ACS Medicinal Chemistry Letters
LETTER
bioavailable in three species and efficacious in three mouse models
of malaria. On the basis of these results and the favorable druglike
properties, 2q has been chosen as a potential drug development
candidate.
of plasmodium falciparum dihydroorotate dehydrogenase. J. Biol. Chem.
2008, 283, 35078–35085.
(10) Booker, M. L.; Bastos, C. M.; Kramer, M. L.; Barker, R. H., Jr.;
Skerlj, R.; Sidhu, A. B.; Deng, X.; Celatka, C.; Cortese, J. F.; Guerrero
Bravo, J. E.; Crespo Llado, K. N.; Serrano, A. E.; Barturen, I. A.; Jimenez
Diaz, M. B.; Viera, S.; Garuti, H.; Wittlin, S.; Papastogiannidis, P.; Lin, J.;
Janse, C. J.; Khan, S. M.; Duraisingh, M.; Coleman, B.; Goldsmith, E. J.;
Phillips, M. A.; Munoz, B.; Wirth, D. F.; Klinger., J. D.; Weigand, R.;
Sybertz, E. Novel inhibitors of plasmodium falciparum dihydroorotate
dehydrogenase with antimalaria activity in the mouse model. J. Biol.
Chem. 2010, 285, 33054–33064.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures and
b
characterization data for the synthesis for compounds 1bÀf,i,k,
m,o, 2aÀx, 3cÀd, and 4a,q. This material is available free of
(11) Altman, R. A.; Koval, E. D.; Buchwald, S. L. Copper-catalyzed
N-arylation of imidazoles and benzimidazoles. J. Org. Chem. 2007,
72, 6190–6199.
(12) Hornberger, K. H.; Badiang, J. G.; Salovich, J. M.; Kuntz, K. W.;
Emmitte, K. A.; Cheung, M. Regioselective synthesis of benzimidazole
thiophene inhibitors of polo-like kinase. Tetrahedron Lett. 2008, 49,
6348–6351.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: renato.skerlj@genzyme.com.
Funding Sources
This work was supported by SPARC funds from the Broad Institute,
with funds from Medicines for Malaria Venture, and with support
from the Humanitarian Assistance for Neglected Diseases In-
itiative at Genzyme Corporation. Genzyme is committed to as-
sisting in discovery of drugs for neglected diseases in collabora-
tion with other partners and seeks no profit from drugs used for
these applications.
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