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

• Published in: Beilstein journal of organic chemistry Vol. 18; no. 1; pp. 524 - 532
• Main Authors: Zapol'skii, Viktor A, Berneburg, Isabell, Bilitewski, Ursula, Dillenberger, Melissa, Becker, Katja, Jungwirth, Stefan, Shekhar, Aditya, Krueger, Bastian, Kaufmann, Dieter E
• Format: Journal Article
• Language: English
• Published: Frankfurt am Main Beilstein-Institut zur Föerderung der Chemischen Wissenschaften 2022; Beilstein-Institut
• Subjects: 1h-pyrazoles; 2-nitroperchlorobutadiene; anti-sars-cov-2 activity; Antimalarial activity; Antiparasitic agents; Chemistry; Chloroquine; Cytotoxicity; Full Research Paper; Malaria; nucleophilic vinylic substitution; Plasmodium falciparum; Pyrazoles; Severe acute respiratory syndrome coronavirus 2
• ISSN: 2195-951X; 1860-5397; 1860-5397
• DOI: 10.3762/bjoc.18.54

A series of 26 novel l-(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-l-amino-, and l-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-l-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.