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Synthesis and labelling with 18 F of an MK 801 analogue: [ 18 F]5‐(β‐fluoruethyl)‐10,11‐dihydro‐5H‐dibenzocycloheptene‐5,10‐imine
Author(s) -
Denis A.,
Crouzel C.
Publication year - 1989
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580270905
Subject(s) - nmda receptor , chemistry , neurotoxicity , glutamate receptor , memantine , imine , receptor , stereochemistry , biochemistry , toxicity , organic chemistry , catalysis
The 5‐(β‐fluoro)ethyl analogue 1 of MK 801 2 was synthesized and labelled with 18 F in order to visualize the NMDA receptors by positron emission tomography. A tosyloxy precursor 3 was synthesized in 8 steps from dibromodibenzosuberone; the nucleophilic substitution of the tosyl group of 3 by the K 18 F/Krytofix 2,2,2 complex in CH 3 CN gave [ 18 F] 1 in 25% radiochemical yield with a specific activity of 40 GBq/μmol (1 Ci/μmol). The major excitatory amino acids in mammalian brain CNS, L.glutamate and L. aspartate, have a neurotoxic activity mediated through excitatory synaptic receptors such as N‐Methyl‐D‐Aspartate (NMDA) receptor subtype. These excitotoxic amino acids have been implicated in several brain damages associated with epilepsy, anoxia‐ischemia and hypoglycemia (1). MK 801 [(+)5‐methyl‐10,11‐dihydro‐5H‐dibenzo‐cycloheptene‐5,10‐imine] 2 is a potent and non‐competitive antagonist of NMDA (2). MK 801 was shown, in animal models, to protect against hypoxic‐ischemic damage and NMDA neurotoxicity (3, 4). These results may have important implications for the treatment in man of stroke and neurodegenerative disorders. In order to visualize the NMDA receptors by positron emission tomography, the synthesis and the labelling with fluorine 18 (β + , t ½ = 110 min) of the 5‐(β fluoro(ethyl 1 analogue of MK 801 2 was undertaken (Scheme I).