Compound having BLT inhibitory activity and composition, for preventing or treating inflammatory diseases, comprising same as active ingredient

Patent metadata

Field	Value
Publication number	US-10179764-B2
Application number	US-201615745337-A
Country	US
Kind code	B2
Filing date	Jul 23, 2016
Priority date	Jul 24, 2015
Publication date	Jan 15, 2019
Grant date	Jan 15, 2019

Abstract

The present invention relates to a novel compound showing leukotriene B4 receptor 2 (BLT2) inhibitory activity and a pharmaceutical composition, for preventing or treating inflammatory diseases, having same as an active ingredient. The inventors identified a novel compound containing BTL2 inhibitory activity, and experimentally confirmed that the present novel compound had an excellent effect on the enhancement of the cancer cell death, on the inhibition of the metastasis and chemotactic mobility, and on the anti-asthma activity. Therefore, the present novel compound can be used as a very effective pharmaceutical component for treating the inflammatory-related diseases.

First claim

The invention claimed is:

1. A compound represented by Formula 1 or a pharmaceutically acceptable salt thereof:

wherein,
R 1 is C 1 to C 10 alkyl;

R 2 is
wherein,
R a is

or hydroxy;
R b is

R c is

R d is hydrogen or

and
R e is

and
R 3 is hydrogen or fluorine.

2. The compound of claim 1 , wherein the compound represented by Formula 1 is selected from the group consisting of:
tert-butyl 4-(4-(3-(N-phenylpentaneamido)prop-1-ynyl)benzoyl)piperazine-1-carboxylate;
N-phenyl-N-(3-(4-(piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(3-(4-(4-methylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(4-(4-ethylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(4-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(4-(4-(2-hydroxyethyl)piperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(4-(4-cyclohexylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(4-(4-(cyclohexylmethyl)piperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(4-(4-isobutylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-phenyl-N-(3-(4-(4-(prop-2-ynyl)piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(3-(4-(4-cyanopiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
tert-butyl 4-(4-(3-(N-(3-fluorophenyl)pentaneamido)prop-1-ynyl)benzoyl)piperazine-1-carboxylate;
N-(3-fluorophenyl)-N-(3-(4-(piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(3-fluorophenyl)-N-(3-(4-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
tert-butyl 4-(4-(3-(N-(4-fluorophenyl)pentaneamido)prop-1-ynyl)benzoyl)piperazine-1-carboxylate;
N-(4-fluorophenyl)-N-(3-(4-(piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(4-fluorophenyl)-N-(3-(4-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(3-(4-(morpholine-4-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-phenyl-N-(3-(4-(piperidine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N,N-diethyl-4-(3-(N-phenylpentaneamido)prop-1-ynyl)benzamide;
N-phenyl-N-(3-(3-(piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(3-(3-(4-methylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(3-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
tert-butyl-4-(3-(3-(N-(4-fluorophenyl)pentaneamido)prop-1-ynyl)benzoyl)piperazine-1-carboxylate;
N-(4-fluorophenyl)-N-(3-(3-(piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(4-fluorophenyl)-N-(3-(3-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(3-(4-hydroxyphenyl)prop-2-ynyl)-N-phenylpentaneamide; 2-(4-(3-(N-phenylpentaneamido)prop-1-ynyl)phenoxy)acetic acid;
tert-butyl 4-(5-(3-((N-phenylpentaneamido)prop-1-yn-1-yl)picolinoyl)piperazine-1-carboxylate;
N-phenyl-N-(3-(6-(piperazine-1-carbonyl)pyridine-3-yl)prop-2-yn-1-yl)pentaneamide;
N-(3-(6-isopropylpiperazine-1-carbonyl)pyridine-3-yl)prop-2-yn-1-yl)pentaneamide;
N,N-diethyl-4-(3-(N-(3-fluorophenyl)pentaneamido)prop-1-yn-1-yl)benzamide;
N,N-diethyl-4-(3-(N-(4-fluorophenyl)pentaneamido)prop-1-yn-1-yl)benzamide;
N-(3-(4-(N,N-diethylsulfamoyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-(3-(4-(N-isopropylsulfamoyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
tert-butyl 4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzoate; 4-(3-(N-phenylpentaneamido)pro-1-yn-1-yl)benzoic acid;
N-ethyl-4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamide;
N-(2-(diethylamino)ethyl)-4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamide;
ethyl 2-(4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamido)acetate;
2-(4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamido)acetic acid;
methyl 2-(4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamido)propanoate;
2-(4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamido)propionic acid;
2-(4-(3-(N-(3-fluorophenyl)pentaneamido)prop-1-ynyl)phenoxy)acetic acid
4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzoic acid;
N-phenyl-N-(3-(4-(piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentanamide;
N-(2-(dimethylamino)ethyl)-4-(3-(N-phenylpentaneamido)prop-1-yn-1-1-yl)benzamide;
2-(4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamido)propanoic acid; and
2-(4-(3-(N-(4-fluorophenyl)pentaneamido)prop-1-ynyl)phenoxy)acetic acid.

3. The compound of claim 1 selected from the group consisting of:
N-(3-(4-(4-methylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-phenyl-N-(3-(4-(piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentanamide;
N-(3-(4-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N-phenyl-N-(3-(3-(piperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(4-fluorophenyl)-N-(3-(4-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
N-(3-(3-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)-N-phenylpentaneamide;
N,N-diethyl-4-(3-(N-phenylpentaneamido)prop-1-ynyl)benzamide;
N-(3-fluorophenyl)-N-(3-(4-(4-isopropylpiperazine-1-carbonyl)phenyl)prop-2-ynyl)pentaneamide;
4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzoic acid;
N-(2-(dimethylamino)ethyl)-4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamide;
methyl 2-(4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamido)propanoate; and
2-(4-(3-(N-phenylpentaneamido)prop-1-yn-1-yl)benzamido)propanoic acid.

4. A pharmaceutical composition comprising:
a pharmaceutically acceptable salt of the compound of claim 1 as an active ingredient.

5. The compound of claim 1 , wherein
R 1 is n-Butyl;
R 2 is

wherein,
R a is

or hydroxy; and
R b is

Assignees

• Univ Dongguk Ind Acad Coop
• Univ Korea Res & Bus Found

Inventors

• Choi Yongseok
• Kim Jae-Hong
• Lee Kyeong
• Han Hyo-Kyung
• Wei Jun Dong
• Kwon Jinsun
• Goo Ja-Il

Classifications

• C07D295/205

  Radicals derived from carbonic acid · CPC title

• A61K31/5375

  1,4-Oxazines, e.g. morpholine · CPC title

• C07C233/51

  having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings · CPC title

• C07D211/06

  having no double bonds between ring members or between ring members and non-ring members · CPC title

• C07C237/42

  having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated · CPC title