Substituted aminoquinoxalines as tyrosine threonine kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9340528-B2
Application number	US-201013393583-A
Country	US
Kind code	B2
Filing date	Aug 24, 2010
Priority date	Sep 4, 2009
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

The present invention relates to substituted aminoquinoxaline compounds of general formula (I) in which (II), R 2 , R 3 , R 4 , R 6 , R 7 , n and m are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

First claim

This invention claimed is:

1. A compound of general formula (I):

in which:

represents a 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocyclic ring, optionally further containing 1 heteroatom-containing group selected from O and NR 1 in which R 1 represents hydrogen, or a group selected from: C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, hydroxyl-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 —, aryloxy-C 1 -C 6 -alkyl-, C 2 -C 10 -alkenyl-, C 2 -C 10 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C 1 -C 6 -alkylene-aryl, a 4- or 5-(1,3-benzodioxolinyl)- group, —C 1 -C 6 -alkylene-heteroaryl, C 1 -C 6 -alkylene-aryl-, C 1 -C 6 -alkylene-heteroaryl-, —C 1 -C 6 -alkylene-C 3 -C 10 -cycloalkyl, —C 1 -C 6 -alkylene-(3- to 10-membered heterocycloalkyl), —C(═O)R 8 , —C(═O)O—C 1 -C 6 -alkyl, —C(═O)O—C 3 -C 10 -cycloalkyl, —C(═O)NR 9 R 10 , —S(═O)R 8 , —S(═O) 2 R 8 , —S(═O) 2 NR 9 R 10 ;
wherein said group is optionally substituted one or more times, identically or differently, with a substituent selected from: halo-, hydroxyl-, cyano-, nitro-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, hydroxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 10 -alkenyl-, C 2 -C 10 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, C 1 -C 6 -alkylene-aryl-, C 1 -C 6 -alkylene-heteroaryl-, —C 1 -C 6 -alkylene-C 3 -C 10 -cycloalkyl, —C 1 -C 6 -alkylene-(3- to 10-membered heterocycloalkyl), —OR 8 , —C(═O)H, —C(═O)R 8 —, C(═O)OH, —C(═O)O—C 1 -C 6 -alkyl, —C(═O)O—C 3 -C 10 -cycloalkyl, —OC(═O)—C 1 -C 6 -alkyl, —OC(═O)—C 3 -C 10 -cycloalkyl, —N(H)C(═O)R 8 , —N(C 1 -C 6 -alkyl)C(═O)R 8 , —N(H)S(═O) 2 R 8 , —N(C 1 -C 6 -alkyl)S(═O) 2 R 8 , —C(═O)NR 9 R 10 , —OC(═O)NR 9 R 10 , —N(H)C(═O)OR 8 , —N(C 1 -C 6 -alkyl)C(═O)OR 8 , —N(H)C(═O)NR 9 R 10 , —N(C 1 -C 6 -alkyl)C(═O)NR 9 R 10 , —SR 8 , —S(═O)R 8 , —S(═O) 2 R 8 , —S(═O) 2 NR 9 R 10 , —NR 9 R 10 ;
R 1 and R 7 can form together a 5-7 membered ring which is optionally substituted with ═O;
R 2 , R 3 , R 4 , R 6 , represent hydrogen;
R 5 , R 7 represent, independently from each other, a substituent selected from hydrogen, halo-, hydroxyl-, cyano-, nitro-, or a substituent group selected from: C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 10 -alkenyl-, C 2 -C 10 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C 1 -C 6 -alkylene-aryl, C 1 -C 6 -alkylene-aryl-, C 1 -C 6 -alkylene-heteroaryl-, —C 1 -C 6 -alkylene-C 3 -C 10 -cycloalkyl, —C 1 -C 6 -alkylene-(3- to 10-membered heterocycloalkyl), —OR 8 , —C(═O)H, —C(═O)R 8 , —C(═O)OH, —C(═O)O—C 1 -C 6 -alkyl, —C(═O)O—C 3 -C 10 -cycloalkyl, —OC(═O)—C 1 -C 6 -alkyl, —OC(═O)—C 3 -C 10 -cycloalkyl, —N(H)C(═O)R 8 , —N(C 1 -C 6 -alkyl)C(═O)R 8 , —N(H)S(═O) 2 R 8 , —N(C 1 -C 6 -alkyl)S(═O) 2 R 8 , —C(═O)NR 9 R 10 , —OC(═O)NR 9 R 10 , —N(H)C(═O)OR 8 , —N(C 1 -C 6 -alkyl)C(═O)OR 8 , —N(H)C(═O)NR 9 R 10 , —N(C 1 -C 6 -alkyl)C(═O)NR 9 R 10 , —SR 8 , —S(═O)R 8 , —S(═O) 2 R 8 , —S(═O) 2 NR 9 R 10 , —NR 9 R 10 ;
wherein, when m or n represent, independently from each other, an integer of 2, or 3, then said substituent or substituent group is, independently from each other, identical or different;
