Macrofilaricidal Benzimidazole–Benzoxaborole Hybrids as an Approach to the Treatment of River Blindness: Part 2. Ketone Linked Analogs
| Autor: | Robert T. Jacobs, Rianna Stefanakis, Nancy Tricoche, Eric E. Easom, Yvonne Freund, Kee Chong Lim, James H. McKerrow, David S. Carter, Christina A. Bulman, Brian M. Suzuki, Christopher S. Lunde, Pamela Berry, Judy A. Sakanari, Jacob J. Plattner, Chelsea Fischer, Sara Lustigman, Tsutomu Akama, Fernando Rock |
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| Rok vydání: | 2019 |
| Předmět: |
Boron Compounds
Male 0301 basic medicine Benzimidazole Letter Ketone 030106 microbiology Administration Oral Flubendazole Pharmacology 03 medical and health sciences chemistry.chemical_compound Pharmacokinetics Onchocerciasis Ocular parasitic diseases medicine Animals lymphatic filariasis chemistry.chemical_classification flubendazole organoboron Blindness biology Chemistry onchocerciasis Ketones medicine.disease biology.organism_classification Onchocerca volvulus Disease Models Animal Filaricides 030104 developmental biology Infectious Diseases Nematode tubulin Benzimidazoles Female Gerbillinae Onchocerciasis |
| Zdroj: | ACS Infectious Diseases |
| ISSN: | 2373-8227 |
| DOI: | 10.1021/acsinfecdis.9b00397 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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