3-indol substituted derivatives, pharmaceutical compositions and methods for use

Patent metadata

Field	Value
Publication number	US-10544095-B2
Application number	US-201615749963-A
Country	US
Kind code	B2
Filing date	Aug 4, 2016
Priority date	Aug 10, 2015
Publication date	Jan 28, 2020
Grant date	Jan 28, 2020

Abstract

A compound of Formula I is provided:

or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula I.

First claim

The invention claimed is:

1. A compound selected from:
6-Fluoro-3-(4-methanesulfonyl-phenyl)-1H-indole,
N-(2-aminoethyl)-4-(6-fluoro-1H-indol-3-yl)benzamide,
(4-(6-fluoro-1H-indol-3-yl)phenyl)(piperazin-1-yl)methanone,
6-fluoro-3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,
4-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)morpholine,
4-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,
6-fluoro-3-(3-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,
N-(2-aminoethyl)-4-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,
N-(2-aminoethyl)-3-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,
3-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,
3-(4-(((cis)-3,5-dimethylpiperazin-1-yl)sulfonyl)phenyl)- 6-fluoro-1H-indole,
(4-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)piperazin-2-yl)methanol,
(1-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)piperazin-2-yl)methanol,
(1-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)piperazin-2-yl)methanol,
3-(4-(((3S,5S)-3,5-dimethylpiperazin-1-yl)sulfonyl)phenyl)-6-fluoro-1H-indole,
N-(2-(4-(6-fluoro-1H-indol-3-yl)phenylsulfonamido)ethyl)acetamide,
(R)-(4-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)piperazin-2-yl)methanol,
(S)-(4-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)piperazin-2-yl)methanol,
6-fluoro-3-(4-((4-(methylsulfonyl)piperazin-1-yl)sulfonyl)phenyl)-1H-indole,
3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,
4-(6-fluoro-1H-indol-3-yl)-N-(2-(methylsulfonamido)-ethyl)benzenesulfonamide,
6-fluoro-3-(2-fluoro-4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,
3-(4-chloro-3-(piperazin-1-ylsulfonyl)phenyl)-6-fluoro-1H-indole,
6-fluoro-3-(4-(piperazin-1-ylsulfonyl)-3-(trifluoromethyl)phenyl)-1H-indole,
6-fluoro-3-(2-methyl-4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,
3-(4-(6-fluoro-1H-indo-3-yl)phenylsulfonamido)propanamide,
3-(4-(6-fluoro-1H-indol-3-yl)-N-methylphenylsulfonamido)-propanamide,
6-fluoro-3-(3-fluoro-4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,
6-fluoro-3-(3-methoxy-4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,
N-(2-aminoethyl)-3-(6-fluoro-1H-indol-3-yl)-5-methylbenzene-sulfonamide,
6-fluoro-3-(3-(methylsulfonyl)phenyl)-1H-indole,
5-(6-Fluoro-1H-indol-3-yl)-2-(piperazine-1-sulfonyl)-benzonitrile,
N-(2-Amino-ethyl)-5-(6-fluoro-1H-indol-3-yl)-2-methyl-benzenesulfonamide,
6-fluoro-3-(3-methyl-4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole,
5-(6-fluoro-1H-indol-3-yl)-2-(piperazin-1-ylsulfonyl)phenol,
N-(2-aminoethyl)-2-chloro-5-(6-fluoro-1H-indol-3-yl)-benzenesulfonamide,
