ArticleJournal of medicinal chemistry2014
Orally bioavailable 6-chloro-7-methoxy-4(1H)-quinolones efficacious against multiple stages of Plasmodium.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Plasmid-mediated quinolone resistance in Enterobacteriaceae: a systematic review with a focus on Mediterranean countries.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2017Pooled it
- Legacy 4(1ACS infectious diseases · 2026Article
- Optimization of diastereomeric dihydropyridines as antimalarials.European journal of medicinal chemistry · 2024Article
- Incorporation of an Isohexide Subunit into the Endochin-like Quinolone Scaffold.Molecules (Basel, Switzerland) · 2024Article
- 3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance.ACS infectious diseases · 2024Article
- Antimalarial Dibenzannulated Medium-Ring Keto Lactams.ACS infectious diseases · 2023Article
- Assessment of the Activity of Decoquinate and Its Quinoline-Molecules (Basel, Switzerland) · 2021Article
- A New Scalable Synthesis of ELQ-300, ELQ-316, and other Antiparasitic Quinolones.Organic process research & development · 2021Article
- Aminoalkoxycarbonyloxymethyl Ether Prodrugs with a pH-Triggered Release Mechanism: A Case Study Improving the Solubility, Bioavailability, and Efficacy of Antimalarial 4(1Journal of medicinal chemistry · 2021Article
- Design and Synthesis of Orally Bioavailable Piperazine Substituted 4(1H)-Quinolones with Potent Antimalarial Activity: Structure-Activity and Structure-Property Relationship Studies.Journal of medicinal chemistry · 2018Article
- Progress in the Optimization of 4(1Chimia · 2017Article
- Antibiotics in malaria therapy: which antibiotics except tetracyclines and macrolides may be used against malaria?Malaria journal · 2016Review
- ICI 56,780 Optimization: Structure-Activity Relationship Studies of 7-(2-Phenoxyethoxy)-4(1H)-quinolones with Antimalarial Activity.Journal of medicinal chemistry · 2016Article
- The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity.Molecules (Basel, Switzerland) · 2016Review
- 3-Trifluoromethyl-3-aryldiazirine photolabels with enhanced ambient light stability.Chemical communications (Cambridge, England) · 2016Article
- Metal-free arylation of ethyl acetoacetate with hypervalent diaryliodonium salts: an immediate access to diverse 3-aryl-4(1H)-quinolones.The Journal of organic chemistry · 2015Article
- Antimalarial chemotherapy: orally curative artemisinin-derived trioxane dimer esters.Bioorganic & medicinal chemistry letters · 2015Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
The continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. Unfortunately, more recent remedies such as artemisinin combination therapies have been rendered less effective due to developing parasite resistance, and new drugs are required that target the parasite in the liver to support the disease elimination efforts. Research was initiated to revisit antimalarials developed in the 1940s and 1960s that were deemed unsuitable for use as therapeutic agents as a result of poor understanding of both physicochemical properties and parasitology. Structure-activity and structure-property relationship studies were conducted to generate a set of compounds with the general 6-chloro-7-methoxy-2-methyl-4(1H)-quinolone scaffold which were substituted at the 3-position with a variety of phenyl moieties possessing various properties. Extensive physicochemical evaluation of the quinolone series was carried out to downselect the most promising 4(1H)-quinolones, 7, 62, 66, and 67, which possessed low-nanomolar EC50 values against W2 and TM90-C2B as well as improved microsomal stability. Additionally, in vivo Thompson test results using Plasmodium berghei in mice showed that these 4(1H)-quinolones were efficacious for the reduction of parasitemia at >99% after 6 days.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.