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Published on: June 23, 2019
Lead optimization of imidazopyrazines: a new class of antimalarial with activity on Plasmodium liver stages
Bin Zou1, Advait Nagle2, Arnab K Chatterjee2
1Novartis Institute for Tropical Diseases , 10 Biopolis Road #05-01 Chromos, 138670 Singapore.
Abstract:
Imidazopyridine 1 was identified from a phenotypic screen against P. falciparum (Pf) blood stages and subsequently optimized for activity on liver-stage schizonts of the rodent parasite P. yoelii (Py) as well as hypnozoites of the simian parasite P. cynomolgi (Pc). We applied these various assays to the cell-based lead optimization of the imidazopyrazines, exemplified by 3 (KAI407), and show that optimized compounds within the series with improved pharmacokinetic properties achieve causal prophylactic activity in vivo and may have the potential to target the dormant stages of P. vivax malaria.
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