2-(6-fluoro-1H-indol-3-yl)-5-(piperazin-1-ylsulfonyl)benzonitrile,
N-(2-aminoethyl)-3-chloro-5-(6-fluoro-1H-indol-3-yl)-benzenesulfonamide,
N-(2-aminoethyl)-5-(6-fluoro-1H-indol-3-yl)-2-hydroxy-benzenesulfonamide,
4-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)piperazin-2-one,
5-(6-fluoro-1H-indol-3-yl)-2-(piperazin-1-ylsulfonyl)benzamide,
4-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)-1-methylpiperazin-2-one,
N-(2-aminoethyl)-2-fluoro-5-(6-fluoro-1H-indol-3-yl)-benzenesulfonamide,
N-(2-aminoethyl)-3-fluoro-5-(6-fluoro-1H-indol-3-yl)-benzenesulfonamide,
3-(3-chloro-4-(piperazin-1-ylsulfonyl)phenyl)-6-fluoro-1H-indole,
4-(6-fluoro-1H-indol-3-yl)-N-(tetrahydro-pyran-4-yl)-benzenesulfonamide,
6-fluoro-N,N-dimethyl-3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole-1-carboxamide,
4-(6-fluoro-1H-indol-3-yl)-N-(2-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-ethyl)benzenesulfonamide,
3-(4-(6-fluoro-1H-indol-3-yl)phenylsulfonamido)-N,N-dimethylpropanamide,
3-(4-(6-fluoro-1H-indol-3-yl)phenylsulfonamido)-N-methylpropanamide,
1-(6-fluoro-3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indol-1-yl)propan-1-one,
1-(6-fluoro-3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indol-1-yl)-3-methyl-butan-1-one,
4-(4-(6-fluoro-1H-indol-3-yl)phenylsulfonamido)butanamide,
4-(4-(6-fluoro-1H-indol-3-yl)-N-methylphenylsulfonamido)-butanamide,
(R)-4-(6-fluoro-1H-indol-3-yl)-N-(tetrahydrofuran-3-yl)benzenesulfon-amide,
N-(2-aminoethyl)-5-(6-fluoro-1H-indol-3-yl)-2-methylbenzenesulfon-amide,
5-(6-fluoro-1H-indol-3-yl)-N-methyl-2-(piperazin-1-ylsulfonyl)-benzamide,
(cis)-1((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)pyrrolidine-3,4-diol,
4-(6-fluoro-1H-indol-3-yl)-N-(2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)-benzenesulfonamide,
6-fluoro-N-methyl-3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole-1-carboxamide,
N-(2-aminoethyl)-3-(6-fluoro-1H-indol-3-yl)-5-methoxybenzenesulfon-amide,
N-(2-aminoethyl)-4-fluoro-3-(6-fluoro-1H-indol-3-yl)benzene-sulfonamide,
(1-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)azetidin-3-yl)methanol,
(S)-4-(6-fluoro-1H-indol-3-yl)-N-(tetrahydrofuran-3-yl)benzenesulfon-amide,
1((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)azetidin-3-ol,
(3S,4S)1-[4-(6-Fluoro-1H-indol-3-yl)-benzenesulfonyl]-pyrrolidine-3,4-diol,
1((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)azetidine-3-carboxamide,
N-(azetidin-3-yl)-4-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,
N-(2-aminoethyl)-3-(6-fluoro-1H-indol-3-yl)-5-hydroxybenzenesulfon-amide,
1-(6-fluoro-3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indol-1-yl)ethanone,
3-(3,5-dimethyl-4-(piperazin-1-ylsulfonyl)phenyl)-6-fluoro-1H-indole,
N-(2-(1H-1,2,3-triazol-4-yl)ethyl)-4-(6-fluoro-1H-indol-3-yl) benzenesulfonamide,
N-(2-(1H-imidazol-2-yl)ethyl)-4-(6-fluoro-1H-indol-3-yl)-benzenesulfonamide,
(3R,4R)-1-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)pyrrolidine-3,4-diol,
