Arylaminoalcohol-substituted 2,3-dihydroimidazo[1,2-C]quinolines

Patent metadata

Field	Value
Publication number	US-9675616-B2
Application number	US-201113884125-A
Country	US
Kind code	B2
Filing date	Nov 8, 2011
Priority date	Nov 11, 2010
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

The present invention relates to substituted phenoxypyridine compounds of general formula (I); in which R1, R2 and R3 are as defined in the claims, to methods of preparing said compounds, to intermediates for the preparation of 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 (I):

wherein:
R 1 is —(CH 2 ) n —(CHR 4 )—(CHR 4 )—(CH 2 ) m —N(R 5 )(R 5′ );
R 2 is a heteroaryl of structure:

optionally substituted with 1, 2 or 3 R 6 groups,
wherein:
* indicates the point of attachment of said heteroaryl with the rest of the structure of formula (I),
X is N or C—R 6 , and
X′ is O, S, NH, N—R 6 , N or C—R 6 ,
with the proviso that when X and X′ are both C—R 6 , then one C—R 6 is C—H;

R 3 is methyl;
R 4 is hydroxy;
R 5 is a hydrogen atom, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl,
wherein said aryl-C 1 -C 6 -alkyl group is substituted, one or more times, in the same way or differently, with R 6 ;
R 5′ is aryl-C 1 -C 6 -alkyl,
wherein said aryl-C 1 -C 6 -alkyl group is substituted, one or more times, in the same way or differently, with R 6 ;
each occurrence of R 6 is the same or different and is independently a hydrogen atom, a halogen atom, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alkyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, heteroaryl-C 1 -C 6 -alkyl, 3- to 8-membered heterocyclic ring, 3- to 8-membered heterocyclyl-C 1 -C 6 -alkyl, —C 1 -C 6 -alkyl-OR 7 , —C 1 -C 6 -alkyl-SR 7 , —C 1 -C 6 -alkyl-N(R 7 )(R 7′ ), —C 1 -C 6 -alkyl-C(═O)R 7 , —CN, —C(═O)OR 7 , —C(═O)N(R 7 )(R 7′ ), —OR 7 , —SR 7 , —N(R 7 )(R 7′ ), or —NR 7 C(═O)R 7 , each of which is optionally substituted with 1 or more R 8 groups;
each occurrence of R 7 and R 7′ is the same or different and is independently a hydrogen atom, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alklyl, C 3 -C 6 -cycloalkenyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, 3- to 8-membered heterocyclic ring, 3- to 8-membered heterocyclyl-C 1 -C 6 -alkyl, or heteroaryl-C 1 -C 6 -alkyl;
each occurrence of R 8 is independently a halogen atom, nitro, hydroxy, cyano, formyl, acetyl, amino, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -cycloalkenyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, 3- to 8-membered heterocyclic ring, heterocyclyl-C 1 -C 6 -alkyl, or heteroaryl-C 1 -C 6 -alkyl; and
n is an integer of 1 and m is an integer of 1,
or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a physiologically acceptable salt thereof, or a mixture of any of the foregoing.

2. The compound according to claim 1 , wherein:
R 1 is —(CH 2 ) n —(CHR 4 )—(CH 2 ) m —N(R 5 )(R 5′ );
R 2 is a heteroaryl of structure:

wherein:
* indicates the point of attachment of said heteroaryl with the rest of the structure of formula (I);

R 3 is methyl;
R 4 is hydroxy;
R 5 is a hydrogen atom, C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl,
wherein said aryl-C 1 -C 6 -alkyl group is substituted, one or more times, in the same way or differently, with R 6 ;
R 5′ is aryl-C 1 -C 6 -alkyl,
wherein said aryl-C 1 -C 6 -alkyl group is substituted, one or more times, in the same way or differently, with R 6 ;
each occurrence of R 6 is the same or different and is independently a hydrogen atom or a methyl group;
each occurrence of R 7 and R 7′ is the same or different and is independently a hydrogen atom, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alklyl, C 3 -C 6 -cycloalkenyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, 3- to 8-membered heterocyclic ring, 3- to 8-membered heterocyclyl-C 1 -C 6 -alkyl, or heteroaryl-C 1 -C 6 -alkyl;
each occurrence of R 8 is independently a halogen atom, nitro, hydroxy, cyano, formyl, acetyl, amino, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -cycloalkenyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, 3- to 8-membered heterocyclic ring, heterocyclyl-C 1 -C 6 -alkyl, or heteroaryl-C 1 -C 6 -alkyl; and
n is an integer of 1 and m is an integer of 1,
or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a physiologically acceptable salt thereof, or a mixture of any of the foregoing.

3. The compound according to claim 1 , wherein:
R 1 is —(CH 2 ) n —(CHR 4 )—(CH 2 ) m —N(R 5 )(R 5 );
R 2 is a heteroaryl of structure:

wherein:
* indicates the point of attachment of said heteroaryl with the rest of the structure of formula (I);

R 3 is methyl;
R 4 is hydroxy;
R 5 is a hydrogen atom, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl,
wherein said aryl-C 1 -C 6 -alkyl group is substituted, one or more times, in the same way or differently, with R 6 ;
R 5′ is aryl-C 1 -C 6 -alkyl,
wherein said aryl-C 1 -C 6 -alkyl group is substituted, one or more times, in the same way or differently, with R 6 ;
each occurrence of R 6 is the same or different and is independently a hydrogen atom or a methyl group;
each occurrence of R 7 and R 7′ is the same or different and is independently a hydrogen atom, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alklyl, C 3 -C 6 -cycloalkenyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, 3- to 8-membered heterocyclic ring, 3- to 8-membered heterocyclyl-C 1 -C 6 -alkyl, or heteroaryl-C 1 -C 6 -alkyl;
each occurrence of R 8 is independently a halogen atom, nitro, hydroxy, cyano, formyl, acetyl, amino, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alkyl, C 1 -C 6 -cycloalkenyl, aryl, aryl-C 1 -C 6 -alkyl, heteroaryl, 3- to 8-membered heterocyclic ring, heterocyclyl-C 1 -C 6 -alkyl, or heteroaryl-C 1 -C 6 -alkyl; and
n is an integer of 1 and m is an integer of 1,
or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a physiologically acceptable salt thereof, or a mixture of any of the foregoing.

4. The compound according to claim 1 , wherein:
R 1 is —(CH 2 ) n —(CHR 4 )—(CH 2 ) m —N(R 5 )(R 5′ );
R 2 is a heteroaryl of structure:

wherein:
* indicates the point of attachment of said heteroaryl with the rest of the structure of formula (I), and
Z is N or C—R 6 ;

R 3 is methyl;
R 4 is hydroxy;
R 5 is a hydrogen atom, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl-C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl,
wherein said aryl-C 1 -C 6 -alkyl group is substituted, one or more times, in the same way or differently, with R 6 ;
R 5′ is aryl-C 1 -C 6 -alkyl,
wherein said aryl-C 1 -C 6 -alkyl group is substituted, one or more times, in the same way or dif

Assignees

• Scott William Johnston
• Petrov Orlin
• Möwes Manfred
• Liu Ningshu
• Bömer Ulf
• Bayer Ip Gmbh

Inventors

• Scott William Johnston
• Petrov Orlin
• Möwes Manfred
• Liu Ningshu
• Bömer Ulf

Classifications

• A61P35/02

  specific for leukemia · 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

• A61P35/04

  specific for metastasis · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title