Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of sub-saharan Africa. There is a high unmet medical need since the approved drugs are poorly efficacious, show considerable toxicity and are not easy to administer. This work describes the optimization of the pharmacokinetic properties of a previously published family of triazine lead compounds. One compound (35 (UAMC-03011)) with potent anti-trypanosomal activity and no cytotoxicity was selected for further study because of its good microsomal stability and high selectivity for Trypanosoma brucei over a panel including Trypanosoma cruzi, L.eishmania infantum, and Plasmodium falciparum. In vivo pharmacokinetic parameters were determined and the compound was studied in an acute in vivo mouse disease model. One of the important learnings of this study was that the rate of trypanocidal activity is an important parameter during the lead optimization process.

非洲人类锥虫病每年在撒哈拉以南非洲的农村地区造成数千人死亡。由于批准的药物疗效差，显示出相当大的毒性并且不易于施用，因此存在高度未满足的医疗需求。这项工作描述了先前发布的三嗪铅化合物家族的药代动力学特性的优化。一种化合物（35（UAMC-03011）），与强效的抗锥虫活性和无细胞毒性被选择用于进一步的研究由于其良好的微粒体稳定性和高选择性为布氏锥虫在包括面板克氏锥虫，L.eishmania婴儿，和疟原虫恶性肿瘤。体内确定了药代动力学参数，并在急性体内小鼠疾病模型中研究了该化合物。这项研究的重要学习之一是锥虫杀灭活性的速率是潜在顾客优化过程中的重要参数。