Total synthesis and evaluation of [18F]MHMZ

Bioorg Med Chem Lett. 2008 Feb 15;18(4):1515-9. doi: 10.1016/j.bmcl.2007.12.054. Epub 2007 Dec 25.

Abstract

Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[(18)F]fluoroethyltosylate ([(18)F]FETos) was carried out in yields of approximately 90% synthesizing [(18)F]MHMZ in a specific activity of approximately 50MBq/nmol with a starting activity of approximately 3GBq. Overall radiochemical yield including [(18)F]FETos synthon synthesis, [(18)F]fluoroalkylation and preparing the injectable [(18)F]MHMZ solution was 42% within a synthesis time of approximately 100 min. The novel compound showed excellent specific binding to the 5-HT(2A) receptor (K(i)=9.0 nM) in vitro and promising in vivo characteristics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Fluorine Radioisotopes / chemistry*
  • Fluorobenzenes / chemical synthesis*
  • Fluorobenzenes / chemistry
  • Isotope Labeling
  • Ketanserin / analogs & derivatives
  • Ketanserin / pharmacokinetics
  • Kinetics
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Radioligand Assay
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Serotonin 5-HT2 Receptor Antagonists*
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / pharmacokinetics

Substances

  • 2-(18F)fluoro-ethoxy-3-methoxyphenyl)-1-(2-(4-fluoro-phenyl)ethyl-4-piperidine-methanol
  • Fluorine Radioisotopes
  • Fluorobenzenes
  • Piperidines
  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists
  • altanserin
  • Ketanserin
  • volinanserin