6734 Journal of Medicinal Chemistry, 2007, Vol. 50, No. 26
Brief Articles
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washed with 500 µL of methanol and aqua bidest, pH 3 (20/80,
v/v), and the substances were eluted with 1000 µL of the same
solvent. The samples were concentrated to dryness. The residues
were taken up in the eluents to be used for HPLC analysis of N,N′-
dihydroxybenzamidine, benzamidoxime, benzamidine, benzhydrox-
amic acid, and benzamide. The plasma samples of N,N′-dihydrox-
ybenzamidine were worked up directly after the blood withdrawal.
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Acknowledgment. We thank Melissa Zietz for the synthesis
of N,N′-dihydroxybenzamidine.
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Supporting Information Available: A figure illustrating the
examples of amidine prodrugs discussed in the introductory
paragraphs, two schemes showing the synthesis of N,N′-dihydroxy-
benzamidine, experimental procedures concerning the in vitro and
in vivo studies, HPLC and LC/MS data for all compounds, and
description of the estimation of the pharmacokinetic parameter. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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