Macrofilaricidal Benzimidazole-Benzoxaborole Hybrids as an Approach to the Treatment of River Blindness. Part 2. Ketone Linked Analogs.

Optimization of a series of benzimidazole-benzoxaborole hybrid molecules linked via a ketone are described that exhibit good activity against Onchocerca volvulus, a filarial nematode responsible for the disease onchocerciasis, also known as River Blindness. The lead identified in this series, AN15470, was found to have acceptable pharmacokinetic properties to enable evaluation following oral dosing in an animal model of onchocerciasis. AN15470 was effective in killing worms implanted in Mongolian gerbils when dosed orally as a suspension at 100 mg/kg/day for 14 days, but not when dosed orally at 100 mg/kg/day for 7 days.