Radiosynthesis of a carbon-11-labeled AMPAR allosteric modulator as a new PET radioligand candidate for imaging of Alzheimer's disease

Caihong Miao, Fugui Dong, Limeng Jia, Wei Li, Min Wang, Qi Huang Zheng, Zhidong Xu

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

To develop PET tracers for imaging of Alzheimer's disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[ 11 C]methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide ([ 11 C]8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide (8) and its corresponding desmethylated precursor 4-cyclopropyl-7-(3-hydroxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide (9) were synthesized from 4-methoxyabiline and chlorosulfonyl isocyanate in eight and nine steps with 3% and 1% overall chemical yield, respectively. The target tracer [ 11 C]8 was prepared from the precursor 9 with [ 11 C]CH 3 OTf through O-[ 11 C]methylation and isolated by HPLC combined with SPE in 10–15% radiochemical yield, based on [ 11 C]CO 2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (A M ) at EOB was 370–740 GBq/μmol with a total synthesis time of 35–40-minutes from EOB.

Original languageEnglish (US)
Pages (from-to)1177-1181
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number10
DOIs
StatePublished - May 15 2019

Keywords

  • Alzheimer's disease (AD)
  • Carbon-11-labeled AMPAR allosteric modulator
  • Positron emission tomography (PET)
  • Radiosynthesis
  • α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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