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Bioorg Med Chem Lett. 2013 Mar 15;23(6):1720-6. doi: 10.1016/j.bmcl.2013.01.068. Epub 2013 Jan 24.

Design, synthesis and structure-activity relationship of rhenium 2-arylbenzothiazoles as β-amyloid plaque binding agents.

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  • 1Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada V5Z1L3.


To continue our efforts toward the development of (99m)Tc PiB analogs, we have synthesized 24 neutral and lipophilic Re (as a surrogate of (99m)Tc) 2-arylbenzothiazoles, and explored their structure-activity relationship for binding to Aβ1-40 fibrils. These Re complexes were designed and synthesized via the integrated approach, so their (99m)Tc analogs would have a greater chance of crossing the blood-brain barrier. While the lipophilicities (logPC18=1.59-3.53) of these Re 2-arylbenzothiazoles were all within suitable range, their binding affinities (Ki=30-617nM) to Aβ1-40 fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2-phenylbenzothiazole pharmacophore. For potential clinical applications, further refinement to obtain Re 2-arylbenzothiazoles with better binding affinities (<10nM) will likely be needed. The integrated approach reported here to generate compact, neutral and lipophilic Re 2-arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current Aβ PET tracers to their (99m)Tc analogs for more widespread application via the use of SPECT scanners.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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