Phenoxypropanol derivative and pharmaceutical composition including the same

Patent metadata

Field	Value
Publication number	US-9458120-B2
Application number	US-201214361844-A
Country	US
Kind code	B2
Filing date	Nov 30, 2012
Priority date	Nov 30, 2011
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

Abstract

The present invention relates to a novel phenoxypropanol derivative, represented by the structure of Chemical Formula I, and a racemate thereof, a pharmaceutically acceptable salt thereof, a solvate thereof and a hydrate thereof,

wherein * represents an (R)-form or an (S)-form, X is selected from the group consisting of hydrogen, halogen and substituted or unsubstituted straight or branched alkyl having 1 to 4 carbon atoms, and n represents the number of X and an integer of 1 to 5, wherein at least a hydrogen is substituted with halogen in the substituted linear or branched alkyl having 1 to 4 carbon atoms. The derivative can be used for blocking T-type calcium channel and/or TREK channel, and for preventing and/or treating T-type calcium channel- and/or TREK channel-associated diseases.

First claim

What is claimed is:

1. A phenoxypropanol derivative having the structure of Chemical Formula I, and a racemate thereof, a pharmaceutically acceptable salt thereof, a solvate thereof and a hydrate thereof,

wherein * represents an (R)-form or an (S)-form,
X is selected from the group consisting of hydrogen, halogen, and substituted or unsubstituted straight or branched alkyl having 1 to 4 carbon atoms, and n represents the number of X and is an integer of 1 to 5, wherein at least a hydrogen is replaced with halogen in the substituted linear or branched alkyl having 1 to 4 carbon atoms,
R is selected from compounds of the following Chemical Formulae IV,

wherein: R2 may be each independently selected from the group consisting of straight or branched alkyl having 1 to 4 carbon atoms and cycloalkyl having 3 to 8 carbon atoms, and one or two thereof may exist,
R3 is a substituent binding to carbon of the phenyl group, and one or two thereof may exist, and may be each independently one or more selected from the group consisting of hydrogen, straight or branched alkyl having 1 to 4 carbon atoms, straight or branched alkyl having 1 to 4 carbon atoms, of which one or more hydrogens are substituted with halogen.

2. The phenoxypropanol derivative, a racemate thereof, a pharmaceutically acceptable salt thereof, a solvate thereof and a hydrate thereof according to claim 1 , wherein
the substituent X is selected from the group consisting of hydrogen, methyl and trifluoromethyl,
the substituent R2 is selected from the group consisting of isobutyl, isopropyl and cyclopropyl,
the substituent R3 is selected from the group consisting of methyl, trifluoromethyl and halogen.

3. The phenoxypropanol derivative, a racemate thereof, a pharmaceutically acceptable salt thereof, a solvate thereof and a hydrate thereof according to claim 1 , wherein the phenoxypropanol derivative may be selected from the group consisting of the following compounds.
(R)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1-yl)-N-((5-isobutyl-1-phenyl-1H-pyrazol-3-yl)methyl)acetamide;
(R)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1-yl)-N-((5-isopropyl-1-phenyl-1H-pyrazol-3-yl)methyl)acetamide;
(R)-N-((5-cyclopropyl-1-phenyl-1H-pyrazol-3-yl)methyl)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1-yl)acetamide;
(R)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1-yl)-N-((5-isobutyl-1-phenyl-1H-pyrazol-3-yl)methyl)acetamide;
(S)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1-yl)-N-((5-isobutyl-1-phenyl-1H-pyrazol-3-yl)methyl)acetamide;
(S)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1-yl)-N-((5-isobutyl-1-phenyl-1H-pyrazol-3-yl)methyl)acetamide;
(R)-N-((1-(5-fluoro-2-methylphenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin- 1-yl)acetamide;
(R)-N-((1-(4-fluoromethyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1- yl)acetamide;
(R)-N-((1-(3,5-dichlorophenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1- yl)acetamide;
(S)-N-((1-(4-fluorophenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1- yl)acetamide;
(S)-N-((1-(3,5-dichlorophenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1- yl)acetamide;
(S)-N-((1-(5-fluoro-2-methylphenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin- 1-yl)acetamide;
(S)-2-(4-(2-hydroxy-3-(4-(trifluoromethyl)phenoxy)propyl)piperazin-1-yl)-N-((5-isobutyl-1-o-tolyl-1H-pyrazol-3-yl)methyl)acetamide;
(R)-N-((1-(3,5-dichlorophenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1-yl)acetamide;
(R)-N-((1-(5-fluoro-2-methylphenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1- yl)acetamide;
(R)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1-yl)-N-((5-isobutyl-1-o-tolyl-1H-pyrazol-3-yl)methyl)acetamide;
(R)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1-yl)-N-((1-(4-fluorophenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)acetamide;
(S)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1-yl)-N-((5-isobutyl-1-o-tolyl-1H-pyrazol-3-yl)methyl)acetamide;
(S)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1-yl)-N-((1-(4-fluorophenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)acetamide;
(S)-N-((1-(5-fluoro-2-methylphenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1- yl)acetamide; and
(S)-N-((1-(3,5-dichlorophenyl)-5-isobutyl-1H-pyrazol-3-yl)methyl)-2-(4-(3-(4-fluorophenoxy)-2-hydroxypropyl)piperazin-1-yl)acetamide.

Assignees

• Korea Inst Sci & Tech
• Korba Inst Of Science And Tech

Inventors

• Roh Eun-Joo
• Shin Kye-Jung
• Lee Changjoon Justin
• Oh Soo Jin
• Park Jung-Eun
• Yang Jeong Eun
• Hwang Eun Mi
• Woo Dong Ho
• Lee Soon-Hyouk
• Kim Dong-Gyu
• Chun Hee-Jung
• Ji Wan-Keun
• Na Yun-Soo

Classifications

• C07D211/58

  attached in position 4 · CPC title

• C07D295/15 Primary

  to an acyclic saturated chain · CPC title

• C07D211/38

  Halogen atoms or nitro radicals · CPC title

• C07D233/64

  with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine · CPC title

• C07D231/40

  Acylated on said nitrogen atom · CPC title