Abstract
Two series of (N-benzylpiperidin-4-yl)- and (9-azabicyclo[3.3.1]nonan- 3 beta-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 alpha 2-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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Baculoviridae / genetics
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Benzamides / chemical synthesis*
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Benzamides / metabolism
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Bridged Bicyclo Compounds / chemical synthesis*
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Bridged Bicyclo Compounds / metabolism
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Bridged Bicyclo Compounds, Heterocyclic*
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Fluorine Radioisotopes*
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Molecular Structure
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Moths
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Piperidines / chemical synthesis*
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Piperidines / metabolism
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Pituitary Neoplasms / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Adrenergic, alpha / metabolism
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Receptors, Dopamine / genetics
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Receptors, Dopamine / metabolism
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Receptors, Dopamine D2 / metabolism*
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Receptors, Dopamine D3
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Receptors, Serotonin / metabolism
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
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Tomography, Emission-Computed*
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Tumor Cells, Cultured
Substances
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Benzamides
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Bridged Bicyclo Compounds
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Bridged Bicyclo Compounds, Heterocyclic
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Drd3 protein, rat
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Fluorine Radioisotopes
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Piperidines
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Receptors, Adrenergic, alpha
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Receptors, Dopamine
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Receptors, Dopamine D2
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Receptors, Dopamine D3
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Receptors, Serotonin
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Recombinant Proteins
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2,3-dimethoxy-N-(1-(4-fluorobenzyl)piperidin-4-yl)benzamide
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2,3-dimethoxy-N-(9-(4-fluorobenzyl)-9-azabicyclo(3.3.1)nonan-3-yl)benzamide