Synthesis and in vitro characterization of trans- and cis-[(18)F]-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoropiperidine-1-carboxylates as new potential PET radiotracer candidates for the NR2B subtype N-methyl-D-aspartate receptor

Eur J Med Chem. 2012 Jul:53:408-15. doi: 10.1016/j.ejmech.2012.04.011. Epub 2012 Apr 19.

Abstract

Diastereoisomeric compounds [(18)F]cis- and [(18)F]trans-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoro-piperidine-1-carboxylates were successfully synthesized as new subtype-selective PET radiotracers for imaging the NR2B subunit containing NMDA receptors. Rat brain section autoradiographies demonstrated a high specific binding in NR2B/NMDA receptor rich regions for both radioligands. The measured logD(7.4) values as well as B(max)/K(d) ratios indicated that both radiotracers possess the adequate properties required for PET radiotracers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Chemistry Techniques, Synthetic
  • Male
  • Piperidines / chemistry
  • Positron-Emission Tomography / methods*
  • Radioactive Tracers
  • Radiochemistry
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Carboxylic Acids
  • NR2B NMDA receptor
  • Piperidines
  • Radioactive Tracers
  • Receptors, N-Methyl-D-Aspartate
  • piperidine