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A Novel Pyrazolopyridine with in Vivo Activity in Plasmodium berghei- and Plasmodium falciparum-Infected Mouse Models from Structure-Activity Relationship Studies around the Core of Recently Identified Antimalarial Imidazopyridazines.
Le Manach, Claire; Paquet, Tanya; Brunschwig, Christel; Njoroge, Mathew; Han, Ze; Gonzàlez Cabrera, Diego; Bashyam, Sridevi; Dhinakaran, Rajkumar; Taylor, Dale; Reader, Janette; Botha, Mariette; Churchyard, Alisje; Lauterbach, Sonja; Coetzer, Theresa L; Birkholtz, Lyn-Marie; Meister, Stephan; Winzeler, Elizabeth A; Waterson, David; Witty, Michael J; Wittlin, Sergio; Jiménez-Díaz, María-Belén; Santos Martínez, María; Ferrer, Santiago; Angulo-Barturen, Iñigo; Street, Leslie J; Chibale, Kelly.
Affiliation
  • Brunschwig C; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Observatory 7925, South Africa.
  • Njoroge M; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Observatory 7925, South Africa.
  • Bashyam S; Syngene International Ltd. , Biocon Park, Plot No. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560099, India.
  • Dhinakaran R; Syngene International Ltd. , Biocon Park, Plot No. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560099, India.
  • Taylor D; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Observatory 7925, South Africa.
  • Reader J; Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private bag X20, Hatfield 0028, South Africa.
  • Botha M; Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private bag X20, Hatfield 0028, South Africa.
  • Churchyard A; Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private bag X20, Hatfield 0028, South Africa.
  • Lauterbach S; Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private bag X20, Hatfield 0028, South Africa.
  • Coetzer TL; Department of Molecular Medicine and Haematology, Wits Research Institute for Malaria, Wits Medical School , 2000 Johannesburg, South Africa.
  • Birkholtz LM; Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria , Private bag X20, Hatfield 0028, South Africa.
  • Meister S; School of Medicine, Department of Pediatrics, Pharmacology & Drug Discovery, University of California, San Diego (UCSD) , 9500 Gilman Drive, La Jolla, California 92093, United States.
  • Winzeler EA; School of Medicine, Department of Pediatrics, Pharmacology & Drug Discovery, University of California, San Diego (UCSD) , 9500 Gilman Drive, La Jolla, California 92093, United States.
  • Waterson D; Medicines for Malaria Venture , ICC, Route de Pré-Bois 20, PO Box 1826, 1215 Geneva, Switzerland.
  • Witty MJ; Medicines for Malaria Venture , ICC, Route de Pré-Bois 20, PO Box 1826, 1215 Geneva, Switzerland.
  • Wittlin S; Swiss Tropical and Public Health Institute , Socinstrasse 57, 4002 Basel, Switzerland.
  • Jiménez-Díaz MB; University of Basel , 4003 Basel, Switzerland.
  • Santos Martínez M; GlaxoSmithKline , Tres Cantos Medicines Development Campus, Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
  • Ferrer S; GlaxoSmithKline , Tres Cantos Medicines Development Campus, Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
  • Angulo-Barturen I; GlaxoSmithKline , Tres Cantos Medicines Development Campus, Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
  • Street LJ; GlaxoSmithKline , Tres Cantos Medicines Development Campus, Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
J Med Chem ; 58(21): 8713-22, 2015 Nov 12.
Article in En | MEDLINE | ID: mdl-26502160
ABSTRACT
Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure-activity relationship studies around the central core of antimalarial imidazopyridazines were conducted. This study led to the identification of potent pyrazolopyridines, which showed good in vivo efficacy and pharmacokinetics profiles. The lead compounds also proved to be very potent in the parasite liver and gametocyte stages, which makes them of high interest.
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Full text: 1 Collection: 01-internacional Health context: 3_ND Database: MEDLINE Main subject: Plasmodium berghei / Plasmodium falciparum / Pyrazoles / Pyridines / Malaria / Antimalarials Limits: Animals / Humans Language: En Journal: J Med Chem Year: 2015 Document type: Article
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Health context: 3_ND Database: MEDLINE Main subject: Plasmodium berghei / Plasmodium falciparum / Pyrazoles / Pyridines / Malaria / Antimalarials Limits: Animals / Humans Language: En Journal: J Med Chem Year: 2015 Document type: Article