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Synthesis and evaluation of [ O‐methyl ‐ 11 C]4‐[3‐[4‐(2‐methoxyphenyl)‐ piperazin‐1‐yl]propoxy]‐4‐aza‐tricyclo[5.2.1.02,6]dec‐8‐ene‐3,5‐dione as a 5‐HT 1A receptor agonist PET ligand
Author(s) -
Majo Vattoly J.,
Parsey Ramin V.,
Prabhakaran Jaya,
Mann J. John,
Dileep Kumar J. S.
Publication year - 2008
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.1475
Subject(s) - chemistry , radiosynthesis , ene reaction , trifluoromethanesulfonate , chemical synthesis , baboon , agonist , yield (engineering) , stereochemistry , desmethyl , in vivo , ligand (biochemistry) , pharmacophore , methylation , bicyclic molecule , total synthesis , medicinal chemistry , in vitro , receptor , organic chemistry , metabolite , biochemistry , medicine , materials science , microbiology and biotechnology , metallurgy , gene , biology , catalysis
4‐[3‐[4‐(2‐Methoxyphenyl)piperazin‐1‐yl]propoxy]‐4‐aza‐tricyclo[5.2.1.02,6]dec‐8‐ene‐3,5‐dione (4), a potent and selective 5‐HT 1A agonist, was labeled by 11 C‐methylation of the corresponding desmethyl analogue 3 with 11 C‐methyl triflate. The precursor molecule 3 was synthesized from commercially available endo ‐ N ‐hydroxy‐5‐norbornene‐2,3‐dicarboximide in two steps with an overall yield of 40%. Radiosynthesis of 11 C‐4 was achieved in 35 min in 20±5% yield ( n =6) at the end of synthesis with a specific activity of 2600±250 Ci/mmol. In vivo positron emission tomography (PET) studies in baboon revealed rapid uptake of the tracer into the brain. However, lack of specific binding indicates that 11 C‐4 is not useful as a 5‐HT 1A agonist PET ligand for clinical studies. Copyright © 2008 John Wiley & Sons, Ltd.