Oxindole compounds and pharmaceutical compositions thereof

Patent metadata

Field	Value
Publication number	US-10370328-B2
Application number	US-201615565820-A
Country	US
Kind code	B2
Filing date	Apr 28, 2016
Priority date	Apr 30, 2015
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

Abstract

Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of degenerative diseases and disorders.

First claim

What is claimed is:

1. A compound, or a pharmaceutically acceptable salt thereof, wherein said compound is:
3-hydroxy-5-methyl-1-(2,2,2-trifluoroethyl)-3-(3,4,5-trimethoxybenzyl)indolin-2-one;
2-((3-hydroxy-5-methyl-1-(4-methylpentyl)-2-oxoindolin-3-yl)methyl)-5-methoxyphenyl isonicotinate;
2-((3-hydroxy-5-methyl-1-(4-methylpentyl)-2-oxoindolin-3-yl)methyl)-5-methoxyphenyl acetate;
2-((3-hydroxy-5-methyl-1-(4-methylpentyl)-2-oxoindolin-3-yl)methyl)-5-methoxyphenyl 2-methoxyacetate;
5-chloro-1-ethyl-3-(2-hydroxy-3-methoxybenzyl)-2-oxoindolin-3-yl isonicotinate;
5-chloro-1-ethyl-3-(2-hydroxy-3-methoxybenzyl)-2-oxoindolin-3-yl picolinate;
5-chloro-1-ethyl-3-(2-hydroxy-3-methoxybenzyl)-2-oxoindolin-3-yl diethyl phosphate;
2-((5-chloro-1-ethyl-3-hydroxy-2-oxoindolin-3-yl)methyl)-6-methoxyphenyl 2-methoxyacetate;
2-((5-chloro-1-ethyl-3-hydroxy-2-oxoindolin-3-yl)methyl)-6-methoxyphenyl butyrate;
5-chloro-1-ethyl-3-(2-hydroxy-3-methoxybenzyl)-2-oxoindolin-3-yl dimethylcarbamate;
(1,3-dioxolan-4-yl)methyl (5-chloro-1-ethyl-3-(2-hydroxy-3-methoxybenzyl)-2-oxoindolin-3-yl) carbonate;
5-chloro-1-ethyl-3-(2-(((2-(2-hydroxyethoxy)ethyl)carbamoyl)oxy)-3-methoxybenzyl)-2-oxoindolin-3-yl benzoate;
2-((5-chloro-1-ethyl-2-oxoindolin-3-yl)methyl)-6-methoxyphenyl dimethylcarbamate;
3-hydroxy-1,5-dimethyl-3-((1-methyl-1H-indazol-4-yl)methyl)indolin-2-one;
1-butyl-3-((1-methyl-1H-indazol-4-yl)methyl)-2-oxoindolin-3-yl benzoate;
3-(benzo[d][1,3]dioxol-4-ylmethyl)-5-chloro-2-oxo-1-propylindolin-3-yl benzoate;
3-(benzo[d][1,3]dioxol-4-ylmethyl)-1-ethyl-3-hydroxy-5-methylindolin-2-one;
3-(benzo[d][1,3]dioxol-4-ylmethyl)-1-butyl-3-hydroxyindolin-2-one;
3-(benzo[d][1,3]dioxol-4-ylmethyl)-3-hydroxy-1-isobutylindolin-2-one;
3-(benzo[d][1,3]dioxol-4-ylmethyl)-1-isopentyl-2-oxoindolin-3-yl benzoate;
3-(benzo[d][1,3]dioxol-4-ylmethyl)-1-isobutyl-5-methyl-2-oxoindolin-3-yl benzoate;
3-(benzo[d][1,3]dioxol-4-ylmethyl)-1-isopentyl-5-methyl-2-oxoindolin-3-yl benzoate;
3-((1H-benzo[d]imidazol-4-yl)methyl)-5-chloro-1-ethyl-3-hydroxyindolin-2-one,
1-ethyl-3-(2-hydroxy-3,4-dimethoxybenzyl)-5-methyl-2-oxoindolin-3-yl dimethylcarbamate;
3-((1-benzoyl-1H-indol-3-yl)methyl)-2-oxo-1-propylindolin-3-yl dimethylcarbamate;
3-((1H-benzo[d]imidazol-4-yl)methyl)-5-chloro-1-methyl-2-oxoindolin-3-yl dimethylcarbamate;
5-chloro-1-ethyl-3-(pyrimidin-4-ylmethyl)indolin-2-one;
5-methyl-1-ethyl-3-(pyrimidin-4-ylmethylene)indolin-2-one;
5-chloro-1-ethyl-3-hydroxy-3-(pyrazin-2-ylmethyl)indolin-2-one;
1-ethyl-5-methyl-3-(pyrazin-2-ylmethylene)indolin-2-one;
1-propyl-3-(pyridazin-3-ylmethyl)indolin-2-one;
