroacetamide;

[(3-{[3-(1-Benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]oxy}propyl)(methyl)oxido-lambda 6 -sulfanylidene]cyanamide;

[(3-{[3-(4-Methoxyfuro[3,2-c]pyridin-2-yl)imidazo[1,2-b]pyridazin-6-yl]oxy}propyl)(methyl)oxido-lambda 6 -sulfanylidene]cyanamide; and

3-(4-Methoxyfuro[3,2-c]pyridin-2-yl)-6-[3-(S-methylsulfonimidoyl)propoxy]-imidazo[1,2-b]pyridazine.

7. A method of preparing a compound according to claim 1 , said method comprising the step of allowing an intermediate compound of formula (E):

in which A, R3, R4 and n are as defined in claim 1 , and X represents a leaving group, to react, in the presence of a base, with a compound of formula (G):

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

in which A, Q R1, R3, R4 and n are defined in claim 1 .

8. A pharmaceutical composition comprising a compound of 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.

9. A pharmaceutical combination comprising:

one or more first active ingredients selected from compounds according to claim 1 , and

one or more second active ingredients selected from chemotherapeutic anti-cancer agents.

10. A method for the treatment of lung cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of 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 .

11. The method according to claim 7 , wherein X is a halogen atom or a perfluoroalkylsulfonate group.

12. The method according to claim 11 , wherein X is selected from chlorine, bromine, iodine, trifluoromethylsulfonate, and nonafluorobutylsulfonate.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 25, 2014
From: EIS, KNUT, DR.; PUEHLER, FLORIAN, DR.; ZORN, LUDWIG, DR.; SCHOLZ, ARNE, DR.; LIENAU, PHILIP, DR.; GNOTH, MARK JEAN, DR.; BÖMER, ULF, DR.; GÜNTHER, JUDITH, DR.
To: BAYER INTELLECTUAL PROPERTY GMBH
Reel/Frame 033176/0160 →
Priority Claims (4)
EP 11182438 · Sep 23, 2011 · regional
EP 11187793 · Nov 4, 2011 · regional
EP 11187794 · Nov 4, 2011 · regional
EP 11187795 · Nov 4, 2011 · regional
Continuity (1)
Related Publication 20140228370A1 · Aug 14, 2014