Concise and Scalable Radiosynthesis of (+)-[F]MDL100907 As a Serotonin 5-HT Receptor Antagonist for PET

Overview

Journal ACS Chem Neurosci

Publisher American Chemical Society

Specialty Neurology

Date 2023 Sep 25

PMID 37748194

Authors

Lahu N Chavan

Ronald Voll

Mar M Sanchez

Jonathon A Nye

Mark M Goodman

Affiliations

Soon will be listed here.

Abstract

5-Hydroxytryptamine (5-HT) receptors play an important role in several psychiatric disorders. In order to investigate the serotonin (5-HT) receptor , reliable syntheses are required for positron emission tomography (PET) 5-HT radioligands. Owing to the excellent properties of [F]MDL100907 for PET, there has been great interest to develop a novel synthetic route for [F]MDL100907. Here, we report a highly efficient, scalable, and expedient synthesis for [F]MDL100907. The radiofluorination was performed on a F-labeling boron pinacol ester precursor, which is synthesized using the Liebeskind-Srogl cross-coupling reaction as a key step. Our method is practically more suitable to employ late-stage Cu-mediated radiofluorination and facilitate the production of the [F]MDL100907 radioligand in excellent decay-corrected RCY of 32 ± 10% ( = 7) within 60 min. We prepared [F]MDL100907 in high molar activity (2.1 Ci/μmol) and compared it to [C]MDL100907 in the brain of a nonhuman primate.

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