Substituted imidazopyridazines

Patent metadata

Field	Value
Publication number	US-9512130-B2
Application number	US-201414771648-A
Country	US
Kind code	B2
Filing date	Feb 25, 2014
Priority date	Mar 1, 2013
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

The present invention relates to substituted imidazopyridazine compounds, 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 formula (A), (B) or (C):

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

2. A pharmaceutical composition comprising a compound according to claim 1 , or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, particularly a pharmaceutically acceptable salt thereof, or a mixture of same, and a pharmaceutically acceptable diluent or carrier.

3. A pharmaceutical combination comprising:
a compound according to claim 1 , or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, or a mixture of same;

and
one or more agents selected from: a taxane, Docetaxel, Paclitaxel, or Taxol; an epothilone, Ixabepilone, Patupilone, or Sagopilone; Mitoxantrone; Predinisolone; Dexamethasone; Estramustin; Vinblastin; Vincristin; Doxorubicin; Adriamycin; Idarubicin; Daunorubicin; Bleomycin; Etoposide; Cyclophosphamide; Ifosfamide; Procarbazine; Melphalan; 5-Fluorouracil; Capecitabine; Fludarabine; Cytarabine; Ara-C; 2-Chloro-2″-deoxyadenosine; Thioguanine; an anti-androgen, Flutamide, Cyproterone acetate, or Bicalutamide; Bortezomib; a platinum derivative, Cisplatin, or Carboplatin; Chlorambucil; Methotrexate; and Rituximab.

4. A method of preparing a compound according to claim 1 , comprising reacting an intermediate compound of formula (A1), (B1) or (C1):

in which Z′ represents a group selected from: —C(═O)OH and —C(═O)O—(C 1 -C 6 -alkyl);
with a compound of formula Ib:

thereby giving, upon optional deprotection, a compound of formula (A), (B) or (C) as defined in claim 1 .

5. A method of preparing a compound according to claim 1 , comprising reacting an intermediate compound of formula (A2), (B2) or (C2):

in which Q 2 is a leaving group;
with a compound of formula IIa:

in which Y is a substituent which is displaced in a coupling reaction;
thereby giving, upon optional deprotection, a compound of formula (A), (B) or (C), as defined in claim 1 .

6. A method of preparing a compound according to claim 1 , comprising reacting an intermediate compound of formula (A3), (B3) or (C3):

in which Q 1 is a leaving group;
with a compound of formula (A4), (B4) or (C4):

thereby giving, upon optional deprotection, a compound of formula (A), (B) or (C), as defined in claim 1 .

7. A method of preparing a compound according to claim 1 , comprising reacting an intermediate compound of formula (A5), (B5) or (C5):

in which Q 3 is an optionally protected NH 2 -group;
with a compound of formula (A6), (B6) or (C6):

thereby giving, after reduction of the imine, and upon optional deprotection, a compound of formula (A), (B) or (C), as defined in claim 1 .

8. A method of preparing a compound according claim 1 , comprising reacting an intermediate compound of formula (A7), (B7) or (C7):

in which R 3′ is a leaving group;
with a compound of formula (A8), (B8) or (C8):

in which Y is a substituent which is displaced in a coupling reaction;
thereby giving a compound of formula (A), (B) or (C), as defined in claim 1 .

9. A compound according to claim 1 , which is

10. A compound according to claim 1 , which is a salt of

Assignees

• Bayer Pharma AG

Inventors

• Koppitz Marcus
• Klar Ulrich
• Wengner Antje Margret
• Neuhaus Roland
• Siemeister Gerhard
• Brüning Michael

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/04

  specific for metastasis · CPC title