Microwave-assisted, rapid synthesis of 2-vinylquinolines and evaluation of their antimalarial activity

Abstract

A rapid and efficient synthesis of 2-vinylquinolines via trifluoromethanesulfonamidemediated olefination of 2-methylquinoline and aldehyde under microwave irradiation is reported. Biological evaluation of these scaffolds demonstrates that 2-vinylquinolines 3x -3z possess excellent antimalarial activities against chloroquine-resistant Dd2 strain of Plasmodium falciparum (IC 50 < 100 nM).

Synthesis, Structure–Activity Relationship, and Antimalarial Efficacy of 6-Chloro-2-arylvinylquinolines

“…Even with an aromatic group, the saturated analogues showed almost an order of magnitude weaker activity than the vinyl analogues, as demonstrated by pyridylethylquinoline 58 (EC 50 = 708.7 ± 58.2 nM) versus 41 (EC 50 = 38.8 ± 4.7 nM) and pyridylethylquinolines 59 (EC 50 = 259.0 ± 15.5 nM) versus 50 (EC 50 = 28.8 ± 5.0 nM). Therefore, these data indicated that the absence of the 2-arylvinyl moiety severely reduced antiplasmodial activity, which was in line with recent studies. , …”

“…(E)-N 1 -(6-Fluoro-2-(2-(furan-2-yl)vinyl)quinolin-4-yl)-N 2 ,N 2 -dimethylethane-1,2-diamine(44). The title compound was synthesized from 6b and 38a.…”

Acylacetylenes in multiple functionalization of hydroxyquinolines and quinolones

“…When choosing the latter, we were guided by the following reasons: (i) the ability of the acylacetylenes to generate chalcone upon adding protogenic (OH or NH) functions to the triple bond; (ii) potential biological activity of the aromatic (aryl) or heteroaromatic (pyrrolyl, furyl, thienyl) substituents; (iii) synthetically suitable balance between high reactivity and stability (convenience to be handled). The merging of biological active chalcone [ [30] , [31] , [32] ] and quinoline [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] ] structures in a one molecule could result in a synergetic effect and extension of the scope of their pharmaceutically important properties. The acetylenic ketone with branched acetal substituents at the triple bond 2i , benzoyloxysecbutylbenzoylacetylene, was specially synthesized to provide additional possibilities for further functionalization (in particular, after deprotection of the hydroxyl group) of adducts as well as to evaluation steric effect of the reaction.…”

“…Functionalized quinolines [ 7 , 8 ] and fluoroquinolines [ [9] , [10] , [11] , [12] , [13] , [14] ] gave rise to a new generation of antibiotics. The modern antimalarial therapy cannot be imaged without the functionalized natural quinoline, quinine, and its later modifications such as chloroquine, amodiaquine, and mefloquine [ [15] , [16] , [17] ] ( Fig. 1 ).…”

Cyanoquinolines and Furo[3,4-b]quinolinones Formation via On-The-Spot 2,3-Functionalization of Quinolines with Cyanopropargylic Alcohols

“…Functionalized quinolines are the object of intensive research owing to their biological activity. These compounds exhibit anticancer, antitubercular, antibacterial, antioxidant, antifungal, and antiviral activities. Of special interest are cyano-substituted quinolines.…”