We recently reported the medicinal chemistry reoptimization of a known human tyrosine kinase inhibitor, lapatinib, against a variety of parasites responsible for numerous tropical diseases, including human African trypanosomiasis (Trypanosoma brucei), Chagas disease (T. cruzi), Leishmaniasis (Leishmania spp.), and malaria (Plasmodium falciparum). Herein, we report our continuing efforts to optimize this series against P. falciparum. Through the design of a library of compounds focused on reducing the lipophilicity and molecular weight, followed by an SAR exploration, we have identified NEU-1953 (40). This compound is a potent inhibitor of P. falciparum with an improved ADME profile over the previously reported compound, NEU-961 (3).

中文翻译：

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恶性疟原虫增殖的4-苯胺喹啉抑制剂理化性质的优化

我们最近报道了一种已知的人类酪氨酸激酶抑制剂lapatinib的药物化学优化，它可应对多种导致多种热带疾病的寄生虫，其中包括非洲非洲锥虫病（Trypanosoma brucei），南美锥虫病（T. cruzi），利什曼病（Leishmania spp。）和疟疾（恶性疟原虫）。在此，我们报告了我们为优化针对恶性疟原虫的本系列产品所做的持续努力。通过设计专注于降低亲脂性和分子量的化合物库，然后进行SAR探索，我们确定了NEU-1953（40）。该化合物是强效的与先前报道的化合物NEU-961（3）相比，恶性疟原虫的ADME谱有所改善。