N-(5-chloro-2-oxo-1-propyl-3-(pyridazin-3-ylmethyl)indolin-3-yl)nicotinamide;
3-((1H-benzo[d]imidazol-2-yl)methylene)-5-chloro-1-ethylindolin-2-one;
5-chloro-3-hydroxy-1-propyl-3-(pyrazin-2-ylmethyl)indolin-2-one;
5-chloro-3-hydroxy-1-methyl-3-(pyridin-4-ylmethyl)indolin-2-one;
5-chloro-3-hydroxy-1-propyl-3-(pyridazin-4-ylmethyl)indolin-2-one;
3-hydroxy-1-methyl-3-(pyridin-4-ylmethyl)indolin-2-one;
(E)-3-((11H-benzo[d]imidazol-2-yl)methylene)-5-chloro-1-methylindolin-2-one;
N-(3-((1H-benzo[d]imidazol-2-yl)methyl)-1-methyl-2-oxoindolin-3-yl)nicotinamide;
1-ethyl-3-hydroxy-3-(pyridazin-3-ylmethyl)indolin-2-one;
1-ethyl-5-methyl-3,3-bis(pyridazin-4-ylmethyl)indolin-2-one;
1-propyl-3,3-bis(pyridazin-4-ylmethyl)indolin-2-one;
1-ethyl-3-hydroxy-5-methyl-3-(pyridazin-3-ylmethyl)indolin-2-one;
N-(3-((1H-benzo[d]imidazol-2-yl)methyl)-5-chloro-1-ethyl-2-oxoindolin-3-yl)isonicotinamide;
3-(benzo[d]oxazol-2-ylmethylene)-5-chloro-1-methylindolin-2-one;
N-(3-((1H-benzo[d]imidazol-2-yl)methyl)-5-chloro-2-oxo-1-propylindolin-3-yl)benzamide;
1-methyl-3-(oxazolo[4,5-b]pyridin-2-ylmethylene)indolin-2-one;
5-chloro-2-oxo-1-(2-(piperidin-1-yl)ethyl)-3-(pyridin-2-ylmethyl)indolin-3-yl dimethylcarbamate;
N-(3-((3-methoxypyridin-2-yl)methyl)-2-oxo-1-propylindolin-3-yl)benzamide;
N-(5-chloro-1-ethyl-2-oxo-3-(pyridin-2-ylmethyl)indolin-3-yl)-4-methylbenzenesulfonamide;
3-(1-ethyl-5-methyl-3-((1-methyl-1H-indazol-4-yl)methyl)-2-oxoindolin-3-yl)-1,1-dimethylurea;
1,1-dimethyl-3-(3-((1-methyl-1H-indazol-4-yl)methyl)-2-oxo-1-propylindolin-3-yl)urea;
3-(3-(benzo[d][1,3]dioxol-4-ylmethyl)-2-oxo-1-propylindolin-3-yl)-1,1-dimethylurea;
3-(3-(benzo[d][1,3]dioxol-4-ylmethyl)-5-chloro-1-methyl-2-oxoindolin-3-yl)-1,1-dimethylurea;
3-(3-(benzo[d][1,3]dioxol-4-ylmethyl)-5-chloro-2-oxo-1-propylindolin-3-yl)-1,1-dimethylurea;
3-(1,5-dimethyl-2-oxo-3-(3,4,5-trimethoxybenzyl)indolin-3-yl)-1,1-dimethylurea;
3-(1-ethyl-2-oxo-3-(3,4,5-tri methoxybenzyl)indolin-3-yl)-1,1-dimethylurea;
3-(3-((1-benzoyl-1H-indol-3-yl)methyl)-1-ethyl-2-oxoindolin-3-yl)-1,1-dimethylurea;
3-(3-((1-benzoyl-1H-indol-3-yl)methyl)-1-methyl-2-oxoindolin-3-yl)-1,1-dimethylurea;
3-(3-((1-benzoyl-1H-indol-3-yl)methyl)-2-oxo-1-propylindolin-3-yl)-1,1-dimethylurea;
3-(3-((1-benzoyl-1H-indol-3-yl)methyl)-5-methyl-2-oxo-1-propylindolin-3-yl)-1,1-dimethylurea;
or
2-((5-chloro-1-ethyl-3-hydroxy-2-oxoindolin-3-yl)methyl)-6-methoxyphenyl dimethylsulfamate.

2. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignees

• Musc Found For Res Dev
• Us Dept Veterans Affairs

Inventors

• Beeson Craig C
• Lindsey Christopher C
• Rohrer Baerbel
• Peterson Yuri Karl

Classifications

• C07D413/06

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

• C07D405/06

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

• C07D209/36

  in position 3, e.g. adrenochrome · CPC title

• C07D405/12

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

• C07D209/38 Primary

  in positions 2 and 3, e.g. isatin · CPC title