Lead optimization of imidazopyrazines: a new class of antimalarial with activity on Plasmodium liver stages.
Lead optimization of imidazopyrazines: a new class of antimalarial with activity on Plasmodium liver stages.
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咪唑并吡嗪的先导化合物优化：一种对疟原虫肝脏阶段具有活性的新型抗疟药。
DOI：
10.1021/ml500244m
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发表时间：
2014
影响因子：
4.2
通讯作者：
Bodenreider,Chr
中科院分区：
文献类型：
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作者：
Zou,Bin;Nagle,Advait;Chatterjee,ArnabK;Leong,SehYong;Tan,LiyingJocelyn;Sim,WeiLinSandra;Mishra,Pranab;Guntapalli,Prasuna;Tully,DavidC;Lakshminarayana,SureshB;Lim,ChekShik;Tan,YongCheng;Abas,SitiNurdiana;Bodenreider,Chr
咪唑并吡啶1是从抗P.恶性疟原虫（Pf）血液阶段，随后针对啮齿动物寄生虫肝脏阶段裂殖体的活性进行优化P。yoelii（Py）以及类人猿寄生虫的催眠虫。食蟹猴（Pc）。我们将这些不同的测定应用于咪唑并吡嗪类药物的基于细胞的先导优化，以3（KAI407）为例，并表明具有改善的药代动力学性质的系列内的优化化合物实现了体内因果预防活性，并且可能具有靶向P的休眠阶段的潜力。间日疟
Imidazopyridine1was identified from a phenotypic screen againstP. falciparum(Pf) blood stages and subsequently optimized for activity on liver-stage schizonts of the rodent parasiteP. yoelii(Py) as well as hypnozoites of the simian parasiteP. cynomolgi(Pc). We applied these various assays to the cell-based lead optimization of the imidazopyrazines, exemplified by3(KAI407), and show that optimized compounds within the series with improved pharmacokinetic properties achieve causal prophylactic activityin vivoand may have the potential to target the dormant stages ofP. vivaxmalaria.