253265-91-7Relevant academic research and scientific papers
Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography
Xu, Rong,Hong, Jinsoo,Morse, Cheryl L.,Pike, Victor W.
experimental part, p. 7035 - 7047 (2010/12/25)
In a search for high-affinity receptor ligands that might serve for development as radioligands for the imaging of brain 5-HT4 receptors in vivo with positron emission tomography (PET), structural modifications were made to the high-affinity 5-HT4 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 (t1/2 = 20.4 min) or fluorine-18 (t1/2 = 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-HT4 receptors with amenability to labeling with a positron emitter and potential for development as imaging probes. The ring-opened radioligand, (([methoxy-11C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [11C]13), showed an especially favorable array of properties for future evaluation as a PET radioligand for brain 5-HT4 receptors. This article not subject to U.S. Copyright. Published 2010 by the American Chemical Society.