3-(3,5-difluoro-4-(piperazin-1-ylsulfonyl)phenyl)-6-fluoro-1H-indole,
3-(3,5-dichloro-4-(piperazin-1-ylsulfonyl)phenyl)-6-fluoro-1H-indole,
(R)-1-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)pyrrolidin-3-ol,
6-fluoro-3-(4-(piperazin-1-ylsulfonyl)phenyl)-1H-indole-1-carboxamide,
(S)-1((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)pyrrolidin-3-ol,
(3S,4S)-4-fluoro-1-{[4-(6-fluoro-1H-indol-3-yl)phenyl]sulfonyl}-pyrrolidin-3-amine,
(+)-(cis)-4-fluoro-1-{[4-(6-fluoro-1H-indol-3-yl)phenyl]sulfonyl}-pyrrolidin-3-amine,
(3R,4R)-4-fluoro-1-{[4-(6-fluoro-1H-indol-3-yl)phenyl]sulfonyl}-pyrrolidin-3-amine,
(−)-(cis)-4-fluoro-1-((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)-pyrrolidin-3-amine,
2-[(1-{[4-(6-fluoro-1H-indol-3-yl)phenyl]sulfonyl}piperidin-4-yl)oxy]-acetamide, 4-(6-fluoro-1H-indol-3-yl)-N-[1-(4-methyl-4H-1,2,4-triazol-3-yl)ethyl]-benzenesulfonamide,
4-(6-fluoro-1H-indol-3-yl)-N-[(4-methyl-5-oxomorpholin-2-yl-methyl]benzenesulfonamide,
N-(1,1-dioxidotetrahydrothiophen-3-yl)-4-(6-fluoro-1H-indol-3-yl)-benzenesulfonamide,
4-(6-fluoro-1H-indol-3-yl)-N-[2-(methylsulfonyl)ethyl]benzenesulfon-amide,
4-(6-fluoro-1H-indol-3-yl)-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-benzenesulfonamide,
1((4-(6-fluoro-1H-indol-3-yl)phenyl)sulfonyl)-1,4-diazepan-5-one,
4-(6-fluoro-1H-indol-3-yl)-N-(1-methyl-1H-pyrazol-5-yl)-benzenesulfonamide,
4-(6-fluoro-1H-indol-3-yl)-N-[(4-methyl-4H-1,2,4-triazol-3-yl)methyl]-benzenesulfonamide,
(−)-(R)-4-(6-fluoro-1H-indol-3-yl)-N-(2-hydroxypropyl)benzenesulfon-amide,
(+)-(S)-4-(6-fluoro-1H-indol-3-yl)-N-(2-hydroxypropyl)benzenesulfon-amide,
(cis)-3-(4-(6-fluoro-1H-indol-3-yl)phenylsulfonamido)cyclobutane-carboxamide,
4-(6-fluoro-1H-indol-3-yl)-N- [(2R)-1-hydroxypropan-2-yl]benzene-sulfonamide,
(Trans)-3-(4-(6-fluoro-1H-indol-3-yl)phenylsulfonamido)cyclobutane-carboxamide,
4-(6-fluoro-1H-indol-3-yl)-N-methyl-N-(2-sulfamoylethyl)-benzenesulfonamide,
4-(6-fluoro-1H-indol-3-yl)-N-[2-(1H-1,2,4-triazol-1-yl)ethyl]benzene-sulfonamide,
4-(6-fluoro-1H-indol-3-yl)-N-methyl-N-[2-(methylsulfamoyl)ethyl]benzenesulfonamide,
(−)-(6-fluoro-1H-indol-3-yl)-N-[(2S)-1-hydroxypropan-2-yl]-benzenesulfonamide,
4-(6-fluoro-1H-indol-3-yl)-N-(3-oxo-3-(piperazin-1-yl)propyl) benzenesulfonamide,
4-(6-fluoro-1H-indol-3-yl)-N-(3-(4-methylpiperazin-1-yl)-3-oxopropyl) benzenesulfonamide,
(−)-(S)-3-(4-(6-fluoro-1H-indol-3-yl)phenylsulfonamido)-N-(tetrahydro-furan-3-yl)propanamide,
(−)-N-(3-((3S,4S)-3-amino-4-fluoropyrrolidin-1-yl)-3-oxopropyl)-4-(6-fluoro-1H-indol-3-yl)benzenesulfonamide,
4-(6-fluoro-1H-indol-3-yl)-N-(3-morpholino-3-oxopropyl)-benzenesulfo

Assignees

• Pfizer
• Iteos Therapeutics

Inventors

• Ninkovic Sacha
• Collins Michael Raymond
• Crosignani Stefano
• Maderna Andreas
• Mcalpine Indrawan James
• Scales Stephanie Anne
• Wythes Martin

Classifications

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07D403/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61P31/18

  for HIV · CPC title