wherein said substituent group is optionally substituted one or more times, identically or differently, with a substituent selected from: halo-, hydroxyl-, cyano-, nitro-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, hydroxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 10 -alkenyl-, C 2 -C 10 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, a 4- or 5-(1,3-benzodioxolinyl)- group, C 1 -C 6 -alkylene-aryl-, C 1 -C 6 -alkylene-heteroaryl-, —C 1 -C 6 -alkylene-C 3 -C 10 -cycloalkyl, —C 1 -C 6 -alkylene-(3- to 10-membered heterocycloalkyl), —C(═O)H, —C(═O)—C 1 -C 6 -alkyl, C(═O)OH, —C(═O)O—C 1 -C 6 -alkyl, —C(═O)O—C 3 -C 10 -cycloalkyl, —OC(═O)—C 1 -C 6 -alkyl, —OC(═O)—C 3 -C 10 -cycloalkyl, —N(H)C(═O)—C 1 -C 6 -alkyl, —N(C 1 -C 6 -alkyl)C(═O)—C 1 -C 6 -alkyl, —N(H)S(═O) 2 —C 1 -C 6 -alkyl, —N(C 1 -C 6 -alkyl)S(═O) 2 —C 1 -C 6 -alkyl, —C(═O)NH 2 , —C(═O)N(H)C 1 -C 6 -alkyl, —C(═O)N(C 1 -C 6 -alkyl) 2 , —OC(═O)N(H)C 1 -C 6 -alkyl, —OC(═O)N(C 1 -C 6 -alkyl) 2 , —N(H)C(═O)O—C 1 -C 6 -alkyl, —N(C 1 -C 6 -alkyl)C(═O)O—C 1 -C 6 -alkyl, —N(H)C(═O)NH 2 , —N(H)C(═O)N(H)C 1 -C 6 -alkyl, —N(H)C(═O)N(C 1 -C 6 -alkyl) 2 , —N(C 1 -C 6 -alkyl)C(═O)NH 2 , —N(C 1 -C 6 -alkyl)C(═O)N(H)C 1 -C 6 -alkyl, —N(C 1 -C 6 -alkyl)C(═O)N(C 1 -C 6 -alkyl) 2 , —S—C 1 -C 6 -alkyl, —S(═O) —C 1 -C 6 -alkyl, —S(═O) 2 —C 1 -C 6 -alkyl, —S(═O) 2 NH 2 , —S(═O) 2 N(H)C 1 -C 6 -alkyl, —S(═O) 2 N(C 1 -C 6 -alkyl) 2 , —NH 2 , —N(H)C 1 -C 6 -alkyl, —N(C 1 -C 6 -alkyl) 2 ;
R 8 represents a group selected from:
C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, hydroxy-C 1 -C 6 -alkyl, C 2 -C 10 -alkenyl-, C 2 -C 10 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, C 1 -C 6 -alkylene-aryl-, C 1 -C 6 -alkylene-heteroaryl-, —C 1 -C 6 -alkylene-C 3 -C 10 -cycloalkyl, —C 1 -C 6 -alkylene-aryl, —C 1 -C 6 -alkylene-heteroaryl, —C 1 -C 6 -alkylene-(3- to 10-membered heterocycloalkyl), —NR 9 R 10 ;
wherein said group is optionally substituted one or more times, identically or differently, with a substituent selected from: halo-, hydroxyl-, cyano-, nitro-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, hydroxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 10 -alkenyl-, C 2 -C 10 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, C 1 -C 6 -alkylene-aryl-, C 1 -C 6 -alkylene-heteroaryl-, —C 1 -C 6 -alkylene-C 3 -C 10 -cycloalkyl, —C 1 -C 6 -alkylene-(3- to 10-membered heterocycloalkyl), —C(═O)H, —C(═O)R 11 —, C(═O)OH, —C(═O)O—C 1 -C 6 -alkyl, —C(═O)O—C 3 -C 10 -cycloalkyl, —OC(═O)—C 1 -C 6 -alkyl, —OC(═O)—C 3 -C 10 -cycloalkyl, —N(H)C(═O)R 11 , —N(C 1 -C 6 -alkyl)C(═O)R 11 , —N(H)S(═O) 2 R 11 , —N(C 1 -C 6 -alkyl)S(═O) 2 R 11 , —C(═O)NR 9 R 10 , —OC(═O)NR 9 R 10 , —N(H)C(═O)OR 11 , —N(C 1 -C 6 -alkyl)C(═O)OR 11 , —N(H)C(═O)NR 9 R 10 , —N(C 1 -C 6 -alkyl)C(═O)NR 9 R 10 , —SR 11 , —S(═O)R 11 , —S(═O) 2 R 11 , —S(═O) 2 NR 9 R 10 , —NR 9 R 10 ;
R 9 , R 10 represent independently from each other hydrogen, or a group selected from: C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 10 -alkenyl-, C 2 -C 10 -alkynyl-, C 3 -C 10 -cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C 1 -C 6 -alkylene-aryl, C 1 -C 6 -alkylene-aryl-, C 1 -C 6 -alkylene-heteroaryl-, —C 1 -C 6 -alkylene-C 3 -C 10 -cycloalkyl, —C 1 -C 6 -alkylene-(3- to 10-membered heterocycloalkyl),
R 9 and R 10 can form together a 5-7 saturated or partially unsaturated heterocyclic ring, which optionally further contains 1 heteroatom-containing group selected from O;
R 11 represents
C 1 -C 6 -alkyl-;
n, m represent, independently from each other, an integer of 0, 1, 2, or 3;
or a stereois

Assignees

• Bader Benjamin
• Bömer Ulf
• Ince Stuart
• Koppitz Marcus
• Lienau Philip
• Marquardt Tobias
• Nguyen Duy
• Prechtl Stefan
• Siemeister Gerhard
• Wegscheid-Gerlach Christof
• Bayer Pharma AG

Inventors

• Bader Benjamin
• Bömer Ulf
• Ince Stuart
• Koppitz Marcus
• Lienau Philip
• Marquardt Tobias
• Nguyen Duy
• Prechtl Stefan
• Siemeister Gerhard
• Wegscheid-Gerlach Christof

Classifications

• A61P43/00

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

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P35/02

  specific for leukemia · CPC title