A series of benzimidazole-benzoxaborole hybrid molecules linked via an amide linker are described that exhibit good in vitro activity against Onchocerca volvulus, a filarial nematode responsible for the disease onchocerciasis, also known as river blindness. The lead identified in this series, 8a (AN8799), was found to have acceptable pharmacokinetic properties to enable evaluation in animal models of human filariasis. Compound 8a was effective in killing Brugia malayi, B. pahangi, and Litomosoides sigmodontis worms present in Mongolian gerbils when dosed subcutaneously as a suspension at 100 mg/kg/day for 14 days but not when dosed orally at 100 mg/kg/day for 28 days. The measurement of plasma levels of 8a at the end of the dosing period and at the time of sacrifice revealed an interesting dependence of activity on the extended exposure for both 8a and the positive control, flubendazole.

中文翻译：

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大型杀虫剂苯并咪唑-苯并恶唑硼烷杂化物作为治疗河盲症的一种方法：第1部分。酰胺连接的类似物。

描述了通过酰胺连接基连接的一系列苯并咪唑-苯并恶唑硼酸酯杂合分子，它们对Onchocerca volvulus（一种引起盘尾丝虫病，也称为河盲症）的丝状线虫表现出良好的体外活性。发现该系列中鉴定的铅8a（AN8799）具有可接受的药代动力学特性，可以在人丝虫病动物模型中进行评估。当以100 mg / kg / day的剂量皮下悬液给药14天时，化合物8a可有效杀死蒙古沙鼠中存在的马来亚布鲁氏菌，帕汉斯B. pahangi和Sigmodontis sigmodontis蠕虫，但当口服100 mg / kg / day时，则无效28天