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3-(Oxazolo[4,5-b]pyridin-2-yl)anilides as a novel class of potent inhibitors for the kinetoplastid Trypanosoma brucei, the causative agent for human African trypanosomiasis
Citation
Ferrins, L and Rahmani, R and Sykes, ML and Jones, AJ and Avery, VM and Teston, E and Almohaywi, B and Yin, JX and Smith, J and Hyland, C and White, KL and Ryan, E and Campbell, M and Charman, SA and Kaiser, M and Baell, JB, 3-(Oxazolo[4,5-b]pyridin-2-yl)anilides as a novel class of potent inhibitors for the kinetoplastid Trypanosoma brucei, the causative agent for human African trypanosomiasis, European Journal of Medicinal Chemistry, 66 pp. 450-465. ISSN 0223-5234 (2013) [Refereed Article]
Copyright Statement
Copyright 2013 Elsevier Masson
DOI: doi:10.1016/j.ejmech.2013.05.007
Abstract
A whole organism high-throughput screen of approximately 87,000 compounds against Trypanosoma
brucei brucei led to the recent discovery of several novel compound classes with low micromolar activity
against this organism and without appreciable cytotoxicity to mammalian cells. Herein we report a
structureeactivity relationship (SAR) investigation around one of these hit classes, the 3-(oxazolo[4,5-b]
pyridin-2-yl)anilides. Sharp SAR is revealed, with our most active compound (5) exhibiting an IC50 of
91 nM against the human pathogenic strain T.b. rhodesiense and being more than 700 times less toxic
towards the L6 mammalian cell line. Physicochemical properties are attractive for many compounds in
this series. For the most potent representatives, we show that solubility and metabolic stability are key
parameters to target during future optimisation.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | 3-(Oxazolo[4,5-b]pyridin-2-yl)anilides, human African trypanosomiasis, sleeping sickness, trypanosomacidal agent, trypanosoma brucei |
| Research Division: | Chemical Sciences |
| Research Group: | Medicinal and biomolecular chemistry |
| Research Field: | Biologically active molecules |
| Objective Division: | Expanding Knowledge |
| Objective Group: | Expanding knowledge |
| Objective Field: | Expanding knowledge in the chemical sciences |
| UTAS Author: | Almohaywi, B (Ms Basmah Almohaywi) |
| UTAS Author: | Yin, JX (Mr JieXiang Yin) |
| UTAS Author: | Smith, J (Associate Professor Jason Smith) |
| UTAS Author: | Hyland, C (Dr Chris Hyland) |
| ID Code: | 88741 |
| Year Published: | 2013 |
| Web of Science® Times Cited: | 21 |
| Deposited By: | Chemistry |
| Deposited On: | 2014-02-13 |
| Last Modified: | 2016-11-07 |
| Downloads: | 0 |
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