[8-(phenylsulfonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-4-yl)methanones

Patent metadata

Field	Value
Publication number	US-10167293-B2
Application number	US-201715596383-A
Country	US
Kind code	B2
Filing date	May 16, 2017
Priority date	May 26, 2016
Publication date	Jan 1, 2019
Grant date	Jan 1, 2019

Abstract

The present invention covers [8-(phenylsulfonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-4-yl)methanone compounds of general formula (I):

in which R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of disorders, in particular of gynecological disorders, hyperproliferative disorders, metabolic disorders, or inflammatory disorders as a sole agent or in combination with other active ingredients.

First claim

The invention claimed is:

1. A compound of general formula (I):

in which:
R 1 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro or cyano;
R 2 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro, cyano or SF 5 ;
R 3 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro or hydroxy;
R 4 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro, cyano or SF 5 ;
R 5 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro or cyano;

wherein R 1 and R 2 or R 2 and R 3 are optionally linked to one another in such a way that they jointly form a methylenedioxy, ethylenedioxy, ethyleneoxy, trimethyleneoxy or a group selected from:

or a stereoisomer, a tautomer, an N-oxide, or a salt thereof, or a mixture of same.

2. The compound according to claim 1 , wherein:
R 1 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro or cyano;
R 2 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro, cyano or SF 5 ;
R 3 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro or hydroxy;
R 4 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro, cyano or SF 5 ;
R 5 represents hydrogen, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 1 -C 3 -alkoxy, C 1 -C 3 -haloalkoxy, nitro or cyano;

or a stereoisomer, a tautomer, an N-oxide, or a salt thereof, or a mixture of same.

3. The compound according to claim 1 , wherein:
R 1 represents hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, trifluoromethoxy or cyano;
R 2 represents hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, trifluoromethoxy, cyano or SF 5 ;
R 3 represents hydrogen;
R 4 represents hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, trifluoromethoxy, cyano or SF 5 ;
R 5 represents hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, trifluoromethoxy or cyano;

or a stereoisomer, a tautomer, an N-oxide, or a salt thereof, or a mixture of same.

4. The compound according to claim 1 , wherein:
R 1 represents hydrogen, fluoro, chloro, bromo, methyl or trifluoromethyl;
R 2 represents hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl or SF 5 ;
R 3 represents hydrogen;
R 4 represents hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl or SF 5 ;
R 5 represents hydrogen, fluoro, chloro, bromo, methyl or trifluoromethyl;

or a stereoisomer, a tautomer, an N-oxide, or a salt thereof, or a mixture of same.

5. The compound according to claim 1 , which is selected from the group consisting of:
1 [8-(phenylsulfonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-4-yl)methanone;
2 1H-1,2,3-triazol-4-yl[8-{[2-(trifluoromethyl)phenyl]sulfonyl}-3,8-diazabicyclo[3.2.1]oct-3-yl]methanone;
3 {8-[(3,5-difluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
4 {8-[(3-fluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
5 {8-[(3-chlorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
6 {8-[(2-methylphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-4-yl)methanone;
7 {8-[(2-chlorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-4-yl)methanone;
8 [8-{[3-(pentafluoro-λ 5 -sulfanyl) phenyl]sulfonyl}-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-4-yl)methanone;
9 {8-[(3,5-dichlorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-4-yl)methanone;
10 [8-{[3,5-bis(trifluoromethyl)phenyl]sulfonyl}-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-5-yl)methanone;
11 {8-[(5-chlorothiophen-2-yl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-4-yl)methanone;
12 {8-[(2,5-difluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-4-yl)methanone;
13 {8-[(3-methylphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
14 {8-[(4-methylphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
15 {8-[(2-fluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
16 {8-[(4-fluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
17 3-{[3-(1H-1,2,3-triazol-5-ylcarbonyl)-3,8-diazabicyclo[3.2.1]oct-8-yl]sulfonyl}benzonitrile;
18 {8-[(3,5-dimethylphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
19 {8-[(2,5-dimethylphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
20 {8-[(3-methoxyphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
21 {8-[(4-methoxyphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
22 {8-[(4-chlorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
23 {8-[(3,4-difluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
24 {8-[(2,6-difluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
25 {8-[(2,4-difluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
26 {8-[(3-chloro-2-methylphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
27 {8-[(3-chloro-2-fluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
28 {8-[(3-chloro-4-fluorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
29 1H-1,2,3-triazol-5-yl[8-{[3-(trifluoromethyl)phenyl]sulfonyl}-3,8-diazabicyclo[3.2.1]oct-3-yl]methanone;
30 {8-[(2,5-dichlorophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
31 {8-[(3-bromophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
32 {8-[(2-bromophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
33 1H-1,2,3-triazol-5-yl[8-{[3-(trifluoromethoxy)phenyl]sulfonyl}-3,8-diazabicyclo[3.2.1]oct-3-yl]methanone;
34 [8-{[5-chloro-2-(trifluoromethyl)phenyl]sulfonyl}-3,8-diazabicyclo [3.2.1]oct-3-yl](1H-1,2,3-triazol-5-yl)methanone;
35 2-{[3-(1H-1,2,3-triazol-5-ylcarbonyl)-3,8-diazabicyclo[3.2.1]oct-8-yl]sulfonyl}benzonitrile;
36 1H-1,2,3-triazol-5-yl[8-{[4-(trifluoromethyl)phenyl]sulfonyl}-3,8-diazabicyclo[3.2.1]oct-3-yl]methanone;
37 {8-[(4-hydroxyphenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
38 {8-[(4-bromophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
39 [8-(naphthalen-1-ylsulfonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-5-yl)methanone;
40 [8-(quinolin-8-ylsulfonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl](1H-1,2,3-triazol-5-yl)methanone;
41 1H-1,2,3-triazol-5-yl[8-{[4-(trifluoromethoxy)phenyl]sulfonyl}-3,8-diazabicyclo[3.2.1]oct-3-yl]methanone;
42 1H-1,2,3-triazol-5-yl[8-{[2-(trifluoromethoxy)phenyl]sulfonyl}-3,8-diazabicyclo[3.2.1]oct-3-yl]methanone;
43 {8-[(4-nitrophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
44 {8-[(3-nitrophenyl)sulfonyl]-3,8-diazabicyclo[3.2.1]oct-3-yl}(1H-1,2,3-triazol-5-yl)methanone;
45 1H-1,2,3-tr

Assignees

• Bayer Pharma AG

Inventors

• Koppitz Marcus
• Siebeneicher Holger
• Steuber Holger
• Ter Laak Antonius
• Nubbemeyer Reinhard
• Rottmann Antje
• Irlbacher Horst
• Bader Benjamin
• Peters Michaele
• Wagenfeld Andrea
• Terebesi Ildiko

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title