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

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Authors

Le Manach, Claire
Paquet, Tanya
Brunschwig, Christel
Njoroge, Mathew
Han, Ze
Cabrera, Diego Gonzaalez
Bashyam, Sridevi
Dhinakaran, Rajkumar
Taylor, Dale
Reader, Janette

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Publisher

American Chemical Society

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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Keywords

Pharmacokinetics, Antimalarial imidazopyridazines, Pyrazolopyridines, Parasite liver

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Citation

Le Manach, C, Paquet, T, Brunschwig, C, Njoroge, M, Han, Z, Gonzalez Cabrera, D, Bashyam, S, Dhinakaran, R, Taylor, D, Reader, J, Botha, M, Churchyard, A, Lauterbach, S, Coetzer, TL, Birkholtz, L-M, Meister, S, Winzeler, EA, Waterson, D, Witty, MJ, Wittlin, S, Jimenez-Diaz, M-B, Santos Martinez, M, Ferrer, S, Angulo-Barturen, I, Street, LJ & Chibale, K 2015, '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', Journal of Medicinal Chemistry, vol. 58, no. 21, pp. 8713-8722.