Synthesis and receptor binding studies of halogenated N,N-dialkylel-(2-phenyl-1H-indol-3-yl)glyoxylamides to visualize peripheral benzodiazepine receptors with SPECT or PET

Bioorg Med Chem. 2006 Nov 15;14(22):7582-91. doi: 10.1016/j.bmc.2006.07.001.

Abstract

A library of halogenated 2-arylindolyl-3-oxocarboxamides was prepared to develop radioligands to visualize cerebral PBR by SPECT and PET imaging. In vitro evaluation showed that most of the synthesized compounds were selective,high-affinity PBR ligands with adequate lipophilicity (log D7.4 in the range of 1.6-2.4). The iodinated derivative 11 (Ki = 2.6 nM) and the fluorinated analog 26 (Ki = 6.2 nM) displayed higher affinity than reference compounds.

Publication types

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

MeSH terms

  • Alkylation
  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / metabolism*
  • Animals
  • Cerebral Cortex / metabolism
  • Guinea Pigs
  • Halogens / chemistry*
  • Indoles / chemistry*
  • Kidney / metabolism
  • Molecular Structure
  • Positron-Emission Tomography
  • Rats
  • Receptors, GABA-A / metabolism*
  • Structure-Activity Relationship
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Amides
  • Halogens
  • Indoles
  • Receptors, GABA-A
  • indole