Aromatic sulfonamide derivatives

Patent metadata

Field	Value
Publication number	US-11524938-B2
Application number	US-202017067434-A
Country	US
Kind code	B2
Filing date	Oct 9, 2020
Priority date	May 3, 2016
Publication date	Dec 13, 2022
Grant date	Dec 13, 2022

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 method for treatment of a disease, comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula (I):

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

wherein * indicates the point of attachment of said group to the rest of the molecule;
R 2 is phenyl or heteroaryl,
wherein said phenyl or heteroaryl 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 , or substituted with two adjacent substituents R 11 which together represent a methylendioxy group to form a 5-membered ring;

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 6a and R 6b adjacent to each other together represent a group selected from —O—CH 2 —CH 2 —, —O—CH 2 —O— or —O—CH 2 —CH 2 —O—;
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
R 9 and R 10 together with the nitrogen atom to which they are attached form a 4- to 6-membered nitrogen containing heterocyclic ring, said ring optionally containing one additional heteroatom selected from the group consisting of O, S, NH, and NR a , wherein R a is a C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl group and wherein said C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl group is optionally substituted, one to three times, independently from each other, with halogen or C 1 -C 4 -alkyl;
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, morpholino,

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 a stereoisomer, a tautomer, an N oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, or a mixture of the same,
wherein said disease is a genitourinary, gastrointestinal, proliferative or pain-related disease, condition or disorder; cancer; fibrotic disease, lung fibrosis; heart fibrosis; kidney fibrosis; fibrosis of other organs; gynaecological disease; dysmenorrhea; dyspareunia; endometriosis; adenomyosis; endometriosis-associated pain; endometriosis-associated symptoms; dysuria; dyschezia; pelvic hypersensitivity; urethritis; prostatitis; prostatodynia; cystitis; idiopathic bladder hypersensitivity; gastrointestinal disorder; irritable bowel syndrome (IBS); inflammatory bowel disease (IBD); biliary colic; other biliary disorders; renal colic; diarrhea-dominant IBS; gastroesophageal reflux, gastrointestinal distension; Crohn's disease; Parkinson's disease; Alzheimer's disease; myocardial infarction; atherosclerosis; lipid disorder; functional bowel disorder; arthritis; osteoarthritis; rheumatoid arthritis; pain-associated disease or syndrome; acute, chronic, inflammatory and neuropathic pain; inflammatory pain; low back pain; surgical pain; visceral pain; dental pain; premenstrual pain; pain associated with fibrotic diseases; central pain; pain due to burning mouth syndrome; pain due to burns; pain due to migraine; cluster headaches; hyperalgesia; allodynia; pain due to traumatic nerve-injury; pain due to post-traumatic injuries; fractures; sport injuries; pain due to trigeminal neuralgia; pain associated with small fiber neuropathy; pain associated with diabetic neuropathy; chronic lower back pain; phantom limb pain; pelvic pain syndrome; chronic pelvic pain; neuroma pain; complex regional pain syndrome; pain associated with gastrointestinal distension; chronic arthritic pain and related neuralgias; pain associated with cancer; pain associated with chemotherapy; HIV and HIV treatment-induced neuropathy; pruritus; impaired wound healing; disease of the skeleton; or ankylosing spondylitis.

2. The method of claim 1 , wherein said disease is a gynaecological disease, dysmenorrhea, dyspareunia, endometriosis, adenomyosis, endometriosis-associated pain, other endometriosis-associated symptoms, dysuria, or dyschezia.

3. The method of claim 1 , wherein said disease is lung fibrosis, liver fibrosis, pruritus, osteoarthritis, or burning mouth syndrome.

4. A method for treatment of a disease, comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound, or a stereoisomer, a tautomer, an N oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, or a mixture of the same,
wherein the compound is selected from the group consisting of:
2-(2-Chlorophenyl)-N-[4-(2-oxopyridin-1(2H)-yl)-3-sulfamoylphenyl]acetamide;
N-[4-(4-Chloro-2-oxopyridin-1(2H)-yl)-3-sulfamoylphenyl]-2-(2-chlorophenyl)acetamide;
2-(2-Chlorophenyl)-N-[4-(3, 5-dichloro-2-oxopyridin-1(2H)-yl)-3-sulfamoylphenyl]acetamide;
N-[4-(3-Chloro-2-oxopyridin-1(2H)-yl)-3-sulfamoylphenyl]-2-(2-chlorophenyl)acetamide;
2-(2-Chlorophenyl)-N-[4-(3-methyl-1H-1,2,4-triazol-1-yl)-3-sulfamoylphenyl]acetamide;
2-(2-Chlorophenyl)-N-[4-(5-methyl-1H-1,2,4-triazol-1-yl)-3-sulfamoylphenyl]acetamide;
2-(2-Chlorophenyl)-N-{3-sulfamoyl-4-[3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl]phenyl}acetamide;
2-(2-Chlorophenyl)-N-{4-[5-methyl-3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl]-3-sulfamoyl

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