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

作者：Le Manach Claire; Paquet Tanya; Brunschwig Christel; Njoroge Mathew; Han Ze; Cabrera Diego Gonzalez; 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; Jimenez Diaz Maria Belen; Santos Martinez Maria; Ferrer Santiago; Angulo Barturen Inigo; Street Leslie J; Chibale Kelly^*

来源：Journal of Medicinal Chemistry, 2015, 58(21): 8713-8722.

DOI：10.1021/acs.jmedchem.5b01605

Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure activity relationship studies around the central core of antimalarial imidazo-pyridazines 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.

• 出版日期2015-11-12