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rdf:type |
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lifeskim:mentions |
umls-concept:C0002641,
umls-concept:C0003374,
umls-concept:C0020792,
umls-concept:C0031330,
umls-concept:C0205198,
umls-concept:C0205314,
umls-concept:C0205549,
umls-concept:C0220781,
umls-concept:C0243071,
umls-concept:C0441655,
umls-concept:C0679622,
umls-concept:C1709630,
umls-concept:C1883254,
umls-concept:C2934901
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pubmed:issue |
7
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pubmed:dateCreated |
2009-4-2
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pubmed:abstractText |
On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline amodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed ADME studies and in vitro and in vivo toxicological assessment. 4'-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as a candidate for further development studies based on potent activity versus chloroquine-sensitive and resistant parasites, moderate to excellent oral bioavailability, low toxicity in in vitro studies, and an acceptable safety profile.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:AsadollahyEghbalehE,
pubmed-author:BambalRamesh BRB,
pubmed-author:BatesMartinM,
pubmed-author:BerryNeilN,
pubmed-author:BiaginiGiancarloG,
pubmed-author:BrayPatrick GPG,
pubmed-author:BrigandiRichard ARA,
pubmed-author:DaviesJillJ,
pubmed-author:DavisCharles BCB,
pubmed-author:GargalloDomingo VDV,
pubmed-author:Gomez-de-Las-HerasFederico MFM,
pubmed-author:GreshamStephanie LSL,
pubmed-author:HallCharlotteC,
pubmed-author:HindleyStephenS,
pubmed-author:LanderHollieH,
pubmed-author:MaggsJames LJL,
pubmed-author:NixonGemmaG,
pubmed-author:O'NeillPaul MPM,
pubmed-author:ParapiniSilviaS,
pubmed-author:ParkB KevinBK,
pubmed-author:RimmerKarenK,
pubmed-author:RobertsPhilP,
pubmed-author:ShoneAlison EAE,
pubmed-author:StanfordDeborahD,
pubmed-author:StocksPaul APA,
pubmed-author:TaramelliDonatellaD,
pubmed-author:VivasLiviaL,
pubmed-author:WardStephen ASA,
pubmed-author:WinstanleyPeter APA
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pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1828-44
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pubmed:meshHeading |
pubmed-meshheading:19284751-Aminoquinolines,
pubmed-meshheading:19284751-Amodiaquine,
pubmed-meshheading:19284751-Animals,
pubmed-meshheading:19284751-Antimalarials,
pubmed-meshheading:19284751-Cell Survival,
pubmed-meshheading:19284751-Chloroquine,
pubmed-meshheading:19284751-Dogs,
pubmed-meshheading:19284751-Drug Resistance,
pubmed-meshheading:19284751-Female,
pubmed-meshheading:19284751-Haplorhini,
pubmed-meshheading:19284751-Hepatocytes,
pubmed-meshheading:19284751-Humans,
pubmed-meshheading:19284751-Malaria,
pubmed-meshheading:19284751-Male,
pubmed-meshheading:19284751-Mice,
pubmed-meshheading:19284751-Parasitic Sensitivity Tests,
pubmed-meshheading:19284751-Plasmodium berghei,
pubmed-meshheading:19284751-Plasmodium falciparum,
pubmed-meshheading:19284751-Plasmodium yoelii,
pubmed-meshheading:19284751-Rats,
pubmed-meshheading:19284751-Rats, Wistar,
pubmed-meshheading:19284751-Structure-Activity Relationship
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pubmed:year |
2009
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pubmed:articleTitle |
Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. Identification of a suitable "back-up" compound for N-tert-butyl isoquine.
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pubmed:affiliation |
Department of Chemistry, University of Liverpool, Liverpool, UK.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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