Fluoroalkyl-substituted aryltriazole derivatives and uses thereof

Patent metadata

Field	Value
Publication number	US-10525041-B2
Application number	US-201716098255-A
Country	US
Kind code	B2
Filing date	May 2, 2017
Priority date	May 3, 2016
Publication date	Jan 7, 2020
Grant date	Jan 7, 2020

Abstract

The present invention relates to novel 5-(fluoroalkyl)-1-aryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

First claim

The invention claimed is:

1. A compound of general formula (I)

in which
R 1 represents a trifluoromethyl group
or
represents a group of the formula —Y—R 2 , wherein
Y represents a group of the formula

in which
# 1 represents the point of attachment to R 2 ,
# 2 represents the point of attachment to the rest of the molecule,

R 2 represents a group selected from a hydrogen atom, (C 1 -C 4 )-alkyl, 5- or 6-membered cycloalkyl, 5- or 6-membered oxaheterocycloalkyl,
wherein any (C 1 -C 4 )-alkyl group and any 5- or 6-membered cycloalkyl group are each optionally substituted with a group selected from amino and hydroxy,

Ar represents a phenyl group or a 5- or 6-membered heteroaryl group attached via a ring carbon atom having one or two ring heteroatoms selected from a nitrogen atom and a sulfur atom,
wherein any phenyl group and any 5- or 6-membered heteroaryl group are each optionally substituted, identically or differently, with one or two groups selected from a halogen atom, nitro, cyano, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylsulfanyl, (C 1 -C 4 )-alkoxycarbonyl, aminocarbonyl and —S(═O) 2 NH 2 ,
wherein said (C 1 -C 4 )-alkyl group, said (C 1 -C 4 )-alkoxy group and said (C 1 -C 4 )-alkylsulfanyl group are each optionally substituted with up to three fluorine atoms,

or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

2. A compound of general formula (I) according to claim 1 , wherein
R 1 represents a trifluoromethyl group
or
represents a group of the formula —Y—R 2 , wherein
Y represents a group of the formula

in which
# 1 represents the point of attachment to R 2 ,
# 2 represents the point of attachment to the rest of the molecule,

R 2 represents a group selected from methyl, aminomethyl, 5-membered cycloalkyl and 4-morpholinyl,
wherein any 5-membered cycloalkyl group is optionally substituted with hydroxy,

Ar represents a phenyl group or a pyridine group attached via a ring carbon atom,
wherein any phenyl group any pyridine group is each optionally substituted with one or two groups selected from a fluorine atom, a chlorine atom, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, nitro, cyano, methylsulfanyl and —S(═O) 2 NH 2 ,
wherein said (C 1 -C 4 )-alkyl group and said (C 1 -C 4 )-alkoxy group are each optionally substituted with up to three fluorine atoms,

or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

3. A compound of general formula (I) according to claim 1 , wherein
R 1 represents a group of the formula —Y—R 2 , wherein
Y represents a group of the formula

in which
# 1 represents the point of attachment to R 2 ,
# 2 represents the point of attachment to the rest of the molecule,

R 2 represents a methyl group

Ar represents a group of the formula

in which
# 1 represents the point of attachment to the nitrogen atom,
R 3A represents a group selected from cyano and trifluoromethoxy,
R 3B represents a group selected from a chlorine atom and trifluoromethyl,

or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

4. A compound of general formula (I) according to claim 1 , wherein
R 1 represents a trifluoromethyl group
or
represents a group of the formula —Y—R 2 , wherein
Y represents a group of the formula

in which
# 1 represents the point of attachment to R 2 ,
# 2 represents the point of attachment to the rest of the molecule,

R 2 represents a methyl group,

Ar represents a group of the formula

in which
# 1 represents the point of attachment to the nitrogen atom,
R 3C represents a group selected from a fluorine atom and a chlorine atom,

or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

5. The compound of formula (I) according to claim 1 , wherein the compound is selected from the group consisting of
5-(4-Chlorophenyl)-2-{[5-(1,1 -difluoroethyl)-1-(2-methylphenyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2({1-(2,6-dichlorophenyl)-5-[1-fluoroethyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-{[1-(2-chlorophenyl)-5-(difluoromethyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-({5-[1-fluoroethyl]-1-(2-methylphenyl)-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-({1-(2,6-difluorophenyl)-5-[1-fluoroethyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-{[5-(1,1-difluoroethyl)-1-(2,6-difluorophenyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-{[1-(2,6-dichlorophenyl)-5-(1,1-difluoroethyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-({5-[1-fluoroethyl]-1-(2-methylphenyl)-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-({5-[1-fluoroethyl]-1-[2-(propan-2-yl)phenyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-({5-(1,1-difluoroethyl)-1-[2-(propan-2-yl)phenyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-({1-(2-chlorophenyl)-5-[1-fluoroethyl]-1H-1,2,4-triazol -3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-({1-(2-ethylphenyl)-5-[1-fluoroethyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-{[5-(1,1-difluoroethyl)-1-(2-ethylphenyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-({1-[2-(difluoromethoxy)phenyl]-5-[1-fluoroethyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;
5-(4-Chlorophenyl)-2-{[5-(1,1-difluoroethyl)-1-(2,6-dimethylphenyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one; and
5-(4-Chlorophenyl)-2-({5-(1,1-difluoroethyl)-1-[2-(methylsulfanyl)phenyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-triflu

Assignees

• Bayer Pharma AG

Inventors

• Neubauer Thomas
• Collin-Kröpelin Marie-Pierre
• Kolkhof Peter
• Pook Elisabeth
• Wittwer Matthias Beat
• Lustig Klemens
• Schmeck Carsten
• Wasnaire Pierre
• Schirmer Heiko

Classifications

• A61P13/12

  of the kidneys · CPC title

• A61K31/4196 Primary

  1,2,4-Triazoles · CPC title

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C07D249/12

  Oxygen or sulfur atoms · CPC title