Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5-HT₇ Receptor: Synthesis, Pharmacology, Radiolabeling, and in Vivo Brain Imaging in Pigs

J Med Chem. 2015 Apr 23;58(8):3631-6. doi: 10.1021/acs.jmedchem.5b00095. Epub 2015 Apr 13.

Abstract

We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent (11)C-labeling and in vivo evaluation in Danish landrace pigs showed that both ligands displayed high brain uptake. However, neither of the radioligands could be displaced by the 5-HT7 receptor selective inverse agonist SB-269970.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Carbon Radioisotopes / chemistry
  • Carbon Radioisotopes / metabolism
  • Indoles / chemistry*
  • Indoles / metabolism
  • Ligands
  • Oxindoles
  • Phenols / metabolism
  • Positron-Emission Tomography* / methods
  • Receptors, Serotonin / analysis*
  • Receptors, Serotonin / metabolism
  • Sulfonamides / metabolism
  • Swine

Substances

  • Carbon Radioisotopes
  • Indoles
  • Ligands
  • Oxindoles
  • Phenols
  • Receptors, Serotonin
  • SB 269970
  • Sulfonamides
  • serotonin 7 receptor
  • 2-oxindole