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Optimization of chloronitrobenzamides (CNBs) as therapeutic leads for Human African Trypanosomiasis (HAT)

Hwang, J. Y. and Smithson, S. C. and Zhu, F. and Holbrook, G. and Connelly, M. C. and Kaiser, M. and Brun, R. and Guy, R. K.. (2013) Optimization of chloronitrobenzamides (CNBs) as therapeutic leads for Human African Trypanosomiasis (HAT). Journal of medicinal chemistry, 56 (7). pp. 2850-2860.

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Official URL: http://edoc.unibas.ch/dok/A6124582

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Abstract

We previously reported the discovery of the activity of chloronitrobenzamides (CNBs) against bloodstream forms of Trypanosoma brucei . Herein we disclose extensive structure-activity relationship and structure-property relationship studies aimed at identification of tractable early leads for clinical development. These studies revealed a promising lead compound, 17b, that exhibited nanomolar potency against T. brucei (EC50 = 27 nM for T. b. brucei , 7 nM for T. b. rhodesiense , and 2 nM for T. b. gambiense ) with excellent selectivity for parasite cells relative to mammalian cell lines (EC50 < 25 ?M). In addition compound 17b displayed suitable physiochemical characteristics and microsomal stability (t1/2 < 4 h for human and mouse) to justify pursuing in vivo 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:Kaiser, Marcel and Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:0022-2623
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:18 Oct 2017 09:15
Deposited On:16 Aug 2013 07:31

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