A new facile synthetic route to [11C]GSK189254, a selective PET radioligand for imaging of CNS histamine H3 receptor

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4713-8. doi: 10.1016/j.bmcl.2012.05.076. Epub 2012 May 26.

Abstract

GSK189254 and its corresponding precursor GSK185071B were synthesized from 3-methoxyphenylacetic acid with 6-chloropyridine-3-carbolic acid or 6-chloronicotinamide in 8 and 7 steps with either 6% or 7% and either 14% or 16% yield, respectively. [(11)C]GSK189254 was prepared from GSK185071B with [(11)C]CH(3)OTf through N-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 50-60% radiochemical yield based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.

Publication types

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

MeSH terms

  • Benzazepines / chemistry*
  • Carbon Isotopes / analysis
  • Molecular Structure
  • Niacinamide / analogs & derivatives*
  • Niacinamide / chemistry
  • Positron-Emission Tomography
  • Radioligand Assay
  • Receptors, Histamine H3 / analysis*

Substances

  • Benzazepines
  • Carbon Isotopes
  • Receptors, Histamine H3
  • Niacinamide
  • 6-((3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy)-N-methyl-3-pyridinecarboxamide