4-aryl-N-phenyl-1,3,5-triazin-2-amines containing a sulfoximine group

Patent metadata

Field	Value
Publication number	US-9962389-B2
Application number	US-201715488155-A
Country	US
Kind code	B2
Filing date	Apr 14, 2017
Priority date	May 24, 2011
Publication date	May 8, 2018
Grant date	May 8, 2018

Abstract

The present invention relates to 4-aryl-N-phenyl-1,3,5-triazin-2-amines containing a sulfoximine group of general formula (I) or (Ia) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I) or (Ia).

First claim

The invention claimed is:

1. A compound of formula (I)

wherein:
R 1 is a group selected from C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, heteroraryl, phenyl-C 1 -C 3 -alkyl-, and heteroaryl-C 1 -C 3 -alkyl-,
wherein said group is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of hydroxy, cyano, halogen, halo-C 1 -C 3 -alkyl-, C 1 -C 6 -alkoxy-, C 1 -C 3 -fluoroalkoxy-, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, and cyclic amines;

R 2 is a group selected from

R 3 and R 4 are independently a group selected from a hydrogen atom, fluoro atom, chloro atom, cyano, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, halo-C 1 -C 3 -alkyl-, and C 1 -C 3 -fluoroalkoxy-;
R 5 is a group selected from a hydrogen atom, cyano, —C(O)R 9 , —C(O)OR 9 , —S(O) 2 R 9 , —C(O)NR 10 R 11 , C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, and heteroaryl,
wherein said C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl or heteroaryl group is optionally substituted with one, two or three substituents, identically or differently, selected from halogen, cyano, hydroxy, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, and C 1 -C 3 -fluoroalkoxy-;

R 6 and R 7 are independently a group selected from a hydrogen atom, fluoro atom, chloro atom, cyano, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, halo-C 1 -C 3 -alkyl-, and C 1 -C 3 -fluoroalkoxy-;
R 8 is a group selected from
a) a C 1 -C 10 -alkyl group, which is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of halogen, hydroxy, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, cyano, C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-, C 1 -C 3 -alkoxy-, C 2 -C 3 -alkenyl-, C 2 -C 3 -alkynyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, and heteroaryl,
wherein said C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl or heteroaryl group is optionally substituted with one, two or three substituents, identically or differently, selected from halogen, hydroxy, cyano, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, and C 1 -C 3 -fluoroalkoxy-;

b) a C 3 -C 7 -cycloalkyl- group, which is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of halogen, hydroxy, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, cyano, C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-, C 1 -C 3 -alkoxy-, C 2 -C 3 -alkenyl-, and C 2 -C 3 -alkynyl-;
c) a heterocyclyl- group, which is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of halogen, hydroxy, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, cyano, C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-, C 1 -C 3 -alkoxy-, C 2 -C 3 -alkenyl-, and C 2 -C 3 -alkynyl-;
d) a phenyl group, which is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of halogen, hydroxy, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, cyano, C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-, and C 1 -C 3 -alkoxy-;
e) a heteroaryl group, which is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of halogen, hydroxy, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, cyano, C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-, and C 1 -C 3 -alkoxy-;
f) a phenyl-C 1 -C 3 -alkyl- group, which is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of halogen, hydroxy, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, cyano, C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-, and C 1 -C 3 -alkoxy-; and
g) a heteroaryl-C 1 -C 3 -alkyl- group, which is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of halogen, hydroxy, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, cyano, C 1 -C 3 -alkyl-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-, and C 1 -C 3 -alkoxy-;

R 9 is a group selected from C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, benzyl and heteroaryl, wherein said group is optionally substituted with one, two or three substituents, identically or differently, selected from halogen, hydroxy, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, and C 1 -C 3 -fluoroalkoxy-; and
R 10 and R 11 are independently a group selected from hydrogen, C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl and heteroaryl, wherein said C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl or heteroaryl group is optionally substituted with one, two or three substituents, identically or differently, selected from halogen, hydroxy, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, amino, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, and C 1 -C 3 -fluoroalkoxy-,
or a salt or solvate thereof, or a salt of the solvate thereof.

2. The compound according to claim 1 , wherein:
R 1 is a group selected from C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl- and heterocyclyl-;
R 2 is a group selected from

R 3 and R 4 are independently a group selected from a hydrogen atom, fluoro atom, chloro atom and C 1 -C 3 -alkyl-;
R 5 is a group selected from a hydrogen atom, cyano, —C(O)R 9 , —C(O)OR 9 , —S(O) 2 R 9 , —C(O)NR 10 R 11 , and C 1 -C 6 -alkyl-;
R 6 and R 7 are independently a group selected from a hydrogen atom, fluoro atom, and chloro atom;
R 8 is a group selected from
a) a C 1 -C 10 -alkyl group, which is optionally substituted with one or two or three substituents, selected from the group consisting of halogen, hydroxy, C 2 -C 3 -alkenyl-, C 2 -C 3 -alkynyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, and heteroaryl,
wherein said C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl or heteroaryl group is optionally substituted with one, two or three substituents, identically or differently, selected from halogen, cyano, C 1 -C 3 -alkyl-, and halo-C 1 -C 3 -alkyl-;

b) a phenyl group;
c) a phenyl-C 1 -C 3 -alkyl- group, the phenyl group of which is optionally substituted with one or two or three substituents, identically or differently, selected from the group consisting of halogen, cyano, C 1 -C 3 -alkyl-, and halo-C 1 -C 3 -alkyl-; and
d) a heteroaryl-C 1 -C 3 -alkyl- group, the heteroaryl group of which is optionally substituted with one halogen;

R 9 is a C 1 -C 6 -alkyl group; and
R 10 and R 11 are independently a group selected from hydrogen and C 1 -C 6 -alkyl-,
or a salt or solvate thereof, or a salt of the solvate thereof.

Assignees

• Bayer Ip Gmbh

Inventors

• Lücking Ulrich
• Bohlmann Rolf
• Scholz Arne
• Siemeister Gerhard
• Gnoth Mark Jean
• Bömer Ulf
• Kosemund Dirk
• Lienau Philip
• Rühter Gerd
• Schultz-Fademrecht Carsten

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/22

  for herpes viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title