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

Autor:	Janette Reader, Claire Le Manach, María Santos Martínez, Leslie J. Street, Mariette Botha, Iñigo Angulo-Barturen, Diego Gonzàlez Cabrera, Dale Taylor, David Waterson, Michael J Witty, María-Belén Jiménez-Díaz, Theresa L. Coetzer, Kelly Chibale, Christel Brunschwig, Rajkumar Dhinakaran, Sergio Wittlin, Tanya Paquet, Alisje Churchyard, Ze Han, Elizabeth A. Winzeler, Sridevi Bashyam, Sonja B Lauterbach, Mathew Njoroge, Stephan Meister, Lyn-Marie Birkholtz, Santiago Ferrer
Rok vydání:	2015
Předmět:	Plasmodium berghei Pyridines Plasmodium falciparum hERG Pharmacology Antimalarials Mice Structure-Activity Relationship Pharmacokinetics In vivo Drug Discovery Pyrazolopyridine Gametocyte Animals Humans Structure–activity relationship Malaria Falciparum biology Chemistry biology.organism_classification Ether-A-Go-Go Potassium Channels Malaria Rats Liver biology.protein Pyrazoles Molecular Medicine
Zdroj:	Journal of Medicinal Chemistry. 58:8713-8722
ISSN:	1520-4804 0022-2623
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f7347d2c9242e676a15e7950bc2118ea https://doi.org/10.1021/acs.jmedchem.5b01605 Zobrazit plný text záznamu