163 research outputs found
Supplemental_Material_for_A_Whole_Cell_Screen_for_Adjunctive_and_Direct_Antimicrobials_Active_Against_Carbapenem-Resistant_Enterobacteriaceae_by_Smith_et_al – Supplemental material for A Whole-Cell Screen for Adjunctive and Direct Antimicrobials Active against Carbapenem-Resistant Enterobacteriaceae
No full textSupplemental material, Supplemental_Material_for_A_Whole_Cell_Screen_for_Adjunctive_and_Direct_Antimicrobials_Active_Against_Carbapenem-Resistant_Enterobacteriaceae_by_Smith_et_al for A Whole-Cell Screen for Adjunctive and Direct Antimicrobials Active against Carbapenem-Resistant Enterobacteriaceae by Kenneth P. Smith, Matthew G. Dowgiallo, Lucius Chiaraviglio, Prakash Parvatkar, Chungsik Kim, Roman Manetsch and James E. Kirby in SLAS Discovery</p
Orally bioavailable 6-chloro-7-methoxy-4(1 H)-quinolones efficacious against multiple stages of plasmodium.
No full textThe 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 lownanomolar 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
Progress in the Optimization of 4(1H)-Quinolone Derivatives as Antimalarials Targeting the Erythrocytic, the Exoerythrocytic and the Transmitting Stages of the Malaria Parasite
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Malaria is one of the leading infectious diseases occurring mainly in tropical and subtropical areas. Although available antimalarial tools have reduced the number of fatalities, there is still an urgent need for the development of new and more efficacious treatments to cure and eradicate
malaria especially due to emerging resistance to all antimalarial drugs. Research was initiated to revisit antimalarial compounds which were deemed unsuitable as a result of poor understanding of physicochemical properties and the optimization thereof. The 4(1H)-quinolones are a class
of compounds with demonstrated activity against malaria parasites. Recent optimization of the long-known core led to two highly promising compounds, i.e. P4Q-391 and ELQ-300, with great selective activity against all stages of the parasite's life cycle and good physicochemical properties.
In this paper, we discuss the key steps on the way to these compounds, which fuel hope to find a suitable treatment for the prevention, cure and eradication of malaria.
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ChemInform Abstract: Divergent Route to Access Structurally Diverse 4-Quinolones via Mono or Sequential Cross-Couplings.
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Divergent Route to Access Structurally Diverse 4-Quinolones via Mono or Sequential Cross-Couplings
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Sulfo-click reaction via in situ generated thioacids and its application in kinetic target-guided synthesis
No full textChemInform Abstract: Sulfo‐Click Reaction via in situ Generated Thioacids and Its Application in Kinetic Target‐Guided Synthesis.
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