Design and evaluation of naphthol- and carbazole-containing fluorescent sigma ligands as potential probes for receptor binding studies

J Med Chem. 2007 Sep 20;50(19):4648-55. doi: 10.1021/jm070373b. Epub 2007 Aug 22.

Abstract

Some 3,3-dimethyl-1-(3-naphthylpropyl)piperidine and 1-cyclohexyl-4-(3-naphthylpropyl)piperazine derivatives, structurally containing naphthol as a fluorescent moiety, were prepared for being potentially used as fluorescent sigma ligands. Structurally related analogs were also prepared, where the naphthalene nucleus was replaced by the fluorescent carbazole moiety and chain length was varied. For all compounds the in vitro affinities toward sigma receptors and Delta8-Delta7 sterol isomerase site were measured, and the fluorescent properties were determined. Compound 19 gave the best results both for sigma receptor affinities (sigma1, Ki = 6.78 nM and sigma2, Ki = 26.4 nM) and fluorescence features; thus, it was chosen for in vitro saturation binding analysis at sigma receptors. The good results obtained in such assay suggested that the fluorescent compound 19 could be used instead of a radioligand in "green" binding assays.

MeSH terms

  • Animals
  • Carbazoles / chemical synthesis*
  • Carbazoles / chemistry
  • Carbazoles / pharmacology
  • Competitive Bidding
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology
  • In Vitro Techniques
  • Ligands
  • Liver / metabolism
  • Naphthols / chemical synthesis*
  • Naphthols / chemistry
  • Naphthols / pharmacology
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Opioid, delta / metabolism*
  • Structure-Activity Relationship

Substances

  • 1-cyclohexyl-4-(3-(6-hydroxynaphthalen-1-yl)propyl)piperazine
  • Carbazoles
  • Fluorescent Dyes
  • Ligands
  • Naphthols
  • Piperazines
  • Piperidines
  • Receptors, Opioid, delta