Aromatic sulfonamide derivatives

Patent metadata

Field	Value
Publication number	US-10844016-B2
Application number	US-201716098767-A
Country	US
Kind code	B2
Filing date	Apr 26, 2017
Priority date	May 3, 2016
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

Abstract

Substituted aromatic sulfonamides of formula (I) pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease.

First claim

The invention claimed is:

1. A compound of formula (I)

wherein:
X is C—R 2a ;
R 1 is a group:

wherein * indicates the point of attachment of said group to the rest of the molecule;
R 2 is pyrazolyl, wherein said pyrazolyl is optionally independently substituted one to three times with R 11 , or
independently substituted one time with R 11a and optionally one to two times with R 11 ,

R 2a is hydrogen, cyano, nitro, halogen, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;
R 2b is hydrogen, halogen, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;
R 2c is hydrogen, halogen, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl,
wherein not less than one of R 2a , R 2b and R 2c is hydrogen;

R 3 is hydrogen or fluoro;
R 4 is hydrogen, fluoro, methyl, or OH;
R 5 is hydrogen or C 1 -C 3 -alkyl;
R 6 is halogen, cyano, nitro, OH, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, or F 3 CS—;
R 6a and R 6b are the same or different, wherein
R 6a is independently hydrogen, halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, HO—(C 2 -C 4 -alkoxy)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkoxy)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)—, or (C 1 -C 4 -alkyl)-SO 2 —;
R 6b is independently hydrogen, halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, HO—(C 2 -C 4 -alkoxy)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkoxy)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)— or (C 1 -C 4 -alkyl)-SO 2 —; or
R 7a and R 7b are the same or different and are independently hydrogen, hydroxy, halogen, C 1 -C 4 -alkyl, or C 1 -C 4 -haloalkyl;
each R 8 is independently C 1 -C 6 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, or C 1 -C 4 -haloalkyl;
R 9 and R 10 are independently hydrogen, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, or (CH 3 ) 2 N—C 1 -C 4 -alkyl, or
each R 11 is independently halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 4 -haloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, (C 1 -C 4 -alkoxy)-(C 1 -C 4 -alkyl)-, (C 1 -C 4 -haloalkoxy)-(C 1 -C 4 -alkyl)-, R 9 R 10 N—(C 1 -C 4 -alkyl)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)—, (C 1 -C 4 -alkyl)-S—, or (C 1 -C 4 -alkyl)-SO 2 —;
R 11a is a group C 3 -C 6 -cycloalkyl,

wherein * indicates the point of attachment of said group to the rest of the molecule;
each R 12 is independently halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, (C 1 -C 4 -haloalkoxy)-(C 2 -C 4 -alkyl)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)—, or (C 1 -C 4 -alkyl)-SO 2 —; and
n is 0, 1, 2 or 3,
or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer.

2. The compound according to claim 1 , of formula (Ia),

wherein:
R 1 is a group:

wherein * indicates the point of attachment of said group to the rest of the molecule;
R 2 is pyrazolyl, wherein said pyrazolyl is optionally independently substituted one to three times with R 11 , or
independently substituted one time with R 11a and optionally one to two times with R 11 ,

R 2 a is hydrogen, cyano, nitro, halogen, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;
R 2b is hydrogen or halogen;
R 2c is hydrogen or halogen;
wherein not less than one of R 2a , R 2b and R 2c is hydrogen;

R 3 is hydrogen or fluoro;
R 4 is hydrogen, fluoro, methyl, or OH;
R 6 is halogen, cyano, nitro, OH, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, or F 3 CS—;
R 6 a and R 6 b are the same or different, wherein
R 6 a is independently hydrogen, halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, HO—(C 2 -C 4 -alkoxy)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkoxy)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)—, or (C 1 -C 4 -alkyl)-SO 2 —;
R 6b is independently hydrogen, halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, HO—(C 2 -C 4 -alkoxy)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkoxy)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)—, or (C 1 -C 4 -alkyl)-SO 2 —; or
R 7a and R 7b are independently hydrogen, hydroxy, halogen, C 1 -C 4 -alkyl, or C 1 -C 4 -haloalkyl;
each R 8 is independently C 1 -C 6 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, or C 1 -C 4 -haloalkyl;
R 9 and R 10 are independently hydrogen, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, or (CH 3 ) 2 N—C 1 -C 4 -alkyl, or
each R 11 is independently halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 4 -haloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, (C 1 -C 4 -alkoxy)-(C 1 -C 4 -alkyl)-, (C 1 -C 4 -haloalkoxy)-(C 1 -C 4 -alkyl)-, R 9 R 10 N—(C 1 -C 4 -alkyl)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)—, (C 1 -C 4 -alkyl)-S—, or (C 1 -C 4 -alkyl)-SO 2 —;
R 11a is a group C 3 -C 6 -cycloalkyl,

wherein * indicates the point of attachment of said group to the rest of the molecule;
each R 12 is independently halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkyl)-, (C 1 -C 4 -haloalkoxy)-(C 2 -C 4 -alkyl)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)—, or (C 1 -C 4 -alkyl)-SO 2 —; and
n is 0, 1, 2 or 3,
or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer.

3. The compound according to claim 1 , wherein:
R 1 is

wherein * indicates the point of attachment of said group to the rest of the molecule;
R 6 is halogen, cyano, nitro, OH, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, or C 1 -C 4 -haloalkoxy;
R 6 a and R 6 b are the same or different, wherein
R 6 a is independently hydrogen, halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, HO—(C 2 -C 4 -alkoxy)-, (C 1 -C 4 -alkoxy)-(C 2 -C 4 -alkoxy)-, R 9 R 10 N—, R 8 —C(O)—NH—, R 8 —C(O)—, R 8 —O—C(O)—, R 9 R 10 N—C(O)—, or (C 1 -C 4 -alkyl)-SO 2 —; and
R 6b is independently hydrogen, halogen, hydroxy, nitro, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -hal

Assignees

• Bayer Pharma AG

Inventors

• Werner Stefan
• Mesch Stefanie
• Cleve Arwed
• Bräuer Nico
• Herbert Simon Anthony
• Koch Markus
• Dahllöf Henrik
• Osmers Maren
• Hardaker Elizabeth
• Lishchynskyi Anton

Classifications

• A61K31/4418 Primary

  having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D405/06

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

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title