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ID: ALA2380237
Journal: Bioorg Med Chem Lett
Title: Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1).
Authors: Chapman TM, Osborne SA, Bouloc N, Large JM, Wallace C, Birchall K, Ansell KH, Jones HM, Taylor D, Clough B, Green JL, Holder AA.
Abstract: A series of imidazopyridazines which are potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was identified from a high-throughput screen against the isolated enzyme. Subsequent exploration of the SAR and optimisation has yielded leading members which show promising in vitro anti-parasite activity along with good in vitro ADME and selectivity against human kinases. Initial in vivo testing has revealed good oral bioavailability in a mouse PK study and modest in vivo efficacy in a Plasmodium berghei mouse model of malaria.
CiteXplore: 23570789