IP Library › Granted Patent US 11,149,033
Granted Patent B2
US 11,149,033 · App. 16/338,237 · Granted Oct 19, 2021

Heteroaryl compound, enantiomer, diastereomer or pharmaceutically acceptable salt thereof, and antiviral composition containing same as active ingredient

Inventors: Ji Young Min (Seoul, KR); So Young Chang (Seoul, KR); Ji Hye Lee (Gyeonggi-do, KR); Sun Hee Kang (Gyeonggi-do, KR); Sun Ju Kong (Gyeonggi-do, KR); Su Yeon Jo (Gyeonggi-do, KR); Young Mi Kim (Gyeonggi-do, KR); Junghwan Choi (Gyeonggi-do, KR)
Assignees: INSTITUT PASTEUR KOREA; ST PHARM CO., LTD.
C07D413/06C07D263/46C07D271/10C07D271/113C07D307/64C07D405/06
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Quick Facts
Patent No.
US 11,149,033
App. No.
16/338,237
Granted
Oct 19, 2021
Kind
B2
Abstract

The present invention relates to a novel heteroaryl compound, an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, and an antiviral composition comprising the same as an active ingredient. The novel compounds represented by formula (I) or formula (II) according to the present invention are remarkably superior in antiviral activity against an influenza virus, and furthermore, have low cytotoxicity and thus low adverse effects on a human body. Therefore, a pharmaceutical composition containing the same as an active ingredient can be effectively used for the prevention or treatment of diseases caused by an influenza virus infection.

Claims (133)

1. A compound, or a pharmaceutically acceptable salt thereof, wherein the compound is one selected from the group consisting of:

(E)-2-((4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)methyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

(E)-2-(4-bromobenzyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(2-isopropylphenethyl)-1,3,4-oxadiazole;

2-(2-isopropylphenethyl)-5-(4-(trifluoromethoxy)benzyl)-1,3,4-oxadiazole;

2-(3,5-dimethylbenzyl)-5-(2-isopropylphenethyl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-isopropylphenethyl)-1,3,4-oxadiazole;

2-(3-chlorobenzyl)-5-(2-isopropylphenethyl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(2-methylphenethyl)-1,3,4-oxadiazole;

2-(3,5-dimethylbenzyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

(E)-2-(4-bromobenzyl)-5-(2-phenoxystyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

2-(3-chloro-4-fluorobenzyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

2-(4-isopropylbenzyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(2,6-dimethylphenethyl)-1,3,4-oxadiazole;

2-([1,1′-biphenyl]-4-ylmethyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(1-(o-tolyl)propan-2-yl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(1-(o-tolyl)prop-1-en-2-yl)-1,3,4-oxadiazole;

2-(3,4-dimethylbenzyl)-5-(2-isopropylstyryl)-1, 3,4-oxadiazole;

2-(2-isopropylstyryl)-5-(1-phenylethyl)-1,3,4-oxadiazole;

2-(1-(4-isobutylphenyl)ethyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(3-isopropylstyryl)-1,3,4-oxadiazole;

(E)-2-(3-chloro-4-fluorobenzyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

(E)-N-(4-bromo-3-fluorophenyl)-5-(2-chloro-4-fluorostyryl)-N-methyl-1,3,4-oxadiazol-2-amine;

2-(4-bromobenzyl)-5-(2-(6-chlorobenzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazole;

2-(4-bromo-3-fluorobenzyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-styryl-1,3,4-oxadiazole;

2-(4-bromo-2-fluorobenzyl)-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(2-methylstyryl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(4-chlorostyryl)-1,3,4-oxadiazole;

2-(2-fluoro-5-methylbenzyl)-5-(2-isopropylstyryl)-1, 3,4-oxadiazole;

(E)-2-(2-chloro-4-fluorostyryl)-5-(2-fluoro-5-methylbenzyl)-1, 3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2-chloro-4-fluorostyryl)-1, 3,4-oxadiazole;

(E)-2-(2-chloro-4-fluorostyryl)-5-(3-chlorobenzyl)-1,3,4-oxadiazole;

(E)-2-(2-chloro-4-fluorostyryl)-54(6-chloropyridin-3-yl)methyl)-1,3,4-oxadiazole;

(E)-2-(3-bromo-4-methylbenzyl)-5-(2-chloro-4-fluorostyryl)-1, 3,4-oxadiazole;

