Skip to main content

Macrofilaricidal Benzimidazole-Benzoxaborole Hybrids as an Approach to the Treatment of River Blindness: Part 1. Amide Linked Analogs.

ACS infectious diseases

Authors: Tsutomu Akama, Yvonne R Freund, Pamela W Berry, David S Carter, Eric E Easom, Kurt Jarnagin, Christopher S Lunde, Jacob J Plattner, Fernando Rock, Rianna Stefanakis, Chelsea Fischer, Christina A Bulman, Kee Chong Lim, Brian M Suzuki, Nancy Tricoche, Abdelmoneim Mansour, Utami DiCosty, Scott McCall, Ben Carson, John W McCall, James McKerrow, Marc P Hübner, Sabine Specht, Achim Hoerauf, Sara Lustigman, Judy A Sakanari, Robert T Jacobs

A series of benzimidazole-benzoxaborole hybrid molecules linked via an amide linker are described that exhibit good activity against , a filarial nematode responsible for the disease onchocerciasis, also known as river blindness. The lead identified in this series,  (AN8799), was found to have acceptable pharmacokinetic properties to enable evaluation in animal models of human filariasis. Compound was effective in killing , , and 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 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 and the positive control, flubendazole.

PMID: 31876154

Participating cluster members