Synthesis and antiplasmodial evaluation of aziridine–(iso)quinoline hybrids and their ring-opening products

Vandekerckhove, Stéphanie; Moor, Sofie De; Segers, Dries; Kock, Carmen de; Smith, Peter J.; Chibale, Kelly; Kimpe, Norbert De; D’hooghe, Matthias

doi:10.1039/c3md20377h

Cited by 30 publications

(12 citation statements)

References 49 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 They also exhibit anti-tubercular 4 and immune depressing 4 activities. There are a few promising compounds with the quinoline ring system, like pamaquine (10), chloroquine (11), tafenoquine (12), bulaquine (13), quinine (14) and meoquine (16) as an antimalarial agents, and amodiaquine (15) as an antimalarial and anti-inammatory agent (Fig. 2).…”

Section: Activities and Applicationsmentioning

confidence: 99%

“…4exhibit potent antiplasmodial activity. 13 A new series of hybrid conjugates of N-(7-chloroquinolin-4yl) piperazine-1-carbothioamide and 1,3,5-triazine derivatives have considerable antimalarial activity against both wild and mutant parasites with marked variations on changing the pattern of substitution. Such derivatives also show excellent antibacterial activity against several Gram-positive and Gramnegative microorganisms.…”

Section: Activities and Applicationsmentioning

confidence: 99%

See 1 more Smart Citation

Recent advances in the synthesis of quinolines: a review

et al. 2014

View full text Add to dashboard Cite

show abstract

Section: Activities and Applicationsmentioning

confidence: 99%

Section: Activities and Applicationsmentioning

confidence: 99%

Recent advances in the synthesis of quinolines: a review

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Due to their considerable ring strain, these molecules show in general a high reactivity that makes them major intermediates for organic synthesis. Furthermore, several biologically active natural products [3], or analogs of them, incorporate the aziridine motif.…”

Section: Introductionmentioning

confidence: 99%

Palladium-catalyzed allylic substitution between C-based nucleophiles and 6-azabicyclo[3.1.0]-hex-3-en-2-oxy derivatives: A new selectivity paradigm

et al. 2020

View full text Add to dashboard Cite

The reaction between a-hydroxy-(or a-acetoxy) cyclopenten-aziridines (6-azabicyclo[3.1.0]hex-3-en-2ols or acetates) and C-based nucleophiles in the presence of Pd(0)-catalysis was investigated. In all the cases studied, the reaction was totally regio-and diastereo-selective, affording a single adduct in moderate to good yields. Specifically, attack of the nucleophile at position 3 of the cyclopentene moiety, anti to the vicinal oxy group, with vinylogous ring opening of the aziridine ring, was observed. When the carbon acid is a very acidic methylene (pK a (DMSO) 7.3), the resulting adduct is a zwitterion, resulting from an intramolecular proton transfer between the amino group and the carbon acid moiety taking place after the CeC bond formation. A plausible mechanism for this transformation is put forward.

show abstract

“…(aminomethyl)quinolines (inspired by quinine 1 and mefloquine 3 ), having an extra methylene linker between the quinoline core and the amino group, was developed, as this part of the antimalarial drug space is mostly untouched. Moreover, a recently reported 3-(aminomethyl)quinoline with promising activity against both a CQ-sensitive (IC 50 = 4.73 μM) and CQ-resistant (IC 50 = 15.25 μM) strain of P. falciparum [ 39 ], prompted us to combine our 1-azabicyclo[2.2.1]heptane with quinolines in this fashion. To that end, free amine 8 was subjected to reductive amination conditions using different commercially available quinoline carboxaldehydes 10a-e and NaBH 4 in methanol.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and biological evaluation of novel quinoline-piperidine scaffolds as antiplasmodium agents

Walle

Boone

Puyvelde

et al. 2020

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

The parasitic disease malaria places almost half of the world’s population at risk of infection and is responsible for more than 400,000 deaths each year. The first-line treatment, artemisinin combination therapies (ACT) regimen, is under threat due to emerging resistance of Plasmodium falciparum strains in e.g. the Mekong delta. Therefore, the development of new antimalarial agents is crucial in order to circumvent the growing resistance. Chloroquine, the long-established antimalarial drug, still serves as model compound for the design of new quinoline analogues, resulting in numerous new active derivatives against chloroquine-resistant P. falciparum strains over the past twenty years. In this work, a set of functionalized quinoline analogues, decorated with a modified piperidine-containing side chain, was synthesized. Both amino- and (aminomethyl)quinolines were prepared, resulting in a total of 18 novel quinoline-piperidine conjugates representing four different chemical series. Evaluation of their in vitro antiplasmodium activity against a CQ-sensitive (NF54) and a CQ-resistant (K1) strain of P. falciparum unveiled highly potent activities in the nanomolar range against both strains for five 4-aminoquinoline derivatives. Moreover, no cytotoxicity was observed for all active compounds at the maximum concentration tested. These five new aminoquinoline hit structures are therefore of considerable value for antimalarial research and have the potency to be transformed into novel antimalarial agents upon further hit-to-lead optimization studies.

show abstract

Synthesis and antiplasmodial evaluation of aziridine–(iso)quinoline hybrids and their ring-opening products

Cited by 30 publications

References 49 publications

Recent advances in the synthesis of quinolines: a review

Recent advances in the synthesis of quinolines: a review

Palladium-catalyzed allylic substitution between C-based nucleophiles and 6-azabicyclo[3.1.0]-hex-3-en-2-oxy derivatives: A new selectivity paradigm

Synthesis and biological evaluation of novel quinoline-piperidine scaffolds as antiplasmodium agents

Contact Info

Product

Resources

About