(E)-2-(2-chloro-4-fluorostyryl)-5-(3-isopropylbenzyl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(4-fluoro-2-methylstyryl)-1, 3,4-oxadiazole;

2-(3-chlorobenzyl)-5-(2-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(4-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2,4-difluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(4-chloro-2-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(3,4-difluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2,4-dichlorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-chloro-3-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-chloro-4-methylstyryl)-1,3,4-oxadiazole;

2-benzyl-5-(2-isopropylstyryl)-1,3,4-oxadiazole;

2-(4-bromobenzyl)-5-(2-(naphthalen-1-yl)vinyl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-methyl-4-(trifluoromethyl)styryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-chloro-5-(trifluoromethyl)styryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2,4-dimethylstyryl)-1,3,4-oxadiazole;

(E)-3-((5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazol-2-yl)methyl)phenol;

(E)-2-(2-chloro-4-fluorostyryl)-5-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2-(2-methylpyridin-3-yl)vinyl)-1,3,4-oxadiazole;

(E)-2-((5-bromopyridin-3-yl)methyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

(E)-2-(2-chloro-4-fluorostyryl)-5-((4-chloropyridin-2-yl)methyl)-1,3,4-oxadiazole;

2-(3-bromo-4-fluorobenzyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(3,4-dichlorobenzyl)-1,3,4-oxadiazole;

2-(2-(5-(4-bromobenzyl)-1,3,4-oxadiazol-2-yl)vinyl)phenol;

2-(2-chloro-4-fluorostyryl)-5-(3-methylbenzyl)-1,3,4-oxadiazole;

2-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazol;

2-(2-chloro-4-fluorostyryl)-5-((1-methyl-1H-indol-3-yl)methyl)-1,3,4-oxadiazole;

(E)-2-(2-chloro-4-fluorostyryl)-5-((1-methyl-1H-indazol-3-yl)methyl)-1,3,4-oxadiazole;

2-(2-bromo-4-fluorostyryl)-5-(3-bromobenzyl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-(3-methylpyridin-4-yl)vinyl)-1,3,4-oxadiazole;

2-(2-(5-(3-bromobenzyl)-1,3,4-oxadiazol-2-yl)vinyl)phenol;

2-(2-chloro-4-fluorostyryl)-5-((6-chloropyridin-2-yl)methyl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-ethylstyryl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(2,3-dimethylbenzyl)-1,3,4-oxadiazole;

2-(2-bromobenzyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-(2-chloropyridin-3-yl)vinyl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(3-fluorobenzyl)-1,3,4-oxadiazole;

(E)-2-(2-(5-(3-bromobenzyl)-1,3,4-oxadiazol-2-yl)vinyl)-5-fluoro-N,N-dimethylaniline;

(E)-2-(3-bromobenzyl)-5-(4-fluoro-2-(pyrrolidin-1-yl)styryl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2,4,6-trifluorostyryl)-1,3,4-oxadiazole;

(E)-3-((5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazol-2-yl)methyl)benzonitrile;

2-(2-chloro-4-fluorostyryl)-5-(quinolin-8-ylmethyl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(isoquinolin-1-ylmethyl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(isoquinolin-4-ylmethyl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-(5-fluoropyridin-2-yl)vinyl)-1,3,4-oxadiazole;

2((6-bromopyridin-3-yl)methyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2((6-bromopyridin-3-yl)methyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

(E)-2-(2-chloro-4-fluorostyryl)-5-(3-(trifluoromethyl)benzyl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2-(1-isopropyl-1H-pyrazol-5-yl)vinyl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(4-fluoro-2-(piperidin-1-yl)styryl)-1,3,4-oxadiazole;

N-(3-bromophenyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole-2-carboxamide;

(E)-2-(3-bromobenzyl)-5-(2-(4-chloro-1-isopropyl-1H-pyrazol-3-ylvinyl)-1, 3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(3-fluoro-5-methylbenzyl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-(trifluoromethoxy)styryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-(3-chloro-5-fluoropyridin-2-yl)vinyl)-1, 3,4-oxadiazole;

2-(5-bromo-2-fluorobenzyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2,6-dichloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromo-4-methylbenzyl)-5-(2,4-difluorostyryl)-1,3,4-oxadiazole;

2-(3-bromo-4-fluorobenzyl)-5-(2,4-difluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(4-fluoro-2-(trifluoromethyl)styryl)-1, 3,4-oxadiazole;

