Journal article
Identification of a Potential Antimalarial Drug Candidate from a Series of 2-Aminopyrazines by Optimization of Aqueous Solubility and Potency across the Parasite Life Cycle.
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Le Manach C
Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
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Nchinda AT
Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
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Paquet T
Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
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Gonzàlez Cabrera D
Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
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Younis Y
Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
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Han Z
Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
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Bashyam S
Syngene International Ltd. , Biocon Park, Plot No. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560099, India.
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Zabiulla M
Syngene International Ltd. , Biocon Park, Plot No. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560099, India.
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Taylor D
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Observatory, Cape Town, 7925, South Africa.
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Lawrence N
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Observatory, Cape Town, 7925, South Africa.
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White KL
Centre for Drug Candidate Optimisation, Monash University , 381 Royal Parade, Parkville, Victoria 3052 Australia.
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Charman SA
Centre for Drug Candidate Optimisation, Monash University , 381 Royal Parade, Parkville, Victoria 3052 Australia.
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Waterson D
Medicines for Malaria Venture , ICC, Route de Pré-Bois 20, P.O. Box 1826, 1215 Geneva, Switzerland.
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Witty MJ
Medicines for Malaria Venture , ICC, Route de Pré-Bois 20, P.O. Box 1826, 1215 Geneva, Switzerland.
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Wittlin S
Swiss Tropical and Public Health Institute , Socinstrasse 57, 4002 Basel, Switzerland.
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Botha ME
Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private Bag X20, Hatfield 0028, South Africa.
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Nondaba SH
Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private Bag X20, Hatfield 0028, South Africa.
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Reader J
Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private Bag X20, Hatfield 0028, South Africa.
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Birkholtz LM
Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private Bag X20, Hatfield 0028, South Africa.
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Jiménez-Díaz MB
GlaxoSmithKline , Tres Cantos Medicines Development Campus, Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
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Martínez MS
GlaxoSmithKline , Tres Cantos Medicines Development Campus, Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
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Ferrer S
GlaxoSmithKline , Tres Cantos Medicines Development Campus, Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
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Angulo-Barturen I
GlaxoSmithKline , Tres Cantos Medicines Development Campus, Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
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Meister S
Department of Pediatrics, Pharmacology and Drug Discovery, School of Medicine, University of California, San Diego (UCSD) , 9500 Gilman Drive, La Jolla, California 92093, United States.
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Antonova-Koch Y
Department of Pediatrics, Pharmacology and Drug Discovery, School of Medicine, University of California, San Diego (UCSD) , 9500 Gilman Drive, La Jolla, California 92093, United States.
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Winzeler EA
Department of Pediatrics, Pharmacology and Drug Discovery, School of Medicine, University of California, San Diego (UCSD) , 9500 Gilman Drive, La Jolla, California 92093, United States.
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Street LJ
Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
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Chibale K
Drug Discovery and Development Center (H3D), Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.
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Published in:
- Journal of medicinal chemistry. - 2016
English
Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγnull mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages.
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Language
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Open access status
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closed
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/231930
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