Premium
Synthesis and preliminary in vitro evaluation of a new memantine derivative 1‐amino‐3‐[ 18 F]fluoromethyl‐5‐methyl‐adamantane: A potential ligand for mapping the N‐methyl‐D‐aspartate receptor complex
Author(s) -
Samnick Samuel,
Ametamey Simon,
Gold Markus R.,
Schubiger Pius A.
Publication year - 1997
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/(sici)1099-1344(199703)39:3<241::aid-jlcr966>3.0.co;2-v
Subject(s) - chemistry , adamantane , memantine , ligand (biochemistry) , stereochemistry , derivative (finance) , lipophilicity , radiosynthesis , nmda receptor , medicinal chemistry , receptor , organic chemistry , biochemistry , in vivo , microbiology and biotechnology , financial economics , economics , biology
The new memantine derivative 1‐amino‐3‐[ 18 F]fluoromethyl‐5‐methyl‐adamantane ( 18 F‐MEM ) was prepared in a two‐step reaction sequence for evaluation as a PET tracer. This involves the no‐carrier‐added nucleophilic radiofluorination of 1‐[N‐(tert‐butyloxy)‐carbamoyl]‐3‐(toluenesulfonyloxy)methyl‐5‐methyl‐adamantane (3) with K 18 F/Kryptofix 2.2.2 in DMSO and the subsequent deprotection of the resulting 18 F‐BOC‐MEM by addition of aqueous HCl. 18 F‐MEM was obtained after purification by reversed phase HPLC in 22±7 % radiochemical yield (decay corrected to EOB) with a radiochemical purity > 99% and a total synthesis time of 100 min. 18 F‐MEM is stable up to 6 h in aqueous solution at room temperature and revealed appropriate lipophilicity for good diffusion through the blood‐brain‐barrier. In vitro studies with the non‐radioactive analog, 1‐amino‐3‐fluoromethyl‐5‐methyl‐adamantane ( 19 F‐MEM ) indicated that this compound binds selectively to the phencyclidine (PCP) binding site within the NMDA receptor complex. © 1997 John Wiley & Sons, Ltd.