N-(4-[(18)F]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}carboxamides as analogs of WAY100635. New PET tracers of serotonin 5-HT(1A) receptors

Eur J Med Chem. 2014 Oct 6:85:795-806. doi: 10.1016/j.ejmech.2014.07.096. Epub 2014 Jul 26.

Abstract

N-(4-[(18)F]-Fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-carboxamides were prepared by labeling their 4-nitropyridin-2-yl precursors through nitro substitution by the (18)F anion. In vitro and in vivo tests showed that the cyclohexanecarboxamide derivative is a reversible, selective and high affinity 5-HT1A receptor antagonist (IC50 = 0.29 nM, ki = 0.18 nM) with high brain uptake, slow brain clearance and stability to defluorination when compared with conventional standards. This PET radioligand is a promising candidate for an improved in vivo quantification of 5-HT1A receptors in neuropsychiatric disorders.

Keywords: 5-HT(1A); Fluorine-18; N-(4-[(18)F]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}carboxamides; Positron emission tomography; Radioligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Fluorine Radioisotopes
  • Male
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Piperazines / pharmacokinetics
  • Positron-Emission Tomography / methods*
  • Pyridines / chemistry*
  • Pyridines / metabolism
  • Pyridines / pharmacokinetics
  • Radioactive Tracers
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / metabolism*

Substances

  • Fluorine Radioisotopes
  • Piperazines
  • Pyridines
  • Radioactive Tracers
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide