Quinolines and structurally related heterocycles as antimalarials

Crystal structure of ethyl 6-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate, C13H13NO3

“…Particularily intriguing are quinoline and its derivatives as these have already found application as anticancer [3], antiviral [4] and antimalarial [5] agents. In view of the biological importance as well as possible pharmacological applications, the title compound was synthesized to study its crystal structure.…”

Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines

“…The improvement of potency against chloroquine resistant strains of P. falciparum of other bis(4-aminoquinoline) derivatives relative to the corresponding monomeric compounds has been ascribed mainly to the doubling of the number of protonatable nitrogen atoms in the dimers, which might lead to more efficient trapping in the acidic digestive vacuole of the parasite and prevention of heme polymerization. 25,29 The failure of bis-huprines to show antiplasmodial activity might be indicative of the fact that these compounds cannot hit the biological target of chloroquine and other 4-aminoquinoline derivatives despite their structural similarity. Indeed, we have recently found that the parent huprine Y, unlike chloroquine, shows no inhibition of β-haematin formation, whereas several huprine analogues that possess antiplasmodial activity are effective inhibitors of β-haematin formation (unpublished results).…”

“…23 Molecular dimerization of compounds with known antiprotozoal activity constitutes a strategy that can be used to overcome drug resistance. 25 This approach has proven successful for dimers of 4-aminoquinolines, in which the two constituting units were connected through linkers of different length or containing different functional groups. [26][27][28][29] Here, we report the synthesis of dimers of huprine Y, in which the two huprine moieties have been connected through oligomethylene linkers of different length, or with a p-phenylenebis(methylene) tether.…”

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

“…For example, chloroquine (46) has been used for its antimalarial activity for more than 60 years; [56][57][58] bedaquiline (47), an inhibitor of the mycobacterial ATP synthase, has been approved to treat multi-drug resistant tuberculosis, [59] and cabozantinib (48), a multitargeted receptor tyrosine kinase inhibitor, showed effective anticancer activity and has been marketed for the treatment of medullary thyroid cancer ( Figure 4) Quinolines and their derivatives are important heterocyclic compounds because of their wide-ranging biological activities [52][53][54] and interesting photochemical properties [55]. For example, chloroquine (46) has been used for its antimalarial activity for more than 60 years; [56][57][58] bedaquiline (47), an inhibitor of the mycobacterial ATP synthase, has been approved to treat multi-drug resistant tuberculosis, [59] and cabozantinib (48), a multitargeted receptor tyrosine kinase inhibitor, showed effective anticancer activity and has been marketed for the treatment of medullary thyroid cancer ( Figure 4) [60]. Therefore, in the last decade, several new synthetic routes to quinoline derivatives under MW-irradiation have been reported [61][62][63][64][65][66].…”