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-10494333-B2
Application number	US-201615745348-A
Country	US
Kind code	B2
Filing date	Jul 23, 2016
Priority date	Jul 24, 2015
Publication date	Dec 3, 2019
Grant date	Dec 3, 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 hydrogen,

R 3 is hydrogen,

R 4 is hydrogen,

wherein R a is hydrogen, C 1 to C 10 alkyl, C 1 to C 5 carboxyl,

and
R 5 , R 6 , and R 7 are each independently hydrogen, halogen, nitro, methyl, trifluoromethyl or methoxy.

2. The compound of claim 1 , wherein
R 1 is methyl, n-butyl, or
R 2 is hydrogen;

R 3 is hydrogen,

R 4 is hydrogen,

where R a is hydrogen, methyl, C 2 to C 3 carboxyl,

and
R 5 , R 6 , and R 7 are each independently hydrogen, halogen, nitro, methyl, trifluoromethyl or methoxy.

3. The compound of claim 1 wherein
R1 is methyl, n-butyl,

R2 is hydrogen;
R3 is hydrogen,

R 4 is hydrogen or

where R a is hydrogen, methyl, C 2 to C 3 carboxyl,

or

and
R 5 , R 6 , and R 7 are each independently hydrogen, halogen, methyl, or trifluoromethyl.

4. The compound of claim 1 , wherein the compound is selected from the group consisting of:
N-((3′-(4-methylphenylsulfonamido)biphenyl-4-yl)methyl)-N-phenylpentaneamide;
N-(4′-((N-phenylpentaneamido)methyl)biphenyl-3-yl)-4-(trifluoromethyl)benzamide;
N-(3-fluorophenyl)-N-((3′-(4-methylphenylsulfonamido)biphenyl-4-yl)methyl)pentaneamide;
N-(4′-((N-3-fluorophenyl)pentaneamido)methyl)biphenyl-3-yl)-4-(trifluoromethyl)benzamide;
1-(3-fluorophenyl)-1-((4′-methoxybiphenyl-4-yl)methyl)-3-(3-(trifluoromethyl)phenyl)urea;
N-(3-fluorophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)-1-(4-methoxyphenylsulfonyl)methaneamide;
1-(3-fluorophenyl)-1-((4′-hydroxybiphenyl-4-yl)methyl)-3-(3-(trifluoromethyl)phenyl)urea;
2-(4′-((1-(3-fluorophenyl)-3-(3-(trifluoromethyl)phenyl)ureido)methyl)biphenyl-4-yloxy)acetic acid;
4-(4′-((N-(3-fluorophenyl)pentaneamido)methyl)biphenyl-4-yloxy)butanoic acid;
2-(4′-((N-(3-fluorophenyl)pentaneamido)methyl)biphenyl-4-yloxy)-2-methylpropanoic acid;
(E)-3-(4′-((N-(3-fluorophenyl)pentaneamido)methyl)biphenyl-4-yloxy)acrylic acid;
3-(4′-((N-(3-fluorophenyl)pentaneamido)methyl)biphenyl-4-yloxy)propanoic acid;
N-(3-fluorophenyl)-N-((4′-(2-(4-methylpiperazine-1-yl)-2-oxoethoxy)biphenyl-4-yl)methyl)pentaneamide;
prop-2-ynyl 2-(4′-((N-(3-fluorophenyl)pentaneamido)methyl)biphenyl-4-yloxy)acetate;
N-(3-fluorophenyl)-N-((4′-(prop-2-ynyloxy)biphenyl-4-yl)methyl)pentaneamide;
4′-((N-(2-fluorophenyl)pentaneamido)methyl)biphenyl-4-carboxylic acid;
4′-((N-(4-fluorophenyl)pentaneamido)methyl)biphenyl-4-carboxylic acid;
4′-((N-(2-methoxyphenyl)pentaneamido)methyl)biphenyl-3-carboxylic acid;
4′-((N-(3-methoxyphenyl)pentaneamido)methyl)biphenyl-3-carboxylic acid;
4′-((N-(4-methoxyphenyl)pentaneamido)methyl)biphenyl-3-carboxylic acid;
N-((2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-N-phenylpentaneamide;
N-((4′-methoxybiphenyl-4-yl)methyl)-N-phenylpentaneamide;
N-((4′-hydroxybiphenyl-4-yl)methyl)-N-phenylpentaneamide;
2-(4′-((N-phenylpentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
N-(3-fluorophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)pentaneamide;
N-(3-fluorophenyl)-N-((4′-hydroxy-[1,1′-biphenyl]-4-yl)methyl)acetamide;
2-((4′-((N-(3-fluorophenyl)acetamido)methyl)-[1,1′-biphenyl]-4-yl)oxy)acetic acid;
N-(3-chlorophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)pentaneamide;
N-(3-chlorophenyl)-N-((4′-hydroxybiphenyl-4-yl)methyl)pentaneamide;
2-(4′-((N-(3-chlorophenyl)pentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
N-(3-bromophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)pentaneamide;
N-((4′-(hydroxybiphenyl-4-yl)methyl)-N-(3-(trifluoromethyl)phenyl)pentaneamide;
2-(4′-((N-(3-bromophenyl)pentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
N-((4′-methoxybiphenyl-4-yl)methyl)-N-(3-(trifluoromethyl)phenyl)pentaneamide;
N-((4′-hydroxybiphenyl-4-yl)methyl)-N-(3-nitrophenyl)pentaneamide;
2-(4′-((N-(3-(trifluoromethyl)phenyl)pentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
N-((4′ methoxybiphenyl-4-yl)methyl)-N-m-tolylpentaneamide;
N-((4′-hydroxydiphenyl-4-yl)methyl)-N-m-tolylpentaneamide
2-(4′-((N-m-tolylpentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
2-(4′-((N-(3-nitrophenyl)pentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
N-(3-iodophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)pentaneamide;
N-((4′-hydroxybiphenyl-4-yl)methyl)-N-(3-iodophenyl)pentaneamide;
2-(4′-((N-(3-iodophenyl)pentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
N-(3-fluorophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)pentaneamide
N-(3-fluorophenyl)-N-((4′-hydroxybiphenyl-4-yl)methyl)pentaneamide;
2-(4′-((N-(3-fluorophenyl)pentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
N-((4′-(4-isopropylpiperazine-1-carbonyl)biphenyl-4-yl)methyl)-N-phenylpentaneamide;
N-(4-fluorophenyl)-N-((4′-(4-isopropylpiperazine-1-carbonyl)-biphenyl-4-yl)methyl)pentaneamide;
N-((3′-(4-isopropylpiperazine-1-carbonyl)biphenyl-4-yl)methyl)-N-phenylpentaneamide;
N-(4-fluorophenyl)-N-((3′-(4-isopropylpiperazine-1-carbonyl)biphenyl-4-yl)methyl)pentaneamide; and
N-(3-bromophenyl)-N-((4′-hydroxybiphenyl-4-yl)methyl)pentaneamide.

