5 research outputs found
Lead Optimization of Imidazopyrazines: A New Class of Antimalarial with Activity on <i>Plasmodium</i> Liver Stages
Imidazopyridine <b>1</b> was identified from a phenotypic
screen against <i>P. falciparum</i> (Pf) blood stages and
subsequently optimized for activity on liver-stage schizonts of the
rodent parasite <i>P. yoelii</i> (Py) as well as hypnozoites
of the simian parasite <i>P. cynomolgi</i> (Pc). We applied
these various assays to the cell-based lead optimization of the imidazopyrazines,
exemplified by <b>3</b> (KAI407), and show that optimized compounds
within the series with improved pharmacokinetic properties achieve
causal prophylactic activity <i>in vivo</i> and may have
the potential to target the dormant stages of <i>P. vivax</i> malaria