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 Articles uri icon

authors

  • 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
  • LAUTERBCH, SONJA
  • COETZER, THERESA L.
  • BIRKHOLTZ, LYN-MARIE
  • MEISTER, STEPHAN
  • WINZELER, ELIZABETH A.
  • WATERSON, DAVID
  • WITTY, MICHAEL J.
  • WITTLIN, SERGIO
  • JIMÉNEZ DÍAZ, MARÍA BELÉN
  • SANTOS MARTINEZ, MARIA
  • FERRER BAZAGA, SANTIAGO
  • ANGULO BARTUREN, ÍÑIGO
  • STREET, LESLIE J.
  • CHIBALE, KELLY

publication date

  • November 2015

start page

  • 8713

end page

  • 8722

issue

  • 21

volume

  • 58

International Standard Serial Number (ISSN)

  • 0022-2623

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

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.

subjects

  • Biology and Biomedicine
  • Medicine

keywords

  • medicinal chemistry optimization; artemisinin-resistant malaria; vitro; hits