Synthesis and receptor binding studies of 3-substituted piperazine derivatives

Eur J Med Chem. 2006 Mar;41(3):387-96. doi: 10.1016/j.ejmech.2005.09.004. Epub 2006 Jan 30.

Abstract

In order to find novel receptor ligands various substituents were introduced into the side chain in position 3 of the piperazine 5. During nucleophilic substitution of the hydroxy group of 5 aziridinium ions were formed, resulting in rearranged 1,4-diazepanes and piperazines as side products. 1,2-anellated piperazines 15, 18 and 19 were prepared by hydrogenation of the alpha,beta-unsaturated ester 13 and by condensation of the primary amine 16b with formaldehyde, respectively. Receptor binding studies with radioligands revealed that the phenylacetamide 17b interacts with moderate affinity (K(i) = 181 nM) and considerable selectivity with sigma(1) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Guinea Pigs
  • Ligands
  • Molecular Structure
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Receptors, Opioid / agonists*
  • Receptors, Opioid / chemistry
  • Receptors, sigma / agonists
  • Receptors, sigma / chemistry
  • Sigma-1 Receptor

Substances

  • Ligands
  • Piperazines
  • Receptors, Opioid
  • Receptors, sigma