Radiosynthesis and preliminary evaluation of 11C-labeled 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e] [1,2,4] thiadiazine 1,1-dioxide for PET imaging AMPA receptors.

• New radiosynthetic route to a 11C-labeled AMPA ligand. • High radiochemical yield and high molar activity. • Pharmacokinetic profile established for further optimization. The α -amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) belong to the family of ionotropic transmembrane receptors for glutamate (iGluRs) that are implicated in the pathology of neurological disorders and neurodegenerative diseases. Inspired by a recently developed positive allosteric modulator of AMPARs, 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2 H -benzo[ e ][1,2,4]thiadiazine 1,1-dioxide (16 ; EC 50 = 2.0 nM), we designed a new synthetic route for N -protected phenolic precursor 13 and efficiently radiolabeled a PET ligand [11C] AMPA-1905 ([11C] 16) using a modified one-pot two-step strategy in high radiochemical yield and high molar activity. Preliminary in vivo evaluation was carried out to investigate the suitability of [11C] 16 as a potential PET probe for AMPAR imaging. [ABSTRACT FROM AUTHOR]