4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amines containing a sulfoximine group

Patent metadata

Field	Value
Publication number	US-9499492-B2
Application number	US-201314443180-A
Country	US
Kind code	B2
Filing date	Nov 11, 2013
Priority date	Nov 15, 2012
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

The present invention relates to 4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amine derivatives containing a sulfoximine group of general formula (I) 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).

First claim

The invention claimed is:

1. A compound of general formula (I)

wherein
R 1 represents a group selected from C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, heteroaryl, phenyl-C 1 -C 3 -alkyl- or 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 of hydroxy, cyano, halogen, halo-C 1 -C 3 -alkyl-, C 1 -C 6 -alkoxy-, C 1 -C 3 -fluoroalkoxy-, —NH 2 , alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, —OP(O)(OH) 2 , —C(O)OH, —C(O)NH 2 ;

R 2 represents the group

R 3 , R 4 represent, independently from each other, a group selected from a hydrogen atom, halogen atom, cyano, —SF 5 , C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, hydroxy, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-;
R 5 represents a group selected from a hydrogen atom, cyano, —C(O)R 8 , —C(O)OR 8 , —S(O) 2 R 8 , —C(O)NR 9 R 10 , —P(O)(OR 11 ) 2 , —CH 2 OP(OR 11 ) 2 , C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, 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, cyano, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, —NH 2 , alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-;

R 6 , R 7 represent, independently from each other, a group selected from a hydrogen atom, fluoro atom, chloro atom, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-;
R 8 represents a group selected from C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, benzyl or 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-, —NH 2 , alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-;

R 9 , R 10 represent, independently from each other, a group selected from hydrogen, C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, benzyl or heteroaryl,
wherein said C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl-, heterocyclyl-, phenyl, benzyl 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-, —NH 2 , alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-, or

R 9 and R 10 , together with the nitrogen atom they are attached to, form a cyclic amine;
R 11 represents a group selected from hydrogen, C 1 -C 4 -alkyl or benzyl,
or an enantiomers, diastereomers, salts, solvates or salts of solvates thereof,
with the proviso that the compound is not
(rac)-ethyl[(3-{[4-(2,4-difluorophenyl)-5-fluoropyrimidin-2-yl]amino}benzyl)(methyl)oxido-λ 6 -sulfanylidene]carbamate.

2. The compound of general formula (I) according to claim 1 , wherein
R 1 represents a group selected from C 1 -C 6 -alkyl-, C 3 -C 7 -cycloalkyl, phenyl, or phenyl-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 of hydroxy, cyano, halogen, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, C 1 -C 3 -fluoroalkoxy-, —NH 2 , alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, —OP(O)(OH) 2 , —C(O)OH, —C(O)NH 2 ;

R 2 represents the group

R 3 , R 4 represent, independently from each other, a group selected from a hydrogen atom, halogen atom, —SF 5 , C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-;
R 5 represents a group selected from a hydrogen atom, cyano, —C(O)R 8 , —S(O) 2 R 8 , —C(O)NR 9 R 10 , —P(O)(OR 11 ) 2 , —CH 2 OP(OR 11 ) 2 , C 1 -C 3 -alkyl-, C 3 -C 5 -cycloalkyl-, phenyl,
wherein said C 1 -C 3 -alkyl, C 3 -C 5 -cycloalkyl- or phenyl group is optionally substituted with one or two substituents, identically or differently, selected from hydroxy, —NH 2 , alkylamino-, dialkylamino-, cyclic amines;

R 6 , R 7 represent, independently from each other, a group selected from a hydrogen atom, fluoro atom, chloro atom, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-;
R 8 represents a group selected from C 1 -C 3 -alkyl-, C 3 -C 5 -cycloalkyl-, heterocyclyl-, phenyl or benzyl,
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-, —NH 2 , alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-;

R 9 , R 10 represent, independently from each other, a group selected from hydrogen, C 1 -C 3 -alkyl-, C 3 -C 5 -cycloalkyl-, heterocyclyl-, phenyl or benzyl,
wherein said C 1 -C 3 -alkyl-, C 3 -C 5 -cycloalkyl-, heterocyclyl-, phenyl or benzyl 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-, —NH 2 , alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C 1 -C 3 -alkyl-, C 1 -C 3 -fluoroalkoxy-; or

R 9 and R 10 , together with the nitrogen atom they are attached to, form a cyclic amine;
R 11 represents a group selected from hydrogen or C 1 -C 4 -alkyl,
or an enantiomer, diastereomer, salt, solvate or salt of a solvate thereof.

3. The compound of general formula (I) according to claim 1 , wherein
R 1 represents a group selected from C 1 -C 6 -alkyl-,
wherein said group is optionally substituted with one substituent selected from the group of C 1 -C 3 -alkoxy, —NH 2 , alkylamino, dialkylamino, cyclic amines, hydroxy, —OP(O)(OH) 2 ;

R 2 represents the group

R 3 represents a group selected from a hydrogen atom, halogen atom, —SF 5 , C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, or halo-C 1 -C 3 -alkyl-;
R 4 represents a hydrogen atom or a fluoro atom;
R 5 represents a group selected from a hydrogen atom, cyano, —C(O)NR 9 R 10 , —P(O)(OR 11 ) 2 , —CH 2 OP(OR 11 ) 2 or C 1 -C 3 -alkyl,
wherein said C 1 -C 3 -alkyl group is optionally substituted with one substituent, selected from —NH 2 , alkylamino-, dialkylamino-, or cyclic amines;

R 6 , R 7 represent, independently from each other, a group selected from a hydrogen atom, fluoro atom, C 1 -C 3 -alkyl-;
R 9 , R 10 represent, independently from each other, a group selected from hydrogen, C 1 -C 3 -alkyl-, C 3 -C 5 -cycloalkyl-, or benzyl,
wherein said C 1 -C 3 -alkyl-, C 3 -C 5 -cycloalkyl- or benzyl group is optionally substituted with one or two substituents, identically or differently, selected from halogen, hydroxy, C 1 -C 3 -alkyl-, C 1 -C 3 -alkoxy-, —NH 2 , alkylamino-, dialkylamino-, or

R 9 and R 10 , together with the nitrogen atom they are attached to, form a cyclic amine;
R 11 represents a group selected from hydrogen or C 1 -C 2 -alkyl,
or an e

Assignees

• Bayer Pharma AG

Inventors

• Lücking Ulrich
• Kosemund Dirk
• Bohlmann Rolf
• Scholz Arne
• Lienau Philip
• Siemeister Gerhard
• Bömer Ulf

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P43/00

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

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title