Akama, T. and Zhang, Y. K. and Freund, Y. R. and Berry, P. and Lee, J. and Easom, E. E. and Jacobs, R. T. and Plattner, J. J. and Witty, M. J. and Peter, R. and Rowan, T. G. and Gillingwater, K. and Brun, R. and Nare, B. and Mercer, L. and Xu, M. and Wang, J. and Liang, H.. (2017) Identification of a 4-fluorobenzyl L-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT). Bioorganic and Medicinal Chemistry Letters, 28. pp. 6-10.
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Abstract
Novel l-valinate amide benzoxaboroles and analogues were designed and synthesized for a structure-activity-relationship (SAR) investigation to optimize the growth inhibitory activity against Trypanosoma congolense (T. congolense) and Trypanosoma vivax (T. vivax) parasites. The study identified 4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-l-valinate (5, AN11736), which showed IC50 values of 0.15 nM against T. congolense and 1.3 nM against T. vivax, and demonstrated 100% efficacy with a single dose of 10 mg/kg against both T. congolense and T. vivax in mouse models of infection (IP dosing) and in the target animal, cattle, dosed intramuscularly. AN11736 has been advanced to early development studies.
| Faculties and Departments: | 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser) |
|---|---|
| UniBasel Contributors: | Gillingwater, Kirsten and Brun, Reto |
| Item Type: | Article, refereed |
| Article Subtype: | Research Article |
| Publisher: | Elsevier |
| ISSN: | 0960-894X |
| e-ISSN: | 1464-3405 |
| Note: | Publication type according to Uni Basel Research Database: Journal article |
| Language: | English |
| Identification Number: | |
| edoc DOI: | |
| Last Modified: | 07 Sep 2018 12:45 |
| Deposited On: | 21 Dec 2017 14:40 |
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