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Substituted 2-phenylimidazopyridines : a new class of drug leads for human African trypanosomiasis

Tatipaka, Hari Babu and Gillespie, J. Robert and Chatterjee, Arnab K. and Norcross, Neil R. and Hulverson, Matthew A. and Ranade, Ranae M. and Nagendar, Pendem and Creason, Sharon A. and McQueen, Joshua and Duster, Nicole A. and Nagle, Advait and Supek, Frantisek and Molteni, Valentina and Wenzler, Tanja and Brun, Reto and Glynne, Richard and Buckner, Frederick S. and Gelb, Michael H.. (2014) Substituted 2-phenylimidazopyridines : a new class of drug leads for human African trypanosomiasis. Journal of medicinal chemistry, 57 (3). pp. 828-835.

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Official URL: http://edoc.unibas.ch/dok/A6243538

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Abstract

A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Wenzler, Tanja and Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Chemical Society
ISSN:0022-2623
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Sep 2018 14:33
Deposited On:15 Aug 2014 07:16

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