Bromophenol-pyrazoline compound and synthesis method and use thereof

Patent metadata

Field	Value
Publication number	US-2022041585-A1
Application number	US-202117375635-A
Country	US
Kind code	A1
Filing date	Jul 14, 2021
Priority date	Aug 4, 2020
Publication date	Feb 10, 2022
Grant date	—

Abstract

The present invention relates to a compound, and in particular to a bromophenol-pyrazoline compound and a synthesis method and use thereof. The bromophenol-pyrazoline compound is represented by a general structural formula below:The bromophenol-pyrazoline compound provided in the present invention has efficient inhibitory activity against the main protease Mpro, and interferes with the replication of coronavirus in cells, indicating that the compound has the effect of treating coronavirus pneumonia and thus has a broad prospect of application in the preparation of drugs for treating coronavirus pneumonia.

First claim

1 . A bromophenol-pyrazoline compound, represented by a general structural formula below:

wherein R 1 , R 2 , and R 3 are respectively any one selected from H, Br, and OH;
R 4 is any one selected from H, CHO, COCH 3 , COCH 2 CH 3 , COCH 2 CH 2 CH 3 , COOCH 3 , COOCH 2 CH 3 , Ph, CH 2 Ph, CONH 2 , CSNH 2 ,

and
R 5 , R 6 , and R 7 are respectively any one selected from H, Br, NO 2 , OH, CH 3 , OCH 3 or

2 . The bromophenol-pyrazoline compound according to claim 1 , wherein R 8 , R 9 , and R 10 in

are respectively any one selected from H, methyl, ethyl, methoxy, ethoxy, isopropyl, and t-butyl.

3 . A method for synthesizing a bromophenol-pyrazoline compound according to claim 1 , having a synthesis route below:

the method comprising: brominating vanillin (1) with bromine to produce bromovanillin (2), then removing the methyl group in the presence of AlCl 3 and pyridine to obtain brominated 3,4-dihydroxybenzaldehyde (3); reacting the compound 3 with a substituted acetophenone (4) in the presence of SOCl 2 , to produce the intermediate product chalcone (5); and cyclizing the compound (5) with a hydrazine in an ethanol solution heated to reflux, to obtain the target product bromophenol-pyrazoline (6);
wherein R 1 , R 2 , and R 3 are respectively any one selected from H, Br, and OH;
R 4 is any one selected from H, CHO, COCH 3 , COCH 2 CH 3 , COCH 2 CH 2 CH 3 , COOCH 3 , COOCH 2 CH 3 , Ph, CH 2 Ph, CONH 2 , CSNH 2 ,

and
R 5 , R 6 , and R 7 are respectively any one selected from H, Br, NO 2 , OH, CH 3 , OCH 3 or

4 . A method for synthesizing a bromophenol-pyrazoline compound according to claim 2 , having a synthesis route below:

the method comprising: brominating vanillin (1) with bromine to produce bromovanillin (2), then removing the methyl group in the presence of AlCl 3 and pyridine to obtain brominated 3,4-dihydroxybenzaldehyde (3); reacting the compound 3 with a substituted acetophenone (4) in the presence of SOCl 2 , to produce the intermediate product chalcone (5); and cyclizing the compound (5) with a hydrazine in an ethanol solution heated to reflux, to obtain the target product bromophenol-pyrazoline (6);
wherein R 1 , R 2 , and R 3 are respectively any one selected from H, Br, and OH;
R 4 is any one selected from H, CHO, COCH 3 , COCH 2 CH 3 , COCH 2 CH 2 CH 3 , COOCH 3 , COOCH 2 CH 3 , Ph, CH 2 Ph, CONH 2 , CSNH 2 ,

and
R 5 , R 6 , and R 7 are respectively any one selected from H, Br, NO 2 , OH, CH 3 , OCH 3 or

5 . The method for synthesizing a bromophenol-pyrazoline compound according to claim 3 , wherein R 8 , R 9 , and R 10 in

are respectively any one selected from H, methyl, ethyl, methoxy, ethoxy, isopropyl, and t-butyl.

6 . Use of a bromophenol-pyrazoline compound according to claim 1 in inhibiting the replication of coronavirus.

7 . Use of a bromophenol-pyrazoline compound according to claim 2 in inhibiting the replication of coronavirus.

8 . Use of a bromophenol-pyrazoline compound according to claim 5 in the preparation of drugs for treating coronavirus pneumonia.

9 . A drug for treating coronavirus pneumonia, comprising an effective dose of one or a mixture of two or more of the a bromophenol-pyrazoline compounds according to claim 1 .

10 . A drug for treating coronavirus pneumonia, comprising an effective dose of a bromophenol-pyrazoline compound according to claim 2 , or a mixture of two or more thereof.

Assignees

• Univ Shandong

Inventors

• Shi Dayong
• Li Xiangqian
• Wang Xin
• Yang Jinbo

Classifications

• C07D417/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61P31/14 Primary

  for RNA viruses · CPC title

• C07D231/06 Primary

  having one double bond between ring members or between a ring member and a non-ring member · CPC title