5. The compound of claim 4 , wherein the compound is selected from the group consisting of:
N-(4′-((N-phenylpentaneamido)methyl)biphenyl-3-yl)-4-(trifluoromethyl)benzamide;
N-(4′-((N-3-fluorophenyl)pentaneamido)methyl)biphenyl-3-yl)-4-(trifluoromethyl)benzamide;
N-(3-fluorophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)-1-(4-methoxyphenylsulfonyl)methaneamide;
N-(3-fluorophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)-1-(4-methoxyphenylsulfonyl)methaneamide;
2-(4′-((1-(3-fluorophenyl)-3-(3-(trifluoromethyl)phenyl)ureido)methyl)biphenyl-4-yloxy)acetic acid;
2-(4′-((N-(3-fluorophenyl)pentaneamido)methyl)biphenyl-4-yloxy)-2-methylpropanoic acid;
N-(3-fluorophenyl)-N-((4′-(2-(4-methylpiperazine-1-yl)-2-oxoethoxy)biphenyl-4-yl)methyl)pentaneamide;
2-(4′-((N-phenylpentaneamido)methyl)biphenyl-4-yloxy)acetic acid;
N-((4′-(hydroxybiphenyl-4-yl)methyl)-N-(3-(trifluoromethyl)phenyl)pentaneamide;
N-((4′-hydroxydiphenyl-4-yl)methyl)-N-m-tolylpentaneamide
N-(3-fluorophenyl)-N-((4′-methoxybiphenyl-4-yl)methyl)pentaneamide
N-(3-fluorophenyl)-N-((4′-hydroxybiphenyl-4

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

• C07D295/192

  from aromatic carboxylic acids · CPC title

• C07D241/04 Primary

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

• A61K31/4965

  Non-condensed pyrazines · CPC title

• C07D257/04

  Five-membered rings · CPC title

• C07D295/205

  Radicals derived from carbonic acid · CPC title