Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1<i>H</i>-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities
Viktor A. Zapol’skii, Isabell Berneburg, Ursula Bilitewski, Melissa Dillenberger, Katja Becker, Stefan Jungwirth, Aditya Shekhar, Bastian Krueger, Dieter Kaufmann
Abstract
A series of 26 novel 1-(7-chloroquinolin-4-yl)-4-nitro-1 H -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-(1 H -1,2,4-triazol-1-yl)-1 H -pyrazol-1-yl)quinoline ( 3b ) and 7-chloro-4-(3-((4-chlorophenyl)thio)-5-(dichloromethyl)-4-nitro-1 H -pyrazol-1-yl)quinoline ( 9e ) inhibited the growth of the chloroquine-sensitive Plasmodium falciparum strain 3D7 with EC 50 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.