1146972-97-5Relevant articles and documents
Synthesis of three novel fluorine-18 labeled analogues of l -deprenyl for Positron Emission Tomography (PET) studies of Monoamine Oxidase B (MAO-B)
Nag, Sangram,Lehmann, Lutz,Heinrich, Tobias,Thiele, Andrea,Kettschau, Georg,Nakao, Ryuji,Gulyás, Balázs,Halldin, Christer
, p. 7023 - 7029 (2011/12/15)
The aim in this project was to synthesize and to study fluorine-18 labeled analogues of l-deprenyl which bind selectively to the enzyme monoamine oxidase B (MAO-B). Three fluorinated l-deprenyl analogues have been generated in multistep organic syntheses. The most promising fluorine-18 compound N-[(2S)-1-[18F]fluoro-3-phenylpropan-2-yl]-N-methylprop-2-yn-1-amine (4c) was synthesized by a one-step fluorine-18 nucleophilic substitution reaction. Autoradiography on human brain tissue sections demonstrated specific binding for compound 4c to brain regions known to have a high content of MAO-B. In addition, the corresponding nonradioactive fluorine-19 compound (13) inhibited recombinant human MAO-B with an IC50 of 170.5 ±29 nM but did not inhibit recombinant human MAO-A (IC50 > 2000 nM), demonstrating its specificity. Biodistribution of 4c in mice showed high initial brain uptake leveling at 5.2 ±0.04%ID/g after 2 min post injection. In conclusion, compound 4c is a specific inhibitor of MAO-B with high initial brain uptake in mice and is, therefore, a candidate for further investigation in PET.
