18F-Labeled Benzamides for Studying the Dopamine D2 Receptor with Positron Emission Tomography

Robert H. Mach, Robert R. Luedtke, Christopher D. Unsworth, Virginia A. Boundy, Peggy A. Nowak, James G. Scripko, S. Todd Elder, Joseph R. Jackson, Patricia L. Hoffman, Paul H. Evora, Anand V. Rao, Perry B. Molinoff, Steven R. Childers, Richard L. Ehrenkaufer

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Abstract

Two series of (N-benzylpiperidin-4-yl)- and (9-azabicyclo[3.3.1]nonan-3β-yl)benzamides were prepared, and in vitro binding assays were used to measure the affinity of these compounds for dopamine D2, dopamine D3, serotonin 5-HT2, and (α2-adrenergic receptors. The results of these studies indicated compounds 23, 26b, and 34 have the selectivity needed for in vivo studies of the D2 (and possibly D3) receptors. 18F-Labeled analogues of 23, 26b and 34 were prepared by N-alkylation of the corresponding desbenzyl precursors with [18F]-4-fluorobenzyl iodide. Preliminary in vivo studies demonstrated that [18F]-23 and [18F]-26b are suitable candidates for further evaluation in positron emission tomography imaging studies. The slow rate of washout of [18F]-34 from nondopaminergic regions and its comparatively high lipophilicity indicates that this compound may not be suitable for imaging studies because of a high level of nonspecific binding.

Original languageEnglish
Pages (from-to)3707-3720
Number of pages14
JournalJournal of Medicinal Chemistry
Volume36
Issue number23
DOIs
StatePublished - 1993

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    Mach, R. H., Luedtke, R. R., Unsworth, C. D., Boundy, V. A., Nowak, P. A., Scripko, J. G., Elder, S. T., Jackson, J. R., Hoffman, P. L., Evora, P. H., Rao, A. V., Molinoff, P. B., Childers, S. R., & Ehrenkaufer, R. L. (1993). 18F-Labeled Benzamides for Studying the Dopamine D2 Receptor with Positron Emission Tomography. Journal of Medicinal Chemistry, 36(23), 3707-3720. https://doi.org/10.1021/jm00075a028