A Novel Pyrazolopyridine with in Vivo Activity in Plasmodium berghei- and Plasmodium falciparum-Infected Mouse Models from Structure鈥揂ctivity Relationship Studies around the Core of Recently Identifie
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- 作者：Claire Le Manach ; Tanya Paquet ; Christel Brunschwig ; Mathew Njoroge ; Ze Han ; Diego Gonz脿lez Cabrera ; Sridevi Bashyam ; Rajkumar Dhinakaran ; Dale Taylor ; Janette Reader ; Mariette Botha ; Alisje Churchyard ; Sonja Lauterbach ; Theresa L. Coetzer ; Lyn-Marie Birkholtz ; Stephan Meister ; Elizabeth A. Winzeler ; David Waterson ; Michael J. Witty ; Sergio Wittlin ; Mar铆a-Bel茅n Jim茅nez-D铆az ; Mar铆a Santos Mart铆nez ; Santiago Ferrer ; I帽igo Angulo-Barturen ; Leslie J. Street ; Kelly Chibale
- 刊名：Journal of Medicinal Chemistry
- 出版年：2015
- 出版时间：November 12, 2015
- 年：2015
- 卷：58
- 期：21
- 页码：8713-8722
- 全文大小：564K
- ISSN：1520-4804
文摘
Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure鈥揳ctivity 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.