Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents
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Author
Comer, Eamon
Beaudoin, Jennifer
A.
Kato, Nobutaka
Fitzgerald, Mark E.
Heidebrecht, Richard
W.
Lee, Maurice duPont
Masi, Daniela
Mercier, Marion
Mulrooney, Carol
Muncipinto, Giovanni
Rowley, Ann
Crespo-Llado, Keila
Serrano, Adelfa E.
Wiegand, Roger
C.
Palmer, Michelle A.
Foley, Michael
A.
Munoz, Benito
Scherer, Christina A.
Duvall, Jeremy R.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1021/jm500994nMetadata
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Comer, E., J. Beaudoin, N. Kato, M. E. Fitzgerald, R. Heidebrecht, M. d. Lee, D. Masi, et al. 2014. “Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents.” Journal of Medicinal Chemistry 57 (20): 8496-8502. doi:10.1021/jm500994n. http://dx.doi.org/10.1021/jm500994n.Abstract
Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure–activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207553/pdf/Terms of Use
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