3-羧基-4(1H)-喹啉类化合物的先导优化，以提供口服生物利用度的抗疟药物。
Lead optimization of 3-carboxyl-4(1H)-quinolones to deliver orally bioavailable antimalarials.
机构信息
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
出版信息
J Med Chem. 2012 May 10;55(9):4205-19. doi: 10.1021/jm201642z. Epub 2012 Apr 18.
Abstract
Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.
摘要
疟疾是一种原虫寄生虫病，广泛分布于非洲、亚洲和美洲的热带和亚热带地区，每年导致超过 80 万人死亡。不断出现的耐多药恶性疟原虫推动了开发新的、有效的抗疟药物的持续需求。我们之前的工作探索了 4(1H)-喹啉酯衍生物的初步结构优化，这是一类与内原蛋白相关的新型抗疟药物。在此，我们报告了以提高抗疟活性和生物利用度为重点的 4(1H)-喹啉的先导优化。这些研究导致了具有口服疗效的抗疟药物的发展，包括喹啉类似物 20g，这是进一步优化的有希望的候选药物。
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