The optimization
of a series of benzimidazole–benzoxaborole hybrid molecules
linked via a ketone that exhibit good activity against Onchocerca
volvulus, a filarial nematode responsible for the disease
onchocerciasis, also known as river blindness, is described. The lead
identified in this series, 21 (AN15470), was found to
have acceptable pharmacokinetic properties to enable an evaluation
following oral dosing in an animal model of onchocerciasis. Compound 21was 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.