Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

Beilstein Journal of Organic Chemistry

Isabell Berneburg¹  Katja Becker¹  Melissa Dillenberger¹  Stefan Jungwirth²  Aditya Shekhar²  Ursula Bilitewski²  Dieter E. Kaufmann³  Bastian Krueger³  Viktor A. Zapol’skii³ 

[1] Biochemistry and Molecular Biology Interdisciplinary Research Center, Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany;Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany;Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany;

关键词: antimalarial activity;    anti-sars-cov-2 activity;    chloroquine;    2-nitroperchlorobutadiene;    nucleophilic vinylic substitution;    1h-pyrazoles;   

DOI  :  10.3762/bjoc.18.54

来源: DOAJ

【 摘 要 】

A series of 26 novel 1-(7-chloroquinolin-4-yl)-4-nitro-1H-pyrazoles bearing a dichloromethyl and an amino or thio moiety at C3 and C5 has been prepared in yields up to 72% from the reaction of 1,1-bisazolyl-, 1-azolyl-1-amino-, and 1-thioperchloro-2-nitrobuta-1,3-dienes with 7-chloro-4-hydrazinylquinoline. A new way for the formation of a pyrazole cycle from 3-methyl-2-(2,3,3-trichloro-1-nitroallylidene)oxazolidine (6) is also described. In addition, the antimalarial activity of the synthesized compounds has been evaluated in vitro against the protozoan malaria parasite Plasmodium falciparum. Notably, the 7-chloro-4-(5-(dichloromethyl)-4-nitro-3-(1H-1,2,4-triazol-1-yl)-1H-pyrazol-1-yl)quinoline (3b) and 7-chloro-4-(3-((4-chlorophenyl)thio)-5-(dichloromethyl)-4-nitro-1H-pyrazol-1-yl)quinoline (9e) inhibited the growth of the chloroquine-sensitive Plasmodium falciparum strain 3D7 with EC50 values of 0.2 ± 0.1 µM (85 ng/mL, 200 nM) and 0.2 ± 0.04 µM (100 ng/mL, 200 nM), respectively. Two compounds (3b and 10d) have also been tested for anti-SARS-CoV-2, antibacterial, and cytotoxic activity.

【 授权许可】

Unknown