Halogenated 4-(phenoxymethyl)piperidines as potential radiolabeled probes for σ-1 receptors: In vivo evaluation of [123I]-1-(iodopropen-2- yl)-4-[(4-cyanophenoxy)methyl] piperidine

Waterhouse, Rikki N., Mardon, Karine, Giles, Katrina M., Collier, T. Lee and O'Brien, Joanne C. (1997) Halogenated 4-(phenoxymethyl)piperidines as potential radiolabeled probes for σ-1 receptors: In vivo evaluation of [123I]-1-(iodopropen-2- yl)-4-[(4-cyanophenoxy)methyl] piperidine. Journal of Medicinal Chemistry, 40 11: 1657-1667. doi:10.1021/jm960720


Author Waterhouse, Rikki N.
Mardon, Karine
Giles, Katrina M.
Collier, T. Lee
O'Brien, Joanne C.
Title Halogenated 4-(phenoxymethyl)piperidines as potential radiolabeled probes for σ-1 receptors: In vivo evaluation of [123I]-1-(iodopropen-2- yl)-4-[(4-cyanophenoxy)methyl] piperidine
Formatted title
Halogenated 4-(phenoxymethyl)piperidines as potential radiolabeled probes for σ-1 receptors: In vivo evaluation of [123I]-1-(iodopropen-2- yl)-4-[(4-cyanophenoxy)methyl] piperidine
Journal name Journal of Medicinal Chemistry   Check publisher's open access policy
ISSN 0022-2623
1520-4804
Publication date 1997-05-23
Sub-type Article (original research)
DOI 10.1021/jm960720
Volume 40
Issue 11
Start page 1657
End page 1667
Total pages 11
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Abstract Several halogenated 4-(4-phenoxymethyl)piperidines were synthesized as potential δ receptor ligands. The affinity and selectivity of these compounds were determined using in vitro receptor binding assays, and their log P values were estimated using HPLC analysis. The effect of various N- substituents on the σ-1 and σ-2 dissociation constants was examined. These substituents included fluoroalkyl, hydroxyalkyl, iodopropenyl, and selected ortho-, meta-, and pare-substituted benzyl groups. Also determined were the effects of various moieties on the phenoxy ring; specifically 4-iodo, 4- bromo, 4-nitro, 4-cyano, 3-bromo, and pentafluoro substituents were examined. The ranges in the dissociation constants of these compounds for σ-1 and σ- 2 receptors were 0.38-24.3 and 3.9-361 nM, respectively. The ratio of Ki (σ- 2/σ-1) ranged from 1.19 to 121. One of the most promising of the iodinated ligands, 1-(trans-iodopropen-2-yl)-4-[(4-cyanophenoxy)methyl]piperidine (4), was labeled with 123I and studied in vivo in adult male rats. High uptake and good retention of radioactivity was observed in the brain and many other organs known to possess o receptors. Blocking studies revealed high specific binding of [123I]-4 to σ receptors in the brain, lung, kidney, heart, muscle, and other organs known to possess these sites. These results indicate that [123I]-4 and other halogenated 4-(phenoxymethyl)piperidines of this series may provide useful probes for in vivo tomographic studies of σ receptors.
Keyword Iodine Radioisotopes
Piperidines
Receptors
Sigma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Advanced Imaging Publications
 
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Created: Fri, 26 Nov 2010, 14:05:32 EST by Dr Karine Mardon on behalf of Centre for Advanced Imaging