Department of Medicinal Chemistry, Jacobus Pharmaceutical Company, 37 Cleveland Lane, Princeton, NJ 08540, USA.
Bioorg Med Chem Lett. 2013 Feb 15;23(4):1022-5. doi: 10.1016/j.bmcl.2012.12.022. Epub 2012 Dec 20.
Exploration of triclosan analogs has led to novel diaryl ureas with significant potency against in vitro cultures of drug-resistant and drug-sensitive strains of the human malaria parasite Plasmodium falciparum. Compound 18 demonstrated EC(50) values of 37 and 55 nM versus in vitro cultured parasite strains and promising in vivo efficacy in a Plasmodium berghei antimalarial mouse model, with >50% survival at day 31 post-treatment when administered subcutaneously at 256 mg/kg. This series of compounds provides a chemical scaffold of novel architecture, as validated by cheminformatics analysis, to pursue antimalarial drug discovery efforts.
三氯生类似物的探索导致了新型二芳基脲类化合物的出现，对体外培养的耐药和敏感株人类疟原虫恶性疟原虫具有显著的活性。化合物 18 对体外培养的寄生虫株的 EC 50 值分别为 37 和 55 nM，并且在伯氏疟原虫抗疟鼠模型中具有良好的体内疗效，当以 256mg/kg 皮下给药时，在治疗后第 31 天的存活率超过 50%。该系列化合物提供了一种新的化学结构骨架，通过化学信息学分析得到验证，可用于抗疟药物的发现。
