Synthesis and In Vitro Binding of N,N-Dialkyl-2-phenylindol-3-ylglyoxylamides for the Peripheral Benzodiazepine Binding Sites

Authors

T. P. Homes, University of WollongongFollow
F. Mattner, ANSTO Radiopharmaceuticals
Paul A. Keller, University of WollongongFollow
A. Katsifis, ANSTO Radiopharmaceuticals

RIS ID

16707

Publication Details

This article was originally published as Homes, TP, Mattner, F, Keller, PA & Katsifis, A, Synthesis and In Vitro Binding of N,N-Dialkyl-2-phenylindol-3-ylglyoxylamides for the Peripheral Benzodiazepine Binding Sites, Bioorganic and Medicinal Chemistry, 14(11), 2006, 3938-3946. Original journal article available here

Abstract

A series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides bearing the halogens iodine and bromine were synthesised and their binding affinity for the peripheral benzodiazepine binding sites (PBBS) in rat kidney mitochondrial membranes were evaluated using [3H]-PK11195. Central benzodiazepine receptor (CBR) affinities were also evaluated in rat cortices using 3H-flumazenil to determine their selectivity for PBBS over CBR. The tested compounds had PBBS binding affinities (IC50) ranging from 7.86 nM to 618 nM, with all compounds showing high selectivity over the CBR (CBR IC50 > 5000 nM). Among the 12 compounds tested, those with a diethylamide group were the most potent. The highest affinity iodinated PBBS ligand, N,N-diethyl-[5-chloro-2-(4-iodophenyl)indol-3-yl]glyoxylamide (4c), was radiolabelled with iodine-123. This high affinity and selective radioligand may be useful for imaging neurodegeneration, inflammation and tumours using single photon emission computed tomography (SPECT).