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

Abstract

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.

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

“…These are usually accessed from the respective amines or organohalides (5 and 6, Scheme 1) [14,[16][17][18]. Few examples of triazole-pyrazole hybrids, such as 13, have also been synthesized through a modified Sakai reaction [19], a reaction cascade involving the elimination of an azole [20] or in the n-butyllithium-mediated reaction with alkyl halides [21]. So far, the literature-reported methods are most often limited to N-unsubstituted pyrazoles or triazoles and pyrazoles being fused to a second (hetero)cycle; the synthesis of promising multi-substituted structures such as 1 has not yet been described systematically.…”

A New Way to 2,3,4-Trisubstituted Benzo[h]quinolines: Synthesis, Consecutive Reactions and Cellular Activities

“…Previous articles in the field of polyhalogenated nitrobutadienes have already demonstrated the enormous potential of pentachloro-2-nitro-1,3-butadiene (1) as a precursor for the "click synthesis" of highly functionalized (hetero)cyclic as well as acyclic compounds [1,2]. The corresponding syntheses that we have developed up to now always start with the attack of an appropriate nucleophile at the activated terminal carbon atom of the nitrodichlorovinyl group within 1 to undergo a vinylic substitution reaction.…”

A New Way to 2,3,4-Trisubstituted Benzo[h]quinolines: Synthesis, Consecutive Reactions and Cellular Activities †

“…Previous articles in the field of polyhalogenated nitrobutadienes have already demonstrated the enormous potential of pentachloro-2-nitro-1,3-butadiene ( 1 ) as a precursor for the “click synthesis” of highly functionalized (hetero)cyclic, as well as acyclic, compounds [ 1 , 2 ]. The corresponding syntheses that we have developed to date always start with the attack of an appropriate nucleophile at the activated terminal carbon atom of the nitrodichlorovinyl group within 1 to undergo a vinylic substitution reaction.…”