Referenced in: none

Automatically associated channels: Kv11.1

Title: 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.

Authors: Claire Le Manach, Tanya Paquet, Christel Brunschwig, Mathew Njoroge, Ze Han, Diego González 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, María-Belén Jiménez-Díaz, María Santos Martínez, Santiago Ferrer, Iñigo Angulo-Barturen, Leslie J Street, Kelly Chibale

Journal, date & volume: J. Med. Chem., 2015 Nov 12 , 58, 8713-22

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/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.