Cell-based optimization of novel benzamides as potential antimalarial leads

Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its...

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Detalles Bibliográficos
Autores principales: Wu, Tao, Nagle, Advait, Sakata, Tomoyo, Henson, Kerstin, Borboa, Rachel, Chen, Zhong, Kuhen, Kelli, Plouffe, David, Winzeler, Elizabeth, Adrian, Francisco, Tuntland, Tove, Chang, Jonathan, Simerson, Susan, Howard, Steven, Ek, Jared, Isbell, John, Deng, Xianming, Gray, Nathanael S., Tully, David C., Chatterjee, Arnab K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Ltd 2009
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532596/
https://www.ncbi.nlm.nih.gov/pubmed/19879133
http://dx.doi.org/10.1016/j.bmcl.2009.10.050
Descripción
Sumario:Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its antiplasmodial activity. The evolution of this compound series leading to optimized candidates with good cellular potency against multiple strains as well as decent in vivo profile is described in this Letter.

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