2. Academic Validation
  3. Synthesis and Characterization of 5-(2-Fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2 H-pyrano[2,3- b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2

Synthesis and Characterization of 5-(2-Fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2 H-pyrano[2,3- b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2

  • J Med Chem. 2022 Feb 10;65(3):2593-2609. doi: 10.1021/acs.jmedchem.1c02004.
Gengyang Yuan 1,  Maeva Dhaynaut 1,  Yu Lan 2,  Nicolas J Guehl 1,  Dalena Huynh 1,  Suhasini M Iyengar 3,  Sepideh Afshar 1,  Manish Kumar Jain 4,  Julie E Pickett 4,  Hye Jin Kang 4,  Hao Wang 2,  Sung-Hyun Moon 1,  Mary Jo Ondrechen 3,  Changning Wang 2,  Timothy M Shoup 1,  Georges El Fakhri 1,  Marc D Normandin 1,  Anna-Liisa Brownell 1
Affiliations

Affiliations

  • 1 Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, 3rd Avenue, Charlestown, Massachusetts 02129, United States.
  • 2 Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, United States.
  • 3 Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
  • 4 Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States.
PMID: 35089713 DOI: 10.1021/acs.jmedchem.1c02004
Abstract

Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for several neuropsychiatric disorders. An mGluR2 function in etiology could be unveiled by positron emission tomography (PET). In this regard, 5-(2-fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide ([11C]13, [11C]mG2N001), a potent negative allosteric modulator (NAM), was developed to support this endeavor. [11C]13 was synthesized via the O-[11C]methylation of phenol 24 with a high molar activity of 212 ± 76 GBq/μmol (n = 5) and excellent radiochemical purity (>99%). PET imaging of [11C]13 in rats demonstrated its superior brain heterogeneity and reduced accumulation with pretreatment of mGluR2 NAMs, VU6001966 (9) and MNI-137 (26), the extent of which revealed a time-dependent drug effect of the blocking agents. In a nonhuman primate, [11C]13 selectively accumulated in mGluR2-rich regions and resulted in high-contrast brain images. Therefore, [11C]13 is a potential candidate for translational PET imaging of the mGluR2 function.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-157998
    mGluR2 Negative Allosteric Modulator