Article
Journal of Medicinal Chemistry, 2009, Vol. 52, No. 19 6081
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(Jung, Nussloch, Germany) and snap frozen in liquid N2. Brain
was cut in coronal 10 μm slices with a cryostat (Microm HM 550,
Walldorf, Germany) and mounted on HistoBond slides
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(Marienfeld, Lauda-Konigshofen, Germany). Brain slices were
preincubated with phosphate-buffered saline (PBS) for 10 min.
Subsequently, the slices were incubated in PBS for 30 min with
either [11C]-1 alone (about 10 MBq) or [11C]-1 and unlabeled 1
(1 μM) and washed two times for 5 min each with 20% (v/v)
EtOH in PBS to remove nonspecifically bound radiotracer. The
slides were then exposed for 2 h to a multisensitive phosphor
screen (type: MS, Perkin-Elmer Life Sciences), which was after-
ward scanned with a phosphor imager (Cyclone, Packard
Instruments, Meriden, CT).
Acknowledgment. The research leading to these results
has received funding from the European Community’s
Seventh Framework Programme (FP7/2007-2013) under
grant agreement number 201380 (“Euripides”) and from
the Austrian Science Fund (FWF) project ‘‘Transmembrane
Transporters in Health and Disease’’ (SFB F35). The authors
thank Thomas Filip and Maria Zsebedics (Seibersdorf
Laboratories GmbH) for their skillful help with laboratory
animal handling, Florian Bauer (University of Vienna) for
technical assistance and the staff of the radiochemistry
laboratory (Seibersdorf Laboratories GmbH) for continuous
support. Elacridar hydrochloride was kindly provided by
Glaxo SmithKline (Research Triangle Park, NC, USA) and
tariquidar dimesylate by Xenova Ltd. (Slough, Berkshire,
UK).
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Supporting Information Available: Experimental and spectro-
scopic data for the nonkey intermediates 2, 3, 7, and 8. HPLC
chromatogram of [11C]-1. TACs for [11C]-1 PET scans during
which 1 or tariquidar was administered. This material is avail-
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