2-(2-bromo-4-fluorostyryl)-5-(3-bromo-4-methylbenzyl)-1,3,4-oxadiazole;

2-(3-bromo-4-fluorobenzyl)-5-(2-bromo-4-fluorostyryl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(3-cyclopropylbenzyl)-1,3,4-oxadiazole;

(E)-2-(2-(5-(3-Bromobenzyl)-1,3,4-oxadiazol-2-yl)vinyl)-5-fluoro-N-(2-methoxyethyl)-N-methylaniline;

(E)-2-(3-bromobenzyl)-5-(4-fluoro-2-(furan-3-yl)styryl)-1, 3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(4-fluoro-2-(thiophen-3-yl)styryl)-1,3,4-oxadiazole;

(E)-4-(2-(2-(5-(3-bromobenzyl)-1,3,4-oxadiazol-2-yl)vinyl)-5-fluorophenyl)morpholine;

(E)-2-(3-bromobenzyl)-5-(4-fluoro-2-isopropylstyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-chloro-4-fluorophenethyl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2-(naphthalen-1-yl)vinyl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2-(4-fluoronaphthalen-1-yl)vinyl)-1,3,4-oxadiazole;

(E)-2-((1H-indazol-3-yl)methyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2,3-difluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-(trifluoromethyl)styryl)-1,3,4-oxadiazole;

2-((4-bromopyridin-2-yl)methyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromobenzyl)-5-(2-(3,5-difluoropyridin-2-yl)vinyl)-1,3,4-oxadiazole;

2-(3-bromo-4-methylbenzyl)-5-(2-chloro-4-fluorophenethyl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2-(naphthalen-2-yl)vinyl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2,3-dimethylstyryl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2-(quinolin-5-yl)vinyl)-1,3,4-oxadiazole;

2-(2-bromo-4,6-difluorostyryl)-5-(3-bromobenzyl)-1,3,4-oxadiazole;

2-(3-chloro-2-fluorobenzyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromo-2-fluorobenzyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(3-bromo-2-methylbenzyl)-5-(2-chloro-4-fluorostyryl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-((3-chloroisoquinolin-1-yl)methyl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-((3-methoxyisoquinolin-1-yl)methyl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-((7-methoxynaphthalen-1-yl)methyl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(3-(difluoromethyl)benzyl)-1,3,4-oxadiazole;

2-(2-chloro-4-fluorostyryl)-5-(3-chloro-4-methylbenzyl)-1,3,4-oxadiazole;

(E)-2-(3-bromobenzyl)-5-(2-(quinolin-8-yl)vinyl)-1,3,4-oxadiazole;

(E)-4-(2-(2-(2-(5-(3-bromobenzyl)-1,3,4-oxadiazol-2-yl)vinyl)-5-fluorophenoxy)ethyl)morpholine;

(E)-2-(3-bromobenzyl)-5-(2-(isoquinolin-5-yl)vinyl)-1,3,4-oxadiazole;

2-(2-(5-(3-bromo-4-methylbenzyl)-1,3,4-oxadiazol-2-yl)vinyl)-5-fluoro-N-methyl-N-phenethylaniline; and

(E)-2-(3-bromobenzyl)-5-(2-(1-methyl-1H-indol-4-yl)vinyl)-1,3,4-oxadiazole.

2. An antiviral pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof as an active ingredient.

3. The pharmaceutical composition according to claim 2 , wherein the virus is an influenza virus.

4. The pharmaceutical composition according to claim 3 , wherein the influenza virus is an A type influenza virus or a B type influenza virus.

5. The pharmaceutical composition according to claim 4 , wherein the influenza virus is A/California/07/2009 (H1N1), A/Perth/16/2009 (H3N2) or B/Florida/04/2006.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 29, 2019
From: MIN, JI YOUNG; CHANG, SO YOUNG; LEE, JI HYE; KANG, SUN HEE; KONG, SUN JU; JO, SU YEON; PARK, KAAPJOO; KIM, YOUNG MI; CHOI, JUNGHWAN
To: INSTITUT PASTEUR KOREA; ST PHARM CO., LTD.
Reel/Frame 048743/0440 →
Priority Claims (1)
KR 10-2016-0126997 · Sep 30, 2016 · national
Continuity (1)
Related Publication 20200031816A1 · Jan 30, 2020
Cited By (2)
US 12,215,102 US 12,404,242