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Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography.

ABSTRACT: In a search for high-affinity receptor ligands that might serve for development as radioligands for the imaging of brain 5-HT(4) receptors in vivo with positron emission tomography (PET), structural modifications were made to the high-affinity 5-HT(4) antagonist (1-butylpiperidin-4-yl)methyl 8-amino-7-iodo-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate (1, SB 207710). These modifications were made mainly on the aryl side of the ester bond to permit possible rapid labeling of the carboxylic acid component with a positron emitter, either carbon-11 (t(1/2) = 20.4 min) or fluorine-18 (t(1/2) = 109.7 min), and included (i) replacement of the iodine atom with a small substituent such as nitrile, methyl, or fluoro, (ii) methylation of the 8-amino group, (iii) opening of the dioxan ring, and (iv) alteration of the length of the N-alkyl goup. High-affinity ligands were discovered for recombinant human 5-HT(4) receptors with amenability to labeling with a positron emitter and potential for development as imaging probes. The ring-opened radioligand, (([methoxy-(11)C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [(11)C]13), showed an especially favorable array of properties for future evaluation as a PET radioligand for brain 5-HT(4) receptors.

SUBMITTER: Xu R

PROVIDER: S-EPMC2951497 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography.

Xu Rong R Hong Jinsoo J Morse Cheryl L CL Pike Victor W VW

Journal of medicinal chemistry 20101001 19

In a search for high-affinity receptor ligands that might serve for development as radioligands for the imaging of brain 5-HT(4) receptors in vivo with positron emission tomography (PET), structural modifications were made to the high-affinity 5-HT(4) antagonist (1-butylpiperidin-4-yl)methyl 8-amino-7-iodo-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate (1, SB 207710). These modifications were made mainly on the aryl side of the ester bond to permit possible rapid labeling of the carboxylic acid c ...[more]

PMID: 20812727

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Dataset Information

Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography.

Publications

Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography.

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