[11C]olanzapine, radiosynthesis and lipophilicity of a new potential PET 5-HT2 and D2 receptor radioligand

Bioorg Med Chem Lett. 2013 Apr 1;23(7):1953-6. doi: 10.1016/j.bmcl.2013.02.045. Epub 2013 Feb 14.

Abstract

Olanzapine and its precursor desmethyl-Olanzapine were synthesized from malononitrile, propionaldehyde, 1-fluoro-2-nitrobenzene, and substituted piperazine in 4, 4, 5, and 5 steps with 35%, 32%, 26%, and 32% overall chemical yield, respectively. [(11)C]Olanzapine was prepared from desmethyl-Olanzapine with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [(11)C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB. The calculated LogP (CLogP) value of [(11)C]Olanzapine is 3.39.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Benzodiazepines / chemical synthesis
  • Benzodiazepines / chemistry
  • Benzodiazepines / pharmacology*
  • Carbon Isotopes
  • Chromatography, High Pressure Liquid
  • Hydrophobic and Hydrophilic Interactions / drug effects
  • Ligands
  • Olanzapine
  • Positron-Emission Tomography*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Serotonin, 5-HT2 / metabolism*
  • Solid Phase Extraction
  • Structure-Activity Relationship

Substances

  • Carbon Isotopes
  • Ligands
  • Receptors, Dopamine D2
  • Receptors, Serotonin, 5-HT2
  • Benzodiazepines
  • Olanzapine