Optimization of 2-(1H-imidazo-2-yl)piperazines series of Trypanosoma brucei growth inhibitors as potential treatment for the second stage of HAT

[Display omitted] A previous publication from our laboratory reported the identification of a new class of 2-(1H-imidazo-2-yl)piperazines as potent T. brucei growth inhibitors as potential treatment for Human African Trypanosomiasis (HAT). This work describes the structure–activity relationship (SAR...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2020-06, Vol.30 (12), p.127207-127207, Article 127207
Main Authors: Ciammaichella, Alina, Ferrigno, Federica, Basta, Andreina, D'Amico, Melania, Biancofiore, Ilaria, Nardi, Valentina, Ponzi, Simona, Graziani, Rita, Gennari, Nadia, Vittoria Orsale, Maria, Fini, Ivan, Paonessa, Giacomo, Summa, Vincenzo, Harper, Steven, Ontoria, Jesus M.
Format: Article
Language:English
Subjects:
Antiparasitic
Human African Trypanosomiasis (HAT)
Sleeping sickness
Trypanosoma brucei
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Summary:[Display omitted] A previous publication from our laboratory reported the identification of a new class of 2-(1H-imidazo-2-yl)piperazines as potent T. brucei growth inhibitors as potential treatment for Human African Trypanosomiasis (HAT). This work describes the structure–activity relationship (SAR) around the hit compound 1, which led to the identification of the optimized compound 18, a single digit nanomolar inhibitor (EC50 7 nM), not cytotoxic and with optimal in vivo profile that made it a suitable candidate for efficacy studies in a mouse model mimicking the second stage of disease.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2020.127207